Serial Diffusion Tensor Imaging Research Articles

Stereotactic diffusion tensor imaging tractography for Gamma Knife radiosurgery.

OBJECTIVE The integration of modern neuroimaging into treatment planning has increased the therapeutic potential and safety of stereotactic radiosurgery. The authors report their method of integrating stereotactic diffusion tensor imaging (DTI) tractography into conventional treatment planning for Gamma Knife radiosurgery (GKRS). The aim of this study was to demonstrate the feasibility of this technique and to address some of the technical limitations of previously reported techniques. METHODS Twenty patients who underwent GKRS composed the study cohort. They consisted of 1 initial test case (a patient with a vestibular schwannoma), 5 patients with arteriovenous malformations, 9 patients with cerebral metastases, 1 patient with parasagittal meningioma, and 4 patients with vestibular schwannoma. DT images were obtained at the time of standard GKRS protocol MRI (T1 and T2 weighted) for treatment, with the patient's head secured by a Leksell stereotactic frame. All studies were performed using a 1.5-T magnet with a single-channel head coil. DTI was performed with diffusion gradients in 32 directions and coregistered with the volumetric T1-weighted study. DTI postprocessing by means of commercially available software allowed tensor computation and the creation of directionally encoded color-, apparent diffusion coefficient-, and fractional anisotropy-mapped sequences. In addition, the software allowed visualized critical tracts to be exported as a structural volume and integrated into GammaPlan as an "organ at risk" during shot planning. Combined images were transferred to GammaPlan and integrated into treatment planning. RESULTS Stereotactic DT images were successfully acquired in all patients, with generation of correct directionally encoded color images. Tract generation with the software was straightforward and reproducible, particularly for axial tracts such as the optic radiation and the arcuate fasciculus. Corticospinal tract visualization was hampered by some artifacts from the base of the stereotactic frame, but this was overcome by a combination of frame/MRI volume adjustment and DTI seeding parameters. Coregistration of the DTI series with the T1-weighted treatment volume at the time of imaging was essential for the generation of correct tensor data. All patients with the exception of the vestibular schwannoma cases had treatment pathology in the vicinity of eloquent tracts and/or the cortex. No new neurological deficits due to radiation were recorded at the short-term follow-up. CONCLUSIONS Recent reports in the medical literature have suggested that white matter tracts (particularly the optic radiation and arcuate fasciculus) are more vulnerable to radiation during stereotactic radiosurgery than previously thought. Integration of stereotactic tractography into GKRS represents a promising tool for preventing GKRS complications by reduction in radiation doses to functional organs at risk, including critical cortical areas and subcortical white matter tracts.

Mild encephalitis/encephalopathy with reversible splenial lesion (MERS) due to dengue virus

A 14-year-old girl presented with encephalopathy, delirium and ophthalmoplegia following a 3day history of high-grade fever. Brain MRI on day 6 of illness showed diffusion restricted ovoid lesion in the splenium of corpus callosum. Dengue virus encephalitis was diagnosed with positive PCR for dengue virus type-2 in both serum and cerebrospinal fluid. She made a complete recovery from day 10 of illness. Repeat brain MRI on day 12 of illness showed resolution of the splenial lesion. Serial diffusion tensor imaging (DTI) showed normal fractional anisotropy values on resolution of splenial lesion indicating that MERS was likely due to transient interstitial oedema with preservation of white matter tracts. This is the first reported case of MERS following dengue virus infection. It highlights the usefulness of performing serial DTI in understanding the underlying pathogenesis of MERS. Our case report widens the neurological manifestations associated with dengue infection and reiterates that patients with MERS should be managed supportively as the splenial white matter tracts are reversibly involved in MERS.

Acute white matter changes following sport-related concussion: A serial diffusion tensor and diffusion kurtosis tensor imaging study.

Recent neuroimaging studies have suggested that following sport-related concussion (SRC) physiological brain alterations may persist after an athlete has shown full symptom recovery. Diffusion MRI is a versatile technique to study white matter injury following SRC, yet serial follow-up studies in the very acute stages following SRC utilizing a comprehensive set of diffusion metrics are lacking. The aim of the current study was to characterize white matter changes within 24 hours of concussion in a group of high school and collegiate athletes, using Diffusion Tensor and Diffusion Kurtosis Tensor metrics. Participants were reassessed a week later. At 24 hours post-injury, the concussed group reported significantly more concussion symptoms than a well-matched control group and demonstrated poorer performance on a cognitive screening measure, yet these differences were nonsignificant at the 8-day follow-up. Similarly, within 24-hours after injury, the concussed group exhibited a widespread decrease in mean diffusivity, increased axial kurtosis and, to a lesser extent, decreased axial and radial diffusivities compared with control subjects. At 8 days post injury, the differences in these diffusion metrics were even more widespread in the injured athletes, despite improvement of symptoms and cognitive performance. These MRI findings suggest that the athletes might not have reached full physiological recovery a week after the injury. These findings have significant implications for the management of SRC because allowing an athlete to return to play before the brain has fully recovered from injury may have negative consequences. Hum Brain Mapp 37:3821-3834, 2016. © 2016 Wiley Periodicals, Inc.

Longitudinal change in white matter in preterm infants without magnetic resonance imaging abnormalities: Assessment of serial diffusion tensor imaging and their relationship to neurodevelopmental outcomes

PurposeWe used diffusion tensor imaging (DTI) to evaluate longitudinal changes in fractional anisotropy (FA) of white matter tracts in preterm infants without abnormal magnetic resonance imaging (MRI) findings. Imaging was conducted at term equivalent age (TEA) and 1year of corrected age. Furthermore, we assessed correlations between FA and neurodevelopmental outcomes at 3years of corrected age to investigate brain prematurity of preterm infants without MRI abnormalities. MethodsPreterm infants underwent serial MRI at TEA and 1year of corrected age. Of these, 13 infants entered a retrospective study, undergoing neurodevelopmental assessment at 3years of corrected age. These infants were divided into two groups depending on gestational age (GA): <26weeks and ⩾26weeks. DTI-based tractography was performed to obtain the FA of the motor tract, sensory tract, superior cerebellar peduncle, middle cerebellar peduncle, and corpus callosum. FA was compared between two groups, and correlations between FA and neurodevelopmental outcomes were assessed. ResultsFA of the splenium at TEA was significantly different between the two groups divided according to GA. However, this difference was no longer observed at 1year of corrected age. There was no correlation between FA of the splenium at TEA and neurodevelopmental assessment scores at 3years of corrected age. ConclusionsAt TEA, FA of the splenium was lower in younger GA infants without MRI abnormalities, but this may not affect subsequent neurodevelopmental outcomes.

Serial Diffusion Tensor Imaging In Vivo Predicts Long-Term Functional Recovery and Histopathology in Rats following Different Severities of Spinal Cord Injury.

The current study demonstrates the feasibility of using serial magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) in vivo to quantify temporally spinal cord injury (SCI) pathology in adult female Sprague-Dawley rats that were scanned prior to a moderate or severe upper lumbar contusion SCI. Injured rats were behaviorally tested for hind limb locomotion (Basso, Beattie, Bresnahan [BBB] scores) weekly for 4 weeks and scanned immediately after each session, ending with terminal gait analyses prior to euthanasia. As a measure of tissue integrity, fractional anisotropy (FA) values were significantly lower throughout the spinal cord in both injury cohorts at all time-points examined versus pre-injury. Moreover, FA values were significantly lower following severe versus moderate SCI at all time-points, and FA values at the injury epicenters at all time-points were significantly correlated with both spared white and gray matter volumes, as well as lesion volumes. Critically, quantified FA values at subacute (24 h) and all subsequent time-points were highly predictive of terminal behavior, reflected in significant correlations with both weekly BBB scores and terminal gait parameters. Critically, the finding that clinically relevant subacute (24 h) FA values accurately predict long-term functional recovery may obviate long-term studies to assess the efficacy of therapeutics tested experimentally or clinically. In summary, this study demonstrates a reproducible serial MRI procedure to predict the long-term impact of contusion SCI on both behavior and histopathology using subacute DTI metrics obtained in vivo to accurately predict multiple terminal outcome measures, which can be particularly valuable when comparing experimental interventions.

Spatial regression analysis of serial DTI for subject-specific longitudinal changes of neurodegenerative disease.

Quantitative measurement of localized longitudinal changes in brain abnormalities at an individual level may offer critical information for disease diagnosis and treatment. The voxel-wise permutation-based method SPREAD/iSPREAD, which combines resampling and spatial regression of neighboring voxels, provides an effective and robust method for detecting subject-specific longitudinal changes within the whole brain, especially for longitudinal studies with a limited number of scans. As an extension of SPREAD/iSPREAD, we present a general method that facilitates analysis of serial Diffusion Tensor Imaging (DTI) measurements (with more than two time points) for testing localized changes in longitudinal studies. Two types of voxel-level test statistics (model-free test statistics, which measure intra-subject variability across time, and test statistics based on general linear model that incorporate specific lesion evolution models) were estimated and tested against the null hypothesis among groups of DTI data across time. The implementation and utility of the proposed statistical method were demonstrated by both Monte Carlo simulations and applications on clinical DTI data from human brain in vivo. By a design of test statistics based on the disease progression model, it was possible to apportion the true significant voxels attributed to the disease progression and those caused by underlying anatomical differences that cannot be explained by the model, which led to improvement in false positive (FP) control in the results. Extension of the proposed method to include other diseases or drug effect models, as well as the feasibility of global statistics, was discussed. The proposed statistical method can be extended to a broad spectrum of longitudinal studies with carefully designed test statistics, which helps to detect localized changes at the individual level.

Serial Diffusion Tensor Imaging of the Optic Radiations after Acute Optic Neuritis.

Previous studies have reported diffusion tensor imaging (DTI) changes within the optic radiations of patients after optic neuritis (ON). We aimed to study optic radiation DTI changes over 12 months following acute ON and to study correlations between DTI parameters and damage to the optic nerve and primary visual cortex (V1). We measured DTI parameters [fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD)] from the optic radiations of 38 acute ON patients at presentation and 6 and 12 months after acute ON. In addition, we measured retinal nerve fibre layer thickness, visual evoked potential amplitude, optic radiation lesion load, and V1 thickness. At baseline, FA was reduced and RD and MD were increased compared to control. Over 12 months, FA reduced in patients at an average rate of −2.6% per annum (control = −0.51%; p = 0.006). Change in FA, RD, and MD correlated with V1 thinning over 12 months (FA: R = 0.450, p = 0.006; RD: R = −0.428, p = 0.009; MD: R = −0.365, p = 0.029). In patients with no optic radiation lesions, AD significantly correlated with RNFL thinning at 12 months (R = 0.489, p = 0.039). In conclusion, DTI can detect optic radiation changes over 12 months following acute ON that correlate with optic nerve and V1 damage.

Characterization of White Matter Injury in a Rat Model of Chronic Cerebral Hypoperfusion

Chronic cerebral hypoperfusion can lead to ischemic white matter injury resulting in vascular dementia. To characterize white matter injury in vascular dementia, we investigated disintegration of diverse white matter components using a rat model of chronic cerebral hypoperfusion. Chronic cerebral hypoperfusion was modeled in Wistar rats by permanent occlusion of the bilateral common carotid arteries. We performed cognitive behavioral tests, including the water maze task, odor discrimination task, and novel object test; histological investigation of neuroinflammation, oligodendrocytes, myelin basic protein, and nodal or paranodal proteins at the nodes of Ranvier; and serial diffusion tensor imaging. Cilostazol was administered to protect against white matter injury. Diverse cognitive impairments were induced by chronic cerebral hypoperfusion. Disintegration of white matter was characterized by neuroinflammation, loss of oligodendrocytes, attenuation of myelin density, structural derangement at the nodes of Ranvier, and disintegration of white matter tracts. Cilostazol protected against cognitive impairments and white matter disintegration. White matter injury induced by chronic cerebral hypoperfusion can be characterized by disintegration of diverse white matter components. Cilostazol might be a therapeutic strategy against white matter disintegration in patients with vascular dementia.

Spotlight on the November 3 Issue

#### Notable in Neurology This issue features an article using serial diffusion tensor imaging to show that cerebral tubers are neither static nor discrete and another article discussing the clinical and genetic analyses of 110 patients with paroxysmal kinesigenic dyskinesia. Another featured article focuses on the risk factors of postictal generalized EEG suppression in generalized convulsive seizures. ### Survival in synucleinopathies: A prospective cohort study This study compared survival in synucleinopathies involving orthostatic hypotension (OH), including Parkinson disease (PD) and multiple system atrophy (MSA). …

Tubers are neither static nor discrete: Evidence from serial diffusion tensor imaging.

To assess the extent and evolution of tissue abnormality of tubers, perituber tissue, and normal-appearing white matter (NAWM) in patients with tuberous sclerosis complex using serial diffusion tensor imaging. We applied automatic segmentation based on a combined global-local intensity mixture model of 3T structural and 35 direction diffusion tensor MRIs (diffusion tensor imaging) to define 3 regions: tuber tissue, an equal volume perituber rim, and the remaining NAWM. For each patient, scan, lobe, and tissue type, we analyzed the averages of mean diffusivity (MD) and fractional anisotropy (FA) in a generalized additive mixed model. Twenty-five patients (mean age 5.9 years; range 0.5-24.5 years) underwent 2 to 6 scans each, totaling 70 scans. Average time between scans was 1.2 years (range 0.4-2.9). Patient scans were compared with those of 73 healthy controls. FA values were lowest, and MD values were highest in tubers, next in perituber tissue, then in NAWM. Longitudinal analysis showed a positive (FA) and negative (MD) correlation with age in tubers, perituber tissue, and NAWM. All 3 tissue types followed a biexponential developmental trajectory, similar to the white matter of controls. An additional qualitative analysis showed a gradual transition of diffusion values across the tissue type boundaries. Similar to NAWM, tuber and perituber tissues in tuberous sclerosis complex undergo microstructural evolution with age. The extent of diffusion abnormality decreases with distance to the tuber, in line with known extension of histologic, immunohistochemical, and molecular abnormalities beyond tuber pathology.

Improvement of Diffusion Tensor Imaging (DTI) Parameters with Decoppering Treatment in Wilson's Disease.

This study was undertaken to analyse serially the effects of decoppering therapy on the clinical features, disability and MRI brain including DTI metrics in patients with Wilson's disease. Thirty-five patients with clinically and serologically confirmed neuropsychiatric form of Wilson's disease (WD) on decoppering therapy were followed for a minimum duration of 1 year with serial assessment of their clinical features, disability status and serial MR imaging of the brain including DTI. The cohort included 18 treatment-naïve patients and 17 patients already on decoppering therapy (M/F = 2.18:1). The mean age at which they underwent baseline assessment for this study was 18.6 ± 7.6 years, and follow-up assessment was done after a mean duration of 23.5 ± 8.8 months (range, 12 to 45 months). Along with the overall clinical improvement noted at follow-up, the disability assessed using Chu staging and MSEADL showed significant reduction in the number of patients with severe disability and the mean NSS reducing from 9.74 to 6.37 (p = 0.002). The mean MRI scores showed significantly reduced disease burden from a baseline score of 5.9 (±4.2) to 4.9 (±4.7) in follow-up scans (p < 0.05). Voxel-wise comparison of serial DTI metrics on TBSS (tract-based spatial statistics) analysis showed that the entire cohort had significant (p < 0.05) improvement in all the four parameters (MD, FA, DA and RD) indicated by a decrease in MD, DA and RD values and increase in FA values. Comparison of whole-brain white matter DTI measures between pre- and posttreatment did not show any significant difference (p < 0.05). Patients with Wilson's disease on decoppering therapy showed clinical improvement accompanied with improvement in DTI metrics. Quantitative DTI metrics may be used as surrogate markers of clinical status following initiation of medical therapy in Wilson's disease.

Global and regional brain mean diffusivity changes in patients with heart failure.

Heart failure (HF) patients show gray and white matter changes in multiple brain sites, including autonomic and motor coordination areas. It is unclear whether the changes represent acute or chronic tissue pathology, a distinction necessary for understanding pathological processes that can be resolved with diffusion tensor imaging (DTI)-based mean diffusivity (MD) procedures. We collected four DTI series from 16 HF (age 55.1 ± 7.8 years, 12 male) and 26 control (49.7 ± 10.8 years, 17 male) subjects with a 3.0-Tesla magnetic resonance imaging scanner. MD maps were realigned, averaged, normalized, and smoothed. Global and regional MD values from autonomic and motor coordination sites were calculated by using normalized MD maps and brain masks; group MD values and whole-brain smoothed MD maps were compared by analysis of covariance (covariates; age and gender). Global brain MD (HF vs. controls, units × 10(-6) mm(2) /sec, 1103.8 ± 76.6 vs. 1035.9 ± 69.4, P = 0.038) and regional autonomic and motor control site values (left insula, 1,085.4 ± 95.7 vs. 975.7 ± 65.4, P = 0.001; right insula, 1,050.2 ± 100.6 vs. 965.7 ± 58.4, P = 0.004; left hypothalamus, 1,419.6 ± 165.2 vs. 1,234.9 ± 136.3, P = 0.002; right hypothalamus, 1,446.5 ± 178.8 vs. 1,273.3 ± 136.9, P = 0.004; left cerebellar cortex, 889.1 ± 81.9 vs. 796.6 ± 46.8, P < 0.001; right cerebellar cortex, 797.8 ± 50.8 vs. 750.3 ± 27.5, P = 0.001; cerebellar deep nuclei, 1,236.1 ± 193.8 vs. 1,071.7 ± 107.1, P = 0.002) were significantly higher in HF vs. control subjects, indicating chronic tissue changes. Whole-brain comparisons showed increased MD values in HF subjects, including limbic, basal-ganglia, thalamic, solitary tract nucleus, frontal, and cerebellar regions. Brain injury occurs in autonomic and motor control areas, which may contribute to deficient function in HF patients. The chronic tissue changes likely result from processes that develop over a prolonged period.

Longitudinal diffusion tensor imaging in frontotemporal dementia.

ObjectiveNovel biomarkers for monitoring progression in neurodegenerative conditions are needed. Measurement of microstructural changes in white matter (WM) using diffusion tensor imaging (DTI) may be a useful outcome measure. Here we report trajectories of WM change using serial DTI in a cohort with behavioral variant frontotemporal dementia (bvFTD).MethodsTwenty-three patients with bvFTD (12 having genetic mutations), and 18 age-matched control participants were assessed using DTI and neuropsychological batteries at baseline and ∼1.3 years later. Baseline and follow-up DTI scans were registered using a groupwise approach. Annualized rates of change for DTI metrics, neuropsychological measures, and whole brain volume were calculated. DTI metric performances were compared, and sample sizes for potential clinical trials were calculated.ResultsIn the bvFTD group as a whole, rates of change in fractional anisotropy (FA) and mean diffusivity (MD) within the right paracallosal cingulum were greatest (FA: −6.8%/yr, p < 0.001; MD: 2.9%/yr, p = 0.01). MAPT carriers had the greatest change within left uncinate fasciculus (FA: −7.9%/yr, p < 0.001; MD: 10.9%/yr, p < 0.001); sporadic bvFTD and C9ORF72 carriers had the greatest change within right paracallosal cingulum (sporadic bvFTD, FA: −6.7%/yr, p < 0.001; MD: 3.8%/yr, p = 0.001; C9ORF72, FA: −6.8%/yr, p = 0.004). Sample size estimates using FA change were substantially lower than neuropsychological or whole brain measures of change.InterpretationSerial DTI scans may be useful for measuring disease progression in bvFTD, with particular trajectories of WM damage emerging. Sample size calculations suggest that longitudinal DTI may be a useful biomarker in future clinical trials.

Serial Diffusion Tensor Images during Infancy and Their Relationship to Neuromotor Outcomes in Preterm Infants

Background: Even preterm infants with normal magnetic resonance imaging (MRI) results are at greater risk for neuromotor dysfunction. Objectives: Our aim was to compare serial diffusion tensor imaging (DTI) data from preterm infants without apparent brain abnormalities on magnetic resonance imaging with those from term controls and to investigate the white matter (WM) region associated with neuromotor outcomes. Methods: We obtained serial DTIs from 21 preterm infants at term-equivalent age (TEA) and 1 year of corrected age. As controls, 15 term neonates and 20 newly recruited term infants aged 1 year underwent DTI. Preterm and term infants at 1 year of age were assessed with the Bayley Scales of Infant Development, second edition. Tract-based spatial statistics and regions of interest were used for analysis. Results: At TEA, the entire WM development was delayed in the preterm infants compared with the term controls, but at 1 year of age, the WM development, except for that of the corpus callosum (CC), had reached the development level of the term controls. The psychomotor developmental index was positively correlated with the fractional anisotropy (FA) in the CC (particularly in the body and splenium) at 1 year of age after correcting for gestational age, chronic lung disease, and postnatal infection. Conclusions: The CC of the preterm infants was consistently underdeveloped compared with that of the term controls. The FA in the CC, particularly in the body and splenium at 1 year of age, well reflected the degree of motor function in infants without apparent brain abnormalities.

Cross-validation of serial optical coherence scanning and diffusion tensor imaging: A study on neural fiber maps in human medulla oblongata

We established a strategy to perform cross-validation of serial optical coherence scanner imaging (SOCS) and diffusion tensor imaging (DTI) on a postmortem human medulla. Following DTI, the sample was serially scanned by SOCS, which integrates a vibratome slicer and a multi-contrast optical coherence tomography rig for large-scale three-dimensional imaging at microscopic resolution. The DTI dataset was registered to the SOCS space. An average correlation coefficient of 0.9 was found between the co-registered fiber maps constructed by fractional anisotropy and retardance contrasts. Pixelwise comparison of fiber orientations demonstrated good agreement between the DTI and SOCS measures. Details of the comparison were studied in regions exhibiting a variety of fiber organizations. DTI estimated the preferential orientation of small fiber tracts; however, it didn't capture their complex patterns as SOCS did. In terms of resolution and imaging depth, SOCS and DTI complement each other, and open new avenues for cross-modality investigations of the brain.

Rasagiline prevents neurodegeneration in thiamine deficient rats—A longitudinal MRI study

Neuroprotection is a therapeutic approach for the management of neurodegenerative diseases. Experimental thiamine deficiency (TD) in rats provides a model for selective neurodegeneration accompanied by chronic oxidative deficits. Rats exhibit neurological and cognitive impairments, which can be partially reversed by thiamine administration, enabling the study of mechanisms of neurodegeneration as well as neuroprotection. In this magnetic resonance (MR) study we used various techniques to characterize the neuroprotective effects of rasagiline, a selective MAO-B inhibitor. TD was induced by a thiamine-deficient diet and daily injections of the central thiamine antagonist, pyrithiamine. Daily injections of either saline or rasagiline (3mg/kg) were also administered to untreated-TD rats and rasagiline-treated TD rats respectively. With the appearance of neurological symptoms, all injections were terminated and thiamine was restored. MRI scans were performed before induction of TD (control values), on days 10, 12 (before symptoms appear), 14 (symptomatic stage) and during the recuperation period. Both groups were assessed using in-vivo serial T2-weighted imaging and diffusion tensor imaging (DTI), from which apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps were calculated. A histopathological evaluation was correlated with the MRI analysis. Thalamic hyperintensities were significantly smaller and less severe in the rasagiline-treated TD rats. Enlargement of the lateral ventricles was significantly less pronounced in the rasagiline-treated TD group. FA values of the untreated-TD group decreased significantly in the thalamic on days 12 and 14 and in the corpus callosum on day 14. These results demonstrate significant neuroprotection by rasagiline which could have implications for clinical neurodegenerative disorders.

Serial Atlas-Based Diffusion Tensor Imaging Study of Uncomplicated Mild Traumatic Brain Injury in Adults

Abstract In this report, we applied diffusion tensor imaging (DTI) methods in 36 patients with uncomplicated mild traumatic brain injury (mTBI) and a comparison group of 37 participants with orthopedic injury. Our aim was to characterize regional and global macro- and microstructural attributes of white matter (WM), gray matter (GM), in addition to volume and diffusivity of cerebrospinal fluid (CSF) to identify and differentiate patterns of acute and short-term recovery. Given that previous DTI reports on mTBI in adults using a region-of-interest approach implicated the corona radiata (CR), corpus callosum, and hippocampus, we analyzed and quantified DTI metrics of these regions using atlas-based methods. The normalized volume percentages of global CSF, GM, and WM were not different between the mTBI and orthopedic comparison (OC) groups at either the baseline or follow-up time points or between the baseline and follow-up time points within the OC group (p>0.17; uncorrected for multiple comparisons). The DTI metrics did not differ between groups at either occasion. However, an increase was noted on follow-up in the OC group in the global mean diffusivity of GM (uncorrected p=0.003) and WM (uncorrected p=0.02), indicating a decrease in diffusivity at the 3-month postinjury, as compared to the baseline scan. An analysis of the DTI data collected longitudinally in the CR show insignificant changes in the OC group (p>0.08; N=37). CR radial diffusivity was found to be elevated in the between-group comparison at baseline (mTBI1 vs. OC1), but did not differ in the within-group comparison (mTBI1 vs. mTBI2; N=19), suggesting the possible resolution of edema. Our analysis of the cross-sectional and follow-up data, which is uncorrected for multiple comparisons, demonstrates dissociation between volumetric (macrostructural) and tissue integrity (microstructural) attributes and shows the potential utility of DTI to capture transient edema in the CR.

Chronic cocaine administration causes extensive white matter damage in brain: Diffusion tensor imaging and immunohistochemistry studies

The effect of chronic cocaine exposure on multiple white matter structures in rodent brain was examined using diffusion tensor imaging (DTI), locomotor behavior, and end point histology. The animals received either cocaine at a dose of 100mg/kg (N=19), or saline (N=17) for 28 days through an implanted osmotic minipump. The animals underwent serial DTI scans, locomotor assessment, and end point histology for determining the expressions of myelin basic protein (MBP), neurofilament-heavy protein (NF-H), proteolipid protein (PLP), Nogo-A, aquaporin-4 (AQP-4), and growth associated protein-43 (GAP-43). Differences in the DTI measures were observed in the splenium (scc) and genu (gcc) of the corpus callosum (cc), fimbria (fi), and the internal capsule (ic). A significant increase in the activity in the fine motor movements and a significant decrease in the number of rearing events were observed in the cocaine-treated animals. Reduced MBP and Nogo-A and increased GAP-43 expressions were most consistently observed in these structures. A decrease in the NF-H expression was observed in fi and ic. The reduced expression of Nogo-A and the increased expression of GAP-43 may suggest destabilization of axonal connectivity and increased neurite growth with aberrant connections. Increased GAP-43 suggests drug-induced plasticity or a possible repair mechanism response. The findings indicated that multiple white matter tracts are affected following chronic cocaine exposure.

Diffusion tensor imaging of pyramidal tract reorganization after pediatric stroke

Plasticity of the developing motor tracts is a contributor to recovery of motor function after pediatric stroke. The mechanism of these plastic changes may be functional and/or structural in nature. The corticospinal tract (CST) represents the major pathway responsible for voluntary movement. Stroke-induced damage to the CST as well as to other motor tracts leads to motor deficits which may show favorable functional recovery particularly in the pediatric population. We report the case of a 3-year-old girl demonstrating reorganization of the pyramidal tracts after an extensive left MCA territory stroke secondary to head trauma. Reorganization is characterized using serial diffusion tensor imaging (DTI) of the pyramidal tracts which contain the CST. Imaging shows decreased ipsi-lesional fractional anisotropy (FA) suggestive of Wallerian degeneration and increased contralesional FA. These results point to plastic reorganization of the pyramidal tract post-stroke and the utility of DTI in recognizing these changes.

Serial diffusion tensor imaging for early detection of radiation‐induced injuries to normal‐appearing white matter in high‐grade glioma patients

To study the potential of diffusion tensor imaging (DTI) to serve as a biomarker for radiation-induced brain injury during chemo-radiotherapy (RT) treatment. Serial DTI data were collected from 18 high-grade glioma (HGG) patients undergoing RT and 7 healthy controls. Changes across time in mean, standard deviation (SD), skewness, and kurtosis of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λa ), and transversal diffusivity (λt ) within the normal-appearing white matter (NAWM) were modeled using a linear mixed-effects model to assess dose dependent changes of five dose bins (0-60 Gy), and global changes compared with a control group. Mean MD, λa and λt were all significantly increasing in >41 Gy dose regions (0.14%, 0.10%, and 0.18% per week) compared with <12 Gy regions. SD λt had significant dose dependent time evolution of 0.019*dose per week. Mean and SD MD, λa and λt in the global NAWM of the patient group significantly increased (mean; 0.06%, 0.03%, 0.09%, and SD; 0.57%, 0.34%, 0.51 per week) compared with the control group. The changes were significant at week 6 of, or immediately after RT. DTI is not sensitive to acute global NAWM changes during the treatment of HGG, but sensitive to early posttreatment changes.