Randall R. Benson

White matter abnormalities in mobility-impaired older persons

Objective: To investigate the relationship between white matter abnormalities and impairment of gait and balance in older persons. Methods: Quantitative MRI was used to evaluate the brain tissue compartments of 28 older individuals separated into normal and impaired groups on the basis of mobility performance testing using the Short Physical Performance Battery. In addition, individuals were tested on six indices of gait and balance. For imaging data, segmentation of intracranial volume into four tissue classes was performed using template-driven segmentation, in which signal-intensity–based statistical tissue classification is refined using a digital brain atlas as anatomic template. Results: Both decreased white matter volume, which was age-related, and increased white matter signal abnormalities, which were not age-related, were observed in the mobility-impaired group compared with the control subjects. The average volume of white matter signal abnormalities for impaired individuals was nearly double that of control subjects. Conclusions: This cross-sectional study suggests that decreased white matter volume is age-related, whereas increased white matter signal abnormalities are most likely to occur as a result of disease. Both of these changes are independently associated with impaired mobility in older persons and therefore likely to be additive factors of motor disability.

Parametrically dissociating speech and nonspeech perception in the brain using fMRI

Candidate brain regions constituting a neural network for preattentive phonetic perception were identified with fMRI and multivariate multiple regression of imaging data. Stimuli contrasted along speech/nonspeech, acoustic, or phonetic complexity (three levels each) and natural/synthetic dimensions. Seven distributed brain regions activity correlated with speech and speech complexity dimensions, including five left-sided foci [posterior superior temporal gyrus (STG), angular gyrus, ventral occipitotemporal cortex, inferior/posterior supramarginal gyrus, and middle frontal gyrus (MFG)] and two right-sided foci (posterior STG and anterior insula). Only the left MFG discriminated natural and synthetic speech. The data also supported a parallel rather than serial model of auditory speech and nonspeech perception.

Quantitative Analysis of MRI Signal Abnormalities of Brain White Matter With High Reproducibility and Accuracy

To assess the reproducibility and accuracy compared to radiologists of three automated segmentation pipelines for quantitative magnetic resonance imaging (MRI) measurement of brain white matter signal abnormalities (WMSA).

The role of advanced MR imaging findings as biomarkers of traumatic brain injury.

Treatment of traumatic brain injury (TBI) requires proper classification of the pathophysiology. Clinical classifiers and conventional neuroimaging are limited in TBI detection, outcome prediction, and treatment guidance. Advanced magnetic resonance imaging (MRI) techniques such as susceptibility weighted imaging, diffusion tensor imaging, and magnetic resonance spectroscopic imaging are sensitive to microhemorrhages, white matter injury, and abnormal metabolic activities, respectively, in brain injury. In this article, we reviewed these 3 advanced MRI methods and their applications in TBI and report some new findings from our research. These MRI techniques have already demonstrated their potential to improve TBI detection and outcome prediction. As such, they have demonstrated the capacity of serving as a set of biomarkers to reveal the heterogeneous and complex nature of brain injury in a regional and temporal manner. Further longitudinal studies using advanced MRI in a synergistic approach are expected to provide insight in understanding TBI and imaging implications for treatment.

Accrual of MRI white matter abnormalities in elderly with normal and impaired mobility

White matter signal abnormality (WMSA) is often present in the MRIs of older persons with mobility impairment. We examined the relationship between impaired mobility and the progressive accrual of WMSA. Mobility was assessed with the Short Physical Performance Battery (SPPB) and quantitative measures of gait and balance. Fourteen subjects had baseline and follow-up MRI scans performed 20 months apart. WMSA was detected and quantified using automated computer algorithms. In the control subjects, WMSA volume increased by 0.02+/-0.05% ICCV (percent intracranial cavity volume)/year while the WMSA of mobility impaired subjects increased five-times faster (0.10+/-0.10 ICCV/year, p=0.03). WMSA volume was related to some of the mobility measures and was sensitive to change which was not true of the other MRI variables. The study demonstrates the sensitivity of longitudinal automated volumetric analysis of WMSA to differentiate differences in the accrual rate of WMSA in groups selected on the basis of mobility. Based on these results, we propose that a subset of subjects with mobility impairment have accelerated, disease related WMSA accrual, thus explaining the rapid progression of mobility impairment in some older persons without apparent cause. This study demonstrates that quantitative MRI and performance measures can provide valuable insight into the rate of progression and pathophysiologic abnormalities underlying mobility impairment.

Use of Functional MRI to Guide Decisions in a Clinical Stroke Trial

Background and Purpose— An investigational trial examined safety and efficacy of targeted subthreshold cortical stimulation in patients with chronic stroke. The anatomical location for the target, hand motor area, varies across subjects, and so was localized with functional MRI (fMRI). This report describes the experience of incorporating standardized fMRI into a multisite stroke trial. Methods— At 3 enrollment centers, patients moved (0.25 Hz) the affected hand during fMRI. Hand motor function was localized at a fourth center guiding intervention for those randomized to stimulation. Results— The fMRI results were available within 24 hours. Across 12 patients, activation site variability was substantial (12, 23, and 11 mm in x, y, and z directions), exceeding stimulating electrode dimensions. Conclusion— Use of fMRI to guide decision-making in a clinical stroke trial is feasible.

Detection of hemorrhagic and axonal pathology in mild traumatic brain injury using advanced MRI: implications for neurorehabilitation.

INTRODUCTIONnThere is a need to more accurately diagnose milder traumatic brain injuries with increasing awareness of the high prevalence in both military and civilian populations. Magnetic resonance imaging methods may be capable of detecting a number of the pathoanatomical and pathophysiological consequences of focal and diffuse traumatic brain injury. Susceptibility-weighted imaging (SWI) detects heme iron and reveals even small venous microhemorrhages occurring in diffuse vascular injury. Diffusion tensor imaging (DTI) reveals axonal injury by detecting alterations in water flow in and around injured axons. The overarching hypothesis of this paper is that newer, advanced MR imaging generates sensitive biomarkers of regional brain injury which allows for correlation with clinical signs and symptoms.nnnMETHODSnStudies involving subjects with a history of traumatic brain injury as well as healthy, non-trauma controls were used. Analysis involved comparison of TBI patients imaging results with healthy controls as well as correlation of imaging findings with clinical measures of injury severity. An additional animal study of Sprague-Dawley albino rats compared imaging results with histopathological findings after the animals were sacrificed and stained for b-APP.nnnRESULTSnSWI revealed small foci of hemosiderin for some patients while aggregate lesion volume on SWI correlated with clinical injury severity indices. Similarly, DTI showed striking group differences for fractional anisotropy over the white matter globally, while tract and voxel-based regional results colocalized with SWI and FLAIR lesions in some cases and correlated with clinical deficits. For the rats, correlations were seen between imaging findings and staining of axonal injury.nnnDISCUSSIONnAnimal data gave important tissue correlations with imaging results. SWI and DTI are commercially available sequences that can improve the diagnostic and prognostic ability of the trauma clinician. These biomarkers of regional brain injury which are present in imaging shortly after acute injury and persist indefinitely can inform clinicians and researchers about not only injury severity but also which neurobehavioral systems were injured. Analogous to stroke rehabilitation, having an understanding of the distribution of brain injury should ultimately allow for development of more effective rehabilitation strategies and more efficient clinical interventional trials.

Resting State Functional Connectivity in Mild Traumatic Brain Injury at the Acute Stage: Independent Component and Seed-Based Analyses

Mild traumatic brain injury (mTBI) accounts for more than 1 million emergency visits each year. Most of the injured stay in the emergency department for a few hours and are discharged home without a specific follow-up plan because of their negative clinical structural imaging. Advanced magnetic resonance imaging (MRI), particularly functional MRI (fMRI), has been reported as being sensitive to functional disturbances after brain injury. In this study, a cohort of 12 patients with mTBI were prospectively recruited from the emergency department of our local Level-1 trauma center for an advanced MRI scan at the acute stage. Sixteen age- and sex-matched controls were also recruited for comparison. Both group-based and individual-based independent component analysis of resting-state fMRI (rsfMRI) demonstrated reduced functional connectivity in both posterior cingulate cortex (PCC) and precuneus regions in comparison with controls, which is part of the default mode network (DMN). Further seed-based analysis confirmed reduced functional connectivity in these two regions and also demonstrated increased connectivity between these regions and other regions of the brain in mTBI. Seed-based analysis using the thalamus, hippocampus, and amygdala regions further demonstrated increased functional connectivity between these regions and other regions of the brain, particularly in the frontal lobe, in mTBI. Our data demonstrate alterations of multiple brain networks at the resting state, particularly increased functional connectivity in the frontal lobe, in response to brain concussion at the acute stage. Resting-state functional connectivity of the DMN could serve as a potential biomarker for improved detection of mTBI in the acute setting.

A Novel Nonrigid Registration Algorithm and Applications

In this paper we describe a new algorithm for nonrigid registration of brain images based on an elastically deformable model. The use of registration methods has become an important tool for computer-assisted diagnosis and surgery. Our goal was to improve analysis in various applications of neurology and neurosurgery by improving nonrigid registration.A local gray level similarity measure is used to make an initial sparse displacement field estimate. The field is initially estimated at locations determined by local features, and then a linear elastic model is used to infer the volumetric deformation across the image. The associated partial differential equation is solved by a finite element approach. A model of empirically observed variability of the brain was created from a dataset of 154 young adults. Both homogeneous and inhomogeneous elasticity models were compared. The algorithm has been applied to medical applications including intraoperative images of neurosurgery showing brain shift and a study of gait and balance disorder.

Paradigm-dependent modulation of event-related fMRI activity evoked by the oddball task.

We have previously shown that event‐related functional magnetic resonance imaging (ER‐fMRI) may be used to record responses to the rapid, interleaved presentation of stimuli in the three‐stimulus oddball task. The present study examined the sensitivity of ER‐fMRI responses to variations in the range of inter‐stimulus intervals (ISIs, calculated as the time from the offset of one stimulus to the onset of the next stimulus) and the type of behavioral response task used. ISIs were varied between a wide ISI range (550–2,050 msec) and a narrow ISI range (800–1,200 msec), while maintaining a similar mean ISI (approximately 1 stimulus per sec) between experiments. The response task was varied between button press and subvocal target counting. Gradient echo, echo planar images were acquired for each of three experiments (wide ISI with button press, narrow ISI with button press, and wide‐ISI with counting) in five subjects. Target stimuli generated increased fMRI signal in a wide range of brain regions. The use of a narrow ISI range generated a greater volume of subcortical activity and a reduced volume of cortical activity relative to a wide ISI range. The counting task generated a larger amplitude and longer lasting evoked response in brain regions that responded during all three experiments. Rare distractor stimuli evoked fMRI signal change primarily in orbitofrontal, ventral‐medial prefrontal and superior parietal cortex. These results illustrate that although ER‐fMRI is relatively insensitive as a technique to small variations in the timing of stimulus‐evoked responses, it is remarkably sensitive to consequences such variations have for the topographic location and amplitude of neural responses to stimuli. Hum. Brain Mapping 14:116–127, 2001.