Longitudinal Assessment of Glymphatic Changes Following Mild Traumatic Brain Injury: Insights from PVS burden and DTI-ALPS Imaging.

Traumatic brain injury (TBI) even in the mild form may result in long-lasting post-concussion symptoms. TBI is also a known risk to late-life neurodegeneration. Recent studies suggest that dysfunction in the glymphatic system, responsible for clearing protein waste from the brain, may play a pivotal role in the development of dementia following TBI. Given the diverse nature of TBI, longitudinal investigations are essential to comprehending the dynamic changes in the glymphatic system and its implications for recovery. In this prospective study, we evaluated two promising glymphatic imaging markers, namely the enlarged perivascular space (ePVS) burden and Diffusion Tensor Imaging-based ALPS index, in 44 patients with mTBI at two early post-injury time points: approximately 14 days (14Day) and 6-12 months (6-12Mon) post-injury, while also examining their associations with post-concussion symptoms. Additionally, 37 controls, comprising both orthopedic patients and healthy individuals, were included for comparative analysis. Our key findings include: 1) White matter ePVS burden (WM-ePVS) and ALPS index exhibit significant correlations with age. 2) Elevated WM-ePVS burden in acute mTBI (14Day) is significantly linked to a higher number of post-concussion symptoms, particularly memory problems. 3) The increase in the ALPS index from acute (14Day) to the chronic (6-12Mon) phases in mTBI patients correlates with improvement in sleep measures. Furthermore, incorporating WM-ePVS burden and the ALPS index from acute phase enhances the prediction of chronic memory problems beyond socio-demographic and basic clinical information, highlighting their distinct roles in assessing glymphatic structure and activity. Early evaluation of glymphatic function could be crucial for understanding TBI recovery and developing targeted interventions to improve patient outcomes.

Simultaneous Measurement of GABA, Glutathione, and Glutamate-Glutamine in the Thalamus using Edited MR Spectroscopy: Feasibility and Applications in Traumatic Brain Injury.

BACKGROUND: MR spectroscopy (MRS) is a noninvasive tool for evaluating biochemical alterations, such as glutamate (Glu)/gamma-aminobutyric acid (GABA) imbalance and depletion of antioxidative glutathione (GSH) after traumatic brain injury (TBI). Thalamus, a critical and vulnerable region post-TBI, is challenging for MRS acquisitions, necessitating optimization to simultaneously measure GABA/Glu and GSH. PURPOSE: To assess the feasibility and optimize acquisition and processing approaches for simultaneously measuring GABA, Glx (Glu + glutamine (Gln)), and GSH in the thalamus, employing Hadamard encoding and reconstruction of MEscher-GArwood (MEGA)-edited spectroscopy (HERMES). STUDY TYPE: Prospective. SUBJECTS: 28 control subjects (age: 35.9 ± 15.1 years), and 17 mild TBI (mTBI) patients (age: 32.4 ± 11.3 years). FIELD STRENGTH/SEQUENCE: 3T/T1-weighted magnetization-prepared rapid gradient-echo (MP-RAGE), HERMES. ASSESSMENT: We evaluated the impact of acquisition with spatial saturation bands and post-processing with spectral alignment on HERMES performance in the thalamus among controls. Within-subject variability was examined in five controls through repeated scans within a week. The HERMES spectra in the posterior cingulate cortex (PCC) of controls were used as a reference for assessing HERMES performance in a reliable target. Furthermore, we compared metabolite levels and fitting quality in the thalamus between mTBI patients and controls. STATISTICAL TESTS: Unpaired t-tests and within-subject coefficient-of-variation (CV). A P-value <0.05 was deemed significant. RESULTS: HERMES spectra, acquired with saturation bands and processed with spectral alignment, yielded reliable metabolite measurements in the thalamus. The mean within-subject CV for GABA, Glx, and GSH levels were 18%, 10%, and 16% in the thalamus (7%, 9%, and 16% in the PCC). GABA (3.20 ± 0.60 vs 2.51 ± 0.55, P < 0.01) and Glx (8.69 ± 1.23 vs 7.72 ± 1.19, P = 0.03) levels in the thalamus were significantly higher in mTBI patients than in controls, with GSH (1.27 ± 0.35 vs 1.22 ± 0.28, P = 0.65) levels showing no significant difference. DATA CONCLUSION: Simultaneous measuring GABA/Glx and GSH using HERMES is feasible in the thalamus, providing valuable insight into TBI. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Automatic Quantification of Enlarged Perivascular Space in Patients With Traumatic Brain Injury Using Super-Resolution of T2-Weighted Images.

The perivascular space (PVS) is important to brain waste clearance and brain metabolic homeostasis. Enlarged PVS (ePVS) becomes visible on magnetic resonance imaging (MRI) and is best appreciated on T2-weighted (T2w) images. However, quantification of ePVS is challenging because standard-of-care T1-weighted (T1w) and T2w images are often obtained via two-dimensional (2D) acquisition, whereas accurate quantification of ePVS normally requires high-resolution volumetric three-dimensional (3D) T1w and T2w images. The purpose of this study was to investigate the use of a deep-learning-based super-resolution (SR) technique to improve ePVS quantification from 2D T2w images for application in patients with traumatic brain injury (TBI). We prospectively recruited 26 volunteers (age: 31 ± 12 years, 12 male/14 female) where both 2D T2w and 3D T2w images were acquired along with 3D T1w images to validate the ePVS quantification using SR T2w images. We then applied the SR method to retrospectively acquired 2D T2w images in 41 patients with chronic TBI (age: 41 ± 16 years, 32 male/9 female). ePVS volumes were automatically quantified within the whole-brain white matter and major brain lobes (temporal, parietal, frontal, occipital) in all subjects. Pittsburgh Sleep Quality Index (PSQI) scores were obtained on all patients with TBI. Compared with the silver standard (3D T2w), in the validation study, the SR T2w provided similar whole-brain white matter ePVS volume (r = 0.98, p < 0.0001), and similar age-related ePVS burden increase (r = 0.80, p < 0.0001). In the patient study, patients with TBI with poor sleep showed a higher age-related ePVS burden increase than those with good sleep. Sleep status is a significant interaction factor in the whole brain (p = 0.047) and the frontal lobe (p = 0.027). We demonstrate that images produced by SR of 2D T2w images can be automatically analyzed to produce results comparable to those obtained by 3D T2 volumes. Reliable age-related ePVS burden across the whole-brain white matter was observed in all subjects. Poor sleep, affecting the glymphatic function, may contribute to the accelerated increase of ePVS burden following TBI.

Association between Sleep Disturbances at Subacute Stage of Mild Traumatic Brain Injury and Long-Term Outcomes.

Mild (mTBI) traumatic brain injury (TBI) accounts for the majority of all TBI cases. Evidence has suggested that patients with mTBI can suffer from long-lasting cognitive deficits, persistent symptoms, and decreased quality of life. Sleep disorders are commonly observed after TBI, with the prevalence rate of sleep disturbances in persons with TBI being much higher than that in the general population. Poor sleep quality can impair cognitive functions in the general population. This effect of sleep disturbances may impede the recovery processes in the population with TBI. The objective of this study is to add to our understanding of the relationship between self-reported sleep problems and other post-concussion symptoms and look at the association between early sleep problems and long-term outcomes in mTBI. Post-concussion symptoms, neurocognitive functions, level of global outcomes, and rating of satisfaction of life were assessed in 64 patients with mTBI. The results revealed that the presence of sleep disturbances co-occur with an increased level of overall post-concussion symptoms at the subacute stage of mTBI, particularly with symptoms including poor concentration, memory problems, and irritability. In addition, sleep disturbance at the subacute stage is associated with persistent poor concentration and memory problems, as well as worse neurocognitive function, slower overall recovery, and lower satisfactory of life at the long term. Our findings suggest that sleep disturbance can be a prognostic factor of long-term outcomes after mTBI. Early interventions to improve sleep quality can have potential benefits to facilitate the recovery process from mTBI.

Early Stage Longitudinal Subcortical Volumetric Changes following Mild Traumatic Brain Injury.

Objective: To investigate early brain volumetric changes from acute to 6 months following mild traumatic brain injury (mTBI) in deep gray matter regions and their association with patient 6-month outcome.Methods: Fifty-six patients with mTBI underwent MRI and behavioral evaluation at acute (<10 days) and approximately 1 and 6 months post injury. Regional volume changes were investigated in key gray matter regions: thalamus, hippocampus, putamen, caudate, pallidum, and amygdala, and compared with volumes from 34 healthy control subjects. In patients with mTBI, we further assessed associations between longitudinal regional volume changes with patient outcome measures at 6 months including post-concussive symptoms, cognitive performance, and overall satisfaction with life.Results: Reduction in thalamic and hippocampal volumes was observed at 1 month among patients with mTBI. Such volume reduction persisted in the thalamus until 6 months. Changes in thalamic volumes also correlated with multiple symptom and functional outcome measures in patients at 6 months.Conclusion: Our results indicate that the thalamus may be differentially affected among patients with mTBI, resulting in both structural and functional deficits with subsequent post-concussive sequelae and may serve as a biomarker for the assessment of efficacy of novel therapeutic interventions.

Prospective motion detection and re-acquisition in diffusion MRI using a phase image-based method-Application to brain and tongue imaging.

PURPOSE: To develop an image-based motion-robust diffusion MRI (dMRI) acquisition framework that is able to minimize motion artifacts caused by rigid and nonrigid motion, applicable to both brain and tongue dMRI. METHODS: We developed a novel prospective motion-correction technique in dMRI using a phase image-based real-time motion-detection method (PITA-MDD) with re-acquisition of motion-corrupted images. The prospective PITA-MDD acquisition technique was tested in the brains and tongues of volunteers. The subjects were instructed to move their heads or swallow, to induce motion. Motion-detection efficacy was validated against visual inspection as the gold standard. The effect of the PITA-MDD technique on diffusion-parameter estimates was evaluated by comparing reconstructed fiber tracts using tractography with and without re-acquisition. RESULTS: The prospective PITA-MDD technique was able to effectively and accurately detect motion-corrupted data as compared with visual inspection. Tractography results demonstrated that PITA-MDD motion detection followed by re-acquisition helps in recovering lost and misshaped fiber tracts in the brain and tongue that would otherwise be corrupted by motion and yield erroneous estimates of the diffusion tensor. CONCLUSION: A prospective PITA-MDD technique was developed for dMRI acquisition, providing improved dMRI image quality and motion-robust diffusion estimation of the brain and tongue.

Phase Image Texture Analysis for Motion Detection in Diffusion MRI (PITA-MDD).

PURPOSE: Pronounced spin phase artifacts appear in diffusion-weighted imaging (DWI) with only minor subject motion. While DWI data corruption is often identified as signal drop out in diffusion-weighted (DW) magnitude images, DW phase images may have higher sensitivity for detecting subtle subject motion. METHODS: This article describes a novel method to return a metric of subject motion, computed using an image texture analysis of the DW phase image. This Phase Image Texture Analysis for Motion Detection in dMRI (PITA-MDD) method is computationally fast and reliably detects subject motion from diffusion-weighted images. A threshold of the motion metric was identified to remove motion-corrupted slices, and the effect of removing corrupted slices was assessed on the reconstructed FA maps and fiber tracts. RESULTS: Using a motion-metric threshold to remove the motion-corrupted slices results in superior fiber tracts and fractional anisotropy maps. When further compared to a state-of-the-art magnitude-based motion correction method, PITA-MDD was able to detect comparable corrupted slices in a more computationally efficient manner. CONCLUSION: In this study, we evaluated the use of DW phase images to detect motion corruption. The proposed method can be a robust and fast alternative for automatic motion detection in the brain with multiple applications to inform prospective motion correction or as real-time feedback for data quality control during scanning, as well as after data is already acquired.

Dynamic Functional Network Analysis in Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) is one of the most common neurological disorders for which a subset of patients develops persistent postconcussive symptoms. Previous studies discovered abnormalities and disruptions in the brain functional networks of mTBI patients principally using static functional connectivity measures which assume that neural communication across the brain is static during resting state conditions. In this study, we examine the differences in dynamic neural communication between mTBI and control participants through the application of a combination of dynamic functional analysis and graph theoretic algorithms. Resting state functional magnetic resonance imaging data was obtained on 47 mTBI patients at the acute stage of injury and 30 demographically matched healthy control participants. Results show unique alterations in both the static and dynamic functional connectivity at the acute stage in mTBI patients who suffer persistent symptoms (≥6 months after injury). In addition, mTBI patients with postconcussion syndrome demonstrated a unique allocation of time in various brain states compared to both control participants and mTBI patients with favorable outcomes. These findings suggest that global damage to the overall communication across the brain in the acute stage may contribute to chronic mTBI symptoms. Dynamic functional analysis is a powerful tool that provides insights into the brain states and the innovative analysis methodology utilized may hold the potential to delineate patients predisposed to poor outcomes upon early presentation following injury.

Structural and Functional Integrity of the Intraparietal Sulcus in Moderate and Severe Traumatic Brain Injury.

Severe and moderate traumatic brain injury (sTBI) often results in long-term cognitive deficits such as reduced processing speed and attention. The intraparietal sulcus (IPS) is a neocortical structure that plays a crucial role in the deeply interrelated processes of multi-sensory processing and top down attention. Therefore, we hypothesized that disruptions in the functional and structural connections of the IPS may play a role in the development of such deficits. To examine these connections, we used resting state magnetic resonance imaging (rsfMRI and diffusion kurtosis imaging (DKI) in a cohort of 27 patients with sTBI (29.3 ± 8.9 years) and 27 control participants (29.8 ± 10.3 years). Participants were prospectively recruited and received rsfMRI and neuropsychological assessments including the Automated Neuropsychological Assessment Metrics (ANAM) at greater than 6 months post-injury. A subset of participants received a DKI scan. Results suggest that patients with sTBI performed worse than control participants on multiple subtests of the ANAM suggesting reduced cognitive performance. Reduced resting state functional connectivity between the IPS and cortical regions associated with multi-sensory processing and the dorsal attention network was observed in the patients with sTBI. The patients also showed reduced structural integrity of the superior longitudinal fasciculus (SLF), a key white matter tract connecting the IPS to anterior frontal areas, as measured by reduced mean kurtosis (MK) and fractional anisotropy (FA) and increased mean diffusivity (MD). Further, this reduced structural integrity of the SLF was associated with a reduction in overall cognitive performance. These findings suggest that disruptions in the structural and functional connectivity of the IPS may contribute to chronic cognitive deficits experienced by these patients.

Predictors and brain connectivity changes associated with arm motor function improvement from intensive practice in chronic stroke.

Background and Purpose: The brain changes that underlie therapy-induced improvement in motor function after stroke remain obscure. This study sought to demonstrate the feasibility and utility of measuring motor system physiology in a clinical trial of intensive upper extremity rehabilitation in chronic stroke-related hemiparesis. Methods: This was a substudy of two multi-center clinical trials of intensive robotic arm therapy in chronic, significantly hemiparetic, stroke patients. Transcranial magnetic stimulation was used to measure motor cortical output to the biceps and extensor digitorum communus muscles. Magnetic resonance imaging (MRI) was used to determine the cortical anatomy, as well as to measure fractional anisotropy, and blood oxygenation (BOLD) during an eyes-closed rest state. Region-of-interest time-series correlation analysis was performed on the BOLD signal to determine interregional connectivity. Functional status was measured with the upper extremity Fugl-Meyer and Wolf Motor Function Test. Results: Motor evoked potential (MEP) presence was associated with better functional outcomes, but the effect was not significant when considering baseline impairment. Affected side internal capsule fractional anisotropy was associated with better function at baseline. Affected side primary motor cortex (M1) activity became more correlated with other frontal motor regions after treatment. Resting state connectivity between affected hemisphere M1 and dorsal premotor area (PMAd) predicted recovery.  Conclusions: Presence of motor evoked potentials in the affected motor cortex and its functional connectivity with PMAd may be useful in predicting recovery. Functional connectivity in the motor network shows a trends towards increasing after intensive robotic or non-robotic arm therapy. Clinical Trial Registration URL:  http://www.clinicaltrials.gov. Unique identifiers:  CT00372411 & NCT00333983.

Disruptions in Resting State Functional Connectivity and Cerebral Blood Flow in Mild Traumatic Brain Injury Patients.

Mild traumatic brain injury (mTBI) is often occult to conventional imaging techniques. However, there is growing evidence that mTBI patients who lack evidence of structural intracranial injury may develop post-concussive syndrome (PCS). We investigated longitudinal alterations in resting state functional connectivity (rs-FC) in brain networks in a population of 28 patients compared to 28 matched control participants. Rs-FC and cerebral blood flow (CBF) within the nodes of the Default Mode Network (DMN) and Task Positive Network (TPN) were assessed at three time points including acute, sub-acute, and chronic stages following mTBI. Participants received the Automated Neuropsychological Assessment Metrics (ANAM) to assess cognitive performance. Main findings indicate that despite normalized cognitive performance, chronic mTBI patients demonstrate increased rs-FC between the DMN and regions associated with the salience network (SN) and TPN compared to the control populations, as well as reduced strength of rs-FC within the DMN at the acute stage of injury. In addition, chronic mTBI patients demonstrate an imbalance in the ratio of CBF between nodes of the DMN and TPN. Furthermore, preliminary exploratory analysis suggests that compared to those without chronic PCS, patients with chronic PCS reveal an imbalance in the ratio of CBF between the DMN nodes and TPN nodes across multiple stages of recovery. Findings suggest that the altered network perfusion with the associated changes in rs-FC may be a possible predictor of which mTBI patients will develop chronic PCS.

Hyper-connectivity of the thalamus during early stages following mild traumatic brain injury.

The thalamo-cortical resting state functional connectivity of seven sub-thalamic regions were examined in a prospectively recruited population of 77 acute mild TBI (mTBI) patients within the first 10 days (mean 6 ± 3 days) of injury and 35 neurologically intact control subjects using the Oxford thalamic connectivity atlas. Neuropsychological assessments were conducted using the Automated Neuropsychological Assessment Metrics (ANAM). A subset of participants received a magentic resonance spectroscopy (MRS) exam to determine metabolite concentrations in the thalamus and the posterior cingulate cortex. Results show that patients performed worse than the control group on various subtests of ANAM and the weighted throughput score, suggesting reduced cognitive performance at this early stage of injury. Both voxel and region of interest based analysis of the resting state fMRI data demonstrated that acute mTBI patients have increased functional connectivity between the various sub-thalamic regions and cortical regions associated with sensory processing and the default mode network (DMN). In addition, a significant reduction in NAA/Cr was observed in the thalamus in the mTBI patients. Furthermore, an increase in Cho/Cr ratio specific to mTBI patients with self-reported sensory symptoms was observed compared to those without self-reported sensory symptoms. These results provide novel insights into the neural mechanisms of the brain state related to internal rumination and arousal, which have implications for new interventions for mTBI patients with persistent symptoms. Furthermore, an understanding of heightened sensitivity to sensory related inputs during early stages of injury may facilitate enhanced prediction of safe return to work.

Investigation of Multiple Frequency Ranges Using Discrete Wavelet Decomposition of Resting-State Functional Connectivity in Mild Traumatic Brain Injury Patients.

The aim of this study was to investigate if discrete wavelet decomposition provides additional insight into resting-state processes through the analysis of functional connectivity within specific frequency ranges within the default mode network (DMN) that may be affected by mild traumatic brain injury (mTBI). Participants included 32 mTBI patients (15 with postconcussive syndrome [PCS+] and 17 without [PCS-]). mTBI patients received resting-state functional magnetic resonance imaging (rs-fMRI) at acute (within 10 days of injury) and chronic (6 months postinjury) time points and were compared with 31 controls (healthy control [HC]). The wavelet decomposition divides the time series into multiple frequency ranges based on four scaling factors (SF1: 0.125-0.250 Hz, SF2: 0.060-0.125 Hz, SF3: 0.030-0.060 Hz, SF4: 0.015-0.030 Hz). Within each SF, wavelet connectivity matrices for nodes of the DMN were created for each group (HC, PCS+, PCS-), and bivariate measures of strength and diversity were calculated. The results demonstrate reduced strength of connectivity in PCS+ patients compared with PCS- patients within SF1 during both the acute and chronic stages of injury, as well as recovery of connectivity within SF1 across the two time points. Furthermore, the PCS- group demonstrated greater network strength compared with controls at both time points, suggesting a potential compensatory or protective mechanism in these patients. These findings stress the importance of investigating resting-state connectivity within multiple frequency ranges; however, many of our findings are within SF1, which may overlap with frequencies associated with cardiac and respiratory activities.

Design, Development, and Evaluation of a Master-Slave Surgical System for Breast Biopsy under Continuous MRI.

Magnetic Resonance Imaging (MRI) provides superior soft-tissue contrast in cancer diagnosis compared to other imaging modalities. However, the strong magnetic field inside the MRI bore along with limited scanner bore size poses significant challenges. Since current approaches in breast biopsy using MR images is primarily a blind targeting approach, it is necessary to develop a MRI-compatible robot that can avoid multiple needle insertions into the breast tissue. This MRI-compatible robotic system could potentially lead to improvement in the targeting accuracy and reduce sampling errors. A master-slave surgical system has been developed comprising of a MRI-compatible slave robot which consists of one piezo motor and five pneumatic cylinders connected by long pneumatic transmission lines. The slave robot follows the configuration of the master robot, which provides an intuitive manipulation interface for the physician and operates inside the MRI bore to adjust the needle position and orientation and perform needle insertion task. Based on the MRI experiments using the slave robot, there was no significant distortion in the images and hence the slave robot can be safely operated inside the MRI with minimal loss in signal-to-noise ratio (SNR). Ex vivo and in vivo experiments have been conducted to evaluate the performance of the master-slave surgical system.

Longitudinal in vivo developmental changes of metabolites in the hippocampus of Fmr1 knockout mice.

Fragile X syndrome (FXS) is the most common form of inherited mental retardation and is studied in the Fmr1 knockout (KO) mouse, which models both the anatomical and behavioral changes observed in FXS patients. In vitro studies have shown many alterations in synaptic plasticity and increased density of immature dendritic spines in the hippocampus, a region involved in learning and memory. In this study, magnetic resonance imaging (MRI) and (1) H magnetic resonance spectroscopy (MRS) were used to determine in vivo longitudinal changes in volume and metabolites in the hippocampus during the critical period of early myelination and synaptogenesis at post-natal days (PND) 18, 21, and 30 in Fmr1 KO mice compared with wild-type (WT) controls. MRI demonstrated an increase in volume of the hippocampus in the Fmr1 KO mouse compared with controls. MRS revealed significant developmental changes in the ratios of hippocampal metabolites N-acetylaspartate (NAA), myo-inositol (Ins), and taurine to total creatine (tCr) in Fmr1 KO mice compared with WT controls. Ins was decreased at PND 30, and taurine was increased at all ages studied in Fmr1 KO mice compared with controls. An imbalance of brain metabolites in the hippocampus of Fmr1 KO mice during the critical developmental period of synaptogenesis and early myelination could have long-lasting effects that adversely affect brain development and contribute to ongoing alterations in brain function.

Early microstructural and metabolic changes following controlled cortical impact injury in rat: a magnetic resonance imaging and spectroscopy study.

Understanding tissue alterations at an early stage following traumatic brain injury (TBI) is critical for injury management and limiting severe consequences from secondary injury. We investigated the early microstructural and metabolic profiles using in vivo diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy ((1)H MRS) at 2 and 4 h following a controlled cortical impact injury in the rat brain using a 7.0 Tesla animal MRI system and compared profiles to baseline. Significant decrease in mean diffusivity (MD) and increased fractional anisotropy (FA) was found near the impact site (hippocampus and bilateral thalamus; p<0.05) immediately following TBI, suggesting cytotoxic edema. Although the DTI parameters largely normalized on the contralateral side by 4 h, a large inter-individual variation was observed with a trend towards recovery of MD and FA in the ipsilateral hippocampus and a sustained elevation of FA in the ipsilateral thalamus (p<0.05). Significant reduction in metabolite to total creatine ratios of N-acetylaspartate (NAA, p=0.0002), glutamate (p=0.0006), myo-inositol (Ins, p=0.04), phosphocholine and glycerophosphocholine (PCh+GPC, p=0.03), and taurine (Tau, p=0.009) were observed ipsilateral to the injury as early as 2 h, while glutamine concentration increased marginally (p=0.07). These metabolic alterations remained sustained over 4 h after TBI. Significant reductions of Ins (p=0.024) and Tau (p=0.013) and marginal reduction of NAA (p=0.06) were also observed on the contralateral side at 4 h after TBI. Overall our findings suggest significant microstructural and metabolic alterations as early as 2 h following injury. The tendency towards normalization at 4 h from the DTI data and no further metabolic changes at 4 h from MRS suggest an optimal temporal window of about 3 h for interventions that might limit secondary damage to the brain. Results indicate that early assessment of TBI patients using DTI and MRS may provide valuable information on the available treatment window to limit secondary brain damage.

Age-related changes in nociceptive processing in the human brain.

Functional magnetic resonance imaging (fMRI) was used to compare cortical nociceptive responses to painful contact heat in healthy young (ages 22-30, n = 7) and older (ages 56-75, n = 7) subjects. Compared to young subjects, older subjects had significantly smaller pain-related fMRI responses in anterior insula (aINS) (P < 0.04), primary somatosensory cortex (S1) (P = 0.03), and supplementary motor area (P = 0.02). Gray matter volumes in S1 and aINS were significantly smaller for the older group (P = 0.02 and 0.0001, respectively), suggesting reduced processing capacity in these regions that might account for smaller pain-related fMRI responses.

Diffusion-weighted magnetic resonance imaging of white matter in bipolar disorder: a pilot study.

OBJECTIVE: Diffusion-weighted magnetic resonance imaging (MRI) has shown increased sensitivity in detecting brain white matter disease compared to traditional T2-weighted MRI. Diffusion-weighted imaging (DWI) can quantitatively assess the microstructural integrity of white matter using the average apparent diffusion coefficient (ADC(av)), a measure of the extent to which water molecules move freely within tissue. On the basis of numerous studies suggesting white matter disease in bipolar patients, particularly patients with more severe illness, this study aimed to test the utility of DWI in assessing the white matter integrity of bipolar patients with severe illness. METHODS: The existing MRI scans of eight bipolar patients and eight age-matched controls with neurological illness were examined retrospectively. ADC(av) values for pixels within white matter regions of interest (ROIs) were calculated and used to plot ADC(av) frequency histograms for each ROI. Mean ADC(av) values for the two groups were then compared by ANCOVA. RESULTS: The bipolar mean ADC(av) (0.855 +/- 0.051 x 10(-3) mm2/s) for combined white matter ROIs significantly exceeded that of controls (0.799 +/- 0.046 x 10(-3) mm2/s), while covarying for age (F = 4.47, df = 3, p = 0.025). CONCLUSIONS: This is the first report of an elevated ADC(av) in the white matter of a group of patients with bipolar disorder. In this group of patients with severe illness, increased white matter ADC(av) suggests microstructural changes consistent with decreased white matter integrity. DWI may be an additional, useful tool to assess white matter abnormalities in bipolar disorder.

Whole-brain apparent diffusion coefficient in traumatic brain injury: correlation with Glasgow Coma Scale score.

BACKGROUND AND PURPOSE: Patients with traumatic brain injury (TBI) and low Glasgow coma scale (GCS) scores may have severe injury associated with cellular disruption that can be studied with whole-brain apparent diffusion coefficient (ADC) histograms. We retrospectively studied this hypothesis and correlated ADC with GCS. METHODS: Twenty-one patients (37.81 +/- 41.3 years) with TBI were enrolled: Group A had normal MR imaging findings but low GCS scores (n = 6). Group B had brain stem injury with low GCS scores (n = 6). Group C had cortical lesions with normal GCS scores (n = 5), and group D had cortical lesions with low GCS scores (n = 4). Eleven control subjects were enrolled (32.7 +/- 19.2 years). Whole-brain ADC maps and histograms were generated and normalized for each subject. Mean and peak ADCs were determined. A one-sided t test was performed for each parameter. Average GCS scores and corresponding peak and mean ADCs were correlated. RESULTS: Peak histogram values significantly differed between controls and groups A, B, and D (P <.0019, P <.00129, and P <.0148, respectively). In groups A and D, values were significantly skewed compared with control values. Mean ADC was significantly different between the control ADC and group A (P <.013) but not group C. In each group, peak ADC and GCS score were strongly correlated (R(2) = 0.67). CONCLUSION: Whole-brain peak ADCs and GCS scores are significantly correlated in patients with TBI. Although conventional MR images were normal, ADC independently indicated TBI and better represents the degree of neurologic dysfunction.

Functional MRI determination of a dose-response relationship to lower extremity neuromuscular electrical stimulation in healthy subjects.

Although empirical evidence supports the use of neuromuscular electrical stimulation (NMES) to treat physical impairments associated with stroke, the mechanisms underlying the efficacy of this modality are poorly understood. Recent studies have employed functional imaging to investigations of brain responses to median nerve stimulation. These studies suggest a dose-response relationship may exist between selected stimulation parameters and hemodynamic responses in sensorimotor regions. However, substantial gaps exist in this literature. The present study was designed to address these deficiencies. Ten healthy subjects participated. In phase one, four stimulus intensity levels were established: (1). sensory threshold [Th], (2). (MM-Th)x0.333+Th [low-intermediate level, LI], (3). (MM-Th)x0.666+Th [high-intermediate level, HI], and (4). maximal motor (MM). In phase two, subjects were scanned using a spiral-echoplanar imaging technique at each stimulus level. Image sets were analyzed to determine hemodynamic responses at the highest Pearson correlation level ( r) ascertained for each of five areas of interest (AOI): (1). primary sensory, (2). primary motor, (3). cingulate gyrus, (4). thalamus, and (5). cerebellum. ANOVA demonstrated significant main effects for BOLD signal amplitude ( p<0.05) changes in all AOI. Similarly, ANOVA showed significant differences in the volume of activation ( p<0.05) with increasing stimulus intensity in four AOI. Secondary analyses of pooled data showed increasing probabilities of activation at higher stimulus intensities within each AOI. Collectively, these data indicate a dose-response relationship exists between lower extremity NMES and brain activation in specific neural regions. The current results, while limited in their generalizability, are foundational for future studies of interventions using NMES.