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Purpose: Lactate is a key metabolite in skeletal muscle and whole‐body physiology. Its MR visibility in muscle is affected by overlapping lipid signals and fiber orientation. Double‐quantum filtered (DQF) 1H MRS selectively detects lactate at 1.3 ppm, but at ultra‐high field the efficiency of slice‐selective 3D‐localization with conventional RF pulses is limited by bandwidth. This novel 3D‐localized 1H DQF MRS sequence uses adiabatic refocusing pulses to unambiguously detect lactate in skeletal muscle at 7 T. Methods: Lactate double‐quantum coherences were 3D‐localized using slice‐selective Shinnar–Le Roux optimized excitation and adiabatic refocusing pulses (similar to semi‐LASER). DQF MR spectra were acquired at 7 T from lactate phantoms, meat specimens with injected lactate (exploring multiple TEs and fiber orientations), and human gastrocnemius in vivo during and after exercise (without cuff ischemia). Results: Lactate was readily detected, achieving the full potential of 50% signal with a DQF, in solution. The effects of fiber orientation and TE on the lactate doublet (peak splitting, amplitude, and phase) were in good agreement with theory and literature. Exercise‐induced lactate accumulation was detected with 30 s time resolution. Conclusion: This novel 3D‐localized 1H DQF MRS sequence can dynamically detect glycolytically generated lactate in muscle during exercise and recovery at 7 T. [ABSTRACT FROM AUTHOR]

Background: Neuroimaging studies in posttraumatic stress disorder (PTSD) have identified various alterations in white matter (WM) microstructural organization. However, it remains unclear whether these are localized to specific regions of fiber tracts, and what diagnostic value they might have. This study set out to explore the spatial profile of WM abnormalities along defined fiber tracts in PTSD. Methods: Diffusion tensor images were obtained from 77 treatment‐naive noncomorbid patients with PTSD and 76 demographically matched trauma‐exposed non‐PTSD (TENP) controls. Using automated fiber quantification, tract profiles of fractional anisotropy, axial diffusivity, mean diffusivity, and radial diffusivity were calculated to evaluate WM microstructural organization. Results were analyzed by pointwise comparisons, by correlation with symptom severity, and for diagnosis‐by‐sex interactions. Support vector machine analyses assessed the ability of tract profiles to discriminate PTSD from TENP. Results: Compared to TENP, PTSD showed lower fractional anisotropy accompanied by higher radial diffusivity and mean diffusivity in the left uncinate fasciculus, and lower fractional anisotropy accompanied by higher radial diffusivity in the right anterior thalamic radiation. Tract profile alterations were correlated with symptom severity, suggesting a pathophysiological relevance. There were no significant differences in diagnosis‐by‐sex interaction. Tract profiles allowed individual classification of PTSD versus TENP with significant accuracy, of potential diagnostic utility. Conclusions: These findings add to the knowledge of the neuropathological basis of PTSD. WM alterations based on a tract‐profile quantification approach are a potential biomarker for PTSD. [ABSTRACT FROM AUTHOR]

Background: The EMPOWER trial aimed to assess the effects of a 9-week exercise prehabilitation programme on physical fitness compared with a usual care control group. Secondary aims were to investigate the effect of (1) the exercise prehabilitation programme on psychological health; and (2) neoadjuvant chemoradiotherapy (NCRT) on physical fitness and psychological health. Methods: Between October 2013 and December 2016, adults with locally advanced rectal cancer undergoing standardised NCRT and surgery were recruited to a multi-centre trial. Patients underwent cardiopulmonary exercise testing (CPET) and completed HRQoL questionnaires (EORTC-QLQ-C30 and EQ-5D-5L) pre-NCRT and post-NCRT (week 0/baseline). At week 0, patients were randomised to exercise prehabilitation or usual care (no intervention). CPET and HRQoL questionnaires were assessed at week 0, 3, 6 and 9, whilst semi-structured interviews were assessed at week 0 and week 9. Changes in oxygen uptake at anaerobic threshold (VO2 at AT (ml kg−1 min−1)) between groups were compared using linear mixed modelling. Results: Thirty-eight patients were recruited, mean age 64 (10.4) years. Of the 38 patients, 33 were randomised: 16 to usual care and 17 to exercise prehabilitation (26 males and 7 females). Exercise prehabilitation significantly improved VO2 at AT at week 9 compared to the usual care. The change from baseline to week 9, when adjusted for baseline, between the randomised groups was + 2.9 ml kg −1 min −1; (95% CI 0.8 to 5.1), p = 0.011. Conclusion: A 9-week exercise prehabilitation programme significantly improved fitness following NCRT. These findings have informed the WesFit trial (NCT03509428) which is investigating the effects of community-based multimodal prehabilitation before cancer surgery. Trial registration: ClinicalTrials.gov NCT01914068. Registered 1 August 2013. [ABSTRACT FROM AUTHOR]

The translation of MRS to clinical practice has been impeded by the lack of technical standardization. There are multiple methods of acquisition, post‐processing, and analysis whose details greatly impact the interpretation of the results. These details are often not fully reported, making it difficult to assess MRS studies on a standardized basis. This hampers the reviewing of manuscripts, limits the reproducibility of study results, and complicates meta‐analysis of the literature. In this paper a consensus group of MRS experts provides minimum guidelines for the reporting of MRS methods and results, including the standardized description of MRS hardware, data acquisition, analysis, and quality assessment. This consensus statement describes each of these requirements in detail and includes a checklist to assist authors and journal reviewers and to provide a practical way for journal editors to ensure that MRS studies are reported in full. [ABSTRACT FROM AUTHOR]

Skeletal muscle phosphorus‐31 31P MRS is the oldest MRS methodology to be applied to in vivo metabolic research. The technical requirements of 31P MRS in skeletal muscle depend on the research question, and to assess those questions requires understanding both the relevant muscle physiology, and how 31P MRS methods can probe it. Here we consider basic signal‐acquisition parameters related to radio frequency excitation, TR, TE, spectral resolution, shim and localisation. We make specific recommendations for studies of resting and exercising muscle, including magnetisation transfer, and for data processing. We summarise the metabolic information that can be quantitatively assessed with 31P MRS, either measured directly or derived by calculations that depend on particular metabolic models, and we give advice on potential problems of interpretation. We give expected values and tolerable ranges for some measured quantities, and minimum requirements for reporting acquisition parameters and experimental results in publications. Reliable examination depends on a reproducible setup, standardised preconditioning of the subject, and careful control of potential difficulties, and we summarise some important considerations and potential confounders. Our recommendations include the quantification and standardisation of contraction intensity, and how best to account for heterogeneous muscle recruitment. We highlight some pitfalls in the assessment of mitochondrial function by analysis of phosphocreatine (PCr) recovery kinetics. Finally, we outline how complementary techniques (near‐infrared spectroscopy, arterial spin labelling, BOLD and various other MRI and 1H MRS measurements) can help in the physiological/metabolic interpretation of 31P MRS studies by providing information about blood flow and oxygen delivery/utilisation. Our recommendations will assist in achieving the fullest possible reliable picture of muscle physiology and pathophysiology. [ABSTRACT FROM AUTHOR]

Key points: The post‐exercise recovery of phosphocreatine, a measure of the oxidative capacity of muscles, as assessed by 31P MR spectroscopy, shows a striking increase from distal to proximal along the human tibialis anterior muscle.To investigate why this muscle exhibits a greater oxidative capacity proximally, we tested whether the spatial variation in phosphocreatine recovery rate is related to oxygen supply, muscle fibre type or type of exercise.We revealed that oxygen supply also increases from distal to proximal along the tibialis anterior, and that it strongly correlated with phosphocreatine recovery. Carnosine level, a surrogate measure for muscle fibre type was not different between proximal and distal, and type of exercise did not affect the gradient in phosphocreatine recovery rate.Taken together, the findings of this study suggest that the post‐exercise spatial gradients in oxygen supply and phosphocreatine recovery are driven by a higher intrinsic mitochondrial oxidative capacity proximally. Phosphorus magnetic resonance spectroscopy (31P MRS) of human tibialis anterior (TA) revealed a strong proximo‐distal gradient in the post‐exercise phosphocreatine (PCr) recovery rate constant (kPCr), a measure of muscle oxidative capacity. The aim of this study was to investigate whether this kPCr gradient is related to O2 supply, resting phosphorylation potential, muscle fibre type, or type of exercise. Fifteen male volunteers performed continuous isometric ankle dorsiflexion at 30% maximum force until exhaustion. At multiple locations along the TA, we measured the oxidative PCr resynthesis rate (VPCr = kPCr × PCr depletion) by 31P MRS, the oxyhaemoglobin recovery rate constant (kO2Hb) by near infrared spectroscopy, and muscle perfusion with MR intravoxel incoherent motion imaging. The kO2Hb, kPCr, VPCr and muscle perfusion depended on measurement location (P < 0.001, P < 0.001, P = 0.032 and P = 0.003, respectively), all being greater proximally. The kO2Hb and muscle perfusion correlated with kPCr (r = 0.956 and r = 0.852, respectively) and VPCr (r = 0.932 and r = 0.985, respectively), the latter reflecting metabolic O2 consumption. Resting phosphorylation potential (PCr/inorganic phosphate) was also higher proximally (P < 0.001). The surrogate for fibre type, carnosine content measured by 1H MRS, did not differ between distal and proximal TA (P = 0.884). Performing intermittent exercise to avoid exercise ischaemia, still led to larger kPCr proximally than distally (P = 0.013). In conclusion, the spatial kPCr gradient is strongly associated with the spatial variation in O2 supply. It cannot be explained by exercise‐induced ischaemia nor by fibre type. Our findings suggest it is driven by a higher proximal intrinsic mitochondrial oxidative capacity, apparently to support contractile performance of the TA. Key points: The post‐exercise recovery of phosphocreatine, a measure of the oxidative capacity of muscles, as assessed by 31P MR spectroscopy, shows a striking increase from distal to proximal along the human tibialis anterior muscle.To investigate why this muscle exhibits a greater oxidative capacity proximally, we tested whether the spatial variation in phosphocreatine recovery rate is related to oxygen supply, muscle fibre type or type of exercise.We revealed that oxygen supply also increases from distal to proximal along the tibialis anterior, and that it strongly correlated with phosphocreatine recovery. Carnosine level, a surrogate measure for muscle fibre type was not different between proximal and distal, and type of exercise did not affect the gradient in phosphocreatine recovery rate.Taken together, the findings of this study suggest that the post‐exercise spatial gradients in oxygen supply and phosphocreatine recovery are driven by a higher intrinsic mitochondrial oxidative capacity proximally. [ABSTRACT FROM AUTHOR]

The hippocampus, a key structure with distinct subfield functions, is strongly implicated in the pathophysiology of post-traumatic stress disorder (PTSD); however, few studies of hippocampus subfields in PTSD have focused on pediatric patients. We therefore investigated the hippocampal subfield volume using an automated segmentation method and explored the subfield-centered functional connectivity aberrations related to the anatomical changes, in a homogenous population of traumatized children with and without PTSD. To investigate the potential diagnostic value in individual patients, we used a machine learning approach to identify features with significant discriminative power for diagnosis of PTSD using random forest classifiers. Compared to controls, we found significant mean volume reductions of 8.4% and 9.7% in the right presubiculum and hippocampal tail in patients, respectively. These two subfields' volumes were the most significant contributors to group discrimination, with a mean classification accuracy of 69% and a specificity of 81%. These anatomical alterations, along with the altered functional connectivity between (pre)subiculum and inferior frontal gyrus, may underlie deficits in fear circuitry leading to dysfunction of fear extinction and episodic memory, causally important in post-traumatic symptoms such as hypervigilance and re-experience. For the first time, we suggest that hippocampal subfield volumes might be useful in discriminating traumatized children with and without PTSD. [ABSTRACT FROM AUTHOR]

Obsessive–compulsive disorder (OCD) is a disabling neuropsychiatric disorder whose neurobiological basis remains unclear. Magnetic resonance imaging (MRI) studies have reported functional and structural alterations of the anterior cingulate cortex (ACC) in OCD. In this study, we explored the functional activity of subregions of the ACC and effective connectivity (EC) between ACC subregions and the whole brain in OCD. We used a Granger causality analysis (GCA) to identify the direction of information flow and whether the impact of that flow was excitatory or inhibitory. We performed resting‐state functional MRI in 31 patients with OCD and 36 healthy controls and analyzed the amplitude of low‐frequency fluctuation (ALFF) and coefficient‐based GCA. The left pregenual ACC (pACC) in patients with OCD showed decreased ALFF relative to controls. There was significantly decreased excitatory output from the left pACC to both right dorsal superior frontal gyrus (dSFG) and left precuneus in patients compared with controls. Patients also had decreased inhibitory input to left pACC from left ventral SFG and left thalamus and caudate relative to controls. Results were similar in drug‐naive patients and those with prior but not current psychopharmacological treatment. In patients, path coefficients of GCA from left pACC to right dSFG showed significant negative correlations with obsession and anxiety ratings. Decreased spontaneous neural activity and altered EC of pACC with widely distributed cortical circuitry, and associations with clinical ratings highlight the importance of pACC functional alteration in OCD. [ABSTRACT FROM AUTHOR]

This study explores the topological properties of brain gray matter (GM) networks in patients with paroxysmal kinesigenic dyskinesia (PKD) and asks whether GM network features have potential diagnostic value. We used 3D T1‐weighted magnetic resonance imaging and graph theoretical approaches to investigate the topological organization of GM morphological networks in 87 PKD patients and 115 age‐ and sex‐matched healthy controls. We applied a support vector machine to GM morphological network matrices to classify PKD patients versus healthy controls. Compared with the HC group, the GM morphological networks of PKD patients showed significant abnormalities at the global level, including an increase in characteristic path length (Lp) and decreases in local efficiency (Eloc), clustering coefficient (Cp), normalized clustering coefficient (γ), and small‐worldness (σ). The decrease in Cp was significantly correlated with disease duration and age of onset. The GM morphological networks of PKD patients also showed significant changes in nodal topological characteristics, mainly in the basal ganglia‐thalamus circuitry, default‐mode network and central executive network. Finally, we used the GM morphological network matrices to classify individuals as PKD patients versus healthy controls, achieving 87.8% accuracy. Overall, this study demonstrated disruption of GM morphological networks in PKD, which might extend our understanding of the pathophysiology of PKD; further, GM morphological network matrices might have the potential to serve as network neuroimaging biomarkers for the diagnosis of PKD. [ABSTRACT FROM AUTHOR]

This study aimed to define the most consistent white matter microarchitecture pattern in Parkinson's disease (PD) reflected by fractional anisotropy (FA), addressing clinical profiles and methodology-related heterogeneity. Web-based publication databases were searched to conduct a meta-analysis of whole-brain diffusion tensor imaging studies comparing PD with healthy controls (HC) using the anisotropic effect size–signed differential mapping. A total of 808 patients with PD and 760 HC coming from 27 databases were finally included. Subgroup analyses were conducted considering heterogeneity with respect to medication status, disease stage, analysis methods, and the number of diffusion directions in acquisition. Compared with HC, patients with PD had decreased FA in the left middle cerebellar peduncle, corpus callosum (CC), left inferior fronto-occipital fasciculus, and right inferior longitudinal fasciculus. Most of the main results remained unchanged in subgroup meta-analyses of medicated patients, early stage patients, voxel-based analysis, and acquisition with 30 diffusion directions. The subgroup meta-analysis of medication-free patients showed FA decrease in the right olfactory cortex. The cerebellum and CC, associated with typical motor impairment, showed the most consistent FA decreases in PD. Medication status, analysis approaches, and the number of diffusion directions have an important impact on the findings, needing careful evaluation in future meta-analyses. [ABSTRACT FROM AUTHOR]