Relationships between diagnostic imaging of first carpometacarpal osteoarthritis and pain, functional status, and disease progression: A systematic review.

OBJECTIVE: To systematically review the association of pain, function, and progression in first carpometacarpal (CMC) osteoarthritis (OA) with imaging biomarkers and radiography-based staging. DESIGN: Database searches in PubMed, Embase, and the Cochrane Library, along with citation searching were conducted in accordance with published guidance. Data on the association of imaging with pain, functional status, and disease progression were extracted and synthesized, along with key information on study methodology such as sample sizes, use of control subjects, study design, number of image raters, and blinding. Methodological quality was assessed using National Heart, Lung, and Blood Institute tools. RESULTS: After duplicate removal, a total of 1969 records were screened. Forty-six articles are included in this review, covering a total of 28,202 study participants, 7263 with first CMC OA. Osteophytes were found to be one of the strongest biomarkers for pain across imaging modalities. Radiographic findings alone showed conflicting relationships with pain. However, Kellgren-Lawrence staging showed consistent associations with pain in various studies. Radiographic, sonographic, and MRI findings and staging showed little association to tools evaluating functional status across imaging modalities. The same imaging methods showed limited ability to predict progression of first CMC OA. A major limitation was the heterogeneity in the study base, limiting synthesis of results. CONCLUSION: Imaging findings and radiography-based staging systems generally showed strong associations with pain, but not with functional status or disease progression. More research and improved imaging techniques are needed to help physicians better manage patients with first CMC OA.

Clinical, functional, and opportunistic CT metrics of sarcopenia at the point of imaging care: analysis of all-cause mortality.

PURPOSE: This study examines clinical, functional, and CT metrics of sarcopenia and all-cause mortality in older adults undergoing outpatient imaging. METHODS: The study included outpatients ≥ 65 years of age undergoing CT or PET/CT at a tertiary care institution. Assessments included screening questionnaires for sarcopenia (SARC-F) and frailty (FRAIL scale), and measurements of grip strength and usual gait speed (6 m course). Skeletal muscle area (SMA), index (SMI, area/height2) and density (SMD) were measured on CT at T12 and L3. A modified SMI was also examined (SMI-m, area/height). Mortality risk was studied with Cox proportional hazard analysis. RESULTS: The study included 416 patients; mean age 73.8 years [sd 6.2]; mean follow-up 2.9 years (sd 1.34). Abnormal grip, SARC-F, and FRAIL scale assessments were associated with higher mortality risk (HR [95%CI] = 2.0 [1.4-2.9], 1.6 [1.1-2.3], 2.0 [1.4-2.8]). Adjusting for age, higher L3-SMA, T12-SMA, T12-SMI and T12-SMI-m were associated with lower mortality risk (HR [95%CI] = 0.80 [0.65-0.90], 0.76 [0.64-0.90], 0.84 [0.70-1.00], and 0.80 [0.67-0.90], respectively). T12-SMD and L3-SMD were not predictive of mortality. After adjusting for abnormal grip strength and FRAIL scale assessments, T12-SMA and T12-SMI-m remained predictive of mortality risk (HR [95%CI] = 0.83 [0.70-1.00] and 0.80 [0.67-0.97], respectively). CONCLUSION: CT areal metrics were weaker predictors of all-cause mortality than clinical and functional metrics of sarcopenia in our older patient cohort; a CT density metric (SMD) was not predictive. Of areal CT metrics, SMI (area/height2) appeared to be less effective than non-normalized SMA or SMA normalized by height1.

Multimodal positron emission tomography (PET) imaging in non-oncologic musculoskeletal radiology.

Musculoskeletal (MSK) disorders are associated with large impacts on patient's pain and quality of life. Conventional morphological imaging of tissue structure is limited in its ability to detect pain generators, early MSK disease, and rapidly assess treatment efficacy. Positron emission tomography (PET), which offers unique capabilities to evaluate molecular and metabolic processes, can provide novel information about early pathophysiologic changes that occur before structural or even microstructural changes can be detected. This sensitivity not only makes it a powerful tool for detection and characterization of disease, but also a tool able to rapidly assess the efficacy of therapies. These benefits have garnered more attention to PET imaging of MSK disorders in recent years. In this narrative review, we discuss several applications of multimodal PET imaging in non-oncologic MSK diseases including arthritis, osteoporosis, and sources of pain and inflammation. We also describe technical considerations and recent advancements in technology and radiotracers as well as areas of emerging interest for future applications of multimodal PET imaging of MSK conditions. Overall, we present evidence that the incorporation of PET through multimodal imaging offers an exciting addition to the field of MSK radiology and will likely prove valuable in the transition to an era of precision medicine.

Time- and region-dependent blood-brain barrier impairment in a rat model of organophosphate-induced status epilepticus.

Acute organophosphate (OP) intoxication can trigger seizures that progress to status epilepticus (SE), and survivors often develop chronic morbidities, including spontaneous recurrent seizures (SRS). The pathogenic mechanisms underlying OP-induced SRS are unknown, but increased BBB permeability is hypothesized to be involved. Previous studies reported BBB leakage following OP-induced SE, but key information regarding time and regional distribution of BBB impairment during the epileptogenic period is missing. To address this data gap, we characterized the spatiotemporal progression of BBB impairment during the first week post-exposure in a rat model of diisopropylfluorophosphate-induced SE, using MRI and albumin immunohistochemistry. Increased BBB permeability, which was detected at 6 h and persisted up to 7 d post-exposure, was most severe and persistent in the piriform cortex and amygdala, moderate but persistent in the thalamus, and less severe and transient in the hippocampus and somatosensory cortex. The extent of BBB leakage was positively correlated with behavioral seizure severity, with the strongest association identified in the piriform cortex and amygdala. These findings provide evidence of the duration, magnitude and spatial breakdown of the BBB during the epileptogenic period following OP-induced SE and support BBB regulation as a viable therapeutic target for preventing SRS following acute OP intoxication.

Neural correlates and effect of jealousy on cognitive flexibility in the female titi monkey (Plecturocebus cupreus).

Jealousy is a social emotion that manifests as behavioral reactions from an individual toward a threat to a valuable relationship. Monogamous species exhibit jealousy-type behaviors as an adaptive response to preserve the relationship. Jealousy is also a complex, negatively-valenced emotion which may include fear of loss, anxiety, suspiciousness, and anger. Negative emotion may impair cognitive processes such as cognitive flexibility, an ability important for coping with new situations. However, little is known about how complex social emotions influence cognitive flexibility. To understand the interaction between jealousy and cognitive flexibility, we examined the neural, physiological, and behavioral factors involved in jealousy and cognitive flexibility in female titi monkeys. We presented subjects with a jealousy provoking scenario, followed by a reversal learning task and a PET scan with a glucose-analog radiotracer. We found that female titi monkeys reacted to a jealousy provoking scenario with increased locomotor behavior and higher glucose uptake in the cerebellum; however, hormone measures and were not affected. As only two females demonstrated cognitive flexibility, the effects of jealousy were difficult to interpret. Locomotion behavior was also negatively correlated with glucose uptake in brain areas linked with motivation, sociality, and cognitive flexibility. Surprisingly, glucose uptake in the orbitofrontal cortex (OFC) was significantly decreased during jealousy scenarios, while uptake in the anterior cingulate cortex (ACC) was decreased during reversal tasks. Our findings suggest that the presence of an intruder produces less visible behavioral reactions in female titis than in males, while still reducing activity in the OFC.

EXPLORing Arthritis with Total-body Positron Emission Tomography.

Arthritis has significant adverse consequences on musculoskeletal tissues and often other organs of the body. Current methods for clinical evaluation of arthritis are suboptimal, and biomarkers that are objective and measurable indicators for monitoring of arthritis disease activity are in critical demand. Recently, total-body positron emission tomography (PET) has been developed that can collect imaging signals synchronously from the entire body at ultra-low doses and reduced scan times. These scanners have increased signal collection efficiency that overcomes several limitations of standard PET scanners in the evaluation of arthritis, and they may potentially provide biomarkers to assess local and systemic impact of the arthritis disease process. This article reviews current results from using total-body PET in the assessment of common arthritic conditions, and it outlines future opportunities and challenges.

Dynamic MRI of the wrist in less than 20 seconds: normal midcarpal motion and reader reliability.

OBJECTIVE: To describe the normal motion pattern at the midcarpal compartment during active radial-ulnar deviation of the wrist using dynamic MRI, and to determine the observer performance for measurements obtained in asymptomatic volunteers. METHODS: Dynamic MRI of 35 wrists in 19 asymptomatic volunteers (age mean 30.4 years, SD 8.6) was performed during active radial-ulnar deviation using a fast gradient-echo pulse sequence with 315 ms temporal resolution (acquisition time, 19 s). Two independent readers measured the transverse translation of the trapezium at the scaphotrapezium joint (STJ) and the capitate-to-triquetrum distance (CTD). Relationships between these measurements and laterality, sex, lunate type, and wrist kinematic pattern were evaluated. RESULTS: At the STJ, the trapezium moved most in radial deviation, with an overall translation of 2.3 mm between ulnar and radial deviation. Mean CTD measurements were the greatest in ulnar deviation and varied 2.4 mm between ulnar and radial deviation. Mean CTD was greater in men than women in the neutral position (p = 0.019), and in wrists with type II lunate morphology during radial and ulnar deviation (p = 0.001, p = 0.014). There were no significant differences in trapezium translation or CTD with wrist laterality and kinematic pattern. Intraobserver and interobserver correlation coefficients were 0.97 and 0.87 for trapezium translation and 0.84 and 0.67 for CTD. CONCLUSION: This study is the first to demonstrate the performance of dynamic MRI to quantify STJ motion and CTD. Dynamic MRI with a short acquisition time may be used as a tool to supplement static MRI in evaluation of the midcarpal compartment.

"Knuckle Cracking": Can Blinded Observers Detect Changes with Physical Examination and Sonography?

BACKGROUND: Voluntary knuckle cracking is a common habit, with a reported prevalence of 25% to 45%. Habitual knuckle cracking also is a frequent source of questions for physicians, and the largest study to date reported an association with functional hand impairments. QUESTIONS/PURPOSES: (1) When compared with subjects who are not habitual knuckle crackers, do habitual knuckle crackers have greater QuickDASH scores, swelling, weakness, joint laxity, or ROM? (2) In subjects who crack their knuckles, does cracking immediately increase ROM? (3) What are the characteristic sonographic findings in joints that crack? METHODS: A prospective, institutional review board-approved study was performed on 400 metacarpophalangeal joints (MPJs) in 40 asymptomatic adult subjects. Of those, 30 subjects had a history of habitual knuckle cracking (defined as daily voluntary popping of MPJs). Clinical history provided by all subjects included a standardized QuickDASH questionnaire. Physical examination was performed by two orthopaedic surgeons (blinded to subjects' knuckle-cracking history and sonographic outcomes). The physical examination included evaluation for swelling, grip strength, and ROM before and after attempted knuckle cracking. Sonographic examination was conducted by one sonographer, with static and real-time cine images recorded before, during, and after MPJ distraction was performed by the subjects. Two musculoskeletal radiologists (blinded to subjects' knuckle-cracking history) interpreted the images for a definite hyperechoic focus during and after MPJ distraction; this was compared against the reference standard of an audible "crack" during joint distraction. RESULTS: Comparing subjects with knuckle cracking with those who did not crack their knuckles, there was no differences in QuickDASH scores (knuckle crackers, 3.7 ± 5.2; nonknuckle crackers, 3.2 ± 6.3; mean difference, 0.6; 95% CI, -3.5 to 4.6; p = 0.786), laxity (knuckle crackers, 2.0 ± 1.8; nonknuckle crackers, 0.3 ± 0.7; mean difference, 1.7; 95% CI, 0.5-2.9; p = 0.191), and grip strength (preultrasound, right hand, p = 0.499, left hand p = 0.575; postultrasound, right hand p = 0.777, left hand p = 0.424); ROM comparisons between subjects with a history of habitual knuckle cracking versus subjects without such a history only yielded increased ROM in joints that cracked during manipulation (knuckle cracking, 143.8° ± 26.5°; nonknuckle cracking, 134.9° ± 28.6°; mean difference, 9.0°; 95% CI, 2.9°-15.1°; p = 0.004). Swelling was not observed in any subjects, including when comparing MPJs before versus after distraction maneuvers that resulted in audible cracks. Immediately after a documented crack, there were greater ranges of motion with active flexion (preultrasound, 85.7° ± 12.4°; postultrasound, 88.6° ± 11.6°; mean difference, -2.9°; 95% CI, -5.1° to -0.8°; p = 0.009), passive flexion (preultrasound, 96.1° ± 12.4°; postultrasound, 100.3° ± 10.4°; mean difference, -4.3°; 95% CI, -6.2° to -2.3°; p < 0.001), passive extension (preultrasound, 41.8° ± 18.1°; postultrasound, 45.2° ± 17.6°; mean difference, -3.5°; 95% CI, -6.9° to -0.1°; p = 0.046), and passive total ROM (preultrasound, 137.8° ± 24.8°; postultrasound, 145.6° ± 23.1°; mean difference, -7.7°; 95% CI, -11.7° to -3.8°; p < 0.001). The characteristic sonographic finding observed during cracking events is an echogenic focus that appears de novo dynamically in the joint during distraction. CONCLUSIONS: We found no evidence of immediate adverse physical examination findings after knuckle cracking. However, we did find a small increase in ROM among joints that cracked compared with those that did not. Future studies should examine if there are any long-term beneficial and adverse clinical outcomes associated with habitual knuckle cracking. LEVEL OF EVIDENCE: Level I, prognostic study.

Association of lunate morphology, sex, and lunotriquetral interosseous ligament injury with radiologic measurement of the capitate-triquetrum joint.

OBJECTIVE: Radiologic presentation of carpal instability at the radial side of the carpus, e.g. scapholunate diastasis following scapholunate interosseous ligament injury, has been studied extensively. By comparison, presentation at the ulnar-sided carpus has not. The purpose of this study was to assess the effects of lunate morphology, sex, and lunotriquetral interosseous ligament (LTIL) status on the radiologic measurement of the capitate-triquetrum joint (C-T distance). Further, we sought to evaluate the diagnostic accuracy of C-T distance for assessing LTIL injuries. MATERIALS AND METHODS: We retrospectively identified 223 wrists with wrist radiographs and MR arthrograms with contrast injection. Data collected included sex, lunate morphology and LTIL status from MR arthrography, and C-T distance from radiography. The effects of lunate morphology, sex, and LTIL injury status on C-T distance were evaluated using generalized linear models. Diagnostic performance of C-T distance was assessed by the area under receiver-operator characteristic curve (AUROC). RESULTS AND CONCLUSION: Lunate morphology, sex, and LTIL injury status all had significant effects on C-T distance; wrists with type II lunates, men, and wrists with LTIL injuries had greater C-T distances than wrists with type I lunates, women, and wrists without LTIL injuries, respectively (p < 0.01). The diagnostic value of the C-T distance for identifying patients with full-thickness LTIL tears was sufficient for women with type I (AUROC = 0.67) and type II lunates (0.60) and good for men with type I (0.72) and type II lunates (0.77). The demonstrated influence of LTIL status on C-T distance supports the use of C-T distance as a tool in assessing for full-thickness LTIL tears.

Fully automated whole brain segmentation from rat MRI scans with a convolutional neural network.

BACKGROUND: Whole brain delineation (WBD) is utilized in neuroimaging analysis for data preprocessing and deriving whole brain image metrics. Current automated WBD techniques for analysis of preclinical brain MRI data show limited accuracy when images present with significant neuropathology and anatomical deformations, such as that resulting from organophosphate intoxication (OPI) and Alzheimer's Disease (AD), and inadequate generalizability. METHODS: A modified 2D U-Net framework was employed for WBD of MRI rodent brains, consisting of 27 convolutional layers, batch normalization, two dropout layers and data augmentation, after training parameter optimization. A total of 265 T2-weighted 7.0 T MRI scans were utilized for the study, including 125 scans of an OPI rat model for neural network training. For testing and validation, 20 OPI rat scans and 120 scans of an AD rat model were utilized. U-Net performance was evaluated using Dice coefficients (DC) and Hausdorff distances (HD) between the U-Net-generated and manually segmented WBDs. RESULTS: The U-Net achieved a DC (median[range]) of 0.984[0.936-0.990] and HD of 1.69[1.01-6.78] mm for OPI rat model scans, and a DC (mean[range]) of 0.975[0.898-0.991] and HD of 1.49[0.86-3.89] for the AD rat model scans. COMPARISON WITH EXISTING METHODS: The proposed approach is fully automated and robust across two rat strains and longitudinal brain changes with a computational speed of 8 seconds/scan, overcoming limitations of manual segmentation. CONCLUSIONS: The modified 2D U-Net provided a fully automated, efficient, and generalizable segmentation approach that achieved high accuracy across two disparate rat models of neurological diseases.

Quantitative T2 mapping-based longitudinal assessment of brain injury and therapeutic rescue in the rat following acute organophosphate intoxication.

Acute intoxication with organophosphate (OP) cholinesterase inhibitors poses a significant public health risk. While currently approved medical countermeasures can improve survival rates, they often fail to prevent chronic neurological damage. Therefore, there is need to develop effective therapies and quantitative metrics for assessing OP-induced brain injury and its rescue by these therapies. In this study we used a rat model of acute intoxication with the OP, diisopropylfluorophosphate (DFP), to test the hypothesis that T2 measures obtained from brain magnetic resonance imaging (MRI) scans provide quantitative metrics of brain injury and therapeutic efficacy. Adult male Sprague Dawley rats were imaged on a 7T MRI scanner at 3, 7 and 28 days post-exposure to DFP or vehicle (VEH) with or without treatment with the standard of care antiseizure drug, midazolam (MDZ); a novel antiseizure medication, allopregnanolone (ALLO); or combination therapy with MDZ and ALLO (DUO). Our results show that mean T2 values in DFP-exposed animals were: (1) higher than VEH in all volumes of interest (VOIs) at day 3; (2) decreased with time; and (3) decreased in the thalamus at day 28. Treatment with ALLO or DUO, but not MDZ alone, significantly decreased mean T2 values relative to untreated DFP animals in the piriform cortex at day 3. On day 28, the DUO group showed the most favorable T2 characteristics. This study supports the utility of T2 mapping for longitudinally monitoring brain injury and highlights the therapeutic potential of ALLO as an adjunct therapy to mitigate chronic morbidity associated with acute OP intoxication.

A longitudinal MRI and TSPO PET-based investigation of brain region-specific neuroprotection by diazepam versus midazolam following organophosphate-induced seizures.

Acute poisoning with organophosphorus cholinesterase inhibitors (OPs), such as OP nerve agents and pesticides, can cause life threatening cholinergic crisis and status epilepticus (SE). Survivors often experience significant morbidity, including brain injury, acquired epilepsy, and cognitive deficits. Current medical countermeasures for acute OP poisoning include a benzodiazepine to mitigate seizures. Diazepam was long the benzodiazepine included in autoinjectors used to treat OP-induced seizures, but it is now being replaced in many guidelines by midazolam, which terminates seizures more quickly, particularly when administered intramuscularly. While a direct correlation between seizure duration and the extent of brain injury has been widely reported, there are limited data comparing the neuroprotective efficacy of diazepam versus midazolam following acute OP intoxication. To address this data gap, we used non-invasive imaging techniques to longitudinally quantify neuropathology in a rat model of acute intoxication with the OP diisopropylfluorophosphate (DFP) with and without post-exposure intervention with diazepam or midazolam. Magnetic resonance imaging (MRI) was used to monitor neuropathology and brain atrophy, while positron emission tomography (PET) with a radiotracer targeting translocator protein (TSPO) was utilized to assess neuroinflammation. Animals were scanned at 3, 7, 28, 65, 91, and 168 days post-DFP and imaging metrics were quantitated for the hippocampus, amygdala, piriform cortex, thalamus, cerebral cortex and lateral ventricles. In the DFP-intoxicated rat, neuroinflammation persisted for the duration of the study coincident with progressive atrophy and ongoing tissue remodeling. Benzodiazepines attenuated neuropathology in a region-dependent manner, but neither benzodiazepine was effective in attenuating long-term neuroinflammation as detected by TSPO PET. Diffusion MRI and TSPO PET metrics were highly correlated with seizure severity, and early MRI and PET metrics were positively correlated with long-term brain atrophy. Collectively, these results suggest that anti-seizure therapy alone is insufficient to prevent long-lasting neuroinflammation and tissue remodeling.

Ultrasound backscatter microscopy for imaging of oral carcinoma.

OBJECTIVES: Ultrasound backscatter microscopy (UBM), or ultrasound biomicroscopy, is a noninvasive, label-free, and ionizing radiation-free technique allowing high-resolution 3-dimensional structural imaging. The goal of this study was to evaluate UBM for resolving anatomic features associated with squamous cell carcinoma of the oral cavity. METHODS: The study was conducted in a hamster buccal pouch model. A carcinogen was topically applied to cheeks of 14 golden Syrian hamsters. Six additional hamsters served as healthy controls. A high-frequency (41 MHz, 6-mm focal depth, lateral and axial resolutions of 65 and 37 µm, respectively) UBM system was used for scanning the oral cavity after 14 weeks of carcinogen application. Histologic analyses were conducted on scanned regions. RESULTS: The histologic structure of buccal tissue and microvasculature networks could be visualized from the UBM images. Epithelial and mucosal hypertrophy and neoplastic changes were identified in animals subjected to the carcinogen. In animals with invasive squamous cell carcinoma, lesion development and destruction of the structural integrity of tissue layers were noted. CONCLUSIONS: In this pilot study, UBM generated sufficient contrast for morphologic features associated with oral carcinoma compared to healthy tissue. This modality may present a practical technique for detection of oral neoplasms that is potentially translatable to humans.

Kinetic Evaluation of the Hypoxia Radiotracers [18F]FMISO and [18F]FAZA in Dogs with Spontaneous Tumors Using Dynamic PET/CT Imaging.

Purpose: We evaluated the kinetics of the hypoxia PET radiotracers, [18F]fluoromisonidazole ([18F]FMISO) and [18F]fluoroazomycin-arabinoside ([18F]FAZA), for tumor hypoxia detection and to assess the correlation of hypoxic kinetic parameters with static imaging measures in canine spontaneous tumors. Methods: Sixteen dogs with spontaneous tumors underwent a 150-min dynamic PET scan using either [18F]FMISO or [18F]FAZA. The maximum tumor-to-muscle ratio (TMRmax) > 1.4 on the last image frame was used as the standard threshold to determine tumor hypoxia. The tumor time-activity curves were analyzed using irreversible and reversible two-tissue compartment models and graphical methods. TMRmax was compared with radiotracer trapping rate (k 3), influx rate (K i), and distribution volume (V T). Results: Tumor hypoxia was detected in 7/8 tumors in the [18F]FMISO group and 4/8 tumors in the [18F]FAZA group. All hypoxic tumors were detected at > 120 min with [18F]FMISO and at > 60 min with [18F]FAZA. [18F]FAZA showed better fit with the reversible model. TMRmax was strongly correlated with the irreversible parameters (k 3 and K i) for [18F]FMISO at > 90 min and with the reversible parameter (V T) for [18F]FAZA at > 120 min. Conclusions: Our results showed that [18F]FAZA provided a promising alternative radiotracer to [18F]FMISO with detecting the presence of tumor hypoxia at an earlier time (60 min), consistent with its favorable faster kinetics. The strong correlation between TMRmax over the 90-150 min and 120-150 min timeframes with [18F]FMISO and [18F]FAZA, respectively, with kinetic parameters associated with tumor hypoxia for each radiotracer, suggests that a static scan measurement (TMRmax) is a good alternative to quantify tumor hypoxia. Supplementary Information: The online version contains supplementary material available at 10.1007/s13139-022-00780-4.

Novel Insights From Basic Science in Psoriatic Disease at the GRAPPA 2022 Annual Meeting.

Recent basic science advances in psoriatic disease (PsD) were presented and discussed at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2022 annual meeting. Topics included clinical applications of biomarkers, what the future of biomarkers for PsD may hold, the challenges of developing biomarker research to the point of clinical utility, advances in total-body positron emission tomography/computed tomography imaging, and emerging concepts from single-cell studies in PsD.

Real-time MRI of the moving wrist at 0.55 tesla.

OBJECTIVES: Magnetic resonance imaging (MRI) using 1.5T or 3.0T systems is routinely employed for assessing wrist pathology; however, due to off-resonance artifacts and high power deposition, these high-field systems have drawbacks for real-time (RT) imaging of the moving wrist. Recently, high-performance 0.55T MRI systems have become available. In this proof-of-concept study, we tested the hypothesis that RT-MRI during continuous, active, and uninterrupted wrist motion is feasible with a high-performance 0.55T system at temporal resolutions below 100 ms and that the resulting images provide visualization of tissues commonly interrogated for assessing dynamic wrist instability. METHODS: Participants were scanned during uninterrupted wrist radial-ulnar deviation and clenched fist maneuvers. Resulting images (nominal temporal resolution of 12.7-164.6 ms per image) were assessed for image quality. Feasibility of static MRI to supplement RT-MRI acquisition was also tested. RESULTS: The RT images with temporal resolutions < 100 ms demonstrated low distortion and image artifacts, and higher reader assessment scores. Static MRI scans showed the ability to assess anatomical structures of interest in the wrist. CONCLUSION: RT-MRI of the wrist at a high temporal resolution, coupled with static MRI, is feasible with a high-performance 0.55T system, and may enable improved assessment of wrist dynamic dysfunction and instability. ADVANCES IN KNOWLEDGE: Real-time MRI of the moving wrist is feasible with high-performance 0.55T and may improve the evaluation of dynamic dysfunction of the wrist.

Total-Body Multiparametric PET Quantification of 18F-FDG Delivery and Metabolism in the Study of Coronavirus Disease 2019 Recovery.

Conventional whole-body static 18F-FDG PET imaging provides a semiquantitative evaluation of overall glucose metabolism without insight into the specific transport and metabolic steps. Here we demonstrate the ability of total-body multiparametric 18F-FDG PET to quantitatively evaluate glucose metabolism using macroparametric quantification and assess specific glucose delivery and phosphorylation processes using microparametric quantification for studying recovery from coronavirus disease 2019 (COVID-19). Methods: The study included 13 healthy subjects and 12 recovering COVID-19 subjects within 8 wk of confirmed diagnosis. Each subject had a 1-h dynamic 18F-FDG scan on the uEXPLORER total-body PET/CT system. Semiquantitative SUV and the SUV ratio relative to blood (SUVR) were calculated for different organs to measure glucose utilization. Tracer kinetic modeling was performed to quantify the microparametric blood-to-tissue 18F-FDG delivery rate [Formula: see text] and the phosphorylation rate k 3, as well as the macroparametric 18F-FDG net influx rate ([Formula: see text]). Statistical tests were performed to examine differences between healthy subjects and recovering COVID-19 subjects. The effect of COVID-19 vaccination was also investigated. Results: We detected no significant difference in lung SUV but significantly higher lung SUVR and [Formula: see text] in COVID-19 recovery, indicating improved sensitivity of kinetic quantification for detecting the difference in glucose metabolism. A significant difference was also observed in the lungs with the phosphorylation rate k 3 but not with [Formula: see text], which suggests that glucose phosphorylation, rather than glucose delivery, drives the observed difference of glucose metabolism. Meanwhile, there was no or little difference in bone marrow 18F-FDG metabolism measured with SUV, SUVR, and [Formula: see text] but a significantly higher bone marrow [Formula: see text] in the COVID-19 group, suggesting a difference in glucose delivery. Vaccinated COVID-19 subjects had a lower lung [Formula: see text] and a higher spleen [Formula: see text] than unvaccinated COVID-19 subjects. Conclusion: Higher lung glucose metabolism and bone marrow glucose delivery were observed with total-body multiparametric 18F-FDG PET in recovering COVID-19 subjects than in healthy subjects, implying continued inflammation during recovery. Vaccination demonstrated potential protection effects. Total-body multiparametric PET of 18F-FDG can provide a more sensitive tool and more insights than conventional whole-body static 18F-FDG imaging to evaluate metabolic changes in systemic diseases such as COVID-19.

Total-Body Multiparametric PET Quantification of 18 F-FDG Delivery and Metabolism in the Study of COVID-19 Recovery.

Conventional whole-body 18 F-FDG PET imaging provides a semi-quantitative evaluation of overall glucose metabolism without gaining insight into the specific transport and metabolic steps. Here we demonstrate the ability of total-body multiparametric 18 F-FDG PET to quantitatively evaluate glucose metabolism using macroparametric quantification and assess specific glucose delivery and phosphorylation processes using microparametric quantification for studying recovery from coronavirus disease 2019 (COVID-19). Methods: The study included thirteen healthy subjects and twelve recovering COVID-19 subjects within eight weeks of confirmed diagnosis. Each subject had a dynamic 18 F-FDG scan on the uEXPLORER total-body PET/CT system for one hour. Semiquantitative standardized uptake value (SUV) and SUV ratio relative to blood (SUVR) were calculated for regions of interest (ROIs) in different organs to measure glucose utilization. Tracer kinetic modeling was performed to quantify microparametric rate constants K 1 and k 3 that characterize 18 F-FDG blood-to-tissue delivery and intracellular phosphorylation, respectively, and a macroparameter K i that represents 18 F-FDG net influx rate. Statistical tests were performed to examine differences between the healthy controls and recovering COVID-19 subjects. Impact of COVID-19 vaccination was investigated. We further generated parametric images to confirm the ROI-based analysis. Results: We detected no significant difference in lung SUV but significantly higher lung SUVR and K i in the recovering COVID-19 subjects, indicating an improved sensitivity of kinetic quantification for detecting the difference in glucose metabolism. A significant difference was also observed in the lungs with the phosphorylation rate k 3 , but not with the delivery rate K 1 , which suggests it is glucose phosphorylation, not glucose delivery, that drives the observed difference of glucose metabolism in the lungs. Meanwhile, there was no or little difference in bone marrow metabolism measured with SUV, SUVR and K i , but a significant increase in bone-marrow 18 F-FDG delivery rate K 1 in the COVID-19 group ( p < 0.05), revealing a difference of glucose delivery in this immune-related organ. The observed differences were lower or similar in vaccinated COVID-19 subjects as compared to unvaccinated ones. The organ ROI-based findings were further supported by parametric images. Conclusions: Higher lung glucose metabolism and bone-marrow glucose delivery were observed with total-body multiparametric 18 F-FDG PET in recovering COVID-19 subjects as compared to healthy subjects, which suggests continued inflammation due to COVID-19 during the early stages of recovery. Total-body multiparametric PET of 18 F-FDG delivery and metabolism can provide a more sensitive tool and more insights than conventional static whole-body 18 F-FDG imaging to evaluate metabolic changes in systemic diseases such as COVID-19.

Regulation of beige adipocyte thermogenesis by the cold-repressed ER protein NNAT.

OBJECTIVE: Cold stimuli trigger the conversion of white adipose tissue into beige adipose tissue, which is capable of non-shivering thermogenesis. However, what process drives this activation of thermogenesis in beige fat is not well understood. Here, we examine the ER protein NNAT as a regulator of thermogenesis in adipose tissue. METHODS: We investigated the regulation of adipose tissue NNAT expression in response to changes in ambient temperature. We also evaluated the functional role of NNAT in thermogenic regulation using Nnat null mice and primary adipocytes that lack or overexpress NNAT. RESULTS: Cold exposure or treatment with a ß3-adrenergic agonist reduces the expression of adipose tissue NNAT in mice. Genetic disruption of Nnat in mice enhances inguinal adipose tissue thermogenesis. Nnat null mice exhibit improved cold tolerance both in the presence and absence of UCP1. Gain-of-function studies indicate that ectopic expression of Nnat abolishes adrenergic receptor-mediated respiration in beige adipocytes. NNAT physically interacts with the ER Ca2+-ATPase (SERCA) in adipocytes and inhibits its activity, impairing Ca2+ transport and heat dissipation. We further demonstrate that NHLRC1, an E3 ubiquitin protein ligase implicated in proteasomal degradation of NNAT, is induced by cold exposure or ß3-adrenergic stimulation, thus providing regulatory control at the protein level. This serves to link cold stimuli to NNAT degradation in adipose tissue, which in turn leads to enhanced SERCA activity. CONCLUSIONS: Our study implicates NNAT in the regulation of adipocyte thermogenesis.