Performance Characteristics of the NeuroEXPLORER, a Next-Generation Human Brain PET/CT Imager.

The collaboration of Yale, the University of California, Davis, and United Imaging Healthcare has successfully developed the NeuroEXPLORER, a dedicated human brain PET imager with high spatial resolution, high sensitivity, and a built-in 3-dimensional camera for markerless continuous motion tracking. It has high depth-of-interaction and time-of-flight resolutions, along with a 52.4-cm transverse field of view (FOV) and an extended axial FOV (49.5 cm) to enhance sensitivity. Here, we present the physical characterization, performance evaluation, and first human images of the NeuroEXPLORER. Methods: Measurements of spatial resolution, sensitivity, count rate performance, energy and timing resolution, and image quality were performed adhering to the National Electrical Manufacturers Association (NEMA) NU 2-2018 standard. The system's performance was demonstrated through imaging studies of the Hoffman 3-dimensional brain phantom and the mini-Derenzo phantom. Initial 18F-FDG images from a healthy volunteer are presented. Results: With filtered backprojection reconstruction, the radial and tangential spatial resolutions (full width at half maximum) averaged 1.64, 2.06, and 2.51 mm, with axial resolutions of 2.73, 2.89, and 2.93 mm for radial offsets of 1, 10, and 20 cm, respectively. The average time-of-flight resolution was 236 ps, and the energy resolution was 10.5%. NEMA sensitivities were 46.0 and 47.6 kcps/MBq at the center and 10-cm offset, respectively. A sensitivity of 11.8% was achieved at the FOV center. The peak noise-equivalent count rate was 1.31 Mcps at 58.0 kBq/mL, and the scatter fraction at 5.3 kBq/mL was 36.5%. The maximum count rate error at the peak noise-equivalent count rate was less than 5%. At 3 iterations, the NEMA image-quality contrast recovery coefficients varied from 74.5% (10-mm sphere) to 92.6% (37-mm sphere), and background variability ranged from 3.1% to 1.4% at a contrast of 4.0:1. An example human brain 18F-FDG image exhibited very high resolution, capturing intricate details in the cortex and subcortical structures. Conclusion: The NeuroEXPLORER offers high sensitivity and high spatial resolution. With its long axial length, it also enables high-quality spinal cord imaging and image-derived input functions from the carotid arteries. These performance enhancements will substantially broaden the range of human brain PET paradigms, protocols, and thereby clinical research applications.

Super-resolution reconstruction of γ-ray CT images for PET-enabled dual-energy CT imaging.

Dual-energy computed tomography (DECT) enables material decomposition for tissues and produces additional information for PET/CT imaging to potentially improve the characterization of diseases. PET-enabled DECT (PDECT) allows the generation of PET and DECT images simultaneously with a conventional PET/CT scanner without the need for a second x-ray CT scan. In PDECT, high-energy γ-ray CT (GCT) images at 511 keV are obtained from time-of-flight (TOF) PET data and are combined with the existing x-ray CT images to form DECT imaging. We have developed a kernel-based maximum-likelihood attenuation and activity (MLAA) method that uses x-ray CT images as a priori information for noise suppression. However, our previous studies focused on GCT image reconstruction at the PET image resolution which is coarser than the image resolution of the x-ray CT. In this work, we explored the feasibility of generating super-resolution GCT images at the corresponding CT resolution. The study was conducted using both phantom and patient scans acquired with the uEXPLORER total-body PET/CT system. GCT images at the PET resolution with a pixel size of 4.0 mm × 4.0 mm and at the CT resolution with a pixel size of 1.2 mm × 1.2 mm were reconstructed using both the standard MLAA and kernel MLAA methods. The results indicated that the GCT images at the CT resolution had sharper edges and revealed more structural details compared to the images reconstructed at the PET resolution. Furthermore, images from the kernel MLAA method showed substantially improved image quality compared to those obtained with the standard MLAA method.

Feasibility of PET-enabled dual-energy CT imaging: First physical phantom and patient results.

X-ray computed tomography (CT) in PET/CT is commonly operated with a single energy, resulting in a limitation of lacking tissue composition information. Dual-energy (DE) spectral CT enables material decomposition by using two different x-ray energies and may be combined with PET for improved multimodality imaging, but would either require hardware upgrade or increase radiation dose due to the added second x-ray CT scan. Recently proposed PET-enabled DECT method allows dual-energy spectral imaging using a conventional PET/CT scanner without the need for a second x-ray CT scan. A gamma-ray CT (gCT) image at 511 keV can be generated from the existing time-of-flight PET data with the maximum-likelihood attenuation and activity (MLAA) approach and is then combined with the low-energy x-ray CT image to form dual-energy spectral imaging. To improve the image quality of gCT, a kernel MLAA method was further proposed by incorporating x-ray CT as a priori information. The concept of this PET-enabled DECT has been validated using simulation studies, but not yet with 3D real data. In this work, we developed a general open-source implementation for gCT reconstruction from PET data and use this implementation for the first real data validation with both a physical phantom study and a human subject study on a uEXPLORER total-body PET/CT system. These results have demonstrated the feasibility of this method for spectral imaging and material decomposition.

Development of a Monte Carlo-based scatter correction method for total-body PET using the uEXPLORER PET/CT scanner.

Objective.This study presents and evaluates a robust Monte Carlo-based scatter correction (SC) method for long axial field of view (FOV) and total-body positron emission tomography (PET) using the uEXPLORER total-body PET/CT scanner.Approach.Our algorithm utilizes the Monte Carlo (MC) tool SimSET to compute SC factors in between individual image reconstruction iterations within our in-house list-mode and time-of-flight-based image reconstruction framework. We also introduced a unique scatter scaling technique at the detector block-level for optimal estimation of the scatter contribution in each line of response. First image evaluations were derived from phantom data spanning the entire axial FOV along with image data from a human subject with a large body mass index. Data was evaluated based on qualitative inspections, and contrast recovery, background variability, residual scatter removal from cold regions, biases and axial uniformity were quantified and compared to non-scatter-corrected images.Main results.All reconstructed images demonstrated qualitative and quantitative improvements compared to non-scatter-corrected images: contrast recovery coefficients improved by up to 17.2% and background variability was reduced by up to 34.3%, and the residual lung error was between 1.26% and 2.08%. Low biases throughout the axial FOV indicate high quantitative accuracy and axial uniformity of the corrections. Up to 99% of residual activity in cold areas in the human subject was removed, and the reliability of the method was demonstrated in challenging body regions like in the proximity of a highly attenuating knee prosthesis.Significance.The MC SC method employed was demonstrated to be accurate and robust in TB-PET. The results of this study can serve as a benchmark for optimizing the quantitative performance of future SC techniques.

Lutetium background radiation in total-body PET-A simulation study on opportunities and challenges in PET attenuation correction.

The current generation of total-body positron emission tomography (PET) scanners offer significant sensitivity increase with an extended axial imaging extent. With the large volume of lutetium-based scintillation crystals that are used as detector elements in these scanners, there is an increased flux of background radiation originating from 176Lu decay in the crystals and higher sensitivity for detecting it. Combined with the ability of scanning the entire body in a single bed position, this allows more effective utilization of the lutetium background as a transmission source for estimating 511 keV attenuation coefficients. In this study, utilization of the lutetium background radiation for attenuation correction in total-body PET was studied using Monte Carlo simulations of a 3D whole-body XCAT phantom in the uEXPLORER PET scanner, with particular focus on ultralow-dose PET scans that are now made possible with these scanners. Effects of an increased acceptance angle, reduced scan durations, and Compton scattering on PET quantification were studied. Furthermore, quantification accuracy of lutetium-based attenuation correction was compared for a 20-min scan of the whole body on the uEXPLORER, a one-meter-long, and a conventional 24-cm-long scanner. Quantification and lesion contrast were minimally affected in both long axial field-of-view scanners and in a whole-body 20-min scan, the mean bias in all analyzed organs of interest were within a ±10% range compared to ground-truth activity maps. Quantification was affected in certain organs, when scan duration was reduced to 5 min or a reduced acceptance angle of 17° was used. Analysis of the Compton scattered events suggests that implementing a scatter correction method for the transmission data will be required, and increasing the energy threshold from 250 keV to 290 keV can reduce the computational costs and data rates, with negligible effects on PET quantification. Finally, the current results can serve as groundwork for transferring lutetium-based attenuation correction into research and clinical practice.

Relating18F-FDG image signal-to-noise ratio to time-of-flight noise-equivalent count rate in total-body PET using the uEXPLORER scanner.

Objective.This work assessed the relationship between image signal-to-noise ratio (SNR) and total-body noise-equivalent count rate (NECR)-for both non-time-of-flight (TOF) NECR and TOF-NECR-in a long uniform water cylinder and 14 healthy human subjects using the uEXPLORER total-body PET/CT scanner.Approach.A TOF-NEC expression was modified for list-mode PET data, and both the non-TOF NECR and TOF-NECR were compared using datasets from a long uniform water cylinder and 14 human subjects scanned up to 12 h after radiotracer injection.Main results.The TOF-NECR for the uniform water cylinder was found to be linearly proportional to the TOF-reconstructed image SNR2in the range of radioactivity concentrations studied, but not for non-TOF NECR as indicated by the reducedR2value. The results suggest that the use of TOF-NECR to estimate the count rate performance of TOF-enabled PET systems may be more appropriate for predicting the SNR of TOF-reconstructed images.Significance.Image quality in PET is commonly characterized by image SNR and, correspondingly, the NECR. While the use of NECR for predicting image quality in conventional PET systems is well-studied, the relationship between SNR and NECR has not been examined in detail in long axial field-of-view total-body PET systems, especially for human subjects. Furthermore, the current NEMA NU 2-2018 standard does not account for count rate performance gains due to TOF in the NECR evaluation. The relationship between image SNR and total-body NECR in long axial FOV PET was assessed for the first time using the uEXPLORER total-body PET/CT scanner.

Blanching Defects at the Pressure Points: Observations from Dynamic Total-Body PET/CT Studies.

Total-body PET/CT allows simultaneous acquisition of all the body parts in a single bed position during the radiotracer uptake phase. Dynamic imaging protocols employing total-body PET could demonstrate findings that may not have been previously visualized or described using conventional PET/CT scanners. We examined the characteristics of blanching defects, areas of markedly reduced (partial defect) or absent (complete defect) radiotracer uptake seen at the skin/subcutaneous tissues opposite the bony prominences at pressure points. Methods: In this observational study, 77 participants underwent dynamic total-body PET/CT imaging using 18F-FDG (Group 1, N = 47, 60-min dynamic, arms-down, divided into 3 subgroups according to the injected dose) or 18F-fluciclovine (Group 2, N = 30, 25-min dynamic, arms above the head). 40 out of 47 participants in Group 1 were re-imaged at 90 min after being allowed off the scanning table. Blanching defects, partial or complete, were characterized opposite the bony prominences at 7 pressure points (the skull, scapula, and calcaneus bilaterally, as well as the sacrum). Association of the blanching defects with different clinical and technical characteristics were analyzed using uni- and multi-variate analyses. Results: A total of 124 blanching defects were seen in 68 out of 77 (88%) participants at one or more pressure points. Blanching defects were higher, on average, in Group 2 participants (3.5±1.7) compared to Group 1 (2.1±1.4; P <0.001), but it did not vary within Group 1 for different 18F-FDG dose subgroups. All defects resumed normal pattern on delayed static (90-min) images except for 14 partial defects. No complete blanching defects were seen on the 90-min images. By multivariate analysis, arm positioning above the head was associated with skull defects; scapular and sacral defects were significantly more encountered in men and with lower BMI, while calcaneal defects could not be associated to any factor. Conclusion: Blanching defects opposite the bony pressure points are common on dynamic total-body PET/CT images using different radiopharmaceuticals and injection doses. Their appearance should not be immediately interpreted as an abnormality. The current findings warrant further exploration in a prospective setting and may be utilized to study various mechano-pathologic conditions, such as pressure ulcers.

Quantitative accuracy in total-body imaging using the uEXPLORER PET/CT scanner.

Absolute quantification of regional tissue concentration of radioactivity in positron emission tomography (PET) is a critical parameter-of-interest across various clinical and research applications and is affected by a complex interplay of factors including scanner calibration, data corrections, and image reconstruction. The emergence of long axial field-of-view (FOV) PET systems widens the dynamic range accessible to PET and creates new opportunities in reducing scan time and radiation dose, delayed or low radioactivity imaging, as well as kinetic modeling of the entire human. However, these imaging regimes impose challenging conditions for accurate quantification due to constraints from image reconstruction, low count conditions, as well as large and rapidly changing radioactivity distribution across a large axial FOV. We comprehensively evaluated the quantitative accuracy of the uEXPLORER total-body scanner in conditions that encompass existing and potential imaging applications (such as dynamic imaging and ultralow-dose imaging) using a set of total-body specific phantom and human measurements. Through these evaluations we demonstrated a relative count rate accuracy of ±3%-4% using the NEMA NU 2-2018 protocol, an axial uniformity spread of ±3% across the central 90% axial FOV, and a 3% activity bias spread from 17 to 474 MBq18F-FDG in a 210 cm long cylindrical phantom. Region-of-interest quantification spread of 1% was found by simultaneously scanning three NEMA NU 2 image quality phantoms, as well as relatively stable volume-of-interest quantification across 0.2%-100% of total counts through re-sampled datasets. In addition, an activity bias spread of -2% to +1% post-bolus injections in human subjects was found. Larger bias changes during the bolus injection phase in humans indicated the difficulty in providing accurate PET data corrections for complex activity distributions across a large dynamic range. Our results overall indicated that the quantitative performance achieved with the uEXPLORER scanner was uniform across the axial FOV and provided the accuracy necessary to support a wide range of imaging applications.

Performance Evaluation of the uEXPLORER Total-Body PET/CT Scanner Based on NEMA NU 2-2018 with Additional Tests to Characterize PET Scanners with a Long Axial Field of View.

The world's first total-body PET scanner with an axial field of view (AFOV) of 194 cm is now in clinical and research use at our institution. The uEXPLORER PET/CT system is the first commercially available total-body PET scanner. Here we present a detailed physical characterization of this scanner based on National Electrical Manufacturers Association (NEMA) NU 2-2018 along with a new set of measurements devised to appropriately characterize the total-body AFOV. Methods: Sensitivity, count-rate performance, time-of-flight resolution, spatial resolution, and image quality were evaluated following the NEMA NU 2-2018 protocol. Additional measurements of sensitivity and count-rate capabilities more representative of total-body imaging were performed using extended-geometry phantoms based on the world-average human height (∼165 cm). Lastly, image quality throughout the long AFOV was assessed with the NEMA image quality (IQ) phantom imaged at 5 axial positions and over a range of expected total-body PET imaging conditions (low dose, delayed imaging, short scan duration). Results: Our performance evaluation demonstrated that the scanner provides a very high sensitivity of 174 kcps/MBq, a count-rate performance with a peak noise-equivalent count rate of approximately 2 Mcps for total-body imaging, and good spatial resolution capabilities for human imaging (≤3.0 mm in full width at half maximum near the center of the AFOV). Excellent IQ, excellent contrast recovery, and low noise properties were illustrated across the AFOV in both NEMA IQ phantom evaluations and human imaging examples. Conclusion: In addition to standard NEMA NU 2-2018 characterization, a new set of measurements based on extending NEMA NU 2-2018 phantoms and experiments was devised to characterize the physical performance of the first total-body PET system. The rationale for these extended measurements was evident from differences in sensitivity, count-rate-activity relationships, and noise-equivalent count-rate limits imposed by differences in dead time and randoms fraction between the NEMA NU 2 70-cm phantoms and the more representative total-body imaging phantoms. Overall, the uEXPLORER PET system provides ultra-high sensitivity that supports excellent spatial resolution and IQ throughout the field of view in both phantom and human imaging.

Mini EXPLORER II: a prototype high-sensitivity PET/CT scanner for companion animal whole body and human brain scanning.

As part of the EXPLORER total-body positron emission tomography (PET) project, we have designed and built a high-resolution, high-sensitivity PET/CT scanner, which is expected to have excellent performance for companion animal whole body and human brain imaging. The PET component has a ring diameter of 52 cm and an axial field of view of 48.3 cm. The detector modules are composed of arrays of lutetium (yttrium) oxyorthosilicate (LYSO) crystals of dimensions 2.76 × 2.76 × 18.1 mm3 coupled to silicon photomultipliers (SiPMs) for read-out. The CT component is a 24 detector row CT scanner with a 50 kW x-ray tube. PET system time-of-flight resolution was measured to be 409 ± 39 ps and average system energy resolution was 11.7% ± 1.5% at 511 keV. The NEMA NU2-2012 system sensitivity was found to be 52-54 kcps MBq-1. Spatial resolution was 2.6 mm at 10 mm from the center of the FOV and 2.0 mm rods were clearly resolved on a mini-Derenzo phantom. Peak noise-equivalent count (NEC) rate, using the NEMA NU 2-2012 phantom, was measured to be 314 kcps at 9.2 kBq cc-1. The CT scanner passed the technical components of the American College of Radiology (ACR) accreditation tests. We have also performed scans of a Hoffman brain phantom and we show images from the first canine patient imaged on this device.

Performance assessment of a software-based coincidence processor for the EXPLORER total-body PET scanner.

Coincidence processing in positron emission tomography (PET) is typically done during acquisition of the data. However, on the EXPLORER total-body PET scanner we plan, in addition, to store unpaired single events (i.e. singles) for post-acquisition coincidence processing. A software-based coincidence processor was developed for EXPLORER and its performance was assessed. Our results showed that the performance of the coincidence processor could be significantly impacted by the type of data storage (Peripheral Component Interconnect Express (PCIe)-attached solid state drive (SSD) versus RAID 6 hard disk drives (HDDs)) especially when multiple data files were processed in parallel. We showed that a 48-thread computer node with dual Intel Xeon E5-2650 v4 central processing units (CPUs) and a PCIe SSD was sufficient to process approximately 120 M singles s-1 at an incoming singles rate of approximately 150 Mcps. With two computer nodes, near real-time coincidence processing became possible at this incoming singles rate.

Concerns for low coverage of influenza vaccination in middle-aged adults.

A survey in Hong Kong on middle-aged adults revealed a low influenza vaccination uptake rate of 13%. As a heterogeneous population comprising individuals at different levels of risk for complications, effective development of strategy for improving vaccination coverage in middle-aged adults should be prioritized.

Parotid swelling and facial nerve palsy: an uncommon presentation of sarcoidosis.

Sarcoidosis is a granulomatous disease of unknown etiology that can affect virtually any organ system. Diagnosing sarcoidosis can be challenging, since manifestations of the disease will vary depending on the organ systems involved. The present case describes a 24-year-old woman with bilateral jaw pain and swelling, who developed bilateral facial nerve palsies secondary to sarcoidosis. Consideration of sarcoidosis in the differential diagnosis of facial nerve palsy or parotid swelling is important to ensure proper treatment.

Concurrent purification of two defense proteins from French bean seeds: a defensin-like antifungal peptide and a hemagglutinin.

A purification protocol is described herein for concurrent isolation of two defense proteins including a 6-kDa defensin-like antifungal peptide and a 60-kDa dimeric hemagglutinin from seeds of the French bean (Phaseolus vulgaris). It involved ion-exchange chromatography on SP-Sepharose, affinity chromatography on Affi-gel blue gel, ion-exchange chromatography on Q-Sepharose, and gel filtration on Superdex Peptide (for defensin-like antifungal peptide) or Superdex 200 (for hemagglutinin). Both antifungal and hemagglutinating activities were adsorbed on SP-Sepharose and then on Affi-gel blue gel. Hemagglutinin was subsequently unadsorbed and defensin-like antifungal peptide adsorbed on Q-Sepharose. The antifungal activity of the antifungal peptide was stable in the temperature range of 0-90 degrees C for 20 min, in the pH range of 4-10, and after exposure to trypsin (1 mg/ml) at 37 degrees C for 1 h. The hemagglutinin was stable from 10 to 80 degrees C, from pH 1 to 12, and after treatment with trypsin at 37 degrees C for 2 h. It inhibited [methyl-(3)H]thymidine incorporation into breast cancer (MCF-7), leukemia (L1210), hepatoma (HepG2) and human embryonic liver (WRL68) cells with an IC50 of 6.6, 7, 13 and 15 microM, respectively, and elicited maximal mitogenic response from mouse splenocytes at 1 microM concentration. It curtailed HIV-1 reverse transcriptase activity with an IC50 of 1.9 microM, but was devoid of antifungal activity.

A relatively stable antifungal peptide from buckwheat seeds with antiproliferative activity toward cancer cells.

An antifungal peptide with a molecular mass of approximately 4 kDa was isolated from buckwheat seeds by using ion-exchange chromatography on SP-Sepharose and Q-Sepharose, and gel filtration on Superdex peptide. The peptide was adsorbed on SP-Sepharose in 10 mM NH(4)OAc buffer (pH 4.5) and on Q-Sepharose in 10 mM NH(4)HCO(3) buffer (pH 9.4), and appeared to be highly purified after these two steps. It inhibited mycelial growth in Fusarium oxysporum and Mycosphaerella arachidicola with an IC(50) of 35 and 40 microM, respectively. Its antifungal activity was stable between 0 and 70 degrees C, and between pH 1.0/2.0 and 13. It inhibited proliferation of Hep G2 (hepatoma) cells, L1210 (leukemia) cells, breast cancer (MCF-7) cells, and liver embryonic WRL 68 cells with an IC(50) of 33, 4, 25, and 37 microM, respectively. On the other hand, the peptide was unable to evoke a mitogenic response from splenocytes or induce nitric oxide production by macrophages. It inhibited HIV-1 reverse transcriptase with an IC(50) of 5.5 microM.