[Direct Positron Emission Imaging Using Ultrafast Timing Performance Detectors].

This is an explanatory paper on Sun Il Kwon et al., Nat. Photon. 15: 914-918, 2021 and some parts of this manuscript are translated from the paper. Medical imaging modalities such as X-ray computed tomography, Magnetic resonance imaging, positron emission tomography (PET), and single photon emission computed tomography, require image reconstruction processes, consequently constraining them to form cylindrical shapes. However, among them, only PET can use additional information, so called time of flight, on an event-by-event basis. If coincidence time resolution (CTR) of PET detectors improved to 30 ps, which corresponds to spatial resolution of 4.5 mm, directly localizing electron-positron annihilation point is possible, allowing us to circumvent image reconstruction processes and free us from the geometric constraint. We call this concept direct positron emission imaging (dPEI). We have developed ultrafast radiation detectors by focusing on Cherenkov photon detection. Furthermore, the CTR of 32 ps being equivalent to 4.8 mm spatial resolution is achieved by combining deep learning-based signal processing with the detectors. In this article, we explain how we developed the detectors and demonstrated the first dPEI using different types of phantoms, how we will tackle limitations to be addressed to make the dPEI more practical, and how dPEI will emerge as an imaging modality in nuclear medicine.

Simulation study of a brain PET scanner using TOF-DOI detectors equipped with first interaction position detection.

Objective. The aim of this study is to evaluate the performance characteristics of a brain positron emission tomography (PET) scanner composed of four-layer independent read-out time-of-flight depth-of-interaction (TOF-DOI) detectors capable of first interaction position (FIP) detection, using Geant4 application for tomographic emission(GATE). This includes the spatial resolution, sensitivity, count rate capability, and reconstructed image quality.Approach. The proposed TOF-DOI PET detector comprises four layers of a 50 × 50 cerium-doped lutetium-yttrium oxyorthosilicate (LYSO:Ce) scintillator array with 1 mm pitch size, coupled to a 16 × 16 multi-pixel photon counter array with 3.0 mm × 3.0 mm photosensitive segments. Along the direction distant from the center field-of-view (FOV), the scintillator thickness of the four layers is 2.5, 3, 4, and 6 mm. The four layers were simulated with a 150 ps coincidence time resolution and the independent readout make the FIP detection capable. The spatial resolution and imaging performance were compared among the true-FIP, winner-takes-all (WTA) and front-layer FIP (FL-FIP) methods (FL-FIP selects the interaction position located on the front-most interaction layer in all the interaction layers). The National Electrical Manufacturers Association NU 2-2018 procedure was referred and modified to evaluate the performance of proposed scanner.Main results. In detector evaluation, the intrinsic spatial resolutions were 0.52 and 0.76 mm full width at half-maximum (FWHM) at 0° and 30° incidentγ-rays in the first layer pair, respectively. The reconstructed spatial resolution by the filter backprojection (FBP) achieved sub-millimeter FWHM on average over the whole FOV. The maximum true count rate was 207.6 kcps at 15 kBq ml-1and the noise equivalent count rate (NECR_2R) was 54.7 kcps at 6.0 kBq ml-1. Total sensitivity was 45.2 cps kBq-1and 48.4 cps kBq-1at the center and 10 cm off-center FOV, respectively. The TOF and DOI reconstructions significantly improved the image quality in the phantom studies. Moreover, the FL-FIP outperformed the conventional WTA method in terms of the spatial resolution and image quality.Significance. The proposed brain PET scanner could achieve sub-millimeter spatial resolution and high image quality with TOF and DOI reconstruction, which is meaningful to the clinical oncology research. Meanwhile, the comparison among the three positioning methods indicated that the FL-FIP decreased the image degradation caused by Compton scatter more than WTA.

Performance evaluation of dedicated brain PET scanner with motion correction system.

OBJECTIVE: Various motion correction (MC) algorithms for positron emission tomography (PET) have been proposed to accelerate the diagnostic performance and research in brain activity and neurology. We have incorporated MC system-based optical motion tracking into the brain-dedicated time-of-flight PET scanner. In this study, we evaluate the performance characteristics of the developed PET scanner when performing MC in accordance with the standards and guidelines for the brain PET scanner. METHODS: We evaluate the spatial resolution, scatter fraction, count rate characteristics, sensitivity, and image quality of PET images. The MC evaluation is measured in terms of the spatial resolution and image quality that affect movement. RESULTS: In the basic performance evaluation, the average spatial resolution by iterative reconstruction was 2.2 mm at 10 mm offset position. The measured peak noise equivalent count rate was 38.0 kcps at 16.7 kBq/mL. The scatter fraction and system sensitivity were 43.9% and 22.4 cps/(Bq/mL), respectively. The image contrast recovery was between 43.2% (10 mm sphere) and 72.0% (37 mm sphere). In the MC performance evaluation, the average spatial resolution was 2.7 mm at 10 mm offset position, when the phantom stage with the point source translates to ± 15 mm along the y-axis. The image contrast recovery was between 34.2 % (10 mm sphere) and 66.8 % (37 mm sphere). CONCLUSIONS: The reconstructed images using MC were restored to their nearly identical state as those at rest. Therefore, it is concluded that this scanner can observe more natural brain activity.

Simulation study of potential time-of-flight capabilities for a multilayer DOI-PET detector with an independent readout structure.

A multilayer depth-of-interaction positron emission tomography (DOI-PET) detector with an independent readout structure has a potential advantage as a time-of-flight (TOF)-PET detector. The thin scintillator block of each detector layer can afford an improved coincidence time resolution (CTR) of ∼100 ps because the photon transfer time spread within the scintillator inherently decreases. To evaluate the potential TOF capabilities of a multilayer DOI-PET detector, which consists of thin layers of a cerium-doped lutetium-yttrium oxyorthosilicate (LYSO:Ce) scintillator coupled to a multi-pixel photon counter (MPPC) array, we examined the detector's CTR performance via Monte Carlo simulations. We used several types of scintillator structures: a monolithic plate, laser-processing array with 3.2 mm pitch, fine laser-processing array with 1.6 mm pitch, and pixelated array with 3.2 mm pitch, with 2, 4, 6, and 8 mm thickness values of a 25.6 mm × 25.6 mm scintillator cross-section. The MPPC array was composed of 3.0 mm × 3.0 mm photosensitive segments arranged in an 8 × 8 array. Here, we note that the CTR performance also significantly depends on the timing detection method, which generates a timing trigger signal for coincidence detection. Thus, we evaluated the CTRs for each scintillator structure by adopting four timing detection methods: using the total sum signal of 64 MPPC chips (T_sum), the maximum signal in the 64 MPPC chips (Max), the sum signal of a partial number of MPPC chips located at and in the vicinity of theγ-ray interaction position (P_sum), and the average of the timestamps generated at several MPPC chips (Ave). When using the T_sum for timing detection, the CTR full width at half-maximum values were ∼100 ps regardless of the scintillator structure. However, when using the Max signal approach, the CTRs of the monolithic plates, laser-processing arrays, and fine-pitch laser-processing arrays were drastically degraded with increasing thickness. On the other hand, the CTRs of the pixelated arrays exhibited almost no degradation. To improve the CTRs of the monolithic plate and the (fine-pitch) laser-processing array that exhibit a large light spread in the scintillator block, we applied the P_sum and Ave methods. The resulting CTRs significantly improved upon using P_sum; however, in the Ave approach the improvement effect disappeared when the thickness was <6 mm in case of our simulation.

Ultrafast timing enables reconstruction-free positron emission imaging.

X-ray and gamma-ray photons are widely used for imaging but require a mathematical reconstruction step, known as tomography, to produce cross-sectional images from the measured data. Theoretically, the back-to-back annihilation photons produced by positron-electron annihilation can be directly localized in three-dimensional space using time-of-flight information without tomographic reconstruction. However, this has not yet been demonstrated due to the insufficient timing performance of available radiation detectors. Here, we develop techniques based on detecting prompt Cerenkov photons, which when combined with a convolutional neural network for timing estimation resulted in an average timing precision of 32 picoseconds, corresponding to a spatial precision of 4.8 mm. We show this is sufficient to produce cross-sectional images of a positron-emitting radionuclide directly from the detected coincident annihilation photons, without using any tomographic reconstruction algorithm. The reconstruction-free imaging demonstrated here directly localizes positron emission, and frees the design of an imaging system from the geometric and sampling constraints that normally present for tomographic reconstruction.

Performance evaluation of a high-resolution brain PET scanner using four-layer MPPC DOI detectors.

A high-resolution positron emission tomography (PET) scanner, dedicated to brain studies, was developed and its performance was evaluated. A four-layer depth of interaction detector was designed containing five detector units axially lined up per layer board. Each of the detector units consists of a finely segmented (1.2 mm) LYSO scintillator array and an 8 × 8 array of multi-pixel photon counters. Each detector layer has independent front-end and signal processing circuits, and the four detector layers are assembled as a detector module. The new scanner was designed to form a detector ring of 430 mm diameter with 32 detector modules and 168 detector rings with a 1.2 mm pitch. The total crystal number is 655 360. The transaxial and axial field of views (FOVs) are 330 mm in diameter and 201.6 mm, respectively, which are sufficient to measure a whole human brain. The single-event data generated at each detector module were transferred to the data acquisition servers through optical fiber cables. The single-event data from all detector modules were merged and processed to create coincidence event data in on-the-fly software in the data acquisition servers. For image reconstruction, the high-resolution mode (HR-mode) used a 1.2 mm2 crystal segment size and the high-speed mode (HS-mode) used a 4.8 mm2 size by collecting 16 crystal segments of 1.2 mm each to reduce the computational cost. The performance of the brain PET scanner was evaluated. For the intrinsic spatial resolution of the detector module, coincidence response functions of the detector module pair, which faced each other at various angles, were measured by scanning a 0.25 mm diameter 22Na point source. The intrinsic resolutions were obtained with 1.08 mm full width at half-maximum (FWHM) and 1.25 mm FWHM on average at 0 and 22.5 degrees in the first layer pair, respectively. The system spatial resolutions were less than 1.0 mm FWHM throughout the whole FOV, using a list-mode dynamic RAMLA (LM-DRAMA). The system sensitivity was 21.4 cps kBq-1 as measured using an 18F line source aligned with the center of the transaxial FOV. High count rate capability was evaluated using a cylindrical phantom (20 cm diameter × 70 cm length), resulting in 249 kcps in true and 27.9 kcps at 11.9 kBq ml-1 at the peak count in a noise equivalent count rate (NECR_2R). Single-event data acquisition and on-the-fly software coincidence detection performed well, exceeding 25 Mcps and 2.3 Mcps for single and coincidence count rates, respectively. Using phantom studies, we also demonstrated its imaging capabilities by means of a 3D Hoffman brain phantom and an ultra-micro hot-spot phantom. The images obtained were of acceptable quality for high-resolution determination. As clinical and pre-clinical studies, we imaged brains of a human and of small animals.

Intrinsic spatial resolution evaluation of the X'tal cube PET detector based on a 3D crystal block segmented by laser processing.

The X'tal cube is a depth-of-interaction (DOI)-PET detector which is aimed at obtaining isotropic resolution by effective readout of scintillation photons from the six sides of a crystal block. The X'tal cube is composed of the 3D crystal block with isotropic resolution and arrays of multi-pixel photon counters (MPPCs). In this study, to fabricate the 3D crystal block efficiently and precisely, we applied a sub-surface laser engraving (SSLE) technique to a monolithic crystal block instead of gluing segmented small crystals. The SSLE technique provided micro-crack walls which carve a groove into a monolithic scintillator block. Using the fabricated X'tal cube, we evaluated its intrinsic spatial resolution to show a proof of concept of isotropic resolution. The 3D grids of 2 mm pitch were fabricated into an 18 × 18 × 18 mm(3) monolithic lutetium yttrium orthosilicate (LYSO) crystal by the SSLE technique. 4 × 4 MPPCs were optically coupled to each surface of the crystal block. The X'tal cube was uniformly irradiated by (22)Na gamma rays, and all of the 3D grids on the 3D position histogram were separated clearly by an Anger-type calculation from the 96-channel MPPC signals. Response functions of the X'tal cube were measured by scanning with a (22)Na point source. The gamma-ray beam with a 1.0 mm slit was scanned in 0.25 mm steps by positioning of the X'tal cube at vertical and 45° incident angles. The average FWHM resolution at both incident angles was 2.1 mm. Therefore, we confirmed the isotropic spatial resolution performance of the X'tal cube.