May 2015ECFA meeting1 Spin-off technologies for cancer diagnosis J. Varela, LIP Lisbon ECFA meeting, Coimbra, 15 May, 2015

May 2015ECFA meeting2 Since ≈10 years there is an active program in Lisbon developing spin-off from HE physics in medical imaging, mainly PET. Main activities are - ClearPEM - EndotofPET - Dedicated readout electronics for TOF-PET - New ClearPEM

May 2015ECFA meeting3 The ClearPEM project A dedicated PET scanner for breast imaging

May 2015ECFA meeting4 Why? - breast cancer is 3 rd most frequent cancer in humans - one in 10 women eventually develops breast cancer - good survival rate if detected at an early stage

May 2015ECFA meeting5 Hamamatsu APD array S8850 How? - take advantage of the (at that time) new APD photodetectors - Use our expertise in using APDs acquired in CMS

The ClearPEM scanners 6 ClearPEM-II in Monza (Italy)ClearPEM (prototype) in Coimbra 3.0 mm 2.5 mm 2.0 mm 1.5 mm 1.2 mm  Spatial resolution : 1.3 mm Obtained with Derenzo phantom (Na22 rods)  Sensitivity: 2 to 5%, depending on the configuration May 2015ECFA meeting

Breast tumor with FDG activity is concentrated in the periphery Clinical studies Tumour heterogeneity is recognised as an important challenge in modern oncology. Tumours consist of different populations of both benign and malignant cells with a specific impact on patient prognosis and outcome of neo-adjuvant treatments.

Tumor Lymph Node PET Whole Body Clinical case: multifocal breast cancer PET/CT exam Resolution is insufficient to identify multiple focus PEM : Multifocal Lesions ClearPEM

May 2015ECFA meeting9 In Monza, after one year of upgrade work on the image reconstruction software and user interface, the patient studies with ClearPEM have resumed very recently. A clinical study (200 patients) will evaluate if FLT (3-deoxy-3-[ 18 F]fluorothymidine) can be used to monitor the stage of the disease reducing the need to perform a biopsies. The performance of ClearPEM will be compared the one of the standard whole-body PET.

May 2015ECFA meeting10 In Coimbra, the team has mainly been using the ClearPEM as a small animal PET, and evaluating the possibility to use it as a brainPET.

May 2015ECFA meeting11 But we have been overtaken by technological progress APD SiPM

May 2015ECFA meeting12 But we have been overtaken by technological progress APD SiPMs allow for a dramatic improvement in time resolution

May 2015ECFA meeting13 The EndoTOFPET-US project EU FP7 project

May 2015ECFA meeting14

May 2015ECFA meeting15 Our role in the EndoTOFPET-US project is to develop the PET Detectors and the readout electronics based on SiPM readout of the scintillation light. The challenge is to have a highly integrated electronics with low power consumption and the best possible time resolution (≈ 200 ps).

May 2015ECFA meeting16 Our new, SiPM based, front end PET detector based on the TOF PET ASIC allows building the most compact PET detector ever.

May 2015ECFA meeting17 And allows building a PET scanner with many 10'000 channels

May 2015ECFA meeting18 Should we revisit ClearPEM? Make sure to keep the physician involved from the design phase I didn’t know I had a problem Hey, I’ve solved your clinical problem Physicist Physician

Thesis Design and Evaluation of a Positron Emission Tomograph for Breast Cancer Imaging, PhD Study and Development of the Clear–PEM Trigger and Data Acquisition System, PhD Development and Experimental Study of a Detector Module for Positron Emission Mammography, PhD The ClearPEM detector in breast cancer: correction methods for improved imaging, PhD Tecnologia de medicina molecular em oncologia. Avaliação da PET Mamografia, PhD Integrated Circuit Design for Time-of-Flight PET, PhD Controlo de Qualidade de matrizes de Fotodíodos de Avalanche, Master Development and Study of the Detector Control System and Calibration Software for the Clear-PEM Scanner, Master Development of an Intelligent Front End Board for a High Performance PET, Master Performance evaluation of new upgrades on ClearPEM detector modules, Master Evaluation of the Clear-PEM scanner in Clinical Environment, Master Development and Implementation of the ClearPEM-Sonic Detector Control System, Master Amplicador CMOS de baixo rudo para imagiologia medica, Master Investigação da detecção do cancro da mama com tomógrafo ClearPEM utilizando fantomas de gelatina, Master Development of an innovative LSO-SiPM detector module for high-performance Positron Emission Tomography, Master Development and Evaluation of Combined PET-MRI Imaging, PhD (on-going) Development of new high-performance Positron Emission Mammography based on silicon photomultipliers and optimized detector geometry, PhD (on-going) May 2015ECFA meeting19 8 PhD, 9 Master

May 2015ECFA meeting20 Thank you for your attention

May 2015ECFA meeting21 Backup slides

May 2015ECFA meeting22

May 2015ECFA meeting23 Time Of Flight > TOF What if we could measure the time difference very accurately ∆t =1 ns >>> ∆x=15 cm => ! If ∆t ≈10 ps events would be space points ! Detector 1 Detector 2

May 2015ECFA meeting24 Simulation: object D=35 cm, TOF=600 ps, Sensitivity gain factor 3.9 Karp JS, Surti S, Daube-Witherspoon ME, Muehllehner G. Benefit of time-of-flight in PET, experimental and clinical results:. J Nucl Med 2008; 49(3):

May 2015ECFA meeting25 Colon cancer, left upper quadrant peritoneal node 114 kg; BMI=32.2 ; 13.4 mCi; 2 hr post-inj Images J. Karp, University of Pennsylvania

May 2015ECFA meeting26 And the internal probe..