Left Ventricular Remodelling Associated with the Transient Elevated [68Ga]Ga-Pentixafor Activity in the Remote Myocardium Following Acute Myocardial Infarction.

BACKGROUND: Previous studies have initially reported accompanying elevated 2-deoxy-2[18F]fluoro-D-glucose ([18F]F-FDG) inflammatory activity in the remote area and its prognostic value after acute myocardial infarction (AMI). Non-invasive characterization of the accompanying inflammation in the remote myocardium may be of potency in guiding future targeted theranostics. [68Ga]Ga-Pentixafor targeting chemokine receptor 4 (CXCR4) on the surface of inflammatory cells is currently one of the promising inflammatory imaging agents. In this study, we sought to focus on the longitudinal evolution of [68Ga]Ga-Pentixafor activities in the remote myocardium following AMI and its association with cardiac function. METHODS: Twelve AMI rats and six Sham rats serially underwent [68Ga]Ga-Pentixafor imaging at pre-operation, and 5, 7, 14 days post-operation. Maximum and mean standard uptake value (SUV) and target-to-background ratio (TBR) were assessed to indicate the uptake intensity. Gated [18F]F-FDG imaging and immunofluorescent staining were performed to obtain cardiac function and responses of pro-inflammatory and reparative macrophages, respectively. RESULTS: The uptake of [68Ga]Ga-Pentixafor in the infarcted myocardium peaked at day 5 (all P = 0.003), retained at day 7 (all P = 0.011), and recovered at day 14 after AMI (P > 0.05), paralleling with the rise-fall pro-inflammatory M1 macrophages (P < 0.05). Correlated with the peak activity in the infarct territory, [68Ga]Ga-Pentixafor uptake in the remote myocardium on day 5 early after AMI significantly increased (AMI vs. Sham: SUVmean, SUVmax, and TBRmean: all P < 0.05), and strongly correlated with contemporaneous EDV and/or ESV (SUVmean and TBRmean: both P < 0.05). The transitory remote activity recovered as of day 7 post-AMI (AMI vs. Sham: P > 0.05). CONCLUSIONS: Corresponding with the peaked [68Ga]Ga-Pentixafor activity in the infarcted myocardium, the activity in the remote region elevated accordingly and led to contemporaneous left ventricular remodelling early after AMI. Further studies are warranted to clarify its clinical application potential.

An Accurate Timing Alignment Method with Time-to-Digital Converter Linearity Calibration for High-Resolution TOF PET.

Accurate PET system timing alignment minimizes the coincidence time window and therefore reduces random events and improves image quality. It is also critical for time-of-flight (TOF) image reconstruction. Here, we use a thin annular cylinder (shell) phantom filled with a radioactive source and located axially and centrally in a PET camera for the timing alignment of a TOF PET system. This timing alignment method involves measuring the time differences between the selected coincidence detector pairs, calibrating the differential and integral nonlinearity of the time-to-digital converter (TDC) with the same raw data and deriving the intrinsic time biases for each detector using an iterative algorithm. The raw time bias for each detector is downloaded to the front-end electronics and the residual fine time bias can be applied during the TOF list-mode reconstruction. Our results showed that a timing alignment accuracy of better than ±25 ps can be achieved, and a preliminary timing resolution of 473 ps (full width at half maximum) was measured in our prototype TOF PET/CT system.

Engineering and performance (NEMA and animal) of a lower-cost higher-resolution animal PET/CT scanner using photomultiplier-quadrant-sharing detectors.

UNLABELLED: The dedicated murine PET (MuPET) scanner is a high-resolution, high-sensitivity, and low-cost preclinical PET camera designed and manufactured at our laboratory. In this article, we report its performance according to the NU 4-2008 standards of the National Electrical Manufacturers Association (NEMA). We also report the results of additional phantom and mouse studies. METHODS: The MuPET scanner, which is integrated with a CT camera, is based on the photomultiplier-quadrant-sharing concept and comprises 180 blocks of 13 × 13 lutetium yttrium oxyorthosilicate crystals (1.24 × 1.4 × 9.5 mm(3)) and 210 low-cost 19-mm photomultipliers. The camera has 78 detector rings, with an 11.6-cm axial field of view and a ring diameter of 16.6 cm. We measured the energy resolution, scatter fraction, sensitivity, spatial resolution, and counting rate performance of the scanner. In addition, we scanned the NEMA image-quality phantom, Micro Deluxe and Ultra-Micro Hot Spot phantoms, and 2 healthy mice. RESULTS: The system average energy resolution was 14% at 511 keV. The average spatial resolution at the center of the field of view was about 1.2 mm, improving to 0.8 mm and remaining below 1.2 mm in the central 6-cm field of view when a resolution-recovery method was used. The absolute sensitivity of the camera was 6.38% for an energy window of 350-650 keV and a coincidence timing window of 3.4 ns. The system scatter fraction was 11.9% for the NEMA mouselike phantom and 28% for the ratlike phantom. The maximum noise-equivalent counting rate was 1,100 at 57 MBq for the mouselike phantom and 352 kcps at 65 MBq for the ratlike phantom. The 1-mm fillable rod was clearly observable using the NEMA image-quality phantom. The images of the Ultra-Micro Hot Spot phantom also showed the 1-mm hot rods. In the mouse studies, both the left and right ventricle walls were clearly observable, as were the Harderian glands. CONCLUSION: The MuPET camera has excellent resolution, sensitivity, counting rate, and imaging performance. The data show it is a powerful scanner for preclinical animal study and pharmaceutical development.

A Real Time Coincidence System for High Count-Rate TOF or Non-TOF PET Cameras Using Hybrid Method Combining AND-Logic and Time-Mark Technology.

A fully digital FPGA-based high count-rate coincidence system has been developed for TOF (Time of Flight) and non-TOF PET cameras. Using a hybrid of AND-logic and Time-mark technology produced both excellent timing resolution and high processing speed. In this hybrid architecture, every gamma event was synchronized by a 125 MHz system clock and generating a trigger associated with a time-mark given by an 8-bit high-resolution TDC (68.3 ps/bin). AND-logic was applied to the synchronized triggers for the real-time raw sorting of coincident events. An efficient FPGA based Time-mark fine-sort algorithm is used to select all the possible coincidence events within the preset coincidence time window. This FPGA-based coincidence system for a modular PET camera offers reprogrammable flexibility and expandability, so the coincidence system is easily employed, regardless of differences in the scale of the PET camera detector setup. A distributed processing method and pipeline technology were adopted in the design to obtain very high processing speed. In this design, both prompt and time-delayed accidental coincidences are simultaneously processed in real time. The real-time digital coincidence system supports coincidence in 2 to 12 detector module setups, capable of processing 72 million single events per second with no digital data loss and captures multiple-event coincidence for better imaging performance evaluation. The coincidence time window-size and time-offset of each coincidence event pair can be programmed independently in 68.3 ps increments (TDC LSB) during the data acquisition in different applications to optimize the signal-to-noise ratio. The complex coincidence system is integrated in one circuit board with 1.5 Gbps fiber optic interface. We demonstrated the system performance using the actual circuit and Monte Carlo simulations.

A New Statistics-Based Online Baseline Restorer for a High Count-Rate Fully Digital System.

The goal of this work is to develop a novel, accurate, real-time digital baseline restorer using online statistical processing for a high count-rate digital system such as positron emission tomography (PET). In high count-rate nuclear instrumentation applications, analog signals are DC-coupled for better performance. However, the detectors, pre-amplifiers and other front-end electronics would cause a signal baseline drift in a DC-coupling system, which will degrade the performance of energy resolution and positioning accuracy. Event pileups normally exist in a high-count rate system and the baseline drift will create errors in the event pileup-correction. Hence, a baseline restorer (BLR) is required in a high count-rate system to remove the DC drift ahead of the pileup correction. Many methods have been reported for BLR from classic analog methods to digital filter solutions. However a single channel BLR with analog method can only work under 500 kcps count-rate, and normally an analog front-end application-specific integrated circuits (ASIC) is required for the application involved hundreds BLR such as a PET camera. We have developed a simple statistics-based online baseline restorer (SOBLR) for a high count-rate fully digital system. In this method, we acquire additional samples, excluding the real gamma pulses, from the existing free-running ADC in the digital system, and perform online statistical processing to generate a baseline value. This baseline value will be subtracted from the digitized waveform to retrieve its original pulse with zero-baseline drift. This method can self-track the baseline without a micro-controller involved. The circuit consists of two digital counter/timers, one comparator, one register and one subtraction unit. Simulation shows a single channel works at 30 Mcps count-rate with pileup condition. 336 baseline restorer circuits have been implemented into 12 field-programmable-gate-arrays (FPGA) for our new fully digital PET system.

The System Design, Engineering Architecture, and Preliminary Results of a Lower-Cost High-Sensitivity High-Resolution Positron Emission Mammography Camera.

A lower-cost high-sensitivity high-resolution positron emission mammography (PEM) camera is developed. It consists of two detector modules with the planar detector bank of 20 × 12 cm(2). Each bank has 60 low-cost PMT-Quadrant-Sharing (PQS) LYSO blocks arranged in a 10 × 6 array with two types of geometries. One is the symmetric 19.36 × 19.36 mm(2) block made of 1.5 × 1.5 × 10 mm(3) crystals in a 12 × 12 array. The other is the 19.36 × 26.05 mm(2) asymmetric block made of 1.5 × 1.9 × 10 mm(3) crystals in 12 × 13 array. One row (10) of the elongated blocks are used along one side of the bank to reclaim the half empty PMT photocathode in the regular PQS design to reduce the dead area at the edge of the module. The bank has a high overall crystal packing fraction of 88%, which results in a very high sensitivity. Mechanical design and electronics have been developed for low-cost, compactness, and stability purposes. Each module has four Anger-HYPER decoding electronics that can handle a count-rate of 3 Mcps for single events. A simple two-module coincidence board with a hardware delay window for random coincidences has been developed with an adjustable window of 6 to 15 ns. Some of the performance parameters have been studied by preliminary tests and Monte Carlo simulations, including the crystal decoding map and the 17% energy resolution of the detectors, the point source sensitivity of 11.5% with 50 mm bank-to-bank distance, the 1.2 mm-spatial resolutions, 42 kcps peak Noise Equivalent Count Rate at 7.0-mCi total activity in human body, and the resolution phantom images. Those results show that the design goal of building a lower-cost, high-sensitivity, high-resolution PEM detector is achieved.

Monte Carlo Simulation Study on the Time Resolution of a PMT-Quadrant-Sharing LSO Detector Block for Time-of-Flight PET.

We developed a detailed Monte Carlo simulation method to study the time resolution of detectors for time-of-flight positron emission tomography (TOF PET). The process of gamma ray interaction in detectors, scintillation light emission and transport inside the detectors, the photoelectron generation and anode signal generation in the photomultiplier tube (PMT), and the electronics process of discriminator are simulated. We tested this simulation method using published experimental data, and found that it can generate reliable results. Using this method, we simulated the time resolution for a 13 × 13 detector block of 4 × 4 × 20 mm(3) lutetium orthosilicate (LSO) crystals coupled to four 2-inch PMTs using PMT-quadrant-sharing (PQS) technology. We analyzed the effects of several factors, including the number of photoelectrons, light transport, transit time spread (TTS), and the depth of interaction (DOI). The simulation results indicated that system time resolution of 360 ps should be possible with currently available fast PMTs. This simulation method can also be used to simulate the time resolution of other detector design method.

A Lower-Cost High-Resolution LYSO Detector Development for Positron Emission Mammography (PEM).

In photomultiplier-quadrant-sharing (PQS) geometry for positron emission tomography applications, each PMT is shared by four blocks and each detector block is optically coupled to four round PMTs. Although this design reduces the cost of high-resolution PET systems, when the camera consists of detector panels that are made up of square blocks, half of the PMT's sensitive window remains unused at the detector panel edge. Our goal was to develop a LYSO detector panel which minimizes the unused portion of the PMTs for a low-cost, high-resolution, and high-sensitivity positron emission mammography (PEM) camera. We modified the PQS design by using elongated blocks at panel edges and square blocks in the inner area. For elongated blocks, symmetric and asymmetrical reflector patterns were developed and PQS and PMT-half-sharing (PHS) arrangements were implemented in order to obtain a suitable decoding. The packing fraction was 96.3% for asymmetric block and 95.5% for symmetric block. Both of the blocks have excellent decoding capability with all crystals clearly identified, 156 for asymmetric and 144 for symmetric and peak-to-valley ratio of 3.0 and 2.3 respectively. The average energy resolution was 14.2% for the asymmetric block and 13.1% for the symmetric block. Using a modified PQS geometry and asymmetric block design, we reduced the unused PMT region at detector panel edges, thereby increased the field-of-view and the overall detection sensitivity and minimized the undetected breast region near the chest wall. This detector design and using regular round PMT allowed building a lower-cost, high-resolution and high-sensitivity PEM camera.