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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.)

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.

Objectives: Myofascial pain syndrome is one of the most common causes of chronic pain and is highlighted by the presence of myofascial trigger points. The current practice of diagnosing myofascial pain syndrome among clinicians involves manual detection of myofascial trigger points, which can be inconsistent. However, the detection process can be strengthened with the assistance of ultrasound (US). Therefore, this study aimed to characterize the upper trapezius by using quantitative techniques in healthy asymptomatic individuals with neck pain., Methods: Study participants were recruited on the basis of the inclusion and exclusion criteria established, and US images of the trapezius, along the axial and longitudinal orientations, were obtained. Each set was obtained by 2 investigators: experienced and inexperienced personnel., Results: Fifteen participants were recruited. The mean gray scale US echo intensity distribution obtained was 41.9. A paired t test of the global mean echo intensity value obtained for each image from the US operators did not show any significant difference (P = .77). A t test was performed, comparing the echo intensity of the group of patients with neck pain and healthy control participants, and the difference was found to be significant (P = .052). The median blob area was 2.71. The quartile range for the blob area was 1.72 for the 25th percentile to 4.90 for the 75th percentile., Conclusions: This study demonstrated that quantitative analysis of the echo intensity of US images can provide important information. However, further research is necessary to explore the relationships among sex, age, blob area, count, body mass index, regional anatomy, and extent of training or exercise of the particular muscle., (© 2017 by the American Institute of Ultrasound in Medicine.)

Magnetic resonance spectroscopy (MRS) is the only biomedical imaging method that can noninvasively detect endogenous signals from the neurotransmitter γ-aminobutyric acid (GABA) in the human brain. Its increasing popularity has been aided by improvements in scanner hardware and acquisition methodology, as well as by broader access to pulse sequences that can selectively detect GABA, in particular J-difference spectral editing sequences. Nevertheless, implementations of GABA-edited MRS remain diverse across research sites, making comparisons between studies challenging. This large-scale multi-vendor, multi-site study seeks to better understand the factors that impact measurement outcomes of GABA-edited MRS. An international consortium of 24 research sites was formed. Data from 272 healthy adults were acquired on scanners from the three major MRI vendors and analyzed using the Gannet processing pipeline. MRS data were acquired in the medial parietal lobe with standard GABA+ and macromolecule- (MM-) suppressed GABA editing. The coefficient of variation across the entire cohort was 12% for GABA+ measurements and 28% for MM-suppressed GABA measurements. A multilevel analysis revealed that most of the variance (72%) in the GABA+ data was accounted for by differences between participants within-site, while site-level differences accounted for comparatively more variance (20%) than vendor-level differences (8%). For MM-suppressed GABA data, the variance was distributed equally between site- (50%) and participant-level (50%) differences. The findings show that GABA+ measurements exhibit strong agreement when implemented with a standard protocol. There is, however, increased variability for MM-suppressed GABA measurements that is attributed in part to differences in site-to-site data acquisition. This study's protocol establishes a framework for future methodological standardization of GABA-edited MRS, while the results provide valuable benchmarks for the MRS community., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to evaluate the effect of the pseudohepatic anisotropy artifact on liver intravoxel incoherent motion (IVIM) metrics and whether the use of multiple gradient directions in the IVIM acquisition minimizes the artifact., Materials and Methods: Multiple breath-holding and forced shallow free-breathing IVIM scans were performed on 8 healthy volunteers using 1 and 6 gradient directions. Cluster analysis was carried out to separate motion-contaminated parenchyma from liver parenchyma and vessels. Nonlinear motion analysis was also performed to look for a possible link between IVIM metrics and nonlinear liver motion., Results: On the basis of the resulted clusters, motion-contaminated parenchyma is often noted in the left liver lobe, where the prominent pseudohepatic artifact has previously been identified. A significant reduction in outliers was obtained with the acquisition of 6 noncoplanar gradient directions and when using forced shallow free-breathing., Conclusion: The pseudohepatic anisotropy artifact can be minimized when using multiple diffusion-encoding gradient directions and forced free-breathing during IVIM acquisition.

Background: Malignant hyperthermia (MH), a pharmacogenetic disorder of skeletal muscle, presents with a potentially lethal hypermetabolic reaction to certain anesthetics. However, some MH-susceptible patients experience muscle weakness, fatigue, and exercise intolerance in the absence of anesthetic triggers. The objective of this exploratory study was to elucidate the pathophysiology of exercise intolerance in patients tested positive for MH with the caffeine-halothane contracture test. To this end, we used phosphorus magnetic resonance spectroscopy, blood oxygen level-dependent functional magnetic resonance imaging (MRI), and traditional exercise testing to compare skeletal muscle metabolism in MH-positive patients and healthy controls., Methods: Skeletal muscle metabolism was assessed using phosphorus magnetic resonance spectroscopy and blood oxygen level-dependent functional MRI in 29 MH-positive patients and 20 healthy controls. Traditional measures of physical capacity were employed to measure aerobic capacity, anaerobic capacity, and muscle strength., Results: During 30- and 60-second exercise, MH-positive patients had significantly lower ATP production via the oxidative pathway compared to healthy controls. MH-positive patients also had a longer recovery time with blood oxygen level-dependent functional MRI compared to healthy controls. Exercise testing revealed lower aerobic and anaerobic capacity in MH-positive patients compared to healthy controls., Conclusions: Results of this exploratory study suggest that MH-positive patients have impaired aerobic metabolism compared to healthy individuals. This could explain the exercise intolerance exhibited in MH-susceptible patient population.

Object: To assess post-exercise recovery of human calf muscles using dynamic diffusion tensor imaging (dDTI)., Materials and Methods: DTI data (6 directions, b = 0 and 400 s/mm 2 ) were acquired every 35 s from seven healthy men using a 3T MRI, prior to (4 volumes) and immediately following exercise (13 volumes, ~7.5 min). Exercise consisted of 5-min in-bore repetitive dorsiflexion-eversion foot motion with 0.78 kg resistance. Diffusion tensors calculated at each time point produced maps of mean diffusivity (MD), fractional anisotropy (FA), radial diffusivity (RD), and signal at b = 0 s/mm 2 (S 0 ). Region-of-interest (ROI) analysis was performed on five calf muscles: tibialis anterior (ATIB), extensor digitorum longus (EDL) peroneus longus (PER), soleus (SOL), and lateral gastrocnemius (LG)., Results: Active muscles (ATIB, EDL, PER) showed significantly elevated initial MD post-exercise, while predicted inactive muscles (SOL, LG) did not (p < 0.0001). The EDL showed a greater initial increase in MD (1.90 × 10 -4 mm 2 /s) than ATIB (1.03 × 10 -4 mm 2 /s) or PER (8.79 × 10 -5 mm 2 /s) (p = 7.40 × 10 -4 ), and remained significantly elevated across more time points than ATIB or PER. Significant increases were observed in post-exercise EDL S 0 relative to other muscles across the majority of time points (p < 0.01 to p < 0.001)., Conclusions: dDTI can be used to differentiate exercise-induced changes between muscles. These differences are suggested to be related to differences in fiber composition.

Objectives: Numerous neuroimaging techniques have been recently used to investigate central mechanisms involved in pain perception and to examine morphological and functional brain alterations associated with chronic pain. Compared to self-reporting approaches, objective imaging techniques are expected to potentially lead to better pain assessment and guide management. This comprehensive scoping review aims to identify recent magnetic resonance imaging (MRI) approaches that have been used to characterize the brain of chronic pain subjects, using structural, chemical and functional MRI techniques., Methods: A systematic search and review of the literature was conducted and the resultant studies were critically examined for relevance., Results: MRI neuroimaging of various chronic pain conditions were summarized. We classified the collected studies into: structural brain alterations, VBM (voxel based morphology) examination of structural changes, DTI, changes in brain chemistry, functional and blood flow brain alterations., Discussion: From our clinical experience, we have noted that most clinicians are not aware of the capabilities of advanced MRI methods in assessing cortical manifestations of chronic pain. In addition, many clinicians are not aware of the cortical alterations present in individuals with chronic pain. This comprehensive scoping review thus sets out to first summarize MRI neuroimaging techniques that are available in the current literature to examine chronic pain. We then identify cortical MR approaches that have been able to reliably predict transition from acute to chronic pain. Finally, we summarize MRI neuroimaging techniques that have been used to track treatment response of individuals with chronic pain.

Background: In individuals with knee osteoarthritis (OA), fatty infiltration into thigh muscle is associated with poor physical performance and strength. However, it is not known whether this also occurs in the calf and if this impacts physical function., Aims: We investigated the relationships between volumes of intramuscular fat (intraMF), intermuscular fat (IMF), subcutaneous fat (SCF), lean muscle and muscle adiposity, in the thighs compared to the calves of women with knee OA., Methods: MRI scans of the thigh and calf were acquired from 20 women over 55 years with knee OA (3.0T Discovery MR750, GE Healthcare). Axial IDEAL (iterative decomposition of water and fat with echo asymmetry and least-squares estimation) fat-separated images were segmented to quantify intraMF, IMF, SCF and lean muscle volumes (SliceOmatic 5.0, Tomovision). Correlation and linear regression analyses were run., Results: We found a positive relationship between thigh and calf intraMF (R 2  = 0.592; B = 5.49; p = 0.001), muscle adiposity (R 2  = 0.539; B = 0.567; p = 0.001), and SCF volume (R 2  = 0.699; B = 12.847; p = 0.001), controlling for waist-to-hip ratio. Relationships between thigh and calf IMF (R 2  = 0.239; B = 7.743; p = 0.061), lean muscle (R 2  = 0.245; B = 4.149; p = 0.047) and combined intraMF and IMF volume (R 2  = 0.242; B = 6.162; p = 0.044) were not significant., Discussion: Although a correlation exists between thigh and calf muscle adiposity, intraMF and SCF, this does not hold true for IMF or lean muscle. A greater amount of intraMF infiltration occurs in the thigh compared to the calf of women with knee OA., Conclusion: The calf and thigh may both be involved in pathologic changes in muscle composition in knee OA.

Background: Advanced magnetic resonance (MR) scanning techniques, such as diffusion tensor imaging (DTI) and proton MR spectroscopy ( 1 H-MRS) permit microstructural evaluation of water diffusivity and intramyocellular lipid content, respectively. We aimed to determine the feasibility of performing advanced MR scanning (proton density [PD] weighted imaging, DTI, and 1 H-MRS) to evaluate properties of leg muscles in older women with respect to: (1) participant recruitment using three community-based strategies; (2) participant tolerance to the MRI scan acquisition protocol; and (3) scan acquisition and analyses protocols., Methods: Recruitment feasibility was evaluated based on the number of participants enrolled using various strategies. Participant tolerance was feasible if the scanning session was uninterrupted and image artifacts were absent. Optimal PD imaging, DTI, and 1 H-MRS acquisition and analyses protocols were established., Results: Nine women (mean age = 71 years) were recruited over four months. The acquisition protocol was well tolerated by all participants. Adaptations were required for women with short stature and vertebral fracture risk. PD-weighted image analyses were improved by using the phased array uniformity enhancement filter to increase tissue contrast., Conclusions: It is feasible to use a combination of MR scanning methods to evaluate muscle macrostructure and microstructure in the leg of older women. Our findings suggest that advanced MR scanning methods can be used for future studies interested in quantifying components of muscle structure in older women, but prospective studies are needed to confirm whether change in microstructure can be detected in response to an intervention., (Copyright © 2016 Canadian Association of Medical Radiation Technologists. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare the acute effect of running and bicycling of an equivalent cumulative load on knee cartilage composition and morphometry in healthy young men. A secondary analysis investigated the relationship between activity history and the change in cartilage composition after activity., Methods: In fifteen men (25.8±4.2 years), the vertical ground reaction force was measured to determine the cumulative load exposure of a 15-min run. The vertical pedal reaction force was recorded during bicycling to define the bicycling duration of an equivalent cumulative load. On separate visits that were spaced on average 17 days apart, participants completed these running and bicycling bouts. Mean cartilage transverse relaxation times (T 2 ) were determined for cartilage on the tibia and weight-bearing femur before and after each exercise. T 2 was measured using a multi-echo spin-echo sequence and 3T MRI. Cartilage of the weight bearing femur and tibia was segmented using a highly-automated segmentation algorithm. Activity history was captured using the International Physical Activity Questionnaire., Results: The response of T 2 to bicycling and running was different (p=0.019; mean T 2 : pre-running=34.27ms, pre-bicycling=32.93ms, post-running=31.82ms, post-bicycling=32.36ms). While bicycling produced no change (-1.7%, p=0.300), running shortened T 2 (-7.1%, p<0.001). Greater activity history predicted smaller changes in tibial, but not femoral, T 2 ., Conclusions: Changes in knee cartilage vary based on activity type, independent of total load exposure, in healthy young men. Smaller changes in T 2 were observed after bicycling relative to running. Activity history was inversely related to tibial T 2 , suggesting cartilage conditioning., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

fMRI and EEG during mental imagery provide alternative methods of detecting awareness in patients with disorders of consciousness (DOC) without reliance on behaviour. Because using fMRI in patients with DOC is difficult, studies increasingly employ EEG. However, there has been no verification that these modalities provide converging information at the individual subject level. The present study examined simultaneous EEG and fMRI in healthy volunteers during six mental imagery tasks to determine whether one mental imagery task generates more robust activation across subjects; whether activation can be predicted from familiarity with the imagined activity; and whether EEG and fMRI converge upon the same conclusions about individual imagery performance. Mental arithmetic generated the most robust activation in the majority of subjects for both EEG and fMRI, and level of activation could not be predicted from familiarity, with either modality. We conclude that overall, EEG and fMRI agree regarding individual mental imagery performance., (Copyright © 2016 Elsevier Inc. All rights reserved.)

This paper examines two artifacts facing researchers who use gradient echo (GRE) echo planar imaging (EPI) for time series studies of skeletal muscles in limbs. The first is through-plane blood flow during the acquisition, causing a vessel motion artifact that inhibits proper motion correction of the data. The second is distortion of EPI images caused by B0 field inhomogeneities. Though software tools are available for correcting these artifacts in brain EPI images, the tools do not perform well on muscle images. The severity of the two artifacts was described using image similarity measures, and the data was processed with both a conventional motion correction program and custom written tools. The conventional program did not perform well on the limb images, in fact significantly degrading image quality in some trials. Data is presented which proves that arterial pulsatile signal caused the impairment in motion correction. The new tools were shown to perform much better, achieving substantial motion correction and distortion correction of the muscle EPI images., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: One disadvantage of magnetic resonance imaging (MRI) is the inability to adequately image the lungs. Recent advances in hyperpolarized gas technology [e.g., helium-3 ((3)He) and xenon-129 ((129)Xe)] have changed this. However, the required technology is expensive and often needing extra physics or engineering staff. Hence there is considerable interest in developing (1)H (proton)-based MRI approaches that can be readily implemented on standard clinical systems. Thus, the purpose of this work was to compare a newly developed free breathing proton-based MR lung imaging method to that of a standard gadolinium (Gd) based perfusion approach., Methods: Healthy volunteers [10] were scanned using a 3-T MRI with 8 parallel receivers, and a cardiac gated fast spin echo (FSE) sequence. Acquisition was cardiac triggered, with different time delays incremented to cover the entire cardiac cycle. Image k-space was filled rectilinearly. But to reduce motion artefacts k-space was retrospectively sorted using the minimal variance algorithm (MVA), based on physiologic data recorded from both the respiratory bellows and electrocardiogram (ECG). Resorted and reconstructed FSE images were compared to contrast enhanced lung images, obtained following intravenous injection of Gd-DTPA-BMA., Results: Biphasic variation in FSE lung signal intensity was observed across the cardiac cycle with a maximal signal change following rapid cardiac ejection (between S and T waves), and following rapid isovolumetric relaxation. A difference image between systolic and diastolic states in the cardiac cycle resulted in images with improved lung contrast to noise ratio (CNR). FSE image intensity was uniform over lung parenchyma while Gd-based enhancement of spoiled gradient recalled echo (SPGR) images showed gravitational dependence., Conclusions: Here we show how 1H-MR images of lung can be obtained during free breathing. The image contrast obtained during this approach is likely the result of flow and oxygen modulation during the cardiac cycle. This free breathing method provides lung images comparable to those obtained using Gd-enhancement. Besides having the advantage of free breathing, this approach doesn't require any Gd-contrast or suffer from methodological problems associated with perfusion (e.g., poor bolus timing). However, as gravitational differences typically observed in lung perfusion are not visible with this method it is not providing exclusive microvascular perfusion information.

Purpose: To explore the effect of diffusion tensor imaging (DTI) acquisition parameters on principal and minor eigenvector stability within human lower leg skeletal muscles., Materials and Methods: Lower leg muscles were evaluated in seven healthy subjects at 3T using an 8-channel transmit/receive coil. Diffusion-encoding was performed with nine signal averages (NSA) using 6, 15, and 25 directions (NDD). Individual DTI volumes were combined into aggregate volumes of 3, 2, and 1 NSA according to number of directions. Tensor eigenvalues (λ1 , λ2 , λ3 ), eigenvectors (ε1 , ε2 , ε3 ), and DTI metrics (fractional anisotropy [FA] and mean diffusivity [MD]) were calculated for each combination of NSA and NDD. Spatial maps of signal-to-noise ratio (SNR), λ3 :λ2 ratio, and zenith angle were also calculated for region of interest (ROI) analysis of vector orientation consistency., Results: ε1 variability was only moderately related to ε2 variability (r = 0.4045). Variation of ε1 was affected by NDD, not NSA (P < 0.0002), while variation of ε2 was affected by NSA, not NDD (P < 0.0003). In terms of tensor shape, vector variability was weakly related to FA (ε1 :r = -0.1854, ε2 : ns), but had a stronger relation to the λ3 :λ2 ratio (ε1 :r = -0.5221, ε2 :r = -0.1771). Vector variability was also weakly related to SNR (ε1 :r = -0.2873, ε2 :r = -0.3483). Zenith angle was found to be strongly associated with variability of ε1 (r = 0.8048) but only weakly with that of ε2 (r = 0.2135)., Conclusion: The second eigenvector (ε2 ) displayed higher directional variability relative to ε1 , and was only marginally affected by experimental conditions that impacted ε1 variability., (© 2015 Wiley Periodicals, Inc.)

The objective of this study was to estimate the associations between muscular fat infiltration, tibia bone mineral quantity and distribution, and physical function in healthy older women. Thirty-five women (aged 60-75 years, mean 70 years) were recruited from the community. Percent intramuscular fat (%IntraMF) within the right leg tibialis anterior, soleus, and gastrocnemius muscles and total intermuscular fat (IMF) were segmented from magnetic resonance imaging scans at the mid-calf. Intramyocellular lipid (IMCL) content in the right tibialis anterior was measured with proton magnetic resonance spectroscopy. Right tibia bone content, area, and strength were measured at the 4, 14, and 66% sites using peripheral quantitative computed tomography. Physical function was assessed by gait speed on the 20 m walking test. After adjusting for age, body size, and activity level, %IntraMF had a negative association with bone content and area at all tibia sites (r = -0.31 to -0.03). Conversely, greater IMF was associated with increased bone content and area (r = 0.04-0.32). Correlation coefficients for the association between IMCL and bone were negative (r = -0.44 to -0.03). All measures of fat infiltration had a negative association with observed physical function (r = -0.42 to -0.04). Our findings suggest that muscular fat infiltration in the leg of healthy postmenopausal women has a compartment-specific relationship with bone status and physical function. Minimizing fat accumulation within and between muscle compartments may prevent bone fragility and functional decline in women.

Object: There have been no studies to investigate the effects of cycling exercise protocols, as well as repeated bouts of exercise, on the blood oxygen level-dependent (BOLD) response in the quadriceps muscles. This study characterized BOLD signal recovery following non-ischemic bouts of exercise in the quadriceps muscles of healthy adults in order to provide a basis for application of a protocol for clinical populations., Materials and Methods: Healthy male subjects (23.7 ± 2.0 years of age, n = 10) completed three cycles of one-minute exercise (65 % of maximum workload), with two minutes of rest between each bout, on an MRI-compatible ergometer. The BOLD responses during recovery were fitted to a sigmoid model, and response kinetics (post-exercise intensity [S0]), response time (α), change in baseline BOLD signal (κ), and inflection point (β)] were measured., Results: The sigmoid function fit well to the post-exercise BOLD data (r (2) = 0.95 ± 0.04). The mean response time was 10.5 ± 3.8 seconds, change in baseline BOLD intensity was 0.15 ± 0.068, and time to half-peak was 20.2 ± 8.6 seconds., Conclusion: The proposed sigmoid model is a robust method for quantifying quadriceps BOLD response post-exercise without induced ischemia. Extension of this model to evaluate microvascular responses in patients with chronic disease could improve our understanding of exercise intolerance.

Object: The object was to assess whether cross-sectional area (CSA) and water diffusion properties of leg muscles in young and older women change with increased time spent in supine rest., Materials and Methods: Healthy young (n = 9, aged 20-30 years) and older (n = 9, aged 65-75 years) women underwent MRI scanning of the right leg at baseline, 30 and 60 min of supine rest. Muscle CSA was derived from proton density images. Water diffusion properties [apparent diffusion coefficient (ADC) and fractional anisotropy (FA)] of the tibialis anterior and posterior, soleus, and medial and lateral heads of the gastrocnemius were derived from diffusion tensor imaging (DTI). Repeated measures ANOVAs and Bonferroni post hoc tests determined the effects of time and group on each muscle outcome., Results: In both groups, muscle CSA and FA did not significantly change over time, whereas ADC significantly decreased. A greater decline at 30 min for young women was only observed for ADC in the medial gastrocnemius., Conclusion: Regardless of age, ADC values decreased with fluid shift associated with time spent supine, whereas CSA and FA were not affected. For leg muscle assessment in young and older women, DTI scanning protocols should consider the amount of time spent in a recumbent position.

Background: Exercise intolerance is prevalent in individuals with Turner Syndrome (TS). We recently demonstrated that girls with TS have normal aerobic but altered skeletal muscle anaerobic metabolism compared to healthy controls (HC). The purpose of this study was to compare peripheral skeletal muscle microvascular function in girls with TS to HC after exercise. We hypothesized that girls with TS would have similar muscle blood-oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) signal responses during recovery from exercise compared to HC., Methods: Thirteen TS participants and 8 HC completed testing. BOLD MRI was used to measure skeletal muscle microvascular response during 60 second recovery, following 60 s of exercise at 65% of maximal workload. Exercise and recovery were repeated four times, and the BOLD signal time course was fit to a four-parameter sigmoid function., Results: Participants were 13.7 ± 3.1 years old and weighed 47.9 ± 14.6 kg. The mean change in BOLD signal intensity following exercise at the end of recovery, the mean response time of the function/the washout of deoxyhemoglobin, and the mean half-time of recovery were similar between the TS and HC groups., Conclusions: Our results demonstrate that compared to HC, peripheral skeletal muscle microvascular function following exercise in girls with TS is not impaired., General Significance: This study supports the idea that the aerobic energy pathway is not impaired in children with TS in response to submaximal exercise. Other mechanisms are likely responsible for exercise intolerance in TS; this needs to be further investigated.

Object: To investigate whether postural change from erect to recumbent position affects calf muscle water diffusivity., Materials and Methods: Ten healthy adults (27.2 ± 4.9 years, 3 females) were imaged at baseline (following assumption of recumbent position), and after 34 min (session 2) and 64 min (session 3) of laying supine within a 3T MRI scanner. Diffusion tensor imaging (DTI) eigenvalues, fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were evaluated in five calf muscles (anterior and posterior tibialis and triceps surae) during each of the three imaging sessions., Results: Significant decreases were observed in all of the eigenvalues and ADC in each of the muscles with postural change. These reductions ranged from 3.2 to 6.7% and 3.4 to 7.5% for the various DTI metrics, following 34 and 64 min of supine rest, respectively (P < 0.05). No significant differences were noted in ADC or eigenvalues between the second and third imaging sessions for any muscle. FA did not change significantly with postural manipulation in any muscle compartment., Conclusion: Diffusion tensor imaging indices were altered with postural change. As differences were not apparent between the latter two imaging sessions, we suggest that a short supine resting period (~34 min) is sufficient for muscle diffusivity to stabilize prior to quantitative MR imaging in healthy young adults.

Object: To study the effect of acute alcohol intoxication on the functional connectivity of the default mode network (DMN) and temporal fractal properties of the healthy adult brain., Materials and Methods: Eleven healthy male volunteers were asked to drink 0.59 g/kg of ethanol. Resting state blood oxygen level dependent (rsBOLD) MRI scans were obtained before consumption, 60 min post-consumption and 90 min post-consumption. Before each rsBOLD scan, pointed-resolved spectroscopy (PRESS) (1)H-MRS (magnetic resonance spectroscopy) scans were acquired to measure ethanol levels in the right basal ganglia., Results: Significant changes in DMN connectivity were found following alcohol consumption (p < 0.01). Both increased and decreased regional connectivity were found after 60 min, whereas mostly decreased connectivity was found after 90 min. The fractal behaviour of the rsBOLD signal, which is believed to help reveal complexity of small-scale neuronal circuitry, became more ordered after both 60 and 90 min of alcohol consumption (p < 0.01)., Conclusion: The DMN has been linked to personal identity and social behavior. As such, our preliminary findings may provide insight into the neuro-functional underpinnings of the cognitive and behavioral changes observed during acute alcohol intoxication. The reduced fractal dimension implies a change in function of small-scale neural networks towards less complex signaling.

Background: Mitochondrial disorders are clinical syndromes associated with mutations in the mitochondrial or nuclear genome that result in impaired oxidative phosphorylation and deficient energy production. Metabolic abnormalities in brain areas associated with cognitive functions could give rise to neuropsychiatric symptomatology. The aim of this study was to use single-voxel proton magnetic resonance spectroscopy to identify metabolic abnormalities in regions implicated in neuropsychiatric symptoms in patients with mitochondrial disorders., Methods: N-acetyl-aspartate and creatine levels were measured in the caudate nucleus, anterior cingulate cortex and hippocampus in 15 patients with mitochondrial disorders compared with 15 healthy controls matched for age and sex., Results: N-acetyl-aspartate levels were significantly lower in the caudate nucleus among patients with mitochondrial disorders (mean 7.04 ± 1.19 standard deviation [SD] institutional units) compared with healthy controls (mean 8.19 ± 1.18 SD institutional units; p = 0.02). Creatine levels were lower in the caudate nucleus among patients compared with controls (patients: mean 6.84 ± 1.42 SD institutional units; controls: mean 7.52 ± 0.76 SD institutional units; p = 0.03), but the results were no longer significant after correction for multiple comparisons. There were no significant differences in metabolite measurements between patients and controls in the anterior cingulate cortex and the hippocampus., Interpretation: Metabolic abnormalities were identified exclusively in the caudate nucleus, with significantly lower N-acetyl-aspartate levels among patients compared with controls. These results suggest that the corpus striatum may be highly susceptible to mitochondrial oxidative phosphorylation defects and resultant cell loss. Given the role of the caudate nucleus in cognitive and executive functions, our findings raise the possibility that metabolic abnormalities in the caudate nucleus may contribute to cognitive impairment and neuropsychiatric symptoms in patients with mitochondrial disorders, which could be investigated in future studies.

Objectives: To correlate temporal fractal structure of resting state blood oxygen level dependent (rsBOLD) functional magnetic resonance imaging (fMRI) with in vivo proton magnetic resonance spectroscopy ((1)H-MRS), in Alzheimer's disease (AD) and healthy age-matched normal controls (NC)., Materials and Methods: High temporal resolution (4 Hz) rsBOLD signal and single voxel (left putamen) magnetic resonance spectroscopy data was acquired in 33 AD patients and 13 NC. The rsBOLD data was analyzed using two types of fractal dimension (FD) analysis based on relative dispersion and frequency power spectrum. Comparisons in FD were performed between AD and NC, and FD measures were correlated with (1)H-MRS findings., Results: Temporal fractal analysis of rsBOLD, was able to differentiate AD from NC subjects (P = 0.03). Low FD correlated with markers of AD severity including decreased concentrations of N-acetyl aspartate (R = 0.44, P = 0.015) and increased myoinositol (mI) (R = -0.45, P = 0.012)., Conclusion: Based on these results we suggest fractal analysis of rsBOLD could provide an early marker of AD.

Typical clinical evaluation of the tumour microvascular environment is performed by dynamic contrast enhanced MRI (dceMRI). However, this approach has been defined by numerous mathematical models each with their own physiologic assumptions which often leads to inconclusive results in the assessment of microstructure. Alternatively, Blood Oxygen Level Dependent (BOLD) Magnetic Resonance Imaging (MRI) is already known to be sensitive to the microvascular environment through fluctuation in the oxyhemoglobin to deoxyhemoglobin ratio. Consequently, quantification of the BOLD signal's temporal complexity using a fractal dimension index allows maps to be generated that are physiologically distinctive in nature and allow potential insight into tumour microvasculature with no a priori assumptions as in dceMRI. Here, using rectal carcinoma as an example, we present this novel approach to tumour microvascular evaluation using fractal dimension parametric mapping.

Purpose: To measure possible positional and diurnal physiological effects on brain metabolites in single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) measurements of the right and left striatum., Methods: (1)H-MRS measurements were performed in 10 healthy adult volunteers using a short echo PRESS sequence (TE=30 ms, TR=3000 ms). Each individual was scanned during both morning and afternoon hours. Regions of interest were right and left striatum. To control for systematic drift in scanner performance, (1)H-MRS measurements of a standard phantom solution were also acquired. Statistical analysis was performed using a repeated measures analysis of variance that included three within-subject factors: metabolite (N-acetyl-aspartate [NAA] or creatine [Cr]), laterality (left or right caudate) and time (morning or afternoon)., Results: A significant interaction (P<.016) between time of day and metabolite levels was observed. Further exploration of this finding revealed a significant difference between morning and afternoon levels of NAA (P<.044) but not Cr. In addition, no significant morning-to-afternoon differences were observed for the (1)H-MRS phantom measurements., Conclusions: Systematic variation due to scanner performance does not account for the changes observed in repeated measurements of striatal NAA levels. This difference may be accounted for by either repositioning effects or circadian physiological effects. Further studies are required to learn whether time of day standardization of (1)H-MRS acquisitions may contribute to improved reproducibility of measurements.

Background and Purpose: MR examination of infants with kernicterus shows abnormal changes in signal intensity in various parts of the brain, including the globus pallidus and subthalamic regions. The purpose of this study was to retrospectively analyze proton ((1)H) MR spectroscopic data to see if the MR spectroscopic profiles of infants with hyperbilirubinemia and symptoms of kernicterus provide new insights into the pathophysiology of bilirubin neurotoxicity., Methods: Six patients aged 3 days to 3 weeks, with hyperbilirubinemia and symptoms of kernicterus underwent MR imaging and MR spectroscopy with a single-voxel point-resolved spectroscopic sequence. The voxel of interest was centered in the basal ganglia with CSF excluded. Quantitative analysis was done by using LCModel. Between-subject comparisons were based on metabolite ratios relative to creatine., Results: Ratios of taurine, glutamate and glutamine, and myoinositol relative to creatine were significantly elevated (P < .001), whereas the ratio of choline to creatine was significantly decreased (P < .001) compared with normal values published for this age group. Lactate levels were not significantly elevated., Conclusion: Kernicterus has a characteristic signature that is detectable on (1)H-MR spectroscopy. Our results are generally in agreement with what is known about bilirubin pathology, and the finding of increased glutamate and glutamine and decreased choline ratios indicates a possible link between hepatic encephalopathy and kernicterus. This observation may help in elucidating the pathophysiology of bilirubin neurotoxicity.