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The MR-induced gradient artifact affects EMG recordings during simultaneous muscle BOLD/EMG acquisitions. However, no dedicated hardware can remove the gradient artifact easily, and alternative methods are expensive and time-consuming. This study aimed to develop three denoising methods requiring different processing levels and MR-compatible hardware. At two time points, surface EMG was recorded from the lower leg of 6 participants (50:50 sex ratio, age = 26.24.6 yrs., height = 173.59.2 cm, weight = 71.511.4 kg) using a plantar flexion-based block design consisting of 30s of rest followed by 30s of flexion for 5 min, under three conditions: inside the MRI bore, with and without a BOLD sequence (3 T, BOLD sequence, GRE EPI, 10 slices, 64×64 matrix, 2 mm thickness, and TE/TR/flip = 35/3000 ms/70), and outside the MRI environment. Simultaneous BOLD/EMG recordings were denoised using average artifact subtraction with three methods of artifact template creation, each having varying timing and hardware requirements. Method M1 builds the artifact template by recording the scanner triggers coming from the MRI; M2 creates the artifact template with a constant artifact period computed as TR/[number of slices]; M3 estimates the artifact template by looking at the periodicity of the gradient artifact located in the EMG recordings. Following postprocessing, SNR analysis was performed, comparing rest-to-flexion periods, to assess the efficacy of denoising methods and to compare differences between conditions. Linear mixed-effects models showed no significant differences in the mean SNR between denoising methods (p = 0.656). Furthermore, EMG SNR measurements were significantly affected by the magnetic environment (p < 0.05) but not by muscle fatigue over time (p = 0.975). EMG recordings contaminated with gradient artifacts during simultaneous BOLD/EMG can be efficiently denoised using all proposed methods, with two methods requiring no extra hardware. With minimal post-processing, EMG can easily be performed during muscle BOLD MRI studies., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Recent scientific evidence has challenged the traditional "rest-is-best" approach for concussion management. It is now thought that "exercise-is-medicine" for concussion, owing to dozens of studies which demonstrate that sub-maximal, graded aerobic exercise can reduce symptom burden and time to symptom resolution. However, the primary neuropathology of concussion is altered functional brain activity. To date, no studies have examined the effects of sub-maximal aerobic exercise on resting state functional brain activity in pediatric concussion. In addition, although exercise is now more widely prescribed following concussion, its cardiopulmonary response is not yet well understood in this population. Our study has two main goals. The first is to understand whether there are exercise-induced resting state functional brain activity differences in children with concussion vs. healthy controls. The second is to profile the physiological response to exercise and understand whether it differs between groups., Methods: We will perform a single-center, controlled, prospective cohort study of pediatric concussion at a large, urban children's hospital and academic center. Children with sport-related concussion (aged 12-17 years) will be recruited within 4-weeks of injury by our clinical study team members. Key inclusion criteria include: medical clearance to exercise, no prior concussion or neurological history, and no implants that would preclude MRI. Age- and sex-matched healthy controls will be required to meet the same inclusion criteria and will be recruited through the community. The study will be performed over two visits separated by 24-48 h. Visit 1 involves exercise testing (following the current clinical standard for concussion) and breath-by-breath gas collection using a metabolic cart. Visit 2 involves two functional MRI (fMRI) scans interspersed by 10-minutes of treadmill walking at an intensity calibrated to Visit 1 findings. To address sub-objectives, all participants will be asked to self-report symptoms daily and wear a waist-worn tri-axial accelerometer for 28-days after Visit 2., Discussion: Our study will advance the growing exercise-concussion field by helping us understand whether exercise impacts outcomes beyond symptoms in pediatric concussion. We will also be able to profile the cardiopulmonary response to exercise, which may allow for further understanding (and eventual optimization) of exercise in concussion management., Trial Registration: Not applicable., (© 2024. The Author(s).)

Although hyperpolarized (HP) 129 Xe ventilation MRI can be carried out within a breath hold, it is still challenging for many sick patients. Compressed sensing (CS) is a viable alternative to accelerate this approach. However, undersampled images with identical sampling ratios differ from one another. Twenty subjects (n = 10 healthy and n = 10 patients with asthma) were scanned using a GE MR750 3 T scanner, acquiring fully sampled 2D multi-slice HP 129 Xe lung ventilation images (10 s breath hold, 128 × 80 (FE × PE-frequency encoding × phase encoding) and 16 slices). Using fully sampled data, 500 variable-density Cartesian random undersampling patterns were generated, each at eight different sampling ratios from 10% to 80%. The parallel imaging and compressed sensing (PICS) command from BART was employed to reconstruct undersampled data. The signal to noise ratio (SNR), structural similarity index measurement (SSIM) and sidelobe to peak ratio of each were subsequently compared. There was a high degree of variation in both SNR and SSIM results from each of the 500 masks of each sampling rate. As the undersampling increases, there is more variation in the quantifying metrics, for both healthy and asthmatic individuals. Our study shows that random undersampling poses a significant challenge when applied at sampling ratios less than 60%, despite fulfilling CS's incoherency criteria. Such low sampling ratios will result in a large variety of undersampling patterns. Therefore, skipped segments of k-space cannot be allowed to happen randomly at low sampling rates. By optimizing the sampling pattern, CS will reach its full potential and be able to be applied to a highly undersampled 129 Xe lung dataset., (© 2024 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

Introduction: Cerebral small vessel disease (SVD) and amyloid beta (Aβ) pathology frequently co-exist. The impact of concurrent pathology on the pattern of hippocampal atrophy, a key substrate of memory impacted early and extensively in dementia, remains poorly understood., Methods: In a unique cohort of mixed Alzheimer's disease and moderate-severe SVD, we examined whether total and regional neuroimaging measures of SVD, white matter hyperintensities (WMH), and Aβ, as assessed by 18 F-AV45 positron emission tomography, exert additive or synergistic effects on hippocampal volume and shape., Results: Frontal WMH, occipital WMH, and Aβ were independently associated with smaller hippocampal volume. Frontal WMH had a spatially distinct impact on hippocampal shape relative to Aβ. In contrast, hippocampal shape alterations associated with occipital WMH spatially overlapped with Aβ-vulnerable subregions., Discussion: Hippocampal degeneration is differentially sensitive to SVD and Aβ pathology. The pattern of hippocampal atrophy could serve as a disease-specific biomarker, and thus guide clinical diagnosis and individualized treatment strategies for mixed dementia., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Purpose: Concussion management is shifting away from a rest-is-best approach, as data now suggest that exercise-is-medicine for this mild brain injury. Despite this, we have limited data on habitual physical activity following concussion. Therefore, our objective was to quantify accelerometer-measured physical activity and sedentary time in children with concussion (within the first month of injury) and healthy controls. We hypothesized that children with concussion would be less active than their healthy peers., Methods: We performed a secondary analysis of prospectively collected accelerometer data. Our sample included children with concussion (n = 60, 31 females) and historical controls (n = 60) matched for age, sex, and season of accelerometer wear., Results: Children with concussion were significantly more sedentary than controls (mean difference [MD], 38.3 min/d, P = .006), and spent less time performing light physical activity (MD, -19.5 min/d, P = .008), moderate physical activity (MD, -9.8 min/d, P < .001), and vigorous physical activity (MD, -12.0 min/d, P < .001); these differences were observed from 8:00 AM to 9:00 PM. Sex-specific analyses identified that girls with concussion were less active and more sedentary than both boys with concussion (P = .010) and healthy girls (P < .010)., Conclusion: There is an activity deficit observed within the first month of pediatric concussion. Physical activity guidelines should address this while considering sex effects.

The human brain is an exceptionally complex organ that is comprised of billions of neurons. Therefore, when a traumatic event such as a concussion occurs, somatic, cognitive, behavioral, and sleep impairments are the common outcome. Each concussion is unique in the sense that the magnitude of biomechanical forces and the direction, rotation, and source of those forces are different for each concussive event. This helps to explain the unpredictable nature of post-concussion symptoms that can arise and resolve. The purpose of this narrative review is to connect the anatomical location, healthy function, and associated post-concussion symptoms of some major cerebral gray and white matter brain regions and the cerebellum. As a non-exhaustive description of post-concussion symptoms nor comprehensive inclusion of all brain regions, we have aimed to amalgamate the research performed for specific brain regions into a single article to clarify and enhance clinical and research concussion assessment. The current status of concussion diagnosis is highly subjective and primarily based on self-report of symptoms, so this review may be able to provide a connection between brain anatomy and the clinical presentation of concussions to enhance medical imaging assessments. By explaining anatomical relevance in terms of clinical concussion symptom presentation, an increased understanding of concussions may also be achieved to improve concussion recognition and diagnosis., Competing Interests: MN, DK, and NS have ownership in a data analytics company called TBIfinder (https://tbifinder.com) that specializes in personalized concussion assessment. ED is a research intern with TBIFinder Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Danielli, Simard, DeMatteo, Kumbhare, Ulmer and Noseworthy.)

White matter (WM) injury is frequently observed along with dementia. Positron emission tomography with amyloid-ligands (Aβ-PET) recently gained interest for detecting WM injury. Yet, little is understood about the origin of the altered Aβ-PET signal in WM regions. Here, we investigated the relative contributions of diffusion MRI-based microstructural alterations, including free water and tissue-specific properties, to Aβ-PET in WM and to cognition. We included a unique cohort of 115 participants covering the spectrum of low-to-severe white matter hyperintensity (WMH) burden and cognitively normal to dementia. We applied a bi-tensor diffusion-MRI model that differentiates between (i) the extracellular WM compartment (represented via free water), and (ii) the fiber-specific compartment (via free water-adjusted fractional anisotropy [FA]). We observed that, in regions of WMH, a decrease in Aβ-PET related most closely to higher free water and higher WMH volume. In contrast, in normal-appearing WM, an increase in Aβ-PET related more closely to higher cortical Aβ (together with lower free water-adjusted FA). In relation to cognitive impairment, we observed a closer relationship with higher free water than with either free water-adjusted FA or WM PET. Our findings support free water and Aβ-PET as markers of WM abnormalities in patients with mixed dementia, and contribute to a better understanding of processes giving rise to the WM PET signal.

Introduction: The ideal contrast agents for ventilation SPECT and MRI are Technegas and 129 Xe gas, respectively. Despite increasing interest in the clinical utility of ventilation imaging, these modalities have not been directly compared. Therefore, our objective was to compare the ventilation defect percent (VDP) assessed by Technegas SPECT and hyperpolarized 129 Xe MRI in patients scheduled to undergo lung cancer resection with and without pre-existing obstructive lung disease. Methods: Forty-one adults scheduled to undergo lung cancer resection performed same-day Technegas SPECT, hyperpolarized 129 Xe MRI, spirometry, and diffusing capacity of the lung for carbon monoxide (DL CO ). Ventilation abnormalities were quantified as the VDP using two different methods: adaptive thresholding (VDP T ) and k-means clustering (VDP K ). Correlation and agreement between VDP quantified by Technegas SPECT and 129 Xe MRI were determined by Spearman correlation and Bland-Altman analysis, respectively. Results: VDP measured by Technegas SPECT and 129 Xe MRI were correlated (VDP T : r = 0.48, p = 0.001; VDP K : r = 0.63, p < 0.0001). A 2.0% and 1.6% bias towards higher Technegas SPECT VDP was measured using the adaptive threshold method (VDP T : 23.0% ± 14.0% vs. 21.0% ± 5.2%, p = 0.81) and k-means method (VDP K : 9.4% ± 9.4% vs. 7.8% ± 10.0%, p = 0.02), respectively. For both modalities, higher VDP was correlated with lower FEV 1 /FVC (SPECT VDP T : r = -0.38, p = 0.01; MRI VDP K : r = -0.46, p = 0.002) and DL CO (SPECT VDP T : r = -0.61, p < 0.0001; MRI VDP K : r = -0.68, p < 0.0001). Subgroup analysis revealed that VDP measured by both modalities was significantly higher for participants with COPD (n = 13) than those with asthma (n = 6; SPECT VDP T : p = 0.007, MRI VDP K : p = 0.006) and those with no history of obstructive lung disease (n = 21; SPECT VDP T : p = 0.0003, MRI VDP K : p = 0.0003). Discussion: The burden of ventilation defects quantified by Technegas SPECT and 129 Xe MRI VDP was correlated and greater in participants with COPD when compared to those without. Our observations indicate that, despite substantial differences between the imaging modalities, quantitative assessment of ventilation defects by Technegas SPECT and 129 Xe MRI is comparable., Competing Interests: The authors declare that this was an investigator-initiated study that received funding from Cyclomedica Australia Pty Ltd. and The Lung Association. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. SS reports a relationship with Polarean that includes: Speaking and lecture fees. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Radadia, Friedlander, Priel, Konyer, Huang, Jamal, Farncombe, Marriott, Finley, Agzarian, Dolovich, Noseworthy, Nair, Shargall and Svenningsen.)

It remains unclear to what extent cerebrovascular burden relates to amyloid beta (Aβ) deposition, neurodegeneration, and cognitive dysfunction in mixed disease populations with small vessel disease and Alzheimer's disease (AD) pathology. In 120 subjects, we investigated the association of vascular burden (white matter hyperintensity [WMH] volumes) with cognition. Using mediation analyses, we tested the indirect effects of WMH on cognition via Aβ deposition ( 18 F-AV45 positron emission tomography [PET]) and neurodegeneration (cortical thickness or 18 F fluorodeoxyglucose PET) in AD signature regions. We observed that increased total WMH volume was associated with poorer performance in all tested cognitive domains, with the strongest effects observed for semantic fluency. These relationships were mediated mainly via cortical thinning, particularly of the temporal lobe, and to a lesser extent serially mediated via Aβ and cortical thinning of AD signature regions. WMH volumes differentially impacted cognition depending on lobar location and Aβ status. In summary, our study suggests mainly an amyloid-independent pathway in which vascular burden affects cognitive function via localized neurodegeneration. HIGHLIGHTS: Alzheimer's disease often co-exists with vascular pathology. We studied a unique cohort enriched for high white matter hyperintensities (WMH). High WMH related to cognitive impairment of semantic fluency and executive function. This relationship was mediated via temporo-parietal atrophy rather than metabolism. This relationship was, to lesser extent, serially mediated via amyloid beta and atrophy., (© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Pediatric 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 pediatric concussion, though no studies have explicitly examined sex-differences with respect to this outcome, precluding a sex-specific understanding of the functional neuropathology of pediatric concussion. Therefore, we performed a secondary data analysis of rs-fMRI data collected on children with concussion (n = 29) recruited from in a pediatric hospital setting, with greater than 12:1 matched control data accessed from the open-source ABIDE-II database. Seed-based 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. In comparing females with concussion to healthy females, groupwise differences were observed irrespective of seed selected. Notably, we observed (in order of largest effect) hypo-connectivity between the anterior cingulate cortex of the salience network and the thalamus and precuneus (TFCE = 1473.5, p-FWE < 0.001) and the cingulate gyrus (TFCE = 769.3, p-FWE = 0.009), and the seed (posterior cingulate cortex (PCC)) of the default mode network and the paracingulate gyrus (TFCE = 1275.7, p-FWE  < 0.001), occipital pole right (TFCE = 1045.0, p-FWE = 0.001), and sub-callosal cortex (TFCE = 844.9, p-FWE = 0.005). Hyper-connectivity was observed between the salience network seed and the cerebellum (TFCE = 1719.3, p-FWE < 0.001) and the PCC and the thalamus (TFCE = 1198.3, p-FWE < 0.001), cuneal cortex (1070.9, p-FWE = 0.001), and lateral occipital cortex left (TFCE = 832.8, p-FWE = 0.006). ROI analyses showed 10 and 5 significant clusters of hypo- and hyper-connectivity in females, respectively. Only one cluster of difference was found between males with concussion and healthy males on seed-based analyses, and 3 clusters on ROI analyses. There are alterations in rs-fMRI in females with concussion at one-month post-injury that are minimally present in males, which provides further evidence that recovery timelines in pediatric concussion may differ by sex., (© 2023. The Author(s).)

Objective: To determine whether nailfold capillary images, acquired using video capillaroscopy, can provide diagnostic information about diabetes and its complications., Research Design and Methods: Nailfold video capillaroscopy was performed in 120 adult patients with and without type 1 or type 2 diabetes, and with and without cardiovascular disease. Nailfold images were analyzed using convolutional neural networks, a deep learning technique. Cross-validation was used to develop and test the ability of models to predict five5 prespecified states (diabetes, high glycosylated hemoglobin, cardiovascular event, retinopathy, albuminuria, and hypertension). The performance of each model for a particular state was assessed by estimating areas under the receiver operating characteristics curves (AUROC) and precision recall curves (AUPR)., Results: A total of 5236 nailfold images were acquired from 120 participants (mean 44 images per participant) and were all available for analysis. Models were able to accurately identify the presence of diabetes, with AUROC 0.84 (95% confidence interval [CI] 0.76, 0.91) and AUPR 0.84 (95% CI 0.78, 0.93), respectively. Models were also able to predict a history of cardiovascular events in patients with diabetes, with AUROC 0.65 (95% CI 0.51, 0.78) and AUPR 0.72 (95% CI 0.62, 0.88) respectively., Conclusions: This proof-of-concept study demonstrates the potential of machine learning for identifying people with microvascular capillary changes from diabetes based on nailfold images, and for possibly identifying those most likely to have diabetes-related complications., (© 2023 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd.)

The landscape of breast cancer diagnostics has significantly evolved over the past decade. With these changes, it is possible to provide a comprehensive assessment of both benign and malignant breast calcifications. The biochemistry of breast cancer and calcifications are thoroughly examined to describe the potential to characterize better different calcium salts composed of calcium carbonate, calcium oxalate, or calcium hydroxyapatite and their associated prognostic implications. Conventional mammographic imaging techniques are compared to available ones, including breast tomosynthesis and contrast-enhanced mammography. Additional methods in computed tomography and magnetic resonance imaging are discussed. The concept of using magnetic resonance imaging particularly magnetic susceptibility to characterize the biochemical characteristics of calcifications is described. As we know magnetic resonance imaging is safe and there is no ionization radiation. Experimental findings through magnetic resonance susceptibility imaging techniques are discussed to illustrate the potential for integrating this technique to provide a quantitative assessment of magnetic susceptibility. Under the right magnetic resonance imaging conditions, a distinct phase variability was isolated amongst different types of calcium salts.

Objective: This proof-of-principle study integrates joint reaction forces (JRFs) and bone shape to assess acute cartilage changes from walking and cycling., Methods: 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 (T 2 relaxation time). Bone shape was quantified using a statistical shape model built from 13 local participants and 100 MRI scans from the Osteoarthritis Initiative. Statistical parametric mapping quantified cartilage change and correlations between cartilage change with JRFs and statistical shape model features., Results: Cartilage thickness (interior lateral, Δ - 0.10 mm) and T 2 (medial, Δ - 4 ms) decreased on the tibial plateau. On the femur, T 2 change depended on the activity. Greater tibiofemoral JRF was associated with more cartilage deformation on the lateral femoral trochlea after walking (r - 0.56). Knees more consistent with osteoarthritis showed smaller decreases in tibial cartilage thickness., Discussion: Walking 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., (© 2022. The Author(s), under exclusive licence to European Society for Magnetic Resonance in Medicine and Biology (ESMRMB).)

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, R a 2  = 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, R a 2  = 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.

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., (© 2022 by the American Diabetes Association.)

Magnetic Resonance Imaging (MRI) is well-suited for imaging peripheral blood flow due to its non-invasive nature and excellent spatial resolution. Although MRI is routinely used in adults to assess physiological changes in chronic diseases, there are currently no MRI-based data quantifying arterial flow in pediatric or adolescent populations during exercise. Therefore the current research sought to document femoral arterial blood flow at rest and following exercise in a pediatric-adolescent population using phase contrast MRI, and to present test-retest reliability data for this method. Ten healthy children and adolescents (4 male; mean age 14.8 ± 2.4 years) completed bloodwork and resting and exercise MRI. Baseline images consisted of PC-MRI of the femoral artery at rest and following a 5 × 30 s of in-magnet exercise. To evaluate test-retest reliability, five participants returned for repeat testing. All participants successfully completed exercise testing in the MRI. Baseline flow demonstrated excellent reliability (ICC = 0.93, p = 0.006), and peak exercise and delta rest-peak flow demonstrated good reliability (peak exercise ICC = 0.89, p = 0.002, delta rest-peak ICC = 0.87, p = 0.003) between-visits. All three flow measurements demonstrated excellent reliability when assessed with coefficients of variance (CV's) (rest: CV = 6.2%; peak exercise: CV = 7.3%; delta rest-peak: CV = 7.1%). The mean bias was small for femoral arterial flow. There was no significant mean bias between femoral artery flow visits 1 and 2 at peak exercise. There were no correlations between age or height and any of the flow measurements. There were no significant differences between male and female participants for any of the flow measurements. The current study determined that peripheral arterial blood flow in children and adolescents can be evaluated using non-invasive phase contrast MRI. The MRI-based techniques that were used in the current study for measuring arterial flow in pediatric and adolescent patients demonstrated acceptable test-retest reliability both at rest and immediately post-exercise., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

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. Methods: Forty healthy adults (17 women, 23 men; mean (SD): 28.6 (7.2) years; 24.2 (2.6) kg/m 2 ) participated. Kinematic analyses were conducted for 18 three-minute bicycling bouts including all combinations of 3 horizontal and 3 vertical saddle positions, and 2 crank arm lengths. For both minimum and maximum knee flexion, predictors were identified using Least Absolute Shrinkage and Selection Operator (LASSO) regression, and final models were fit using linear regression. Secondary analyses determined if saddle height equations were sex dependent. Results: The equation to predict saddle position from minimum knee flexion angle (R 2 =0.97; root mean squared error (RMSE) = 1.15 cm) was: Saddle height (cm) = 7.41 + 0.82(inseam cm) - 0.1(minimum knee flexion °) + 0.003(inseam cm)(seat tube angle °). The maximum knee flexion equation (R 2 =0.97; RMSE=1.15 cm) was: Saddle height (cm) = 41.63 + 0.78(inseam cm) - 0.25(maximum knee flexion °) + 0.002(inseam cm)(seat tube angle °). The saddle height equations were not dependent on sex. Conclusions: These equations provide a novel, practical strategy for bicycle-fit that accounts for rider anthropometrics, bicycle geometry and user-defined kinematics. Highlights This work developed simple equations to prescribed bicycle saddle height that elicits desired knee kinematics.Separate equations are presented for prescribing minimum or maximum knee flexion angle.Equations can be generalized to riders of both sexes, and a breadth of anthropometrics and ages.

Despite the technical challenges that require lengthy acquisitions to overcome poor signal-to-noise ratio (SNR), sodium ( 23 Na) magnetic resonance imaging (MRI) is an intriguing area of research due to its essential role in human metabolism. Low SNR images can impact the measurement of the point-spread function (PSF) by adding uncertainty into the resulting quantities. Here, we present methods to calculate the PSF by using the modulation transfer function (MTF), and a 3D-printed line-pair phantom in the context of 23 Na MRI. A simulation study investigated the effect of noise on the resulting MTF curves, which were derived by direct modulation (DM) and a method utilizing Fourier harmonics (FHs). Experimental data utilized a line-pair phantom with nine spatial frequencies, filled with different concentrations (15, 30, and 60 mM) of sodium in 3% agar. MTF curves were calculated using both methods from data acquired from density-adapted 3D radial projections (DA-3DRP) and Fermat looped orthogonally encoded trajectories (FLORET). Simulations indicated that the DM method increased variability in the MTF curves at all tested noise levels over the FH method. For the experimental data, the FH method resulted in PSFs with a narrower full width half maximum with reduced variability, although the improvement in variability was not as pronounced as predicted by simulations. The DA-3DRP data indicated an improvement in the PSF over FLORET. It was concluded that a 3D-printed line-pair phantom represents a convenient method to measure the PSF experimentally. The MTFs from the noisy images in 23 Na MRI have reduced variability from a FH method over DM., (© 2021 John Wiley & Sons, Ltd.)

Objective: The need to have a pediatric-specific concussion management protocol on Return to School (RTS) and Return to Activity (RTA) after concussion has been recognized internationally. The first step to evaluate the protocol effectiveness is to establish whether children and youth are adhering to these recommendations. The objective of this study was to explore the prevalence and predictors of adherence to RTS and RTA concussion management protocols for children/youth., Design: A prospective cohort of children/youth with concussion., Setting: Childhood Disability Research Centre., Participants: One hundred thirty-nine children/youth aged 5 to 18 years, diagnosed with concussion and symptomatic upon enrollment, were followed for up to 6 months. Primary recruitment occurred from a Children's Hospital Emergency Department., Intervention: Provision of RTS/RTA guidelines., Main Outcome Measures: Measurement of adherence came from multiple sources, including the child's and parent's knowledge of protocols, research personnel evaluations, and self-reported stages of RTS/RTA and Post-Concussion Symptom Scale (PCSS) scores., Results: Spearman correlations and logistic regression were used, investigating the relationship between PCSS and progression of protocols and determining predictors of adherence. Significant negative associations between total PCSS score and stage of RTS/RTA protocols were found. Fifty-three percent and 56% of the participants adhered to the RTS and RTA protocols, respectively., Conclusions: Children's knowledge of protocols and total PCSS scores significantly predicted adherence to RTS/RTA and may be the most important factors in predicting adherence during recovery from concussion., Competing Interests: The authors report no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: To determine whether cognitive reserve attenuates the association of vascular brain injury with cognition., Methods: Cross-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)., Results: There 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 (interaction p = 0.59 for MoCA and p = 0.72 for DSST)., Conclusions: Both 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., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

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., Competing Interests: Disclosures of Conflicts of Interest: B.M. Institution received grant from Defence Research and Development Canada (grant number CFPMN2-017-McMaster) for the Innovation for Defence Excellence and Security program presented by the DRDC. K.Z. Consultant for the Centre for Probe Development and Commercialization. T.E.D. No relevant relationships. M.D.N. Data analytics consultant for MCI OneHealth; CEO and cofounder of TBI Finder., (2021 by the Radiological Society of North America, Inc.)

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., Competing Interests: B.A.A. holds the Lau Family scholarship for science and engineering and was funded by the Ontario graduate scholarship. D.P.B. holds the GlaxoSmithKline (GSK) Chair in Diabetes of Université de Sherbrooke, which was created in part through a donation of $1 million by GSK to Université de Sherbrooke. D.P.B. has received honoraria and consulting fees from Boehringer Ingelheim. S.A.S. holds a CIHR Vanier Canada Graduate Scholarship. E.M.D. holds a CIHR Vanier Canada Graduate Scholarship. F.F.A. holds a CIHR postdoctoral fellowship and Diabetes Canada incentive funding. A.C.H. holds research funding from the CIHR and the Natural Sciences and Engineering Research Council of Canada. A.C.C. holds the Canada Research Chair in Molecular Imaging of Diabetes and research funding from the CIHR, Fonds de recherche Québec – Santé, and has participated in advisory boards for Amgen, UniQure, Merck, Janssen, Novo Nordisk, Novartis, HLS Therapeutics Inc., TVM Life Science Management, AstraZeneca, and Eli Lilly and participated in one conference sponsored by AstraZeneca. M.G.S. is funded by the CIHR, Genome Canada, and the W. Garfield Weston Foundation and holds a Tier 1 Canada Research Chair in Interdisciplinary Microbiome Research. J.D.S. receives funding from the CIHR (FDN-154295) and holds a Canada Research Chair in Metabolic Inflammation. Z.P. has received honoraria for advice and speaking from Abbott, Astra Zeneca/Bristol Myers Squibb, Boehringer Ingelheim/Eli Lilly, Janssen, Merck, Novo Nordisk, Pfizer, and Sanofi, and has received research funds from Amgen, Astra Zeneca/Bristol Myers Squibb, Lexicon, Merck, Novo Nordisk, Sanofi, and the CIHR. G.R.S. receives funding from the CIHR (201709FDN-CEBA-116200), Diabetes Canada Investigator Award (DI-5-17-5302-GS), a Tier 1 Canada Research Chair, and the J. Bruce Duncan Endowed Chair in Metabolic Diseases. He also receives research funding from Espervita Therapeutics, Esperion Therapeutics, Novo Nordisk, and Poxel Pharma and honoraria and consulting fees from Astra Zeneca, Eli Lilly, Esperion Therapeutics, Poxel, and Merck. K.M.M. holds research funding from the CIHR, Heart and Stroke Foundation of Canada, McMaster Children’s Hospital Foundation, and McMaster University. She has received research funds from Astra Zeneca and is an advisory board member for Novo Nordisk and Akcea Therapeutics, Canada., (© 2021 The Author(s).)

Rationale and Objectives: 129 Xe 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 129 Xe ventilation MRI measurements in severe asthmatics at two sites., Materials and Methods: In seven adults with severe asthma, 129 Xe ventilation MRI was acquired pre- and post-bronchodilator at two geographic sites within 24-hours. 129 Xe 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 129 Xe VDP reproducibility and agreement., Results: Whole-lung and slice-by-slice 129 Xe 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 < 0.0001; post-bronchodilator: whole-lung ICC = 0.94, p < 0.0001, slice-by-slice ICC = 0.83, p < 0.0001) notwithstanding intersite differences in the 129 Xe-dose-equivalent-volume (101 ± 15 mL site 1, 49 ± 6 mL site 2, p < 0.0001), gas-mixture ( 129 Xe/ 4 He site 1; 129 Xe/N 2 site 2) and SNR (40 ± 19 site 1, 23 ± 5 site 2, p = 0.02). Qualitative 129 Xe gas distribution differences were observed between sites and slice-by-slice 129 Xe VDP, but not whole-lung 129 Xe VDP, was significantly lower at site 1 (pre-bronchodilator VDP: whole-lung bias = -3%, 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: 129 Xe MRI VDP at two different sites measured within 24-hours in the same severe asthmatics were correlated. Qualitative and quantitative intersite differences in 129 Xe regional gas distribution and VDP point to site-specific variability that may be due to differences in gas-mixture composition or SNR., (Copyright © 2020 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background Individuals with knee osteoarthritis have elevated circulating inflammatory markers and altered cartilage properties but it is unclear if these features adapt to exercise. We aimed to determine (1) whether inflammatory markers, cartilage transverse relaxation time and thickness mediate the effect of body mass index (BMI) on quadriceps strength at baseline; and (2) whether these changes explain variance in quadriceps strength improvements after 12 weeks of exercise in women with knee osteoarthritis. Methods This secondary analysis (17 women with clinical knee osteoarthritis) of a randomized control trial compared supervised group interventions, 3 times/week for 12 weeks (36 sessions): (a) weight-bearing progressive resistive quadriceps exercise or (b) attention control. (1) From baseline, separate linear regressions were conducted with strength (Nm/kg) as the dependent, BMI as the predictor, and c-reactive protein, tumor necrosis factor, interleukin-6, cartilage transverse relaxation time or thickness as potential mediators. (2) Multiple linear regression analyses were completed with 12-week strength change (post-pre) as the dependent, change in serum inflammatory markers and cartilage measurements as predictors, and age, BMI and adherence as covariates. Findings (1) At baseline, there was no mediation. (2) A decrease in each of interleukin-6 (β = -0.104 (95% confidence intervals: -0.172, -0.036), R 2  = 0.51, P < 0.007) and tumor necrosis factor (β = -0.024 (-0.038, -0.009), R 2  = 0.54, P < 0.005) was associated with strength gains. Interpretation At baseline, inflammatory markers and cartilage measurements do not act as mediators of BMI on quadriceps strength. After 12 weeks of exercise, reduced interleukin-6 and tumor necrosis factor were associated with increased quadriceps strength in women with knee osteoarthritis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In the United States, approximately 2.53 million people sustain a concussion each year. Relative to adults, youth show greater cognitive deficits following concussion and a longer recovery. An accurate and reliable imaging method is needed to determine injury severity and symptom resolution. The primary objective of this study was to characterize concussions with diffusion tensor imaging (DTI). This was performed through a normative Z -scoring analysis of DTI metrics, fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD), to quantify patient-specific injuries and identify commonly damaged brain regions in paediatric concussion patients relative to healthy controls. It was hypothesized that personalizing the detection analysis through normative Z -scoring would provide an understanding of trauma-induced microstructural damage. Concussion patients were volunteers recruited from the Emergency Department of the McMaster Children's Hospital with a recent concussion ( n = 26), 9 males and 17 females, mean age 14.22 ± 2.64, while healthy paediatric brain DTI datasets (25 males and 24 females, mean age 13.52 ± 1.03) were obtained from an MRI data repository. Significant abnormalities were commonly found in the longitudinal fasciculus, fronto-occipital fasciculus, and corticospinal tract, while unique abnormalities were localized in a number of other areas reflecting the individuality of each child's injury. Total injury burden, determined by the number of regions containing outliers per DTI metric per patient, was used as the metric to quantify the overall injury severity of each patient. The primary outcome of this analysis found that younger patients experienced a significantly greater injury burden when measured using fractional anisotropy ( p < 0.001). These results show that DTI was able to detect microstructural changes caused by concussion, on a per-person basis, and has the potential to be a useful tool for improving diagnostic accuracy and prognosis of a concussion., Competing Interests: MN is the Co-Founder and CEO of TBIfinder, a data analytics company. No technology or funding from TBIfinder was contributed to this submitted study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Stillo, Danielli, Ho, DeMatteo, Hall, Bock, Connolly and Noseworthy.)

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., Competing Interests: Dr Michael D Noseworthy is the co-founder and CEO of TBIfinder Inc., a Data Analytics Company. None of the authors have any conflict of interest to disclose., (© 2021 Evans et al.)

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/m 2 , 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 (R 2 =0.90). Tibiofemoral shear (R 2 =0.86) and the resultant patellofemoral JRF (R 2 =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., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

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.

Objective: It is unclear why specific individuals incur chronic symptoms following a concussion. This exploratory research aims to identify and characterize any neurophysiological differences that may exist in motor cortex function in post-concussion syndrome (PCS)., Methods: Fifteen adults with PCS and 13 healthy, non-injured adults were tested. All participants completed symptom questionnaires, and transcranial magnetic stimulation (TMS) was used to measure intracortical and transcallosal excitability and inhibition in the dominant motor cortex., Results: Cortical silent period (p = 0.02, g = 0.96) and ipsilateral silent period (p = 0.04, g = 0.78) were shorter in the PCS group compared to the control group which may reflect reduced GABA-mediated inhibition in PCS. Furthermore, increased corticomotor excitability was observed in the left hemisphere but not the right hemisphere., Conclusions: These data suggest that persistent neurophysiological differences are present in those with PCS. The exact contributing factors to such changes remain to be investigated by future studies., Significance: This study provides novel evidence of lasting neurophysiological changes in PCS., (© 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V.)

Aims: Cardiovascular risk factors are used for risk stratification in primary prevention. We sought to determine if simple cardiac risk scores are associated with magnetic resonance imaging (MRI)-detected subclinical cerebrovascular disease including carotid wall volume (CWV), carotid intraplaque haemorrhage (IPH), and silent brain infarction (SBI)., Methods and Results: A total of 7594 adults with no history of cardiovascular disease (CVD) underwent risk factor assessment and a non-contrast enhanced MRI of the carotid arteries and brain using a standardized protocol in a population-based cohort recruited between 2014 and 2018. The non-lab-based INTERHEART risk score (IHRS) was calculated in all participants; the Framingham Risk Score was calculated in a subset who provided blood samples (n = 3889). The association between these risk scores and MRI measures of CWV, carotid IPH, and SBI was determined. The mean age of the cohort was 58 (8.9) years, 55% were women. Each 5-point increase (∼1 SD) in the IHRS was associated with a 9 mm3 increase in CWV, adjusted for sex (P < 0.0001), a 23% increase in IPH [95% confidence interval (CI) 9-38%], and a 32% (95% CI 20-45%) increase in SBI. These associations were consistent for lacunar and non-lacunar brain infarction. The Framingham Risk Score was also significantly associated with CWV, IPH, and SBI. CWV was additive and independent to the risk scores in its association with IPH and SBI., Conclusion: Simple cardiovascular risk scores are significantly associated with the presence of MRI-detected subclinical cerebrovascular disease, including CWV, IPH, and SBI in an adult population without known clinical CVD., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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.

Aerobic exercise has both neuroprotective and neurorehabilitative benefits. However, the underlying mechanisms are not fully understood and need to be investigated, especially in postmenopausal women, who are at increased risk of age-related disorders such as Alzheimer's disease and stroke. To advance our understanding of the potential neurological benefits of aerobic exercise in aging women, we examined anatomical and functional responses that may differentiate women of varying cardiorespiratory fitness using neuroimaging and neurophysiology. A total of 35 healthy postmenopausal women were recruited (59 ± 3 years) and cardiorespiratory fitness estimated (22-70 mL/kg/min). Transcranial magnetic stimulation was used to assess -aminobutyric acid (GABA) and glutamate (Glu) receptor function in the primary motor cortex (M1), and magnetic resonance spectroscopy (MRS) was used to quantify GABA and Glu concentrations in M1. Magnetic resonance imaging was used to assess mean cortical thickness (MCT) of sensorimotor and frontal regions, while the microstructure of sensorimotor and other white matter tracts was evaluated through diffusion tensor imaging. Regression analysis revealed that higher fitness levels were associated with improved microstructure in pre-motor and sensory tracts, and the hippocampal cingulum. Fitness level was not associated with MCT, MRS, or neurophysiology measures. These data indicate that, in postmenopausal women, higher cardiorespiratory fitness is linked with preserved selective white matter microstructure, particularly in areas that influence sensorimotor control and memory., (Copyright © 2020 Harasym, Turco, Nicolini, Toepp, Jenkins, Gibala, Noseworthy and Nelson.)

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 <0.0001), INTERHEART risk score ( P <0.0001), and among individuals with high white matter hyperintensities, nonlacunar brain infarction, and individuals with 3+ silent brain infarctions. Adjusted for age, sex, education, ethnicity covariates, Digital Symbol Substitution test was significantly lowered by 1.0 (95% CI, -1.3 to -0.7) point per 5-point cardiovascular risk score increase, 1.9 (95% CI, -3.2 to -0.6) per high white matter hyperintensities, 3.5 (95% CI, -6.4 to -0.7) per nonlacunar stroke, and 6.8 (95% CI, -11.5 to -2.2) when 3+ silent brain infarctions were present. No postsecondary education accounted for 15% (95% CI, 12-17), moderate and high levels of cardiovascular risk factors accounted for 19% (95% CI, 8-30), and MRI vascular brain injury accounted for 10% (95% CI, -3 to 22) of low test scores. 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.

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 P boot ). 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 ( P boot > .90), N -acetylaspartate and N -acetylaspartylglutamate ( P boot = .13), or glutamate and glutamine ( P boot = .11). Among the smaller resonances, no vendor effects were found for ascorbate ( P boot = .08), aspartate ( P boot > .90), glutathione ( P boot > .90), or lactate ( P boot = .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.

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.

Purpose: Ultrasound is a non-invasive quantitative method to characterize sonographic textures of skeletal muscles. To date, there is no information available on the trapezius muscle. This study assessed the trapezius muscles of patients with myofascial pain compared with normal healthy participants., Methods: The trapezius muscles of 15 healthy and 17 myofascial pain participants were assessed using B-mode ultrasound to obtain 120 images for healthy and 162 images from myofascial pain participants. Texture features such as blob area, count and local binary patterns (LBP) were calculated. Multi-feature classification and analysis were performed using principal component analysis (PCA) and MANOVA to determine whether there were statistical differences., Results: We demonstrate the two principal components composed of a combination of LBP and blob parameters which explain 92.55% of the cumulative variance of our data set. In addition, blob characteristics were significantly different between healthy and myofascial pain participants., Conclusion: Our study provides evidence that texture analysis techniques can differentiate between healthy and myofascial pain affected trapezius muscles. Further research is necessary to evaluate the nature of these differences.

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.

Purpose: 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., Methods: 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., Results: 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)., Conclusions: Random forests can classify brain PET as positive or negative for amyloid deposition and suggest key clinically relevant, regional features for classification.

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 B 0 -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 B 0 -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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Phosphorus MR spectroscopy and spectroscopic imaging ( 31 P-MRS/MRSI) provide information about energy metabolism, membrane degradation and pH in vivo. In spite of their proven utility, 31 P-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 31 P-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 31 P-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 31 P-MRSI as well as the better suitability of a low rank reconstruction approach., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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 cm 2 resolution over a 18 × 18 cm 2 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., (© 2019 International Society for Magnetic Resonance in Medicine.)

Accurate and reliable quantification of brain metabolites measured in vivo using 1 H 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 T 1 -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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.

Objective: To report additional gadolinium bone and urine data that can contribute to gaps in knowledge with respect to gadolinium uptake and retention in the body., Approach: In vivo measurements of gadolinium retention in the tibia bone were performed on individuals self-identified as exhibiting symptoms of gadolinium toxicity as a result of receiving GBCA, as well as on control individuals. Gadolinium urine measurements for controls, symptomatic exposed, and non-symptomatic exposed were conducted through Mayo Medical Laboratories., Main Results: Gadolinium bone concentration in the exposed group is significantly higher than the control group (p < 0.01), with a significant difference between symptomatic and non-symptomatic (p < 0.01), using a one-tailed t test on variance-weighted means. Gadolinium urine levels in both control subjects and non-symptomatic exposed subjects are significantly lower than symptomatic exposed subjects (p ≤ 0.05). A linear regression analysis for gadolinium urine levels and GBCA dose resulted in a positive linear relationship (R 2 = 0.91, p < 0.01). Gadolinium levels in urine and gadolinium concentration in bone were found to have a non-significant relationship (R 2 = 0.11, p = 0.3)., Significance: Significant differences in gadolinium levels in bone and urine are observed between individuals experiencing symptoms of gadolinium toxicity and for those who are not exhibiting symptoms. No correlation was observed between gadolinium in bone and gadolinium excreted in urine, suggesting that the retention of gadolinium in the body is complicated, involving multiple long-term storage sites.

Magnetic resonance imaging (MRI) has superior soft tissue contrast and lower interobserver variability compared to computed tomography and advances in equipment and pseudo-CT estimation have allowed for MR-only radiation therapy planning. Dedicated MR sequences have been used to localize paramagnetic structures with positive contrast, and most implanted seeds are gold fiducial markers (GFMs). We used a fast, dual-plane co-RASOR sequence to localize implanted GFMs with positive contrast in phantom and tissue to assess their resolution and registration accuracy of registration to CT. Off-resonant reconstructions of co-RASOR images were able to resolve GFMs down to 5 mm apart at 12 cm FOV. No systematic biases were observed by comparing registration of co-RASOR and bSSFP to CT images in an MR-compatible Lego phantom with a set of highly visible known points. The standard deviations of the MR to CT distance errors were  <0.5 mm in all directions. We separated the component due to registration by comparing the two MR sequences, which had a maximum standard deviation of 0.36 mm in the SI-direction. Registration using the positive contrast points in a porcine sample phantom showed increased errors, but co-RASOR still performs acceptably with a target registration error of  <0.75 mm. The dual-plane co-RASOR sequence could then be used for both registration and image tracking when performing MR-only radiation therapy planning.

Background: Following concussion, adolescents may experience both poor inhibitory control and increased depressive symptoms. fMRI research suggests that adolescents with major depressive disorder have abnormal physiological responses in the frontostriatal pathway, and exhibit poorer inhibitory control in the presence of negatively-aroused images. The scarcity of information surrounding depression following concussion in adolescents makes it difficult to identify patients at risk of depression after injury. This is the first study to examine neural activity patterns in adolescents with post-concussive depressive symptoms., Purpose: To explore the effect of depressive symptoms on inhibitory control in adolescents with concussion in the presence of emotional stimuli using fMRI., Methods: Using a prospective cohort design, 30 adolescents diagnosed with concussion between 10 and 17years were recruited. The Children's Depression Inventory questionnaire was used to divide participants into two groups: average or elevated levels of depressive symptoms. Participants completed an Emotional Go/No-Go task involving angry or neutral faces in a 3Telsa MRI scanner., Results: Eleven participants had elevated depressive symptoms, of which 72% were hit in the occipital region of the head at the time of injury. fMRI results from the Emotional Go/No-Go task revealed activity patterns in the overall sample. Faces activated regions associated with both facial and cognitive processing. However, frontal regions that are usually associated with inhibitory control were not activated. Adolescents with elevated levels of depressive symptoms engaged more frontal lobe regions during the task than the average group. They also showed a trend towards worse symptoms following MRI scanning., Conclusions: Adolescents with elevated depressive symptoms engaged brain regions subserving evaluative processing of social interactions. This finding provides insight into the role the environment plays in contributing to the cognitive demands placed on adolescents recovering from concussion., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Object: To present and evaluate a fast phosphorus magnetic resonance spectroscopic imaging (MRSI) sequence using echo planar spectroscopic imaging with flyback readout gradient trajectories., Materials and Methods: Waveforms were designed and implemented using a 3 Tesla MRI system. 31 P spectra were acquired with 2 × 2 cm 2 and 3 × 3 cm 2 resolution over a 20- and 21-cm field of view and spectral bandwidths up to 1923 Hz. The sequence was first tested using a 20-cm-diameter phosphate phantom, and subsequent in vivo tests were performed on healthy human calf muscles and brains from five volunteers., Results: Flyback EPSI achieved 10× and 7× reductions in acquisition time, with 68.0 ± 1.2 and 69.8 ± 2.2% signal-to-noise ratio (SNR) per unit of time efficiency (theoretical SNR efficiency was 74.5 and 76.4%) for the in vivo experiments, compared to conventional phase-encoded MRSI for the 2 × 2 cm 2 and 3 × 3 cm 2 resolution waveforms, respectively. Statistical analysis showed no difference in the quantification of most metabolites. Time savings and SNR comparisons were consistent across phantom, leg and brain experiments., Conclusion: EPSI using flyback readout trajectories was found to be a reliable alternative for acquiring 31 P-MRSI data in a shorter acquisition time.

The activation of brown adipose tissue (BAT) is associated with reductions in circulating lipids and glucose in rodents and contributes to energy expenditure in humans indicating the potential therapeutic importance of targetting this tissue for the treatment of a variety of metabolic disorders. In order to evaluate the therapeutic potential of human BAT, a variety of methodologies for assessing the volume and metabolic activity of BAT are utilized. Cold exposure is often utilized to increase BAT activity but inconsistencies in the characteristics of the exposure protocols make it challenging to compare findings. The metabolic activity of BAT in response to cold exposure has most commonly been measured by static positron emission tomography of 18 F-fluorodeoxyglucose in combination with computed tomography ( 18 F-FDG PET-CT) imaging, but recent studies suggest that under some conditions this may not always reflect BAT thermogenic activity. Therefore, recent studies have used alternative positron emission tomography and computed tomography (PET-CT) imaging strategies and radiotracers that may offer important insights. In addition to PET-CT, there are numerous emerging techniques that may have utility for assessing BAT metabolic activity including magnetic resonance imaging (MRI), skin temperature measurements, near-infrared spectroscopy (NIRS) and contrast ultrasound (CU). In this review, we discuss and critically evaluate the various methodologies used to measure BAT metabolic activity in humans and provide a contemporary assessment of protocols which may be useful in interpreting research findings and guiding the development of future studies., (© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

The goal of this work was to use an undersampled, dual-plane centre-out radial sampling acquisition pulse sequence, with off-resonance reception, to localize fiducial markers with reduced acquisition time. Two iterative reconstruction techniques, conjugate gradient CG-SENSE and the variational penalty Total Generalized Variation (TGV), were investigated to minimize the undersampling artifacts in off-resonant radial imaging. Simulations of a field perturber were performed at sub-millimeter resolution and reconstructed to display signal pileups that can be radially compressed towards the geometric centre of the perturber for high contrast visualization, but contrast is non-recoverable as the echo time increases. A cylindrical platinum fiducial marker, placed in a phantom parallel and perpendicular to the B 0 -field was imaged with a short-TE half-echo readout. Contrast-to-Noise (CNR) between the signal of the fiducial its adjacent surrounding shell and half-maximum area were used to compare reconstruction methods and undersampling factors. For single slice acquisitions centred about the fiducial, each slice can be performed in as little as 2.8s. The total acquisition time to localize the fiducial marker in a phantom was reduced to 73s by undersampling (R=8) 37 axial and 15 coronal slices, effectively encoding 1.4s/slice. The noise present in undersampled images, for both scan planes and fiducial orientations, decreased significantly using TGV and CG-SENSE reconstructions, with TGV displaying better spatial resolution from reduced half-maximum area., (Copyright © 2017 Elsevier Inc. All rights reserved.)