A Prototype Ultrahigh Resolution PET Imaging System based on Hybrid Pixel-Waveform (HPWF) CdTe Detectors: Evaluation of CdTe PET for In Vivo Investigation of Neurodegenerative Disorders in Transgenic Mouse Models

257 Objectives We have demonstrated a prototype PET imaging setup based on HPWF CdTe pixel detectors that could offer a sub-500 μm spatial resolution for PET imaging of small animals. Our HPWF CdTe detectors offer a hybrid electronics circuitry which utilizes a 2048-channel ASIC connected to the anode pixels to readout the X-Y positions of gamma interactions, and a high-speed digitizer connected to the large cathode to sample the signal waveform and to derive energy, timing, and DOI (Z position). This detector architecture mediates many challenges present in small-pixel CdTe/CZT detectors and provides an improved timing resolution over anode triggering, an excellent energy resolution not affected by the charge sharing and loss effects associated with the small anode pixels, an excellent DOI resolution and allows the use of a highly simplified circuitry to handle the very high pixel density. The key objectives of this work are (a) to evaluate the intrinsic imaging performance of the HPWF-detector-based prototype PET setup, and (b) to demonstrate its unique capability for in vivo studying neurodegenerative diseases in transgenic mouse models. Methods The prototype PET system is composed of two HPWF CdTe detector panels aligned around a 4-D sample stage (X-Y-Z and rotation). Each detector panel can be configured to operate 1-4 detector hybrids, and each hybrid has a CdTe detector of 1.1 cm x 2.2 cm x 2 mm [1]. The anode of the CdTe detector has an array of 32x64 pixels of 350 μm x 350 μm in size read out by a custom-designed 2048-channel ASIC with a matching pixel pattern. The cathode of each CdTe detector (1.1 cm x 2.2 cm in size) is digitized by a discrete multi-channel high-speed digitizer (Gage CSE 1242). The interaction energy, timing, and DOI are determined from the sampled cathode waveform [2]. Results We have carried out various imaging studies to understand the preliminary imaging performance of the prototype system. Fig. 1C-1F shows a comparative imaging study of a mouse brain phantom using the Siemens Inveon Micro-CT/PET system and our CdTe PET system. Fig. 1G-1I shows the reconstructed image of a multiple point source phantom that demonstrates the ability of the system to resolve 250 μm diameter point sources separated by as small as 350 μm center-to-center spacing. In this study, we will further study the performance of this prototype PET imaging setup for specifically imaging neural degenerative disorders in transgenic mouse models. We will use 3-D printed mouse brain phantoms mimicking the tracer distribution associated with various NDD mouse models (ex. PiB/APPPS1). This study would allow us to quantify the potential impact of the unmatched spatial resolution for early diagnosis of Alzheimer’s disease, and for assessing treatment responses. Conclusions Our preliminary results have shown that HPWF CdTe detectors have the potential of making a great impact in PET imaging studying of neurodegenerative disease. A PET system constructed with the HPWF detectors could offer an ultrahigh spatial resolution (sub-400 μm), an excellent energy resolution (5 %), and a modest timing resolution. The compact and high-performance CdTe detector modules could be used to construct miniaturized and relatively low-cost mouse-brain scanners that offer an excellent balance of spatial resolution and sensitivity.