Alberto Del Guerra(PI), Georgos Loudos(Athens), N. Jon Shah(Institute of Neuroscience and Medicine - 4, Forschungszentrum Juelich)
As diagnostic techniques evolve from the systems to the molecular level, the role of multimodality molecular imaging becomes increasingly important. PET, SPECT and MRI are powerful techniques for in vivo molecular imaging. The hybrid combination of PET (or SPECT) and MRI, enabling truly simultaneous acquisition, is expected to bridge the gap between molecular and systems diagnosis.
By continuing the newly established and successful series of PET-MR/SPECT-MR Conference (2012-Elba Island- Italy, 2013 Julich-Germany, 2014-Kos, Greece) we are delighted to announce that in 2015 we return to Italy for the PSMR2015, the Fourth Conference on PET-MR and SPECT-MR, sponsored by Pisa University-INFN, the Technological Institute of Athens, Juelich Forschungszentrum, and the COST Action PET-MRI TD-1007, The conference is scheduled for May 17-20, 2015 at the Hotel Hermitage on “la Biodola” gulf , in the beautiful Elba island near Pisa (Italy).
The conference will not only cover all the technological aspects of both sequential and simultaneous PET/MR and SPECT/MR systems and their clinical and preclinical application, but also ample space will be given to dedicated systems, novel technologies and new tracers. An industrial session is scheduled where the various companies can provide the latest information on their products in this field.
We are looking forward to welcoming you at the Conference. Alberto Del Guerra George Loudos Jon Shah
Session 1 - MR-PET and MR-SPECT Instrumentation: DetectorsRoom Maria Luisa
Room Maria Luisa
Maria Giuseppina Bisogni(University of Pisa)
Final Report on WG1 of PET-MR COST (invited talk)
Dennis Shaart(Delft University of Technology, The Netherlands)
SPAD Array Chips with Full Frame Readout for Crystal Characterization
We present single photon sensitive 2D camera chips containing 88x88 avalanche photo diodes which can be read out in full frame mode with up to 400.000 frames per second. The sensors have an imaging area of ~5mm x 5mm covered by square pixels of ~56um x 56um with a ~55\% fill factor in the latest chip generation. The chips contain a self triggering logic with selectable (column) multiplicities of up to >=4 hits within an adjustable coincidence time window. The photon accumulation time window is programmable as well. First prototypes have demonstrated low dark count rates of <50kHz/mm2 (SPAD area) at 10 degree C for 10% masked pixels. One chip version contains an automated readout of the photon cluster position. The readout of the detailed photon distribution for single events allows the characterization of light sharing, optical crosstalk etc. in crystals or crystal arrays as they are used in PET instrumentation. This knowledge could lead to improvements in spatial or temporal resolution.
Peter Fischer(Heidelberg University)
The Performance of Silicon Photomultipliers in Cherenkov TOF PET
In time-of-flight positron emission tomography (TOF PET) one of the main factors limiting the time resolution is the time evolution of the scintillation process. This can be avoided by using exclusively the Cherenkov light produced in a suitable material. Sub 100 ps FWHM timing has already been experimentally demonstrated but with a drawback of relatively low detection efficiency due to the photodetectors used. In this work silicon photomultipliers (SiPMs) are considered as a photodetector in Cherenkov TOF PET. The detection efficiency can be significantly improved by using SiPMs, however, at room temperature the SiPM dark counts introduce a significant source of fake coincidences. SiPM samples from different producers were tested in a simple back-to-back setup in combination with lead fluoride Cherenkov radiators. Results for coincidence timing, detection efficiency and effects of dark counts at different temperatures and SiPM overvoltages are presented.
Rok Dolenec(Faculty of Chemistry and Chemical Engineering, University of Maribor, Slovenia)
coffee breakparking area
Session 2 - MR-PET and MR-SPECT Instrumentation: SystemsRoom Maria Luisa
Room Maria Luisa
Nicola Belcari(University of Pisa)
Successful Demonstration of Simultaneous PET/MR Imaging with a RF-Penetrable PET Insert
The integration of PET’s ability to visualize and quantify molecular signatures and MRI’s excellent anatomical information shows great promise to be a powerful tool for disease characterization. However, the high cost of simultaneous PET/MRI has limited its availability. To address this problem, we have developed an RF-penetrable PET insert that can be placed in the bore of any MRI system without requiring modifications to the latter.
The PET insert consists of 16 PET detector modules within Faraday cages in a 32 cm inner diameter ring pattern with small gaps. These gaps, along with electro-optical signal transmission technology that allows the PET insert to electrically float relative to the MRI RF ground, enable RF fields to pass through the PET ring with some attenuation.
In this study, we investigated the feasibility of the RF-penetrable PET insert placed inside a 3T MR system using the body coils for the RF transmit/receive coil. We analyzed the transmit and receive penetration of the RF fields by acquiring B1 maps and MR images. When the PET insert was placed inside the MRI bore, compared to the case with no PET insert, the mean B1 field amplitude (transmitted RF field) was attenuated by -3.47 dB. The SNR (received MR signal) was attenuated by similar factors of -3.4 dB and -3.9 dB with GRE and FSE sequences, respectively. In addition, we acquired simultaneous PET/MR images. The PET images acquired inside the MRI bore were equivalent to those acquired outside the MR system.
We have shown that the RF-penetrable PET technology allows the RF field of an MR body coil to penetrate into the field-of-view, enabling acquisition of simultaneous PET/MR images via a PET insert, without modification to the MR system.
Brian Lee(Stanford University)
Imaging Performance of a Full-Ring Prototype PET-MRI System Based on Four-Layer DOI-PET Detectors Integrated with a RF Coil
We are developing a PET system integrated with a birdcage RF-coil for PET-MRI in order to realize both high sensitivity and high spatial resolution of the PET image by using the 4-layered depth-of-interaction (DOI) PET detector. We constructed a full-ring prototype system and evaluated performances, especially imaging performance, of the prototype system in simultaneous measurement.
The prototype system consists of eight four-layer DOI-PET detectors and a prototype birdcage RF-coil developed for the proposed system. The PET detectors consist of six monolithic multi-pixel photon counter array (S11064-050P), a readout circuit, four-layer DOI scintillator arrays and a shielding box made of 35 μm thick copper foil. The crystal array consists of 2.0 mm × 2.0 mm × 5.0 mm LYSO crystals arranged in 38 × 6 × 4 layer. The RF-coil has eight coil elements and the eight PET detectors are positioned at each element gap. The diameter of the RF-coil elements is 261mm.
We conducted performance tests of the prototype system with a 3.0 T MRI (MAGNETOM Verio). Only the PET detectors, the RF-coil and the cables were in an MRI room during measurements. A data acquisition system and power supplies for the MPPCs and preamplifiers were outside the MRI room and connected to all the detectors through a penetration panel.
As a result, the spatial resolutions of a Na-22 point source in the PET image were lower than 1.6 mm in whole the FOV due to the DOI capability. In addition, the influence of the simultaneous measurements on the PET performance is negligible. On the other hand, the SNR of the phantom image in the magnitude images was degraded from 259.7 to 209.4 due to noise contamination from the power supplies.
Fumihiko Nishikido(National Institute of Radiological Sciences)
A Single-Mode Data Acquisition Architecture for PET/MRI
The development of MRI compatible detectors based on compact solid state photomultipliers has recently led to simultaneous fully integrated PET/MRI systems for human imaging. The PET acquisition design for MRI integration is known to have several additional constraints, including smaller space, electromagnetic compatibility issues and thermal management.
The current work presents the PET acquisition architecture that has been developed for the TRIMAGE project, whose aim is to provide a cost effective, commercial grade trimodality PET/MRI/EEG scanner. The TRIMAGE PET component consists of 216 modules of 2.5 cm x 2.5 cm, arranged in 18 rectangular detectors of 5 cm x 15 cm, the latter in the axial direction, to form a full ring of 31 cm diameter. Each module consists of a staggered dual layer LYSO matrix read out by two arrays of 4 x 8 SiPMs and an ASIC. The detector board hosts a low-power low-end FPGA that performs pixel identification, energy calibration and handles the communication between the ASICs and the motherboard, which is located in proximity of the scanner.
Data is streamed using high-density shielded cables and high-speed LVDS transmission to 9 low-end SoC FPGAs and from there to a central mainboard where coincidences and events statistics are processed. Coincidence data is finally transmitted to a host PC for image reconstruction.
The proposed architecture and technological solutions will be presented and discussed.
Giancarlo Sportelli(Department of Physics, University of Pisa and INFN, Pisa, Italy)
Evaluation of a Partial Ring Design for the INSERT SPECT/MRI System
The aim of the INSERT project is to develop a SPECT insert for a commercial MRI system, for performing simultaneous SPECT/MRI brain studies in humans. We have previously investigated various design options for the detector system, based on a complete ring of detectors. We are now considering a partial ring, due to space limitations. We have investigated the degradation in image quality with a partial ring as compared to a full ring, and the possibility of addressing the limitations by utilising MRI data during reconstruction.
Noise-free data were generated by forward-projecting a cylindrical phantom with spherical inserts for a full-ring and a partial ring system, equipped with multi-slit-slat (MSS) and multi-pinhole (MPH) collimators. Poisson noise was added and images were reconstructed using ML-EM and MAP-EM with a smoothing prior and an anatomical prior. Contrast-recovery (CR) was calculated for the spheres in the lower part of the phantom compared to the top ones. Background CoV was also calculated.
With noise-free data, CR was 77-84% for the MSS and 82-88% for the MPH partial-ring system with 400-1600 iterations. For noisy data and MAP-EM with a smoothing prior, CR was 78-80% and 81-82%, and CoV 22-28% and 26-31%, for the MSS and MPH systems, respectively. With the anatomical prior, CR was 85-89% and 87-91%, respectively.
With the partial ring-systems, the transaxial resolution in the lower part of the image is reduced. The degradation is slightly larger with MSS than MPH collimators, but the MSS collimator results in a lower noise-level. Some resolution can be recovered with more iterations, but the improvement is limited when regularisation is included. The anatomical prior offers both qualitative and quantitative improvement in image quality.
Kjell Erlandsson(University College London)
MRC-SPECT-DF: An MR-Compatible SPECT System with Dual-FOV Collimation Design for Microscopic SPECT Imaging
We will report the design and performance of a MR-compatible SPECT system that utilizes a dual-FOV aperture design for microscopic SPECT imaging of small animals inside an pre-existing MR scanner. The MRC-SPECT-DF system consists of a full ring of high resolution CdTe detectors and an aperture that consists of dual-FOV aperture system design that has two sets of aperture rings along the axis, one providing a large FOV and the other one allowing an ultrahigh resolution microscopic imaging of a selected target region in the object. The switching between apertures does not require mechanical shifting of either the aperture or the CdTe detector ring. This is critical for integrating the SPECT system with the MR scanner, and minimizing the interference between both sub-system while operation.
Ling-Jian Meng(University of Illinois)
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fuoco di bosco
Session 3 - Advances in MR-PET and MR-SPECT Software and QuantificationRoom Maria Luisa
Respiratory Motion Compensation for Simultaneous PET/MR Based on Strongly Undersampled Radial MR Data
We propose a new method for PET/MR respiratory motion compensation, which is based on strongly undersampled measured MR data and a) runs in parallel with the PET acquisition, b) can be interlaced with clinical MR sequences, and c) can be acquired with measurement times as short as 0.5 min per bed position.
An MR dataset covering the free-breathing thorax and abdomen of a volunteer was acquired with a Siemens Biograph mMR system. We applied a 3D encoded radial stack-of-stars sequence with a Golden angle radial spacing (acquisition time: 5.0 min). Respiratory motion amplitudes were estimated from measured k-space centers allowing for a retrospective gating into 20 overlapping motion phase bins with a width of 10%. In addition, two highly undersampled datasets consisting of 300 and 600 spokes were created corresponding to acquisition times of 0.5 min and 1.0 min, respectively. 4D gated MR images of the three datasets (0.5, 1.0 and 5.0 min acquisition time) were reconstructed iteratively. For each of the three resulting image sets, MVFs were estimated.
A 4D PET volume of the volunteer with four artificial hot lesions in the lungs and abdomen was simulated. 3D PET and MoCo 4D PET images based on the three sets of motion vector fields derived from MR were reconstructed and compared to a reference gated 4D reconstruction with ten-fold acquisition time. Visual inspection of the reconstructed PET images showed that blurring was reduced in MoCo 4D images for all acquisition times compared to the 3D reconstruction. A quantitative evaluation in the end-exhale and a mid-ventilation motion phase demonstrated that MoCo 4D reconstructions outperformed the 3D reconstruction in terms of SUVmean values for all lesions and acquisition times compared to the reference gated 4D reconstruction.
Christopher M Rank(German Cancer Research Center (DKFZ), Heidelberg, Germany)
Improved Parameter-Estimation with Combined PET-MRI Kinetic Modelling
Kinetic analysis can be applied both to dynamic PET and dynamic contrast enhanced (DCE) MRI data. We have investigated the potential of combined PET-MRI kinetic modelling using simulated FDG data.
The volume of distribution, Ve, for the extra-vascular extra-cellular space (EES) can be estimated by DCE-MRI, and used to reduce the number of parameters in the PET model. We use a 3 tissue-compartment model with 5 rate constants (3TC/5k), in order to distinguish between EES and the intra-cellular space (EIS). In the standard models, k3 represents transfer from the un-metabolised to the metabolised (M) extra-vascular compartment. In our new model, k3’ represents transfer from EES to the EIS M-compartment. We also define the more biologically relevant constant, k3"=Vek3’, to be used together with the true EES tracer-concentration.
Time-activity curves were generated using the 3TC/5k-model with 3 different Ve-values, but constant k3". Noise was added and the data were fitted with the 2TC/3k model and with the constrained and-un-constrained 3TC/5k model. 100 noise-realisations were generated at 4 different noise-levels.
For the standard 2TC/3k-model, the estimated k3-values were in the range [0.053, 0.094] with SD in the range [0.002,0.043] /min. For the un-constrained 3TC/5k-model, the k3"-values were in the range [0.041,0.187] and SD in [0.053,0.208] /min. With fixed Ve the range of k3" is reduced to [0.083,0.091] with SD in [0.002,0.017] /min. The true k3" value was 0.091/min.
By incorporating information from DCE-MRI into the PET kinetic model, we obtained a good estimate of the parameter k3", independent of Ve.
Kjell Erlandsson(Institute of Nuclear Medicine, University College London, London, UK)
Tissue Probability-Based AC for Neurological PET/MR Using SPM8
The quantitative accuracy of brain PET/MR has been reported to be reduced compared to PET/CT due to difficulties related to bone in MR-based attenuation correction (MRAC), especially in regions near the skull.
To reduce these effects, we designed an offline, tissue probability-based (TPB-AC) using SPM8, which includes soft tissue, air and bone. Thus, both the increased attenuation due to skull and the reduced attenuation due to sinuses are taken into account. The method was developed to use the data collected with the standard anatomical MRAC consisting of 3D T1 FFE, with isotropic voxel size of 2 mm. Thus, collection of additional sequences or modifications to the standard attenuation correction sequence are not required.
Data from F18-FDG brain studies performed both with PET/CT and PET/MR was used in AC validation. Seven patients were reconstructed with the standard attenuation map, TPB -AC and CTAC in PET/MR. Regional analysis between attenuation corrected PET images was conducted using CTAC as reference.
Using TPB-AC, the relative difference in seven subjects when compared to CTAC in all regions was -3 %, -2 %, -5 %, 4 %, -3 %, 1 %, 0 %. In clinical AC the difference was -9 %, -8 %, -9 %, -3 %, -10 %, -5 %, -6 %. Region-wise, the benefit from TPB-AC was most pronounced in precentral, superior frontal and middle frontal gyrus where underestimation from clinical AC of: -11 %, -12 % and -12 % was reduced to: -1%, -2 % and -1 % when using TPB-AC.
Tissue probability-based AC was deemed a promising interim method for PET/MR AC until standardized, commercialized solutions become widely available. To test the robustness of the method, patients with dental implants or deformed anatomy would have to be included in the study group.
Jarmo Teuho(Turku PET Centre)
coffee breakparking area
Session 4 - Advances in MR-PET and MR-SPECT Software and QuantificationRoom Maria Luisa
Room Maria Luisa
Automatic Derivation of an MR-PET Image-Based Input Function for Quantification of 18F-FET
Aim: Fully quantitative PET data requires an input function (IF) for kinetic modelling that is often acquired via arterial blood sampling. Here, an automatic method to obtain an image-derived input function (IDIF) using MR-PET data is presented and several partial volume correction methods (PVC) are evaluated.
Material and methods: Data from three tumour patients were acquired in a 3T MR-BrainPET. A bolus of 3MBq/Kg of body weight of 18F-FET was administrated to each subject and a dynamic PET scan (dPET) was performed during 60min. PET data were reconstructed in 23 frames with variable frame length using OP-OSEM (32it, 4sub) including all the corrections. An MPRAGE scan was acquired (TE/TR/TI = 3/2250/900ms, FA = 9°). Five venous blood samples (VBS) were drawn at the later times later times each 10min. To estimate an IDIF, internal carotid arteries were segmented automatically and these regions were transferred to dPET. After, 4 post-reconstruction PVC were applied and the impact of a scaling factor based on a single VBS was also evaluated based on the area under the curve (AUC).
Results and Discussion: All the tested PVC methods resulted in an under estimation of the AUC at later frames which was mitigated after scaling with a VBS at 50 min. In the earlier frames the different PVC resulted in different AUC, which were not possible to validate.
Conclusion: The fully automated procedure presented allows one to obtain an IDIF without user interaction. Nevertheless, the initial findings regarding the PVC require further validation with a larger data set.
Nuno André da Silva(Institute of Neuroscience and Medicine - 4, Forschungszentrum Juelich)
Cross Calibration of the Siemens mMR: Easily Acquired Accurate PET Phantom Measurements, Long Term Stability and Reproducibility
We present a quick and easy method to perform quantitatively accurate PET scans of typical water-filled PET plastic shell phantoms on the Siemens mMR PET/MR scanner.
We perform regular cross calibrations (Xcals) of our PET scanners, including the Siemens mMR PET/MR, with a Siemens mCT water phantom. We evaluate the mMR cross calibration stability over a 3-year period. Recently, the mMR software (VB20P) offered the option of using predefined μ-maps. We evaluated this option by using either the predefined μ-map of the long mMR water phantom or a system-integrated user defined CT-based μ-map of the mCT water phantom used for Xcal.
On 54 cross calibrations that were acquired over 3 years, the mMR on average underestimated the concentration by 16% due to the use of MR-based μ-maps. The mMR produced the narrowest range and lowest standard deviation of the Xcal ratios, implying it and is the most stable of the 6 scanners included in this study over a 3 year period.
With correctly segmented μ-maps, the mMR produced Xcal ratios of 1.00-1.02, well within the acceptance range [0.95-1.05]. Measuring the concentration in a centrally placed cylindrical VOI allows for some robustness against misregistration of the μ-maps but it should be no more than a few millimeters in the x-y plane, while the tolerance is larger on the z-axis (when, as always with PET, keeping clear of the axial edges of the FOV).
The mMR is the most stable scanner in this study and the mean underestimation is no longer an issue with the easily accessible μ-map, which in all 7 tests resulted in correct Xcal ratios. We will share the user defined μ-map of the mCT phantom and the protocol with interested mMR users.
Sune H. Keller(Rigshospitalet, University of Copenhagen, Denmark)
Pseudo-CT Generation in Brain MR-PET Attenuation Correction: Comparison of Several Multi-Atlas Methods
Simultaneous MR-PET imaging opens new perspectives for understanding many aspects of brain function. However, accurate brain attenuation correction (AC) is required for absolute PET quantification. Radiodensity maps for AC are not readily available in PET-MR. Various strategies have been proposed to generate substitute attenuation maps. Recently, it has been shown that multiatlas techniques for AC outperform methods based on MR imaging sequences, such as Ultrashort-Echo-Time.
We recently investigated several multiatlas methods to build a patient-specific pseudoCT, all based on multiatlas registration and label propagation, and introduced a novel maximum probability method (MaxProb) (Merida et al., ISBI 2015).
Here, a new database of 40 MR/CT image pairs (atlases) was used. Pairwise nonrigid registration of each atlas MR image to the target MR image yielded a geometric transformation that we used for propagating the atlas CT into the target’s space. The synthetic CT was generated by voxelwise atlas selection and intensity averaging. We implemented a state-of-the-art algorithm (Ref) (Burgos et al., IEEE TMI, 2014) along with two variants and MaxProb. A pseudoCT was generated for each subject of the database and assessed by comparison with the real CT in a leave-one-out scheme. Jaccard overlap indices were computed per tissue class (air, soft tissue, and bone). Voxel classification error was also assessed.
The Jaccard indices and voxel classification error showed that MaxProb (8.31±1.12%) performed slightly better than Ref (8.65±0.93%). The influence of the number of atlases fused in pseudoCT generation was studied, showing that an optimal number improves accuracy. By adjusting the number of fused atlases, it was possible to significantly improve on Ref (8.46±0.96%).
The methods now need evaluation on quantitative PET data to identify potential benefits in PET analysis.
Inés Mérida(1 - Université de Lyon 1, INSERM, CNRS, Lyon Neuroscience Research Center, France, 2 - LILI-EQUIPEX – Lyon Integrated Life Imaging: hybrid MR-PET, 3 - Siemens Healthcare France SAS, Saint-Denis, France)
Simultaneous Reconstruction of Attenuation and Activity for non–TOF PET/MR Using MR Prior Information
Accurate quantification of the activity distribution in positron emission tomography (PET) mandates attenuation correction (AC). Unlike in PET/CT, AC in PET/MR is, however, challenging, since direct information about the attenuation properties of the patient tissue distribution is not available directly. Standard MR-based AC (MRAC) does not account for the presence of bone and, thus, yields an underestimation of the activity distribution. We propose an algorithm to simultaneously reconstruct the activity and attenuation distribution using MR images as anatomical prior information for non time-of-flight PET/MR.
The proposed algorithm is an extension of the existing maximum-likelihood reconstruction of attenuation and activity (MLAA). The MR images are used to obtain an initial attenuation map and to derive voxel-dependent expectations on the attenuation coefficients. These expectations are modeled using pre-defined attenuation values and Gaussian-like probability functions. An iterative reconstruction scheme incorporating the prior information on the attenuation coefficients is used to update attenuation and activity distribution in an alternating manner. The algorithm, called MR-MLAA, is evaluated for simulated 2D PET data for two patients with artificial lesions in the head region.
The proposed algorithm helps recover bone attenuation information. However, for both patients, some misclassifications of air (considered as bone) and bone (considered as air or soft tissue) were observed. Nevertheless, PET quantification in lesions located close to bone tissue is greatly improved when using MR-MLAA. Errors in activity estimation are reduced to ranges of -9% to +1% whereas MRAC yields errors of -22% to -10%.
In conclusion, MR-MLAA has the potential to improve quantification in hybrid PET/MR, especially in regions adjacent to dense bone tissue.
Thorsten Heußer(German Cancer Research Center (DKFZ), Heidelberg, Germany)
A Multi-Modal Fusion Scheme for the Enhancement of PET/MR Viewing
PET/MR imaging offers the possibility to achieve in one-shot both functional information provided by PET imaging and morpho-functional information with excellent soft tissue contrast provided by MRI.
As a result of a typical PET/MR acquisition, each voxel carries a large amount of multivariate information that can be combined into a single image for a synthetic multi-parametric viewing (image fusion).
This work is aimed to explore and introduce a reliable fusion scheme able to blend the useful information carried out from each modality into a single meaningful image. The proposed approach consists of a transformation of the source images followed by a blending and a consecutive reconstruction of fused image into the original domain.
Following this scheme, three different transformations of source images (wavelet domain, Fourier domain and identity) and two blending procedures (alpha-blending and gamma-blending) were considered.
For a comprehensive assessment of the fusion schemes under investigation, the results were evaluated both qualitatively and quantitatively on a dataset of 60 naturally co-registered FDG-PET/MR studies of different anatomical districts in presence of neurological as well as oncological findings. The quality of fused images was assessed by experts who visually evaluated the loss of useful information with respect to the original modalities. Quantitatively, the information loss was estimated by means of a boundaries-preservation based metric as well as a metric based on mutual information.
Preliminary results show that the fusion scheme composed by a wavelet-domain transform and a gamma-blending better depicts useful information of the original modalities. In particular, the proposed approach allows to better unveil the MR signal underlying PET signal in fused images in oncological as well as neurological studies. Furthermore, the use of a gamma-blending procedure ensures the best performances in a fully automated manner.
Evaluation of PET Performance and MR Compatibility of a Preclinical PET/MR Insert with Digital Silicon Photomultiplier Technology
In this work we present detailed characterizations of our preclinical high resolution PET/MR insert based on the Hyperion-IID platform. The PET/MR insert consists of a ring of 10 singles detection modules, each comprising 2x3 scintillation detector stacks. Each detector stack features a 30x30 pixelated LYSO crystal array with a heigh of 12 mm and a pitch of 1 mm, coupled via a slit 2 mm light guide to a digital SiPM tile.
The PET performance is stable under a wide range of operating points. The spatial resolution is below 1\,mm and the CRT reaches 260 or 450 ps depending on trigger settings. The energy resolution is 12.6% FWHM.
The characterization of the MR compatibility showed no relevant degradation in PET performance during MRI operation. On the MRI side, we observe a degradation in B0 homogeneity from a VRMS of 0.03 ppm to 0.08 ppm with active shimming, while observing only minor degradations in the B0 field. The noise floor is slightly increased by 2-15% without any observable dependence on the activity. The Z gradients induces an observable eddy current inside the PET inserts which can lead to ghosting artifacts for EPI sequences. However, we don't observe any visible image degradation for widely used anatomical imaging sequences such as gradient echo and turbo spin echo sequences.
To prove the viability of our PET/MR insert for in vivo small animal studies, we successfully performed a longitudinal mouse study with subcutaneously injected tumor model cells. The simultaneously acquired PET/MR images provide a high level of anatomical information and soft tissue contrast in the MR layer together with a high resolution image of the FDG tracer distribution in the PET layer.
Patrick Hallen(Department of Physics of Molecular Imaging Systems, RWTH Aachen University)
First Results from a High-Resolution Small Animal PET Insert for PET/MRI Imaging
We have recently completed construction of a high resolution small animal PET insert designed for operatation inside a Bruker 7T MRI. The PET insert is designed to achieve a 1 mm spatial resolution in the centre of its field of view (FOV) and fit within the 114 mm inner diameter of the Bruker BGA-12S gradient coil while accommodating the Bruker 35 mm volume RF coil (outer diameter 60 mm). The PET insert is a ring geometry with a single ring of 16 detectors. Each detector uses a dual-layer offset (DLO) LYSO scintillator array (bottom/top layer: 22x10/21x9 of 1.2x1.2x6/4 mm crystals, 409 crystals per block), with total axial extent of 28.3 mm, readout by two SensL SPMArray4B SiPM arrays. The detector outputs are multiplexed to four signals using a custom readout board and digitized using the OpenPET data acquisition platform. Detector flood image quality is sufficient to resolve >99% of the crystals in the system. The average energy resolution of the 6544 crystals is 11.94%+/-1.77% at 511keV. MR compatibility testing of the complete PET system conducted with a 7T Bruker Avance III MRI showed that the operating PET insert had no effect on MRI image homogeneity and only a small effect on EPI signal to noise ratio (SNR) (-15%). Initial PET data were collected using a Ge68 line source with the PET system on the benchtop. For this first acquisition, the OpenPET system was operating in oscilloscope mode, limiting the total singles event rate to 18kcps. The sinogram and initial reconstructed images showed no obvious artefacts. We have recently implemented an OpenPET firmware upgrade that will support a singles rate of 280kcps; this will allow us to acquire first simultaneous phantom and mouse PET/MR images.
Andrew Goertzen(University of Manitoba)
The SAFIR Project: An Innovative High Rate Preclinical PET/MR Detector Towards Dynamic Multimodal Imaging
SAFIR (Small Animal Fast Insert for mRi) is an innovative, high rate, PET detector insert for MRI, to be used for quantitative dynamic pre-clinical imaging, with very high activities injected in the animals, up to 500 MBq. The PET detector will be designed to allow for ultra short acquisition periods (of the order of a few seconds) simultaneously with the MRI, permitting unprecedented temporal resolutions in preclinical dynamic multimodal imaging.
High sensitivity (~ 6%), high spatial resolution (~1.5 mm FWHM), excellent coincidence timing resolution (CTR ~ 300 ps FWHM) and a fast DAQ system able to cope with the huge data throughput are required. Parallel with the hardware efforts, dedicated 4D algorithms for image reconstruction must be developed.
The overall state of the project will be presented, including ongoing activities towards the choice and characterization of the detector components (crystals, SiPMs and readout chips), MonteCarlo simulations, and first reconstruction of various simulated sources. Special emphasis will be given to the results of a recent high rate test, where the TOFPET ASIC has been tested with Hamamatsu S12642-0404PB-50 SiPM arrays coupled to matrices of LYSO:Ce crystals (3.1x3.1x12 mm3 each), exposed to a 500 MBq activity of FDG radiotracer in a volume of about 0.5 cm3.
Werner Lustermann(ETH Zurich)
Small Animal PET Based on 16x16 TSV-MPPCs and Monolithic Crystals
In this work we present the design of a small animal PET based on 8 high-density arrays of MPPCs and monolithic scintillators. The MPPCs arrays are composed of 16x16 TSV-type (3x3 mm2) elements covering a rough active area of 5x5 cm2. A single LYSO block with a thickness of 10mm has been mounted on each detector. Black paint has been applied to the entrance and lateral faces of the crystal to preserve the scintillation light distribution. The axial and transaxial FOVs of one ring are 48 mm and 80 mm, respectively.
Each MPPC array has been directly attached to a resistive readout circuit that provides outputs for each row and column of the array. These 32 signals are read with flexible boards 30 cm apart from the PET detector without any additional connectors in between. The PET-system is intended for in-line acquisition in front of MR-scanners and as PET-insert inside the sensitive MRI volume. For this purpose, it is necessary to avoid magnetic sensible materials, such as nickel, and to prevent eddy currents in metallic structures induced by the MRI gradients. All detectors are air cooled and kept at temperatures of approximately 20ºC with a variation below 0.05ºC.
The intrinsic resolution is 2.2mm at the crystal center (averaged over all 2.6 mm) when Center of Gravity methods are used to resolve the impact position. This value is about a factor 1.5 better than results obtained with the H8500 PSPMT (64 PADs) and similar scintillators. With an improved collimator with holes with only 0.8mm diameter and a length of 70mm, an intrinsic detector resolution of 1.1mm was reached. The energy resolutions of ROIs of 1x1cm2 showed FWHM values in the range of (14±2)%.
Antonio Gonzalez(Institute for Instrumentation in Molecular Imaging, i3M-CSIC)
Authentically Radiolabelled Mn(II) Complexes as Bimodal PET/MR Tracers
The development of small molecule bimodal PET/MR tracers is mainly hampered by the lack of dedicated preparation methods. Authentic radiolabelling of MR contrast agents ensures easy access to such probes: a ligand, chelating a paramagnetic metal ion (e.g. Mn2+) and the corresponding PET isotope (e.g. 52gMn), leads to a “cocktail mixture” where both imaging reporters exhibit the same pharmacokinetics. Paramagnetic [55Mn(CDTA)]2- shows an excellent compromise between thermodynamic stability, kinetic inertness and MR contrast enhancement. Therefore, the aim of this study was to develop new PET/MR tracers by labelling CDTA ligands with paramagnetic manganese and the β+-emitter 52gMn.
N.c.a. 52gMn (t1/2: 5.6 d; Eβ+: 575.8 keV (29.6%)) was produced by proton irradiation of a natCr target followed by cation-exchange chromatography. CDTA was radiolabelled with n.c.a. 52gMn2+ in NaOAc buffer (pH 6) at RT. The complex was purified by RP-HPLC and its stability tested in PBS and blood plasma at 37°C. The redox stability was assessed by monitoring the T1 relaxation (20 MHz) in HEPES buffer (pH 7.4). A functionalized CDTA ligand was synthesized in 5 steps.
[52gMn(CDTA)]2- was quantitatively formed within 30 min at RT. The complex was stable for at least 6 days in PBS and blood plasma at 37°C and no oxidation occurred within 7 months storage at RT. Labelling CDTA with an isotopic 52g/55Mn2+ mixture led to the corresponding bimodal PET/MR tracer. Furthermore, a functionalized CDTA ligand was synthesized with an overall yield of 18-25%.
[52g/55Mn(CDTA)]2-, the first manganese-based bimodal PET/MR tracer prepared, exhibits excellent stability towards decomplexation and oxidation. This makes the functionalized CDTA ligand highly suitable for designing PET/MR tracers with high relaxivity or targeting properties.
Heinz H. Coenen(Institute of Neuroscience and Medicine, INM-5 - Nuclear Chemistry, Forschungszentrum Jülich)
Lymph Node Imaging Using Novel Simultaneous PET/MRI and Dual-Modality Imaging Agent
Lymph node (LN) imaging has clinical significance because the invasion status of the LN is crucial information for disease stratification, staging, and management. Compared with conventional method, simultaneous PET/MRI using the multi-modal imaging marker can offer synergistic advantages. Here, we present LN mapping using self-developed PET/MRI and novel bimodal biomarker.
The SiPM-based PET insert which has peak sensitivity of 3.4% and center volumetric resolution of 0.57 cubic mm was developed. The PET insert was placed between the RF and gradient coil of Bruker 7T MRI. For LN targeting, 64Cu-NOTA-ironoxide-mannose, a new LN targeted dualmodality probe yielding superior T2 contrast was used. The relaxivity of the probe was measured by phantom study. Before the simultaneous imaging, MRI of the left and right popliteal lymph node of an anaesthetized BALB/c mouse was acquired as the control. 10 μL of the tracer was then injected into the left hindpaw of same mouse. Simultaneous PET/MRI was acquired for 10 minutes after 10-min and 120-min uptake period.
The r2 of the probe was 845.3 at 7T magnetic field. The simultaneous PET/MRI has sufficient resolution and sensitivity to imaging tiny organ like mouse LN. A left popliteal LN in the 120-min post-injection MRI resulted in a remarkable signal decrease compared to those in the pre-injection MRI and that was good agreement with PET. The 10-min post-injection PET also showed clear regional activity in the LN, but the 10-min uptake period was not sufficient to generate MR contrast. It is due to the large difference in the sensitivities of the two modality.
The simultaneous PET/MRI is useful for in vivo imaging and bimodal imaging probe development particularly to generating negative T2 contrast.
Guen Bae Ko(Seoul National University)
coffee breakparking area
Session 6 - Whole-body and dedicated organ MR-PETRoom Maria Luisa
Room Maria Luisa
Stan Majewski(West Virginia University)
PET/MR: Improvement of the UTE μ-Maps Using Modified MLAA
For a quantitative analysis in positron emission tomography (PET) or single-photon emission computed tomography (SPECT), attenuation correction (AC) is mandatory. CT-scans or transmission scans are common tools for determination of the attenuation μ-map, but in the case of a PET/MR hybrid system it is difficult to associate one of these scans. Many techniques have been developed in order to improve AC for PET/MR. Some methods are based on template- or atlas techniques, other methods apply a segmentation technique based on Dixon or UTE (Ultrashort Echo Time) MR to create the μ-map, followed by a standard OSEM reconstruction (OSEM/DIXON and OSEM/UTE). A different approach for AC has been developed by employing the emission sinogram data in the μ-map derivation. In this context, we modified the iterative MLAA (Maximum-Likelihood reconstruction of Attenuation and Activity) algorithm to improve the resulting emission image from the PET/MR system. We constrained the attenuation map update using the UTE μ-map and the T1-weighted (T1w) MR image in order to improve convergence towards a solution. Results show that the modified MLAA algorithm improved the estimated emission image compared to standard OSEM/UTE and OSEM/DIXON. In certain regions of the brain, in particular close to the skull and the air cavities, the modified MLAA algorithm generated less error than OSEM/UTE and OSEM/Dixon. The modified MLAA algorithm is able to compute an attenuation μ-map that is slightly more similar to the aligned CT μ-map than the UTE μ-map.
Dynamic Brain PET/MR Using TOF Reconstruction
In a functional PET/MR study, it is difficult to get good temporal resolution of activity distribution from PET images because of the need to image for a certain length of time to get sufficient count statistics (image SNR). Time-of-flight (TOF) reconstruction can be used to increase PET images SNR and therefore increase the temporal resolution. Five patients were injected with 410±80 MBq of FDG and scanned 140±30 minutes post-injection on a simultaneous TOF-enabled PET/MR scanner. PET images were reconstructed with and without TOF. TOF reconstruction shows faster convergence while it achieves a temporal SNR improvement of 5-45% (25±15%) compared to non-TOF reconstruction. With this additional SNR gain, frame durations as short as 30s are possible while preserving reasonable image quality. This in turn effectively increases the temporal resolution of dynamic brain studies using simultaneous PET/MR imaging.
Mohammad Mehdi Khalighi(GE Healthcare)
Congruency of Tumour Volume Delineated by FET PET and MRSI
In addition to MR imaging, PET imaging of O-(2-[18F]Fluorethyl)-L-Tyrosine (FET) uptake provides information on brain tumour extent and metabolic activity . Similarly, MRS has been shown to be of value for distinguishing high- from low-grade gliomas . Based on 2D spatially resolved MRSI, an overlap between 18FET uptake and the choline/N-acetyl-aspartate (Cho/NAA) ratio of more than 75 % has been reported .
Aim: To measure spatial correlation of 18FET-PET with 3D spatially resolved MRSI in patients with gliomas.
Methods: 14 patients (46±16 y) with gliomas (WHO grade II-IV) were examined by simultaneous 18FET-PET-3D-MRSI measurements which covered the whole brain (Siemens BrainPET/3T MR TIM Trio; MRSI: EPSI sequence , TE=17.6 ms). The data were analysed with respect to the congruency of the suspicious tissue delineated by the FET uptake and the Cho/NAA ratio. Locations of individual maxima and distances in between were determined. The congruency of the tumour was assessed using Dice’s coefficients for assumed same tumour volume. All comparisons were carried out at the spatial resolution of the whole brain spectroscopic image (64x64x32 vxl, 5.6x5.6x10mm3 each).
Results: The intensity maxima of both modalities were (61±51) mm distant from each other. The average level of congruency between the tumour volumes delineated in the FET uptake and MRSI data was (33±25)%.
Discussion – Conclusion: Metabolically active tumour tissue, as depicted by FET uptake, is represented to a low extent by the choline/N-acetyl-aspartate ratio measured by spatially resolved 3D MRSI, which is in contrast to previous findings . Both modalities may reflect independent physiological properties of gliomas.
 Pauleit, Brain 128.
 Zeng,Magn Reson Imag 29.
 Stadlbauer, J Nucl Med 49.
 Ebel, MRM 53.
Jörg Mauler(Institute of Neuroscience and Medicine, Forschungszentrum Jülich, Jülich, Germany)
Do Carotid MR Surface Coils Affect PET Quantification in PET/MR Imaging?
To evaluate the effect of surface coils for carotid MR imaging on PET quantification in a clinical simultaneous whole-body PET/MR scanner.
Methods and materials
A cylindrical phantom was filled with a homogeneous 2L water-FDG mixture at a starting dose of 301.2MBq. Clinical PET/MR and PET/CT systems were used to acquire PET-data without a coil (reference standard) and with two carotid MRI coils (Siemens Special Purpose 8-Channel and Machnet 4-Channel Phased Array). PET-signal attenuation was evaluated with Osirix using 51 (PET/MR) and 37 (PET/CT) circular ROIs. Mean and maximum standardized uptake values (SUVs) were quantified for each ROI. Furthermore, SUVs of PET/MR and PET/CT were compared. For validation, a patient was scanned with an injected dose of 407.7MBq on both a PET/CT and a PET/MR system without a coil and with both coils.
PET/MR underestimations were -2.2% (Siemens) and -7.8% (Machnet) for SUVmean, and -1.2% (Siemens) and -3.3% (Machnet) for SUVmax, respectively. For PET/CT, underestimations were -1.3% (Siemens) and -1.4% (Machnet) for SUVmean and -0.5% (both Siemens and Machnet) for SUVmax, respectively using no coil data as reference. Except for PET/CT SUVmax values all differences were significant. SUVs differed significantly between PET/MR and PET/CT with SUVmean values of 0.51-0.55 for PET/MR and 0.68-0.69 for PET/CT, respectively. The patient examination showed that median SUVmean values measured in the carotid arteries decreased from 0.97 without a coil to 0.96 (Siemens) and 0.88 (Machnet).
Discussion - Conclusion
Carotid surface coils do affect attenuation correction in both PET/MR and PET/CT imaging. Furthermore, SUVs differed significantly between PET/MR and PET/CT.
Martin J Willemink(Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York)
Rapid workflow of mMR PET list-mode data processing using CUDA
The purpose of this work is to provide a software solution which would enable very fast list-mode data processing offered by the massively parallel graphics processor units (GPU) while dealing efficiently with the common bottleneck of data transfers between hard disk storage, host (CPU) memory and device (GPU) memory. This software is dedicated to the PETLINK™ list-mode data format which is used by the Siemens’ hybrid Biograph Molecular MR (mMR) scanner. This software is developed as part of our platform for mMR 3D and 4D PET image reconstruction and will be freely accessible to the community.
The aim is to perform real time processing (i.e. without perceivable delay) of the list-mode data during data transfers from hard disk to the CPU memory. The output of the processing includes:
(1) The count-rate data (head curve: prompts, randoms and singles per second).
(2) Plot of the variation of the centre of mass due to kinetics and motion (crude motion detection and quantification).
(3) Projection movies (sagittal and coronal) for visual inspection
for motion and data quality.
(4) Crystal fan-sums for any time frame (used for randoms noise reduction).
(5) Singles rate for each detector bucket (used for dead-time correction during normalisation).
(6) Static and dynamic sinograms of span-1 and span-11.
This workflow enables list-mode data processing synchronously with data transfer from disk to CPU memory. It opens a way for fast creation of multiple bootstrap realisations and multiple image reconstructions for a single dataset providing valuable insight into distributions of any statistic used in the development of robust image bio-markers. Also, the proposed workflow is advantageous for list-mode image reconstruction.
DrPawel Markiewicz(University College London, CMIC, Translational Imaging Group)
lunch breakfuoco di bosco
fuoco di bosco
Session 7 - Industrial SeminarsRoom Maria Luisa
Room Maria Luisa
Giancarlo Sportelli(University of Pisa)
Avances in PET and PET/MR: Bruker solutions
State-Of-The-Art Multimodal PET, SPECT and MRI Imaging by Mediso
SensL SiPM MR Compatible TSV product preview
Session 8 - Poster Session IRoom Elena
Harry Tsoumpas(University of Leeds), Jae Sung Lee(South Korea)
3D Photon Impact Determination in Monolithic Crystals Based on Autocorrelation Filters and RTP Methods
In PET detectors based on monolithic scintillators, the photon impact position can be estimated from the light intensity distribution (LD) on the photodetector pixels. Typically, there is a poor estimation of the interaction positions towards the edges when linear algorithms such as Center of Gravity (CoG) are used. We present a novel method to determine the interaction coordinates in thick monolithic crystals filtering the digitized LDs from each gamma-event by means of an autocorrelation filter and the raise to power (RTP) positioning algorithm to reduce the border effects.
The experimental setup was based on two detector blocks based on monolithic LYSO scintillator crystals (50x50x20 mm3). Each crystal is coupled to a SiPMs array as 12x12 photosensors and an electronic readout that outputs information of each SiPM row and column. Between the detector blocks, a collimated array of 9x9 22Na sources, separated 5 mm each other, was placed.
The optimum power to use in the RTP positioning algorithm was determined using the third order intercept point (IP3) from plots of the measured coordinates versus known positions. After applying the autocorrelation and RTP fifth to the data, we found an improvement of the spatial resolution from 2.5 mm when CoG is used, to 1.2 mm in the crystal center region.
In this work we show how to accurately resolve 3D photon impact coordinates in thick monolithic crystals using autocorrelation filters merged with RTP methods. After applying the new approach it is possible to accurately resolve impacts close to the entrance of 20 mm thick LYSO scintillators. The reached spatial resolution at any photon depth of interaction is comparable with state-of-the-art crystal array approaches with the advantage of the proposed work to also provide continuous depth of interaction information.
Pablo Conde(Institute for Instrumentation in Molecular Imaging, I3M-CSIC)
A Close Link Between Metabolic Activity and Functional Connectivity in the Resting Human Brain
Default-mode network (DMN) functional connectivity and its task-dependent down-regulation have attracted a lot of attention in the field of neuroscience. Nevertheless, the exact underlying mechanisms of DMN functional connectivity, or more specifically, the blood oxygen level-dependent (BOLD) signal, are still not completely understood. To investigate more directly the association between local glucose consumption, local glutamatergic neurotransmission and DMN functional connectivity during rest, the present study combined for the first time 2-Deoxy-2-[18F]fluoroglucose positron emission tomography (FDG-PET), proton magnetic resonance spectroscopy (1H-MRS), and resting-state functional magnetic resonance imaging (rs-fMRI). Seed-based correlation analyses, using a key region of the DMN i.e. the dorsal posterior cingulate cortex as seed, revealed overall striking spatial similarities between fluctuations in FDG-uptake and the BOLD signal. More specifically, a conjunction analysis across both modalities showed that DMN areas as the inferior parietal lobe, angular gyrus, precuneus, middle and medial frontal gyrus were positively correlated with the dorsal posterior cingulate cortex. Furthermore, we could demonstrate that local glucose consumption in the medial frontal gyrus, posterior cingulate cortex and left angular gyrus was associated with functional connectivity within the DMN. We did not find a relationship between glutamatergic neurotransmission and functional connectivity. In line with very recent findings, our results provide further evidence for a close association between local metabolic activity and functional connectivity and enable further insights towards a better understanding of the underlying mechanism of the BOLD signal.
Susanne Passow(Department of Biological and Medical Psychology, University of Bergen, Norway; NORMENT Center of Excellence, University of Oslo, Norway)
A Compact PET Detector Module Using SiPMs and MVT Digitizers
Nowadays the simultaneous PET/MRI is being paid more and more attentions. Since MRI provides a high resolution, unsurpassed soft tissue contrast imaging and PET reveal the metabolism progress in molecular level, it is reasonable to believe the PET/MRI will be a powerful tool to improve the understanding of pathogenesis and mechanism of brain disease. Such a simultaneous system can be implemented by integrating the RF coil with a PET scanner or inserting the PET scanner inside a MRI. In these solutions, one of the challenges is to develop compact and magnetic ﬁeld compatible PET detectors. Thanks to the SiPMs, such detectors now are realizable. Aim for the simultaneous PET/MRI system, we have developed a compact PET detector module by using of the SiPMs and MVT digitizers. In the module, output signals from the LYSO/SiPM detector blocks are sampled by the MVT digitizers and then sent out via the Ethernet communicator. The timing, energy and position information will be picked up by digitally analyzing the resulted samples in a PC. In the LYSO/SiPM detector blocks, we use cross-wire method to readout the signals from SiPMs and further using transmission-line method to multiplex the signals. In this way, we get a 36:4 readout channel reducing. In this work, we have setup a dual-panel coincidence detection and imaging system by using a pair of the detector modules. The timing and energy resolution of the system are measured to be 1.67nS FWMH and 16.8%@511keV, respectively. With the system, We also obtained the imaging of a home-made mirco-Derenzo phantom which successfully resolved the 1.6mm hollows. In future, we will investigate the feasibility of building a simultaneous PET/MRI system by using these modules.
Chen Zeng(Huazhong University of Science & Technology), MrDaoming Xi(Huazhong University of Science & Technology), MrXiang Liu(Huazhong University of Science & Technology)
A Theoretical Comparison of Position Estimation Methods for Determining the Interaction Position of Gamma Rays in Monolithic Scintillators
In this paper we report on the development of a mathematical model, based on the estimation theory, for the performance analysis of different gamma-ray interaction position estimation methods applied to gamma cameras based on monolithic scintillators. The gamma camera performance is expressed in terms of bias and spatial resolution. We propose a method to investigate performances of various detection system configurations, used in recent papers, when different image reconstruction algorithms are used. The results are obtained for the whole field of view, with a computational time five order of magnitude lower than a Monte Carlo simulation. We developed a mathematical model for four estimation methods: the classical Center of Gravity method (Anger Logic), an enhanced Center of Gravity method, a Mean Square Error fitting method and the Maximum Likelihood method. Moreover, those models can be used to investigate edge effects and performance of a detector with an arbitrary pattern of active elements and dead areas, in order to study systems with more multi-anode PMTs or SiPM array modules. The bias and spatial resolution results obtained with those mathematical model were compared with the ones obtained from Monte Carlo simulations, made with GEANT4, showing a very good agreement for all the methods.
Alternating-Direction Method of Multipliers Estimation of Attenuation and Activity Distributions in Time-of-Flight Flat-Panel Positron Emission Tomography
A quantitative reconstruction of radiotracer activity distribution in positron emission tomography (PET) requires correction of attenuation, which was typically estimated through transmission measurements. The advancement in hardware development has prompted the use of time-of-flight (TOF) to improve PET imaging. Recently, the application of TOF-PET has been further extended to obtain attenuation map in addition to activity distribution simultaneously by use of iterative algorithms. Two flat-panel detectors are employed thus many transaxial lines of response are not detected. In this work, we applied the alternating-direction method of multipliers (ADMM) to simultaneously reconstruct TOF-PET and attenuation estimation in a dual-head small-animal PET system. The results were compared with those obtained by use of the maximum-likelihood algorithm. The computer simulation results showed that the application of the ADMM algorithm could greatly improve the image quality and reduce noisy appearance.
Yueh Hsu(National Taiwan University)
Attenuation Correction for Hybrid MR/PET Scanners: a Comparison Study
Attenuation correction of PET data acquired in hybrid MR/PET scanners is still a challenge. Different methods have been adopted by several groups to obtain reliable attenuation maps (mu-maps). In this study we compare three methods: MGH, UCL, Neural-Network. The MGH method is based on an MR/CT template obtained with the SPM8 software. The UCL method uses a database of MR/CT pairs. Both generate mu-maps from MP-RAGE images. The feed-forward neural-network from Juelich (NN-Juelich) requires two UTE images; it generates segmented mu-maps. Data from eight subjects (S1-S8) measured in the Siemens 3T MR-BrainPET scanner were used. Corresponding CT images were acquired. The resulting mu-maps were compared against the CT-based mu-maps for each subject and method. Overlapped voxels and Dice similarity coefficients, D, for bone, soft-tissue and air regions, and relative differences images were calculated.
The true positive (TP) recognized voxels for the whole head were 79.9% (NN-Juelich, S7) to 92.1% (UCL method, S1). D values of the bone were D=0.65 (NN-Juelich, S1) to D=0.87 (UCL method, S1). For S8 the MHG method failed (TP=76.4%; D=0.46 for bone). D values shared a common tendency in all subjects and methods to recognize soft-tissue as bone. The relative difference images showed a variation of -10.9% - +10.1%; for S8 and MHG method the values were -24.5% and +14.2%.
A preliminary comparison of three methods for generation of mu-maps for MR/PET scanners is presented. The continuous methods (MGH, UCL) seem to generate reliable mu-maps, whilst the binary method seems to need further improvement. Future work will include more subjects, the reconstruction of corresponding PET data and their comparison.
Elena Rota Kops(Forschungszentrum Juelich, Juelich, Germany)
Dedicated Brain PET System of PET/MR for Brain Research
Aims: This work is to replace PET ring in human brain PET/MR system with a dedicated wearable PET insert, aimed at improving both patient feasibility and system performance for brain imaging.
Methods and materials: The designed PET/MR system include two parts: the inside parts, including a radio frequency (RF) coil and PET ring, are mounted on patient’ head, and the outside part, a MR imager, is dependent of patient. The RF coil is the innermost layer, surrounded by an outer PET-ring layer. They are supported by a MR-compatible structure. And both RF coil and PET detectors are placed inside a standard clinical 3–T MR imager
Discussion: From the design of the system we can infer that some advantages can be achieved. First, high sensitivity will be achieved with the same amount crystals as the PET ring is more close to region-of-interest area, at a reduced cost. Second, by using a 2-layer depth of interaction (DOI) detector, the parallax effect can be minimized. The resolution will benefit from short positron range caused by magnetic field and smaller ring diameter will also reduce the effect of non-collinearity. Thirdly, as the PET ring is mounted on head, impact of patient motion will be reduced .
LI CHENG(Institute of Medical Physics, Department of Engineering Physics, Tsinghua University, Beijing, China)
Determination of Position and Shape of Flexible MRI Surface Coils Using the Microsoft Kinect for Attenuation Correction in PET/MRI
Due to the varying position and shape of flexible MRI RF surface coils, the creation of attenuation maps for these coils is a challenging task. Nevertheless, coil material (metal, plastic, rubber) attenuates the PET signal to a considerable amount. Thus, including a coil µ-map into the human µ-map is essential. In this work, we present a method to determine the position and shape of flexible coils with the help of the Microsoft Kinect depth camera.
Phantom PET/MRI (Siemens Biograph mMR) and CT scans (Siemens Biograph mCT) were performed with and without the flexible 32-channel coil equipped with 15 markers visible in CT and Kinect. Prior to the PET/MRI acquisition, Kinect data is acquired of the phantom with the coil on top. The manually extracted marker positions from CT and Kinect are used to non-rigidly transform the template CT according to the Kinect marker positions describing the shape of the coil during PET/MRI acquisition. An appropriate µ-map can then be calculated from the transformed CT dataset. Subsequently, the µ-map is placed in relation to the patient table according to the Kinect-derived marker positions.
First results show that the coil shape can be determined with the help of the Kinect camera. The transformation of the template CT dataset according to Kinect marker positions during PET/MRI leads to appropriate results. Furthermore, the position of the coil can also be determined for an accurate placement of the µ-map in relation to the patient table.
The determination of position and shape of flexible surface coils using the Kinect camera can be a way to include the CT-based coil µ-map in PET/MRI acquisitions without the need for additional MRI scans. Accuracy and practicability of the method have to be tested in further experiments.
Lynn J. Frohwein(European Institute for Molecular Imaging, University of Muenster, Germany)
Development of a MR-Compatible DOI-PET Detector Module
Silicon Photomultiplier (SiPM) is a promising sensor for PET detector which is able to work normally in the MR environment. In this paper, we developed a compact DOI-PET detector based on an 8x8 SiPM (MicroFB-30035-SMT) array and two layers of LYSO arrays. A 15x15 top layer placed half crystal offset on a 16x16 bottom layer and then coupled to the SiPM array. Size of the LYSO crystals in both layers is 2x2x7mm3. Sixty-four channels of SiPMs are multiplexed by an ASIC chip with in-chip resistor networks into 3 analog outputs and then fully digitized by 3 ADC chips. The energy is calculated by averaging the 3 points around the peak of the pulse. Experiments with two 22Na point sources were studied. The results show that the detector module achieves good crystal identification capability and energy resolution in both layers.
Qingyang Wei(Tsinghua University)
Development of a PET Insert for Simultaneously Small Animal PET/MRI
PET/MR is a new multi-modality imaging system which provide both structural and functional information with good soft tissue imaging ability and no ionizing radiation. In recent years, PET/MR is under major progress because of the development of silicon photomultipliers (SiPM). The goal of this study is to develop a MRI compatible PET insert based on SiPM and LYSO scintillator. The PET system was constituted by the detector ring, electronics and software. The detector ring consists of 16 detector module. The inner diameter of the ring was 151mm, the external diameter was 216mm, which was big enough for small animal research, e.g. rat, rabbit and tupaia. The sensor of each module was 2*2 SensL SPMArraySL, coupled with an array of 14*14 LYSO crystals, each crystal measuring 2mm*2mm*10mm. The detector was encapsulated in a copper box for light and magnetic shielding. Resister charge multiplexing circuit was used in the front end electronics. Each detector output 8X and 8Y position signals. One summed timing signal was extracted from the common cathode of all 64 channels. All these signals were transmitted to digital electronic board by a 3m long coaxial cable from inside of the MR to the outside. Each digital electronic board handled 8 detector modules based on FPGA to obtain the timing, position and energy information of a single event. And then these single events were sent to the coincidence processing board to produce coincidence packets which are prepared for further processing. A 0.2mCi 68Ge line source was used to do the preliminary imaging test. The image was reconstructed by 3D-OSEM algorithm. The initial result proved the system to be feasible as a PET. FDG phantom imaging and simultaneous PET/MR imaging are in progress.
Yingjie Wang(Institute of High Energy Physics, Chinese Academy of Sciences)
Evaluation of a SIPM Array Detector Coupled to a LFS-3 Pixellated Scintillator for PET/MR Applications
SiPM arrays are insensitive to magnetic fields and thus good candidates for hybrid PET/MR imaging systems. Moreover, due to their small size and flexibility can be used in dedicated small field of view small animal imaging detectors and especially in head PET/MR studies in mice. Co-doped LFS-3 scintillator crystals have higher light yield and slightly faster response than that of LSO:Ce mainly due to the co‐doped activation of emission centers with varying materials such as Ce, Gd, Sc, Y, La, Tb, or Ca distributed at the molecular scale through the lutetium silicate crystal host.
The purpose of this study is to investigate the behavior of the SensL ArraySL-4 (4x4 element array of 3x3mm^2 silicon photomultipliers) optical detector coupled to a 6x6 LFS-3 scintillator array, with 2x2x5mm^3 crystal size elements, for possible applications in small field of view PET/MR imaging detectors. We have designed a symmetric resistive charge division circuit to read out the signal outputs of 4x4 pixel SiPM array reducing the 16 pixel outputs of the photodetector to 4 position signals. The 4 position signals were digitized using free running Analog to Digital Converters. The ADCs sampling rate was 50 MHz. An FPGA (Spartan 6 LX150T) was used for triggering and digital signal processing of the pulses. Experimental evaluation was carried out with 22Na radioactive source and the parameters studied where energy resolution and peak to valley ratio.
The first preliminary results of the evaluation shows a clear visualization of the discrete 2x2x5mm^3 LFS-3 scintillator elements. The mean peak to valley ratio of the horizontal profiles on the raw image was measured equal to 11 while the energy resolution was calculated equal to 30% at the central pixels.
Stratos David(Department of Biomedical Engineering, Technological Educational Institute of Athens, Athens, Greece.)
Evaluation of Large-Area, Low-Noise, Arrays of SiPMs
In this work we present the first evaluation results of an array of 12x12 SiPMs MicroFC-30035-SMT from SensL. These sensors are basically identical to those custom fabricated for the brain PET insert of the MindView project, except for the larger package. Both the C-Series and MindView parts are built with the same principle resulting on low dark noise contributions. These arrays cover an active area of approximately 5x5cm2 with a pitch of 4.2mm.
We have especially evaluated the 12x12 MicroFC array with monolithic scintillators. The new results are compared to former findings with the B-Series arrays. In the tests shown here, 10 mm thick black-painted crystals are used, which exit surface dimensions matches the photosensor active area. The photosensor blocks are always run at a stable temperature in the range of 20-22C (+/- 0.05C). Typical operation bias of the arrays was 30V, inferring about 600 kHz dark counts rate for each SiPM (67 kcps/mm2). A resistive readout has been designed to provide information for each row and column of the SiPMs matrix. Thus, 24 signals are being digitalized, with 250 ns integration time.
9x9 Na-22 collimated sources are used in the experiments. The sources have dimensions of 1mm in diameter and 1 mm height, and the collimators are 1.2mm aperture. Spatial resolution results (FWHM) along the crystal surface below 2.5mm, including source dimensions, have been found. These values are significantly improved compared to 3.5mm obtained with the B-Series in the past. At a distance of 20mm off-center, the system shows a negligible edge effect. These tests also showed a good energy resolution in the range of 16-17%.
Antonio Gonzalez(Institute for Instrumentation in Molecular Imaging, i3M-CSIC)
Image Artifacts from MR-Based Attenuation Correction in Dedicated PET/MR Breast Coil for PET/MR Mammography
Purpose: We evaluated the artifacts in segmentation-based attenuation correction maps (μ-maps) of hybrid positron emission tomography/magnetic resonance (PET/MR) mammography using dedicated PET/MR breast coil in breast cancer patients. Materials and Methods: Attenuation map of hybrid F-18 FDG PET/MR mammography in 38 patients diagnosed with invasive breast carcinoma were retrospectively inspected for artifacts. The artifacts were subdivided into 2 groups with minor (group A) and major artifacts (group B) on the basis of their severity. The impact of μ-map artifacts on PET interpretation was evaluated qualitatively via visual analysis as well as quantitatively by comparing SUVmax of breast cancer between PET/MR mammography and whole body PET/MR. Results: Minor Attenuation map artifacts were found in 22 patients and major artifacts in 16 patients. Minor artifacts were field of view edge artifacts, lung boarder artifacts, small body contour artifacts, respiratory artifacts and trachea artifacts. Major artifacts were body contour artifact with missing dorsal body contour including both lungs (n=10), left lung (n=5) and wide expanded areas around breast and chest (n=1). All FDG-avid malignant mass were not affected by artifacts on visual PET interpretation. SUVmax in PET/MR mammography and whole body PET/MR in group A and B were 8.31±6.31, 6.15±4.20, 4.75±3.70 and 4.70±4.10, respectively. The changes in group A and B was 31.11% and 14.08%, respectively. Quantitatively, major μ-map artifacts led to significant SUVmax changes (p<0.001). No change in diagnosis was caused by μ-map artifacts. Conclusions: Major attenuation map artifacts that occur in a considerable percentage of hybrid PET/MR mammography have the potential to falsify PET quantification. However, there was no change in clinical diagnosis due to μ-map artifacts.
Ihnho Cho(Department of nuclear medicine, Yeungnam University Hospital)
Initial Reconstruction Results from a Simulated Adaptive Small Animal C Shaped PET/MR Insert
Traditionally, most clinical and preclinical PET scanners, rely on full cylindrical geometry for whole body as well as dedicated organ scans, which is not optimized with regards to sensitivity and resolution.
Several groups proposed the construction of dedicated PET inserts for MR scanners, rather than the construction of new integrated PET/MR scanners. The space inside an MR scanner is a limiting factor which can be reduced further with the use of extra coils, and render the use of non-flexible cylindrical PET scanners difficult if not impossible.
The incorporation of small SiPM arrays, can provide the means to design adaptive PET scanners to fit in tight locations, which, makes imaging possible and improve the sensitivity, due to the closer approximation to the organ of interest.
In order to assess the performance of such a device we simulated the geometry of a C shaped PET, using GATE. The design of the C-PET was based on a realistic SiPM-BGO scenario. In order reconstruct the simulated data, with STIR, we had to calculate system probability matrix which corresponds to this non standart geometry. For this purpose we developed an efficient multi threaded ray tracing technique to calculate the line integral paths in voxel arrays. One of the major features is the ability to automatically adjust the size of FOV according to the geometry of the detectors.
The initial results showed that the sensitivity improved as the angle between the detector arrays increases, thus better angular sampling the scanner's field of view (FOV). The more complete angular coverage helped in improving the shape of the source in the reconstructed images, as well. Furthermore, by adapting the FOV to the closer to the size of the source, the sensitivity per voxel is improved.
Nikos Efthimiou(Technological Educational Institute of Athens)
Long-Term Stability of the MR System of the Philips Ingenuity TF
The Philips Ingenuity TF is a sequential PET/MR with an Achieva 3T X-series MR and Gemini TF PET system connected with a rotating table. Both the PET and MR systems are designed to minimize mutual system interference.
However, a longitudinal study concerning the stability of the MR system has not been conducted before. The stability of the MR system affects diffusion weighted imaging (DWI), diffusion tensor imaging (DTI) and functional MRI (fMRI), especially in long-term and multi-center studies. In addition, the variation of geometric distortions and consistency of MR image quality is important for clinical studies and radiotherapy planning.
The long-term stability of the MR system was monitored by weekly quality control (QC) scans during one year. For measuring DWI, DTI and fMRI stability, protocols from fBIRN and vendor QA were implemented by using a spherical agar phantom and a liquid sphere phantom. For measuring the variations of image quality, ACR phantom measurements were performed.
For the fBIRN and vendor QA protocols, automatic QC programs provided by the consortium and manufacturer were used. For the ACR phantom, an automatic quality control measurement was developed in MATLAB 2011b.
Analysis of the QC scans did not show any significant variations with the fBIRN, vendor QA or ACR protocols. Thus, the MR system of the Ingenuity TF was deemed to be stable in the longitudinal study. Automated analysis of QC measurements was deemed necessary for implementing multiple, weekly measurements for PET/MR.
Jarmo Teuho(Turku PET Centre)
Measuring the Mutual Effects Between a CZT Detector and MRI for the Development of a Simultaneous MBI/MRI Insert
While mammography is the gold standard for breast cancer screening, it suffers from poor sensitivity in women with dense breast tissue. Both breast MRI and molecular breast imaging (MBI) have been used as secondary imaging techniques. However, breast MRI suffers from low specificity and low sensitivity in MBI. A CZT based detector system has been developed with the goal of simultaneous MBI/MRI imaging to address the shortcomings of each modality. The performance of each modality needs to be addressed separately and together. The CZT system is comprised of four Redlen CZT modules tiled in a 2x2 array. Each module consists of 256 pixels and feature a built-in on-board ASIC and FPGA. A custom digital readout circuit board was designed to interface the four modules with a microcontroller to a PC.
MR images were acquired with a 3T GE Discovery MR750 and Hologic breast coils. A gradient echo imaging sequence was used for all image acquisitions. A tissue-mimicking phantom with a plastic grid insert (1 cm spacing) was used to evaluate geometric accuracy with the CZT detectors in the MRI bore. The average distance between the grid markers was 1±0.2cm indicating negligible geometric distortion. Field maps were generated with a uniform phantom to quantify the effect on magnetic field homogeneity. Early results indicate a significant distortion (~10ppm) in the magnetic field closest to the coil. Further analysis of the MR images will determine the extent of image quality degradation.
A flood map of Tc-99m was acquired to evaluate and implement an energy correction map and a uniformity map. In the absence of a magnetic field, the mean energy resolution at 140keV was 6.3%. After fully characterizing the uniformity, geometric accuracy and sensitivity, the same metrics will be evaluated in the MRI bore.
Ashley Tao(McMaster University)
New Nontoxic Double Information Magnetic and Fluorescent MRI Agent.
Today sensitivity of the MRI is not enough compared to the nuclear methods, such as positron emission tomography and single photon emission computed tomography.Challenging, its extension to the nanometre scale could provide a powerful new tool for the nanosciences and nanomedicine.To achieve this potential, innovative new detection strategies are required to overcome the severe sensitivity limitations of conventional inductive detection techniques In this regard, we perform embodiment of nanodiamonds in dendrimer matrix as additional fluorescent optical and magnetic (together with Gd (III)) imaging modalities of the MRI. New hybrid system composed of dendrimer-gadolinium Gd (III) - nanodiamond as a new contrast agent for MRI was studied. Poly(propilene-imine) PPI and poly(amidoamine) PAMAM dendrimers with fixed size of nanocavities will be used as host material to protect organism against the toxicity and also to increase relaxivity of contrast agent (resulting in the increases MRI resolution). Nanodiamond as biocompatible platform to functionalize the contrast agent will be used. This bimodal hybrid system enables to use smaller amount of the contrast agent and could permit the decrease of the lateral toxicity. This bimodal hybrid system as MRI agent is providing double information (magnetic and fluorescent) about the damaged cell.
Aim: investigation of new hybrid system composed of dendrimer-gadolinium Gd(III)-nanodiamond as a new contrast agent to improve the MRI resolution and to reduce lateral toxicity in comparison with today used. The main idea is to use this bimodal contrast agent allowing more efficient performance of the MRI with attractive
biological applications in diagnosis and therapy. In this report structural investigations by SEM and TEM, spectroscopic studies by Raman scattering, absorption, fluorescence and magnetic features by EPR measurements are discussed.Obtained results are demonstrating great potential of this bimodal imaging agent with unique magnetic and optical imaging capabilities.
Rimas Vaisnoras(Crystals Laboratory,Institute of Science and Technology, Lithuanian University of Educational Sciences, Lithuania)
Performance Evaluation of Two SiPMs Arrays Coupled to Pixelated Scintillations for PET/MR Applications
The purpose of this study is to investigate the behavior of the new generation of SensL SiPM arrays, ArrayB and ArrayM, for PET/MR applications.
The evaluation of the SiPMs performance underwent with pixelated GaGG and BGO scintillators with 2x2x5mm3 pixel size and various coupling schemes for 511keV and 662keV energies. To acquire raw images, we used a symmetric resistive voltage division network and the 4x4 SiPMs anodes reduced to 2X and 2Y position signals. A FPGA Spartan 6 LX150T was used for triggering and digital processing of the pulses acquired using free running ADCs.
The first step of our work was optimization of the bias voltage of the two SiPM arrays. The optimal bias voltage is a tradeoff between high photon detection efficiency and low excess noise factor. The SiPMs were coupled to homogeneous 16x16x10mm3 CsITl scintillator and irradiated with 137Cs source. The energy resolution calculated in overvoltages between 26.5V and 30.5V for ArrayB and between 28.3V and 31.3V for ArrayM. The bias voltage with the best energy resolution was used for the evaluation of the SiPMs.
The clear visualization of the GaGG and BGO crystal elements is expressed quantitatively by the mean peak-valley ratio of a horizontal profile in the raw images. The best optical coupling for the BGO was 2mm thick glass. In the case of the GaGG 1mm thick glass was adequate. The mean energy resolution of the GaGG scintillator is about two times better than the BGO for both type of SiPMs, after applying correction for their non-linear response. The low light output of the BGO scintillator in comparison with the GaGG as well as different emission spectra and the different PDE of the two types of SiPMs explain the differences in the behavior of the tested SiPMs arrays.
Maria Georgiou(Technological Educational Institute of Athens)
PET/MR and SPECT/MR Multimodal Imaging Constructs: Direct Radiolabelling of Silica Shell Iron Oxide Nanorods for Use in Liver Imaging and Potential for Hyperthermia Therapy
Superparamagnetic iron oxide nanoparticles (SPIONs) are used as T2 magnetic resonance (MR) contrast agents. Nanorods (NRs) offer an interesting alternative to the more widely used nanospheres as they have enhanced T2 relaxivities. The combination of MRI with nuclear imaging modalities such as positron emission tomography (PET) or single photon emission computed tomography (SPECT) increases the data available from a single diagnostic scan (e.g. quantification, multiple image overlay). Radiolabelling of SPIONs allows high sensitivity nanoparticle biodistribution data which can both aid in future construct design and be used directly for precise liver lesion imaging.
In this work, we report the synthesis and characterisation of silica shell iron oxide NRs functionalised with varying ratios of polyethylene glycol (PEG) and the tetrazamacrocyclic chelator, DO3A. Direct and facile radiolabelling of the constructs with the radioisotope gallium-68 (t1/2 = 68 min) proceeded with quantitative radiochemical yields in 15 min and no evidence of radioisotope dissociation was observed after 3 h in both serum and in competition with apo-transferrin. Interestingly, it was observed that neither the radiolabelling process nor stability in vitro or in vivo was compromised by the absence of the bifunctional chelating moiety. Consequently, silica shell NRs with 100 % PEG coating were evaluated for potential use as SPECT/MR imaging agents; direct radiolabelling with technetium-99m (t1/2 = 6.02 h) proceeded with analogous radiochemical yields and stabilities. In vivo imaging studies showed rapid liver uptake with high T2 contrast, demonstrating the application of silica shell iron oxide NRs as bimodal PET/MR and SPECT/MR liver imaging agents. Preliminary magnetic hyperthermia evaluation indicates the potential future use of the constructs developed as multimodal theranostic agents.
Hayley Bignell(University of Hull)
PET/MR Attenuation Correction in Brain Imaging Using a Continuous Bone Signal Derived from UTE
In the absence of transmission sources in combined clinical PET/MR systems, MR images are used for MR-based attenuation correction (MRAC). The main challenge in MR-AC is to separate the bone and air, as neither have a signal in the MR images. In the attenuation maps supplied by the vendor, a single value is assigned to bone using an ultra-short echo time (UTE) MR sequence. The purpose of this study was to develop a new multi-class segmentation-based MR-AC method, employing Continuous-Bone-using-R2* (MRAC_CBuR2*), and evaluate it on a large patient cohort.
METHODS. 53 [18F]-FDG PET/MR brain patients were included in this study. MRAC was based on an aligned CT (MRAC_CT, used as reference), standard MRAC_UTE and MRAC_CBuR2*. Our method segments the air, brain, CSF and soft tissue voxels on the UTE images, and uses a mapping of R2* values to HU to measure the density in bone voxels. Aligned anatomical masks are used to improve accuracy in noisy regions. Region-based analysis was performed using ICBM 2009a brain atlas with anatomical labels pre-defined.
RESULTS. Using CBuR2*, 82% of the voxels in the brain are within ±5% of PET_CT, compared to 27% when using UTE. Using our method, there are clear improvements over UTE. The average error over the full brain is 0.8% (±1.7%), compared to -7.1% (±2.4%) in UTE. Of note, the maximum error in the cerebellum is -15% and 7% in UTE and CBuR2*, respectively.
CONCLUSIONS. The proposed method uses the available UTE images to segment tissue classes, and uses the R2* map to measure a continuous bone signal. The improvement over the vendor provided UTE reduces both the global and local error on the reconstructed PET images.
Claes Ladefoged(Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet Copenhagen, DK)
Preliminary Evaluation of MRI-Derived Input Function for Quantitative Measurement of Glucose Metabolism in an Integrated PET-MRI
PET semi-quantitative methods such as relative uptake value can be robust but offer no biological information and do not account for intra-subject variability in tracer administration or clearance. Simultaneous multimodal measurements that combine PET and MRI not only permit crucial multiparametric measurements, it provides means of applying tracer kinetic modelling without the need for serial arterial blood sampling. In this study we adapted an image-derived input function (IDIF) method to improve characterization of glucose metabolism in an ongoing dementia study. Here we present preliminary results in a small group of frontotemporal dementia patients and controls.
IDIF was obtained directly from dynamic PET data guided by regions of interest drawn on carotid vessels on high resolution T1-weighted MR Images. IDIF was corrected for contamination of non-arterial voxels. A validation of the method was performed in a porcine model in a PET-CT scanner comparing IDIF to direct arterial blood samples. Metabolic rate of glucose (CMRglc) was measured voxel-by-voxel in gray matter producing maps that were compared between groups. Net influx rate (Ki) and global mean CMRglc are reported.
A good correlation (r = 0.9 p<0.0001) was found between corrected IDIF and input function measured from direct arterial blood sampling in the validation study. In 3 FTD and 3 controls, a trend towards hypometabolism was found in frontal, temporal and parietal lobes similar to significant differences previously reported by other groups. The global mean CMRglc and Ki observed in control subjects are in line with previous reports. In general, kinetic modelling of PET-FDG using an MR-IDIF can improve characterization of glucose metabolism in dementia. This method is feasible in multimodal studies that aim to combine PET molecular imaging with MRI as dynamic PET can be acquired along with multiple MRI measurements.
Udunna C Anazodo(Lawson Health Research Institute, Department of Medical Biophysics, Western University, London, ON, Canada)
SiPM-MAROC Gamma-Camera Prototype with Monolithic NaI(Tl) Scintillator
A full-body gamma-camera based on SiPM readout is currently under development as a part of MEPHI R&D activity supported in the framework of Russian Megagrants program. A goal of this development is a fast upgrade of existing medical equipment with minor changes in a system design and construction in order to combine SPECT and MR instruments.
A monolithic NaI(Tl) scintillator commonly used for conventional PMT-based gamma-cameras has been chosen for this study. SiPMs will be coupled with the scintillator via an optical guide. To cover scintillator surface thousands of SiPMs are required, together with multichannel front-end electronics. That means that readout electronics have to be very compact, with low power consumption and low cost. 64 – channel ASIC MAROC from Weeroc provides individual readout of each SiPM and has been considered as the best choice among electronics solutions available on the market. As the photodetector parameters are the key issues here, KETEK SiPMs with high detection efficiency, low crosstalk and low noise have been chosen for this study.
In order to study the proposed detection system in detail and obtain detector module parameters, required for MC simulation, a 64-channel small prototype with 6x6mm2 SiPMs has been constructed and tested. SiPMs in SMD packages have been assembled as a matrix of 8x8 elements and readout by MAROC-based board. Prototype has been tested with different shape NaI(Tl) scintillators and gammas with different energy.
Dedicated algorithms for extraction of gamma-event’s energy and position are under development. They are based on fitting a matrix of individual SiPMs responses by an analytical function F(x,y). They will be tested with GEANT-simulated events and experimental data.
Development of the next (engineering) prototype of SiPM’s module for gamma-camera will be started soon.
Dmitry Philippov(National Research Nuclear University MEPhI (Moscow Engineering Physics Institute))
The Potential of TOF PET-MRI for Reducing Artifacts in PET Images
Aim: Here we evaluated the potential of TOF PET/MRI to reduce various PET image artifacts, by comparing the images to non-TOF PET/MRI, TOF PET/CT and non-TOF PET/CT.
Methods and materials: All patients underwent a single-injection of FDG, followed first by PET-CT and subsequently by PET-MRI scan. The PET/CT exams were performed using a GE Discovery 690 PET/CT scanner The PET/MRI images were acquired on a GE Signa PET/MRI scanner. All PET images were reconstructed with and without the TOF data. Visual analysis of these series was performed for dental metal / breathing artifcats and 3) artifacts caused by high excretion of FDG in the bladder. PET image quality was evaluated using a 3-point scale (1 - clinically significant artifact; 2 – non clinically-significant artifact; and 3 - no artifact).
Results: Data from 18 oncologic patients (mean ± SD age: 55 ± 10 years; female 7, male 11) were used. The average scores of TOF PET/MRI, non-TOF PET/MRI, TOF PET/CT and non-TOF PET/CT for dental artifacts were 3.0, 2.8, 2.4 and 2.3, respectively; for breathing artifacts were 3.0, 2.5, 2.5 and 2.3, respectively; and for pelvic artifacts were 2.9, 1.6, 2.1 and 1.4, respectively. TOF PET/MRI had the highest image quality scores among the 4 series of PET data analyzed for these types of artifacts.
Conclusion: TOF PET/MRI showed promising results in reduction of various PET artifacts in this cohort, when compared to non-TOF PET/MRI, TOF PET/CT and non-TOF PET/CT. This may be due to the better timing resolution (<400 ps) for the PET/MR system compared to the PET/CT system (>600 ps).
Andrei Iagaru(Stanford University)
Ultra Fast, Accurate PET Image Reconstruction for the Siemens Hybrid MR/BrainPET Scanner using Raw LOR Data
Fast PET image reconstruction algorithms usually use a Line-of-Response (LOR) preprocessing step where the detected raw LOR data are interpolated either to evenly spaced sinogram projection bins or alternatively to a generic projection space as for example proposed by the PET Reconstruction Software Toolkit (PRESTO) . In this way, speed-optimised, versatile geometrical projectors can be implemented for iterative image reconstruction independent of the underlying scanner geometry. However, all strategies of projection data interpolation unavoidably lead to a loss of original information and result in some degradation of image quality. Here, direct LOR reconstructions overcome this evident drawback at cost of a massively enhanced computational burden. Therefore, computational optimisation techniques are essential to make such demanding approaches attractive and economical for widespread usage in the clinical environment.
In this paper, we demonstrate for the Siemens Hybrid MR/BrainPET with 240 million physical LORs that a very fast quantitative direct LOR reconstruction can be realised using a modified version of PRESTO. Now, PRESTO is also capable to directly use sets of symmetric physical LORs instead of interpolating LORs to a generic projection space. Exploiting basic scanner symmetries together with the technique of Single Instruction Multipe Data (SIMD) and Simultaneous Multi-Threading (SMT) results in an overall calculation time of 2-3 minutes per frame on a single multi-core machine, i.e. neither requiring a cluster of mutliple machines nor Graphics Processing Units (GPUs).
Session 9 - MR-PET and MR-SPECT software and quantificationRoom Maria Luisa
Room Maria Luisa
Jorge Cabello(Klinikum rechts der Isar (TUM))
CT Synthesis in the Head & Neck Region for PET/MR Attenuation Correction: an Iterative Multi-atlas Approach
In this work, we propose to tackle the problem of attenuation correction in the head & neck by synthesising CT from MR images using an iterative multi-atlas approach.
The proposed method relies on pre-acquired T2-weighted MRI and CT images of the neck. For each subject, the MRI is non-rigidly mapped to the CT.
To synthesise a pseudo CT, all the MRIs in the database are first registered to the target MRI. This registration consists of a robust affine followed by a non-rigid registration. The pseudo CT is obtained by fusing the mapped atlases according to their morphological similarity to the target.
In contrast to CTs, T2 images do not provide a good estimate of the bone location. Combining multiple modalities at both the registration and image similarity stages is expected to provide more realistic mappings and to reduce the bias. An initial pseudo CT (pCT) is combined with the target MRI to form a MRI-pCT pair. The MRI-pCT pair is registered to all the MRI-CT pairs from the database. An improved pseudo CT is obtained by fusing the mapped MRI-CT pairs according to their morphological similarity to the target MRI-pCT pair.
Results showed that the proposed CT synthesis algorithm based on a multi-atlas information propagation scheme and iterative process is able to synthesise pseudo CT images in a region challenging for registration algorithms. The results also demonstrate that the robust affine decreases the absolute error compared to the classic approach and that the bone refinement process reduces the bias in the bone region. The proposed method could be used to correct for attenuation PET/MR data, but also for dosimetry calculations in the context of MR-based radiotherapy treatment planning.
Ninon Burgos(University College London)
Simultaneous Reconstruction of Attenuation and Activity in ToF PET/MRI with Additional Transmission Data
In Time-of-Flight PET/MRI systems accurate attenuation correction, based on the MRI image, is not straight forward. An alternative is attenuation correction based on emission data only. This is for instance done by simultaneous reconstruction of attenuation and activity with the MLAA algorithm, but the method as originally proposed has certain limits. The attenuation can only be determined up to a constant and in regions of low tracer uptake, the method results in less accurate attenuation values.
An adapted MLAA algorithm has been proposed to overcome this issues and was successfully applied on simulation studies. The so called MLAA+ algorithm uses regular PET emission data as well as transmission data. This transmission data is acquired after insertion of an annulus shaped transmission source into the scanner bore. The Time-of-Flight information allows to separate transmission and emission data in a simultaneous acquisition. With the transmission data, an MLTR-based reference attenuation image is reconstructed. Afterwards, this attenuation image is used in the MLAA+ simultaneous reconstruction of attenuation and emission as a reference.
We here propose the results of the reconstruction of patient data, based on the MLAA+ algorithm. In total, seven patients were scanned in a sequential PET/MRI scanner and afterwards in a CT scanner. The CT scan is used as an attenuation map to reconstruct the PET emission data with the well established MLEM algorithm. This reconstruction can be seen as the gold standard to which we can compare the MLAA and MLAA+ reconstructions. We can conclude that the MLAA+ algorithm results in better reconstructed emission and attenuation images as compared to the MLAA algorithm. If we compare the MLAA+ method to the gold standard, there is still room for improvement.
Ester D'Hoe(MEDISIP Medical Imaging and Signal Processing group, Ghent University, Belgium)
Imaging the Attenuation Coefficients of Positron Beams in Matter: Positron Attenuation Tomography
A new positron annihilation imaging modality is described that enables non-destructive measurement of the linear attenuation coefficients (LACs) of positron beams in heterogeneous materials. This positron attenuation tomography (PAT) technique utilizes a positron emission tomography (PET) system embedded within a uniform static magnetic field, such as is found in integrated PET/MRI scanners. A Ga68-generated positron beam constrained by a 3T magnetic field penetrates objects placed within the scanner. The positrons slow down and annihilate within the object. The resulting annihilation distribution is tomographically imaged by the PET camera. This image may be interpreted as a map of the product of the positron beam's flux and its LAC at each point in the volume. It is shown that under certain easily achieved conditions this image can be decomposed into separate maps of the flux and the LACs, without need for auxiliary measurements. Although these LACs may depend on both beam and material properties, a beam softening correction is demonstrated that effectively removes the dependence on beam variation, leaving a relative LAC that is characteristic of the material. Unlike x-ray, gamma-ray or other transmission techniques, PAT does not require the penetration of the beam entirely through the object. High resolution and high contrast images of positron beam LACs in objects may be produced over nearly the full range of the positron beam, which for Ga68 beta-rays in a 3T field is about 0.5 g/cm^2. The first examples of PAT images and an initial characterization of performance will be presented.
Heinz H. Coenen(Research Centre Juelich)
Development of Compact DOI-Measurable PET Detectors for Simultaneous PET/MR Imaging
It is critically needed yet challenging to develop compact PET detectors with high sensitivity and uniform, high imaging resolution for improving the performance of simultaneous PET/MR imaging, particularly for an integrated/inserted small-bore system. Using latest “edge-less” SiPM arrays for DOI measurement using the design of dual-ended-scintillator readout, we developed several compact PET detectors suited for PET/MR imaging. Each detector consists of one LYSO array with each end coupled to a SiPM array. Multiple detectors can be seamlessly tiled together along all sides to form a large detector panel. Detectors with 1.5x1.5 and 2.0x2.0 mm crystals at 20 or 30 mm lengths were studied. Readout of individual SiPM or capacitor-based signal multiplexing was used to transfer 3D interaction position-coded analog signals through flexible-print-circuit cables to dedicated ASIC front-end electronics to output digital timing pulses that encode interaction information. These digital pulses can be transferred to, through standard LVDS cables, and decoded by a FPGA-based data acquisition positioned outside the MRI scanner for coincidence event selection. Initial detector performance measurement shows excellent crystal identification even with 30 mm long crystals, ~18% and 2.8 ns energy and timing resolutions, and around 2-3 mm DOI resolution. A large size detector panel can be scaled up with these modular detectors and different PET systems can be flexibly configured with the scalable readout electronics and data acquisition, providing an important design advantage for different system and application requirements. It is expected that standard shielding of detectors, electronics and signal transfer lines can be applied for simultaneous PET/MR imaging applications, with desired DOI-measurement capability to enhance the PET performance and image quality.
Yiping Shao(University of Texas MD Anderson Cancer Center)
Imaging Patients with Breast and Prostate Cancers Using Combined 18F NaF/18F FDG and TOF simultaneous PET/ MRI
Introduction: Here we prospectively compared the combined 18F NaF/18F FDG PET/ MRI against 99mTc-MDP in patients with breast and prostate cancers.
Methods: Twelve patients referred for 99mTc-MDP bone scans were prospectively enrolled from Oct 14 - Jan 15. The cohort included 6 men with prostate cancer and 6 women with breast cancer, 41 – 85 year-old (average 63 ± 15). 18F NaF (0.7-2.2 mCi, mean: 1.33 mCi) and 18F FDG (3.9-5.2 mCi, mean: 4.6 mCi) were subsequently injected from separate syringes. The PET/MRI was done 6-12 days (average 9.3 ± 3.2) after bone scan. The whole body MRI protocol consisted of T2-weighted, DWI, and contrast-enhanced T1-weighted imaging. Lesions detected with each test were tabulated and the results were compared.
Results: All patients tolerated the PET/MRI exam, and PET image quality was diagnostic despite the marked reduction in the administered dosage of radiopharmaceuticals (80% less for 18F NaF and 67% less for 18F FDG). Five patients had no bone metastases identified on either scans. Bone scintigraphy and PET/MRI showed osseous metastases in 7 patients, but more numerous bone findings were noted on PET/MRI than on bone scintigraphy in 3 patients. Lesions outside the skeleton were identified by PET/MRI in 2 patients.
Conclusion: The combined 18F NaF/18F FDG PET/MRI is superior to 99mTc-MDP scintigraphy for evaluation of skeletal disease extent. Further, it detected extra-skeletal disease that may change the management of these patients, while allowing a significant reduction in radiation exposure from lower dosages of PET radiopharmaceuticals administered. A combination of 18F NaF/18F FDG PET/MRI may provide the most accurate staging of patients with breast and prostate cancers prior to the start of treatment.
Andrei Iagaru(Stanford University)
Simultaneous Functional Imaging Using fPET and fMRI
Brain mapping of task-associated changes in metabolism with PET has been accomplished by subtracting scans acquired during two distinct static states . We have demonstrated that PET can provide truly dynamic information on cerebral energy metabolism using constant infusion of FDG and multiple stimuli in a single experiment . We demonstrate here that the functional PET (fPET-FDG) method accomplished simultaneously with fMRI, can enables the first direct comparisons in time, space and magnitude of hemodynamics and oxygen and glucose consumption.
The imaging studies were performed on a 3T Tim-Trio MR scanner modified to support an MR-compatible BrainPET insert. Ten healthy subjects were included. The total PET acquisition and infusion time was 90 minutes. We did 3 blocks of right hand fingers tapping for 10 minutes at 30, 50 and 70 minutes after the beginning of the PET acquisition. ASL and BOLD imaging were acquired simultaneously during the motor paradigm.
Changes in glucose utilization are easily observed as changes in the TAC slope of the PET data (FDG utilization rate) and in the derivative signal during motor stimuli in the activated voxels. PET and MRI (ASL, and BOLD) activations are largely co-localized but with very different statistical significance and temporal dynamic, especially in the ipsilateral side of the stimuli.
This study demonstrated that motor activation can be measured dynamically during a single FDG PET scan. The complementary nature of fPET-FDG to fMRI capitalizes on the emerging technology of hybrid MR-PET scanners. fPET-FDG, combined with quantitative fMRI methods, allow us to simultaneously measure dynamic changes in glucose utilization and hemodynamic, addressing vital questions about neurovascular coupling.
References :  Fox P.T. et al. Nature 1986 323.806-809  Villien M. et al. NeuroImage 2014 1053-8119
Stability of MR Brain-Perfusion Measurement Using Arterial Spin Labeling
Arterial spin labeling (ASL) is an MR technique for assessment of cerebral blood flow (CBF) that does not require use of contrast agents which makes it a less invasive alternative to the 15O-H2O-PET measurement. The repeatability of ASL has been studied extensively but mainly in young healthy volunteers. We have tested repeatability of ASL under realistic clinical conditions in elderly brain tumor patients acquired with a Philips Ingenuity TF PET/MR in the context of an ongoing 11C-Methionine PET/MR study. Twenty three patients (age 54.8±13.0 y) were scanned on two or more session. The patients underwent 6 weeks of concurrent radiochemotherapy with Temozolomide between the first session and second measurement. The mean relative difference of gray matter CBF was 18.6% between the first two session and 13.0% for the second session and further on. The mean gray matter CBF was 46.6±7.2 mL/min/100 g on the first sessions and there was a significant decrease of 9.8% between first and second session (p=0.027). In summary, the ASL presents measurement of CBF with reasonable repeatability also in elderly patients under clinical conditions when it is not possible to control for all sources of variation. Significant decrease of CBF in healthy tissue was observed after the radiochemotherapy. Prospectively, the ASL data together with the also acquired 11C-Methionine PET will be evaluated regarding their separate and combined ability to predict patient outcome and effectiveness of the performed radiochemotherapy.
Jan Petr(Helmholtz-Center Dresden-Rossendorf, PET Center, Institute of Radiopharmaceutical Cancer Research)
Impact of Atlas-CT-Based Bone Anatomy Compensation on MR-Based Attenuation Correction for Brain PET Imaging in a Time-of-Flight PET/MRI System: A Direct Comparison to a Patient-CT-Based Approach
An atlas-CT-based bone-anatomy compensation for MR-based attenuation correction (MRAC) in brain PET/MRI imaging is a current standard. However, the impact of an anatomical difference has not been clinically evaluated. Thus, we aim to evaluate the impact of the anatomical dissimilarity on MRAC. Whole-body FDG-PET/CT followed by PET/MRI were performed for twelve patients in an integrated TOF PET/MRI system. The MRAC utilized an atlas-CT (MRAC-atlas) as well as a patient-specific-CT (MRAC-patient) to produce AC maps (pseudoCT). Instead of using atlas-CT, the MRAC-patient approach derived pseudoCT from patient-specific-CT aligned to MR. For quantitative evaluation, CTAC was considered as gold standard for AC, and PET mean activity concentration values were measured and compared in eight 10 ml volumes-of-interest (VOI). PET activity concentration with MRAC, compared to CTAC, were systematically underestimated on average by 0.63±0.34 kBq/ml (4.0±2.2%) and 0.22±0.21 kBq/ml (1.4±1.5%) for the MRAC-atlas and the MRAC-patient, respectively: using the MRAC-atlas, the error was increased to 0.41±0.25 kBq/ml (2.6±1.8%) on average (p≈0). However, the error increase was patient-dependent (highest: 5.7% vs. lowest: 0.3%) and VOI dependent (highest 3.1% vs. lowest: 1.9%). For the first time, the atlas-CT-based MRAC was compared to the patient-specific-CT-based MRAC for brain PET imaging in an integrated TOF PET/MRI system. Overall, the MRAC-atlas achieves quantification accuracy similar to CTAC with a small but measurable difference of 5% in values, which is 2.6% higher than the error of the MRAC-patient.
Simultaneous Acquisition of Dynamic PET-MRI: Arterial Input Function Using DSC-MRI and [18F]-FET
Aim: This work focuses on the study of simultaneous dynamic MR-PET acquisition in brain tumour patients. MR-based perfusion-weighted imaging (PWI) and PET [18F]-FET are dynamic methods, which allow to evaluate tumour metabolism in a quantitative way. In both methods, arterial input function (AIF) is necessary for quantification. However, the AIF estimation is a challenging task. In this work, we explore the possibilities to combine dynamic MR and PET AIF. Materials/Methods: Data of 11 brain tumour patients was acquired in a hybrid 3TMR-BrainPET (Siemens). The PET acquisition took one hour while several MRI sequences were simultaneously acquired, including DSC-MRI (Dynamic Susceptibility Contrast MRI) and MPRAGE. Two DSC-MRI sequences for PWI were investigated: 1) echo planar imaging (EPI) and 2) EPI Keyhole (EPIK). For three patients venous blood samples were available at later times. For DSC-MRI AIF estimation an automatic in-house algorithm was used and for PET AIF estimation an automatic segmentation of the carotid arteries in MPRAGE images was used. Furthermore, several anatomical-based partial volume correction (PVC) methods were applied to images using the carotid artery segmentation. Results: The gamma fitting is useful in MR studies where the first pass of the bolus is used for quantification and can also aid the estimation of the peak of the PET AIF due to the similar peak shape. For the later PET frames, a three exponential model provided a good fitting. The iterative Yang PVC provided results closer to the venous blood samples than the other PVC methods. Conclusion: PET quantification can be improved by using MR data for: automatic carotid segmentation, partial volume correction and estimation of AIF using dynamic MRI. Furthermore, the estimation of MR AIF using EPIK instead of EPI was more robust and consequently PET AIF.
Christoph Lerche(Forschungszentrum Jülich GmbH), Dennis Schaart(Delft University of Technology)
[18F]FDG PET/MRI Of Patients With Chronic Pain Alters Management: Early Experience
The chronic pain sufferer is currently faced with a lack of objective tools to identify the source of their pain. The overarching goal is to develop clinical [18F]FDG PET/MRI methods to more accurately localize sites of increased neuronal and muscular metabolism or inflammation as it relates to neurogenic sources of pain and to ultimately improve outcomes of chronic pain sufferers. The aims are to 1) correlate imaging findings with location of pain symptomology, 2) predict location of symptoms based on imaging findings alone and 3) to determine whether the imaging results affect current management decisions.
METHOD: Six patients suffering from chronic lower extremity neuropathic pain (4 complex regional pain syndrome, 1 chronic sciatica and 1 neuropathic pain) have been imaged with a PET/MRI system (time-of-flight PET; 3.0T bore) from mid thorax through the feet. All patients underwent PET/MR imaging one hour after a injection of 10mCi [18F]FDG. Two radiologists evaluated PET/MR images (one blinded and the other unblinded to patient exam/history).
RESULTS: ROI analysis showed focal increased [18F]FDG uptake in affected nerves and muscle (approx 2-4 times more) over background tissue in various regions of the body in 5 of 6 patients at the site of greatest pain symptoms and other areas of the body (SUVmax of Target 0.9-4.2 vs. Background 0.2-1.2). The radiologist blind to the patient history/exam was able to correctly identify side/location of the symptoms in 5 out of 6 patients. Imaging results were reviewed with the referring physician, who then determined whether a modification in the management plan was needed: 1/6 no change, 2/6 mild modification (e.g., additional diagnostic test ordered) and 3/6 significant modification.
DrSandip Biswal(Stanford University)
A Monte Carlo Study of Scattered and Random Coincidences for MADPET-4
MADPET4 is a high resolution PET insert under development for use in a 7 T MR. To fully exploit the capabilities of the insert, a good understanding of the physical interactions, which take place in the active and passive components of the insert, is necessary. The goal of this study was to investigate the effects of different physical interactions in an accurate model of MADPET4 using Monte Carlo (MC) simulations. The main focus of the study was on the impact of the different active and passive components of the system on the amount of random and scattered events, including scattering in the passive components and between the crystals. The influence of low energy thresholds (50-350 keV) and different geometrical conditions in the coincidence sorting process was of particular interest. The effect of including triple coincidences was also considered in the present study. The highest sensitivity with a 3.7 MBq point source at the center of the scanner with an energy threshold of 50 keV and no geometrical condition was 3.4% with having only the crystals in the model and 3.6% with the complete model including all system components. This is expected to be a result of having scattering in the structure, which increases the probability of detecting the scattered photons in their neighbor crystals. Including triple coincidences showed no benefit for energy thresholds above 250 keV. However, low energy thresholds provided a relative gain in sensitivity, reaching 12-26% for 200 keV and a maximum of 25-71% at 50 keV.
Jorge Cabello(Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany), Negar Omidvari(Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany)
A Novel Method for Y Photons Depth of Interaction Discrimination on Monolithic LYSO Crystals for Brain PET/MRI
The MindView European Project pursues the development of a high efficiency and high resolution brain dedicated PET detector, simultaneously working with a Magnetic Resonance Imaging (MRI) system. Since the PET scanner is based on a small diameter ring and on thick monolithic scintillation crystals to assess high efficiency, the parallax error related to off-center positron annihilation is a critical issue. The Depth of Interaction (DoI) discrimination can reduce the blurring due to this phenomenon.
In this work, we propose a novel DoI estimator, based on the ratio of the integral of scintillation light distribution to its maximum (named N/I). In a preliminary way, by means of Monte Carlo simulation, we have validated the correlation between this parameter and the DoI. Furthermore, we have experimentally tested the capability of such DoI estimator on a monolithic 20mm-thick LYSO crystal optically coupled to a 12x12 silicon photomultipliers (SiPMs) array.
Thanks to the proposed method, it is possible to select interaction events coming from different depths of the crystal. The DoI discrimination capability has been confirmed by using a collimated slanted pencil-beam: the proposed estimator allows to produce different images coming from events belonging to different depths of the crystal. From the experimental results a DoI discrimination resolution ranging from 4mm to 6mm has been obtained. The proposed method is expected to reduce the parallax error and, consequently, the width of lines of response coming from off- center positron annihilation of about 70% respect to the method without DoI discrimination.
Marco Bettiol(Dept. of Molecular Medicine, Sapienza University of Rome)
A Practical Depth-of-Interaction PET/MR Detector with Dichotomous-Orthogonal-Symmetry Decoding
Conventional dual-end depth-of-interaction (DOI) PET detector readout requires two 2D SiPM arrays; with top and bottom SiPM reading the same pixel, there is information redundancy. We proposed a dichotomous-orthogonal-symmetric (DOS) dual-end DOI readout to eliminate this redundancy to significantly reduce SiPM usage, electronic channels, and heat load. Reflecting films are used within the scintillator array to channel light exiting the top along the X-direction, while light exiting the bottom is channeled along the orthogonal Y-direction. Despite the unidirectional channeling on each end, the top readout can provide X-Y information using two 1-D SiPM arrays; similarly, the bottom readout also provides X-Y information with two 1-D SiPM arrays. Thus four 1-D SiPM arrays (4xN) are used to decode XYZ to replace two 2D SiPM arrays (2NxN); SiPM usage is reduced from 2N**2 to 4N. Monte Carlo simulations (GATE) were carried out to study the XY decoding accuracy, energy resolution, and DOI resolution. Coupling the DOS-DOI design with a channel-decoding scheme, an array of 15x15 LSO (2.4x2.4x20mm pixels) can be decoded by 18 SiPMs (2 rows of nine 3x3mm SiPM) on top and 18 SiPMs at bottom, thus achieving a 10X reduction in SiPM usage, electronic channels and heat load. For BGO detectors, an 8x8 array (2.4x2.4x20mm pixels) can be achieved with 6.4X reduction. Simulations show 5-6mm DOI resolution, 0.45-0.96mm XY-decoding blurring, 20-24% energy resolution. This study shows the feasibility of the DOS-DOI design. Even comparing to non-DOI detectors, there is a 5X/3X SiPM reduction for LSO/BGO. The proposed detector may yield practical ultrahigh-resolution PET/MR systems with depth-of-interaction with a production cost below current non-DOI systems.
Prof.Wai-Hoi Wong(University of Texas MD Anderson Cancer Center)
Analysis and reduction of eddy current effects induced by tesseral end zonal gradient coils in different collimator geometries for SPECT/MRI integration
SPECT and MRI each have their respective advantages and limitations. Combining these two technologies in a synergistic manner allows researchers to exploit the strengths of both techniques but also result in disturbing eddy currents. In this paper, we studied the temporal variation of the induced magnetic field due to the transverse and longitudinal gradient coils, in a full-ring multi-pinhole collimator. We also investigated the effect of the ring geometry (hexagonal or pentagonal) on the resulting eddy currents and reduced the eddy currents by adding gaps between the collimators.
We modeled x, y, and z-gradient coils and different arrangements of the SPECT collimators using FEKO. We arranged the collimators in pentagonal and hexagonal arrangements and we added gaps between the collimators in the pentagonal arrangement. The setup was simulated with a broadband simulation from 0 to 10 kHz with a step of 400 Hz to cover the frequency range of the gradient on-off switching (a sinusoidal ramp from 500 mT/m to 0 mT/m within 0.25 ms). The collimator design contains 20 loftholes with 500-μm-diameter pinhole openings. The density of the collimator is equal to 17.31±0.10 g/cm^3, and the conductivity equal to 108 nΩ.m.
Simulations showed that the hexagonal geometry induces larger eddy currents. By adding relatively small gaps between the collimators (1.7 mm), the maximum value of the induced magnetic field is reduced by 50.6 % and 75.8 % for transverse and longitudinal gradient coils, respectively. As a result, the maximum value of the induced field is now less than 2 % of the applied gradient field.
MrAmine Samoudi(Ghent University/iMinds), MsKaren Van Audenhaege(MEDISIP, IBBT-IBiTech, Ghent University)
Assessment of the quality of brain regions and neuroimaging metrics as biomarkers of Alzheimer’s Disease
Alzheimer Disease (AD) is characterized by progressive cognitive decline and dementia. Earlier diagnosis and classification of different stages of the disease are currently the main challenges and can be assessed by neuroimaging. With this work we aim to evaluate the quality of brain regions and neuroimaging metrics as biomarkers of AD.
Multimodal Imaging Brain Connectivity Analysis (MIBCA) toolbox functionalities were used to study AD by T1weighted, Diffusion Tensor Imaging and 18FAV45 PET, with data obtained from the AD Neuroimaging Initiative database, specifically 12healthy controls (CTRL) and 33patients with early mild cognitive impairment (EMCI), late MCI (LMCI) and AD (11patients/group). The metrics evaluated were gray-matter volume (GMV), cortical thickness (CThk), mean diffusivity (MD), fractional anisotropy (FA), fiber count (FiberConn), node degree (Deg), cluster coefficient (ClusC) and relative standard-uptake-values (rSUV). Receiver Operating Characteristic (ROC) curves were used to evaluate and compare the diagnostic accuracy of the most significant metrics and brain regions and expressed as area under the curve (AUC). Comparisons were performed between groups.
The RH-Accumbens/Deg demonstrated the highest AUC when differentiating between CTRL-EMCI (82%), whether rSUV presented it in several brain regions when distinguishing CTRL-LMCI (99%). Regarding CTRL-AD, highest AUC were found with LH-STG/FiberConn and RH-FP/FiberConn (≈100%).
A larger number of neuroimaging metrics related with cortical atrophy with AUC>70% was found in CTRL-AD in both hemispheres, while in earlier stages, cortical metrics showed in more confined areas of the temporal region and mainly in LH, indicating an increasing of the spread of cortical atrophy that is characteristic of disease progression.
In CTRL-EMCI several brain regions and neuroimaging metrics presented AUC>70% with a worst result in later stages suggesting these indicators as biomarkers for an earlier stage of MCI, although further research is necessary.
MsTânia F. Vaz(Institute of Biophysics and Biomedical Engineering of the Faculty of Sciences of the University of Lisbon, Lisboa, Portugal / Lisbon School of Health Technology of the Polytechnic Institute of Lisbon, Lisboa, Portugal)
Biocompatible Branched Copolymer Nanoparticles Prepared by RAFT Polymerization as MRI /PET Bimodal Tracers
Stable branched copolymer nanoparticles of varying size (Dh = 20 – 35 nm) have been developed and employed as MRI nano-sized contrast agents. RAFT polymerization has been employed to prepare these novel nanoparticles possessing DO3A macrocycles within their cores and succinimidyl ester benzoate functionalities within their coronas. It has been demonstrated that these nanoparticles can chelate gadolinium and in vitro cytotoxicity studies using HK-2 cells established their negligible toxicity profile. In vivo MRI experiments showed that these nanoparticles have a high relaxivity and a long blood retention time. Xenograft experiments further illustrated the ability of these nanoparticles to perfuse and passively accumulate in tumor cells, presumably through the enhanced EPR effect. The presence of the succinimidyl ester benzoate functionalities within the nanoparticle coronas will permit future surface modification with fluorophores or targeting moieties to generate nanoparticles to study opportunities for bimodal imaging nano-probes or active cell targeting contrast agents. The chelation with PET radioisotopes (68Ga(III) or 64Cu(II)) can afford various PET tracers.
Chang-Tong Yang(Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore)
Clinical Evaluation of PET Image Quality as a Function of Acquisition Time in a New TOF-PET/MR Compared to TOF-PET/CT - Initial Results
The recently available integrated PET/MR imaging can offer significant additional advances in clinical imaging. The purpose of this study was to compare the PET performance between a PET/CT scanner and an integrated TOF-PET/MR scanner concerning image quality parameters and quantification in terms of SUV as a function of acquisition time (a surrogate of dose).
Five brain and five whole body patients were included in the study. The PET/CT scan was used as a reference and the PET/MR acquisition time was consecutively adjusted, taking into account the decay between the scans in order to expose both systems to the same amount of emitted signal. The acquisition times were then retrospectively reduced to assess the performance of the PET/MRI for lower count rates. Image quality, image sharpness, artifacts and noise were evaluated. SUV measurements were taken in the liver and in white matter to compare quantification.
Quantitative evaluation showed good correlation between PET/CT and PET/MR brain SUVs. Liver correlation was lower, with uptake underestimation in PET/MR, partially justified by bio-redistribution. The clinical evaluation showed that PET/MR offers higher image quality and sharpness with lower levels of noise and artefacts compared to PET/CT with reduced acquisition times for whole body scans [see attached file] while for brain scans there is no significant difference.
The PET-component of the TOF-PET/MR showed higher image quality compared to PET/CT as tested with reduced imaging times. However, these results account mainly for body imaging, while no significant difference were found in brain imaging. This overall higher image quality suggests that the acquisition time or injected activity can be reduced by at least 37% on the PET/MR scanner.
Konstantinos Zeimpekis(Nuclear Medicine, University Hospital Zurich)
Comparison of different tube-of-response (TOR) models for resolution recovery in PET image reconstruction for the Philips Ingenuity TF PET/MR
Recently, we have proposed a method for on-the-fly system matrix computation where the tube-of-response (TOR) is approximated as a cylinder with constant density (TOR-CD) and the cubic voxels are replaced by spheres. We could show that with this model the PET image quality can be notably improved compared to the vendor provided image reconstruction of our Philips Ingenuity-TF PET/MR. In this work we address the question whether image quality can be further improved by using a variable density TOR (TOR-VD).
The radial variability of TOR-VD was modelled by a Kaiser-Bessel function. Free parameters of this density model were used to optimize image properties regarding resolution, noise, and Gibbs artifacts. Additional, a TOR-VD model accounting for position dependent effects along the TOR caused by the finite solid angles of the detectors is under investigation. Phantom measurement were performed with a Philips Ingenuity-TF PET/MR scanner. Listmode data were reconstructed using TOR-CD and TOR-VD, respectively on two different grids with cubic voxel size of 2mm and 4mm. Image quality was assessed with resolution-noise curves and investigation of the radial position dependence of the spatial resolution.
For 2mm voxels, TOR-VD consistently yields a slight improvement of the investigated image quality measures compared to TOR-CD. For 4mm voxels both models lead essentially to the same results. These findings can be understood as a consequence of the relative size of voxel and TOR.
For typical whole body studies (4mm voxel size) a variable TOR does not improve image quality beyond what is achievable with a constant density TOR. For smaller voxel size the image quality can indeed be somewhat improved with a variable TOR but at the expense of drastically increased computation time.
DrFrank Hofheinz(Helmholtz-Center Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, PET Center)
Compatibility of Metal Additive Manufactured Tungsten Collimator for SPECT/MRI Integration
We optimized the MR-compatibility of a novel tungsten collimator, produced with metal additive manufacturing that is part of a microSPECT insert for a preclinical SPECT/MRI scanner. We characterized the current density due to the gradient field and adapted the collimators by smart design to reduce the induced eddy currents.
The z-gradient coil and the collimator were modeled with SEMCAD. The gradient strength was 510 mT/m, the gradient efficiency was about 3.4 mT/m/A. The setup was simulated with a working frequency of 10 kHz. The system consists of 7 identical collimators and digital silicon photomultipliers assembled in a ring. We evaluated the global reduction in current density J(reduction) based on the sum of all current densities in the collimator. We applied the following optimizations on the collimator:
1. We reduced the excessive material in the flanges.
2. We applied horizontal slits of 2 mm in the collimator surface.
3. We reduced material in the core; the photons are attenuated before they reach the core. The collimator will need a supporting structure.
4. The supporting structure can be avoided by using two vertical slits in the middle of the collimator.
5. We used a Z-shaped slit instead of the vertical slit.
Results of simulations show that smaller flanges reduce the current density with 23%. The horizontal slits reduce the eddy currents with 6%. Using less material in the core or applying vertical slits results in the same reduction of current density. However, the vertical slits are cheaper because a hollow collimator requires supporting structures during production. Both can be combined if z-shaped slits are used to prevent attenuation problems. The reduction is then 27%. Finally, when all previous adaptations are combined, the reduction in eddy currents is about 56.3%.
Amine Samoudi(Ghent University/iMinds)
Correlation Between Arterial Spin Labeling MRI and Dynamic FDG on PET-MR in Alzheimer’s Disease and non-Alzhiemer’s Disease patients
Background: Regional hypoperfusion on Arterial Spin Labeling (ASL) MRI and corresponding regions of hypometabolism on FDG PET have been reported in Alzheimer’s Disease (AD). To our knowledge these correlations have not been studied under simultaneous acquisition. The purpose of this study is to investigate the correlation of ASL with FDG PET under simultaneous acquisition on PET-MR and to explore this correlation as a possible biomarker for AD.
Materials and Methods: Dynamic FDG and ASL imaging was performed using a simultaneous TOF-enabled PET-MR scanner in 7 subjects without AD and 3 subjects with AD. Average age was 68±5 years. Automated atlas-based segmentation was performed using T2 MRI using the Talairach atlas. Quantitative analysis of ASL and FDG (delayed 45-75 minute scan) was performed in five regions using the pons as a reference region for both perfusion and metabolism. Statistical analyses included Spearman’s correlation and student’s t-test.
Results: Significant correlation of relative perfusion and metabolism was found in two of the five brain regions including the putamen (p = 0.018) and the hippocampus (p = 0.031). In addition, there was significant difference between the relative perfusion and metabolism of the thalamus (p = 0.04). No difference was seen between the AD and non-AD groups.
Conclusions: Simultaneous PET-MR demonstrates a positive correlation of perfusion of ASL with metabolism on FDG PET in the hippocampus and putamen. The putamen correlation has previously been reported in the literature on a non-simultaneous ASL and FDG imaging. The thalamus was noted to have a difference in the relative perfusion and metabolism representing a perfusion-metabolism mismatch. Future studies should explore the correlation in additional brain regions and the meaning of perfusion-metabolism mismatches as potential imaging biomarkers for patients with and without AD.
Corticospinal MRI tractography in space-occupying brain lesions by diffusion tensor and kurtosis imaging methods
Recently, DKI-based tractography has been developed, showing improved crossing-fiber resolution in comparison to deterministic DTI-based tractography in healthy subjects. In this work, DTI and DKI-based tractography methods were compared regarding the assessment of the corticospinal tract in patients presenting space-occupying brain lesions near cortical motor areas. Nine patients (4 males)aged 23 to 62 years old, with space-occupying brain lesions (e.g. tumors) were studied for pre-surgical planning using a 1.5T MRI scanner and a 12-channel head coil. In 5 patients diffusion data was acquired along 64 directions and in 4 patients along 32 directions both with b-values 0, 1000 and 2000 s/mm2. Corticospinal tracts were estimated using deterministic DTI and DKI methods and also using probabilistic DTI. The superior cerebellar peduncles and the motor cortical areas, ipsilateral and contralateral to the lesions, were used as seed regions-of-interest for fiber tracking. Tracts courses and volumes were documented and compared between methods. Results showed that it was possible to estimate fiber tracts using deterministic DTI and DKI methods in 8/9 patients, and using the probabilistic DTI method in all patients. Overall, it was observed that DKI-based tractography showed more voluminous fiber tracts than when using deterministic DTI. The DKI method also showed curvilinear fibers mainly above lesions margins, which were not visible with deterministic DTI in 5 patients. Similar tracts were observed when using probabilistic DTI in 3 of those patients. Results suggest that the DKI method contribute with additional information about the corticospinal tract course in comparison with the DTI method, especially with subcortical lesions and near lesions’ margins. Therefore, this study suggests that DKI-based tractography could be useful in MRI and hybrid PET-MRI pre-surgical planning protocols for improved corticospinal tract evaluation.
DrHugo Ferreira(2Institute of Biophysics and Biomedical Engineering, Faculty of Sciences of the University of Lisbon, Lisboa, Portugal.), MrJoao Leote(1Department of Neurosurgery, Hospital Garcia de Orta, Almada, Portugal;2Institute of Biophysics and Biomedical Engineering, Faculty of Sciences of the University of Lisbon, Lisboa, Portugal), Prof.Rita Nunes(2Institute of Biophysics and Biomedical Engineering, Faculty of Sciences of the University of Lisbon, Lisboa, Portugal)
Epileptogenic focus localization: a new approach
Epilepsy is one of the most important chronic neurological disorders worldwide affecting more than 50 million people of all ages. Among these, almost 20% of epilepsy cases are uncontrollable and have an unknown source of this abnormal electrical activity.
Present techniques for the detection of epileptogenic foci include electroencephalography (EEG), positron emission tomography, and multimodal EEG/functional magnetic resonance imaging (fMRI), all with limitations in terms of spatial and temporal resolutions. In order to overcome some of those limitations a novel approach using fMRI alone was developed based on the hypotheses that the epileptogenic focus shows Blood Oxygen Level Dependent (BOLD) temporal profiles distinct from the remaining brain parenchyma during interictal activity and that the epileptogenic focus BOLD signals show lower complexity than healthy parenchyma.
In this novel approach, bi-dimensional temporal clustering analysis, a data-driven technique, was used to identify brain regions with similar temporal profiles. Then, the BOLD signals of these regions were assessed regarding complexity using detrended fluctuation analysis and also using a modified multiscale entropy algorithm in order to identify which of those regions corresponded to epileptogenic tissue.
In order to demonstrate the applicability of the developed method three epileptic patients were analyzed comprising two types of epilepsy: unilateral and bilateral temporal lobe epilepsies. The results showed that this method is able to detect the brain regions associated with epileptogenic tissue. The results also showed that the epileptogenic focus influences the dynamics of related brain networks. This could be a key factor in the applicability of this method to other epilepsy cases.
Finally, new perspectives are envisioned concerning the use of this method in the medical care of epilepsy. In particular, by improving this method using simultaneous structural, functional, and metabolic information with hybrid MRI-PET scanners for the validation of epileptogenic focus.
MsVânia Tavares(Institute of Biophysics and Biomedical Engineering, Faculty of Sciences of the University of Lisbon, Lisboa, Portugal)
Establishment of an open database of realistic simulated data for evaluation of partial volume correction techniques in brain PET/MR
The Partial Volume (PV) effect in Positron Emission Tomography (PET) imaging leads to loss in quantification accuracy, which manifests in PV effects (small objects occupy partially the sensitive volume of the imaging instrument, resulting in blurred images). Simultaneous acquisition of PET and Magnetic Resonance Imaging (MRI) produces concurrent metabolic and anatomical information. The latter has proved to be very helpful for the correction of PV effects. Currently, there are several techniques used for PV correction. They can be applied directly during the reconstruction process or as a post-processing step after image reconstruction. In order to evaluate the efficacy of the different PV correction techniques in brain-PET, we are constructing a database of simulated data. Here we present the framework and steps involved in constructing this database.
Static 18F-FDG epilepsy and 18F-Florbetapir amyloid dementia PET/MR were selected because of their very different characteristics. The methodology followed was based on four main steps: Image pre-processing, Ground Truth (GT) generation, MRI and PET data simulation and reconstruction. All steps used Open Source software and can therefore be repeated at any centre. The framework as well as the database will be freely accessible. Tools used included GIF, FSL, POSSUM, GATE and STIR.
The final data obtained after simulation, involving raw or reconstructed PET data together with corresponding MRI datasets, were close to the original patient data. Besides, there is the advantage that data can be compared with the GT. We indicate several parameters that can be improved and optimized.
Ana Mota(Instituto de Biofísica e Engenharia Biomédica, FC-UL, Lisboa, Portugal; Institute of Nuclear Medicine, UCL, London, UK)
Evaluation of algorithms for photon depth of interaction estimation for the TRIMAGE PET component
The TRIMAGE consortium aims to develop a multimodal PET/MR/EEG brain scanner dedicated to the early diagnosis of schizophrenia and other mental health disorders.
The PET component features a full ring made of 18 detectors, each one consisting of twelve 8x8 Silicon PhotoMultipliers (SiPMs) tiles coupled to two segmented LYSO crystal matrices with staggered layers.
In each module, the crystals belonging to the bottom layer are coupled one to one to the SiPMs, while each crystal of the top layer is coupled to four crystals of the bottom layer. This configuration allows to increase the crystal thickness while reducing the depth of interaction uncertainty, as photons interacting in different layers are expected to produce different light patterns on the SiPMs.
The PET scanner will implement the pixel/layer identification on a front-end FPGA. This will allow increasing the effective bandwidth, setting at the same time restrictions on the complexity of the algorithms to be implemented.
In this work two algorithms whose implementation is feasible directly on an FPGA are presented and evaluated. The first algorithm implements a method based on adaptive thresholding, while the other uses a linear Support Vector Machine (SVM) trained to distinguish the light pattern coming from two different layers.
The validation of the algorithm performance is carried out by using simulated data generated with the GAMOS Monte Carlo.
The obtained results show that the achieved accuracy in layer and pixel identification is above the 90% for both the proposed approaches.
MrNiccolo' Camarlinghi(Universita' di Pisa)
First results with SiPM tiles for TOF PET based on FBK RGB-HD technology
We present the first results of timing and energy resolution of two newly developed tiles based on FBK RGB-HD SiPMs. The first tile has dimensions of 32x32 mm2 and is composed of 8x8 SiPMs, with a regular pitch of 4 mm and a cell size of 25x25 µm2. Although manufactured with a standard bond wire technology, the tile achieves a fill factor at the tile level of 85%. We produced two versions: one with a single-ended and the other with differential readout. We tested the first prototypes with single-ended readout with a scintillator array, perfectly matching the tile pitch and composed of 8x8 LYSO crystals with dimensions of 4x4x22 mm3.
First, we tested the tile using a single-channel setup, based on a fast, discrete amplifier, a digital oscilloscope and a PC, reading one SiPM at a time. At 20 °C, we measured an energy resolution of 10.7% FWHM. For the timing measurements we compared two conditions: when only one SiPM was biased and read, and when all the 64 SiPMs were biased but only one was read. At 20 °C, we measured a timing resolution of 200 ps FWHM in the first case, and 220 ps FWHM in the second case. Then, we tested the whole tile with a dedicated ASIC (PETA3), and measured the energy and timing resolution of two tiles in coincidence.
The second tile is composed of 144 SiPMs, mounted on a water cooled, ceramic LTCC substrate. On the top side, it contains 12x12 SiPMs with a regular pitch of 2.5 mm. Also in this case, the SiPM technology is the RGB-HD with a cell size of 25x25 µm2. On the bottom side, four readout ASICs of the latest generation (PETA5) are flip-chip mounted. First results will be presented.
Peter Fischer(Heidelberg University)
Geometric Optimization of an Ultralow-dose High-resolution Pediatric PET Scanner Based on Monolithic Scintillators with dSiPM Readout
A potential design for a high-resolution, ultralow-dose multimodal PET insert for pediatric medicine is presented. Several new technologies are combined to develop a unique, mobile, CT- and MRI-compatible PET system. The system is intended for diagnosis, staging, monitoring, and follow-up in the treatment of cancer as well as cardiac and neurological diseases, inflammation, and hyperinsulinism in children of up to about 12 years of age. The design is based on a recently developed monolithic scintillator detector, consisting of a 32 x 32 x 22 mm3 LYSO:Ce crystal with dual-sided readout (DSR) using digital silicon photomultiplier (dSiPM) arrays. The aim is to achieve an isotropic spatial resolution of < 2 mm full width at half maximum (FWHM) in the entire field-of-view (FOV), as well as < 150 ps FWHM time-of-flight (TOF) resolution. The central goal of this work is the simulation, geometric design optimization, and preliminary performance evaluation of the pediatric system. The scanner geometry is simulated by means of the GEANT4 Application for Tomographic Emission (GATE) software, using the measured spatial-, energy- and timing-response of the DSR monolithic scintillator detectors as input. The performance of pediatric PET inserts with different axial lengths (between 6.8 cm and 102 cm) is assessed following the NEMA NU2-2012 protocol. Preliminary results show that the system can achieve a spatial resolution as good as ~2.0 mm FWHM in each direction, a scatter fraction (SF) of ~32%, and a line source sensitivity as high as ~188 cps/kBq for 1 m long scanner. Further work includes the simulation of different potential geometries of the pediatric PET and the comparison of their performance. Additionally, a more complete and accurate model of the detector response based on experimental data will be implemented for better spatial resolution.
DrEkaterina Mikhaylova(MEDISIP, Departement of Electronics and Information Systems, Ghent University-iMinds Medical IT.)
Initial in Vitro and in Vivo Assessment of Au@DTDTPA-RGD Nanoparticles for Gd-MRI and 68Ga-PET Dual Modality Imaging
Gadolinium chelate coated gold nanoparticles (Au@DTDTPA) can be applied as contrast agents for both in vivo X-ray and magnetic resonance imaging. In this work, our aim was to radiolabel and evaluate this gold nanoparticle with Ga-68, in order to produce a dual modality PET/MRI imaging probe.
Materials and Methods
For a typical preparation of 68Ga-labeled nanoparticles, the Au@DTDTPA nanoparticles (Au@DTDTPA/Au@DTDTPA-RGD) were mixed with ammonium acetate buffer, pH 5 and 40 MBq of 68Ga eluate. The mixture was then incubated for 45 min at 65 °C. Radiochemical purity was determined by ITLC. In vitro stability of both radiolabeled species was assessed in saline and serum. In vitro cell binding experiments were performed on integrin ανβ3 receptor-positive U87MG cancer cells. Non-specific Au@DTDTPA was used for comparison. Ex vivo biodistribution studies and in vivo PET and MRI imaging studies in U87MG tumor-bearing SCID mice followed.
The Au@DTDTPA nanoparticles were labeled with Gallium-68 at high radiochemical yield (>95%) and were stable at RT, and in the presence of serum, for up to 3 h. The cell binding assay on U87MG glioma cells proved that 68Ga-cRGD-Au@DTDTPA had specific recognition for these cells. Biodistribution studies in U87MG tumor-bearing SCID mice showed that the tumor to muscle ratio increased from 1 to 2 h p.i. (3,71 ± 0.22 and 4,69 ± 0.09 respectively), showing a clear differentiation between the affected and the non-affected tissue. The acquired PET and MRI images were in accordance to the ex vivo biodistribution results.
The preliminary results of this study warrant the need for further development of Au@DTDTPA nanoparticles radiolabeled with Ga-68, as possible dual-modality PET/MRI imaging agents.
Penelope Bouziotis(National Center for Scientific Research "Demokritos")
Measurement of the Point Spread Function of a Pixelated Detector Array
In order to further understand the PET/MRI scanner of our group, we measured the point spread function of a preclinical scintillation
crystal array with a pitch of 1 mm and a total size of 30 mm × 30 mm × 12 mm. It is coupled via a lightguide to a dSiPM from Philips Digital Photon
Counting, used on the TEK-setup. Crystal identification is done with a centre of gravity algorithm and the whole data analysis is performed with the same processing software as for the PET insert, giving comparable results. The beam is created with a 22 NA-Point-Source and a lead collimator, with 0.5 mm bore diameter. The algorithm sorted 62 % of the coincidences into the correct crystal.
Christian Ritzer(Department of Physics of Molecular Imaging Systems, Institute for Experimental Molecular Imaging, RWTH Aachen University, Aachen, Germany)
Multi-modality image reconstruction for dual-head small-animal PET
The hybrid positron emission tomography/computed tomography (PET/CT) or positron emission tomography/magnetic resonance imaging (PET/MRI) has become routine practice in clinics. The applications of multi-modality imaging can also benefit research advances. Consequently, dedicated small-imaging system like dual-head small-animal PET (DHAPET) that possesses the advantages of high detection sensitivity and high resolution can exploit the structural information from CT or MRI. It should be noted that the special detector arrangement in DHAPET leads to severe data truncation, thereby degrading the image quality. We proposed to take advantage of anatomical priors and total variation (TV) minimization methods to reconstruct PET activity distribution form incomplete measurement data. The objective is to solve the penalized least-squares function consisted of data fidelity term, TV norm and medium root priors. In this work, we employed the splitting-based fast iterative shrinkage-thresholding algorithm to split smooth and nonsmooth functions in the convex optimization problems. Our simulations studies validated that the images reconstructed by use of the proposed method can outperform those obtained by use of conventional expectation maximization algorithms or that without considering the anatomical prior information. Additionally, the convergence rate is also accelerated.
Respiratory and cardiac motion correction in dual gated PET/MR imaging
Aim: Respiratory and cardiac motion in PET/MR imaging leads to reduced quantitative and qualitative image accuracy. Correction methodologies involve the use of double gated acquisitions which lead to low signal-to-noise ratio (SNR) and to issues concerning the combination of cardiac and respiratory frames. The objective of this work is to use a generalized reconstruction by inversion of coupled systems (GRICS) approach, previously used for PET/MR respiratory motion correction, combined with a cardiac phase signal and a reconstruction incorporated PET motion correction approach in order to reconstruct motion free images from dual gated PET acquisitions.
Methods and Materials: The GRICS method consists of formulating parallel MRI in the presence of patient motion as a coupled inverse problem. Its resolution, using a fixed-point method, allows the reconstructed image to be improved using a motion model constructed from the raw MR data and two respiratory belts. GRICS obtained respiratory displacements are interpolated using the cardiac phase derived from an ECG to model simultaneous cardiac and respiratory motion. Three different volunteer datasets (4DMR acquisitions) were used for evaluation. GATE was used to simulate 4DPET datasets corresponding to the acquired 4DMR images. Simulated data were subsequently binned using 16 cardiac phases (M1) vs diastole only (M2), in combination with 8 respiratory amplitude gates. Respiratory and cardiac motion corrected PET images using either M1 or M2 were compared to respiratory only corrected images and evaluated in terms of SNR and contrast improvement.
Results: Significant visual improvements were obtained when correcting simultaneously for respiratory and cardiac motion (using 16 cardiac phase or diastole only) compared to respiratory motion only compensation. Results were confirmed by an associated increased SNR and contrast.
Conclusion: Results indicate that using GRICS is an efficient tool for respiratory and cardiac motion correction in dual gated PET/MR imaging.
MrHadi Fayad(INSERM, UMR 1101)
Validation of a Simultaneous PET/MR System Model for PET Simulation Using GATE
Simultaneous PET/MR acquisition shows promise in a range of applications. Simulation using GATE is an essential tool that allows obtaining the ground truth for such acquisitions and therefore helping in the development and the validation of innovative processing methods such as PET image reconstruction, attenuation correction and motion correction. The purpose of this work is to validate the GATE simulation of the Siemens Biograph mMR PET/MR system.
Methods and materials:
A model of the Siemens Biograph mMR was developed. This model includes the geometry and spatial positioning of the crystals inside the scanner and the characteristics of the detection process. The accuracy of the model was tested by comparing, on a real physical phantom study, GATE simulated results to reconstructed PET images using measured results obtained from a Siemens Biograph mMR system. The same parameters such as the acquisition time and phantom position inside the scanner were fixed for our simulations. List-mode outputs were recovered in both cases and reconstructed using the OPL-EM algorithm. Several parameters were used to compare the two reconstructed images such as profile comparison, signal-to-noise ratio and activity contrast analysis. Finally patient acquired MR images were segmented and used for the simulation of corresponding PET images.
The simulated and acquired sets of reconstructed phantom images showed close emission values in regions of interest with relative differences lower than 5%. The scatter fraction was within a <3% agreement. Close matching of profiles and contrast indices were obtained between simulated and corresponding acquired PET images.
Our results indicate that the GATE developed Biograph mMR model is accurate in comparison to the real scanner performance and can be used for evaluating innovative processing methods for applications in clinical PET/MR protocols.
Florian Monnier(LaTIM UMR 1101)
Whole-body Simultaneous Time-of-flight PET-MRI: Early Experience with Clinical Studies
Purpose: Recently, a whole-body, simultaneous positron emission tomography - magnetic resonance imaging (PET-MRI) system combing MRI with time-of-flight (TOF) PET has been developed. We present our initial experience with human clinical studies using 18F-fluorodeoxyglucase (FDG) with this scanner, in comparison to PET-CT.
Methods: All patients underwent a single-injection of 18F-FDG, with a dual-imaging protocol consisting of PET-CT followed by PET-MRI scan.PET-MR attenuation correction used a two point Dixon fat-water separated method for the body, combined with registration to an atlas for the head.Two radiologists evaluated MRI image quality using the following scale (0 non-diagnostic; 1 poor; 2 good; 3 excellent). PET-MRI and PET-CT images were reviewed for FDG uptake thought to be consistent with malignancy by two readers independently, and categorized into 5 groups (1 both PET-MRI and PET-CT positive, 2 PET-MRI positive, PET-CT positive in retrospect; 3 PET-CT positive, PET-MRI positive in retrospect; 4: PET-MRI positive, PET-CT negative; 5: PET-MRI negative, PET-CT positive) by consensus. Results: Twenty-six oncologic patients (average age: 63±14 yrs) with were enrolled in the study. PET-CT and PET-MRI scan started 71±14 and 144±22 minutes after injection of 10±1 mCi FDG, respectively. The average length of the PET-CT and PET-MRI scan was 20±7, and 55±15 minutes, respectively. All MRI images were rated to be diagnostic; 64% were rated excellent, 32% were rated good, and 4% were rated poor. 64% (34/53) of FDG intense lesions were observed in the same location for both PET-CT and PET-MRI. TOF PET-MRI provided comparable image quality and diagnostic ability with PET-CT, despite imaging at a later time point.
DrRyogo Minamimoto(Stanford University, Department of Radiology, Division of Nuclear Medicine and Molecular Imaging)
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fuoco di bosco
Session 12 - Clinical MR-PETRoom Maria Luisa
Room Maria Luisa
Craig Levin(Stanford University)
Simultaneous Trimodal MR-PET-EEG Imaging for the Investigation of Resting State Networks in Humans
Glucose is the principal source of energy for the brain and its relationship to neuronal activity are poorly understood. The human brain uses 80% of its energy for ongoing neural activity that occurs in isolation from any particular stimulus. A promising tool for the investigation of glucose metabolism and its relationship to neuronal activity is simultaneous trimodal MR-PET-EEG data imaging. We here demonstrate the first in vivo human trimodal data at 3T.
In one session MR, FDG-PET and EEG data were recorded simultaneously at a 3T hybrid MR-BrainPET scanner (Siemens, Germany) equipped with a 32 channel MR-compatible EEG system (Brain Products, Germany) in 11 healthy volunteers (11 males, mean age: 25.2 years SD: 1.2). MR and EEG data acquisition MP-RAGE (TR = 2250 ms, TE= 3.03 ms, 176 sagittal slices á 1 mm,GRAPPA factor 2. MR-based attenuation correction of PET data via UTE: flip angle=15º, two different echo times TE1=0.07 and TE2=2.46 ms, TR=200 ms. EPI sequence (TR: 2.2 s, TE: 30 ms, FOV: 200 mm, 165 volumes, The subjects were requested to close their eyes and relax EEG data were recorded using a 32-channel MR compatible EEG system.
App. 200 MBq/μmol FDG were injected, data were acquired in list mode and iteratively reconstructed with all necessary corrections into 153 slices with 256 x 256 voxels sized 1.25 mm3.
The trimodal approach, recording PET data, MR data and EEG data simultaneously was successful. The high neuronal activity of the structures within the default mode network occurs on the basis of a high glucose consumption rate within the default node network. The activity of the default mode is not tied to a special EEG frequency band.
DrIrene Neuner(RWTH Aachen / FZ Jülich)
Resolution improvement of brain PET images using prior information from MRI: clinical application on refractory epilepsy
An important counterpart of clinical Positron Emission Tomography (PET) for early diagnosis of neurological diseases is its low resolution. This is particularly important when evaluating diseases related to small hypometabolisms such as epilepsy. The last years, new hybrid systems combining PET with Magnetic Resonance (MR) has been increasingly used for several different clinical applications. One of the advantages of MR is the production of high spatial resolution images and a potential application of PET-MR imaging is the improvement of PET resolution using MR information. A potential advantage of resolution recovery of PET images is the enhancement of contrast delivering at the same time better detectability of small lesions or hypometabolic areas and more accurate quantification over these areas. Recently, Shidahara et al (2009) proposed a new method using wavelet transforms in order to produce PET images with higher resolution.
We optimised Shidahara’s method (SFS-RR) to take into account possible shortcomings on the particular clinical datasets, and applied it to a group of patients diagnosed with refractory epilepsy. FDG-PET and MRI images were acquired sequentially and then co-registered using software tools. A complete evaluation of the PET/MR images was performed before and after the correction, including different parameters related with PET quantification, such as atlas-based metabolism asymmetry coefficients and Statistical Parametric Mapping results comparing to a database of 87 healthy subjects. Furthermore, an experienced physician analysed the results of non-corrected and corrected images in order to evaluate improvements of detectability on a visual inspection. Clinical outcome was used as a gold standard.
SFS-RR demonstrated to have a positive impact on clinical diagnosis of small hypometabolisms. New lesions were detected providing additional clinically relevant information on the visual inspection. SPM sensitivity for the detection of small lesions was increased from 70% to 90%.
MrJesús Silva-Rodríguez(Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela, Spain)
Brain connectivity study of brain tumor patients using MR-PET data: preliminary results
Brain activity results from anatomical and functional connections that can be disrupted or altered due to trauma or lesion. This work presents a first approach on the study of whole-brain connectivity of brain tumor patients using the Multimodal Imaging Brain Connectivity (MIBCA) toolbox.
Two patients with glioblastoma lesions located in the left hemisphere (one in the motor cortex and the other in the temporal lobe) underwent simultaneous MRI and dynamic PET scans using a 3T MRI scanner with a BrainPET insert. The following data was acquired: T1-w MPRAGE (1x1x1mm3), DTI (dir=30, b=0,800s/mm2, 2x2x2mm3), and dynamic 18F-FET PET.
The MIBCA toolbox was used to automatically pre-process MRI-PET data and to derive imaging and connectivity metrics from the multimodal data. Computed metrics included: cortical thickness from T1-w data; mean diffusivity (MD), fractional anisotropy (FA), node degree, clustering coefficient and pairwise ROI fibre tracking (structural connectivity) from DTI data; and standardized uptake value (SUV) from PET data. For all the metrics, the differences between left and right hemispherical structures were obtained, followed by a 25% threshold (except for SUV thresholded at 15%). Data was visualized in a connectogram, and both structural connectivity and metrics were studied in regions surrounding lesions.
Preliminary results showed increased SUV values in regions surrounding the tumor for both patients. Patients also showed changes in structural connectivity involving these regions and also other more spatially distant regions such as the putamen and the pallidum, including decreased number of fibers between the subcortical structures themselves and with frontal regions. These findings suggest that the presence of a tumor may alter both local and more distant structural connections.
Presently, a larger patient sample is being studied along with the inclusion of a control group to test the consistency of the findings.
Ana Carina Mendes(University of Lisbon)
coffee breakparking area
Session 13 - Clinical MR-PETRoom Maria Luisa
Room Maria Luisa
Irene Neuner(JARA Brain)
Quantitative impact of Dixon µmap variability in dual-time-point brain PET/MR
Background: Dixon-based MR is acquired for attenuation correction of brain PET during PET/MR. Early adopters of PET/MR have noted variability in the performance of Dixon-based tissue segmentation, and questions exist regarding potential impacts on quantitative accuracy in dual-time-point studies.
Methods: Ten patients injected with 10 mCi FDG underwent dual-time-point clinical brain PET/MR on a Siemens mMR, with image reconstructions based on data acquired at 45 – 60 and 75 – 90 minutes. Dixon µmaps were obtained the time of FDG injection and at 75 minutes. 8 cc of Gadavist was injected for post-contrast MR at 30 minutes. Subjects were removed from the table and re-positioned prior to the 75 minute scan. The delayed µmap was registered to the original µmap using MIMneuro. The aligned image data was copied onto the original µmap DICOM file using Matlab. Early time-point PET data was reconstructed using both the early and delayed µmaps. Atlas-based segmentation was performed to compare regional SUV values.
Results: When comparing the delayed versus original µmap reconstructions, regional SUV values varied on average by +1.9% for both SUVmax and SUVmean. For large brain structures, SUVmax and SUVmean varied by -0.5% to +5.6% and -0.2 to +4.7%, respectively. For deep brain structures, SUVmax using the delayed reconstruction varied by -0.5% to +3.7% and SUVmean varied by -0.3% to +3.6%. Most differences in SUV were higher when using the delayed µmap.
Conclusion: There is variability in regional SUV values for brain PET data reconstructed using two different aligned Dixon acquisitions performed on subjects undergoing repeat same-day PET/MR imaging, with SUV values ~2% higher using the delayed µmap. This variability may impact results in dual-time-point brain PET/MR.
MsKimberly Jackson(Center for Biomedical Imaging, Department of Radiology, NYU Langone Medical Center, New York, NY USA)
Assessment of PET & ASL metabolism in the hippocampal subfields of MCI and AD using simultaneous PET-MR
Alzheimer’s disease (AD) has been reported to show decreased metabolic activity in the hippocampus using FDG PET-MR. Histological data suggests that the hippocampal subfields are selectively affected in AD. Given the simultaneous imaging nature of integrated PET-MR scanners and the multimodal capabilities of PET-MR, our purpose here is to assess FDG activity, as well as ASL perfusion in the subfields of MCI and AD patients. 10 consecutive subjects were recruited for this study 3 MCI, 3 AD patients and 4 age-matched controls. The scanning was performed on a simultaneous 3T PET/MR scanner. To delineate the hippocampal subfields, automatic segmentation of hippocampal subfields (ASHS) was employed. Static FDG-PET series were reconstructed for analysis at 45-75 min for all subjects. All imaging sequences were automatically registered to the oblique coronal T2-weighted images (segmentation space). PET standardized uptake values (SUV) in the hippocampal subfields were normalized by the pons. FDG PET metabolism was reduced significantly in AD, as well as MCI patients as compared to controls, with the highest effect demonstrated in the CA3/DG and CA1/2 (p = 0.047, subfields. Patients (MCI and AD combined) had decreased metabolism as compared to controls in CA1/2 and significantly smaller volumes the Subiculum. When assessing CBF across groups, a significant decrease in CBF was found in the Subiculum. Our preliminary results demonstrate that PET-MRI may potentially be a sensitive biomarker and tool for early diagnosis of AD. They also confirm the importance of assessing metabolic and structural changes of neurodegenerative diseases at the subfield level.