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SUMMARY: Background and aims: Preoperative fasting induces metabolic stress and leads to reduced postoperative insulin sensitivity, changes attenuated by preoperative carbohydrate loading. However, the mechanisms underlying these effects remain unknown. We investigated the dynamic changes in substrate metabolism and mononuclear cell mitochondrial function after fasting followed by refeeding with a drink [ONS (Fresenius Kabi, Germany)] designed to improve metabolic function preoperatively. Methods: Twelve healthy volunteers took part in this study. They were fed a standardized meal and studied 4h later (baseline ‘fed’ state), after 12 and 24h of fasting, and 2, 4 and 6h after ingestion of ONS (contained 100g carbohydrate, 30g glutamine, and antioxidants). Changes in liver and muscle glycogen and lipids were studied using 13C and 1H magnetic resonance spectroscopy. The activities of mitochondrial electron transport chain complexes I, II and IV in blood mononuclear cells were measured spectrophotometrically. Results: Compared to the baseline fed state, 12 and 24h fasts led to 29% and 57% decreases (P <0.001) in liver glycogen content, respectively. Fasting for 24h decreased mitochondrial membrane complexes I (−72%, P <0.05), II (−49%, P <0.01) and IV (−41%, P <0.05) activities compared to those following a 12h fast. A 23% increase (P <0.05) in calf intramyocellular lipid (IMCL) content occurred after a 24h fast. Liver glycogen reserves increased by 47% (P<0.05) by 2h following ingestion of ONS. Conclusions: Short-term fasting (up to 24h) affected mononuclear cell mitochondrial function adversely and increased IMCL content. Refeeding with ONS partially reversed the changes in liver glycogen. [ABSTRACT FROM AUTHOR]

Background: Excessive heat exposure can lead to hyperthermia in humans, which impairs physical performance and disrupts cognitive function. While heat is a known physiological stressor, it is unclear how severe heat stress affects brain physiology and function., Methods: Eleven healthy participants were subjected to heat stress from prolonged exercise or warm water immersion until their rectal temperatures (T re ) attained 39.5°C, inducing exertional or passive hyperthermia, respectively. In a separate trial, blended ice was ingested before and during exercise as a cooling strategy. Data were compared to a control condition with seated rest (normothermic). Brain temperature (T br ), cerebral perfusion, and task-based brain activity were assessed using magnetic resonance imaging techniques., Results: T br in motor cortex was found to be tightly regulated at rest (37.3°C ± 0.4°C (mean ± SD)) despite fluctuations in T re . With the development of hyperthermia, T br increases and dovetails with the rising T re . Bilateral motor cortical activity was suppressed during high-intensity plantarflexion tasks, implying a reduced central motor drive in hyperthermic participants (T re  = 38.5°C ± 0.1°C). Global gray matter perfusion and regional perfusion in sensorimotor cortex were reduced with passive hyperthermia. Executive function was poorer under a passive hyperthermic state, and this could relate to compromised visual processing as indicated by the reduced activation of left lateral-occipital cortex. Conversely, ingestion of blended ice before and during exercise alleviated the rise in both T re and T br and mitigated heat-related neural perturbations., Conclusion: Severe heat exposure elevates T br , disrupts motor cortical activity and executive function, and this can lead to impairment of physical and cognitive performance., (Copyright © 2023. Production and hosting by Elsevier B.V.)

Objective: To study whether multimodal brain MRI comprising permeability and perfusion measures coupled with machine learning can predict neurocognitive function in young patients with SLE without neuropsychiatric manifestations., Methods: SLE patients and healthy controls (HCs) (≤40 years of age) underwent multimodal structural brain MRI that comprised voxel-based morphometry (VBM), magnetization transfer ratio (MTR) and dynamic contrast-enhanced (DCE) MRI in this cross-sectional study. Neurocognitive function assessed by Automated Neuropsychological Assessment Metrics was reported as the total throughput score (TTS). Olfactory function was assessed. A machine learning-based model (i.e. glmnet) was constructed to predict TTS., Results: Thirty SLE patients and 10 HCs were studied. Both groups had comparable VBM, MTR, olfactory bulb volume (OBV), olfactory function and TTS. While after correction for multiple comparisons the uncorrected increase in the blood-brain barrier (BBB) permeability parameters compared with HCs did not remain evident in SLE patients, DCE-MRI perfusion parameters, notably an increase in right amygdala perfusion, was positively correlated with TTS in SLE patients (r = 0.636, false discovery rate P < 0.05). A machine learning-trained multimodal MRI model comprising alterations of VBM, MTR, OBV and DCE-MRI parameters mainly in the limbic system regions predicted TTS in SLE patients (r = 0.644, P < 0.0005)., Conclusion: Multimodal brain MRI demonstrated increased right amygdala perfusion that was associated with better neurocognitive performance in young SLE patients without statistically significant BBB leakage and microstructural abnormalities. A machine learning-constructed multimodal model comprising microstructural, perfusion and permeability parameters accurately predicted neurocognitive performance in SLE patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: Provider bias has been shown to be a contributing factor to racial and ethnic disparities observed in health care settings. The purpose of this study was to examine implicit racial bias among dental hygienists., Methods: A convenience sample of licensed and practicing dental hygienists within the United States was recruited through email and national dental hygiene social media groups via snowball sampling. A two-part survey design was used for data collection. Participants completed a 10-item demographic survey through an online platform and were then routed to the Race Implicit Association Test (IAT). Descriptive statistics and linear regression analyses were used to compare demographic data and implicit racial preference scores (d-scores)., Results: Data from 404 licensed dental hygienists were included in this study. Over two-thirds (67.8%) of participants showed a preference for European Americans over African Americans. A significant difference was found between implicit racial preference scores and participant age (Estimate: 0.01, 95% CI: 0.00, 0.01), years worked comparing <5 years to 21 or more years (Estimate: 0.19, 95% CI: -0.30, -0.09) and race comparing non-White to White (Estimate: -0.17, 95% CI: -0.27, -0.07). No difference was found with task order, previous Race IAT experience, or previous self-reported implicit bias training., Conclusions: Findings suggest that dental hygienists may harbor implicit racial preferences for European Americans over African Americans. Non-White participants had more positive implicit preferences toward African Americans compared to White participants. Further research is needed to determine the extent to which implicit racial biases contribute to disparities in oral health., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose Provider bias has been shown to be a contributing factor to racial and ethnic disparities observed in health care settings. The purpose of this study was to examine implicit racial bias among dental hygienists. Methods A convenience sample of licensed and practicing dental hygienists within the United States was recruited through email and national dental hygiene social media groups via snowball sampling. A two-part survey design was used for data collection. Participants completed a 10-item demographic survey through an online platform and were then routed to the Race Implicit Association Test (IAT). Descriptive statistics and linear regression analyses were used to compare demographic data and implicit racial preference scores (d-scores). Results Data from 404 licensed dental hygienists were included in this study. Over two-thirds (67.8%) of participants showed a preference for European Americans over African Americans. A significant difference was found between implicit racial preference scores and participant age (Estimate: 0.01, 95% CI: 0.00, 0.01), years worked comparing <5 years to 21 or more years (Estimate: 0.19, 95% CI: -0.30, -0.09), and race comparing non-White to White (Estimate: -0.17, 95% CI: -0.27, -0.07). No difference was found with task order, previous Race IAT experience, or previous self-reported implicit bias training. Conclusion Findings suggest that dental hygienists may harbor implicit racial preferences for European Americans over African Americans. Non-White participants had more positive implicit preferences toward African Americans compared to White participants. Further research is needed to determine the extent to which implicit racial biases contribute to disparities in oral health., (Copyright © 2023 The American Dental Hygienists’ Association.)

Introduction: The classification of prostate cancer (PCa) lesions using Prostate Imaging Reporting and Data System (PI-RADS) suffers from poor inter-reader agreement. This study compared quantitative parameters or radiomic features from multiparametric magnetic resonance imaging (mpMRI) or positron emission tomography (PET), as inputs into machine learning (ML) to predict the Gleason scores (GS) of detected lesions for improved PCa lesion classification., Methods: 20 biopsy-confirmed PCa subjects underwent imaging before radical prostatectomy. A pathologist assigned GS from tumour tissue. Two radiologists and one nuclear medicine physician delineated the lesions on the mpMR and PET images, yielding 45 lesion inputs. Seven quantitative parameters were extracted from the lesions, namely T2-weighted (T2w) image intensity, apparent diffusion coefficient (ADC), transfer constant (K TRANS ), efflux rate constant (K ep ), and extracellular volume ratio (V e ) from mpMR images, and SUV mean and SUV max from PET images. Eight radiomic features were selected out of 109 radiomic features from T2w, ADC and PET images. Quantitative parameters or radiomic features, with risk factors of age, prostate-specific antigen (PSA), PSA density and volume, of 45 different lesion inputs were input in different combinations into four ML models - Decision Tree (DT), Support Vector Machine (SVM), k-Nearest-Neighbour (kNN), Ensembles model (EM)., Results: SUV max yielded the highest accuracy in discriminating detected lesions. Among the 4 ML models, kNN yielded the highest accuracies of 0.929 using either quantitative parameters or radiomic features with risk factors as input., Conclusions: ML models' performance is dependent on the input combinations and risk factors further improve ML classification accuracy., Competing Interests: Declaration of Competing Interest Josh Schaefferkoetter, Maurizio Conti and Lars Eriksson have full-time employment with Siemens Medical Solutions USA, Inc. The other authors declare that they have no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Mitochondrial dysfunction has been implicated in sarcopenia. 31 P magnetic resonance spectroscopy (MRS) enables non-invasive measurement of adenosine triphosphate (ATP) synthesis rates to probe mitochondrial function. Here, we assessed muscle energetics in older sarcopenic and non-sarcopenic men and compared with muscle biopsy-derived markers of mitochondrial function., Methods: Twenty Chinese men with sarcopenia (SARC, age = 73.1 ± 4.1 years) and 19 healthy aged and sex-matched controls (CON, age = 70.3 ± 4.2 years) underwent assessment of strength, physical performance, and magnetic resonance imaging. Concentrations of phosphocreatine (PCr), ATP and inorganic phosphate (Pi) as well as muscle pH were measured at rest and during an interleaved rest-exercise protocol to probe muscle mitochondrial function. Results were compared to biopsy-derived mitochondrial complex activity and expression to understand underlying metabolic perturbations., Results: Despite matched muscle contractile power (strength/cross-sectional area), the ATP contractile cost was higher in SARC compared with CON (low-intensity exercise: 1.06 ± 0.59 vs. 0.57 ± 0.22, moderate: 0.93 ± 0.43 vs. 0.58 ± 0.68, high: 0.70 ± 0.57 vs. 0.43 ± 0.51 mmol L -1  min -1  bar -1  cm -2 , P = 0.003, <0.0001 and <0.0001, respectively). Post-exercise mitochondrial oxidative synthesis rates (a marker of mitochondrial function) tended to be longer in SARC but did not reach significance (17.3 ± 6.4 vs. 14.6 ± 6.5 mmol L -1  min -1 , P = 0.2). However, relative increases in end-exercise ADP in SARC (31.8 ± 9.9 vs. 24.0 ± 7.3 mmol L -1 , P = 0.008) may have been a compensatory mechanism. Mitochondrial complex activity was found to be associated with exercise-induced drops in PCr [citrate synthetase activity (CS), Spearman correlation rho = -0.42, P = 0.03] and end-exercise ADP (complex III, rho = -0.52, P = 0.01; CS rho = -0.45, P = 0.02; SDH rho = -0.45, P = 0.03), with CS also being strongly associated with the PCr recovery rate following low intensity exercise (rho = -0.47, P = 0.02), and the cost of contraction at high intensity (rho = -0.54, P = 0.02). Interestingly, at high intensity, the fractional contribution of oxidative phosphorylation to exercise was correlated with activity in complex II (rho = 0.5, P = 0.03), CS (rho = 0.47, P = 0.02) and SDH (rho = 0.46, P = 0.03), linking increased mitochondrial complex activity with increased ability to generate energy through oxidative pathways., Conclusions: This study used 31 P MRS to assess ATP utilization and resynthesis in sarcopenic muscle and demonstrated abnormal increases in the energy cost during exercise and perturbed mitochondrial energetics in recovery. Associations between mitochondrial complex activity and the fractional contribution to energy requirement during exercise indicate increased ability to generate energy oxidatively in those with better mitochondrial complex activity., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Introduction: Links between maternal sensitivity, hippocampal development, and memory abilities suggests early life insensitive care may shape structures and schemas influencing future decisions and stress management, biasing children to negative information. While it is possible that this pattern of neurodevelopment may have adaptive consequences, for example, preventing children from encountering untoward experience with future adversity, it may also leave some children at risk for the development of internalizing problems., Methods: Here, in a Two Wave Study, we examine whether insensitive care predicts sub sequentially assessed memory biases for threatening (but not happy) stimuli in preschoolers ( n = 49), and if such relations cut across different forms of relational memory, i.e., memory for relations between two "items," between an "item" and its spatial location, and an "item" and its temporal sequence. In a subset ( n = 18) we also examine links between caregiving, memory, and hippocampal subregion volume., Results: Results indicate no main or interactive influence of gender on relational memory. However, insensitive caregiving predicted the difference between Angry and Happy memory during the Item-Space condition ( B = 2.451, se = 0.969, p = 0.014, 95% CI (0.572, 4.340)], as well as memory for Angry (but not Happy) items [ B = -2.203, se = 0.551, p < 0.001, 95% CI (-3.264,-1.094)]. Memory for the difference between Angry and Happy stimuli in the Space condition associated with larger right hippocampal body volumes (Rho = 0.639, p = 0.004). No relations were observed with internalizing problems., Discussion: Results are discussed with reference to developmental stage and in consideration of whether negative biases may serve as an intermediate factor linking early life insensitive care and later socioemotional problems including an increased incidence of internalizing disorders., Competing Interests: The 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 Rifkin-Graboi, Tsotsi, Syazwana, Stephenson, Sim and Lee.)

Background: Metabolic disruption commonly follows Anterior Cruciate Ligament Reconstruction (ACLR) surgery. Brief exposure to low amplitude and frequency pulsed electromagnetic fields (PEMFs) has been shown to promote in vitro and in vivo murine myogeneses via the activation of a calcium-mitochondrial axis conferring systemic metabolic adaptations. This randomized-controlled pilot trial sought to detect local changes in muscle structure and function using MRI, and systemic changes in metabolism using plasma biomarker analyses resulting from ACLR, with or without accompanying PEMF therapy., Methods: 20 patients requiring ACLR were randomized into two groups either undergoing PEMF or sham exposure for 16 weeks following surgery. The operated thighs of 10 patients were exposed weekly to PEMFs (1 ​mT for 10 ​min) for 4 months following surgery. Another 10 patients were subjected to sham exposure and served as controls to allow assessment of the metabolic repercussions of ACLR and PEMF therapy. Blood samples were collected prior to surgery and at 16 weeks for plasma analyses. Magnetic resonance data were acquired at 1 and 16 weeks post-surgery using a Siemens 3T Tim Trio system. Phosphorus ( 31 P) Magnetic Resonance Spectroscopy (MRS) was utilized to monitor changes in high-energy phosphate metabolism (inorganic phosphate (P i ), adenosine triphosphate (ATP) and phosphocreatine (PCr)) as well as markers of membrane synthesis and breakdown (phosphomonoesters (PME) and phosphodiester (PDE)). Quantitative Magnetization Transfer (qMT) imaging was used to elucidate changes in the underlying tissue structure, with T1-weighted and 2-point Dixon imaging used to calculate muscle volumes and muscle fat content., Results: Improvements in markers of high-energy phosphate metabolism including reductions in ΔP i /ATP, P i /PCr and (P i  ​+ ​PCr)/ATP, and membrane kinetics, including reductions in PDE/ATP were detected in the PEMF-treated cohort relative to the control cohort at study termination. These were associated with reductions in the plasma levels of certain ceramides and lysophosphatidylcholine species. The plasma levels of biomarkers predictive of muscle regeneration and degeneration, including osteopontin and TNNT1, respectively, were improved, whilst changes in follistatin failed to achieve statistical significance. Liquid chromatography with tandem mass spectrometry revealed reductions in small molecule biomarkers of metabolic disruption, including cysteine, homocysteine, and methionine in the PEMF-treated cohort relative to the control cohort at study termination. Differences in measurements of force, muscle and fat volumes did not achieve statistical significance between the cohorts after 16 weeks post-ACLR., Conclusion: The detected changes suggest improvements in systemic metabolism in the post-surgical PEMF-treated cohort that accords with previous preclinical murine studies. PEMF-based therapies may potentially serve as a manner to ameliorate post-surgery metabolic disruptions and warrant future examination in more adequately powered clinical trials., The Translational Potential of This Article: Some degree of physical immobilisation must inevitably follow orthopaedic surgical intervention. The clinical paradox of such a scenario is that the regenerative potential of the muscle mitochondrial pool is silenced. The unmet need was hence a manner to maintain mitochondrial activation when movement is restricted and without producing potentially damaging mechanical stress. PEMF-based therapies may satisfy the requirement of non-invasively activating the requisite mitochondrial respiration when mobility is restricted for improved metabolic and regenerative recovery., Competing Interests: AFO, JF and CB are inventors on patent WO 2019/17863 A1, System, and Method for Applying Pulsed Electromagnetic Fields, AFO and JF are contributors to QuantumTx Pte. Ltd., which elaborates electromagnetic field devices for human use. JZL is currently an employee of QuantumTx Pte. Ltd, but at the time of writing the manuscript was an employee of the NUS, Department of Surgery. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Nine previously proposed segmentation evaluation metrics, targeting medical relevance, accounting for holes, and added regions or differentiating over- and under-segmentation, were compared with 24 traditional metrics to identify those which better capture the requirements for clinical segmentation evaluation. Evaluation was first performed using 2D synthetic shapes to highlight features and pitfalls of the metrics with known ground truths (GTs) and machine segmentations (MSs). Clinical evaluation was then performed using publicly-available prostate images of 20 subjects with MSs generated by 3 different deep learning networks (DenseVNet, HighRes3DNet, and ScaleNet) and GTs drawn by 2 readers. The same readers also performed the 2D visual assessment of the MSs using a dual negative-positive grading of -5 to 5 to reflect over- and under-estimation. Nine metrics that correlated well with visual assessment were selected for further evaluation using 3 different network ranking methods - based on a single metric, normalizing the metric using 2 GTs, and ranking the network based on a metric then averaging, including leave-one-out evaluation. These metrics yielded consistent ranking with HighRes3DNet ranked first then DenseVNet and ScaleNet using all ranking methods. Relative volume difference yielded the best positivity-agreement and correlation with dual visual assessment, and thus is better for providing over- and under-estimation. Interclass Correlation yielded the strongest correlation with the absolute visual assessment (0-5). Symmetric-boundary dice consistently yielded good discrimination of the networks for all three ranking methods with relatively small variations within network. Good rank discrimination may be an additional metric feature required for better network performance evaluation., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Purpose: Various blood biomarkers reflecting brain amyloid-β (Aβ) load have recently been proposed with promising results. However, to date, no comparative study amongst blood biomarkers has been reported. Our objective was to examine the diagnostic performance and cost effectiveness of three blood biomarkers on the same cohort., Methods: Using the same cohort (n = 68), the performances of the single-molecule array (Simoa) Aβ40, Aβ42, Aβ42/Aβ40 and the amplified plasmonic exosome (APEX) Aβ42 blood biomarkers were compared using amyloid positron emission tomography (PET) as the reference standard. The extent to which these blood tests can reduce the recruitment cost of clinical trials was also determined by identifying amyloid positive (Aβ+) participants., Results: Compared to Simoa biomarkers, APEX-Aβ42 showed significantly higher correlations with amyloid PET retention values and excellent diagnostic performance (sensitivity 100%, specificity 93.3%, area under the curve 0.995). When utilized for clinical trial recruitment, our simulation showed that pre-screening with blood biomarkers followed by a confirmatory amyloid PET imaging would roughly half the cost (56.8% reduction for APEX-Aβ42 and 48.6% for Simoa-Aβ42/Aβ40) compared to the situation where only PET imaging is used. Moreover, with 100% sensitivity, APEX-Aβ42 pre-screening does not increase the required number of initial participants., Conclusions: With its high diagnostic performance, APEX is an ideal candidate for Aβ+ subject identification, monitoring and primary care screening, and could efficiently enrich clinical trials with Aβ+ participants whilst halving recruitment costs., (© 2020 European Academy of Neurology.)

Objective: To evaluate the association between brain amyloid β (Aβ) and cerebral small vessel disease (CSVD) markers, as well as their joint effect on cognition, in a memory clinic study., Methods: A total of 186 individuals visiting a memory clinic, diagnosed with no cognitive impairment, cognitive impairment no dementia (CIND), Alzheimer dementia (AD), or vascular dementia were included. Brain Aβ was measured by [ 11 C] Pittsburgh compound B-PET global standardized uptake value ratio (SUVR). CSVD markers including white matter hyperintensities (WMH), lacunes, and cerebral microbleeds (CMBs) were graded on MRI. Cognition was assessed by neuropsychological testing., Results: An increase in global SUVR is associated with a decrease in Mini-Mental State Examination (MMSE) in CIND and AD, as well as a decrease in global cognition Z score in AD, independent of age, education, hippocampal volume, and markers of CSVD. A significant interaction between global SUVR and WMH was found in relation to MMSE in CIND ( P for interaction: 0.009), with an increase of the effect size of Aβ (β = -6.57 [-9.62 to -3.54], p < 0.001) compared to the model without the interaction term (β = -2.91 [-4.54 to -1.29], p = 0.001)., Conclusion: Higher global SUVR was associated with worse cognition in CIND and AD, but was augmented by an interaction between global SUVR and WMH only in CIND. This suggests that Aβ and CSVD are independent processes with a possible synergistic effect between Aβ and WMH in individuals with CIND. There was no interaction effect between Aβ and lacunes or CMBs. Therefore, in preclinical phases of AD, WMH should be targeted as a potentially modifiable factor to prevent worsening of cognitive dysfunction., (© 2020 American Academy of Neurology.)

Prostate segmentation in multiparametric magnetic resonance imaging (mpMRI) can help to support prostate cancer diagnosis and therapy treatment. However, manual segmentation of the prostate is subjective and time-consuming. Many deep learning monomodal networks have been developed for automatic whole prostate segmentation from T2-weighted MR images. We aimed to investigate the added value of multimodal networks in segmenting the prostate into the peripheral zone (PZ) and central gland (CG). We optimized and evaluated monomodal DenseVNet, multimodal ScaleNet, and monomodal and multimodal HighRes3DNet, which yielded dice score coefficients (DSC) of 0.875, 0.848, 0.858, and 0.890 in WG, respectively. Multimodal HighRes3DNet and ScaleNet yielded higher DSC with statistical differences in PZ and CG only compared to monomodal DenseVNet, indicating that multimodal networks added value by generating better segmentation between PZ and CG regions but did not improve the WG segmentation. No significant difference was observed in the apex and base of WG segmentation between monomodal and multimodal networks, indicating that the segmentations at the apex and base were more affected by the general network architecture. The number of training data was also varied for DenseVNet and HighRes3DNet, from 20 to 120 in steps of 20. DenseVNet was able to yield DSC of higher than 0.65 even for special cases, such as TURP or abnormal prostate, whereas HighRes3DNet's performance fluctuated with no trend despite being the best network overall. Multimodal networks did not add value in segmenting special cases but generally reduced variations in segmentation compared to the same matched monomodal network., Competing Interests: The authors have no conflict of interest., (Copyright © 2020 Ying-Hwey Nai et al.)

Hippocampal atrophy and abnormal β-Amyloid (Aβ) deposition are established markers of Alzheimer's disease (AD). Nonetheless, longitudinal trajectory of Aβ-associated hippocampal subfield atrophy prior to dementia remains unclear. We hypothesized that elevated Aβ correlated with longitudinal subfield atrophy selectively in no cognitive impairment (NCI), spreading to other subfields in mild cognitive impairment (MCI). We analyzed data from two independent longitudinal cohorts of nondemented elderly, including global PET-Aβ in AD-vulnerable cortical regions and longitudinal subfield volumes quantified with a novel auto-segmentation method (FreeSurfer v.6.0). Moreover, we investigated associations of Aβ-related progressive subfield atrophy with memory decline. Across both datasets, we found a converging pattern that higher Aβ correlated with faster CA1 volume decline in NCI. This pattern spread to other hippocampal subfields in MCI group, correlating with memory decline. Our results for the first time suggest a longitudinal focal-to-widespread trajectory of Aβ-associated hippocampal subfield atrophy over disease progression in nondemented elderly., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Purpose: The analysis of the [ 11 C]PiB-PET amyloid images of a unique Asian cohort of 186 participants featuring overlapping vascular diseases raised the question about the validity of current standards for amyloid quantification under abnormal conditions. In this work, we implemented a novel pipeline for improved amyloid PET quantification of this atypical cohort., Methods: The investigated data correction and amyloid quantification methods included motion correction, standardized uptake value ratio (SUVr) quantification using the parcellated MRI (standard method) and SUVr quantification without MRI. We introduced a novel amyloid analysis method yielding 2 biomarkers: Aβ L which quantifies the global Aβ burden and ns that characterizes the non-specific uptake. Cut-off points were first determined using visual assessment as ground truth and then using unsupervised classification techniques., Results: Subject's motion impacts the accuracy of the measurement outcome but has however a limited effect on the visual rating and cut-off point determination. SUVr computation can be reliably performed for all the subjects without MRI parcellation while, when required, the parcellation failed or was of mediocre quality in 10% of the cases. The novel biomarker Aβ L showed an association increase of 29.5% with the cognitive tests and increased effect size between positive and negative scans compared with SUVr. ns was found sensitive to cerebral microbleeds, white matter hyperintensity, volume, and age. The cut-off points for SUVr using parcellated MRI, SUVr without parcellation, and Aβ L were 1.56, 1.39, and 25.5. Finally, k-means produced valid cut-off points without the requirement of visual assessment., Conclusion: The optimal processing for the amyloid quantification of this atypical cohort allows the quantification of all the subjects, producing SUVr values and two novel biomarkers: Aβ L , showing important increased in their association with various cognitive tests, and ns, a parameter sensitive to non-specific retention variations caused by age and cerebrovascular diseases.

Hypohydration exceeding 2% body mass can impair endurance capacity. It is postulated that the brain could be perturbed by hypohydration, leading to impaired motor performance. We investigated the neural effects of hypohydration with magnetic resonance imaging (MRI). Ten men were dehydrated to approximately -3% body mass by running on a treadmill at 65% maximal oxygen consumption (V̇o 2max ) before drinking to replace either 100% [euhydration (EU)] or 0% [hypohydration (HH)] of fluid losses. MRI was performed before start of trial (baseline) and after rehydration phase (post) to evaluate brain structure, cerebral perfusion, and functional activity. Endurance capacity assessed with a time-to-exhaustion run at 75% V̇o 2max was reduced with hypohydration (EU: 45.2 ± 9.3 min, HH: 38.4 ± 10.7 min; P = 0.033). Mean heart rates were comparable between trials (EU: 162 ± 5 beats/min, HH: 162 ± 4 beats/min; P = 0.605), but the rate of rise in rectal temperature was higher in HH trials (EU: 0.06 ± 0.01°C/min, HH: 0.07 ± 0.02°C/min; P < 0.01). In HH trials, a reduction in total brain volume (EU: +0.7 ± 0.6%, HH: -0.7 ± 0.9%) with expansion of ventricles (EU: -2.7 ± 1.6%, HH: +3.7 ± 3.3%) was observed, and vice versa in EU trials. Global and regional cerebral perfusion remained unchanged between conditions. Functional activation in the primary motor cortex in left hemisphere during a plantar-flexion task was similar between conditions (EU: +0.10 ± 1.30%, HH: -0.11 ± 0.31%; P = 0.637). Our findings demonstrate that with exertional hypohydration, brain volumes were altered but the motor-related functional activity was unperturbed. NEW & NOTEWORTHY Dehydration occurs rapidly during prolonged or intensive physical activity, leading to hypohydration if fluid replenishment is insufficient to replace sweat losses. Altered hydration status poses an osmotic challenge for the brain, leading to transient fluctuations in brain tissue and ventricle volumes. Therefore, the amount of fluid ingestion during exercise plays a critical role in preserving the integrity of brain architecture. These structural changes, however, did not translate directly to motor functional deficits in a simple motor task.

Despite intense interests in developing blood measurements of Alzheimer's disease (AD), the progress has been confounded by limited sensitivity and poor correlation to brain pathology. Here, we present a dedicated analytical platform for measuring different populations of circulating amyloid β (Aβ) proteins - exosome-bound vs. unbound - directly from blood. The technology, termed amplified plasmonic exosome (APEX), leverages in situ enzymatic conversion of localized optical deposits and double-layered plasmonic nanostructures to enable sensitive, multiplexed population analysis. It demonstrates superior sensitivity (~200 exosomes), and enables diverse target co-localization in exosomes. Employing the platform, we find that prefibrillar Aβ aggregates preferentially bind with exosomes. We thus define a population of Aβ as exosome-bound (Aβ42+ CD63+) and measure its abundance directly from AD and control blood samples. As compared to the unbound or total circulating Aβ, the exosome-bound Aβ measurement could better reflect PET imaging of brain amyloid plaques and differentiate various clinical groups.

Head motion occurring during brain PET studies leads to image blurring and to bias in measured local quantities. The objective of this work was to implement a correction method for PET data acquired with the mMR synchronous PET/MR scanner. Methods: A list-mode-based motion-correction approach has been designed. The developed rebinner chronologically reads the recorded events from the Siemens list-mode file, applies the estimated geometric transformations, and frames the detected counts into sinograms. The rigid-body motion parameters were estimated from an initial dynamic reconstruction of the PET data. We then optimized the correction for 11 C-Pittsburgh compound B ( 11 C-PIB) scans using simulated and actual data with well-controlled motion. Results: An efficient list-mode-based motion correction approach has been implemented, fully optimized, and validated using simulated and actual PET data. The average spatial resolution loss induced by inaccuracies in motion parameter estimates and by the rebinning process was estimated to correspond to a 1-mm increase in full width at half maximum with motion parameters estimated directly from the PET data with a temporal frequency of 20 s. The results show that the rebinner can be safely applied to the 11 C-PIB scans, allowing almost complete removal of motion-induced artifacts. The application of the correction method to a large cohort of 11 C-PIB scans led to the following observations: first, that more than 21% of the scans were affected by motion greater than 10 mm (39% for subjects with Mini-Mental State Examination scores below 20), and second, that the correction led to quantitative changes in Alzheimer-specific cortical regions of up to 30%. Conclusion: The rebinner allows accurate motion correction at a cost of minimal resolution reduction. Application of the correction to a large cohort of 11 C-PIB scans confirmed the necessity of systematically correcting for motion to obtain quantitative results., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

Mapping the brain alterations post stroke and post intervention is important for rehabilitation therapy development. Previous work has shown changes in functional connectivity based on resting-state fMRI, structural connectivity derived from diffusion MRI and perfusion as a result of brain-computer interface-assisted motor imagery (MI-BCI) and transcranial direct current stimulation (tDCS) in upper-limb stroke rehabilitation. Besides functional connectivity, regional amplitude of local low-frequency fluctuations (ALFF) may provide complementary information on the underlying neural mechanism in disease. Yet, findings on spontaneous brain activity during resting-state in stroke patients after intervention are limited and inconsistent. Here, we sought to investigate the different brain alteration patterns induced by tDCS compared to MI-BCI for upper-limb rehabilitation in chronic stroke patients using resting-state fMRI-based ALFF method. Our results suggested that stroke patients have lower ALFF in the ipsilesional somatomotor network compared to controls at baseline. Increased ALFF at contralesional somatomotor network and alterations in higher-level cognitive networks such as the default mode network (DMN) and salience networks accompany motor recovery after intervention; though the MI-BCI alone group and MI-BCI combined with tDCS group exhibit differential patterns.

The central nervous system, specifically the brain, is implicated in the development of exertional fatigue under a hot environment. Diverse neuroimaging techniques have been used to visualize the brain activity during or after exercise. Notably, the use of magnetic resonance imaging (MRI) has become prevalent due to its excellent spatial resolution and versatility. This review evaluates the significance and limitations of various brain MRI techniques in exercise studies-brain volumetric analysis, functional MRI, functional connectivity MRI, and arterial spin labeling. The review aims to provide a summary on the neural basis of exertional fatigue and proposes future directions for brain MRI studies. A systematic literature search was performed where a total of thirty-seven brain MRI studies associated with exercise, fatigue, or related physiological factors were reviewed. The findings suggest that with moderate dehydration, there is a decrease in total brain volume accompanied with expansion of ventricular volume. With exercise fatigue, there is increased activation of sensorimotor and cognitive brain areas, increased thalamo-insular activation and decreased interhemispheric connectivity in motor cortex. Under passive hyperthermia, there are regional changes in cerebral perfusion, a reduction in local connectivity in functional brain networks and an impairment to executive function. Current literature suggests that the brain structure and function are influenced by exercise, fatigue, and related physiological perturbations. However, there is still a dearth of knowledge and it is hoped that through understanding of MRI advantages and limitations, future studies will shed light on the central origin of exertional fatigue in the heat., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: In vivo 31 P magnetic resonance spectroscopy (MRS) magnetization transfer (MT) provides a direct measure of neuronal activity at the metabolic level. This work aims to use functional 31 P MRS-MT to investigate the change in cerebral adenosine triphosphate (ATP) metabolic rates in healthy adults upon repeated visual stimuli., Methods: A magnetization saturation transfer sequence with narrowband selective saturation of γ-ATP was developed for 31 P MT experiments at 3 T., Results: Using progressive saturation of γ-ATP, the intrinsic T 1 relaxation times of phosphocreatine (PCr) and inorganic phosphate (Pi) at 3 T were measured to be 5.1 ± 0.8 s and 3.0 ± 1.4 s, respectively. Using steady-state saturation of γ-ATP, a significant 24% ± 14% and 11% ± 7% increase in the forward creatine kinase (CK) pseudo-first-order reaction rate constant, k 1 , was observed upon visual stimulation in the first and second cycles, respectively, of a paradigm consisting of 10-minute rest followed by 10-minute stimulation, with the measured baseline k 1 being 0.35 ± 0.04 s -1 . No significant changes in forward ATP synthase reaction rate, PCr/γ-ATP, Pi/γ-ATP, and nicotinamide adenine dinucleotide/γ-ATP ratios, or intracellular pH were detected upon stimulation., Conclusion: This work demonstrates the potential of studying cerebral bioenergetics using functional 31 P MRS-MT to determine the change in the forward CK reaction rate at 3 T. Magn Reson Med 79:22-30, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., (© 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc.)

Background: The use of radiolabeled choline as a positron emission tomography (PET) agent for imaging primary tumors in the prostate has been evaluated extensively over the past two decades. There are, however, conflicting reports of its sensitivity and the relationship between choline PET imaging and disease staging is not fully understood. Moreover, relatively few studies have investigated the correlation between tracer uptake and histological tumor grade. This work quantified 18 F-fluorocholine in tumor and healthy prostate tissue using pharmacokinetic modeling and stratified uptake parameters by histology grade. Additionally, the effect of scan time on the estimation of the kinetic exchange rate constants was evaluated, and the tracer influx parameters from full compartmental analysis were compared to uptake values quantified by Patlak and standardized uptake value (SUV) analyses. 18 F-fluorocholine was administered as a 222 MBq bolus injection to ten patients with biopsy-confirmed prostate tumors, and dynamic PET data were acquired for 60 min. Image-derived arterial input functions were scaled by discrete blood samples, and a 2-tissue, 4-parameter model accounting for blood volume (2T4k+Vb) was used to perform fully quantitative compartmental modeling on tumor, healthy prostate, and muscle tissue. Subsequently, all patients underwent radical prostatectomy, and histological analyses were performed on the prostate specimens; kinetic parameters for tumors were stratified by Gleason score. Correlations were investigated between compartmental K 1 and K i parameters and SUV and Patlak slope; the effect of scan time on parameter bias was also evaluated., Results: Choline activity curves in seven tumors, eight healthy prostate regions, and nine muscle regions were analyzed. Net tracer influx was generally higher in tumor relative to healthy prostate, with the values in the highest grade tumors markedly higher than those in lower grade tumors. Influx terms from Patlak and full compartmental modeling showed good correlation within individual tissue groups. Kinetic parameters calculated from the entire 60-min scan data were accurately reproduced from the first 30 min of acquired data (R 2  ≈ 0.9)., Conclusions: Strong correlations were observed between K i and Patlak slope in tumor tissue, and K 1 and SUV were also correlated but to a lesser degree. Reliable estimates of all kinetic parameters can be achieved from the first 30 min of dynamic 18 F-choline data. Although SUV, K 1 , K i , and Patlak slope were found to be poor differentiators of low-grade tumor compared to healthy prostate tissue, they are strong indicators of aggressive disease.

Purpose: The purpose of this pilot study was to compare public perceptions of Idaho adults regarding oral cancer (OC) screening with other common cancer screenings including breast cancer (BC), prostate cancer (PC), and colon cancer (CC) screenings. Methods: This study utilized a convenience sample (N=100) of Idaho residents. A self-designed, validated interview-administered questionnaire was administered by a data collection service using computer-assisted telephone interview software to assess consumer perceptions about cancer screenings. Data were analyzed using descriptive statistics, frequencies, and Pearson's Chi-Square tests. Results: Participants were predominantly white (90%) with a mean age of 52.7 years with some post-high school education (80%) and the majority had received OC screenings (54%).The majority of participants perceived benefits of each specific cancer screening as very helpful: (a) OC screening (60%), (b) BC screening (79.2% females), (c) PC screening (63.8% males), and (d) CC screening (84%), and also reported no perceived risks regarding OC (80%), BC (60.4%), PC (66%) screening. Only 11% reported fear of finding cancer with an OC screening. The study findings supported significant associations (p<0.05) between consumer perceptions of cost and time as barriers to accessing all of the selected cancer screenings. Conclusion: This study identified associations between consumer perceptions of OC screening when compared with BC, PC, and CC. Concerns about cost and time for cancer screenings may reflect low consumer awareness regarding differences between OC and other cancer screenings. Future studies including larger samples representing more diverse populations are recommended to further explore the basis of participants' perceptions of cancer screenings and to identify ways to minimize barriers to cancer screenings., (Copyright © 2017 The American Dental Hygienists’ Association.)

Background: Impaired homeostasis of hepatic ATP has been associated with NAFLD. An intravenous fructose infusion has been shown to be an effective challenge to monitor the depletion and subsequent recovery of hepatic ATP reserves using (31)P MRS., Aims: The purpose of this study was to evaluate the effects of an oral rather than intravenous fructose challenge on hepatic ATP reserves in healthy subjects., Methods: Self-reported healthy males were recruited. Following an overnight fast, baseline liver glycogen and lipid levels were measured using Magnetic Resonance Spectroscopy (MRS). Immediately after consuming a 500 ml 75 g fructose drink (1275 kJ) subjects were scanned continuously for 90 min to acquire dynamic (31)P MRS measurements of liver ATP reserves., Results: A significant effect on ATP reserves was observed across the time course (P < 0.05). Mean ATP levels reached a minimum at 50 min which was markedly lower than baseline (80 ± 17% baseline, P < 0.05). Subsequently, mean values tended to rise but did not reach statistical significance above minimum. The time to minimum ATP levels across subjects was negatively correlated with BMI (R(2) = 0.74, P < 0.005). Rates of ATP recovery were not significantly correlated with BMI or liver fat levels, but were negatively correlated with baseline glycogen levels (R(2) = 0.7, P < 0.05)., Conclusions: Depletion of ATP reserves can be measured non-invasively following an oral fructose challenge using (31)P MRS. BMI is the best predictor of postprandial ATP homeostasis following fructose consumption., (Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Intragastric creaming and droplet size of fat emulsions may affect intragastric behavior and gastrointestinal and satiety responses., Objectives: We tested the hypotheses that gastrointestinal physiologic responses and satiety will be increased by an increase in intragastric stability and by a decrease in fat droplet size of a fat emulsion., Methods: This was a double-blind, randomized crossover study in 11 healthy persons [8 men and 3 women, aged 24 ± 1 y; body mass index (in kg/m(2)): 24.4 ± 0.9] who consumed meals containing 300-g 20% oil and water emulsion (2220 kJ) with 1) larger, 6-μm mean droplet size (Coarse treatment) expected to cream in the stomach; 2) larger, 6-μm mean droplet size with 0.5% locust bean gum (LBG; Coarse+LBG treatment) to prevent creaming; or 3) smaller, 0.4-μm mean droplet size with LBG (Fine+LBG treatment). The participants were imaged hourly by using MRI and food intake was assessed by using a meal that participants consumed ad libitum., Results: The Coarse+LBG treatment (preventing creaming in the stomach) slowed gastric emptying, resulting in 12% higher gastric volume over time (P < 0.001), increased small bowel water content (SBWC) by 11% (P < 0.01), slowed appearance of the (13)C label in the breath by 17% (P < 0.01), and reduced food intake by 9% (P < 0.05) compared with the Coarse treatment. The Fine+LBG treatment (smaller droplet size) slowed gastric emptying, resulting in 18% higher gastric volume (P < 0.001), increased SBWC content by 15% (P < 0.01), and significantly reduced food intake by 11% (P < 0.05, equivalent to an average of 411 kJ less energy consumed) compared with the Coarse+LBG treatment. These high-fat meals stimulated substantial increases in SBWC, which increased to a peak at 4 h at 568 mL (range: 150-854 mL; P < 0.01) for the Fine+LBG treatment., Conclusion: Manipulating intragastric stability and fat emulsion droplet size can influence human gastrointestinal physiology and food intake.

Tourette syndrome (TS) is a developmental neurological disorder characterized by vocal and motor tics and associated with cortical-striatal-thalamic-cortical circuit dysfunction, hyperexcitability within cortical motor areas, and altered intracortical inhibition. TS often follows a developmental time course in which tics become increasingly more controlled during adolescence in many individuals, who exhibit enhanced control over their volitional movements. Importantly, control over motor outputs appears to be brought about by a reduction in the gain of motor excitability. Here we present a neurochemical basis for a localized gain control mechanism. We used ultra-high-field (7 T) magnetic resonance spectroscopy to investigate in vivo concentrations of γ-aminobutyric acid (GABA) within primary and secondary motor areas of individuals with TS. We demonstrate that GABA concentrations within the supplementary motor area (SMA)--a region strongly associated with the genesis of motor tics in TS--are paradoxically elevated in individuals with TS and inversely related to fMRI blood oxygen level-dependent activation. By contrast, GABA concentrations in control sites do not differ from those of a matched control group. Importantly, we also show that GABA concentrations within the SMA are inversely correlated with cortical excitability in primary motor cortex and are predicted by motor tic severity and white-matter microstructure (FA) within a region of the corpus callosum that projects to the SMA within each hemisphere. Based upon these findings, we propose that extrasynaptic GABA contributes to a form of control, based upon localized tonic inhibition within the SMA, that may lead to the suppression of tics., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that alters cortical excitability in a polarity specific manner and has been shown to influence learning and memory. tDCS may have both on-line and after-effects on learning and memory, and the latter are thought to be based upon tDCS-induced alterations in neurochemistry and synaptic function. We used ultra-high-field (7 T) magnetic resonance spectroscopy (MRS), together with a robotic force adaptation and de-adaptation task, to investigate whether tDCS-induced alterations in GABA and Glutamate within motor cortex predict motor learning and memory. Note that adaptation to a robot-induced force field has long been considered to be a form of model-based learning that is closely associated with the computation and 'supervised' learning of internal 'forward' models within the cerebellum. Importantly, previous studies have shown that on-line tDCS to the cerebellum, but not to motor cortex, enhances model-based motor learning. Here we demonstrate that anodal tDCS delivered to the hand area of the left primary motor cortex induces a significant reduction in GABA concentration. This effect was specific to GABA, localised to the left motor cortex, and was polarity specific insofar as it was not observed following either cathodal or sham stimulation. Importantly, we show that the magnitude of tDCS-induced alterations in GABA concentration within motor cortex predicts individual differences in both motor learning and motor memory on the robotic force adaptation and de-adaptation task., (Copyright © 2014. Published by Elsevier Inc.)

Previous studies have reported a meal-induced rise in hepatic glycogen stores from baseline levels following a fast and it is generally assumed that glycogen levels rise steadily following meals throughout the day. However, measurements are normally taken in conditions that are not typical of the Western breakfast, which is relatively carbohydrate rich with a lower calorific content than most experimental test meals. As such, little is known about the normal metabolic response to a realistic, low calorie morning meal. Therefore, the aim of this pilot study was to evaluate the effects of a low dose oral glucose intake on hepatic glycogen levels following an overnight fast in healthy subjects. Glycogen levels were monitored in vivo using (13)C Magnetic Resonance Spectroscopy at baseline and hourly for 4 hours following either a 50 g glucose drink (773 kJ) or a control drink (0 kJ) given over two different visits. During the control visit hepatic glycogen levels decreased throughout the experiment with statistically significant decreases from baseline at 190 minutes (P < 0.05) and 250 minutes (P < 0.05). By contrast, the low dose glucose intake maintained glycogen concentrations with no significant decrease from baseline over 4 hours. A comparison between visits revealed that mean glycogen concentrations were significantly greater during the glucose visit (control visit, AUC = 218 ± 39 mol L(-1) min(-1); glucose visit, AUC = 305 ± 49 mol L(-1) min(-1); P < 0.05). Liver volume decreased significantly from baseline at 180 minutes (P < 0.05) post consumption in both groups, with no significant difference found between visits. Gastric content volumes were significantly higher for the glucose visit immediately following consumption (P < 0.001) and at 60 minutes (P = 0.007) indicating slower gastric emptying for the glucose compared with the control. In conclusion, following an overnight fast, a low dose oral glucose challenge prevents a reduction in hepatic glycogen content but does not increase it above fasted levels.

State of the art magnetic resonance imaging (MRI) scanners are generally equipped with multi-element receive coils; 16 or 32 channel coils are common. Their development has been predominant for parallel imaging to enable faster scanning. Less consideration has been given to localized magnetic resonance spectroscopy (MRS). Multinuclear studies, for example (31)P or (13)C MRS, are often conducted with a single element coil located over the region of interest. (1)H MRS studies have generally employed the same multi-element coils used for MRI, but little consideration has been given as to how the spectroscopic data from the different channels are combined. In many cases it is simply co-added with detrimental effect on the signal to noise ratio. In this study, we derive the optimum method for combining multi-coil data, namely weighting with the ratio of signal to the square of the noise. We show that provided that the noise is uncorrelated, this is the theoretical optimal combination. The method is demonstrated for in vivo proton MRS data acquired using a 32 channel receive coil at 7T in four different brain areas; left motor and right motor, occipital cortex and medial frontal cortex., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background & Aims: Diets high in fructose have been proposed to contribute to nonalcoholic fatty liver disease. We compared the effects of high-fructose and matched glucose intake on hepatic triacylglycerol (TAG) concentration and other liver parameters., Design: In a double-blind study, we randomly assigned 32 healthy but centrally overweight men to groups that received either a high-fructose or high-glucose diet (25% energy). These diets were provided during an initial isocaloric period of 2 weeks, followed by a 6-week washout period, and then again during a hypercaloric 2-week period. The primary outcome measure was hepatic level of TAG, with additional assessments of TAG levels in serum and soleus muscle, hepatic levels of adenosine triphosphate, and systemic and hepatic insulin resistance., Results: During the isocaloric period of the study, both groups had stable body weights and concentrations of TAG in liver, serum, and soleus muscle. The high-fructose diet produced an increase of 22 ± 52 μmol/L in the serum level of uric acid, whereas the high-glucose diet led to a reduction of 23 ± 25 μmol/L (P < .01). The high-fructose diet also produced an increase of 0.8 ± 0.9 in the homeostasis model assessment of insulin resistance, whereas the high-glucose diet produced an increase of only 0.1 ± 0.7 (P = .03). During the hypercaloric period, participants in the high-fructose and high-glucose groups had similar increases in weight (1.0 ± 1.4 vs 0.6 ± 1.0 kg; P = .29) and absolute concentration of TAG in liver (1.70% ± 2.6% vs 2.05% ± 2.9%; P = .73) and serum (0.36 ± 0.75 vs 0.33 ± 0.38 mmol/L; P = .91), and similar results in biochemical assays of liver function. Body weight changes were associated with changes in liver biochemistry and concentration of TAGs., Conclusions: In the isocaloric period, overweight men who were on a high-fructose or a high-glucose diet did not develop any significant changes in hepatic concentration of TAGs or serum levels of liver enzymes. However, in the hypercaloric period, both high-fructose and high-glucose diets produced significant increases in these parameters without any significant difference between the 2 groups. This indicates an energy-mediated, rather than a specific macronutrient-mediated, effect. Clinical trials.gov no: NCT01050140., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The measurement of tissue lipid and glycogen contents and the establishment of normal levels of variability are important when assessing changes caused by pathology or treatment. We measured hepatic and skeletal muscle lipid and glycogen levels using (1)H and (13)C MRS at 3 T in groups of subjects with and without type 2 diabetes. Within-visit reproducibility, due to repositioning and instrument errors was determined from repeat measurements made over 1 h. Natural variability was assessed from separate measurements made on three occasions over 1 month. Hepatic lipid content was greater in subjects with diabetes relative to healthy subjects (p = 0.03), whereas levels of hepatic and skeletal muscle glycogen, and of intra- and extra-myocellular lipid, were similar. The single-session reproducibility values (coefficient of variation, CV) for hepatic lipid content were 12% and 7% in groups of subjects with and without diabetes, respectively. The variability of hepatic lipid content over 1 month was greater than the reproducibility, with CV = 22% (p = 0.08) and CV = 44% (p = 0.004) in subjects with and without diabetes, respectively. Similarly, levels of variation in basal hepatic glycogen concentrations (subjects with diabetes, CV = 38%; healthy volunteers, CV = 35%) were significantly larger than single-session reproducibility values (CV = 17%, p = 0.02 and CV = 13%, p = 0.05, respectively), indicating substantial biological changes in basal concentrations over 1 month. There was a decreasing correlation in measurements of both hepatic lipid and glycogen content with increasing time between scans. Levels of variability in intra- and extra-myocellular lipid in the soleus muscle, and glycogen concentrations in the gastrocnemius muscle, tended to be larger than expected from single-session reproducibility, although these did not reach significance., (Copyright © 2013 John Wiley & Sons, Ltd.)

Objective: This study assessed whether high-resolution 7 T MRI allowed direct in vivo visualization of nigrosomes, substructures of the substantia nigra pars compacta (SNpc) undergoing the greatest and earliest dopaminergic cell loss in Parkinson disease (PD), and whether any disease-specific changes could be detected in patients with PD., Methods: Postmortem (PM) midbrains, 2 from healthy controls (HCs) and 1 from a patient with PD, were scanned with high-resolution T2*-weighted MRI scans, sectioned, and stained for iron and neuromelanin (Perl), TH, and calbindin. To confirm the identification of nigrosomes in vivo on 7 T T2*-weighted scans, we assessed colocalization with neuromelanin-sensitive T1-weighted scans. We then assessed the ability to depict PD pathology on in vivo T2*-weighted scans by comparing data from 10 patients with PD and 8 age- and sex-matched HCs., Results: A hyperintense, ovoid area within the dorsolateral border of the otherwise hypointense SNpc was identified in the HC brains on in vivo and PM T2*-weighted MRI. Location, size, shape, and staining characteristics conform to nigrosome 1. Blinded assessment by 2 neuroradiologists showed consistent bilateral absence of this nigrosome feature in all 10 patients with PD, and bilateral presence in 7/8 HC., Conclusions: In vivo and PM MRI with histologic correlation demonstrates that high-resolution 7 T MRI can directly visualize nigrosome 1. The absence of nigrosome 1 in the SNpc on MRI scans might prove useful in developing a neuroimaging diagnostic test for PD.

Proton magnetic resonance spectroscopy ((1)H-MRS) has been used to demonstrate metabolic changes in the visual cortex on visual stimulation. Small (2% to 11%) but significant stimulation induced increases in lactate, glutamate, and glutathione were observed along with decreases in aspartate, glutamine, and glycine, using (1)H-MRS at 7 T during single and repeated visual stimulation. In addition, decreases in glucose and increases in γ-aminobutyric acid (GABA) were seen but did not reach significance. Changes in glutamate and aspartate are indicative of increased activity of the malate-aspartate shuttle, which taken together with the opposite changes in glucose and lactate, reflect the expected increase in brain energy metabolism. These results are in agreement with those of Mangia et al. In addition, increases in glutamate and GABA coupled with the decrease in glutamine can be interpreted in terms of increased activity of the neurotransmitter cycles. An entirely new observation is the increase of glutathione during prolonged visual stimuli. The similarity of its time course to that of glutamate suggests that it may be a response to the increased release of glutamate or to the increased production of reactive oxygen species. Together, these observations constitute the most detailed analysis to date of functional changes in human brain metabolites.

In recent years the study of resting state brain networks (RSNs) has become an important area of neuroimaging. The majority of studies have used functional magnetic resonance imaging (fMRI) to measure temporal correlation between blood-oxygenation-level-dependent (BOLD) signals from different brain areas. However, BOLD is an indirect measure related to hemodynamics, and the electrophysiological basis of connectivity between spatially separate network nodes cannot be comprehensively assessed using this technique. In this paper we describe a means to characterize resting state brain networks independently using magnetoencephalography (MEG), a neuroimaging modality that bypasses the hemodynamic response and measures the magnetic fields associated with electrophysiological brain activity. The MEG data are analyzed using a unique combination of beamformer spatial filtering and independent component analysis (ICA) and require no prior assumptions about the spatial locations or patterns of the networks. This method results in RSNs with significant similarity in their spatial structure compared with RSNs derived independently using fMRI. This outcome confirms the neural basis of hemodynamic networks and demonstrates the potential of MEG as a tool for understanding the mechanisms that underlie RSNs and the nature of connectivity that binds network nodes.

Aim: To discuss the advantages of ultra-high field (7T) for (1)H and (13)C magnetic resonance spectroscopy (MRS) studies of metabolism., Methods: Measurements of brain metabolites were made at both 3 and 7T using (1)H MRS. Measurements of glycogen and lipids in muscle were measured using (13)C and (1)H MRS respectively., Results: In the brain, increased signal-to-noise ratio (SNR) and dispersion allows spectral separation of the amino-acids glutamate, glutamine and γ-aminobutyric acid (GABA), without the need for sophisticated editing sequences. Improved quantification of these metabolites is demonstrated at 7T relative to 3T. SNR was 36% higher, and measurement repeatability (% coefficients of variation) was 4%, 10% and 10% at 7T, vs 8%, 29% and 21% at 3T for glutamate, glutamine and GABA respectively. Measurements at 7T were used to compare metabolite levels in the anterior cingulate cortex (ACC) and insula. Creatine and glutamate levels were found to be significantly higher in the insula compared to the ACC (P < 0.05). In muscle, the increased SNR and spectral resolution at 7T enables interleaved studies of glycogen ((13)C) and intra-myocellular lipid (IMCL) and extra-myocellular lipid (EMCL) ((1)H) following exercise and re-feeding. Glycogen levels were significantly decreased following exercise (-28% at 50% VO(2) max; -58% at 75% VO(2) max). Interestingly, levels of glycogen in the hamstrings followed those in the quadriceps, despite reduce exercise loading. No changes in IMCL and EMCL were found in the study., Conclusion: The demonstrated improvements in brain and muscle MRS measurements at 7T will increase the potential for use in investigating human metabolism and changes due to pathologies.

Transcranial direct current stimulation (tDCS) modulates cortical excitability and is being used for human studies more frequently. Here we probe the underlying neuronal mechanisms by measuring polarity-specific changes in neurotransmitter concentrations using magnetic resonance spectroscopy (MRS). MRS provides evidence that excitatory (anodal) tDCS causes locally reduced GABA while inhibitory (cathodal) stimulation causes reduced glutamatergic neuronal activity with a highly correlated reduction in GABA, presumably due to the close biochemical relationship between the two neurotransmitters.

The transport of alpha-aminoisobutyrate into Pseudomonas fluorescens NCIB 8865 and membrane vesicles prepared from this organism has been studied. Uptake by cells was mediated by two active transport systems with different apparent Km values, while transport into membrane vesicles was mediated by a single component. The effect of inhibitors on the energy-coupling mechanism for alpha-aminoisobutyrate transport in these systems suggests that a membrane potential may play a significant role in supporting alpha-aminoisobutyrate transport. The magnitude of the membrane potential in the vesicle system, and the sensitivity of its generation to inhibitors, has been measured using 137Cs in the presence of valinomycin. Direct attempts to demonstrate a protonsymport mechanism for alpha-aminoisobutyrate transport were negative.

Iron chelated to the water-soluble extracellular iron-binding compound (exochelin) from Mycobacterium smegmatis was taken up by that organism by an energy-coupled transport system which was not found in M. bovis BCG or M. intracellulare. The uptake of iron from the chloroform-soluble exochelins produced by the latter two species was by an inhibitor-insenstive system which was also found in M. smegmatis.