Blood pressure, executive function, and network connectivity in middle-aged adults at risk of dementia in late life.

Midlife blood pressure is associated with structural brain changes, cognitive decline, and dementia in late life. However, the relationship between early adulthood blood pressure exposure, brain structure and function, and cognitive performance in midlife is not known. A better understanding of these relationships in the preclinical stage may advance our mechanistic understanding of vascular contributions to late-life cognitive decline and dementia and may provide early therapeutic targets. To identify resting-state functional connectivity of executive control networks (ECNs), a group independent components analysis was performed of functional MRI scans of 600 individuals from the Coronary Artery Risk Development in Young Adults longitudinal cohort study, with cumulative systolic blood pressure (cSBP) measured at nine visits over the preceding 30 y. Dual regression analysis investigated performance-related connectivity of ECNs in 578 individuals (mean age 55.5 ± 3.6 y, 323 female, 243 Black) with data from the Stroop color-word task of executive function. Greater connectivity of a left ECN to the bilateral anterior gyrus rectus, right posterior orbitofrontal cortex, and nucleus accumbens was associated with better executive control performance on the Stroop. Mediation analyses showed that while the relationship between cSBP and Stroop performance was mediated by white matter hyperintensities (WMH), resting-state connectivity of the ECN mediated the relationship between WMH and executive function. Increased connectivity of the left ECN to regions involved in reward processing appears to compensate for the deleterious effects of WMH on executive function in individuals across the burden of cumulative systolic blood pressure exposure in midlife.

Mapping the Microstructure and Striae of the Human Olfactory Tract with Diffusion MRI.

The human sense of smell plays an important role in appetite and food intake, detecting environmental threats, social interactions, and memory processing. However, little is known about the neural circuity supporting its function. The olfactory tracts project from the olfactory bulb along the base of the frontal cortex, branching into several striae to meet diverse cortical regions. Historically, using diffusion magnetic resonance imaging (dMRI) to reconstruct the human olfactory tracts has been prevented by susceptibility and motion artifacts. Here, we used a dMRI method with readout segmentation of long variable echo-trains (RESOLVE) to minimize image distortions and characterize the human olfactory tracts in vivo We collected high-resolution dMRI data from 25 healthy human participants (12 male and 13 female) and performed probabilistic tractography using constrained spherical deconvolution (CSD). At the individual subject level, we identified the lateral, medial, and intermediate striae with their respective cortical connections to the piriform cortex and amygdala (AMY), olfactory tubercle (OT), and anterior olfactory nucleus (AON). We combined individual results across subjects to create a normalized, probabilistic atlas of the olfactory tracts. We then investigated the relationship between olfactory perceptual scores and measures of white matter integrity, including mean diffusivity (MD). Importantly, we found that olfactory tract MD negatively correlated with odor discrimination performance. In summary, our results provide a detailed characterization of the connectivity of the human olfactory tracts and demonstrate an association between their structural integrity and olfactory perceptual function.SIGNIFICANCE STATEMENT This study provides the first detailed in vivo description of the cortical connectivity of the three olfactory tract striae in the human brain, using diffusion magnetic resonance imaging (dMRI). Additionally, we show that tract microstructure correlates with performance on an odor discrimination task, suggesting a link between the structural integrity of the olfactory tracts and odor perception. Lastly, we generated a normalized probabilistic atlas of the olfactory tracts that may be used in future research to study its integrity in health and disease.

Spatial distribution of hand-grasp motor task activity in spinal cord functional magnetic resonance imaging.

Upper extremity motor paradigms during spinal cord functional magnetic resonance imaging (fMRI) can provide insight into the functional organization of the cord. Hand-grasping is an important daily function with clinical significance, but previous studies of similar squeezing movements have not reported consistent areas of activity and are limited by sample size and simplistic analysis methods. Here, we study spinal cord fMRI activation using a unimanual isometric hand-grasping task that is calibrated to participant maximum voluntary contraction (MVC). Two task modeling methods were considered: (1) a task regressor derived from an idealized block design (Ideal) and (2) a task regressor based on the recorded force trace normalized to individual MVC (%MVC). Across these two methods, group motor activity was highly lateralized to the hemicord ipsilateral to the side of the task. Activation spanned C5-C8 and was primarily localized to the C7 spinal cord segment. Specific differences in spatial distribution are also observed, such as an increase in C8 and dorsal cord activity when using the %MVC regressor. Furthermore, we explored the impact of data quantity and spatial smoothing on sensitivity to hand-grasp motor task activation. This analysis shows a large increase in number of active voxels associated with the number of fMRI runs, sample size, and spatial smoothing, demonstrating the impact of experimental design choices on motor activation.

Multimodal Neural and Behavioral Data Predict Response to Rehabilitation in Chronic Poststroke Aphasia.

BACKGROUND: Poststroke recovery depends on multiple factors and varies greatly across individuals. Using machine learning models, this study investigated the independent and complementary prognostic role of different patient-related factors in predicting response to language rehabilitation after a stroke. METHODS: Fifty-five individuals with chronic poststroke aphasia underwent a battery of standardized assessments and structural and functional magnetic resonance imaging scans, and received 12 weeks of language treatment. Support vector machine and random forest models were constructed to predict responsiveness to treatment using pretreatment behavioral, demographic, and structural and functional neuroimaging data. RESULTS: The best prediction performance was achieved by a support vector machine model trained on aphasia severity, demographics, measures of anatomic integrity and resting-state functional connectivity (F1=0.94). This model resulted in a significantly superior prediction performance compared with support vector machine models trained on all feature sets (F1=0.82, P<0.001) or a single feature set (F1 range=0.68-0.84, P<0.001). Across random forest models, training on resting-state functional magnetic resonance imaging connectivity data yielded the best F1 score (F1=0.87). CONCLUSIONS: While behavioral, multimodal neuroimaging data and demographic information carry complementary information in predicting response to rehabilitation in chronic poststroke aphasia, functional connectivity of the brain at rest after stroke is a particularly important predictor of responsiveness to treatment, both alone and combined with other patient-related factors.

Modulation of brain networks during MR-compatible transcranial direct current stimulation.

Transcranial direct current stimulation (tDCS) can influence performance on behavioral tasks and improve symptoms of brain conditions. Yet, it remains unclear precisely how tDCS affects brain function and connectivity. Here, we measured changes in functional connectivity (FC) metrics in blood-oxygenation-level-dependent (BOLD) fMRI data acquired during MR-compatible tDCS in a whole-brain analysis with corrections for false discovery rate. Volunteers (n = 64) received active tDCS, sham tDCS, and rest (no stimulation), using one of three previously established electrode tDCS montages targeting left dorsolateral prefrontal cortex (DLPFC, n = 37), lateral temporoparietal area (LTA, n = 16), or superior temporal cortex (STC, n = 11). In brain networks where simulated E field was highest in each montage, connectivity with remote nodes decreased during active tDCS. During active DLPFC-tDCS, connectivity decreased between a fronto-parietal network and subgenual ACC, while during LTA-tDCS connectivity decreased between an auditory-somatomotor network and frontal operculum. Active DLPFC-tDCS was also associated with increased connectivity within an orbitofrontal network overlapping subgenual ACC. Irrespective of montage, FC metrics increased in sensorimotor and attention regions during both active and sham tDCS, which may reflect the cognitive-perceptual demands of tDCS. Taken together, these results indicate that tDCS may have both intended and unintended effects on ongoing brain activity, stressing the importance of including sham, stimulation-absent, and active comparators in basic science and clinical trials of tDCS.

Evidence for Immediate Enhancement of Hippocampal Memory Encoding by Network-Targeted Theta-Burst Stimulation during Concurrent fMRI.

The hippocampus supports episodic memory via interaction with a distributed brain network. Previous experiments using network-targeted noninvasive brain stimulation have identified episodic memory enhancements and modulation of activity within the hippocampal network. However, mechanistic insights were limited because these effects were measured long after stimulation and therefore could have reflected various neuroplastic aftereffects with extended time courses. In this experiment with human subjects of both sexes, we tested for immediate stimulation impact on encoding-related activity of the hippocampus and immediately adjacent medial-temporal cortex by delivering theta-burst transcranial magnetic stimulation (TBS) concurrent with fMRI, as an immediate impact of stimulation would suggest an influence on neural activity. We reasoned that TBS would be particularly effective for influencing the hippocampus because rhythmic neural activity in the theta band is associated with hippocampal memory processing. First, we demonstrated that it is possible to obtain robust fMRI correlates of task-related activity during concurrent TBS. We then identified immediate effects of TBS on encoding of visual scenes. Brief volleys of TBS targeting the hippocampal network increased activity of the targeted (left) hippocampus during scene encoding and increased subsequent recollection. Stimulation did not influence activity during an intermixed numerical task with no memory demand. Control conditions using beta band and out-of-network stimulation also did not influence hippocampal activity or recollection. TBS targeting the hippocampal network therefore immediately impacted hippocampal memory processing. This suggests direct, beneficial influence of stimulation on hippocampal neural activity related to memory and supports the role of theta-band activity in human episodic memory.SIGNIFICANCE STATEMENT Can noninvasive stimulation directly impact function of indirect, deep-brain targets, such as the hippocampus? We tested this by targeting an accessible region of the hippocampal network via transcranial magnetic stimulation during concurrent fMRI. We reasoned that theta-burst stimulation would be particularly effective for impacting hippocampal function, as this stimulation rhythm should resonate with the endogenous theta-nested-gamma activity prominent in hippocampus. Indeed, theta-burst stimulation targeting the hippocampal network immediately impacted hippocampal activity during encoding, improving memory formation as indicated by enhanced later recollection. Rhythm- and location-control stimulation conditions had no such effects. These findings suggest a direct influence of noninvasive stimulation on hippocampal neural activity and highlight that the theta-burst rhythm is relatively privileged in its ability to influence hippocampal memory function.

Common and distinct neural substrates of sentence production and comprehension.

Functional neuroimaging and lesion-symptom mapping investigations implicate a left frontal-temporal-parietal network for sentence processing. The majority of studies have focused on sentence comprehension, with fewer in the domain of sentence production, which have not fully elucidated overlapping and/or unique brain structures associated with the two domains, particularly for sentences with noncanonical word order. Using voxel-based lesion symptom mapping (VLSM) we examined the relationship between lesions within the left hemisphere language network and both sentence comprehension and production of simple and complex syntactic structures in 76 participants with chronic stroke-induced aphasia. Results revealed shared regions across domains in the anterior and posterior superior temporal gyri (aSTG, pSTG), and the temporal pole (adjusted for verb production/comprehension). Additionally, comprehension was associated with lesions in the anterior and posterior middle temporal gyri (aMTG, pMTG), the MTG temporooccipital regions, SMG/AG, central and parietal operculum, and the insula. Subsequent VLSM analyses (production versus comprehension) revealed critical regions associated with each domain: anterior temporal lesions were associated with production; posterior temporo-parietal lesions were associated with comprehension, implicating important roles for regions within the ventral and dorsal stream processing routes, respectively. Processing of syntactically complex, noncanonical (adjusted for canonical), sentences was associated with damage to the pSTG across domains, with additional damage to the pMTG and IPL associated with impaired sentence comprehension, suggesting that the pSTG is crucial for computing noncanonical sentences across domains and that the pMTG, and IPL are necessary for re-analysis of thematic roles as required for resolution of long-distance dependencies. These findings converge with previous studies and extend our knowledge of the neural mechanisms of sentence comprehension to production, highlighting critical regions associated with both domains, and further address the mechanism engaged for syntactic computation, controlled for the contribution of verb processing.

Functional connectivity in central executive network protects youth against cardiometabolic risks linked with neighborhood violence.

Although violent crime has declined in recent decades, it remains a recurring feature of daily life in some neighborhoods. Mounting evidence indicates that such violence has a long reach, which goes beyond family and friends of the victim and undermines the health of people in the surrounding community. However, like all forms of adversity, community violence elicits a heterogeneous response: Some remain healthy, but others deteriorate. Despite much scientific attention, the neural circuitries that contribute to differential adaptation remain poorly understood. Drawing on knowledge of the brain's intrinsic functional architecture, we predicted that individual differences in resting-state connectivity would explain variability in the strength of the association between neighborhood violence and cardiometabolic health. We enrolled 218 urban youth (age 12-14 years, 66% female; 65% black or Latino) and used geocoding to characterize their exposure to neighborhood murder over the past five years. Multiple aspects of cardiometabolic health were assessed, including obesity, insulin resistance, and metabolic syndrome. Functional MRI was used to quantify the connectivity of major intrinsic networks. Consistent with predictions, resting-state connectivity within the central executive network (CEN) emerged as a moderator of adaptation. Across six distinct outcomes, a higher neighborhood murder rate was associated with greater cardiometabolic risk, but this relationship was apparent only among youth who displayed lower CEN resting-state connectivity. By contrast, there was little evidence of moderation by the anterior salience and default mode networks. These findings advance basic and applied knowledge about adaptation by highlighting intrinsic CEN connectivity as a potential neurobiological contributor to resilience.

Assessing the spatial distribution of cervical spinal cord activity during tactile stimulation of the upper extremity in humans with functional magnetic resonance imaging.

Dermatomal maps are a mainstay of clinical practice and provide information on the spatial distribution of the cutaneous innervation of spinal nerves. Dermatomal deficits can help isolate the level of spinal nerve root involvement in spinal conditions and guide clinicians in diagnosis and treatment. Dermatomal maps, however, have limitations, and the spatial distribution of spinal cord sensory activity in humans remains to be quantitatively assessed. Here we used spinal cord functional MRI to map and quantitatively compare the spatial distribution of sensory spinal cord activity during tactile stimulation of the left and right lateral shoulders (i.e. C5 dermatome) and dorsal third digits of the hands (i.e., C7 dermatome) in healthy humans (n â€‹= â€‹24, age â€‹= â€‹36.8 â€‹± â€‹11.8 years). Based on the central sites for processing of innocuous tactile sensory information, we hypothesized that the activity would be localized more to the ipsilateral dorsal spinal cord with the lateral shoulder stimulation activity being localized more superiorly than the dorsal third digit. The findings demonstrate lateralization of the activity with the left- and right-sided stimuli having more activation in the ipsilateral hemicord. Contradictory to our hypotheses, the activity for both stimulation sites was spread across the dorsal and ventral hemicords and did not demonstrate a clear superior-inferior localization. Instead, the activity for both stimuli had a broader than expected distribution, extending across the C5, C6, and C7 spinal cord segments. We highlight the complexity of the human spinal cord neuroanatomy and several sources of variability that may explain the observed patterns of activity. While the findings were not completely consistent with our a priori hypotheses, this study provides a foundation for continued work and is an important step towards developing normative quantitative spinal cord measures of sensory function, which may become useful objective MRI-based biomarkers of neurological injury and improve the management of spinal disorders.

Reliability of BOLD signals in chronic stroke-induced aphasia.

Investigating the neurobiology of language impairment and treatment in chronic stroke aphasia using fMRI requires an understanding of measurement variability within and between participants. In this multicenter study, we evaluated the scan-rescan reliability of an auditory and visual (written) story comprehension paradigm in stroke participants with aphasia (N = 65) and healthy controls (N = 22). The multi-modal task was conducted twice (~1 week apart) on separate visits upon study enrolment and twice again at completion three months later. A non-language visuomotor task was studied in the aphasia group only, which was conducted once per time point (3 months apart). While participants were asked to make responses during the comprehension task, these in-scanner responses were not recorded. Reliability was assessed using intraclass correlation coefficient (ICC) at both group and individual participant levels. The visual story comprehension condition had higher reliability than the auditory condition in both groups, with participants with aphasia exhibiting lower reliability than controls in both conditions (stroke ICC = .43, healthy ICC = .81). Differences in reliability within the group of participants with aphasia were found to be partially explained by overall language impairment as well as greater head motion. In the participants with aphasia, the visuomotor paradigm was found to have greater reliability than the story comprehension task at equivalent interscan intervals (visuomotor = 0.50, comprehension = 0.34), and its reliability was not associated with language impairment. This work highlights the importance of considering the reliability of fMRI tasks in aphasia research, provides strategies to improve reliability and has potential implications for the field of clinical neuroimaging in general.

Subcortical structural variations associated with low socioeconomic status in adolescents.

Low socioeconomic status (SES) is associated with a higher probability of multiple exposures (e.g., neighborhood violence, poor nutrition, housing instability, air pollution, and insensitive caregiving) known to affect structural development of subcortical brain regions that subserve threat and reward processing, however, few studies have examined the relationship between SES and such subcortical structures in adolescents. We examined SES variations in volume and surface morphometry of subcortical regions. The sample comprised 256 youth in eighth grade (mean age = 13.9 years), in whom high dimensional deformation mapping of structural 3T magnetic resonance imaging scans was performed. Vertex-wise linear regression analyses examined associations between income to poverty ratio and surfaces of the hippocampus, amygdala, thalamus, caudate, putamen, nucleus accumbens and pallidum, with the covariates age, pubertal status, and intracranial volume. Given sex differences in pubertal development and subcortical maturation at this age, the analyses were stratified by sex. Among males, who at this age average an earlier pubertal stage than females, the relationship between SES and local shape variation in subcortical regions was almost entirely positive. For females, the relationship between SES and local shape variation was negative. Racial identity was associated with SES in our sample, however supplementary analyses indicated that most of the associations between SES and subcortical structure were independent of it. Although these cross-sectional results are not definitive, they are consistent with a scenario where low SES delays structural maturation of subcortical regions involved with threat and reward processing. Future longitudinal studies are needed to test this hypothesis.

Phantom validation of quantitative susceptibility and dynamic contrast-enhanced permeability MR sequences across instruments and sites.

BACKGROUND: Quantitative susceptibility mapping (QSM) and dynamic contrast-enhanced quantitative permeability (DCEQP) on magnetic resonance (MR) have been shown to correlate with neurovascular disease progression as markers of vascular leakage and hemosiderin deposition. Applying these techniques as monitoring biomarkers in clinical trials will be necessary; however, their validation across multiple MR platforms and institutions has not been rigorously verified. PURPOSE: To validate quantitative measurement of MR biomarkers on multiple instruments at different institutions. STUDY TYPE: Phantom validation between platforms and institutions. PHANTOM MODEL: T1 /susceptibility phantom, two-compartment dynamic flow phantom. FIELD STRENGTH/SEQUENCE: 3T/QSM, T1 mapping, dynamic 2D SPGR. ASSESSMENT: Philips Ingenia, Siemens Prisma, and Siemens Skyra at three different institutions were assessed. A QSM phantom with concentrations of gadolinium, corresponding to magnetic susceptibilities of 0, 0.1, 0.2, 0.4, and 0.8 ppm was assayed. DCEQP was assessed by measuring a MultiHance bolus as the consistency of the width ratio of the curves at the input and outputs over a range of flow ratios between outputs. STATISTICAL TESTS: Each biomarker was assessed by measures of accuracy (Pearson correlation), precision (paired t-test between repeated measurements), and reproducibility (analysis of covariance [ANCOVA] between instruments). RESULTS: QSM accuracy of r2 > 0.997 on all three platforms was measured. Precision (P = 0.66 Achieva, P = 0.76 Prisma, P = 0.69 Skyra) and reproducibility (P = 0.89) were good. T1 mapping of accuracy was r2 > 0.98. No significant difference between width ratio regression slopes at site 2 (P = 0.669) or site 3 (P = 0.305), and no significant difference between width ratio regression slopes between sites was detected by ANCOVA (P = 0.48). DATA CONCLUSION: The phantom performed as expected and determined that MR measures of QSM and DCEQP are accurate and consistent across repeated measurements and between platforms. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1192-1199.

Does Overall Cervical Spine Pathology Relate to the Clinical Heterogeneity of Chronic Whiplash?

BACKGROUND AND PURPOSE: There remains limited evidence for the clinical importance of most imaging findings in whiplash. However, it is possible the type and number of findings on Computed Tomography (CT) may contribute to prognostic recovery models. The purpose is to interpret cervical spine pathologies in the context of known factors influencing recovery. MATERIALS AND METHODS: This is a secondary analysis from a database of 97 acutely injured participants enrolled in a prospective inception cohort study. Thirty-eight participants underwent standard of care cervical spine CT in the emergency medicine department. All 38 participants were assessed at <1-week, 2-weeks, and 3-months post-injury and classified using percentage scores on the Neck Disability Index (recovered/mild (NDI of 0-28%) or moderate/severe (NDI ≥ 30%)). Between-group comparison of categorical variables (gender (male/female), presence of at least one CT finding (yes/no), and presence of ≥3 pathologies on CT (yes/no)) was conducted using 2-tailed Fisher's exact test. RESULTS: Participants from both groups demonstrated at least one observable pathology. The group with persistent moderate/severe symptoms presented with significantly more pathology at baseline than those who later reported recovery or milder symptoms at 3-months post injury (p = 0.02). CONCLUSIONS: This preliminary study, which needs replication in a larger cohort, provides foundation that the number of degenerative pathologies seen on initial post MVC CT may be associated with the subsequent clinical course of whiplash.

A Pilot Trial Examining the Merits of Combining Amantadine and Repetitive Transcranial Magnetic Stimulation as an Intervention for Persons With Disordered Consciousness After TBI.

OBJECTIVE: Report pilot findings of neurobehavioral gains and network changes observed in persons with disordered consciousness (DoC) who received repetitive transcranial magnetic stimulation (rTMS) or amantadine (AMA), and then rTMS+AMA. PARTICIPANTS: Four persons with DoC 1 to 15 years after traumatic brain injury (TBI). DESIGN: Alternate treatment-order, within-subject, baseline-controlled trial. MAIN MEASURES: For group and individual neurobehavioral analyses, predetermined thresholds, based on mixed linear-effects models and conditional minimally detectable change, were used to define meaningful neurobehavioral change for the Disorders of Consciousness Scale-25 (DOCS) total and Auditory-Language measures. Resting-state functional connectivity (rsFC) of the default mode and 6 other networks was examined. RESULTS: Meaningful gains in DOCS total measures were observed for 75% of treatment segments and auditory-language gains were observed after rTMS, which doubled when rTMS preceded rTMS+AMA. Neurobehavioral changes were reflected in rsFC for language, salience, and sensorimotor networks. Between networks interactions were modulated, globally, after all treatments. CONCLUSIONS: For persons with DoC 1 to 15 years after TBI, meaningful neurobehavioral gains were observed after provision of rTMS, AMA, and rTMS+AMA. Sequencing and combining of treatments to modulate broad-scale neural activity, via differing mechanisms, merits investigation in a future study powered to determine efficacy of this approach to enabling neurobehavioral recovery.

Neurite orientation dispersion and density imaging (NODDI) and free-water imaging in Parkinsonism.

Neurite orientation dispersion and density imaging (NODDI) uses a three-compartment model to probe brain tissue microstructure, whereas free-water (FW) imaging models two-compartments. It is unknown if NODDI detects more disease-specific effects related to neurodegeneration in Parkinson's disease (PD) and atypical Parkinsonism. We acquired multi- and single-shell diffusion imaging at 3 Tesla across two sites. NODDI (using multi-shell; isotropic volume [Viso]; intracellular volume [Vic]; orientation dispersion [ODI]) and FW imaging (using single-shell; FW; free-water corrected fractional anisotropy [FAt]) were compared with 44 PD, 21 multiple system atrophy Parkinsonian variant (MSAp), 26 progressive supranuclear palsy (PSP), and 24 healthy control subjects in the basal ganglia, midbrain/thalamus, cerebellum, and corpus callosum. There was elevated Viso in posterior substantia nigra across Parkinsonisms, and Viso, Vic, and ODI were altered in MSAp and PSP in the striatum, globus pallidus, midbrain, thalamus, cerebellum, and corpus callosum relative to controls. The mean effect size across regions for Viso was 0.163, ODI 0.131, Vic 0.122, FW 0.359, and FAt 0.125, with extracellular compartments having the greatest effect size. A key question addressed was if these techniques discriminate PD and atypical Parkinsonism. Both NODDI (AUC: 0.945) and FW imaging (AUC: 0.969) had high accuracy, with no significant difference between models. This study provides new evidence that NODDI and FW imaging offer similar discriminability between PD and atypical Parkinsonism, and FW had higher effect sizes for detecting Parkinsonism within regions across the basal ganglia and cerebellum.

Development of 3D method to assess intramuscular spatial distribution of fat infiltration in patients with rotator cuff tear: reliability and concurrent validity.

BACKGROUND: Intramuscular fat infiltration is a critical factor in surgical decision-making and is the most important factor used to prognosticate surgical repair outcomes in patients with rotator cuff tears. Quantitative 3D assessment of total rotator cuff fat infiltration in patients with rotator cuff tears has been realized. However, a reproducible method to evaluate 3D spatial distribution of rotator cuff intramuscular fat has not been established. The objective of this study was to establish the reproducibility, change detectable beyond error, and concurrent validity of a semi-automated method to evaluate the 3D spatial distribution of fat infiltration and muscle volume in patients with rotator cuff tears. METHODS: Thirteen consecutive patients diagnosed with symptomatic rotator cuff pathology and 3.0 T MRI confirmation at a single center were included. Fat-water imaging was used to quantify 3D intramuscular fat (%fat) in sagittal oblique sequences and intramuscular spatial distribution with the semi-automated technique. Each rotator cuff muscle was manually segmented yielding %fat in four axial intramuscular quartile-regions (superior-inferior; Q1-4) and three sagittal (medial/ intermediate/ lateral) regions. Reliability and concurrent validity of %fat and whole muscle volume were calculated with intraclass correlation coefficients (ICC). RESULTS: Intra-rater reliability for intramuscular sagittal divisions (ICC = 0.93-0.99) and axial divisions (ICC = 0.78-0.99) was good/excellent. Inter-rater reliability for %fat (ICC = 0.82-0.99) and volume (ICC = 0.92-0.99) was good/excellent. Concurrent validity with commercialized software showed good/excellent agreement (ICC = 0.66-0.99). CONCLUSIONS: A new semi-automated method to assess 3-dimensional intramuscular distribution of fat infiltration in patients with rotator cuff tears using advanced MR imaging demonstrates high intra and inter-rater reliability and good concurrent validity. Minimal detectable change thresholds established facilitate clinical interpretation for future clinical application of this technique to assess change and treatment efficacy in patients with rotator cuff tears.

Optimizing methods to quantify intramuscular fat in rotator cuff tears with normalization.

OBJECTIVE: To determine which normalization method may best account for confounding individual factors, such as age or BMI, when quantifying fat infiltration on MRI in patients with rotator cuff tears, the effects of normalization using three different muscles (teres major; triceps brachii; teres minor) were compared. METHODS: Thirty-seven consecutive patients diagnosed with rotator cuff pathology were included. MRI fat-water sequences were used to quantify rotator cuff intramuscular fat (%fat). Three reference muscles (teres major, triceps, teres minor) were used to derive normalized %fat. Relationships between intramuscular %fat and tear size, age, and BMI in each rotator cuff muscle, before and after normalization, were compared with Fisher transformations (α = 0.05). RESULTS: Normalization with teres major ameliorated confounding relationships of age and BMI on rotator cuff %fat. In contrast, normalization with triceps maintained the confounding relationships between %fat and age in supraspinatus (p = 0.03) and infraspinatus/teres minor (p = 0.028). Normalization with teres minor maintained the confounding relationship between %fat and BMI in subscapularis (p = 0.039). Normalization with teres major best-maintained relationships between tear size and infraspinatus/teres minor %fat (p = 0.021). In contrast, normalization with triceps or teres minor eliminated all significant relationships with tear size. CONCLUSIONS: Results of this pilot study suggest normalization to teres major using MRI-based %fat quantification methods can effectively control for individual factors, such as BMI or age, and may have utility in evaluating and monitoring rotator cuff fat infiltration attributed specifically to a tendon tear.

Lateral Corticospinal Tract Damage Correlates With Motor Output in Incomplete Spinal Cord Injury.

OBJECTIVE: To investigate the relationship between spinal cord damage and specific motor function in participants with incomplete spinal cord injury (iSCI). DESIGN: Single-blinded, cross-sectional study design. SETTING: University setting research laboratory. PARTICIPANTS: Individuals with chronic cervical iSCI (N=14; 1 woman, 13 men; average age ± SD, 43±12y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Axial T2-weighted magnetic resonance imaging (MRI) of spinal cord damage was performed in 14 participants with iSCI. Each participant's damage was processed for total damage quantification, lateral corticospinal tract (LCST) and gracile fasciculus (GF) analysis. Plantarflexion and knee extension were quantified using an isokinetic dynamometer. Walking ability was assessed using a 6-minute walk test. RESULTS: Total damage was correlated with plantarflexion, knee extension, and distance walked in 6 minutes. Right LCST damage was correlated with right plantarflexion and right knee extension, while left LCST damage was correlated with left-sided measures. Right and left GF damage was not correlated with the motor output measures. CONCLUSIONS: MRI measures of spinal cord damage were correlated to motor function, and this measure appears to have spatial specificity to descending tracts, which may offer prognostic value after SCI.

Short- and long-term reproducibility of diffusion-weighted magnetic resonance imaging of lower extremity musculature in asymptomatic individuals and a comparison to individuals with spinal cord injury.

BACKGROUND: Diffusion-weighted magnetic resonance imaging (DW-MRI) of skeletal muscle has the potential to be a sensitive diagnostic and/or prognostic tool in complex, enigmatic neuromusculoskeletal conditions such as spinal cord injury and whiplash associated disorder. However, the reliability and reproducibility of clinically accessible DW-MRI parameters in skeletal muscle remains incompletely characterized - even in individuals without neuromusculoskeletal injury - and these parameters have yet to be characterized for many clinical populations. Here, we provide normative measures of the apparent diffusion coefficient (ADC) in healthy muscles of the lower limb; assess the rater-based reliability and short- and long-term reproducibility of the ADC in the same muscles; and quantify ADC of these muscles in individuals with motor incomplete spinal cord injury. METHODS: Twenty individuals without neuromusculoskeletal injury and 14 individuals with motor incomplete spinal cord injury (SCI) participated in this investigation. We acquired bilateral diffusion-weighted MRI of the lower limb musculature in all participants at 3 T using a multi-shot echo-planar imaging sequence with b-values of 0, 100, 300 and 500 s/mm2 and diffusion-probing gradients applied in 3 orthogonal directions. Outcome measures included: (1) average ADC in the lateral and medial gastrocnemius, tibialis anterior, and soleus of individuals without neurological or musculoskeletal injury; (2) intra- and inter-rater reliability, as well as short and long-term reproducibility of the ADC; and (3) estimation of average muscle ADC in individuals with SCI. RESULTS: Intra- and inter-rater reliability of the ADC averaged 0.89 and 0.79, respectively, across muscles. Least significant change, a measure of temporal reproducibility, was 4.50 and 11.98% for short (same day) and long (9-month) inter-scan intervals, respectively. Average ADC was significantly elevated across muscles in individuals with SCI compared to individuals without neurological or musculoskeletal injury (1.655 vs. 1.615 mm2/s, respectively). CONCLUSIONS: These findings provide a foundation for future studies that track longitudinal changes in skeletal muscle ADC of the lower extremity and/or investigate the mechanisms underlying ADC changes in cases of known or suspected pathology.

Right Hemisphere Grey Matter Volume and Language Functions in Stroke Aphasia.

The role of the right hemisphere (RH) in recovery from aphasia is incompletely understood. The present study quantified RH grey matter (GM) volume in individuals with chronic stroke-induced aphasia and cognitively healthy people using voxel-based morphometry. We compared group differences in GM volume in the entire RH and in RH regions-of-interest. Given that lesion site is a critical source of heterogeneity associated with poststroke language ability, we used voxel-based lesion symptom mapping (VLSM) to examine the relation between lesion site and language performance in the aphasic participants. Finally, using results derived from the VLSM as a covariate, we evaluated the relation between GM volume in the RH and language ability across domains, including comprehension and production processes both at the word and sentence levels and across spoken and written modalities. Between-subject comparisons showed that GM volume in the RH SMA was reduced in the aphasic group compared to the healthy controls. We also found that, for the aphasic group, increased RH volume in the MTG and the SMA was associated with better language comprehension and production scores, respectively. These data suggest that the RH may support functions previously performed by LH regions and have important implications for understanding poststroke reorganization.