MEDAMI 2014 - III MEDITERRANEAN THEMATIC WORKSHOP IN ADVANCED MOLECULAR IMAGING

2 Sept 2014, 08:00 → 7 Sept 2014, 19:00 Europe/Rome

Hotel Portoconte

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TRANSLATING TECHNOLOGY FROM NUCLEAR
AND PARTICLE PHYSICS TO THE CLINIC:
ADDRESSING MEDICAL NEEDS BY DETECTOR
KNOW-HOW WITH A FOCUS ON ORGAN-SPECIFIC IMAGING

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Collaboration between the physics-, medical- and industrial communities

 
September 3 – 7 – 2014
Alghero (Sardinia - Italy)
 

   
 

In order to address the issues of efficient technology transfer and translational research, the meeting in Sardinia will bring together all the major stakeholders, including imaging scientists, practicing physicians from radiology, oncology, neuroimaging, surgery and radiation therapy, representatives of the manufacturers, both big and small, of medical imaging instrumentation and components, radiopharmaceutical company representatives, and, if possible, officials from funding agencies.
 
The primary goal of the meeting will be to identify the conditions and requirements (medical, technical and societal) for an expansion of medical diagnostic imaging into dedicated, application and/or organ-specific fields in order to improve quality of diagnoses, efficacy of treatment and to reduce overall healthcare costs.
Therefore application areas with high societal impact and strong medical need are to be indentified and strategies for addressing them both technologically as well as organizationally have to be developed.
Some of the topics that will certainly be discussed are:

• MR-compatible inserts for surgical and other applications,
• therapy monitoring in both radiation and medical oncology
• potential and usefulness of screening

It is the intention to review the complete spectrum of potential applications and, at the end of the meeting, having achieved a better understanding of the role of dedicated, organ-specific instrumentation and the potential translation of such technologies into the clinic.
 
The meeting shall start with introductory keynote talks by opinion leaders in the field, followed by a series of sessions on organs/diseases (breast, prostate and OB/GYN, endoscopy, surgery, brain, heart, radiotherapy), each one with clinician (and/or surgeon), radiologist, and technologist talks and with a round table (or a panel) at the end of each session to maximize the discussion and interaction between multidisciplinary participants. An important component of this meeting will be the talks given by company representatives, in addition to the physician and surgeon talks describing the uses of a particular technology or instrument.

HOTEL PORTO CONTE
Alghero

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with support from

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webmaster and webdesigner: Alessandro Spurio (2014)

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Tuesday, 2 September

18:00 → 20:00 Registration

Wednesday, 3 September

08:00 → 08:30 Registration

Registration

08:30 → 10:30 KEY NOTE SESSION 1

Convener: Franco Garibaldi (ISS)

08:30 Welcome addresses

Speaker: Franco Garibaldi (ISS)

Slides Garibaldi_-_Welcome-alghero.pptx

08:45 Lost in Translation: from nuclear science to clinical reality

Nuclear science is a very productive environment for the development of instrumentation for the detection and imaging of particles. Over many decades, advances in this field have resulted in the transfer of technology into other related fields, and specifically for this conference, translation into medical imaging. Although performance specifications may differ, there are many common aspects such as detectors, acquisition electronics, trigger and filtering requirements, data storage, image reconstruction and processing. This presentation will stress the importance of first understanding the medical problem and review some of the technological elements that the fields have in common and that have translated from nuclear science into medical imaging, sometimes successfully and sometimes not so successfully. One specific example, the PET/CT scanner, will be briefly described and the lessons learned over many years from this exercise will be summarized. The demand for lower radiation dose, better spatial resolution and higher sensitivity devices has driven proposals to explore organ-specific (dedicated) imaging systems as a complement to whole-body imagers. The role for such dedicated devices within the medical imaging armamentarium will be discussed.

Speaker: David Townsend (CIRC, University of Singapore)

Slides TOWNSEND,_David_–_Lost_in_Translation_–_From_nuclear_science.pptx

09:20 PET technology across different scales: designs driven by applications

Positron emission tomography is a powerful technology with biomedical applications that span humans, animals and plants.  This presentation will focus on the use of PET across a wide range of different scales, and the design of PET technology and systems appropriate for these scales.  In particular recent progress in developing very small field-of-view PET scanners for preclinical research into rheumatoid arthritis, as well as large PET scanners capable of imaging the entire human body, will be highlighted as examples at either end of this scale.

Speaker: Prof. Simon Cherry (University of California - Davis)

Slides CHERRY,_Simon_–_PET_Technology_across_different_scales.pdf

09:55 TOF-PET: from the idea to clinics

Hal Anger is credited with suggesting the use of time-of-flight (TOF) as far back as 1966 to localize the activity due to positron annihilation, even though his sodium iodide dual Anger camera from that time did not achieve very good timing resolution. Although plastic detectors and fast PMTs were capable of 200 ps timing resolution, it wasn't until the early 1980's that scintillation materials, including cesium fluoride and barium fluoride, became available which had a combination of fast timing and reasonable detection efficiency. These early TOF systems were capable of meeting the high count-rate demands of research brain and heart studies using short-lived isotopes, however, by the late 1980’s they could match neither the improvements made in spatial resolution using detector blocks capable of decoding many small crystals, nor the improvements in sensitivity with BGO – even with the effective TOF sensitivity gain. By the early 1990’s, these early TOF scanners were all retired just before whole-body FDG oncology studies became prevalent. Renewed interest in TOF after 2000 began once new scintillation materials, in particular LSO and LYSO made it possible to achieve very good timing resolution as well as high sensitivity. Along with better detectors came improved electronics and more powerful computers to meet the practical needs of the clinic and allow the use of sophisticated iterative image reconstruction algorithms which include modeling of the TOF information as well as other physical effects, such as attenuation and spatial resolution. Following a brief summary of development of TOF PET, this presentation will include discussion of how the benefit of TOF is realized with clinical and research studies in terms of image quality and quantitation. Although TOF is now considered to be a key ingredient for high quality clinical whole-body imaging, a better understanding of the gain with TOF and its relevance for clinical practice is needed to optimize the use of TOF instruments and to help guide further development of the technology. All major PET manufacturers now offer TOF PET/CT systems, and TOF is also available for combined PET/MR imaging. In fact, the current spurt of activity and advancements in TOF is likely to accelerate as new scintillation materials and solid-state photo-sensors are incorporated into systems leading to improved timing resolution. The significance of this new technology will be discussed in terms of its potential to expand the range of applications that are enabled by TOF due to improvements in image quality and data quantitation

Speaker: Joel Karp (University of Pensilvania)

Slides KARP,_Joel_–_TOF-PET_–_from_the_idea_to_the_clinic.pptx

10:30 → 11:00 Coffee break

11:00 → 12:45 KEY NOTE SESSION 1

Convener: Franco Garibaldi (ISS)

11:00 PET-MR:from the idea to the working detector

Speaker: Bernd Pichler (Univeristy of Tubingen)

Slides PICHLER,_Bernd_–_Pet-Mri_from_the_idea_to_the_working_detector.ppt

11:35 PET-MR –Clinical rationale for PET/MRI

Speaker: George El Fakhri (University of Harward)

Slides EL_FAHKRI,_George_–_Clinical_Rationale_for_simultaneous_Pet-Mri.pdf

12:10 Clinical applications and limitations of PET/CT. When other technologies can help

PET/CT is an imaging device which allows to have information “in vivo” about biology (PET) and morphology (CT) of tissues. Many radiopharmaceuticals are available to evaluate the functional aspects of tumors and organs. The most common agent is 18F-fluorodeoxyglucose (FDG), expression of glucose metabolism, mainly used in oncology but other interesting radiotracers can evaluate cell proliferation, hypoxia and receptor expression. Clinical applications of PET/CT are also in inflammation, neurology and cardiology diseases. PET/CT imaging has often a strong impact on patient management but sometimes the information is not sufficient or optimal. Limitations are due to radiotracer characteristics, technical and physical aspects and methodology. These limitations can be filled by other technologies (PET/MRI? Endoscopy? Dedicated detectors?) and it is an interesting challenge for present and future.

Speaker: Annibale Versari (Azienda Ospedaliera Arcispedale Santa Maria Nuova)

Slides VERSARI,_Annibale_–_Clinical_Applications_and_Limitations_of_PET-CT.ppt

12:45 → 14:30 Lunch break

14:30 → 16:30 KEY NOTE SESSION 2

Convener: York Haemisch (Philips)

14:30 PET Radiotracer Discovery and Development for Neuroimaging

The discovery and development of a successful CNS radiotracer is challenging and is akin to a mini drug discovery and development process itself, although with a different set of criteria (e.g. fast clearance and low bioavailability are not good for drugs but are often ideal for radioligands). Key parameters guiding tractability have previously centered on labeling feasibility, lipophilicity (to predict brain entry) and affinity (to predict a target signal). However, these factors alone are not sufficient to satisfactorily de-risk putative compounds initially selected for labelling with factors such as non-specific binding (which can obscure the target signal) and irreversible kinetics (leading to flow limitation problems) not accounted for. Recently, biomathematical techniques have been introduced that provide a more comprehensive and quantitative approach to radiotracer discovery. These methods are able to de-risk the process by using mathematical equations that describe the tracer’s kinetics in conjunction with in silico and in vitro data. Finally, the development of all successful radiotracers requires suitable validation with appropriate in vivo experiments and the selection of optimal analysis methods.

Speaker: Roger Gunn (Imperial College)

Slides GUNN,_Roger_–_PET_radiotracer_discovery_and_development_for_neuroimaging.pdf

15:00 PET Neuroimaging in Early Phase Drug Development

The discovery and development of central nervous system (CNS) drugs is a complex task that requires large investments of time and money with no guarantee of success. Currently it is estimated that it costs around €1 billion to bring each successful drug to market. Imaging techniques, such as positron emission tomography (PET), can provide important information by taking direct biological measurements in tissues of interest in preclinical and clinical species in vivo. These measurements can be divided into three types: 1. Biodistribution - Direct radiolabelling of the drug candidate itself with a positron emitter does not change the properties of the drug and allows for direct measurements of the drugs concentration in tissues of interest. These studies can provide confidence that the drug is crossing the blood brain barrier in humans. 2. Target Engagement - Radiolabelling of the drug target with a probe that provides a specific signal allows for the assessment of whether a cold drug candidate interacts with the target. Such studies, often referred to as occupancy studies, provide valuable information on dose selection early in Phase 1. 3. Measuring Downstream Responses – By employing radiolabelled probes that directly measure physiological or biochemical processes, it is possible measured to measure the downstream impact of drugs on these key biological processes in the body.

Speaker: Roger Gunn (Imperial College)

Slides GUNN,_Roger_–_PET_neuroimaging_in_early_phase_drug_development.pdf

15:30 The role of medical imaging in pharmaceutical industry

Speaker: Nicholas Seneca (Roche)

16:00 The role of equipment industry in the translation from research ideas into medical (imaging) devices - a personal view

This talk will try to determine stimulating and hindering factors in the translation of research ideas and projects into new medical imaging devices. The focus will be on ideas originating from the particle physics/detector research community applied to isotope based imaging. Recent and past examples of successful and failed projects will be discussed with a special attention to the respective roles of the manufacturers involved. Questions that will be brought up for discussion also in the following round table are: Are the developments by the medical instrumentation industry impacted by the work of the research instrumentation community? If so, to what degree? How can that impact be increased? What are the success factors for an efficient translation? What are the reasons for failure? Does the size/location/ownership structure of the partnering company have an impact on the chances for success? Particular attention will be given to the role of clinicians in that translation process. The talk shall conclude with an assessment of the current role of medical equipment manufacturers in the process and an analysis of factors that have changed over the past 20 years.

Speaker: York Haemisch

Slides HAEMISCH,_York_–_1_–_The_role_of_equipment_industry_in_the_translation_of_research.pdf

16:30 → 17:00 Coffee break

17:00 → 17:35 CARDIAC SESSION

Convener: Marie Alix Duval

17:00 The role of molecular imaging in cardiology. Limits of cardiac imagers available. Is there a need for new devices?

Molecular Imaging (MI) using tracer techniques and multimodal instrumentation allows integrative tissue characterization. PET/CT offers excellent spatial resolution to delineate coronary anatomy and myocardial dimensions by fast CT, while PET in combination with a variety of tracers provides unique insights in processes like substrate metabolism, inflammation and innervation of the heart. Starting from the identification of tissue viability in ischemic heart disease to local delineation of cardiac innervation in patients with arrhythmias, PET has become a source of important clinical information. Most recently FDG has been used to identify and quantitate the extent of sarcoidosis in the heart. PET/MR adds to the spectrum of noninvasive techniques to link contrast kinetics( delayed enhancement) with metabolic information to assess the extent of ischemic injury after infarction. The future diagnostic and prognostic role of MI will be defined by the relative value of molecular imaging in management of cardiovascular diseases, currently most evident in ischemic heart disease

Speaker: Markus Schwaiger (Technische Universität München)

17:35 → 19:05 ROUND TABLE / DISCUSSION SESSION: Imaging - from detector development to clinics: key elements, hurdles and opportunities

Conveners: Prof. David Townsend (University of Singapore), Markus Schwaiger

Thursday, 4 September

08:30 → 10:00 RADIOTHERAPY SESSION

Conveners: Giacomo Cuttone (LNS), Prof. Roberto Orecchia (european institute of oncology)

08:30 The role of the radiotherapy in cancer therapy

Cancer remains leading cause of death globally. Epidemiology studies estimated that 7.6 million deaths worldwide were due to cancer with 12.7 million new cases per year being reported worldwide. A significant proportion of this burden is borne by developing countries; 63% of cancer deaths are reported to be from developing countries. If uncontrolled cell growth or metastatic spread occurs it will result in death of the individual. The past decade has witnessed a considerable progress towards the treatment and understanding of the earlier proposed hallmarks of cancer and together with advances in early detection and in the various treatment modalities, many cancers have become curable. Along with surgery and chemotherapy, radiation therapy remains an important modality used in cancer treatment being a highly cost effective single modality treatment accounting about only 5% of the total cost of cancer care. Furthermore, approximately 50% of all cancer patients will receive radiation therapy during their course of illness with an estimation that radiation therapy contributes to around 40% towards curative treatment. Rapid progress in this field continues to be boosted by advances in imaging techniques, computerized treatment planning systems, radiation treatment machines (with improved X-ray or particle beam production and treatment delivery) as well as improved understanding of the radiobiology of radiation therapy. Radiation can be given with the intent of cure as well as being used as a very effective modality of palliative treatment to relieve patients from symptoms caused by the cancer. Further indications of radiation therapy include combination strategies with other treatment modalities such as surgery, chemotherapy or immunotherapy. If used before surgery (neoadjuvant therapy), radiation will aim to shrink the tumor. If used after surgery (adjuvant therapy), radiation will destroy microscopic tumor cells that may have been left behind. It is well known that tumors differ in their sensitivity to radiation treatment. The goal of radiotherapy is to deliver as much dose to the tumour whilst sparing normal tissue. Technological advances incorporating new imaging modalities, more powerful computers and software, and new delivery systems such as advanced linear accelerators have helped achieve this. 3D radiation therapy based on CT imaging which allows accurate localization of the tumour and critical normal organ structures for optimal beam placement and shielding. IMRT allows the oncologist to create irregular-shaped radiation doses that conform to the tumour whilst simultaneously avoiding critical organs. IMRT is made possible through: a) inverse planning software and b) computer-controlled intensity-modulation of multiple radiation beams during treatment. IMRT is now available in many clinical departments and can be delivered by linear accelerators with static or dynamic multi-leaf collimators or tomotherapy machines. As treatment margins become tighter and more conformal, the potential to miss tumour due to organ motion and patient setup variations become greater. When critical structures are close to the tumour, a slight positional error may also lead to inadvertent radiation of the normal organs. IGRT allows the detection of such errors by information acquired through pre-radiotherapy imaging which allows for correction. One such example is with daily cone-beam CT scans acquired before each treatment. The improved accuracy has made dose escalation feasible, and this has allowed an improvement in the therapeutic ratio for several tumor sites. The above technological advancements have enabled SBRT, which precisely delivers very high individual doses of radiation over only a few treatment fractions to ablate small, well-defined primary and oligometastatic tumours anywhere in the body. Due to the high radiation dose, any tissue immediately adjacent to the tumour is likely to be damaged. However as the amount of normal tissue in the high dose region is small and non-eloquent, clinically significant toxicity is low. External beam radiation therapy is also carried out with heavier particles such as: neutrons produced by neutron generators and cyclotrons; protons produced by cyclotrons and synchrotrons; and heavy ions (helium, carbon, nitrogen, argon, neon) produced by synchrocyclotrons and synchrotrons. Proton beams are a newer form of particle beam radiation used to treat cancer. It can offer better dose distribution due to its unique absorption profile in tissues, known as the Bragg's peak, allowing deposition of maximum destructive energy at the tumor site while minimizing the damage to healthy tissues along their path. Neutron beams are generated inside neutron generators after proton beams are deflected to a target. They have high LET and can cause more DNA damage than photons. The limitations have been mainly due to difficulty in generating neutron particles as well as the construction of such treatment facilities. Particle radiation has higher LET than photons with higher biological effectiveness. Therefore, these forms of radiations may be more effective to the radioresistant cancers. However, equipment for production of particle radiation therapy is considerably more expensive than for photons. The decreasing costs of cyclotrons are likely to result in a wider use of proton beam therapy in the future.

Speaker: Prof. Roberto Orecchia (european institute of oncology)

Slides ORECCHIA,_Roberto_–_the_role_of_radiotherapy_in_cancer_therapy.ppt

09:00 Particle radiation therapy: the promise, the current status, the perspectives

The clinical development of radiation oncology has been historically connected to particle accelerator development and availability. In hadrontherapy this statement is even more true even considering complexity and cost investment. In this contribution will be presented the history of particle accelerator for hadrontherapy together with their actual status . In order to have a wider application of this clinical approach, it will presented the possible future accelerator development having as main goal their cost and size reduction maintaining and improving the clinical performance nowadays available.

Speaker: Giacomo Cuttone (LNS)

Slides CUTTONE,_Giacomo_–_Particle_Radiation_Therapy_-promise,_status.ppt

09:30 A Linac for hadrotherapy

The TOP IMPLART project is a program aiming the construction of a prototype facility for protontherapy application carried on in ENEA (Italian National agency for new technologies, Energy and sustainable economic development) in collaboration with con ISS (Italian National Institute of Health) and IFO-IRE (Regina Elena National Cancer Institute in Rome) and with a Regione Lazio grant.  The project is centered on a medium energy proton accelerator designed as a sequence of linear accelerators. Two phases of construction are foreseen: the first, with a maximum energy of 150 MeV and the second up to 230 MeV. The segment up to 150 MeV is under construction and the various accelerating modules are in construction and being tested. The basic concepts of the design and future perspectives are described here.

Speaker: Luigi Picardi (ENEA Frascati)

Slides PICARDI,_Luigi_–_Important_aspects_of_Top_Implart_Technology.pptx

10:00 → 10:30 Coffee Break

10:00 → 10:30 Poster

10:30 → 12:00 RADIOTHERAPY SESSION

Conveners: Giacomo Cuttone (LNS), Prof. Roberto Orecchia (european institute of oncology)

10:30 PET imaging in radiation therapy

Speaker: George El Fakhri (University of Harward)

Slides EL_FAHKRI,_George_–_In-Room_Pet-Ct_verification_of_Proton_Therapy.pdf

11:00 External/ internal correlation models for motion Management in radiotherapy

A key challenge in radiation oncology is accurate delivery of the prescribed dose to tumours that move due to respiratory activity. Tumour tracking involves real-time target localisation and correction of radiation beam geometry to compensate for motion. Intra-fractional uncertainties in tumour localisation are crucial issue in particle therapy (proton therapy, carbon-ion therapy), because charged particle beams are highly sensitive to geometrical and beam path length variations, which ultimately may affect the planned dose delivery. Target localisation and motion compensation methods applied in x-ray photon radiotherapy require careful performance assessment for a clinical applications in particle therapy. Efforts required for an application of real-time tumour tracking in particle therapy are reported, by comparing and assessing competing strategies for time-resolved target localisation and related clinical outcomes in x-ray radiation oncology.

Speaker: Prof. Guido Baroni (Politecnico di Milano - Fondazione CNAO)

Slides BARONI,_Guido_–_External-internal_correlation_models_et_al..pdf

11:30 Novel techniques for dose monitoring in particle therapy

The use of proton and carbon beams to cure deep solid tumors (particle therapy) has became a widespread clinical practice. The favorable dose deposition pattern and the enhanced radiobiological effectiveness of light ion beams are valid tools to increase the local control probability and to spare the surrounding healthy tissues. The superior ballistic precision in dose release of these treatments must be marche by an accurate monitoring procedure. However, due to the complete absorption of the beam inside the patient, the monitoring in particle therapy must rely on the secondary particles emitted by the beam in its track inside the patients. A typical approach has been the use of the PET technique, namely the use of annihilation photons produced by the positron emitters created by the beam. In this talk will be presented charged particles. Both measurements of these secondary fluxes and the corresponding design of future detector will be reviewed.

Speaker: Vincenzo Patera (ROMA1;LNF)

Slides PATERA,_Vincenzo_–_Novel_techniques_for_dose_monitoring_in_particle_therapy.pdf

12:00 → 12:30 Round table/discussion session: The role of imaging in radiotherapy

Conveners: Giacomo Cuttone (LNS), Prof. Roberto Orecchia (european institute of oncology)

12:30 → 15:30 Lunch break

15:30 → 17:10 Combined prostate/OB/GYN and endoscopic session

Conveners: Markus Schwaiger, Dr Stan Majewski (West Virginia University)

15:30 Gastrointestinal endoscopy I

In the past three decades gastrointestinal endoscopy has dramatically evolved. This evolution passed from rigid endoscopes trough fiber optic endoscopes to high definition video endoscopes that are used today. Physics and medicine has always been in symbiosis, especially in the field of development of devices and accessories. Gastrointestinal endoscopy endoscopy today is either diagnostic and therapeutic. Endoscopic Ultrasound, Narrow Band Imaging, Intraductal Ultrasound, Confocal Laser Endomicroscopy and Optical Coherence Tomography are only some of the diagnostic tools that have enriched GI endoscopy and give the possibility to diagnose dysplasia and cancer, and that literally can see over the walls of the gut. With the speed of the actual development in the field of endoscopy, in future we will probably have endoscopes that can diagnose pre-dysplastic changes of the GI mucosa and ducts, and that will be capable of injecting drugs that will block all dysplastic processes.

Speaker: Ivo Boskowski (Catholic University of Rome, Digestive Endoscopy Unit)

15:55 Role of EndoTOF PET_US in pancreatic pathology

Pancreas is a deep organ in the abdominal cavity and endoscopy has followed immense improvements thanks to technology advances. Pancreatic cancer frightens everyone in view of its growing incidence and hopeless prognosis still in 2014. It is not conceivable to imagine a program of pancreatic cancer screening in the general population due to the lack of early symptoms. By contrast, some pancreatic diseases, which are now well defined, are considered as premalignant lesions: they need thus a careful surveillance to indicate a surgical resection in the good timing. Indeed, pancreatic surgery is not a simple one and it is as risky to operate a patient too early as to delay too much a surgical indication, which would have avoided the presence and the consequences of a cancer. Although, CTscan, endosonography, MRI, PET technology have considerably improved in the last 2 decades, decision making is still very difficult in these patients: among them IPMN, late stage of chronic pancreatitis, chronic hereditary pancreatitis, mucinous neoplasms or some endocrine tumors already gain benefit from those improvements, especially from EUS-guided fine needle aspiration cytology. The combination of endoscopy and ultrasonography already exists in the form of EUS. A new probe combining EUS and PET technology should guide our examinations of the pancreas towards possible areas of interest in term of biochemical activity and thus may improve our efficacy in terms of surveillance of patients with pancreatic premalignant diseases.

Speaker: R. Laugier (University of Nice)

Slides LAUGIER,_Renè_–_Pancreatic_endoscopy_–_role_of_endo_TOF_PET_US.pdf LAUGIER,_Renè_–_Pancreatic_endoscopy_–_role_of_endo_TOF_PET_US.pptx

16:20 Present status of prostate cancer treatment and the role of imaging

Speaker: César David Vera Donoso (La Fe Universitary Hospital)

Slides VERA_DONOSO,_Cesar_David_–_Present_status_of_prostate_cancer_treatment_and_the_role_of_imaging.pptx

16:45 Present status of OB/GYN cancer treatment and the role of imaging

Improvement in treatment for gynecological carcinoma makes it possible to offer optimal and personalized treatment. Pretreatment staging is crucial to plan the best treatment strategy. Gynecological cancer staging is based on clinical examination and histological findings. However, many diagnostic methods are entered into clinical practice. Between the more sophisticated imaging techniques, magnetic resonance imaging and computed tomography are considered the optimal methods in staging uterine and ovarian carcinoma, due to the high accuracy in the assessment of local extension of the disease and distant metastases. Ultrasound has gained increased attention in recent years: it is faster, cheaper and more widely available than other imaging techniques and high accuracy in detecting tumour presence as well as in evaluating the local extension of the disease has been reported. Both magnetic resonance imaging/ computed tomography and ultrasound are often used together, in order to achieve the assessment of the whole body, a more accurate detection of pathological lymph nodes and metabolic information of the disease.

Speaker: Alessia Di Legge (University Cattolica Rome)

Slides DI_LEGGE,_Alessia_–_Present_status_of_obstetric-gynecologic_cancer.pptx

17:10 → 17:40 Coffee break

17:10 → 17:40 Poster

17:40 → 19:30 Combined prostate/OB/GYN and endoscopic session

Conveners: Markus Schwaiger, Dr Stan Majewski (West Virginia University)

17:40 Prospects for imaging prostate cancer with PET/CT and PET/MR

Prostate cancer is one of the most common forms of cancer among men. Early diagnosis, correct staging, accurate detection of metastasis, and monitoring of the therapy are the key tasks that could greatly benefit from medical imaging. After a review of the main developments in the field of PET tracers for prostate cancer, the impact of improved PET instrumentation with good spatial resolution and high sensitivity are discussed, together with the latest development in PET technology: LSO/LYSO scintillators, resolution recovery, and time-of-flight reconstruction. New directions and multiple approaches in PET instrumentation for prostate cancer are presented and discussed. In particular, improved hardware and noise suppressing reconstruction algorithms allow for higher detectability of small lesions and better spatial resolution in PET/CT and PET/MR. This can be beneficial for guiding biopsy and surgery, and for accurate therapy monitoring.

Speaker: Maurizio Conti (Siemens)

Slides CONTI,_Maurizio_-_Prospect_for_Imaging_Prostate.pptx

18:05 18F-Choline: Is shine-effect an issue for prostate SUV quantification? An evaluation based on Monte Carlo simulations of the XCAT phantom

18-fluorine-choline (18F-Choline) is a relatively new radiopharmaceutical for Positron Emission Tomography (PET), proposed as an alternative for 11-carbon-choline (11C-Choline), and indicated for staging, restaging and therapy monitoring in prostate cancer. In clinical routine, 18F-Choline images are eventually evaluated using a quantitative parameter known as Standardized Uptake Value (SUV). Nevertheless, recently published data about “shine-through” effect in PET with other radiopharmaceuticals such as FDG, suggests that urinary excretion with high accumulation in the bladder can compromise a correct evaluation of the prostatic region in 18F-Choline PET studies, thus affecting both detectability and quantification values. Under this hypothesis, we conducted an evaluation of the impact of bladder “shine-through” on prostate cancer quantitative evaluation. Monte Carlo simulation package SimSET and the XCAT Phantom were used to produce realistic images in a well-controlled framework for different tumor and bladder activity concentrations. Our results showed that “shine-through” contribution is highly dependent on bladder/tumor contrast ratio, leading to clear SUV overestimations for high bladder/tumor ratios. Our findings suggest that 18F-Choline SUV values obtained for prostate cancer evaluations has to be used with extreme caution, and must be dropped when bladder is visually more active than the lesion. It is valuable to mention that 11C-Choline PET studies avoid this problem and is more suitable for quantitative evaluation of the prostatic region.

Speaker: Jesus Silva-Rodriguez (Health Research Institute)

Slides SILVA,_Jesùs_et_al._-__Is_shine-through_effect_an_issue_for_prostate_SUV_quantification.pptx

18:30 TRUS_Tof_PET Project

The most certain diagnosis of prostate cancer is based on histopathology analysis of biopsy samples. Biopsy decision is based on highly non-specific elevated PSA (Prostate Specific Antigen) factor in blood. Currently biopsy is realized with use of TRUS. Samples are taken by ~2mm biopsy needle. TRUS is not sensitive for small cancer lesions, therefore it is generally used for biopsy needle location control only. During standard biopsy about 12-14 samples are taken from statistically distributed sites. Therefore this kind of biopsy is called “blind”. Negative result cannot confirm absence of the cancer. If PSA remains elevated the biopsy procedure is repeated up to a few dozen times. Multiple biopsies expose patients to potential complications and diminish life quality, and what is most important, cause delay in therapy until first positive evidence of cancer is acquired. And quick and accurate therapy is the best way to fight with prostate as well as other cancers. We propose a hybrid system of external PET detectors and TRUS probe integrated with detector-probe PET and with biopsy needle. Combined with the new more specific PET imaging agents for the prostate cancer, the proposed improved biopsy system will not be “blind” anymore, but guided by the molecular PET images. We expect that the diagnosis process will be shortened: the number of biopsies will diminish from a few dozen to hopefully only one to a few, while the number of punctures will diminish from a few hundred to several. This approach will substantially enhance the efficacy of the biopsy procedure and accelerate the beginning of treatment. Additional challenge is to achieve the MR-compatibility, with MRI currently being the best choice to obtain structural information in case of the prostate, due to its soft tissue differentiating power. Therefore, our system will be constructed from MR-compatible components. From the beginning we initiated discussions with the urologists to set optimal requirements and to participate in the design of the system and the protocol. During multi-center clinical trials the optimal examination protocol will be prepared, and optimal PET radiopharmaceutical will be defined. Also industrial partners were invited to join and play an important role in the development, to facilitate the translational process resulting in a practical marketable system. Our success will be judged by the acceptance by the urologists and ability to convert into marketable clinically useful system.

Speaker: Dr Stan Majewski

Slides MAJEWSKI,_Stan_–_Dedicated_Breast_Imaging_–_The_Journey_so_Far.ppt

Friday, 5 September

08:30 → 10:00 Endoscopic session

Conveners: Markus Schwaiger, Dr Stan Majewski (West Virginia University)

08:30 EndoTOF PET-US, a dedicated detector for pancreas and prostate biomarkers developments

In the scope of the EndoTOFPET-US project, a novel multimodal device for Ultrasound (US) Endoscopy and Positron Emission Tomography (PET) is being developed. The project aims at detecting and quantifying morphologic and functional markers and developing new biomarkers for pancreas and prostate oncology. Exploiting the Time-of-Flight (TOF) information of the gamma rays allows for a more sensitive, more precise and lower radiation-dose imaging and intervention on small internal structures. The detection of the gamma rays is realized with the help of scintillator crystals with Silicon Photomultiplier (SiPM) read-out, aiming at a coincidence time resolution of 200 ps and a spatial resolution of ≈ 1 mm. For the endoscopic detector, digital SiPMs are used for the first time in an instrument planned for clinical applications. The functionality of the instrument as well as the challenges that accompany the high miniaturization of the endoscopic detector and the asymmetric and variable geometry of the system, are presented. The demands on the system involve the fields of scintillating crystallography, ultra-fast photon detection, highly integrated electronics, system integration as well as image reconstruction. The single detector components have been fully characterized and are performing up to specifications. Two concurrent ASIC chips have been developed for the project. The first PET images have been acquired with a test setup that consists solely of hardware and software developed within the collaboration and demonstrate that the data acquisition and reconstruction chain is operational. In this talk, the characterization of the single components and the status of the detector integration and commissioning is presented.

Speaker: Dr Paul Lecoq (CERN)

Slides LECOQ,_Paul_–_Endo_TofPet_Us_–_a_Dedicated_detector_for_pancreas.ppt

08:55 Dedicated detectors for OB/GYN

Endocervical adenocarcinoma, endometrial and ovarian cancer in Lynch syndrome, and neuroendocrine prostate are examples of rare serious diseases of the pelvic region, whose early diagnosis is very difficult. with the present day diagnostic technology. Moreover, surgical treatment of these cancers is invasive, expensive and inefficient, in particular in their advanced stages. As a result, radical surgery, radiotherapy and chemotherapy applied in these cases treat the involved organ in a standard uniform way instead of offering a patient/case-tailored approach. Improved early diagnosis defining the exact cancer location, spread, and its margins, could lead to targeted treatments, thus raising over-all survival and sparing from side effects such as infertility in women and incontinence and impotence in men. A powerful novel multimodality imaging system of the pelvic region composed of an endorectal/intravaginal TOF-PET (or SPECT) MR-compatible imaging probe operating with a set of external TOF-PET panels is proposed Application of the probe would lead to unprecedented improved performances in spatial resolution and efficiency that would be of fundamental importance in the diagnosis and management of the mentioned diseases. Image fusion with MRI would enable co-registered merged visualization of anatomic and metabolic information.

Speaker: Franco Garibaldi (ISS)

Slides GARIBALDI,_Franco_–_Dedicated_Detectors_for_OB-GYN.pptx

09:20 The role of optical techniques in diagnosis and surgery

Speaker: Joackim Klode (Essen University)

10:00 → 10:30 Round table/Discussion session: The role of imaging in endoscopy: crucial parameters for detectors. Do we need multimodality?

Convener: M. Conti

10:30 → 10:50 Coffee break

10:50 → 12:35 Breast session

Conveners: Prof. Iraj Khalkhali (Harbor - UCLA Medical center), Joel Karp

10:50 The role of dedicated single photon detectors in breast diagnosis

On November 2012, a paper was published in the New England Journal of Nuclear Medicine stating the effect of three decades of screening mammography on breast cancer incidence in the U.S. It has demonstrated that introduction of screening mammography in the U.S. has doubled the number of cases of early-stage breast cancer that are detected each year. At the same time, the rate at which women present with late-stage cancer has decreased by 8%, from 102 to 94 cases per 100,000 women. Excluding the transient access incidence associated hormone replacement therapy and adjusting for trends in the incidence of breast cancer among women younger than 40 years of age. They estimated that breast cancer was over diagnosed in 1.3 million women in the past 30 years. According to their estimate in 2008, breast cancer over diagnosed in more than 70,000 women; this accounted for 31% of all breast cancers diagnosed. Subsequently, several papers also demonstrated large numbers of false positive results with screening mammography. In early 1993, we initiated prone scintimammography. The goal was to reduce the number of “unnecessary” breast biopsies that are created with screening mammogram. Since then, we have performed well over 2000 exams with technique using Tc 99m Sestamibi breast imaging. From the very beginning, we realized large field of view cameras that we were using for breast imaging with a large field of view was unable to detect small cancers as well as cancers in larger breasts and those at the medial portion of the breast. Since then there are several dedicated nuclear medicine breast imagers that have been developed, some of which are commercially available. With the use of a dedicated breast imager we have a tool to evaluate the metabolic and biologic aspects of breast cancer rather than anatomic findings. We and others found out that the major obstacle for nuclear medicine technology either single photon or PET imaging is the size of the tumor in the breast. However, with the advent of a dedicated breast imager our intrinsic resolution has significantly improved. Our next step is to improve the imaging technology with the use of hybrids scanner, i.e. combining and co-registration of nuclear medicine images with either digital mammogram or tomosynthisis. This will provide with ideal technology to image anatomic and molecular behavior of breast cancer. The preliminary result of this type of approach is encouraging. We propose, with the preliminary data that is available, to initial a large scale of screening women with a combination of digital mammogram and dedicated molecular breast imager.

Speaker: Prof. Iraj Khalkhali (Harbor - UCLA Medical center)

Slides KHALKHALI,_Iraj_–_Role_of_dedicated_single_photon_detectors_in_breast.pptx

11:20 Review of surgical imagers

Speaker: Dr Marie-Alix Duval (IMNC, Orsay, France)

Slides DUVAL,_Marie-Alix_–_Use_of_mobile_gamma_cameras_in_breast_cancer.pptx

11:50 Review of surgical imagers

Speaker: Marie-­‐Alix Duval (IMNC, IN2P3)

Slides DUVAL,_Marie-Alix_–_Use_of_mobile_gamma_cameras_in_breast_cancer.pptx

12:15 Molecular Breast Imaging unit - ISO 13485 requirements for management of the process of production from the feasibility study to the clinical validation

# Background The ISO 13485 specifies requirements for a quality management system where an organization needs to demonstrate its ability to provide medical devices and related services that meet customer requirements and meet the legislative requirements relating to medical devices and related services. The ISO 13485 was created with the intent to merge together the previous ISO 13485-13488 supplementing and updating the content. # Methods The primary objective of ISO 13485: 2003 is to facilitate harmonized medical device regulatory requirements for quality management systems. Consequently includes some specific requirements for medical devices and excludes some of the requirements of ISO 9001 that are not suitable for the purpose of regulation. For this reason, organizations that conform to ISO 13485: 2003 can not require compliance to ISO 9001 unless their quality management systems do not comply with all the requirements of ISO 9001. # Finding According to ISO 13485, the validation of the design must be carried out the validation of the design and development in accordance with planned to ensure that the resulting product from design and development to be able to meet the requirements for the application specified or intended use. The validation shall be completed prior to the delivery or use of the product. Records of the results of validation and any necessary actions shall be maintained. As part of the design validation, the organization shall perform clinical evaluations and / or assessments of the performance of the medical device, as required by national or regional laws. Monitoring and measurement are necessary to prepare documented procedures for a system of feedback, to provide for any problems quickly and focused, was added to the paragraph relating to medical systems active / non-active implantable. Control of non-conforming products in which the non-conforming product is accepted on concession only if regulatory requirements are met if the product is to be revoked, it must document the process of withdrawing with a statement of work that is subject to the same authorization and approval procedures equal education original. Analysis of the data has to be established in documented procedures to determine, collect and analyze the data necessary to demonstrate the suitability and effectiveness of the quality management system and to evaluate whether improvements can be made, including the introduction of the feedback and recording of the data analysis. Improvement has to be identified and implemented. Any changes necessary to ensure and maintain the adequacy and effectiveness of the quality management system through quality policy, quality objectives, audit results, analysis of data, corrective and preventive actions and revisions management, it is necessary to draw up procedures so that their implementation at any time and that if you do not follow complaints from customers, the reason must be authorized and registered. Corrective actions foresee to update the documents, record the results of any investigation or action taken, we must evaluate the correctness of the action taken and its effectiveness Preventive actions foresee to evaluate the correctness of the action taken and its effectiveness. # Conclusions Even if the path from the feasibility study to the clinical validation is complex from a bureaucratic and legislative point of view, especially in the field of nuclear medicine, we can not ignore the great benefits that are derived from ISO 13485: - For manufacturers of medical devices subject to procedures of conformity assessment with intervention of the Notified Body in Accordance with Annexes II, V, and VI, the certification EN ISO 13485: 2003 provides a presumption of conformity of the quality system ADOPTED; - For manufacturers of medical devices of class I (self-certification) certification 13485 allows for direct and independent verification activities prepared to meet the requirements of Directive 47/2007 and in preparation for the Eventual market surveillance activities Carried out by the Ministry of Health ; - For companies That distribute or sell medical products and companies that shops provide services related to devices, the 13485 certification allows you to participate on tenders published by the PA.

Speaker: Fortunato Cirillo (Metaltronica)

Slides CIRILLO,_Fortunato_–_Molecular_Breast_Imaging_–_State_of_the_Art.ppt

12:35 → 13:05 Round table/Discussion session: The role of NM techniques in the management of breast cancer

Conveners: Prof. Iraj Khalkhali (Harbor - UCLA Medical center), Joel Karp

13:05 → 15:00 Lunch break

16:00 → 20:00 GUIDED TOUR --- (VISIT OF ALGHERO)

20:30 → 22:30 CONFERENCE DINNER

Saturday, 6 September

08:15 → 09:20 Brain Session and Head and Neck Session: degenerative diseases and mental disorders

Convener: Vesna Sossi

08:15 Molecular brain imaging: recent advances in relation to pathology and treatment

Introduction Molecular imaging of the brain using nuclear medicine techniques such as single-photon emission tomography (SPECT) and positron emission tomography (PET) has developed rapidly over the last decade, due to major advancements in radioligand development and imaging systems. This development has been particularly important in the context of neurodegenerative disorders. Advancement in PET technology, in combination with the development of new radioligands targeting specific pathological abnormalities, such as amyloid plaques or tau aggregates, has provided new tools for better examination of neurodegenerative disorders in vivo. Amyloid imaging At present there are several radioligands for imaging A with PET. In addition to [11C]PIB that has been the first to be introduced for amyloid imaging there are new 18F-labelled radioligands available for more routine clinical use. Florbetapir (Amyvid, Eli Lilly and Company), flutemetamol (Vizamyl, GE Healthcare) and Florbetaben (Neuraceq, Piramal Imaging) have received approval from FDA. Amyloid imaging can be used clinically in patients with persistent or progressive cognitive impairment or in patients with unclear or atypical dementia syndrome to confirm or rule out the presence of A pathology. In such cases the presence or absence of A pathology can help establishing the correct treatment for the patient. Clinical trials with immunotherapy for Alzheimer´s disease are ongoing. In such trials, amyloid imaging can be used as marker to demonstrate target engagement and also as enrichment tool to include in the trials only those patients with confirmed A pathology in vivo. Tau imaging In Alzheimer´s disease, amyloid plaques accumulate extracellularly whereas aggregates of hyperphosphorylated tau accumulate intracellularly. It is well known that tau deposition has better correlation with dementia severity than amyloid deposition and tau aggregates are topographically distributed differently as compared with amyloid plaques, accumulating selectively in the hippocampus. At present, there are radioligands for imaging tau that have shown promising results in first human studies. [11C]PBB3 is a tau radioligand that binds to both isoforms of tau, 3R and 4R. This radioligand has been shown to image both AD-type and non-AD type of tau and enables the detection of tau pathology in AD and tauopathies such as progressive supranuclear palsy and corticobasal degeneration. Other tau radioligands such as [18F]T807 and [18F]THK5117 have shown promising results in vivo in AD patients. Future studies are needed to assess whether these tracers can be useful as diagnostic tools or as markers in clinical trials aimed at targeting hyperphosphorylated tau aggregates. Movement disorders Other neurodegenerative disorders associated to specific pathological abnormalities are Parkinson´s disease and Huntington´s disease. The pathological hallmark of Parkinson´s disease is the formation of aggregates of alpha-synuclein in Lewy bodies. At present, there are no radioligands that show selectivity for alpha-synuclein, but the search of suitable imaging probes for alpha-synuclein is an area of intensive research. Degeneration of the nigrostriatal dopaminergic projection is a pathological feature of degenerative parkinsonism. Markers for dopaminergic terminals such as the dopamine transporter or the vescicular monamine transporter type 2 are suitable imaging targets for in vivo assessment of dopaminergic degeneration. Radioligands for these pre-synaptic targets, such as [123I]FP-CIT (DaTSCAN, GE-Healthcare) or [18F]FP-DTBZ (AV-133, Ely Lilly) are suitable imaging tools for the assessment of nigrostriatal degeneration. These radioligands can be used to examine the presence of degenerative parkinsonism in patients with unclear diagnosis and to identify those patients with dopaminergic deficit that can be enrolled in clinical trials of neuroprotection. In Huntington´s disease, the presence of intracellular aggregates of mutated huntingtin is a pathological feature of the disorder that is characterized by the loss of medium-sized spiny neurons of the striatum. Although radioligands for imaging mutated huntingtin are not yet available, imaging targets of the dopaminergic system, such as D1 and D2 receptors, can be used to assess the integrity of the striatal neurons. Another important target in HD is the phosphodiesterase 10 A (PDE10A) enzyme. PDE10A is highly expressed in medium-sized spiny neurons. Recent PET studies with different PDE10A radioligands have shown that PDE10A is severely affected in HD patients already at a pre-manifest stage of the disease. Clinical trials aimed at specifically targeting PDE10A enzyme are ongoing and future trials are under design to specifically target mutated huntingtin. In this context, PDE10A imaging can be a suitable marker for the assessment of the effect of lowering huntingtin in HD. Conclusions The development of radioligands for A has contributed to major changes in molecular neuroimaging, providing tools for the in vivo examination of disease pathology. The field is expanding and new pathological imaging tools are under development. The discovery of new tools to directly examine the pathological abnormalities associated with major neurodegenerative disorders will likely provide biomarkers of great utility in the clinical setting and for optimal design and evaluation of treatment efficacy in clinical trials.

Speaker: Andrea Varrone (Karolinska Stoccolma)

Slides VARRONE,_Andrea_–_Molecular_brain_imaging_in_neurodegenerative_disorders.pdf

08:55 Dedicated detector systems for brain imaging

The aim of this contribution is to show the need for dedicated Brain PET imagers in the clinical practice. A review of former designs of such system will be shown, as well as new developed ideas# and running projects. Dedicated Brain PET could be used as a standalone solution but also combined with other imaging techniques such as MRI. Novel ideas from Majewski’s group to use a Flexible PET configuration in the operation room could help clinicians to carry out surgery procedures with the help of complementary PET information. The aim of the adaptive configuration is to better position the PET system around the head without disturbing the surgeon work. An “ambulatory” neuroscience version is also suggested by this group. The major idea behind this design is to provide the user with a portable Brain PET system, that is, motion tolerant but also imaging agents on-demand. Currently, at least two EU projects are undergoing, with the aim to design and develop, Brain PET detector, with the capability of being MR compatible. They are led by Del Guerra in Italy (Trimage) and Benlloch in Spain (MindView). They have different approaches that will be shown in this contribution. A deeper view to the MindView idea will be described. Pilot tests with 3 layers of staggered 1.5 mm pixels have been tried with 12x12 SiPM arrays providing encouraging results. Alternatively to the pixelated approach, monolithic slabs 50x50x20 mm3 have also being successfully tried. The special readout returning information on each SiPM array row and column, offers an innovative method to characterize the light distribution within the crystal. Center of Gravity methods, as well as Fitting tools to the light distribution and Neuronal Networks are being tested. The aim of both pixelated and monolithic approaches is to reach an intrinsic detector resolution in the 1-1.5 mm regime and, therefore, reconstructed images nearing 1 mm FWHM resolution.

Speaker: Antonio J. Gonzales Martinez (I3M)

Slides GONZALES,_Antonio_–_Dedicated_detector_systems_for_brain_imaging.pdf

09:20 → 09:35 Coffee break

09:35 → 10:00 Brain Session and Head and Neck Session

Convener: Vesna Sossi

09:35 Head and neck cancers, what the surgeon expect from imaging

Speaker: Jacopo Galli (Universita' Cattolica)

Slides GALLI,_Jacopo_–_Head_and_Neck_cancers.ppt

10:00 → 10:30 Round table/discussion session: Do we need dedicated detectors for brain and head and neck?

Convener: Vesna Sossi

10:30 → 15:30 Lunch - Visit of "grotta di Nettuno" (TBC)

15:30 → 16:50 Technology session I

Conveners: Dr Paul Lecoq (CERN), Dr Stan Majewski (West Virginia University)

15:30 Is sub-100 picosecond time resolution feasible in realistic TOF PET systems?

The use of time-of-flight (TOF) information in positron emission tomography (PET) significantly improves image quality. Commercially available TOF-PET systems currently have a coincidence resolving time (CRT) of ~500 ps FWHM. The TOF benefit is inversely proportional to the CRT. In recent years, several groups have achieved experimental CRTs of about ~100 ps FWHM at the bench-top level, using small (~mm) scintillation crystals in combination with PMTs or SiPMs. An intriguing question is whether sub-100 picosecond CRT’s will be feasible in clinical PET systems. In 2012 we have shown how the statistical lower bound on the time resolution of a scintillation detector can be calculated as a function of the pertinent scintillator and photosensor properties. It seems reasonable to expect that future photosensors with low single-photon timing resolution (SPTR) and high photodetection efficiency (PDE) will enable CRTs << 100 ps FWHM in small scintillators. It is less obvious whether sub-100 ps CRT’s can be achieved in large (~cm) crystals that are typically used in clinical PET systems. One important bottleneck is the variation of the optical path lengths of scintillation photons within the crystal, which is a function of the varying position of interaction of the annihilation photons. Furthermore, improvement of the CRT only makes sense if it can be achieved without sacrificing other important performance parameters, such as spatial resolution, energy resolution, and system sensitivity. These topics will be discussed from a theoretical as well as a practical point of view, including examples of recent experimental approaches towards sub-100 ps PET.

Speaker: Dr Dennis Schaart (Delft University of Technology)

Slides SCHAART,_Dennis_-_Is_sub-100_picosecond_time_resolution_feasible_in_realistic_TOF-PET_systems.pdf

15:50 Electronics and data acquisition for PET systems based on silicon photosensors in general

We present the requirements, challenges and possible implementations of the frontend electronics and the data acquisition systems for high-performance PET systems based on silicon photosensors. Two use cases, namely the APD-based breast scanner ClearPEM and the SiPM-based detector of EndoTOFPET-US, are used as illustrations. The application to a large sensitivity whole-body scanner with long axial field-of -view is also discussed.

Speaker: Joao Varela (Univeristy of Lisbon)

Slides VARELA,_Joao_–_Electronics_and_data_acquisition_in_medical_imaging.pdf

16:10 TOFPET ASICS

The TOFPET is a low power, low noise SiPM readout ASIC targeted, but not limited to, Time-of-Flight applications. It consists of a 64-channel analogue block, calibration circuitry, golden-references, bias generators and a global controller, featuring all-LVDS digital interface. It integrates signal conditioning and discrimination circuitry and high-performance TDCs for each of its 64 independent channels. One edge is free of pins, such that a rotated twin chip can be abutted to build a compact 128 channel module. Time and energy information are extracted with a dual-threshold technique. The time information is extracted with a leading edge discriminator and a low-power TDC with 50 ps (option 25 ps) time binning. The intrinsic time resolution of the channel is below 25 ps r.m.s., owing to the good SNR of the front-end. A second time stamp, derived from the falling edge of the pulse, is used for energy measurements using the information of the time-over- threshold. The rate capability per channel was proven with laser tests to exceed 80 kHz without measurable degradation due to baseline drift. Using Hamamatsu S12643-050CN MPPC 4x4 pixel matrices, the single-photon time resolution measured is 235 ps FWHM. System-level tests with 2 ASICs on board reading eight 3.5x3.5x15 mm3 LYSO 4x4 crystal matrices (128 active channels) show a CTR of 300 ps FWHM.

Speaker: Manuel Rolo (INFN - Torino)

Slides ROLO,_Manuel_–_TofPet_Asic_–_status_and_perspectives.pdf

16:30 PET signal optimization for different tasks: from lesion detection to pattern definition

Important goals in clinical medical imaging are early disease detection, disease staging and ability to establish treatment efficacy; they all require the ability to reliably detect small changes in the appropriate biomarker distribution. High imaging resolution and sensitivity and accurate data quantification are important elements, but so is the use of appropriate tracers and image analysis methodology. This talk will discuss different metrics used in image analysis, such as value, regional shape and texture based approaches in relationship with expected disease characteristics. The synergy of multi-modality based images will also be presented.

Speaker: Vesna Sossi (University of British Columbia)

16:50 → 17:10 Coffee break

17:10 → 18:30 Technology session I

Conveners: Dr Paul Lecoq (CERN), Dr Stan Majewski (West Virginia University)

17:10 Silicon Photo-Multipliers: status and perspectives

Silicon photo-multipliers (SiPM) are novel type of photo-detectors whose success is growing in various scientific fields. They are compact devices composed of a few thousands of tiny avalanche photo-diode pixels grown on a common silicon substrate. The diodes are operated in Geiger mode so that any single carrier, generated either by photons or thermally in the depletion region, might trigger a self-sustaining avalanche. Avalanche quenching is obtained either passively, by means of resistors, or actively, by means of transistors integrated in the pixel. In the former case, because all SiPM pixels work in parallel, the output signal is the sum of the signals from all fired pixels: while each pixel is an independent binary photon counter, the SiPM as a whole works as an analog detector where the signal amplitude is proportional to the number of impinging photons (analog SiPM). In the latter case, the digital signal produced by each pixel is readout yielding a measurement of the total number of photons and their arrival time information (digital SiPM).In this talk SiPMs will be introduced, showing how they combine the advantages of vacuum photomultiplier tubes and avalanche photodiodes: indeed they have high gain, exceptional charge resolution, do not require pre-amplification, are operated at low bias voltages (below 100V) and are insensitive to magnetic fields. The basic device working principles and the most relevant figures of merit will be discussed. Some emphasis will be given on the differences between the analog and the digital types of SiPM, in view of a more detailed discussion during the workshop. Few examples of application will be illustrated in order to discuss additional factors (e.g. bias voltage uniformity, temperature stability and cost) which are relevant to the performances of complete detector systems

Speaker: Dr Gianmaria Collazuol (PD)

Slides COLLAZUOL,_Gianmaria_–_Silicon_Photo-Multipliers_status_et_perspectives.pdf

17:30 Analog SiPM

Speaker: Hamamatsu

17:50 Digital Photon Counting (DPC, dSiPM) technology - Scalable light detection for high sensitivity medical systems

Solid-state light detectors have significant advantages over photomultiplier tubes (PMT’s) such as ruggedness, compactness and insensitivity to magnetic fields, low operating voltage, power consumption and large scale fabrication possibilities using proven technologies and processes such as CMOS. Recently, the Silicon Photomultiplier (SiPM) gained momentum as a candidate to replace PMT’s in particular applications requiring precise timing and/or low-level light detection. The timing resolution of detectors is of particular interest not only for applications such as Time-of-Flight whole-body PET (WB-ToF-PET), increasing signal-to-noise ratio (SNR) and thus relative sensitivity enabling essentially lower dose/dynamic imaging. In addition, precise timing information can be a benefit also for applications such as in-beam therapy monitoring or organ specific imaging due to reduced or suppressed background. In addition, their compact size and insensitivity to magnetic fields enable opening new areas of application such as PET/MR. Since solid state detectors can be configured and adapted more easily than PMT’s new and more efficient detector designs are enabled (e.g. 1:1 coupling). However, as miniaturized SiPM’s allow attaining much more information about the source of light, this represents a challenge: this information needs to be channeled, transferred and processed. In the case of analog sensors this has to be accomplished by mixed-signal processing with extensive electronics using ASICs. The fully digital approach laterally embedded in CMOS, utilizing the intrinsically binary nature of Single-Photon-Avalanche-Diodes (SPADs) operated in Geiger-Mode avoids this additional complexity and, as will be shown, maintains intrinsic performance. The digital approach will be compared to the analog one. Early digitization also aids in scaling up such technology on all levels: power supply, configuration, data readout and timing. Inherent digitization plus integration at sensor level are key to an all-digital subsequent data chain and large-scale application possibilities while maintaining intrinsic performance parameters such as timing and energy resolution. This will be demonstrated on first application examples, for instance a prototype PET ring and a Cherenkov light detector.

Speaker: York Haemisch

Slides HAEMISCH,_York_–_2_–_The_digital_photon_counter_(DPC,_dSiPM).pptx

18:10 Reconstruction software

Speaker: Charalampos Tsoumpas (University of Leeds, United Kingdom)

Slides TSOUMPAS,_Charalampos_–_Software_for_tomographic_image_reconstruction.pptx

18:30 → 19:00 Round table/discussion session: SiPM: analog vs digital, benefits and drawbacks

Convener: Dr Gianmaria Collazuol (PD)

19:00 → 19:30 Round table/Discussion session

Conveners: Dr Paul Lecoq (CERN), Dr Stan Majewski (West Virginia University)

Sunday, 7 September

08:30 → 09:20 Intraoperative Guidance Session

Convener: Nathan Hall

08:30 Differentiation between cancer and inflammation, the role of the imagers

Speaker: Chumy Nwogu (Rosswell Park Cancer Institute, Buffalo)

Slides NWOGU,_Chumi_–_Differentiation_between_cancer_and_inflammation.ppt

08:55 Review of non-imaging surgical probes

Speaker: Riccardo Faccini (ROMA1)

Slides FACCINI,_Riccardo_–_Non_Imaging_Surgical_Probes.pptx

09:20 → 09:50 Coffee break

09:20 → 09:50 Poster

09:50 → 10:40 Intraoperative Guidance Session

Convener: Nathan Hall

09:50 Lymphoseek: Clinical validation of a design model for a receptor-­‐targeted SLN imaging agent

Tilmanocept is a synthetic molecular radiopharmaceutical  designed to minimize the limitations of currently used agents for sentinel lymph node identification. Its molecular properties and specific receptor binding allow for improved lymphatic entrance and high retention in the sentinel node, ultimately allowing for an improvement in the accuracy of cancer staging in diseases that utilize sentinel lymph node mapping. It avoids dangers associated with the use of human-derived substances. Furthermore, its chemical properties allow for attachment of additional imaging reporters, permitting future multi-modal imaging of the sentinel lymph node via a molecular target.

Speaker: David R. Vera (Univeristy of California S. Diego)

Slides VERA,_David_–_A_new_liver_imaging_agent.ppt VERA,_David_–_Lymphoseek_–_clinical_validation.pptx

10:15 Perioperative and intraoperative molecular imaging for tumor localization in surgical oncology

Speaker: Nathan Hall (Ohio State University, Columbus)

Slides HALL,_Nathan_–_Perioperative_and_intraoperative_molecular_imaging.pdf

10:40 → 11:10 ROUND TABLE / DISCUSSION SESSION: Multimodality detectors for surgery?

Convener: Chumy Nwogu

11:10 → 12:00 Summary and Conclusion

Conveners: David Townsend, Nathan Hall

11:10 Closing the Meeting

Speaker: David Townsend

Slides TOWNSEND,_David_–_Closing_the_Meeting.pptx

12:00 → 14:00 Lunch

14:00 → 16:00 Bus(es) for the airport (15 - 20 minutes)