Third-trimester in utero fetal brain diffusion tensor imaging fiber tractography: a prospective longitudinal characterization of normal white matter tract development.

BACKGROUND: White matter is responsible for inter-neuronal connections throughout the brain that are a driving force in cognitive development. Diffusion tensor imaging (DTI) fiber tractography has been used to evaluate white matter development in the fetal brain; however, longitudinal studies of DTI fiber tractography to assess white matter development in the third trimester are lacking. OBJECTIVE: To characterize in utero longitudinal changes in the fetal brain DTI fiber tracts of normal third-trimester fetuses. MATERIALS AND METHODS: For this single-center prospective longitudinal observational pilot study, we recruited 28 pregnant females with normal third-trimester pregnancies who had routine prenatal ultrasound. MRI of the in utero fetal brain was performed with a Siemens 1.5-tesla (T) Espree scanner at 31 weeks, 33 weeks and 36 weeks of gestation, with 14 DTI tractography parameters quantified in 7 brain regions using DTI-studio version 2.4 (Johns Hopkins University, Baltimore, MD; n=98 measurements). We used multilevel mixed models to examine the relationship between longitudinal changes in DTI measurements and between 98 DTI measurements at 31 weeks and 4 routine fetal brain anatomical biometrics (n=392 assessments). RESULTS: We observed statistically significant decreases in radial diffusivity and apparent diffusion coefficient in 13 of 14 brain regions from 31 weeks to 36 weeks of gestation (P<0.001 for all regions except the genu of the corpus callosum). Significant decreases in radial diffusivity from weeks 33 to 36 and weeks 31 to 36 were seen in the corticospinal tracts, centrum semiovale, posterior limb of the internal capsule, and crus cerebri (P<0.001 for all). When considering all possible combinations of DTI fiber tract measurements and the routine morphological fetal brain biometrics, only 6% (24/392) had a significant association (P<0.05), indicating relative independence of the DTI fiber tract measurements from anatomical biometrics. CONCLUSION: In utero longitudinal changes in fetal brain DTI fiber tractography are quantifiable in normal third-trimester fetuses and are largely independent of morphological brain changes.

Neural response to stress and perceived stress differ in patients with left temporal lobe epilepsy.

Patients with epilepsy are often able to predict seizure occurrence subsequent to an acute stress experience. However, neuroimaging investigations into the neural basis of this relationship or the potential influence of perceived life stress are limited. The current study assessed the relationship between perceived stress and the neurobehavioral response to stress in patients with left temporal lobe epilepsy (LTLE) and healthy controls (HCs) using heart rate, salivary cortisol level, and functional magnetic resonance imaging and compared these effects between HCs and LTLE. Matched on perceived stress levels, groups of 36 patients with LTLE and 36 HCs completed the Montreal Imaging Stress Task, with control and stress math task conditions. Among LTLEs, 27 reported that prior (acute) stress affected their seizures (LTLES+), while nine did not (LTLES-). The results revealed that increased perceived stress was associated with seizure frequency in LTLE. Further, cortisol secretion was greater in LTLE, but did not vary with perceived stress as observed in HCs. A linear mixed-effects analysis revealed that as perceived stress increased, activation in the hippocampal complex (parahippocampal gyrus and hippocampus) decreased during stressful math in the LTLES+, increased in HCs, but did not vary in the LTLES-. Task-based functional connectivity analyses revealed LTLE differences in hippocampal functional connectivity with sensory cortex specific to stressor modalities. We argue that the current study demonstrates an inhibitory hippocampal mechanism underlying differences in resilience to stress between HCs and LTLE, as well as LTLE patients who report stress as a precipitant of seizures.

A comparison of manual tracing and FreeSurfer for estimating hippocampal volume over the adult lifespan.

MRI has become an indispensable tool for brain volumetric studies, with the hippocampus an important region of interest. Automation of the MRI segmentation process has helped advance the field by facilitating the volumetric analysis of larger cohorts and more studies. FreeSurfer has emerged as the de facto standard tool for these analyses, but studies validating its output are all based on older versions. To characterize FreeSurfer's validity, we compare several versions of FreeSurfer software with traditional hand-tracing. Using MRI images of 262 males and 402 females aged 38 to 84, we directly compare estimates of hippocampal volume from multiple versions of FreeSurfer, its hippocampal subfield routines, and our manual tracing protocol. We then use those estimates to assess asymmetry and atrophy, comparing performance of different estimators with each other and with brain atrophy measures. FreeSurfer consistently reports larger volumes than manual tracing. This difference is smaller in larger hippocampi or older people, with these biases weaker in version 6.0.0 than prior versions. All methods tested agree qualitatively on rightward asymmetry and increasing atrophy in older people. FreeSurfer saves time and money, and approximates the same atrophy measures as manual tracing, but it introduces biases that could require statistical adjustments in some studies.

Physiologic and cortical response to acute psychosocial stress in left temporal lobe epilepsy - a pilot cross-sectional fMRI study.

Stress is commonly reported as a seizure precipitant in individuals with poorly controlled seizures including temporal lobe epilepsy. The aim of the study was to assess the neural and physiologic correlates of psychosocial stress response during functional magnetic resonance imaging (fMRI) and their relationship with seizure occurrence in patients with left temporal lobe epilepsy (LTLE). We enrolled 23 patients with LTLE and 23 age- and sex-matched healthy controls (HCs); all underwent fMRI with control math task (CMT) and stress math task (SMT) and pre-/post-fMRI salivary cortisol analysis (acute stress reactivity calculated as % reduction from post-stress to recovery baseline; dCORT). The Beck Depression Inventory-II (BDI-II) and Perceived Stress Scale (PSS-10) were administered. T-tests of performance and cortisol variables were performed. Processing and single-subject modeling of fMRI response to CMT positive feedback and SMT negative feedback, group comparisons, and whole-brain correlation of seizure occurrence and fMRI response in patients with poorly controlled LTLE were performed. Patients with LTLE and healthy controls were similar in demographics, math performance, heart rate, and PSS-10 scores (all p>0.05). Patients with LTLE exhibited greater dCORT (p=0.048) and lower BDI-II scores (p=0.016) compared with HCs. Patients with poorly controlled LTLE showed a positive association between seizure frequency and dCORT (r=0.73, p=0.016). Functional MRI activation to feedback was similar between groups, including midfrontal, temporal, parietal, and occipital regions. Regression analyses revealed no group differences to positive feedback, but, compared with HCs, patients with LTLE showed decreased activation to negative feedback in the left cerebellum/middle occipital/fusiform gyri, left hippocampus/parahippocampus, bilateral medial frontal/cingulate/superior frontal gyri, right postcentral gyrus/inferior parietal lobule, and right insula/postcentral gyrus (p<0.05, corrected). Patients with poorly controlled LTLE showed negative association between seizure frequency and activation in the bilateral subgenual anterior cingulate (p<0.05, corrected). This study is the first to characterize the cortical and physiologic responses to acute psychosocial stress and to show a significant relationship between seizure control in LTLE and both the hypothalamic-pituitary-adrenal axis and fMRI signal reactivity to acute psychosocial stress. These findings extend our understanding of the complex interplay between stress, physiologic stress markers, and seizures/epilepsy.

Mean diffusivity as a potential diffusion tensor biomarker of motor rehabilitation after electrical stimulation incorporating task specific exercise in stroke: a pilot study.

Changes in diffusion tensor imaging (DTI) values co-occur with neurological and functional changes after stroke. However, quantitative DTI metrics have not been examined in response to participation in targeted rehabilitative interventions in chronic stroke. The primary purpose of this pilot study was to examine whether changes in DTI metrics co-occur with paretic arm movement changes among chronic stroke patients participating in a regimen of electrical stimulation targeting the paretic arm. Three subjects exhibiting stable arm hemiparesis were administered 30-minute (n = 1) or 120-minute (n = 2) therapy sessions emphasizing paretic arm use during valued, functional tasks and incorporating an electrical stimulation device. These sessions occurred every weekday for 8 weeks. A fourth subject served as a treatment control, participating in a 30-minute home exercise regimen without electrical stimulation every weekday for 8 weeks. DTI and behavioral outcome measures were acquired at baseline and after intervention. DTI data were analyzed using a region of interest (ROI) approach, with ROIs chosen based on tract involvement in sensorimotor function or as control regions. Behavioral outcome measures were the Fugl-Meyer Scale (FM) and the Action Research Arm Test (ARAT). The treatment control subject exhibited gains in pinch and grasp, as shown by a 5-point increase on the ARAT. The subject who participated in 30-minute therapy sessions exhibited no behavioral gains. Subjects participating in 120-minute therapy sessions displayed consistent impairment reductions and distal movement changes. DTI changes were largest in subjects two and three, with mean diffusivity (MD) decreases in the middle cerebellar peduncle and posterior limb of the internal capsule following treatment. No changes in fractional anisotropy (FA) were observed for sensorimotor tracts. Our preliminary results suggest that active rehabilitative therapies augmented by electrical stimulation may induce positive behavioral changes which are underscored by DTI changes indicative of increased white matter tract integrity in regions specific to sensory-motor function.

Changes in white matter integrity follow excitatory rTMS treatment of post-stroke aphasia.

PURPOSE: In this study, we examine whether an excitatory repetitive transcranial magnetic stimulation (rTMS) protocol called intermittent theta burst stimulation (iTBS) applied to the affected left hemisphere leads to changes in white matter fractional anisotropy (FA). METHODS: Diffusion tensor imaging (DTI) data were collected in 8 aphasic stroke patients before and after 10 daily iTBS treatments. Alignment of structural and DTI data and derivation of diffusion index maps were performed using Analysis of Functional NeuroImages software followed by Tract-Based Spatial Statistics using FMRIB Software Library. Paired t-tests were performed to compare pre- to post-rTMS changes in FA. RESULTS: There were significant (p < 0.001) left-hemispheric FA increases near the inferior and superior frontal gyri and anterior corpus callosum. FA also increased in the right midbrain and bilaterally near temporal, parietal and posterior cingulate regions. FA decreased bilaterally near the fusiform gyrus and in left cerebellum. CONCLUSIONS: Overall, left-hemispheric regions that showed increased FA corresponded to areas previously shown to have increases in fMRI language activation after iTBS. The increased white matter integrity near the stimulation sites may reflect improvements in cortical function mediated by excitatory rTMS through its ability to facilitate synaptic connections.

Automated spine survey iterative scan technique.

Institutional review board approval, with waived consent, was obtained to develop a spine-labeling algorithm with retrospectively obtained deidentified HIPAA-compliant data. An automated magnetic resonance (MR) imaging technique to rapidly survey the entire spine and provide definitive numbering of disks and vertebrae was compared with neuroradiologist assignments in 50 cases. Contiguous two-station sagittal fast gradient-recalled-echo sequences with 35-cm fields of view (FOVs) were preprogrammed for full cervical, thoracic, and lumbar spine coverage (combined 70-cm FOV, seven sections, 15 mm left of to 15 mm right of midline, 4-mm section thickness, 1-mm intersection gap, 512 x 352 matrix, 58/2.0 [repetition time msec/echo time msec], 30 degrees flip angle, 15.6-kHz bandwidth, 42-second acquisition time). In all cases, the neuroradiologist could visualize and definitively number all cervical, thoracic, and lumbar levels on automated spine survey iterative scan technique localizer studies. Automated disk-vertebra detection and numbering were concordant with neuroradiologist assignments in all cases. The entire spine can be surveyed with subminute, submillimeter in-plane resolution MR imaging. Cervical, thoracic, and lumbar vertebrae and disks can be readily identified and definitively numbered by means of visual inspection or semiautomated computer algorithm.