Ultrahigh Resolution Coplanar PET Imaging of Microfluidic Devices for Synthesizing PET Radiopharmaceuticals

Objectives: We will present experimental imaging results from a compact coplanar PET system based on ultrahigh resolution semiconductor detectors. This system offers an intrinsic resolution of sub-250 μm, which would be ideally suited for imaging microfluidic features in PET radiopharmaceutical synthesis micro-reactors. This work focuses on the development of an ultrahigh resolution coplanar Hybrid Pixel-Waveform (HPWF) CdTe PET system, which uniquely combines cathode and anode information for optimizing system performance. We aim to (a) experimentally demonstrate our ultrahigh sub-250 μm spatial resolution capability for visualizing the microfluidic features (made possible in part by the combination of small pixel sizes and positron range limiting material), (b) prove reasonable sensitivity through the selection of a coplanar geometry absent of angular sampling, (c) identifying signal to noise limiting factors, (d) optimize timing resolution by cathode waveform investigation, and (e) providing a quantitative analysis of feature size.

Methods: Our setup consists of two HPWF CdTe detectors operated in coincidence. This detector design utilizes information from the highly-pixelated anode and cathode waveform to improve intrinsic performance. The HPWF design uses the anode for only the X-Y spatial interaction position and course timing information. The detector cathode waveform is digitized and is fitted to pre-existing waveform models to determine interaction parameters, such as interaction time, electron and hole drifting times, total energy deposition, and the depth of interaction (DOI). Each detector has a 11 mm x 22 mm x 2 mm CdTe crystal which is bump bonded onto a CMOS ASIC composed of 2048 anode pixels arranged in 64 x 32 array with each pixel of 350 µm x 350 µm in size [1]. The HPWF readout system allows us to record the anode pixel addresses of gamma ray interactions, as well as cathode waveform for deriving the interaction timing and DOI information [2,3]. This readout scheme ensures an ultrahigh resolution localization of gamma ray interactions in 3-D and hence an ultrahigh PET imaging resolution as shown in [3] and in the supporting images. In this study, we will illustrate the imaging capability of the dual-panel PET setup for imaging microfluidic chips with features of various sizes (ranging from 50 μm to 500 μm) and filled with a variety of Cu-64 activities. We will also explore different ML image reconstruction approaches that are implemented either in 2-D or 3-D object space, and potentially making use of the known design of the microfluidic design as image prior. The resulting images will be discussed in this presentation.

Results: We have experimentally demonstrated the ultrahigh resolution capability by imaging a 250 μm Na-22 point source, as shown in Fig. 1I. A preliminary evaluation of system’s spatial resolution performance was assessed by imaging a microfluidic device featuring channels of 500 μm width and separation with a depth of 100 μm (Fig. 1D). The device was prepped with 50 μCi of Cu-64 and was imaged for 20 hrs at a single angular position. Image formation was performed by simple back projection onto a 2-D plane in our geometrically calibrated 3-D object space represented by 201 x 201 pixels of 250 μm x 250 μm each. Preliminary PET image of the microfluidic device is shown in Fig 1.F, which confirms the potential of using this system for resolving even smaller structures in either 2-D or 3-D mode. We will carry out future imaging studies to verify the full capability for this specialized PET setup.

Conclusion: We have developed a compact planar PET system that could deliver an ultrahigh spatial resolution of sub-250 μm and a reasonable sensitivity using a closely spaced geometry. Complementary to existing PET imaging systems, this system could find its application in imaging microstructures containing PET radiotracers, such as in micro-reactors used for PET radiochemical development. Research Support: N/A