Pathophysiology characterization of Alzheimer's disease in South China's aging population: for the Greater-Bay-Area Healthy Aging Brain Study (GHABS).

INTRODUCTION: The Guangdong-Hong Kong-Macao Greater-Bay-Area of South China has an 86 million population and faces a significant challenge of Alzheimer's disease (AD). However, the characteristics and prevalence of AD in this area are still unclear due to the rarely available community-based neuroimaging AD cohort. METHODS: Following the standard protocols of the Alzheimer's Disease Neuroimaging Initiative, the Greater-Bay-Area Healthy Aging Brain Study (GHABS) was initiated in 2021. GHABS participants completed clinical assessments, plasma biomarkers, genotyping, magnetic resonance imaging (MRI), ß-amyloid (Aß) positron emission tomography (PET) imaging, and tau PET imaging. The GHABS cohort focuses on pathophysiology characterization and early AD detection in the Guangdong-Hong Kong-Macao Greater Bay Area. In this study, we analyzed plasma Aß42/Aß40 (A), p-Tau181 (T), neurofilament light, and GFAP by Simoa in 470 Chinese older adults, and 301, 195, and 70 had MRI, Aß PET, and tau PET, respectively. Plasma biomarkers, Aß PET, tau PET, hippocampal volume, and temporal-metaROI cortical thickness were compared between normal control (NC), subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia groups, controlling for age, sex, and APOE-ε4. The prevalence of plasma A/T profiles and Aß PET positivity were also determined in different diagnostic groups. RESULTS: The aims, study design, data collection, and potential applications of GHABS are summarized. SCD individuals had significantly higher plasma p-Tau181 and plasma GFAP than the NC individuals. MCI and dementia patients showed more abnormal changes in all the plasma and neuroimaging biomarkers than NC and SCD individuals. The frequencies of plasma A+/T+ (NC; 5.9%, SCD: 8.2%, MCI: 25.3%, dementia: 64.9%) and Aß PET positivity (NC: 25.6%, SCD: 22.5%, MCI: 47.7%, dementia: 89.3%) were reported. DISCUSSION: The GHABS cohort may provide helpful guidance toward designing standard AD community cohorts in South China. This study, for the first time, reported the pathophysiology characterization of plasma biomarkers, Aß PET, tau PET, hippocampal atrophy, and AD-signature cortical thinning, as well as the prevalence of Aß PET positivity in the Guangdong-Hong Kong-Macao Greater Bay Area of China. These findings provide novel insights into understanding the characteristics of abnormal AD pathological changes in South China's older population.

[Application of PET-LINAC in Biology-guided Radiotherapy].

Biology-guided radiotherapy (BgRT) is a novel technique of external beam radiotherapy, combining positron emission tomography-computed tomography (PET-CT) with a linear accelerator (LINAC). The key innovation is to utilize PET signals from tracers in tumor tissues for real-time tracking and guiding beamlets. Compared with a traditional LINAC system, a BgRT system is more complex in hardware design, software algorithm, system integration and clinical workflow. RefleXion Medical has developed the world's first BgRT system. Nevertheless, its actively advertised function, PET-guided radiotherapy, is still in the research and development phase. In this review study, we presented a number of issues related to BgRT, including its technical advantages and potential challenges.

ß-Amyloid discordance of cerebrospinal fluid and positron emission tomography imaging shows distinct spatial tau patterns.

Extracellular ß-amyloid plaques and intracellular neurofibrillary tau tangles are the primary hallmarks of Alzheimer's disease. ß-Amyloid pathology can be directly quantified by positron emission tomography imaging or indirectly by measuring the decrease of cerebrospinal fluid ß-amyloid42/ß-amyloid40 ratio. Although these two ß-amyloid biomarkers may be considered interchangeable, they sometimes show discordance, particularly in early stage of Alzheimer's disease. Individuals with cerebrospinal fluid ß-amyloid positive only or ß-amyloid positron emission tomography positive only may be at early amyloidosis stage compared to those who are cerebrospinal fluid ß-amyloid negative and ß-amyloid positron emission tomography negative orcerebrospinal fluid ß-amyloid positive and ß-amyloid positron emission tomography positive. Besides, ß-amyloid pathology may play an initiating role in Alzheimer's disease onset, leading to subsequent tau increases. However, it is still unclear whether individuals with different ß-amyloid pathways have distinct spatial patterns of cortical tau tangles in early amyloidosis stage. In this study, we analyzed 238 cognitively unimpaired and 77 mild cognitive impairment individuals with concurrent (interval of acquisition <1 year) 18F-flortaucipir tau positron emission tomography, ß-amyloid (18F-florbetapir or 18F-florbetaben) positron emission tomography and cerebrospinal fluid ß-amyloid42 and ß-amyloid40 and cerebrospinal fluid p-Tau181 and divided them into four different cerebrospinal fluid/positron emission tomography groups based on the abnormal status of cerebrospinal fluid ß-amyloid42/ß-amyloid40 (cerebrospinal fluid±) and ß-amyloid positron emission tomography (±). We determined the cortical regions with significant tau elevations of different cerebrospinal fluid/positron emission tomography groups and investigated the region-wise and voxel-wise associations of tau positron emission tomography images with cerebrospinal fluid ß-amyloid42/ß-amyloid40, ß-amyloid positron emission tomography and cerebrospinal fluid p-Tau/ß-amyloid40 in early (cerebrospinal fluid positive/positron emission tomography negative and cerebrospinal fluid negative/positron emission tomography positive) and late (cerebrospinal fluid positive/positron emission tomography positive) amyloidosis stages. By compared to the cerebrospinal fluid negative/positron emission tomography negative individuals (Ref) without evidence of tau increase measured by cerebrospinal fluid or positron emission tomography, cerebrospinal fluid positive/positron emission tomography negative individuals showed higher tau in entorhinal but not in BraakIII/IV and BraakV/VI, whereas cerebrospinal fluid negative/positron emission tomography positive individuals had significant tau elevations in BraakV/VI but not in entorhinal and BraakIII/IV. In contrast, cerebrospinal fluid positive/positron emission tomography positive individuals showed significant tau increases in all the cortical regions than the Ref group. The voxel-wise analyses provided further evidence that lower cerebrospinal fluid ß-amyloid42/ß-amyloid40 was associated with higher tau in entorhinal, whilst higher ß-amyloid positron emission tomography was related to higher tau in BraakV/VI regions in early amyloidosis stage. Both lower cerebrospinal fluid ß-amyloid42/ß-amyloid40 and higher ß-amyloid positron emission tomography were correlated with tau aggregation in all the Braak stages regions in late amyloidosis stage. These findings provide novel insights into the spatial patterns of cortical tau tangles in different amyloidosis stages of Alzheimer's disease, suggesting cerebrospinal fluid ß-amyloid and ß-amyloid positron emission tomography discordant groups may have distinct characteristics of cortical tau tangles in early amyloidosis stage.

Optical Simulation and Experimental Assessment with Time-Walk Correction of TOF-PET Detectors with Multi-Ended Readouts.

As a commonly used solution, the multi-ended readout can measure the depth-of-interaction (DOI) for positron emission tomography (PET) detectors. In the present study, the effects of the multi-ended readout design were investigated using the leading-edge discriminator (LED) triggers on the timing performance of time-of-flight (TOF) PET detectors. At the very first, the photon transmission model of the four detectors, namely, single-ended readout, dual-ended readout, side dual-ended readout, and triple-ended readout, was established in Tracepro. The optical simulation revealed that the light output of the multi-ended readout was higher. Meanwhile, the readout circuit could be triggered earlier. Especially, in the triple-ended readout, the light output at 0.5 ns was observed to be nearly twice that of the single-ended readout after the first scintillating photon was generated. Subsequently, a reference detector was applied to test the multi-ended readout detectors that were constructed from a 6 × 6 × 25 mm3 LYSO crystal. Each module is composed of a crystal coupled with multiple SiPMs. Accordingly, its timing performance was improved by approximately 10% after the compensation of fourth-order polynomial fitting. Finally, the compensated full-width-at-half-maximum (FWHM) coincidence timing resolutions (CTR) of the dual-ended readout, side dual-ended readout, and triple-ended readout were 216.9 ps, 231.0 ps, and 203.6 ps, respectively.

A Novel Portable Gamma Radiation Sensor Based on a Monolithic Lutetium-Yttrium Oxyorthosilicate Ring.

Portable radiation detectors are widely used in environmental radiation detection and medical imaging due to their portability feature, high detection efficiency, and large field of view. Lutetium-yttrium oxyorthosilicate (LYSO) is a widely used scintillator in gamma radiation detection. However, the structure and the arrangement of scintillators limit the sensitivity and detection accuracy of these radiation detectors. In this study, a novel portable sensor based on a monolithic LYSO ring was developed for the detection of environmental radiation through simulation, followed by construction and assessments. Monte Carlo simulations were utilized to prove the detection of gamma rays at 511 keV by the developed sensor. The simulations data, including energy resolutions, decoding errors, and sensitivity, showed good potential for the detection of gamma rays by the as-obtained sensor. The experimental results using the VA method revealed decoding errors in the energy window width of 50 keV less than 2°. The average error was estimated at 0.67°, a sufficient value for the detection of gamma radiation. In sum, the proposed radiation sensor appears promising for the construction of high-performance radiation detectors and systems.

Design study of a PET detector with 0.5 mm crystal pitch for high-resolution preclinical imaging.

Preclinical positron emission tomography (PET) is a sensitive and quantitative molecule imaging modality widely used in characterizing the biological processes and diseases in small animals. The purpose of this study is to investigate the methods to optimize a PET detector for high-resolution preclinical imaging. The PET detector proposed in this study consists of a 28 × 28 array of LYSO crystals 0.5 × 0.5 × 6.25 mm3in size, a wedged lightguide, and a 6 × 6 array of SiPMs 3 × 3 mm2in size. The simulation results showed that the most uniform flood map was achieved when the thickness of the lightguide was 2.35 mm. The quality of the flood map was significantly improved by suppressing the electronics noises using the simple threshold method with a best threshold. The peak-to-valley ratio of flood map improved 25.4% when the algorithm of ICS rejection was applied. An energy resolution (12.96% ± 1.03%) was measured on the prototype scanner constructed with 12 proposed detectors. Lastly, a prototype preclinic PET imager was constructed with 12 optimized detectors. The point source experiment was performed and an excellent spatial resolution (axial: 0.56 mm, tangential: 0.46 mm, radial: 0.42 mm) was achieved with the proposed high-performance PET detectors.

An 8.8 ps RMS Resolution Time-To-Digital Converter Implemented in a 60 nm FPGA with Real-Time Temperature Correction.

This paper presented a non-uniform multiphase (NUMP) time-to-digital converter (TDC) implemented in a field-programmable gate array (FPGA) with real-time automatic temperature compensation. NUMP-TDC is a novel, low-cost, high-performance TDC that has achieved an excellent performance in Altera Cyclone V FPGA. The root mean square (RMS) for the intrinsic timing resolution was 2.3 ps. However, the propagation delays in the delay chain of some FPGAs (for example, the Altera Cyclone 10 LP) vary significantly as the temperature changes. Thus, the timing performances of NUMP-TDCs implemented in those FPGAs are significantly impacted by temperature fluctuations. In this study, a simple method was developed to monitor variations in propagation delays using two registers deployed at both ends of the delay chain and compensate for changes in propagation delay using a look-up table (LUT). When the variations exceeded a certain threshold, the LUT for the delay correction was updated, and a bin-by-bin correction was launched. Using this correction approach, a resolution of 8.8 ps RMS over a wide temperature range (5 °C to 80 °C) had been achieved in a NUMP-TDC implemented in a Cyclone 10 LP FPGA.

Design study of fully wearable high-performance brain PETs for neuroimaging in free movement.

A practical wearable brain PET scanner capable of dynamic neuroimaging during free bodily movement will enable potential breakthrough basic neuroscience studies and help develop imaging-based neurological diagnoses and treatments. Weight, brain coverage, and sensitivity are three fundamental technical obstacles in the development of Fully Wearable High-Performance (FWHP) brain PET scanners. The purpose of this study is to investigate the feasibility of building a FWHP brain PET using a limited volume of lutetium-yttrium oxyorthosilicate (LYSO) scintillator crystals. Six scanners, consisted of the same volume (2.66 kg) of LYSO scintillators with combinations of 2 different crystal pitches (3 mm and 1.5 mm) and 3 different crystal lengths (20 mm, 10 mm, and 5 mm), were simulated. The performances of the six scanners were assessed and compared with Siemen's HRRT brain PET and mCT whole-body PET, in terms of aperture, axial field of views (AFOV), sensitivity, spatial resolution, count rates, and image noise property. The time-of-flight (TOF) information was included in the image reconstruction to improve the effective sensitivity. The effects of the TOF was assessed by scanning a Jaszczak phantom and reconstructing images with the maximum likelihood expectation maximization (MLEM) algorithm with different timing settings (non-TOF, 500 ps, 200 ps, 100 ps and 50 ps Coincidence Time Resolution, CTR). The signal-noise ratio (SNR) of the images were assessed and compared with those of the HRRT scanner and mCT scanner. The results show that it is possible to construct a FWHP brain PET with better spatial resolution than the dedicated HRRT brain PET, comparable effective sensitivity (with 50 ∼ 100 ps CTR), and whole-brain coverage (23.7 cm inner diameter and 13.4 cm axial field of view) using 2.66 kg of LYSO.

Maximum likelihood activity and attenuation estimation using both emission and transmission data with application to utilization of Lu-176 background radiation in TOF PET.

PURPOSE: We present a new method for joint reconstruction of activity and attenuation images using both emission and transmission data and demonstrate its advantage over the standard maximum likelihood activity and attenuation (MLAA) reconstruction using emission data alone. METHODS: We define a joint likelihood function including both time-of-flight (TOF) emission data and transmission data. The latter can be obtained from an external source or from Lu-176 background radiation. Activity and attenuation images are estimated jointly by maximizing the likelihood function. The proposed method solves the undetermined scale problem in the conventional MLAA. A monotonically convergent algorithm was derived to optimize the objective function. Furthermore, we present a theoretical analysis of the noise propagation in the joint reconstruction. Simulations and phantom experiments were conducted to validate the feasibility of the proposed method. RESULTS: Quantitatively correct and less noisy images were reconstructed with the proposed method. Artifacts in the attenuation map reconstructed from the standard MLAA were removed by incorporating transmission data. Noise analysis was validated with different transmission sources and transmission count levels. The theoretical prediction indicated that noise of activity map would not change in a large range of transmission count level and a very low transmission count level could result in good estimation. CONCLUSIONS: The results demonstrate the feasibility of obtaining quantitatively correct images in TOF PET by using both emission and (weak) transmission data. The noise analysis also provides guidance for choosing a proper transmission source configuration to reduce noise propagation.

An Advanced 100-Channel Readout System for Nuclear Imaging.

Reading out from large-scale silicon photomultiplier (SiPM) arrays is a fundamental technical obstacle blocking the application of revolutionary SiPM technologies in nuclear imaging systems. Typically, it requires using dedicated application-specific integrated circuits (ASICs) that need a long iterative process, special expertise, and tools to develop. The pico-positron emission tomography (Pico-PET) electronics system is an advanced 100-channel readout system based on 1-bit sigma-delta modulation and a field-programmable gate array (FPGA). It is compact (6 × 6 × 0.8 cm3 in size), consumes little power (less than 3W), and is constructed with off-the-shelf low-cost components. In experimental studies, the Pico-PET system demonstrates excellent and consistent performance. In addition, it has some unique features that are essential for nuclear imaging systems, such as its ability to measure V-I curves, breakdown voltages, and the dark currents of 100 SiPMs accurately, simultaneously, and in real time. The flexibility afforded by FPGAs allows multiple-channel clustering and intelligent triggering for different detector designs. These highly sought-after features are not offered by any other ASICs and electronics systems developed for nuclear imaging. We conclude that the Pico-PET electronics system provides a practical solution to the long-standing bottleneck problem that has limited the development of potentially advanced nuclear imaging technology using SiPMs.

A preclinical PET detector constructed with a monolithic scintillator ring.

This paper presents a unique preclinical positron emission tomography (PET) detector constructed with a monolithic scintillator ring (MSR) and two rings of silicon photomultipliers (SiPM). The inner diameter, outer diameter and length of the MSR were 48.5 mm, 58.5 mm, and 25.1 mm, respectively. The two SiPM rings, constructed with 46 SiPMs, were air-coupled to the two ends of the MSR detector. The center of gravity (COG) and artificial neural network (ANN) methods were adapted to decode the positions of the gamma interactions in the circumferential (θ) and axial (Z) directions, respectively. Collimating systems, consisting of a tungsten collimator and a high-precision displacement and rotating platform, were constructed to assess the decoding accuracies of the MSR detector in both θ and Z directions. The average intrinsic full-width half maximums (FWHMs) and mean absolute errors (MAEs) of the decoding accuracies were 0.94 mm and 0.33 mm in the circumferential direction, 2.45 mm and 1.08 mm in the axial direction. An energy resolution of 10.7% was measured at 511 keV. The scintillating photons generated by a pair of coincidence gamma photons overlap with each other, and cause circumferential parallax errors in the lines of response (LOR). The experimental results show that the average FWHM errors in the θ direction increased slightly from 0.94 mm to 1.14 mm when Δθ of the two single events was larger than 70°. The imaging performance of the MSR detector was also initially assessed with a Derenzo phantom filled with 18F-FDG. The rods with a diameter larger than 1.2 mm can be resolved. The energy resolutions were 12.3% at 511 keV (single events), and 11.4% at 1022 keV (coincidence events). We concluded that it is feasible to construct the high-performance preclinical PET scanners using one or multiple MSR detectors.

A depth encoding PET detector using four-crystals-to-one-SiPM coupling and light-sharing window method.

PURPOSE: Depth of interaction (DOI) decoding capability is of great importance for positron emission tomography (PET) requiring high resolution. In this study, we presented a novel low-cost DOI detector design with four crystals coupling to one SiPM, based on the method of rectangular light-sharing window (RLSW). A prototype detector was constructed, calibrated, and assessed using the methods of homogeneous radiation and flood map analysis. METHODS: The DOI detector was constructed with a 4 × 4 array of lutetium-yttrium oxyorthosilicate (LYSO) crystals (2.95 mm × 2.95 mm × 20 mm3 ), barium sulfate (BaSO4 ) reflectors, and optical glues. A RLSW 7 mm in height was deployed in the BaSO4 reflectors. A non-DOI detector with identical dimensions and without RLSW was also constructed for comparison. The light-output surface of the detector was air-coupled with a 4 × 4 array of SiPMs (3 mm × 3 mm2 ). The signals generated from the 16 SiPMs were read out by a custom-designed electronic system, and the signals from four adjacent 3 mm SiPMs were summed into one signal to emulate a 2 × 2 array of 6 mm SiPMs. The RLSW caused the DOI-related position shifts of the crystal spots in the flood map. A homogeneous radiation method was used to establish the transfer functions to convert the spot shifts measured from the flood map into DOI measurements. The accuracy of the DOI measurements was assessed with data acquired using the conventional collimated radiation method. RESULTS: All 16 crystals are distinctly separated from each other in the flood map. Twelve crystals, including four central crystals and eight edge crystals, have the DOI capability. The full width half maximum (FWHM) of the DOI measurements of the central crystals and the edge crystals are 3.06 ± 0.08 and 3.79 ± 0.15 mm, respectively, for the configuration with four crystals coupling to one SiPM. By contrast, the FWHMs (3.98 ± 0.16 and 5.12 ± 0.38 mm, respectively) are slightly worse for the configuration with one crystal coupling to one SiPM. The average and standard deviation (STD) of the FWHM energy resolutions of the DOI detector and non-DOI detector were 10.2% ± 0.7% and 10.7% ± 1.7%, respectively. Their FWHM coincidence timing resolutions were 197.0 ± 9.6 and 206.4 ± 13.3 ps, respectively. The RLSW had no significant impact on the energy resolutions and timing resolutions of the DOI detector. CONCLUSIONS: The novel four-crystals-to-one-SiPM coupling technology is a cost-efficient approach to construct high-performance detector modules with DOI capability. The methods of homogeneous radiation and flood map analysis are easy to perform and of good performance. Those methods can be adapted in the clinic PET scanners to enable the capability of DOI measurements.

Two-crossed-polarizers based optical property modulation method for ionizing radiation detection for positron emission tomography.

Recent work shows that Pockels effect and optics pump-probe measurement could be utilized as a novel method for 511 keV ionizing radiation photon detection for positron emission tomography (PET) which could potentially overcome the inherent physical limitation for coincidence time resolution of around 100 ps (Tao et al 2016 Phys. Med. Biol. 61 7600-22). In this paper, we embrace this observation and introduce a two-crossed-polarizers based setup to achieve similar detection concept, which is a simpler and more compact setup with comparable ionizing radiation detection capability as the setup used in the previously proposed work. We evaluated the performance of our experimental setup with Lithium Niobate (LiNbO3) and Cadmium Telluride (CdTe) detector crystals, and the desired properties of an ideal detector crystal were discussed. The modulation signal induced by 511 keV photons in both LiNbO3 and CdTe can be detected with repeatable signal amplitude using two-crossed-polarizers based method, while CdTe could provide eight times higher detection sensitivity to 511 keV photons than LiNbO3 under the same bias voltage, suggesting high effective Z number and high density properties of CdTe, as well as a shorter carrier lifetime and lower carrier mobility of LiNbO3. In addition, the strength of modulation signal increased linearly with bias voltage before saturation. The modulation signal strength in LiNbO3 continued to increase after 2000 V due to its high resistivity which could reduce the dark current in the detector, while the modulation signal of CdTe with low resistivity tended to be saturated at a bias voltage higher than 1200 V. Therefore, further increasing the bias voltage for detector crystals (especially for LiNbO3) may enhance the modulation strength and improve the detection sensitivity for annihilation photons.

A 2.3-ps RMS Resolution Time-to-Digital Converter Implemented in a Low-Cost Cyclone V FPGA.

We present a nonuniform multiphase (NUMP) method to construct a high-resolution time-to-digital converter (TDC) for low-cost field-programmable gate array (FPGA) devices. The NUMP method involves a system clock being passed through a series of delay elements to generate multiple clocks with different phase shifts. The phases of the rising and falling edges of all the clocks are sorted in order and the states of all the clocks are latched when a hit signal arrives. The sizes of the time bins (and precision) of the NUMP method are not limited by the uniformity and minimum value of the time delays of the delay lines. In theory, any delay sources with small jitters in an FPGA, not just very fine carry chains, can be used in the NUMP method to delay and randomize the clocks. Thus, the NUMP method can achieve excellent TDC timing resolutions in low-cost FPGAs without very fine delay lines. We implemented four NUMP TDC channels in a low-cost FPGA device (an Altera Cyclone V 5CEBA4F23C7N). The performance of the four NUMP TDCs was evaluated using both internal and external pulses. The root mean square (rms) for the timing resolution measured using the internal and the external pulses with short-time intervals (less than 1 ns) was 2.3 and 5.2 ps, respectively. A 14.1-ps rms timing resolution was measured at a time interval of 517 ns. The NUMP method is suitable for applications that require a number of high-performance TDC channels in a low-cost FPGA.

PET detectors with 127 ps CTR for the Tachyon-II time-of-flight PET scanner.

The signal-to-noise ratio (SNR) of the reconstructed image of Positron Emission Tomography (PET) can be improved by the timing measurement. In this article, we designed, fabricated and tested 32 time-of-flight (TOF) detectors for the second generation of Tachyon TOF-PET scanners. The detector module consists of two arrays of 2 × 12 lutetium-yttrium oxyorthosilicate (LYSO) crystal cubes of 6 ×6× 6 mm3. The discrete crystals were coupled to the 6 mm silicon photomultipliers (SiPMs) with optical glue. All the SiPM were tested for dark current. To correct the errors in the timing measurements caused by time-walk, two compensation methods (log-correction and linear-correction) based on the relationship between energy and timing information were purposed. As a comparison, the SiPM arrays coupled to 4 mm and 6 mm side crystal cube without optical glue were tested for coincidence timing resolution (CTR). The mean and standard deviations (SD) of dark current for the 1536 tested SiPMs were 12.72 +/- 1.70 µA at the bias voltage of 31.5 V and the temperature of 20 °C (±1 °C). CTR performance has increased by ~5% within a narrow energy window, and ~10% in a wide energy window by log-correction. The mean and SD of the CTR of 6 mm side crystal cube glue coupled was 126.9 +/- 3.6 ps for the 768 pairs of tested SiPMs. The detector is expected to provide a technical reference for the next generation of ultra-fast CTR commercial PET scanner using multilayer detectors.

Ultra-precise surface processing of LYSO scintillator crystals for Positron Emission Tomography.

The Lutetium-Yttrium Oxyorthosilicate (LYSO) is one of the most widely used scintillation crystal in the high-performance Positron Emission Tomography (PET) systems. The quality of the surface finish of the LYSO has an important impact on the light output, the decoding performance, the energy resolution and timing resolution of the PET detectors and systems. In this paper, we present an ultra-precise method for processing the surface of LYSO crystals. The hardness and elastic modulus of the crystals were initially measured using Nano indentation technology. The scintillators were fixed onto the plate in sparse, serried and continuous arrangements and polished using an alumina (Al2O3) and cerium oxide (CeO2) polishing solution with particles of varying size. We used a magnetorheological-polishing technique to polish the LYSO crystals. The polishing solution here included hydroxyl iron powder and hard abrasives. The hardness and elastic modulus of the crystals in question was, respectively, 11.18 ± 0.50 and 155.78 ± 4gigapascals (GPa). A 3D optical surface profiler (3D-OPS) and an atomic force microscope (AFM) were used to evaluate the quality of the polished surfaces. The average roughness of Ra 0.55 nm measured by 3D-OPS was achieved using a precise plate grinding and polishing technique. The magnetorheological-polishing method also obtained an excellent roughness of Ra 0.75 nm (3D-OPS). Our report of the use of these processing technologies can serve as a foundation for further in-depth research regarding the optimal techniques for scintillator surface processing.

Developing a 'multiPatchPET' system in GATE for a PET system design with irregular geometries.

This work modified the commonly used Monte Carlo tool package GATE by developing a new 'multiPatchPET' system so that GATE users can easily simulate PET systems with irregular geometries. The motivation was to design a brain PET scanner with high sensitivity. It is known that compact PET scanners with a large solid coverage angle can achieve high sensitivity with fewer scintillation detectors, and thus have the potential to provide better image quality in brain PET imaging than conventional ring PET scanners. However, considering a straightforward example with the largest possible solid angle, a spherical PET scanner is hard to manufacture. A more practical alternative would be a sphere-like polyhedral PET scanner with flat detector patches. Moreover, when monolithic scintillators are chosen to construct these flat detector modules, detection efficiency is further improved. Thus, we plan to design a sphere-like polyhedral PET scanner made up of monolithic scintillators. Unfortunately, in our design study, we found that simulating such a scanner with the latest GATE version (8.0) was not trivial, since no predefined systems could be used. In this work we introduced a 'multiPatchPET' system to GATE, which we and other GATE users will be able to use to develop PET scanners with any irregular geometry and any shape of patch. To validate our modification, a single block detector and an mCT scanner were simulated via both the original 'ecat' system and the new 'multiPatchPET' system. The results show no difference in terms of the detecting efficiency and reconstruction image. Then we used the 'multiPatchPET' system to simulate an 86 surface polyhedral brain PET scanner. Compared with two cylindrical brain scanners, the polyhedral brain scanner shows a higher sensitivity and has fewer noisy images. Thus, it was proved that our modification, which is accessible to the nuclear imaging research community, equipped GATE with a powerful and user-friendly tool to simulate complex scanners with irregular patches easily.

Enhancing the Image Quality via Transferred Deep Residual Learning of Coarse PET Sinograms.

Increasing the image quality of positron emission tomography (PET) is an essential topic in the PET community. For instance, thin-pixelated crystals have been used to provide high spatial resolution images but at the cost of sensitivity and manufacture expense. In this paper, we proposed an approach to enhance the PET image resolution and noise property for PET scanners with large pixelated crystals. To address the problem of coarse blurred sinograms with large parallax errors associated with large crystals, we developed a data-driven, single-image super-resolution (SISR) method for sinograms, based on the novel deep residual convolutional neural network (CNN). Unlike the CNN-based SISR on natural images, periodically padded sinogram data and dedicated network architecture were used to make it more efficient for PET imaging. Moreover, we included the transfer learning scheme in the approach to process cases with poor labeling and small training data set. The approach was validated via analytically simulated data (with and without noise), Monte Carlo simulated data, and pre-clinical data. Using the proposed method, we could achieve comparable image resolution and better noise property with large crystals of bin sizes of thin crystals with a bin size from to . Our approach uses external PET data as the prior knowledge for training and does not require additional information during inference. Meanwhile, the method can be added into the normal PET imaging framework seamlessly, thus potentially finds its application in designing low-cost high-performance PET systems.

Simulation study of a high-performance brain PET system with dodecahedral geometry.

PURPOSE: In brain imaging, the spherical PET system achieves the highest sensitivity when the solid angle is concerned. However, it is not practical. In this work, we designed an alternative sphere-like scanner, the dodecahedral scanner, which has a high sensitivity in imaging and a high feasibility to manufacture. We simulated this system and compared the performance with a few other dedicated brain PET systems. METHODS: Monte Carlo simulations were conducted to generate data of the dedicated brain PET system with the dodecahedral geometry (11 regular pentagon detectors). The data were then reconstructed using the in-house developed software with the fully three-dimensional maximum-likelihood expectation maximization (3D-MLEM) algorithm. RESULTS: Results show that the proposed system has a high-sensitivity distribution for the whole field of view (FOV). With a depth-of-interaction (DOI) resolution around 6.67 mm, the proposed system achieves the spatial resolution of 1.98 mm. Our simulation study also shows that the proposed system improves the image contrast and reduces noise compared with a few other dedicated brain PET systems. Finally, simulations with the Hoffman phantom show the potential application of the proposed system in clinical applications. CONCLUSIONS: In conclusion, the proposed dodecahedral PET system is potential for widespread applications in high-sensitivity, high-resolution PET imaging, to lower the injected dose.