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Our objective was to explore the association between resting-state functional connectivity and accelerometer-measured physical activity in pediatric concussion. Fourteen children with concussion (aged 14.54 ± 2.39 years, 8 female) were included in this secondary data analysis of a larger study. Participants had neuroimaging at 15.3 ± 6.7 days postinjury and subsequently a mean of 11.1 ± 5.0 days of accelerometer data. Intra-network connectivity of the default mode network (DMN), sensorimotor network (SMN), salience network (SN), and frontoparietal network (FPN) was computed using resting-state MRI. We found that, per general linear models (GLMs), only intra-network connectivity of the DMN was associated with physical activity levels. More specifically, increased intra-network connectivity of the DMN was significantly associated with higher levels of subsequent accelerometer-measured light physical activity (LPA; F(2, 11) = 7.053, p = 0.011, Ra2 = 0.562; β = 0.469), moderate physical activity (MPA; F(2, 11) = 6.159, p = 0.016, Ra2 = 0.528; β = 0.725), and vigorous physical activity (VPA; F(2, 11) = 10.855, p = 0.002, Ra2 = 0.664; β = 0.792). Intra-network connectivity of the DMN did not significantly predict sedentary time. Therefore, these preliminary findings suggest that there is a positive association between the intra-network connectivity of the DMN and device-measured physical activity in children with concussion.

INTRODUCTIONIt remains unclear to which extent vascular burden promotes neurodegeneration and cognitive dysfunction in a cohort spanning low-to-severe small vessel disease (SVD) and amyloid-beta pathology.METHODSIn 120 subjects, we investigated 1) whether vascular burden, quantified as total or lobar white matter hyperintensity (WMH) volumes, is associated with different cognitive domains; and 2) whether the total WMH effect on cognition is mediated by amyloid (18F-AV45-PET), glucose metabolism (18F-FDG-PET), and/or cortical atrophy.RESULTSIncreased total WMH volume was associated with poorer performance in all cognitive domains tested, with the strongest effects observed for semantic fluency. These relationships were mediated mainly through cortical atrophy, particularly in the temporal lobe, and to a lesser extent through amyloid and metabolism. WMH volumes differentially impacted cognition depending on lobar location and amyloid status.DISCUSSIONOur study suggests mainly an amyloid-independent pathway in which vascular burden affects cognitive impairment through temporal lobe atrophy.

Childhood obesity is a growing worldwide problem. In adults, lower cold-induced brown adipose tissue (BAT) activity is linked to obesity and metabolic dysfunction; this relationship remains uncertain in children. In this cross-sectional study, we compared cold-induced supraclavicular (SCV) BAT activity (percent change in proton density fat fraction [PDFF]) within the SCV region after 1 h of whole-body cold exposure (18°C), using MRI in 26 boys aged 8–10 years: 13 with normal BMI and 13 with overweight/obesity. Anthropometry, body composition, hepatic fat, visceral adipose tissue (VAT), and pre- and postcold PDFF of the subcutaneous adipose tissue (SAT) in the posterior neck region and the abdomen were measured. Boys with overweight/obesity had lower cold-induced percent decline in SCV PDFF compared with those with normal BMI (1.6 ± 0.8 vs. 4.7 ± 1.2%, P = 0.044). SCV PDFF declined significantly in boys with normal BMI (2.7 ± 0.7%, P = 0.003) but not in boys with overweight/obesity (1.1 ± 0.5%, P = 0.053). No cold-induced changes in the PDFF of either neck SAT (−0.89 ± 0.7%, P = 0.250, vs. 0.37 ± 0.3%, P = 0.230) or abdominal SAT (−0.39 ± 0.5%, P = 0.409, and 0.25 ± 0.2%, P = 0.139, for normal BMI and overweight/obesity groups, respectively) were seen. The cold-induced percent decline in SCV PDFF was inversely related to BMI (r = −0.39, P = 0.047), waist circumference (r = −0.48, P = 0.014), and VAT (r = −0.47, P = 0.014). Thus, in young boys, as in adults, BAT activity is lower in those with overweight/obesity, suggesting that restoring activity may be important for improving metabolic health.

Background and ObjectivesTo determine whether cognitive reserve attenuates the association of vascular brain injury with cognition.MethodsCross-sectional data were analyzed from 2 harmonized studies: the Canadian Alliance for Healthy Hearts and Healthy Minds (CAHHM) and the Prospective Urban and Rural Epidemiology (PURE) study. Markers of cognitive reserve were education, involvement in social activities, marital status, height, and leisure physical activity, which were combined into a composite score. Vascular brain injury was defined as nonlacunar brain infarcts or high white matter hyperintensity (WMH) burden on MRI. Cognition was assessed using the Montreal Cognitive Assessment Tool (MoCA) and the Digit Symbol Substitution Test (DSST).ResultsThere were 10,916 participants age 35–81. Mean age was 58.8 years (range 35–81) and 55.8% were female. Education, moderate leisure physical activity, being in a marital partnership, being taller, and participating in social groups were each independently associated with higher cognition, as was the composite cognitive reserve score. Vascular brain injury was associated with lower cognition (β –0.35 [95% confidence interval [CI] –0.53 to −0.17] for MoCA and β −2.19 [95% CI −3.22 to −1.15] for DSST) but the association was not modified by the composite cognitive reserve variable (interactionp= 0.59 for MoCA andp= 0.72 for DSST).ConclusionsBoth vascular brain injury and markers of cognitive reserve are associated with cognition. However, the effects were independent such that the adverse effects of covert vascular brain injury were not attenuated by higher cognitive reserve. To improve cognitive brain health, interventions to both prevent cerebrovascular disease and promote positive lifestyles are needed.

Overuse knee injuries are common in bicycling and are often attributed to poor bicycle-fit. Bicycle-fit for knee health focuses on setting saddle height to elicit a minimum knee flexion angle of 25-40°. Equations to predict saddle height include a single input, resulting in a likely suboptimal bicycle-fit. The purpose of this work was to develop an equation to predict saddle height from anthropometrics, bicycle geometry, and user-defined joint kinematics.

Numerous studies have stressed the importance of exercise in promoting physical and mental health and for aiding in cognition. Encouragingly, physical exercise has been shown to reduce the risk of developing Alzheimer's disease and to mitigate hemiparesis experienced by stroke patients. Additionally, today where over 1.9 billion are overweight, physical exercise is imperative to save lives and to mitigate the burden on the healthcare system. Although the benefits of physical exercise have been explored, the underlying mechanisms to enact these benefits have not been well-characterized. Here we review exercise-induced changes in regional brain activation and modulation. Paradigms differing in intensity, duration, and type of motor movement have been used to assess exercise effects on memory, cognition, and disease mitigation in youth and elderly populations. To evaluate exercise-induced changes in neural activity, the noninvasive imaging technique, functional magnetic resonance imaging (fMRI), is employed. fMRI is recorded either during or after exercise intervention. Post-exercise fMRI is often paired with in-bore tests of cognition to provide insight into the associated brain regions. Whereas, during intervention, fMRI is used to detail muscle-associated neural activation profiles. Characterization of the region and magnitude of brain activation has been used to perform comparative studies and identify specific characteristics from individuals with varying motor and cognitive abilities. Further fMRI and exercise research, with the use of these metrics, could facilitate the development of tools for disease diagnosis or to assess level of dysfunction or progression.

Childhood obesity is a growing worldwide problem. In adults, lower cold-induced brown adipose tissue (BAT) activity is linked to obesity and metabolic dysfunction; this relationship remains uncertain in children. In this cross-sectional study, we compared cold-induced supraclavicular (SCV) BAT activity (percent change in proton density fat fraction (PDFF)) within the SCV region after one hour of whole-body cold exposure (18°C), using magnetic resonance imaging (MRI) in 26 boys aged 8-10 years: 13 with normal body mass index (BMI), and 13 with overweight/obesity. Anthropometry, body composition, hepatic, and visceral fat (VAT), and pre-and post-cold PDFF of the subcutaneous adipose tissue (SAT) in the posterior neck region and the abdomen were measured. Boys with overweight/obesity had lower cold-induced percent decline in SCV PDFF compared to those with normal BMI (1.6±0.8 vs 4.7±1.2 %, p=0.044). SCV PDFF declined significantly in boys with normal BMI (2.7±0.7 %, p=0.003) but not in boys with overweight/obesity (1.1±0.5 %, p=0.053). No cold-induced changes in the PDFF of either the neck SAT (-0.89±0.7 %, p= 0.250 vs 0.37±0.3 %, p= 0.230) or the abdominal SAT (-0.39±0.5 %, p=0.409 and 0.25±0.2 %, p= 0.139 for normal BMI and overweight/obesity groups respectively) were seen. The cold-induced percent decline in SCV PDFF was inversely related to BMI (r=-0.39, p= 0.047), waist circumference (r= -0.48, p= 0.014), and VAT (r= -0.47, p= 0.014). Thus, in young boys, as in adults, BAT activity is lower in those with overweight/obesity, suggesting that restoring activity may be important for improving metabolic health.

Concussions are a major health concern due to the unpredictable onset and resolution of debilitating post-concussion symptoms. This review discusses physiological, structural and functional brain changes post-concussion, novel non-invasive medical imaging techniques to improve diagnosis, and the role exercise could play in concussion recovery. After sustaining a concussion, about 50% of youth and 20% of adults have symptoms that last for more than a month. Understanding concussion severity has become consequential in recent years as professional sports leagues have acknowledged their harmful short- and long-term effects. Despite these effects, concussed children and adults continue to return to activity and sport prior to a full recovery. This premature return can be enabled because routine clinical medical imaging techniques are unable to detect post-concussion brain damage. However, there have been advances in MRI approaches that clearly indicate brain damage due to concussion. In terms of recovery, rest has been the long-standing prescribed concussion treatment; however, subsymptom exacerbating exercise has been shown to be a safe and effective treatment option. Novel controlled aerobic exercise interventions have improved concussion outcomes by reducing recovery time and symptom severity.

This proof-of-principle study integrates joint reaction forces (JRFs) and bone shape to assess acute cartilage changes from walking and cycling.Sixteen women with symptomatic knee osteoarthritis were recruited. Biomechanical assessment estimated JRFs during walking and cycling. Subsamples had magnetic resonance imaging (MRI) performed before and after a 25-min walking (n = 7) and/or cycling (n = 9) activity. MRI scans were obtained to assess cartilage shape and composition (TCartilage thickness (interior lateral, Δ - 0.10 mm) and TWalking and cycling caused distinct patterns of cartilage deformation, which depended on knee JRFs and bone morphology. For the first time, these results show that cartilage deformation is dependent on bone shapes and JRFs in vivo.

Summary In rodents, lower brown adipose tissue (BAT) activity is associated with greater liver steatosis and changes in the gut microbiome. However, little is known about these relationships in humans. In adults (n = 60), we assessed hepatic fat and cold-stimulated BAT activity using magnetic resonance imaging and the gut microbiota with 16S sequencing. We transplanted gnotobiotic mice with feces from humans to assess the transferability of BAT activity through the microbiota. Individuals with NAFLD (n = 29) have lower BAT activity than those without, and BAT activity is inversely related to hepatic fat content. BAT activity is not related to the characteristics of the fecal microbiota and is not transmissible through fecal transplantation to mice. Thus, low BAT activity is associated with higher hepatic fat accumulation in human adults, but this does not appear to have been mediated through the gut microbiota., Graphical abstract, Highlights Adults with NAFLD have lower brown adipose tissue activity compared with controls Brown adipose tissue (BAT) activity is not linked to fecal gut microbiota BAT activity is not transmissible to mice via fecal transplantation, Ahmed et al. show, using MRI, that higher cold-stimulated BAT activity is linked to lower hepatic fat in 60 adults. BAT activity is not linked to fecal gut microbiota characteristics and is not transmissible to germ-free mice. Gut microbiota does not link BAT activity and liver fat.

Despite the technical challenges that require lengthy acquisitions to overcome poor signal-to-noise ratio (SNR), sodium (

ObjectivesTo explore the association between resting state functional connectivity and accelerometer-measured physical activity in pediatric concussion.MethodsFourteen children with concussion (aged 14.54 ± 2.39 years, 8 female) were included in this secondary data-analysis. Participants had neuroimaging at 15.3 ± 6.7 days post-injury and subsequently a mean of 11.1 ± 5.0 days of accelerometer data. Intra-network connectivity of the default mode network (DMN), sensorimotor network (SMN), salience network (SN), and fronto-parietal network (FPN) was computed.ResultsPer general linear models, only intra-network connectivity of the DMN was associated with habitual physical activity levels. More specifically, increased intra-network connectivity of the DMN was significantly associated with higher levels of subsequent accelerometer-measured light physical activity (F(2,11) = 7.053, p = 0.011, Ra2 = 0.562; β = 0.469), moderate physical activity (F(2,11) = 7.053, p = 0.011, Ra2 = 0.562; β = 0.725), and vigorous physical activity (F(2,11) = 10.855, p = 0.002, Ra2 = 0.664; β = 0.79). Intra-network connectivity of the DMN did not significantly predict sedentary time. Likewise, the SMN, SA, and FPN were not significantly associated with either sedentary time or physical activity.ConclusionThese findings suggest that there is a positive association between the intra-network connectivity of the DMN and device-measured physical activity in children with concussion. Given that DMN impairment can be commonplace following concussion, this may be associated with lower levels of habitual physical activity, which can preclude children from experiencing the symptom-improving benefits of sub-maximal physical activity.KEY FINDINGSWhat are the new findings?Intra-network connectivity of the default mode network is associated with subsequent accelerometer-measured light, moderate, and vigorous physical activity within the first-month of pediatric concussionSimilar associations with physical activity are not observed when examining the intra-network connectivity of the sensorimotor network, salience network, or fronto-parietal networkImproved connectivity within the default mode network may lead to increased participation in light to vigorous physical activity in pediatric concussionHow might it impact on clinical practice in the future?Default mode network impairment is commonplace in concussion, and this may limit children from experiencing the symptom-improving benefits of physical activityAdjunctive interventions (e.g., mindfulness) that improve the health of the default mode network should be further studied in pediatric concussion

ObjectivesTo characterize and quantify differences in accelerometer-measured physical activity and sedentary time between children with concussion (within the first month of injury) and 1:1 matched healthy controls.MethodsSecondary analysis of accelerometer data collected on 60 children with concussion and 60 healthy controls matched for age, sex, and season of accelerometer wear. Daily and hourly sedentary time, light physical activity (LPA), moderate physical activity (MPA), and vigorous physical activity (VPA) were compared between groups per independent samples t-tests.ResultsChildren with concussion (12.74 ± 2.85 years, 31 females) were significantly more sedentary than controls (12.43 ± 2.71 years, 31 females; mean difference [MD], 38.3 minutes/day, p=0.006), and spent less time performing LPA (MD, -19.5 minutes/day, p=0.008), MPA (MD, -9.8 minutes/day, pConclusionClinical management should continue to advise against prolonged rest following pediatric concussion, given the activity debt observed within the first-month of injury. Currently, clinical management of concussion is shifting towards prescribing a single bout of daily sub-maximal aerobic exercise. Interventions aimed at reducing overall sedentary time and increasing habitual physical activity in pediatric concussion also warrant study.KEY FINDINGSWhat are the new findings?Per accelerometry, children with concussion are significantly more sedentary than healthy controls within the first-month of injuryRelative to healthy controls, in the first-month of injury, children with concussion perform less accelerometer-measured light, moderate, and vigorous physical activityThese patterns of increased sedentary time and reduced physical activity are seen throughout the day, from 8:00 AM to 9:00 PMModerate and vigorous physical activity levels are predicted by days-post injury in children with concussion, and may increase naturally as a consequence of recoveryHow might it impact on clinical practice in the future?Given the accumulating evidence that prolonged rest should be avoided following concussion, primary care clinicians should continue to advocate for light physical activity post-concussion to limit increased sedentary time

ImportancePediatric concussion has a rising incidence and can lead to long-term symptoms in nearly 30% of children. Resting state functional magnetic resonance imaging (rs-fMRI) disturbances are a common pathological feature of concussion, though no studies have examined sex-differences with respect to this outcome. Despite known sex-differences in how pediatric concussion presents, females have remained understudied in rs-fMRI studies, precluding a sex-specific understanding of the functional neuropathology of pediatric concussion.ObjectiveTo provide the first insights into sex-specific rs-fMRI differences in pediatric concussion.Design, setting, and participantsSecondary data analysis of rs-fMRI data collected on children with concussion recruited from in a pediatric hospital setting, with control data accessed from the open-source ABIDE-II database. In total, 27 children with concussion (14 females) approximately one-month post-injury and 1:1 age- and sex-matched healthy controls comprised our sample.ExposurePatients received a physician diagnosis of concussion. ABIDE-II healthy controls were typically developing.Main outcomes & measuresSeed-based (which permitted an examination of whole-brain connectivity, fitting with the exploratory nature of the present study) and region of interest (ROI) analyses were used to examine sex-based rs-fMRI differences. Threshold-free cluster enhancement (TFCE) and a family-wise error (FWE) corrected p-values were used to identify significantly different clusters.ResultsIn comparing females with concussion to healthy females, seed-based analyses (in order of largest effect) showed hypo-connectivity between the anterior cingulate cortex of the salience network and the precuneus (TFCE=1173.6, p=FWE=0.002) and cingulate gyrus (TFCE=1039.7, p-FWE=0.008), and the posterior cingulate cortex (PCC) of the default mode network and the paracingulate gyrus (TFCE=870.1, p-FWE=0.015) and sub-callosal cortex (TFCE=795.4, p-FWE=0.037); hyper-connectivity was observed between the lateral pre-frontal cortex and inferior frontal gyrus (TFCE=1215.4, p-FWE=0.002) and lateral occipital cortex (TFCE=854.9, p-FWE=0.020) and between the PCC and cerebellum (TFCE=791.0, p-FWE=0.038). ROI analyses showed primarily patterns of hyper-connectivity in females. No differences were observed between males with concussion and healthy males on seed-based or ROI analyses.Conclusions and relevanceThere are alterations in rs-fMRI in females with concussion at one-month post-injury that are not present in males, which provides further evidence that recovery timelines in pediatric concussion may differ by sex.KEY FINDINGSQuestionAre there sex-differences in resting state functional brain activity in pediatric concussion?FindingsFemales with concussion show both hyper- and hypo-connectivity between multiple brain regions when compared to healthy age- and sex-matched controls. The same analyses revealed no differences in resting state brain activity when comparing males with concussion to their age- and sex-matched healthy peers.MeaningThere are sex-differences in resting state brain activity in pediatric concussion. This suggests that the functional neuropathology of the injury differs between males and females, which may account for sex-differences in the clinical presentation of pediatric concussion.

Context In rodents, cold exposure induces the activation of brown adipose tissue (BAT) and the induction of intracellular triacylglycerol (TAG) lipolysis. However, in humans, the kinetics of supraclavicular (SCV) BAT activation and the potential importance of TAG stores remain poorly defined. Objective To determine the time course of BAT activation and changes in intracellular TAG using MRI assessment of the SCV (i.e., BAT depot) and fat in the posterior neck region (i.e., non-BAT). Design Cross-sectional. Setting Clinical research center. Patients or Other Participants Twelve healthy male volunteers aged 18 to 29 years [body mass index = 24.7 ± 2.8 kg/m2 and body fat percentage = 25.0% ± 7.4% (both, mean ± SD)]. Intervention(s) Standardized whole-body cold exposure (180 minutes at 18°C) and immediate rewarming (30 minutes at 32°C). Main Outcome Measure(s) Proton density fat fraction (PDFF) and T2* of the SCV and posterior neck fat pads. Acquisitions occurred at 5- to 15-minute intervals during cooling and subsequent warming. Results SCV PDFF declined significantly after only 10 minutes of cold exposure [−1.6% (SE: 0.44%; P = 0.007)] and continued to decline until 35 minutes, after which time it remained stable until 180 minutes. A similar time course was also observed for SCV T2*. In the posterior neck fat (non-BAT), there were no cold-induced changes in PDFF or T2*. Rewarming did not result in a change in SCV PDFF or T2*. Conclusions The rapid cold-induced decline in SCV PDFF suggests that in humans BAT is activated quickly in response to cold and that TAG is a primary substrate.

Purpose To develop an off-resonant frequency filtered method to selectively differentiate between implanted gold fiducial markers and platinum coated brachytherapy seeds. Materials and methods The magnetic susceptibilities for gold fiducial markers and brachytherapy seeds differ in magnitude and also in their signs, resulting in B0-field inhomogeneity patterns with opposite main lobes. A pulse sequence used to localize brachytherapy seeds with positive contrast, centre-out radial sampling with off-resonance reception (co-RASOR), was used to reconstruct images with a range of off-resonant frequency offsets. The proposed method utilizes two frequency filters to selectively reconstruct maximum intensity projections through band-pass regions where each seed has its maximal localized hyperintensity. Seeds were simulated and then placed in gel and tissue phantoms to validate the technique using orthogonal 2D slices with seeds both parallel and perpendicular to the B0-field. Results Dual-plane 2D co-RASOR sequences were reconstructed off-resonance with applied frequency filters to create two projections displaying each seed, which were then colour-coded to negative and positive frequencies. Phantom validation showed that each seed contains its maximal CNR in opposing frequency regions as predicted. Local maxima can also appear in both negative and positive frequency regions. The relative difference between the signal of each seed and these local maxima ranged from 1.19 to 3.73, and an image threshold was determined in all cases. Tissue validation showed the technique differentiates seeds correctly and is limited by the hyperintensity patterns observed in the co-RASOR method. Conclusions Dual-plane co-RASOR offers sub-millimetre positive contrast from implanted seeds that contain unique off-resonant frequency maxima, which frequency filters can selectively differentiate.

Phosphorus MR spectroscopy and spectroscopic imaging (31P-MRS/MRSI) provide information about energy metabolism, membrane degradation and pH in vivo. In spite of their proven utility, 31P-MRS/MRSI are not often used primarily because of the challenges imposed by the low sensitivity and low concentration of metabolites leading to low signal to noise ratio (SNR), coarse spatial resolution and prolonged acquisition time. More recently there has been considerable interest in compressed sensing as an acceleration method for MR signal acquisition. This approach takes advantage of the intrinsic sparsity of the spectral data. In this work, we present a 31P-MRSI sequence that combines a flyback EPSI trajectory and compressed sensing, and we compared two different reconstruction methods, L1 norm minimization and low rank Hankel matrix completion. Our phantom results showed good preservation of spectral quality for both ×2.0 and ×3.0 acceleration factors, using both CS reconstruction methods. However, in vivo 31P-MRS brain data showed the low rank reconstruction approach was most suitable. Overall, this study shows the feasibility of combining a flyback EPSI trajectory and compressed sensing in the acquisition of 31P-MRSI as well as the better suitability of a low rank reconstruction approach.

To evaluate random forests (RFs) as a supervised machine learning algorithm to classify amyloid brain PET as positive or negative for amyloid deposition and identify key regions of interest for stratification.The data set included 57 baseline F-florbetapir (Amyvid; Lilly, Indianapolis, IN) brain PET scans in participants with severe white matter disease, presenting with either transient ischemic attack/lacunar stroke or mild cognitive impairment from early Alzheimer disease, enrolled in a multicenter prospective observational trial. Scans were processed using the MINC toolkit to generate SUV ratios, normalized to cerebellar gray matter, and clinically read by 2 nuclear medicine physicians with interpretation based on consensus (35 negative, 22 positive). SUV ratio data and clinical reads were used for supervised training of an RF classifier programmed in MATLAB.A 10,000-tree RF, each tree using 15 randomly selected cases and 20 randomly selected features (SUV ratio per region of interest), with 37 cases for training and 20 cases for testing, had sensitivity = 86% (95% confidence interval [CI], 42%-100%), specificity = 92% (CI, 64%-100%), and classification accuracy = 90% (CI, 68%-99%). The most common features at the root node (key regions for stratification) were (1) left posterior cingulate (1039 trees), (2) left middle frontal gyrus (1038 trees), (3) left precuneus (857 trees), (4) right anterior cingulate gyrus (655 trees), and (5) right posterior cingulate (588 trees).Random forests can classify brain PET as positive or negative for amyloid deposition and suggest key clinically relevant, regional features for classification.

Accurate and reliable quantification of brain metabolites measured in vivo using 1H magnetic resonance spectroscopy (MRS) is a topic of continued interest. Aside from differences in the basic approach to quantification, the quantification of metabolite data acquired at different sites and on different platforms poses an additional methodological challenge. In this study, spectrally edited γ-aminobutyric acid (GABA) MRS data were analyzed and GABA levels were quantified relative to an internal tissue water reference. Data from 284 volunteers scanned across 25 research sites were collected using GABA+ (GABA + co-edited macromolecules (MM)) and MM-suppressed GABA editing. The unsuppressed water signal from the volume of interest was acquired for concentration referencing. Whole-brain T1-weighted structural images were acquired and segmented to determine gray matter, white matter and cerebrospinal fluid voxel tissue fractions. Water-referenced GABA measurements were fully corrected for tissue-dependent signal relaxation and water visibility effects. The cohort-wide coefficient of variation was 17% for the GABA + data and 29% for the MM-suppressed GABA data. The mean within-site coefficient of variation was 10% for the GABA + data and 19% for the MM-suppressed GABA data. Vendor differences contributed 53% to the total variance in the GABA + data, while the remaining variance was attributed to site- (11%) and participant-level (36%) effects. For the MM-suppressed data, 54% of the variance was attributed to site differences, while the remaining 46% was attributed to participant differences. Results from an exploratory analysis suggested that the vendor differences were related to the unsuppressed water signal acquisition. Discounting the observed vendor-specific effects, water-referenced GABA measurements exhibit similar levels of variance to creatine-referenced GABA measurements. It is concluded that quantification using internal tissue water referencing is a viable and reliable method for the quantification of in vivo GABA levels. ispartof: NEUROIMAGE vol:191 pages:537-548 ispartof: location:United States status: published

PURPOSE Dynamic phosphorus MR spectroscopic imaging (31 P-MRSI) experiments require temporal resolution on the order of seconds to concurrently assess different muscle groups. A highly accelerated pulse sequence combining flyback echo-planar spectroscopic imaging (EPSI) and compressed sensing was developed and tested in a phantom and healthy humans during an exercise-recovery challenge of the lower leg muscles, using a clinical 3T MRI. METHODS A flyback EPSI readout designed to achieve 2.25 × 2.25 cm2 resolution over a 18 × 18 cm2 field of view (i.e., 8 × 8 matrix) was combined with compressed sensing through the inclusion of pseudorandom gradient blips to sub-sample the ky-kt dimensions by a factor of 2.7×, achieving a temporal resolution of 9 s. The sequence was first tested in a phantom to assess performance compared to fully sampled EPSI (fidEPSI) and phase encoded chemical shift imaging (fidCSI). Then, tests were performed in 11 healthy volunteers during an exercise-recovery challenge of the lower leg muscles. Voxels containing tissue from different muscle groups were evaluated measuring percentage phosphocreatine (%PCr) depletion, time constant of PCr recovery (τPCr) and intracellular pH at rest and following exercise. RESULTS The sequence was capable to track the dynamic PCr response of multiple muscles simultaneously. No statistical differences were found in the metabolite ratio, pH or linewidth when compared with fidEPSI and fidCSI in the phantom study. Dynamic experiments showed differences in PCr depletion when comparing soleus with gastrocnemius muscles. Intracellular pH, τPCr and %PCr decrease were consistent with reported values. CONCLUSION Highly accelerated 31 P-MRSI combining flyback EPSI and compressed sensing is capable of assessing concurrent energy metabolism in multiple muscle groups using a clinical 3T MR system.

The recent advances and availability of computer hardware, software tools, and massive digital data archives have enabled the rapid development of artificial intelligence (AI) applications. Concerns over whether AI tools can “communicate” decisions to radiologists and primary care physicians is of particular importance because automated clinical decisions can substantially impact patient outcome. A challenge facing the clinical implementation of AI stems from the potential lack of trust clinicians have in these predictive models. This review will expand on the existing literature on interpretability methods for deep learning and review the state-of-the-art methods for predictive uncertainty estimation for computer-assisted segmentation tasks. Last, we discuss how uncertainty can improve predictive performance and model interpretability and can act as a tool to help foster trust. Keywords: Segmentation, Quantification, Ethics, Bayesian Network (BN) © RSNA, 2021

The most common cause of chronic musculoskeletal pain is chronic myofascial pain syndrome (MPS). MPS often presents with increased muscle stiffness, and the myofascial trigger point (MTrP). Imaging modalities have been used to identify the MTrP, but their role in the detection and diagnosis of MPS remains unclear. The purpose of this review was to identify evidence in literature for the use of imaging in the role of classifying and explaining the physiology of MTrPs. Since few imaging techniques have been performed on MTrPs, we explored the imaging techniques that can effectively image complex skeletal muscle microstructure, and how they could be used. As part of a scoping review, we conducted a systematic search from three medical databases (CINAHL, EMBASE and MEDLINE) from year to year to analyze past MTrP imaging, as well as analyzing imaging techniques performed on the microstructure of muscle. Previously, ultrasound has been used to differentiate active, latent MTrPs, but these studies do not adequately address their underlying anatomical structure. MRI remains the standard method of imaging skeletal muscle. The existing MRI literature suggests that the DTI technique can quantify muscle injury, strain, and structure. However, theoretically, HARDI and DKI techniques seem to provide more information for complex structural areas, although these modalities have a disadvantage of longer scan times and have not been widely used on skeletal muscle. Our review suggests that DTI is the most effective imaging modality that has been used to define the microstructure of muscle and hence, could be optimal to image the MTrP. HARDI and DKI are techniques with theoretical potential for analysis of muscle, which may provide more detailed information representative of finer muscle structural features. Future research utilizing MRI techniques to image muscle are necessary to provide a more robust means of imaging skeletal muscle and the MTrP.

The first stage of testing towards the further development of a full-ring SPECT/MR system has been evaluated. Performance of the cadmium zinc telluride (CZT) detectors were found to be unaffected by the static magnetic field, however they were found to react unreliably during simultaneous imaging when the MR sequence repetition time (TR) was less than 400ms and were influenced significantly by the imaging gradients. In an effort to better understand this phenomenon, component testing was performed by subjecting the CZT detector modules and electronics to various gradient sequences in a stand-alone gradient testing apparatus. We exposed the modules to 31 unique gradient sequence shapes of varying power and duration, typical of those used in clinical MR devices while simultaneously operating the CZT modules in event readout mode. Results indicate that certain detector pixels were preferentially affected (typically around the periphery of the detector array), leading to induced currents in the detector material and significant increases in erroneous event rates during the gradient ramp-up and ramp-down phases. The shape of the gradient waveform was also seen to have an effect on the detector performance with higher slew rates leading to impaired performance. Hardware disabling of the most severely affected pixels led to some reduction in erroneous background events, however, it also resulted in reduced detector resolution and sensitivity. Subsequent work led to the development of a gradient triggering circuit to momentarily suspend CZT event detection during the MR gradient ramp up and ramp down intervals. Subsequent testing of this circuit in a clinical 3T MR was performed. When gradient triggering was enabled, erroneous event data was reduced to near zero levels and resultant images show no structural differences when compared to control acquisitions. During gradient application, the CZT modules are suspended, thus yielding a 60% drop in sensitivity due to the additional deadtime of the triggering. The produced MR image showed a reduction in SNR of 92%. Co-registration of the MR and gamma camera images was successfully performed, showing both the structural and activity makeup of the phantom.

With the emergence of research investigating the role of gamma-aminobutyric acid (GABA) in neurological and neuropsychiatric diseases, it is important to understand the variability in GABA as measured through magnetic resonance spectroscopy (MRS) and how this variability may affect the interpretation of results. This review addresses methodological sources of variation documented in the current literature on the measurement of GABA. GABA differences related to hardware, acquisition, post-processing and quantification are discussed, and methods to account for or remove this variability are highlighted. Additionally, factors such as time, age, biological sex, hormones, and brain region, which may affect GABA MRS, are reviewed to aid in study design. This review is meant to assist in measuring GABA comparably between studies and improve GABA methodology to allow the use of GABA MRS in a clinical setting in the future.

Purpose The aim of this study was to evaluate random forests (RFs) to identify ROIs on F-florbetapir and F-FDG PET associated with Montreal Cognitive Assessment (MoCA) score. Materials and methods Fifty-seven subjects with significant white matter disease presenting with either transient ischemic attack/lacunar stroke or mild cognitive impairment from early Alzheimer disease, enrolled in a multicenter prospective observational trial, had MoCA and F-florbetapir PET; 55 had F-FDG PET. Scans were processed using the MINC toolkit to generate SUV ratios, normalized to cerebellar gray matter (F-florbetapir PET), or pons (F-FDG PET). SUV ratio data and MoCA score were used for supervised training of RFs programmed in MATLAB. Results F-Florbetapir PETs were randomly divided into 40 training and 17 testing scans; 100 RFs of 1000 trees, constructed from a random subset of 16 training scans and 20 ROIs, identified ROIs associated with MoCA score: right posterior cingulate gyrus, right anterior cingulate gyrus, left precuneus, left posterior cingulate gyrus, and right precuneus. Amyloid increased with decreasing MoCA score. F-FDG PETs were randomly divided into 40 training and 15 testing scans; 100 RFs of 1000 trees, each tree constructed from a random subset of 16 training scans and 20 ROIs, identified ROIs associated with MoCA score: left fusiform gyrus, left precuneus, left posterior cingulate gyrus, right precuneus, and left middle orbitofrontal gyrus. F-FDG decreased with decreasing MoCA score. Conclusions Random forests help pinpoint clinically relevant ROIs associated with MoCA score; amyloid increased and F-FDG decreased with decreasing MoCA score, most significantly in the posterior cingulate gyrus.

Rationale and Objectives 129Xe MRI has been developed to noninvasively visualize and quantify the functional consequence of airway obstruction in asthma. Its widespread application requires evidence of intersite reproducibility and agreement. Our objective was to evaluate reproducibility and agreement of 129Xe ventilation MRI measurements in severe asthmatics at two sites. Materials and Methods In seven adults with severe asthma, 129Xe ventilation MRI was acquired pre- and post-bronchodilator at two geographic sites within 24-hours. 129Xe MRI signal-to-noise ratio (SNR) was calculated and ventilation abnormalities were quantified as the whole-lung and slice-by-slice ventilation defect percent (VDP). Intraclass correlation coefficients (ICC) and Bland-Altman analysis were used to determine intersite 129Xe VDP reproducibility and agreement. Results Whole-lung and slice-by-slice 129Xe VDP measured at both sites were correlated and reproducible (pre-bronchodilator: whole-lung ICC = 0.90, p = 0.005, slice-by-slice ICC = 0.78, p 0.99, slice-by-slice bias = −3%, p = 0.0001; post-bronchodilator VDP: whole-lung bias = −2%, p = 0.59, slice-by-slice-bias = −2%, p = 0.0003). Conclusion 129Xe MRI VDP at two different sites measured within 24-hours in the same severe asthmatics were correlated. Qualitative and quantitative intersite differences in 129Xe regional gas distribution and VDP point to site-specific variability that may be due to differences in gas-mixture composition or SNR.

Background and Purpose— Little is known about the association between covert vascular brain injury and cognitive impairment in middle-aged populations. We investigated if scores on a cognitive screen were lower in individuals with higher cardiovascular risk, and those with covert vascular brain injury. Methods— Seven thousand five hundred forty-seven adults, aged 35 to 69 years, free of cardiovascular disease underwent a cognitive assessment using the Digital Symbol Substitution test and Montreal Cognitive Assessment, and magnetic resonance imaging (MRI) to detect covert vascular brain injury (high white matter hyperintensities, lacunar, and nonlacunar brain infarctions). Cardiovascular risk factors were quantified using the INTERHEART (A Global Study of Risk Factors for Acute Myocardial Infarction) risk score. Multivariable mixed models tested for independent determinants of reduced cognitive scores. The population attributable risk of risk factors and MRI vascular brain injury on low cognitive scores was calculated. Results— The mean age of participants was 58 (SD, 9) years; 55% were women. Montreal Cognitive Assessment and Digital Symbol Substitution test scores decreased significantly with increasing age ( P P Conclusions— Among a middle-aged community-dwelling population, scores on a cognitive screen were lower in individuals with higher cardiovascular risk factors or MRI vascular brain injury. Much of the population attributable risk of low cognitive scores can be attributed to lower educational attainment, higher cardiovascular risk factors, and MRI vascular brain injury.

Objectives To assess the effect of ankle, knee, and hip kinematics on patellofemoral and tibiofemoral joint reaction forces (JRF) during bicycling. Secondarily, to assess if sex, horizontal saddle position, or crank arm length were related to JRFs, after accounting for kinematics. Design Experimental cross-sectional study. Methods Forty healthy adults (mean (SD); 28.6 (7.2) years, 24.2 (2.6) kg/m2, 17 women) bicycled under 18 bicycling positions. One position used commercial guidelines and 17 randomly deviated from commercial. Resultant patellofemoral as well as compressive and shear tibiofemoral JRFs were calculated. Linear mixed-effects models with a random intercept of leg-nested-in-participant were used. Results Patellofemoral resultant forces were most sensitive to all joint kinematics (i.e., sensitivity was defined as the slope of single predictor models); all JRFs were least sensitive to minimum knee flexion. Tibiofemoral compression was predicted by minimum hip flexion and maximum ankle dorsiflexion (R2 = 0.90). Tibiofemoral shear (R2 = 0.86) and the resultant patellofemoral JRF (R2 = 0.90) were predicted by minimum hip flexion, maximum ankle dorsiflexion, minimum knee flexion, and the interaction between minimum hip flexion and minimum knee flexion. Adding sex as a factor improved fit of all models. This sex-effect was driven by differences in cycling intensity, reflected by the tangential crank arm force. Horizontal saddle position and crank arm length were not related to JRFs. Conclusions Optimizing joint kinematics should be the primary goal of bicycle-fit. JRFs were least sensitive to the current gold standard for assessing bicycle-fit, minimum knee flexion. Bicycle-fit is of particular importance for those working at high intensities.

Background: Post-concussive depression describes an elevation of depressive symptoms following concussion that occurs in conjunction with other symptoms of concussion. Children with concussion are more likely to diagnosed with depression. The overlapping symptoms between clinical depression and concussion make the diagnosis of depression difficult. The purpose of this study is to explore how post-concussive depression relates to post-concussion symptoms and cognition by investigating symptom-reporting in youth with post-concussive depression and executive function.Methods: Adolescents (age 10-17 years) diagnosed with concussion were divided into two groups based on depression scores on the Children's Depression Inventory (post-concussion depression; non-depression groups). Symptom reporting on the Post-Concussion Symptom Inventory and performance on Immediate Post-concussion Assessment and Cognitive Testing (ImPACT) were compared.Results: Participants with post-concussive depression had heightened emotionality, irritability, and nervousness. Sadness and fatigue were reported by both groups. ImPACT was unable to distinguish between groups but the group overall demonstrated severe neurocognitive deficits.Conclusion: Reports of greater emotionality, irritability, and nervousness on concussion symptom scales may be indicators of post-concussion depression. It is important for clinicians to take note when an adolescent with concussion scores high on these three emotional symptoms as they may be indicative of greater emotional distress.

Background The hardware and software differences between MR vendors and individual sites influence the quantification of MR spectroscopy data. An analysis of a large data set may help to better understand sources of the total variance in quantified metabolite levels. Purpose To compare multisite quantitative brain MR spectroscopy data acquired in healthy participants at 26 sites by using the vendor-supplied single-voxel point-resolved spectroscopy (PRESS) sequence. Materials and Methods An MR spectroscopy protocol to acquire short-echo-time PRESS data from the midparietal region of the brain was disseminated to 26 research sites operating 3.0-T MR scanners from three different vendors. In this prospective study, healthy participants were scanned between July 2016 and December 2017. Data were analyzed by using software with simulated basis sets customized for each vendor implementation. The proportion of total variance attributed to vendor-, site-, and participant-related effects was estimated by using a linear mixed-effects model. P values were derived through parametric bootstrapping of the linear mixed-effects models (denoted Pboot). Results In total, 296 participants (mean age, 26 years ± 4.6; 155 women and 141 men) were scanned. Good-quality data were recorded from all sites, as evidenced by a consistent linewidth of N-acetylaspartate (range, 4.4-5.0 Hz), signal-to-noise ratio (range, 174-289), and low Cramér-Rao lower bounds (≤5%) for all of the major metabolites. Among the major metabolites, no vendor effects were found for levels of myo-inositol (Pboot > .90), N-acetylaspartate and N-acetylaspartylglutamate (Pboot = .13), or glutamate and glutamine (Pboot = .11). Among the smaller resonances, no vendor effects were found for ascorbate (Pboot = .08), aspartate (Pboot > .90), glutathione (Pboot > .90), or lactate (Pboot = .28). Conclusion Multisite multivendor single-voxel MR spectroscopy studies performed at 3.0 T can yield results that are coherent across vendors, provided that vendor differences in pulse sequence implementation are accounted for in data analysis. However, the site-related effects on variability were more profound and suggest the need for further standardization of spectroscopic protocols. © RSNA, 2020 Online supplemental material is available for this article. ispartof: RADIOLOGY vol:295 issue:1 pages:171-180 ispartof: location:United States status: published