Limb Preference Changes after Focused-Ultrasound Thalamotomy for Tremor.

BACKGROUND: Magnetic resonance-guided focused-ultrasound (MRgFUS) thalamotomy is an effective treatment for essential and other tremors. It targets the ventrointermedius (Vim) nucleus, which is the thalamic relay in a proprioceptive pathway, and contains kinesthetic cells. Although MRgFUS thalamotomy reduces some risks associated with more invasive surgeries, it still has side effects, such as balance and gait disturbances; these may be caused by the lesion impacting proprioception. OBJECTIVES: Our aim was to quantitatively measure the effects of MRgFUS on proprioception and limb use in essential tremor patients. We hypothesized that this thalamotomy alters proprioception, because the sensorimotor Vim thalamus is lesioned. METHODS: Proprioception was measured using the Kinarm exoskeleton robot in 18 patients. Data were collected pre-operatively, and then 1 day, 3 months, and 1 year after surgery. Patients completed four tasks, assessing motor coordination and postural control, goal-directed movement and bimanual planning, position sense, and kinesthesia. RESULTS: Immediately after surgery there were changes in posture speed (indicating tremor improvement), and in bimanual hand use, with the untreated limb being preferred. However, these measures returned to pre-operative baseline over time. There were no changes in parameters related to proprioception. None of these measures correlated with lesion size or lesion-overlap with the dentato-rubro-thalamic tract. CONCLUSIONS: This is the first quantitative assessment of proprioception and limb preference following MRgFUS thalamotomy. Our results suggest that focused-ultrasound lesioning of the Vim thalamus does not degrade proprioception but alters limb preference. This change may indicate a required "relearning" in the treated limb, because the effect is transient. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Microstructural Abnormalities of the Dentatorubrothalamic Tract in Cervical Dystonia.

BACKGROUND: The dentatorubrothalamic tract (DRTT) remains understudied in idiopathic cervical dystonia (CD), despite evidence that the pathway is relevant in the pathophysiology of the disorder. OBJECTIVE: The aim of this study was to examine the DRTT in patients with CD using diffusion tensor imaging (DTI)-based tractography. METHODS: Magnetic resonance imaging scans from 67 participants were collected to calculate diffusion tractography metrics using a binary tractography-based DRTT template. Fractional anisotropy and diffusivity measures of left and right DRTT were computed and compared between 32 subjects with CD and 35 age-matched healthy volunteers. RESULTS: Fractional anisotropy of right DRTT and mean and axial diffusivity of left DRTT were significantly reduced in patients with CD. Similar abnormalities were observed in patients with focal CD and patients with CD without tremor. DTI metrics did not correlate with disease duration or severity. CONCLUSIONS: Significant reductions in DTI measures suggest microstructural abnormalities within the DRTT in CD, characterized by a tractography pattern consistent with decreased axonal integrity. © 2021 International Parkinson and Movement Disorder Society.

Development of short-range white matter in healthy children and adolescents.

Neural communication is facilitated by intricate networks of white matter (WM) comprised of both long and short range connections. The maturation of long range WM connections has been extensively characterized, with projection, commissural, and association tracts showing unique trajectories with age. There, however, remains a limited understanding of age-related changes occurring within short range WM connections, or U-fibers. These connections are important for local connectivity within lobes and facilitate regional cortical function and greater network economy. Recent studies have explored the maturation of U-fibers primarily using cross-sectional study designs. Here, we analyzed diffusion tensor imaging (DTI) data for healthy children and adolescents in both a cross-sectional (n = 78; mean age = 13.04 ± 3.27 years) and a primarily longitudinal (n = 26; mean age = 10.78 ± 2.69 years) cohort. We found significant age-related differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) across the frontal, parietal, and temporal lobes of participants within the cross-sectional cohort. By contrast, we report significant age-related differences in only FA for participants within the longitudinal cohort. Specifically, larger FA values were observed with age in frontal, parietal, and temporal lobes of the left hemisphere. Our results extend previous findings restricted to long range WM to demonstrate regional changes in the microstructure of short range WM during childhood and adolescence. These changes possibly reflect continued myelination and axonal organization of short range WM with increasing age in more anterior regions of the left hemisphere. Hum Brain Mapp 39:204-217, 2018. © 2017 Wiley Periodicals, Inc.

Dynamic DTI (dDTI) shows differing temporal activation patterns in post-exercise skeletal muscles.

OBJECT: To assess post-exercise recovery of human calf muscles using dynamic diffusion tensor imaging (dDTI). MATERIALS AND METHODS: DTI data (6 directions, b = 0 and 400 s/mm2) were acquired every 35 s from seven healthy men using a 3T MRI, prior to (4 volumes) and immediately following exercise (13 volumes, ~7.5 min). Exercise consisted of 5-min in-bore repetitive dorsiflexion-eversion foot motion with 0.78 kg resistance. Diffusion tensors calculated at each time point produced maps of mean diffusivity (MD), fractional anisotropy (FA), radial diffusivity (RD), and signal at b = 0 s/mm2 (S0). Region-of-interest (ROI) analysis was performed on five calf muscles: tibialis anterior (ATIB), extensor digitorum longus (EDL) peroneus longus (PER), soleus (SOL), and lateral gastrocnemius (LG). RESULTS: Active muscles (ATIB, EDL, PER) showed significantly elevated initial MD post-exercise, while predicted inactive muscles (SOL, LG) did not (p < 0.0001). The EDL showed a greater initial increase in MD (1.90 × 10-4mm2/s) than ATIB (1.03 × 10-4mm2/s) or PER (8.79 × 10-5 mm2/s) (p = 7.40 × 10-4), and remained significantly elevated across more time points than ATIB or PER. Significant increases were observed in post-exercise EDL S0 relative to other muscles across the majority of time points (p < 0.01 to p < 0.001). CONCLUSIONS: dDTI can be used to differentiate exercise-induced changes between muscles. These differences are suggested to be related to differences in fiber composition.

An exploration of diffusion tensor eigenvector variability within human calf muscles.

PURPOSE: To explore the effect of diffusion tensor imaging (DTI) acquisition parameters on principal and minor eigenvector stability within human lower leg skeletal muscles. MATERIALS AND METHODS: Lower leg muscles were evaluated in seven healthy subjects at 3T using an 8-channel transmit/receive coil. Diffusion-encoding was performed with nine signal averages (NSA) using 6, 15, and 25 directions (NDD). Individual DTI volumes were combined into aggregate volumes of 3, 2, and 1 NSA according to number of directions. Tensor eigenvalues (λ1 , λ2 , λ3 ), eigenvectors (ε1 , ε2 , ε3 ), and DTI metrics (fractional anisotropy [FA] and mean diffusivity [MD]) were calculated for each combination of NSA and NDD. Spatial maps of signal-to-noise ratio (SNR), λ3 :λ2 ratio, and zenith angle were also calculated for region of interest (ROI) analysis of vector orientation consistency. RESULTS: ε1 variability was only moderately related to ε2 variability (r = 0.4045). Variation of ε1 was affected by NDD, not NSA (P < 0.0002), while variation of ε2 was affected by NSA, not NDD (P < 0.0003). In terms of tensor shape, vector variability was weakly related to FA (ε1 :r = -0.1854, ε2 : ns), but had a stronger relation to the λ3 :λ2 ratio (ε1 :r = -0.5221, ε2 :r = -0.1771). Vector variability was also weakly related to SNR (ε1 :r = -0.2873, ε2 :r = -0.3483). Zenith angle was found to be strongly associated with variability of ε1 (r = 0.8048) but only weakly with that of ε2 (r = 0.2135). CONCLUSION: The second eigenvector (ε2 ) displayed higher directional variability relative to ε1 , and was only marginally affected by experimental conditions that impacted ε1 variability.

Safe MRI-Compatible electrical muscle stimulation (EMS) system.

PURPOSE: To develop an inexpensive magnetic resonance imaging (MRI)-compatible electrical muscle stimulation (EMS) unit and test it for safety and efficacy. MATERIALS AND METHODS: A simple MRI-compatible EMS device was developed using radiofrequency (RF) translucent electrodes at 3T. RF heating concerns were assessed using optical temperature measurements at electrode sites, during scanning of a phantom. EMS efficacy and consistency was investigated through in vivo (n = 5) measures of 31 P-MRS phosphocreatine (PCr) reduction, and altered blood oxygen level-dependent (BOLD) signal and the results were compared to effects from equivalent voluntary effort on the same subjects. RESULTS: The presence of an EMS pulse did not interfere with the T2 * signal in a phantom. However, signal-to-noise ratio (SNR) was reduced by 70% at electrode sites, but only by 10% 4 cm distally. Under RF intense conditions, the temperature at the electrode site increased by only 4.7°C over a 16-minute time span. In vivo muscle stimulation resulted in 13.5 ± 1.8% reduction in PCr, which was not significantly (P < 0.195) different from voluntary contraction. Reproducible muscle BOLD signal changes following EMS were noted, with a maximal increase of 10.0 ± 2.6% seen in the central soleus. For soleus and gastrocnemius compartments, EMS produced significantly higher BOLD signal change compared to voluntary contraction (P < 0.05). CONCLUSION: A safe and inexpensive MRI-compatible EMS unit can be easily built for evaluating muscle function and metabolism within a 3T MRI scanner. Clinical applications might include evaluating skeletal muscle function in patients with limited or absent voluntary skeletal motor function or inadequate exercise capacity. J. Magn. Reson. Imaging 2016;44:1530-1538.

Tumor volumetric measurements in surgically inaccessible pediatric low-grade glioma.

Tumor measurement is important in unresectable pediatric low-grade gliomas (pLGGs) to determine either the need for treatment or assess response. Standard methods measure the product of the largest 2 lengths from transverse, anterior-posterior, and cranio-caudal dimensions (SM, cm). This single-institution study evaluated tumor volume measurements (VM, cm) in such pLGGs. Of 50 patients treated with chemotherapy for surgically inaccessible pLGG, 8 met the inclusion criteria of having 2 or more sequential MRI studies of T1-weighted Fast-Spoiled Gradient Recalled acquisition. SM and VM were performed by 2 independent neuroradiologists. Associations of measurement methods with defined therapeutic response criteria and patient clinical status were assessed. The mean tumor size at the first MRI scan was 20 cm and 398 cm according to SM and VM, respectively. VM results did not differ significantly from SM-derived spherical volume calculations (Pearson correlation, P<0.0001) with a high interrater reliability. Both methods were concordant in defining the tumor response according to the current criteria, although radiologic progressive disease was not associated with clinical status (SM: P=0.491, VM: P=0.208). In this limited experience, volumetric analysis of unresectable pLGGs did not seem superior to the standard linear measurements for defining tumor response.

Relations between white matter maturation and reaction time in childhood.

White matter matures with age and is important for the efficient transmission of neuronal signals. Consequently, white matter growth may underlie the development of cognitive processes important for learning, including the speed of information processing. To dissect the relationship between white matter structure and information processing speed, we administered a reaction time task (finger abduction in response to visual cue) to 27 typically developing, right-handed children aged 4 to 13. Magnetoencephalography and Diffusion Tensor Imaging were used to delineate white matter connections implicated in visual-motor information processing. Fractional anisotropy (FA) and radial diffusivity (RD) of the optic radiation in the left hemisphere, and FA and mean diffusivity (MD) of the optic radiation in the right hemisphere changed significantly with age. MD and RD decreased with age in the right inferior fronto-occipital fasciculus, and bilaterally in the cortico-spinal tracts. No age-related changes were evident in the inferior longitudinal fasciculus. FA of the cortico-spinal tract in the left hemisphere and MD of the inferior fronto-occipital fasciculus of the right hemisphere contributed uniquely beyond the effect of age in accounting for reaction time performance of the right hand. Our findings support the role of white matter maturation in the development of information processing speed.

Altered cingulum bundle microstructure in autism spectrum disorder.

OBJECTIVE: Here, we examined the cingulum bundle, a long-range white matter tract mediating dorsal limbic connectivity, using diffusion tensor imaging (DTI) tractography, in children and adolescents with autism spectrum disorder (ASD) versus controls. We hypothesised that cingulum bundle microstructure would be altered in ASD, based on evidence implicating abnormal white matter connectivity in this disorder. METHODS: DTI data were acquired for 19 ASD participants (IQ ⩾ 70; 7-18 years; mean = 12.4 ± 3.1) and 16 age-matched controls (7-18 years; mean = 12.3 ± 3.6) on a 3 T magnetic resonance imaging system. Deterministic tractography was used to isolate the cingulum bundle. Left and right cingulum bundles were examined for differences in several DTI metrics in ASD children/adolescents versus controls, including: fractional anisotropy (FA), mean, axial, and radial diffusivity. RESULTS: Significant age × group interaction effects were found for all DTI metrics (mean diffusivity: F 1,28 = 9.5, p = 0.005, radial diffusivity: F 1,28 = 7.8, p = 0.009, axial diffusivity: F 1,28 = 5.2, p = 0.03, FA: F 1,28 = 4.4, p = 0.04). Interaction effects were driven by increases in cingulum bundle diffusivity (mean, radial, and axial diffusivity), and decreased FA, in younger ASD participants within our sample versus controls. CONCLUSION: Our results point to immature microstructural organisation of the cingulum bundle in ASD, particularly during the early years of life, with implications for limbic network synchronisation and complex socio-emotional performance.

White matter maturation in visual and motor areas predicts the latency of visual activation in children.

In humans, white matter maturation is important for the improvement of cognitive function and performance with age. Across studies the variables of white matter maturity and age are highly correlated; however, the unique contributions of white matter to information processing speed remain relatively unknown. We investigated the relations between the speed of the visually-evoked P100m response and the biophysical properties of white matter in 11 healthy children performing a simple, visually-cued finger movement. We found that: (1) the latency of the early, visually-evoked response was related to the integrity of white matter in both visual and motor association areas and (2) white matter maturation in these areas accounted for the variations in visual processing speed, independent of age. Our study is a novel investigation of spatial-temporal dynamics in the developing brain and provides evidence that white matter maturation accounts for age-related decreases in the speed of visual response. Developmental models of cortical specialization should incorporate the unique role of white matter maturation in mediating changes in performance during tasks involving visual processing.

Cerebello-thalamo-cerebral connections in pediatric brain tumor patients: impact on working memory.

Brain tumors are the leading cause of death and disability from childhood disease in developed countries. Pediatric posterior fossa tumors are often effectively controlled with a combination of surgery, radiation, and chemotherapy, depending on tumor type. White matter injury following resection of tumor and radiation treatment is associated with cognitive declines, including working memory deficits. We investigated how brain injury following treatment for posterior fossa tumors results in deficits in working memory. We used diffusion tensor imaging and probabilistic tractography to examine the structural integrity of cerebello-thalamo-cerebral tracts in patients and healthy children. We also compared working memory outcome in patients versus controls, and related this function to integrity of cerebello-thalamo-cerebral tracts. Bilateral cerebello-thalamo-cerebral tracts were delineated in all participants. Patients treated with a combination of surgery and radiation had lower mean anisotropy and higher mean radial diffusivity within the cerebellar regions of the cerebello-thalamo-cerebral tract compared to patients treated with surgery only and healthy controls. Poorer working memory scores were observed for the cranial radiation group relative to controls. Reduced anisotropy and higher radial diffusivity within the entire cerebello-thalamo-cerebral pathway predicted lower working memory. Our finding that working memory function is related to the integrity of cerebello-thalamo-cerebral connections is a novel contribution to the understanding of cerebral-cerebellar communication. Identifying differences in the structural integrity of white matter for specific pathways is an essential step in attempting to localize the effects of posterior fossa tumors and their treatment methods.

White matter integrity and core cognitive function in children diagnosed with sickle cell disease.

Children diagnosed with sickle cell disease (SCD) have an increased risk of stroke, often associated with white matter damage and neurocognitive morbidity. Growing evidence suggests that subtle changes in white matter integrity, which do not pass the threshold to be visible on a clinical magnetic resonance image and classified as stroke, may contribute to decreased cognitive performance. We used archived diffusion-weighted imaging and neurocognitive assessment data to identify associations between microstructural changes in normal-appearing white matter and cognitive performance in children with SCD. Study participants included 10 healthy children and 15 pediatric SCD patients (5 with identified lesions and 10 without lesion). After excluding lesioned tissue from analyses, we detected significant increases in apparent diffusion coefficient across the brains of patients in comparison with control children, suggesting compromise to the structure of normal-appearing white matter. Deficits in working memory and processing speed were also apparent in patients. Increased apparent diffusion coefficient and deficiencies in processing speed were again detected in a subanalysis including only the patients without lesion. Correlation analyses evidenced associations between the microstructure of the right frontal lobe and cerebellum, and processing speed. This outcome suggests a relationship between tissue integrity and cognitive morbidity in SCD patients.

Mapping of the cortical spinal tracts using magnetoencephalography and diffusion tensor tractography in pediatric brain tumor patients.

Prior to resection of a cerebral brain tumor, mapping of the functional and structural anatomy of the adjacent tissue is essential to reduce the risk of damage to descending and ascending pathways. We investigated the effectiveness of concurrent magnetoencephalography (MEG) and diffusion tensor imaging (DTI) tractography to delineate the motor cortex and associated corticospinal tract (CST) in a case series of children with brain tumors seen for pre-surgical evaluation. Using activation points generated from MEG to launch tractography, we delineated the CST of four patients and eight control subjects. Displacement of the CST was considerably larger in children with tumors located in the center of the hemisphere than in children whose tumors were more posteriorly located. Our findings suggest that the use of concurrent MEG and DTI may be an effective tool in the pre-surgical evaluation of eloquent cortex and associated white matter tracts in pediatric brain tumor patients.

Diffusion tensor imaging of white matter after cranial radiation in children for medulloblastoma: correlation with IQ.

Treatment of children with cranial-spinal radiation (CSR) for brain tumors is associated with adverse intellectual outcome and white matter damage. However, the correlation between IQ and measures of white matter integrity has received little attention. We examined apparent diffusion coefficient (ADC), fractional anisotropy (FA), and intelligence in pediatric patients treated with CSR for medulloblastoma relative to control subjects. ADC and FA measures were obtained for eight patients and eight control children and evaluated in multiple regions of interest in the cerebral hemispheres. Mean ADC and mean FA for each region were calculated, group differences were evaluated, and the relationship between these measures and intelligence were examined. In our study group, decreased IQ was associated with increased ADC and decreased FA (P < 0.01). Mean IQ for the CSR group was lower than that for the control group, but the difference was not significant when controlling for overall mean FA or ADC (P > 0.10). Overall mean FA was lower and ADC was higher in the CSR group relative to controls (P < 0.01). Specifically, FA was lower in the genu of the corpus callosum, the anterior and posterior limbs of the internal capsule, inferior frontal white matter, and high frontal white matter, and ADC was higher in all regions in patients relative to controls (P < 0.01). Compromised white matter integrity was observed for multiple regions within the cerebral hemispheres following CSR. A novel finding was that microscopic damage in normal-appearing white matter, as indexed by higher ADC and lower FA, was related to poor intellectual outcome relative to age-matched controls.

Utility of simultaneous brain, CSF and hyperintensity quantification in dementia.

Improved methods of quantifying MRI are needed to study brain-behavior relationships in dementia. Rating scales are variable; lesion-tracing approaches can be subjective and ignore atrophy; segmentation of MRI hyperintensities is complicated by partial volume effects; and hyperintense lesions in different anatomical areas may have different effects. The goal of this study was to extend existing segmentation approaches to include hyperintensities and to demonstrate the utility of simultaneously assessing atrophy and lesion compartments in dementia. A semi-automated method was applied to quantify brain and cerebrospinal fluid (CSF) compartments and to subclassify hyperintensities into periventricular, deep white matter, thalamic and basal ganglia compartments. Twenty MR scans from participants in an ongoing dementia study were used to generate intra- and inter-rater reliability estimates. High intra- and inter-class correlation coefficients (0.83-0.99) were obtained for all measures and the semi-automated measurements were highly correlated with traced volumes. Brain, CSF and specific lesion volumes were significantly correlated with neuropsychological functions. In models using only total hyperintensity volumes, the effects of lesion compartments (such as thalamic) were masked. Simultaneous quantification of atrophy and anatomically distinct hyperintensities is important for understanding cognitive impairments in dementia.

Functional reorganization of the corticospinal tract in a pediatric patient with an arteriovenous malformation.

Presurgical mapping in a pediatric patient diagnosed with arteriovenous malformation in the left hemisphere revealed a case of apparent functional reorganization of a white matter tract. Magnetoencephalography (MEG) was used to identify the motor fields following hand movement. As expected, motor field activity for the left hand was detected in the right hemisphere. Surprisingly, MEG activity was also detected in the right hemisphere following movement of the right hand. MEG activations served as seeds from which to launch diffusion tensor imaging tractography to delineate the corticospinal tracts (CSTs). Using the MEG activation for movement of the right hand, we delineated a tract in the right hemisphere. A tract corresponding to motor function for the left hand was also delineated in the right hemisphere. For comparison, the CSTs of the patient were launched from anatomical landmarks at the precentral gyrus, and were successfully delineated in each hemisphere. Our findings suggest that the functional delineation of white matter pathways may be more sensitive than anatomical delineation for identifying reorganization of the developing brain in response to a lesion. This study is, to our knowledge, the first description of a functional reorganization of an existing tract to serve as a CST in children.

Impaired structural connectivity of socio-emotional circuits in autism spectrum disorders: a diffusion tensor imaging study.

BACKGROUND: Abnormal white matter development may disrupt integration within neural circuits, causing particular impairments in higher-order behaviours. In autism spectrum disorders (ASDs), white matter alterations may contribute to characteristic deficits in complex socio-emotional and communication domains. Here, we used diffusion tensor imaging (DTI) and tract based spatial statistics (TBSS) to evaluate white matter microstructure in ASD. METHODS/PRINCIPAL FINDINGS: DTI scans were acquired for 19 children and adolescents with ASD (∼8-18 years; mean 12.4±3.1) and 16 age and IQ matched controls (∼8-18 years; mean 12.3±3.6) on a 3T MRI system. DTI values for fractional anisotropy, mean diffusivity, radial diffusivity and axial diffusivity, were measured. Age by group interactions for global and voxel-wise white matter indices were examined. Voxel-wise analyses comparing ASD with controls in: (i) the full cohort (ii), children only (≤12 yrs.), and (iii) adolescents only (>12 yrs.) were performed, followed by tract-specific comparisons. Significant age-by-group interactions on global DTI indices were found for all three diffusivity measures, but not for fractional anisotropy. Voxel-wise analyses revealed prominent diffusion measure differences in ASD children but not adolescents, when compared to healthy controls. Widespread increases in mean and radial diffusivity in ASD children were prominent in frontal white matter voxels. Follow-up tract-specific analyses highlighted disruption to pathways integrating frontal, temporal, and occipital structures involved in socio-emotional processing. CONCLUSIONS/SIGNIFICANCE: Our findings highlight disruption of neural circuitry in ASD, particularly in those white matter tracts that integrate the complex socio-emotional processing that is impaired in this disorder.

The relations between white matter and declarative memory in older children and adolescents.

Neural communication between the temporal and frontal cortex underlies mature declarative memory skills. The integrity of white matter pathways connecting these regions is likely critical in supporting this communication. Little is known about the relationship between white matter and declarative memory in older children and adolescents, an age period when advanced function in this domain is established. We acquired diffusion tensor imaging (DTI) data for 22 participants (9-15 years). Multiple DTI indices were calculated for the uncinate fasciculus - the major white matter tract connecting temporal and prefrontal regions. Indices were also calculated for compartments of lobar and posterior fossa white matter. Measures of visual-perceptual and auditory-verbal memory were administered. Correlation analyses were used to examine the relations between age, DTI indices, and memory. Voxel-wise analyses were also conducted. Age-related increases in FA were evident for frontal, parietal, and temporal hemispheric white matter. Proficiency in auditory-verbal memory was related to white matter integrity in the left uncinate fasciculus as well as parietal and cerebellar white matter. Proficiency in recall of a complex design was related to integrity within parietal and temporal regions. Our findings support the role of white matter in facilitating connectivity between cerebral regions important for declarative memory.