Functional activation of pyruvate dehydrogenase in human brain using hyperpolarized [1-13 C]pyruvate.

PURPOSE: Pyruvate, produced from either glucose, glycogen, or lactate, is the dominant precursor of cerebral oxidative metabolism. Pyruvate dehydrogenase (PDH) flux is a direct measure of cerebral mitochondrial function and metabolism. Detection of [13 C]bicarbonate in the brain from hyperpolarized [1-13 C]pyruvate using carbon-13 (13 C) MRI provides a unique opportunity for assessing PDH flux in vivo. This study is to assess changes in cerebral PDH flux in response to visual stimuli using in vivo 13 C MRS with hyperpolarized [1-13 C]pyruvate. METHODS: From seven sedentary adults in good general health, time-resolved [13 C]bicarbonate production was measured in the brain using 90° flip angles with minimal perturbation of its precursors, [1-13 C]pyruvate and [1-13 C]lactate, to test the hypothesis that the appearance of [13 C]bicarbonate signals in the brain reflects the metabolic changes associated with neuronal activation. With a separate group of healthy participants (n = 3), the likelihood of the bolus-injected [1-13 C]pyruvate being converted to [1-13 C]lactate prior to decarboxylation was investigated by measuring [13 C]bicarbonate production with and without [1-13 C]lactate saturation. RESULTS: In the course of visual stimulation, the measured [13 C]bicarbonate signal normalized to the total 13 C signal in the visual cortex increased by 17.1% ± 15.9% (p = 0.017), whereas no significant change was detected in [1-13 C]lactate. Proton BOLD fMRI confirmed the regional activation in the visual cortex with the stimuli. Lactate saturation decreased bicarbonate-to-pyruvate ratio by 44.4% ± 9.3% (p < 0.01). CONCLUSION: We demonstrated the utility of 13 C MRS with hyperpolarized [1-13 C]pyruvate for assessing the activation of cerebral PDH flux via the detection of [13 C]bicarbonate production.

Altered linear coupling between stimulus-evoked blood flow and oxygen metabolism in the aging human brain.

Neural-vascular coupling (NVC) is the process by which oxygen and nutrients are delivered to metabolically active neurons by blood vessels. Murine models of NVC disruption have revealed its critical role in healthy neural function. We hypothesized that, in humans, aging exerts detrimental effects upon the integrity of the neural-glial-vascular system that underlies NVC. To test this hypothesis, calibrated functional magnetic resonance imaging (cfMRI) was used to characterize age-related changes in cerebral blood flow (CBF) and oxygen metabolism during visual cortex stimulation. Thirty-three younger and 27 older participants underwent cfMRI scanning during both an attention-controlled visual stimulation task and a hypercapnia paradigm used to calibrate the blood-oxygen-level-dependent signal. Measurement of stimulus-evoked blood flow and oxygen metabolism permitted calculation of the NVC ratio to assess the integrity of neural-vascular communication. Consistent with our hypothesis, we observed monotonic NVC ratio increases with increasing visual stimulation frequency in younger adults but not in older adults. Age-related changes in stimulus-evoked cerebrovascular and neurometabolic signal could not fully explain this disruption; increases in stimulus-evoked neurometabolic activity elicited corresponding increases in stimulus-evoked CBF in younger but not in older adults. These results implicate age-related, demand-dependent failures of the neural-glial-vascular structures that comprise the NVC system.

Resting cerebral oxygen metabolism exhibits archetypal network features.

Standard magnetic resonance imaging approaches offer high-resolution but indirect measures of neural activity, limiting understanding of the physiological processes associated with imaging findings. Here, we used calibrated functional magnetic resonance imaging during the resting state to recover low-frequency fluctuations of the cerebral metabolic rate of oxygen (CMRO2 ). We tested whether functional connections derived from these fluctuations exhibited organization properties similar to those established by previous standard functional and anatomical connectivity studies. Seventeen participants underwent 20 min of resting imaging during dual-echo, pseudocontinuous arterial spin labeling, and blood-oxygen-level dependent (BOLD) signal acquisition. Participants also underwent a 10 min normocapnic and hypercapnic procedure. Brain-wide, CMRO2 low-frequency fluctuations were subjected to graph-based and voxel-wise functional connectivity analyses. Results demonstrated that connections derived from resting CMRO2 fluctuations exhibited complex, small-world topological properties (i.e., high integration and segregation, cost efficiency) consistent with those observed in previous studies using functional and anatomical connectivity approaches. Voxel-wise CMRO2 connectivity also exhibited spatial patterns consistent with four targeted resting-state subnetworks: two association (i.e., frontoparietal and default mode) and two perceptual (i.e., auditory and occipital-visual). These are the first findings to support the use of calibration-derived CMRO2 low-frequency fluctuations for detecting brain-wide organizational properties typical of healthy participants. We discuss interpretations, advantages, and challenges in using calibration-derived oxygen metabolism signals for examining the intrinsic organization of the human brain.

Cerebrovascular Reactivity Mapping Using Resting-State BOLD Functional MRI in Healthy Adults and Patients with Moyamoya Disease.

Background Cerebrovascular reserve, the potential capacity of brain tissue to receive more blood flow when needed, is a desirable marker in evaluating ischemic risk. However, current measurement methods require acetazolamide injection or hypercapnia challenge, prompting a clinical need for resting-state (RS) blood oxygen level-dependent (BOLD) functional MRI data to measure cerebrovascular reactivity (CVR). Purpose To optimize and evaluate an RS CVR MRI technique and demonstrate its relationship to neurosurgical treatment. Materials and Methods In this HIPAA-compliant study, RS BOLD functional MRI data collected in 170 healthy controls between December 2008 and September 2010 were retrospectively evaluated to identify the optimal frequency range of temporal filtering on the basis of spatial correlation with the reference standard CVR map obtained with CO2 inhalation. Next, the optimized RS method was applied in a new, prospective cohort of 50 participants with Moyamoya disease who underwent imaging between June 2014 and August 2019. Finally, CVR values were compared between brain hemispheres with and brain hemispheres without revascularization surgery by using Mann-Whitney U test. Results A total of 170 healthy controls (mean age ± standard deviation, 51 years ± 20; 105 women) and 100 brain hemispheres of 50 participants with Moyamoya disease (mean age, 41 years ± 12; 43 women) were evaluated. RS CVR maps based on a temporal filtering frequency of [0, 0.1164 Hz] yielded the highest spatial correlation (r = 0.74) with the CO2 inhalation CVR results. In patients with Moyamoya disease, 77 middle cerebral arteries (MCAs) had stenosis. RS CVR in the MCA territory was lower in the group that did not undergo surgery (n = 30) than in the group that underwent surgery (n = 47) (mean, 0.407 relative units [ru] ± 0.208 vs 0.532 ru ± 0.182, respectively; P = .006), which is corroborated with the CO2 inhalation CVR data (mean, 0.242 ru ± 0.273 vs 0.437 ru ± 0.200; P = .003). Conclusion Cerebrovascular reactivity mapping performed by using resting-state blood oxygen level-dependent functional MRI provided a task-free method to measure cerebrovascular reserve and depicted treatment effect of revascularization surgery in patients with Moyamoya disease comparable to that with the reference standard of CO2 inhalation MRI. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Wolf and Ware in this issue.

Accurate determination of fractional retardations in photoelasticity through digital fringe multiplication.

Digital fringe multiplication is a useful technique for obtaining fractional fringe orders in photoelasticity at regions with very feeble retardations. In this paper, the effectiveness of the existing fringe multiplication techniques is investigated theoretically and experimentally. A new approach for fringe multiplication, using background nullified fringes, is developed to overcome the prevailing issues. Three options for obtaining background nullified fringe patterns are explained. Further, quadrature transformation of these fringe patterns is carried out to fetch uniform modulation. Moreover, a simplified fringe multiplication method is worked out to obtain fractional fringes from the uniformly modulated fringe patterns. The proposed procedures have been demonstrated through simulated as well as experimental images. A parametric study is carried out to understand the influence of pixel resolution and bit depth of the images on fringe multiplication. A criterion is established for finding out the maximum possible fringe multiplication for a given initial pixel/fringe resolution. It is observed that, for higher levels of fringe multiplication, larger bit depth of the image in conjunction with sufficient fringe resolution would be essential. The same also holds for fringe multiplication at areas with stress concentrations.

Computed time average digital holographic fringe pattern under random excitation.

Time average digital holography under random excitation or square wave excitation is established as an on-site non-destructive testing tool for defect detection in large metallic and composite sandwich structures due to its high sensitivity, single exposure interferogram, and fast inspection capability. However, extensive calibration studies are necessary to corroborate the defect type and defect size with the excitation frequency range and excitation magnitude. In this paper, a method to simulate a time average digital holographic fringe pattern under random excitation is proposed with the idea to minimize the number of calibration experiments and also for better evaluation of the size and type of defect. The proposed method circumvents the requirement for a closed form expression for the complex characteristic fringe function for time average interferometry under random excitation. The computed fringe pattern is illustratively compared with an experimental time average digital holographic fringe pattern.

The Vascular Basis of the Pronator Quadratus Muscle Flap and Its Use in Clinical Cases.

Background Pronator quadratus (PQ) is a deeply situated muscle in the forearm which may occasionally be utilized for soft-tissue reconstruction. The purpose of this anatomical and clinical study was to confirm vascular supply of PQ muscle (PQM) in order to optimize its transfer and confirm its utility in clinical situations. Methods In Part A of the anatomical study, fresh human cadavers ( n = 7) were prepared with an intra-arterial injection of lead oxide and gelatin solution, and PQM and neurovascular pedicle were dissected ( n = 14). In the anatomical study Part B, isolated limbs of embalmed human cadavers ( n = 12) were injected with India ink-gelatin mixture and PQ were dissected. Results PQ is a type II muscle flap, with one major pedicle, the anterior interosseous (AI) vessels and two minor pedicles from the radial and ulnar vessels. The mean dimensions of the muscle were 5.5 × 5.0 × 1.0 cm 3 , mean pedicle length was 9.6 cm, and the mean diameter of the artery and the vein was 2.3 mm and 2.8 mm, respectively. The dorsal cutaneous perforating branch (DPB) of the artery supplied the skin over the dorsal forearm and wrist. This branch also anastomosed with the 1, 2 intercompartmental supraretinacular artery (ICSRA). Conclusion This study confirms the potential utility and vascular basis of the PQM flap and its associated cutaneous paddle. In the clinical part, two patients with nonhealing wounds exposing the median nerve and flexor tendons in the distal forearm were treated using the PQM flap with good results.

Digital holographic study on the dynamic response of plates with geometric and material discontinuities simulating potted-insert metallic honeycomb sandwich structures.

The inspection of face sheet bonding, through optical interferometry techniques like holography and shearography, in potted-insert honeycomb-cored sandwich panels is different from the inspection of panels without inserts due to their complex response toward thermal and vibration stressing. In this paper, the dynamic responses of metallic honeycomb-cored sandwich structures with bonded and debonded inserts are studied using time-averaged digital holography and illustrated. At high frequencies, the face sheet regions at perfectly bonded inserts act as hard points, and regions across a debonded insert locally resonate in the sensitivity range of interferometry. Since the discontinuities created by such inserts are very complex to simulate numerically, we simulate potted-insert sandwich structures through plates with multiple holes and with multiple fully and partially bonded local stiffeners to validate this fast inspection procedure. The simulated dynamic response of the plates is compared with the time-averaged digital holography results. The operational deflection shapes near stiffeners are similar to those of fully potted inserts in a sandwich panel. Thus, the extent of debond can be evaluated at high frequencies as simulated through partially bonded stiffeners.

Calibrated imaging reveals altered grey matter metabolism related to white matter microstructure and symptom severity in multiple sclerosis.

Multiple sclerosis (MS) involves damage to white matter microstructures. This damage has been related to grey matter function as measured by standard, physiologically-nonspecific neuroimaging indices (i.e., blood-oxygen-level dependent signal [BOLD]). Here, we used calibrated functional magnetic resonance imaging and diffusion tensor imaging to examine the extent to which specific, evoked grey matter physiological processes were associated with white matter diffusion in MS. Evoked changes in BOLD, cerebral blood flow (CBF), and oxygen metabolism (CMRO2 ) were measured in visual cortex. Individual differences in the diffusion tensor measure, radial diffusivity, within occipital tracts were strongly associated with MS patients' BOLD and CMRO2 . However, these relationships were in opposite directions, complicating the interpretation of the relationship between BOLD and white matter microstructural damage in MS. CMRO2 was strongly associated with individual differences in patients' fatigue and neurological disability, suggesting that alterations to evoked oxygen metabolic processes may be taken as a marker for primary symptoms of MS. This work demonstrates the first application of calibrated and diffusion imaging together and details the first application of calibrated functional MRI in a neurological population. Results lend support for neuroenergetic hypotheses of MS pathophysiology and provide an initial demonstration of the utility of evoked oxygen metabolism signals for neurology research. Hum Brain Mapp 38:5375-5390, 2017. © 2017 Wiley Periodicals, Inc.

Investigation on vibration excitation of debonded sandwich structures using time-average digital holography.

Sandwich structures, in the modern aerospace industry, are more sought after due to their high strength to stiffness ratio resulting in significant weight gains. Optical techniques like time-average holography and shearography are preferred in industries for inspection of huge sandwich and composite panels because of whole-field (full coverage) inspection in a lesser time leading to large savings in cost. These techniques conventionally use sinusoidal frequency sweep to capture the local resonance of defective regions. This paper highlights the difficulties with the conventional approach of time-average digital holography (TADH) and proposes a novel defect identification strategy through square wave excitation. The proposed method enhances the speed and accuracy of inspection; thereby it saves cost and increases confidence level. Extensive experiments have been carried out using honeycomb sandwich panels to demonstrate the methodology.

On the optimization of imaging protocol for the mapping of cerebrovascular reactivity.

BACKGROUND: To devise an improved blood-oxygen-level-dependent (BOLD) imaging protocol for cerebrovascular reactivity (CVR) measurement that can remove a known artifact of negative values. METHODS: Theoretical and simulation studies were first performed to understand the biophysical mechanism of the negative CVR signals, through which improved BOLD sequence parameters were proposed. This was achieved by equating signal intensities between cerebrospinal fluid and blood, by means of shortening the echo time (TE) of the BOLD sequence. Then, 10 healthy volunteers were recruited to participate in an experimental study, in which we compared the CVR results of two versions of the optimized ("Opt1" and "Opt2") protocols with that of the standard protocol at 3 Tesla. Two sessions were performed for each subject to test the reproducibility of all three protocols. RESULTS: Experimental results demonstrated that the optimized protocols resulted in elimination of negative-CVR voxels. Quantitative CVR results were compared across protocols, which show that the optimized protocols yielded smaller CVR values (Opt1: 0.16 ± 0.01 %BOLD/mmHg CO2 ; Opt2: 0.15 ± 0.01 %BOLD/mmHg CO2 ) than (P < 0.001) the standard protocol (0.21 ± 0.01 %BOLD/mmHg CO2 ), but the CNR was comparable (P = 0.1) to the standard protocol. The coefficient-of-variation between repetitions was found to be 5.6 ± 1.4%, 6.3 ± 1.6%, and 6.9 ± 0.9% for the three protocols, but there were no significant differences (P = 0.65). CONCLUSION: Based on the theoretical and experimental results obtained from this study, we suggest that the use of a TE shorter than those used in fMRI is necessary to minimize negative artifact in CVR results.

An algorithmic approach to the management of peripheral nerve tumours.

This article reviews the pathology and management of peripheral nerve tumours, including a framework for investigation and decision-making. Most tumours are benign, including schwannomas and neurofibromas, but malignant peripheral nerve sheath tumours can occur. The risk of malignant change is remote for schwannomas but higher for neurofibromas, particularly in neurofibromatosis type 1. Magnetic resonance imaging is useful for defining the relationship of a swelling with adjacent nerves but is not definitive for tissue diagnosis. Increasing size, pain and neurological deficit suggest malignant change and TruCut needle biopsy is indicated, although there is a risk of sampling error. Excision biopsy preserving nerve function may be carried out for benign tumours to relieve symptoms. Malignant tumours require a multidisciplinary approach. Complete surgical excision with clear margins is the only curative treatment and may be supplemented with radiotherapy and chemotherapy. However, prognosis remains poor, particularly for patients with neurofibromatosis.

Physiologic underpinnings of negative BOLD cerebrovascular reactivity in brain ventricles.

With a growing need for specific biomarkers in vascular diseases, there has been a surging interest in mapping cerebrovascular reactivity (CVR) of the brain. This index can be measured by conducting a hypercapnia challenge while acquiring blood-oxygenation-level-dependent (BOLD) signals. A BOLD signal increase with hypercapnia is the expected outcome and represents the majority of literature reports; in this work we report an intriguing observation of an apparently negative BOLD CVR response at 3T, during inhalation of 5% CO2 with balance medical air. These "negative-CVR" clusters were specifically located in the ventricular regions of the brain, where CSF is abundant and results in an intense baseline signal. The amplitude of the CVR response was -0.51±0.44% (N=14, age 26±4 years). We hypothesized that this observation might not be due to a decrease in oxygenation but rather a volume effect in which bright CSF signal is replaced by a less intensive blood signal as a result of vasodilation. To test this, we performed an inversion-recovery (IR) experiment to suppress the CSF signal (N=10, age 27±5 years). This maneuver in imaging sequence reversed the sign of the signal response (to 0.66±0.25%), suggesting that the volume change was the predominant reason for the apparently negative CVR in the BOLD experiment. Further support of this hypothesis was provided by a BOLD hyperoxia experiment, in which no voxels showed a negative response, presumably because vasodilation is not usually associated with this challenge. Absolute CBF response to hypercapnia was measured in a new group of subjects (N=8, age 29±7 years) and it was found that CBF in ventricular regions increased by 48% upon CO2 inhalation, suggesting that blood oxygenation most likely increased rather than decreased. The findings from this study suggest that CO2 inhalation results in the dilation of ventricular vessels accompanied by shrinkage in CSF space, which is responsible for the apparently negative CVR in brain ventricles.

Life-long aerobic exercise preserved baseline cerebral blood flow but reduced vascular reactivity to CO2.

PURPOSE: To examine the potential benefits of life-long aerobic exercise on brain health, in particular cerebrovascular function. MATERIALS AND METHODS: Ten Masters athletes (MA) (seven males, three females; 74.5 ± 5.8 years) and 10 sedentary elderly individuals (SE) (eight males, two females; 75.4 ± 5.6 years) were recruited and baseline cerebral blood flow (CBF) and cerebral vascular reactivity (CVR) to CO2 were measured on a 3T MRI scanner. Nine sedentary young subjects were also recruited to serve as a control group to verify the age effect. RESULTS: When compared to the SE group, MA showed higher CBF in posterior cingulate cortex/precuneus, which are key regions of the default-mode-network and are known to be highly sensitive to age and dementia. CVR in the MA brains were paradoxically lower than that in SE. This effect was present throughout the brain. Within the MA group, individuals with higher VO2max had an even lower CVR, suggesting a dose-response relationship. CONCLUSION: Life-long aerobic exercise preserved blood supply in the brain's default-mode-network against age-related degradation. On the other hand, its impact on the cerebral vascular system seems to be characterized by a dampening of CO2 reactivity, possibly because of desensitization effects due to a higher lifetime exposure.

Deep-learning-enabled brain hemodynamic mapping using resting-state fMRI.

Cerebrovascular disease is a leading cause of death globally. Prevention and early intervention are known to be the most effective forms of its management. Non-invasive imaging methods hold great promises for early stratification, but at present lack the sensitivity for personalized prognosis. Resting-state functional magnetic resonance imaging (rs-fMRI), a powerful tool previously used for mapping neural activity, is available in most hospitals. Here we show that rs-fMRI can be used to map cerebral hemodynamic function and delineate impairment. By exploiting time variations in breathing pattern during rs-fMRI, deep learning enables reproducible mapping of cerebrovascular reactivity (CVR) and bolus arrival time (BAT) of the human brain using resting-state CO2 fluctuations as a natural "contrast media". The deep-learning network is trained with CVR and BAT maps obtained with a reference method of CO2-inhalation MRI, which includes data from young and older healthy subjects and patients with Moyamoya disease and brain tumors. We demonstrate the performance of deep-learning cerebrovascular mapping in the detection of vascular abnormalities, evaluation of revascularization effects, and vascular alterations in normal aging. In addition, cerebrovascular maps obtained with the proposed method exhibit excellent reproducibility in both healthy volunteers and stroke patients. Deep-learning resting-state vascular imaging has the potential to become a useful tool in clinical cerebrovascular imaging.

Non-contrast hemodynamic imaging of Moyamoya disease with MR fingerprinting ASL: A feasibility study.

PURPOSE: MR Fingerprinting (MRF) Arterial Spin Labeling (ASL) is a non-contrast technique to estimate multiple brain hemodynamic and structural parameters in a single scan. The purpose of this study is to examine the feasibility and initial utility of MRF-ASL in Moyamoya disease. METHODS: MRF-ASL, conventional single-delay ASL, Time-of-flight (TOF) MR angiography, and contrast-based dynamic-susceptibility-contrast (DSC) MRI were prospectively collected from a group of Moyamoya patients in North America (N = 21, 4 men and 17 women). Sixteen healthy subjects (7 men and 9 women) also underwent an MRF-ASL scan. Cerebral blood flow (CBF), bolus arrival time (BAT), and tissue T1 were compared between Moyamoya patients and healthy controls. Perfusion parameters from MRF-ASL were compared to those from other MRI sequences. Multi-linear regression was used for comparisons of parameter values between Moyamoya and control groups. Linear mixed-effects models was used when comparing MRF-ASL to PCASL and DSC parameters. Spearman's Rank Correlation Coefficient was calculated when comparing MRF-ASL to and MRA grades. A P value of 0.05 or less was considered significant. RESULTS: BAT in stenotic internal carotid artery (ICA) territories was prolonged (P < 0.001) in Moyamoya patients, when compared with healthy controls. CBF in stenotic ICA territories of Moyamoya patients was not different from CBF in healthy controls; but in the PCA territories, CBF in Moyamoya patients was higher (P < 0.01) than controls. Quantitative T1 values in the stenotic ICA territories was longer (P < 0.05) than that in controls. Hemodynamic parameters estimated from MRF-ASL were significantly correlated with single-delay ASL and DSC. Longer BAT was associated with more severe intracranial artery stenosis in ICA. CONCLUSIONS: MRF-ASL is a promising technique to assess perfusion and structural abnormalities in Moyamoya patients.

Cognition and brain oxygen metabolism improves after bariatric surgery-induced weight loss: A pilot study.

Objective: The primary objectives of this pilot study were to assess cognition and cerebral metabolic rate of oxygen (CMRO2) consumption in people with severe obesity before (baseline), and again, 2- and 14-weeks after sleeve gastrectomy bariatric surgery. Methods: Six people with severe/class 3 obesity (52 ± 10 years, five females, body mass index (BMI) = 41.9 ± 3.9 kg/m2), and 10 normal weight sex- and age-matched healthy controls (HC) (48 ± 6 years, eight females, 22.8 ± 1.9 kg/m2). Global CMRO2 was measured non-invasively using MRI and cognition using the Integneuro testing battery. Results: Following a sleeve gastrectomy induced weight loss of 6.4 ± 2.5 kg (% total-body-weight-lost = 5.4) over two-weeks, cognition total scores improved by 0.8 ± 0.5 T-scores (p=0.03, 15.8% improvement from baseline). Weight loss over 14-weeks post-surgery was 15.4 ± 3.6 kg (% total-body-weight-lost = 13.0%) and cognition improved by 1.1 ± 0.4 (p=0.003, 20.6% improvement from baseline). At 14-weeks, cognition was 6.4 ± 0.7, comparable to 6.0 ± 0.6 observed in the HC group. Baseline CMRO2 was significantly higher compared to the HC (230.4 ± 32.9 vs. 177.9 ± 33.9 µmol O2/100 g/min, p=0.02). Compared to baseline, CMRO2 was 234.3 ± 16.2 µmol O2/100 g/min at 2-weeks after surgery (p=0.8, 1.7% higher) and 217.3 ± 50.4 at 14-weeks (p=0.5, 5.7% lower) after surgery. 14-weeks following surgery, CMRO2 was similar to HC (p=0.17). Conclusion: Sleeve gastrectomy induced weight loss was associated with an increase in cognition and a decrease in CMRO2 observed 14-weeks after surgery. The association between weight loss, improved cognition and CMRO2 decrease should be evaluated in larger future studies.

Evaluation of noise regression techniques in resting-state fMRI studies using data of 434 older adults.

Subject motion is a well-known confound in resting-state functional MRI (rs-fMRI) and the analysis of functional connectivity. Consequently, several clean-up strategies have been established to minimize the impact of subject motion. Physiological signals in response to cardiac activity and respiration are also known to alter the apparent rs-fMRI connectivity. Comprehensive comparisons of common noise regression techniques showed that the "Independent Component Analysis based strategy for Automatic Removal of Motion Artifacts" (ICA-AROMA) was a preferred pre-processing technique for teenagers and adults. However, motion and physiological noise characteristics may differ substantially for older adults. Here, we present a comprehensive comparison of noise-regression techniques for older adults from a large multi-site clinical trial of exercise and intensive pharmacological vascular risk factor reduction. The Risk Reduction for Alzheimer's Disease (rrAD) trial included hypertensive older adults (60-84 years old) at elevated risk of developing Alzheimer's Disease (AD). We compared the performance of censoring, censoring combined with global signal regression, non-aggressive and aggressive ICA-AROMA, as well as the Spatially Organized Component Klassifikator (SOCK) on the rs-fMRI baseline scans from 434 rrAD subjects. All techniques were rated based on network reproducibility, network identifiability, edge activity, spatial smoothness, and loss of temporal degrees of freedom (tDOF). We found that non-aggressive ICA-AROMA did not perform as well as the other four techniques, which performed table with marginal differences, demonstrating the validity of these techniques. Considering reproducibility as the most important factor for longitudinal studies, given low false-positive rates and a better preserved, more cohesive temporal structure, currently aggressive ICA-AROMA is likely the most suitable noise regression technique for rs-fMRI studies of older adults.

Hippocampal and rostral anterior cingulate blood flow is associated with affective symptoms in chronic traumatic brain injury.

OBJECTIVE: The purpose of this study was to assess cerebral blood flow (CBF) and its association with self-reported symptoms in chronic traumatic brain injury (TBI). PARTICIPANTS: Sixteen participants with mild to severe TBI and persistent self-reported neurological symptoms, 6 to 72 months post-injury were included. For comparison, 16 age- and gender-matched healthy normal control participants were also included. MAIN MEASURES: Regional CBF and brain volume were assessed using pseudo-continuous Arterial Spin Labeling (PCASL) and T1-weighted data respectively. Cognitive function and self-reported symptoms were assessed in TBI participants using the national institutes of health (NIH) Toolbox Cognition Battery and Patient-Reported Outcome Measurement Information System respectively. Associations between CBF and cognitive function, symptoms were assessed. RESULTS: Global CBF and regional brain volumes were similar between groups, but region of interest (ROI) analysis revealed lower CBF bilaterally in the thalamus, hippocampus, left caudate, and left amygdala in the TBI group. Voxel-wise analysis revealed that CBF in the hippocampus, parahippocampus, rostral anterior cingulate, inferior frontal gyrus, and other temporal regions were negatively associated with self-reported anger, anxiety, and depression symptoms. Furthermore, region of interest (ROI) analysis revealed that hippocampal and rostral anterior cingulate CBF were negatively associated with symptoms of fatigue, anxiety, depression, and sleep issues. CONCLUSION: Regional CBF deficit was observed in the group with chronic TBI compared to the normal control (NC) group despite similar volume of cerebral structures. The observed negative correlation between regional CBF and affective symptoms suggests that CBF-targeted intervention may potentially improve affective symptoms and quality of life after TBI, which needs to be assessed in future studies.

Congenital thumb differences- current concepts.

Anomalies of the thumb development are not uncommon and may be associated with a number of syndromes also. These anomalies range from total absence to duplication. Reconstructive surgery for the creation of an opposable thumb is the most rewarding aspect of Hand Surgery and also the most challenging. Classification systems have been modified for better description. A number of procedures have been introduced to improve the functionality of the hand in anomalies and age old concepts are undergoing a metamorphosis to further this. A brief description of the common conditions and their treatment are discussed here and highlighted by selected clinical cases.