The potential utility of (2S,4R)-4-[18F] fluoroglutamine as a novel metabolic imaging marker for inflammation explored by rat models of arthritis and paw edema.

Purpose: (2S,4R)-4-[18F]fluoroglutamine ([18F]FGln) is a promising metabolic imaging marker in cancer. Based on the fact that major inflammatory cells are heavily dependent on glutamine metabolism like cancer cells, we explored the potential utility of [18F]FGln as a metabolic imaging marker for inflammation in two rat models: carrageenan-induced paw edema (CIPE) and collagen-induced arthritis (CIA). Procedures: The CIPE model (n = 4) was generated by injecting 200 µL of 3% carrageenan solution into the left hind paw three hours before the PET. The CIA model (n = 4) was generated by injecting 200 µg of collagen emulsion subcutaneously at the tail base 3-4 weeks before the PET. A qualitative scoring system was used to assess the severity of paw inflammation. After a CT scan, 15.7 ± 4.9 MBq of [18F]FGln was injected via the tail vein, followed by a dynamic micro-PET scan for 90 minutes under anesthesia with isoflurane. The standard uptake value of [18F]FGln was measured by placing a volume of interest in each paw. The non-injected right hind paws of the CIPE model rats served as controls for both models. The paws with CIA were pathologically examined after PET. Results: In CIPE models, uptake in the injected paw was higher compared to the non-injected paw by 52-83%. In CIA models, uptake in the paws with severe inflammation was higher than the averaged controls by 54-173%, while that with mild and no inflammation was slightly higher (33%) and lower (-7%), respectively. Combined overall, the [18F]FGln uptake in CIA showed a significant positive correlation with inflammation severity (r = 0.88, P = 0.009). The pathological findings confirmed profound inflammation in CIA. Conclusions: [18F]FGln uptake was increased in both acute and chronic inflammation, and the uptake level was significantly correlated with the severity, suggesting its potential utility as a novel metabolic imaging marker for inflammation.

Proceedings of the 17th International Meeting on Fully 3D Image Reconstruction in Radiology and Nuclear Medicine.

Contained within this volume are the scholarly contributions presented in both oral and poster formats at Fully3D 2023: The 17th International Meeting on Fully Three-Dimensional Image Reconstruction in Radiology and Nuclear Medicine. This conference convened from July 16-21, 2023, at Stony Brook University in New York. For ease of reference, all papers are organized alphabetically according to the last names of the primary authors. Our heartfelt appreciation goes out to all participants who took the time to submit, present, and revise their work for inclusion in these proceedings. Collectively, we would also like to express our profound gratitude to our generous sponsors, detailed in subsequent pages, who have played an instrumental role in offering awards and facilitating the various conference activities. Additionally, our thanks extend to the diligent reporter who collated invaluable feedback from attendees, which can be found in the pages that follow. September 7, 2023 Fully3D 2023 Co-Chairs: Jerome Liang, Paul Vaska, and Chuan Huang.

Quantitative functional imaging of the pigeon brain: implications for the evolution of avian powered flight.

The evolution of flight is a rare event in vertebrate history, and one that demands functional integration across multiple anatomical/physiological systems. The neuroanatomical basis for such integration and the role that brain evolution assumes in behavioural transformations remain poorly understood. We make progress by (i) generating a positron emission tomography (PET)-based map of brain activity for pigeons during rest and flight, (ii) using these maps in a functional analysis of the brain during flight, and (iii) interpreting these data within a macroevolutionary context shaped by non-avian dinosaurs. Although neural activity is generally conserved from rest to flight, we found significant increases in the cerebellum as a whole and optic flow pathways. Conserved activity suggests processing of self-movement and image stabilization are critical when a bird takes to the air, while increased visual and cerebellar activity reflects the importance of integrating multimodal sensory information for flight-related movements. A derived cerebellar capability likely arose at the base of maniraptoran dinosaurs, where volumetric expansion and possible folding directly preceded paravian flight. These data represent an important step toward establishing how the brain of modern birds supports their unique behavioural repertoire and provide novel insights into the neurobiology of the bird-like dinosaurs that first achieved powered flight.

Assessment of Alzheimer's Disease Imaging Biomarkers in World Trade Center Responders with Cognitive Impairment at Midlife.

Purpose Incidence of early onset neurocognitive dysfunction has been reported in World Trade Center (WTC) responders. Ongoing studies are investigating the underlying etiology, as we are concerned that an underlying risk of neurodegenerative dementia may be occurring because of their stressful and neurotoxic exposures to particulate matter when they responded to the search and rescue efforts on September 11, 2001. The purpose of this study is to report preliminary results from two ongoing positron emission tomography (PET)/magnetic resonance imaging (MRI) imaging studies investigating the presence of Alzheimer's disease (AD) biomarkers, such as ß-amyloid, tau, and neurodegeneration, and compare our findings to published norms. Methods We present findings on 12 WTC responders diagnosed with either cognitive impairment (CI) or mild cognitive impairment (MCI), now at midlife, who underwent PET/MRI brain imaging as part of ongoing studies. Six responders with CI received [ 18 F] florbetaben (FBB) to detect ß-amyloidosis and six separate responders with MCI received [ 18 F] flortaucipir (FTP) to detect tauopathy. All 12 responders underwent concomitant MRI scans for gray matter volume analysis of neurodegeneration. Results PET analysis revealed 50% FBB and 50% of FTP scans were clinically read as positive and that 50% of FTP scans identified as consistent with Braak's stage I or II. Furthermore, one responder identified as centiloid positive for AD. Gray matter volumes from MRI analyses were compared with age/sex-matched norms (Neuroquant), identifying abnormally low cortical volumes in the occipital and temporal lobes, as well as the inferior temporal gyri and the entorhinal cortex. Conclusion These preliminary results suggest that WTC responders with neurocognitive dysfunction may be at increased risk for a neurodegenerative dementia process as a result of their exposures at September 11, 2001.

PET Imaging of Leg Arteries for Determining the Input Function in PET/MRI Brain Studies Using a Compact, MRI-compatible PET System.

In this study, we used a compact, high-resolution, and MRI-compatible PET camera (VersaPET) to assess the feasibility of measuring the image-derived input function (IDIF) from arteries in the leg with the ultimate goal of enabling fully quantitative PET brain imaging without blood sampling. We used this approach in five 18F-FDG PET/MRI brain studies in which the input function was also acquired using the gold standard of serial arterial blood sampling. After accounting for partial volume, dispersion, and calibration effects, we compared the metabolic rates of glucose (MRglu) quantified from VersaPET IDIFs in 80 brain regions to those using the gold standard and achieved a bias and variability of <5% which is within the range of reported test-retest values for this type of study. We also achieved a strong linear relationship (R2 >0.97) against the gold standard across regions. The results of this preliminary study are promising and support further studies to optimize methods, validate in a larger cohort, and extend to the modeling of other radiotracers.

Reduced cerebellar cortical thickness in World Trade Center responders with cognitive impairment.

Prior research has demonstrated high levels of cognitive and physical functional impairments in World Trade Center (WTC) responders. A follow-up neuroimaging study identified changes to white matter connectivity within the cerebellum in responders with cognitive impairment (CI). In the first study to examine cerebellar cortical thickness in WTC responders with CI, we fielded a structural magnetic resonance imaging protocol. WTC responders (N = 99) participated in a structural magnetic resonance imaging (MRI) study, of whom 48 had CI. Participants with CI did not differ demographically or by intracranial volume when compared to cognitively unimpaired participants. MRIs were processed using the CERES imaging pipeline; bilateral cortical thickness in 12 cerebellar lobules was reported. Analyses were completed comparing mean cerebellar cortical thickness across groups. Lobules were examined to determine the location and functional correlates of reduced cerebellar cortical thickness. Multivariable-adjusted analyses accounted for the false discovery rate. Mean cerebellar cortical thickness was reduced by 0.17 mm in responders with CI. Decrements in cerebellar cortical thickness were symmetric and located in the Cerebellar Crus (I and II), and in Lobules IV, VI, VIIb, VIIIa, VIIIb, and IX. Cerebellar cortical thickness was associated with episodic memory, response speed, and tandem balance. WTC responders with CI had evidence of reduced cerebellar cortical thickness that was present across lobules in a pattern unique to this cohort.

Glymphatic Cerebrospinal Fluid and Solute Transport Quantified by MRI and PET Imaging.

Over the past decade there has been an enormous progress in our understanding of fluid and solute transport in the central nervous system (CNS). This is due to a number of factors, including important developments in whole brain imaging technology and computational fluid dynamics analysis employed for the elucidation of glymphatic transport function in the live animal and human brain. In this paper, we review the technical aspects of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in combination with administration of Gd-based tracers into the cerebrospinal fluid (CSF) for tracking glymphatic solute and fluid transport in the CNS as well as lymphatic drainage. Used in conjunction with advanced computational processing methods including optimal mass transport analysis, one gains new insights into the biophysical forces governing solute transport in the CNS which leads to intriguing new research directions. Considering drainage pathways, we review the novel T1 mapping technique for quantifying glymphatic transport and cervical lymph node drainage concurrently in the same subject. We provide an overview of knowledge gleaned from DCE-MRI studies of glymphatic transport and meningeal lymphatic drainage. Finally, we introduce positron emission tomography (PET) and CSF administration of radiotracers as an alternative method to explore other pharmacokinetic aspects of CSF transport into brain parenchyma as well as efflux pathways.

PET/MRI reveals ongoing metabolic activity in ACL grafts one year post-ACL reconstruction.

PURPOSE: To use serial PET/MRI imaging to radiographically evaluate the metabolic activity of the ACL graft over the first post-operative year. METHODS: Six patients undergoing primary ACL reconstruction were recruited in this prospective study in an inpatient university hospital. All patients underwent femoral and tibial suspensory cortical fixation with quadrupled semitendinosus autograft hamstring ACL reconstruction by an orthopaedic surgeon. Simultaneous 18F-FDG PET and MRI of both the operative and non-operative knee was performed at three, six, and 12 months post-operatively. Quantification of the mean standardized uptake value (SUV) within the whole-knee, as well as tibial tunnel, femoral tunnel, and intra-articular graft regions of interest (ROIs). RESULTS: PET whole-knee activity was increased at all time-points post-operatively compared to the control, non-operative knee. Activity decreased over time, yet considerable generalized activity remained 1 year post-operatively, with relative intensity 34% percent higher than control. When the operative knee was divided into three whole-regions, there was greater activity in the tibia at three than 12 months, the femur at six than 12 months, and in the tibia compared to the intra-articular region at 3 months. When they were separated into sub-regions, results demonstrated greater activity closer to the joint surface. CONCLUSIONS: PET/MRI evaluation of ACL graft reconstructions demonstrates evolving biologic activity within the graft and both tunnels. Focal areas of increased activity within the tunnels may indicate of ligamento-osseous morphologic changes. These data suggest that graft incorporation continues well beyond 1 year post-operatively. LEVEL OF EVIDENCE: Level IV.

Positron emission tomography-magnetic resonance liver parenchyma attenuation correction artifact in secondary hemochromatosis.

Positron emission tomography-magnetic resonance (PET-MR) hybrid imaging is a relatively new imaging modality combining the superb MR contrast capabilities among different soft-tissue structures with the high sensitivity of PET functional imaging. With the development of any new technology, a variety of limitations will be encountered including the introduction of new types of artifacts. In this case report, we present a restaging PET-MR scan for multiple myeloma that showed severely decreased fluorodeoxyglucose activity in the liver on the PET attenuated corrected images. Careful analysis showed the cause of the decreased activity to be the improper density assignment on the mu map caused by iron deposition within the liver. Follow-up imaging showed reversal of the phenomena following improvement of liver disease.

Evaluation of quantitative, efficient image reconstruction for VersaPET, a compact PET system.

PURPOSE: Previously we developed a high-resolution positron emission tomography (PET) system-VersaPET-characterized by a block geometry with relatively large axial and transaxial interblock gaps and a compact geometry susceptible to parallax blurring effects. In this work, we report the qualitative and quantitative evaluation of a graphic processing unit (GPU)-accelerated maximum-likelihood by expectation-maximization (MLEM) image reconstruction framework for VersaPET which features accurate system geometry and projection space point-spread-function (PSF) modeling. METHODS: We combined the ray-tracing module from software for tomographic image reconstruction (STIR), an open-source PET image reconstruction package, with VersaPET's exact block geometry for the geometric system matrix. Point-spread-function modeling of crystal penetration and scattering was achieved by a custom Monte-Carlo simulation for projection space blurring in all dimensions. We also parallelized the reconstruction in GPU taking advantage of the system's symmetry for PSF computation. To investigate the effects of PSF width, we generated and studied multiple kernels between one that reflects the true LYSO density in the MC simulation and another that reflects geometry only (no PSF). GATE simulations of hot and cold-sphere phantoms with spheres of different sizes, real microDerenzo phantom, and human blood vessel data were used to characterize the quantitative and qualitative performances of the reconstruction. RESULTS: Reconstruction with an accurate system geometry effectively improved image quality compared to STIR (version 3.0) which assumes an idealized system geometry. Reconstructions of GATE-simulated hot-sphere phantom data showed that all PSF kernels achieved superior performance in contrast recovery and bias reduction compared to using no PSF, but may introduce edge artifact and lumped background noise pattern depending on the width of PSF kernels. Cold-sphere phantom simulation results also indicated improvement in contrast recovery and quantification with PSF modeling (compared to no PSF) for 5 and 10 mm cold spheres. Real microDerenzo phantom images with the PSF kernel that reflects the true LYSO density showed degraded resolving power of small sectors that could be resolved more clearly by underestimated PSF kernels, which is consistent with recent literature despite differences in scanner geometries and in approaches to system model estimation. The human vessel results resemble those of the hot-sphere phantom simulation with the PSF kernel that reflects the true LYSO density achieving the highest peak in the time activity curve (TAC) and similar lumped noise pattern. CONCLUSIONS: We fully evaluated a practical MLEM reconstruction framework that we developed for VersaPET in terms of qualitative and quantitative performance. Different PSF kernels may be adopted for improving the results of specific imaging tasks but the underlying reasons for the variation in optimal kernel for the real and simulation studies requires further study.