We present the most recent advances in photo-detector design employed in time of flight positron emission tomography (ToF-PET). PET is a molecular imaging modality that collects pairs of coincident (temporally correlated) annihilation photons emitted from the patient body. The annihilation photon detector typically comprises a scintillation crystal coupled to a fast photo-detector. ToF information provides better localization of the annihilation event along the line formed by each detector pair, resulting in an overall improvement in signal to noise ratio (SNR) of the reconstructed image. Apart from the demand for high luminosity and fast decay time of the scintillation crystal, proper design and selection of the photo-detector and methods for arrival time pick-off are a prerequisite for achieving excellent time resolution required for ToF-PET. We review the two types of photo-detectors used in ToF-PET: photomultiplier tubes (PMTs) and silicon photo-multipliers (SiPMs) with a special focus on SiPMs.

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This study investigates the physical limitations involved in the extraction of accurate timing information from pixellated scintillation detectors for positron emission tomography (PET). Accurate physical modeling of the scintillation detection process, from scintillation light generation through detection, is devised and performed for varying detector attributes, such as the crystal element length, light yield, decay time and surface treatment. The dependence of light output and time resolution on these attributes, as well as on the photon interaction depth (DoI) of the annihilation quanta within the crystal volume, is studied and compared with experimental results. A theoretical background which highlights the importance of different time blurring factors for instantaneous ('ideal') and exponential ('realistic') scintillation decay is developed and compared with simulated data. For the case of a realistic scintillator, our experimental and simulation findings suggest that dependence of detector performance on DoI is more evident for crystal elements with rough ('as cut') compared to polished surfaces (maximum observed difference of 64% (25%) and 22% (19%) in simulation (measurement) for light output and time resolution, respectively). Furthermore we observe distinct trends of the detector performance dependence on detector element length and surface treatment. For short crystals (3 × 3 × 5 mm(3)) an improvement in light output and time resolution for 'as cut' compared to polished crystals is observed (3% (7%) and 9% (9%) for simulation (measurement), respectively). The trend is reversed for longer crystals (3 × 3 × 20 mm(3)) and an improvement in light output and time uncertainty for polished compared to 'as cut' crystals is observed (36% (6%) and 40% (20%) for simulation (measurement), respectively). The results of this study are used to guide the design of PET detectors with combined time of flight (ToF) and DoI features.

Monte Carlo simulations are increasingly used in scintigraphic imaging to model imaging systems and to develop and assess tomographic reconstruction algorithms and correction methods for improved image quantitation. GATE (GEANT4 application for tomographic emission) is a new Monte Carlo simulation platform based on GEANT4 dedicated to nuclear imaging applications. This paper describes the GATE simulation of a prototype of scintillation camera dedicated to small-animal imaging and consisting of a CsI(Tl) crystal array coupled to a position-sensitive photomultiplier tube. The relevance of GATE to model the camera prototype was assessed by comparing simulated 99mTc point spread functions, energy spectra, sensitivities, scatter fractions and image of a capillary phantom with the corresponding experimental measurements. Results showed an excellent agreement between simulated and experimental data: experimental spatial resolutions were predicted with an error less than 100 microns. The difference between experimental and simulated system sensitivities for different source-to-collimator distances was within 2%. Simulated and experimental scatter fractions in a [98-182 keV] energy window differed by less than 2% for sources located in water. Simulated and experimental energy spectra agreed very well between 40 and 180 keV. These results demonstrate the ability and flexibility of GATE for simulating original detector designs. The main weakness of GATE concerns the long computation time it requires: this issue is currently under investigation by the GEANT4 and the GATE collaborations.

Direct injection of therapies into tumors has emerged as an administration route capable of achieving high local drug exposure and strong anti-tumor response. A diverse array of immune agonists ranging in size and target are under development as local immunotherapies. However, due to the relatively recent adoption of intratumoral administration, the pharmacokinetics of locally-injected biologics remains poorly defined, limiting rational design of tumor-localized immunotherapies. Here we define a pharmacokinetic framework for biologics injected intratumorally that can predict tumor exposure and effectiveness. We find empirically and computationally that extending the tumor exposure of locally-injected interleukin-2 by increasing molecular size and/or improving matrix-targeting affinity improves therapeutic efficacy in mice. By tracking the distribution of intratumorally-injected proteins using positron emission tomography, we observe size-dependent enhancement in tumor exposure occurs by slowing the rate of diffusive escape from the tumor and by increasing partitioning to an apparent viscous region of the tumor. In elucidating how molecular weight and matrix binding interplay to determine tumor exposure, our model can aid in the design of intratumoral therapies to exert maximal therapeutic effect.

We present a unique data acquisition system designed to read out signals from the MADPET-II small animal LSO-APD PET tomograph. The scanner consists of 36 independent detector modules arranged in a dual-radial layer ring (phi 71 mm). Each module contains a 4 x 8 array of optically isolated, 2 x 2 mm LSO crystals, coupled one-to-one to a 32 channel APD. To take full advantage of the detector geometry, signals from each crystal are individually processed without any data reduction. This is realized using custom designed mixed-signal ASICs for analogue signal processing, and FPGAs to control the digitization of analogue signals and subsequent multiplexing. Analogue to digital converters (ADCs) digitize the signal peak height, time to digital converters (TDCs) time stamp each event relative to a system clock and two 32 bit words containing the energy, time and position information for each singles event are multiplexed through three FIFO stages before being written to disk via gigabit Ethernet. Every singles event is processed and stored in list-mode format, and coincidences are sorted post-acquisition in software. The 1152 channel data acquisition system was designed to be able to handle sustained data rates of up to 11 520 000 cps without loss (10 000 cps/channel). The timing resolution of the TDC was measured to be 1 ns FWHM. In addition to describing the data acquisition system, performance measurements made using a 128-channel detector prototype will be presented.

We propose in this study a novel PET detector concept as insert for simultaneous PET/MR imaging, using arrays of Silicon Photomultipliers (SiPMs) as photodetectors, read out by a data acquisition system based on sampling ADCs. A 2 × 2 LSO-SiPM detector array and four single channel LYSO-SiPM detectors have been evaluated and compared to a LSO-APD detector. A 17.9% energy resolution and a 1.4 ns time resolution have been measured. No degradation of these values could be detected when simultaneous MR acquisitions were performed. The nonlinear detector behaviour due to the limited dynamic range and recovery time effects has been studied. In addition, the contribution of dark counts and optical crosstalk for PET applications was also addressed. The feasibility for position localization of the incident light to a SiPM array using Anger logic has been investigated.

MADPET-II is a small animal PET tomograph that features individual Lutetium Oxyorthosilicate (LSO) crystal readout from Avalanche PhotoDiodes (APDs). The detector signals are preamplified by 16-channel fully integrated ASICs which are placed as close as possible to the detector in order to avoid attenuation of the signal or unwanted stray capacitance. However, the power consumption of the preamplifier (30 mW per channel) can cause heat transfer and, consequently, gain drift to temperature sensitive detectors. Temperature measurements on the front-end electronics of MADPET-II have shown a maximum increase of approximately 30 C in the area around the preamplifier and 10 C in the area around the APD-LSO detector with respect to room temperature. In the presence of this temperature gradient, energy spectra have been acquired from which a significant drift of the photopeak (3.4% per C) and a small increase of the mean energy resolution (3% over the whole temperature range studied) with increasing temperature has been observed. The effect of temperature on the time resolution is small in comparison to the effect of walk and jitter introduced by the analog processing electronics. The behavior of two 4 8 LSO-APD front-end detector arrays in coincidence at temperatures below ambient and at various values of the APD bias voltage in terms of energy and time resolution has also been studied. The total current drawn by the APDs (leakage current and photocurrent) has been monitored at various temperatures T and APD bias and was modelled and fitted by a theoretical function demonstrating a T and 1 dependence. No significant improvement on time resolution with decreasing temperature has been observed. For temperature stabilization and monitoring, thermoelectric cooling is considered appropriate for mounting in the limited free space of a PET scanner, especially when this is inside an MR scanner for simultaneous PET/MR imaging.