Longitudinal Diffusion Tensor Imaging Study Research Articles

Secondary Degeneration of White Matter Tract following Basal Ganglia Infarction: A Longitudinal Diffusion Tensor Imaging Study.

We explored the relationship between secondary degeneration of white matter (WM) tracts and motor outcomes after left basal ganglia infarction and investigated alterations in the diffusion indices of WM tracts in distal areas. Clinical neurological evaluations were accomplished using the Fugl-Meyer scale (FMS). Then, the fractional anisotropy (FA) of the bilateral superior corona radiata (SCR), cerebral peduncle (CP), corticospinal tracts (CST), and corpus callosum (CC) were measured in all patients and control subjects. Regional-based analysis revealed decreased FA values in the ipsilesional SCR, CP, and CST of the patients, compared to the control subjects at 5- time points. The relative FA (rFA) values of the SCR, CP, and CST decreased progressively with time, the lowest values recorded at 90 days before increasing slightly at 180 days after stroke. Compared to the contralateral areas, the FA values of the ipsilesional SCR and CST areas were significantly decreased (P=0.023), while those of the CP decreased at 180 days (P=0.008). Compared with the values at 7 days, the rFA values of the ipsilesional SCR and CP areas were significantly reduced at 14, 30, and 90 days, while those in the CST area were significantly reduced at 14, 90, and 180 days. The CP rFA value at 7 days correlated positively with the FM scores at 180 days (r=0.469, P=0.037). This study provides an objective, comprehensive, and automated protocol for detecting secondary degeneration of WM, which is important in understanding rehabilitation mechanisms after stroke.

PROFIT: projection-based test in longitudinal functional data

In many modern applications, a dependent functional response is observed for each subject over repeated time, leading to longitudinal functional data. In this paper, we propose a novel statistical procedure to test whether the mean function varies over time. Our approach relies on reducing the dimension of the response using data-driven orthogonal projections, and employs likelihood-based hypothesis testing. We investigate the methodology theoretically and discuss a computationally efficient implementation. The proposed test maintains the Type-1 error rate, and shows excellent power to detect departures from the null hypothesis in finite sample simulation studies. We apply our method to the longitudinal diffusion tensor imaging study of multiple sclerosis (MS) patients to formally assess whether the brain's healthy tissue, as summarised by the fractional anisotropy (FA) profile, degrades over time during the study period.

Prenatal alcohol exposure and white matter microstructural changes across the first 6–7 years of life: A longitudinal diffusion tensor imaging study of a South African birth cohort

Prenatal alcohol exposure (PAE) can affect brain development in early life, but few studies have investigated the effects of PAE on trajectories of white matter tract maturation in young children. Here we used diffusion weighted imaging (DWI) repeated over three time points, to measure the effects of PAE on patterns of white matter microstructural development during the pre-school years. Participants were drawn from the Drakenstein Child Health Study (DCHS), an ongoing birth cohort study conducted in a peri-urban community in the Western Cape, South Africa. A total of 342 scans acquired from 237 children as neonates (N = 82 scans: 30 PAE; 52 controls) and at ages 2–3 (N = 121 scans: 27 PAE; 94 controls) and 6–7 years (N = 139 scans: 45 PAE; 94 controls) were included. Maternal alcohol use during pregnancy and other antenatal covariates were collected from 28 to 32 weeks’ gestation. Linear mixed effects models with restricted maxium likelihood to accommodate missing data were implemented to investigate the effects of PAE on fractional anisotropy (FA) and mean diffusivity (MD) in specific white matter tracts over time, while adjusting for child sex and maternal education. We found significant PAE-by-time effects on trajectories of FA development in the left superior cerebellar peduncle (SCP-L: p = 0.001; survived FDR correction) and right superior longitudinal fasciculus (SLF-R: p = 0.046), suggesting altered white matter development among children with PAE. Compared with controls, children with PAE demonstrated a more rapid change in FA in these tracts from the neonatal period to 2–3 years of age, followed by a more tapered trajectory for the period from 2–3 to 6–7 years of age, with these trajectories differing from unexposed control children. Given their supporting roles in various aspects of neurocognitive functioning (i.e., motor regulation, learning, memory, language), altered patterns of maturation in the SCP and SLF may contribute to a spectrum of physical, social, emotional, and cognitive difficulties often experienced by children with PAE. This study highlights the value of repeated early imaging in longitudinal studies of PAE, and focus for early childhood as a critical window of potential susceptibility as well as an opportunity for early intervention.

Within-person changes in the aging white matter microstructure and their modifiers: A meta-analysis and systematic review of longitudinal diffusion tensor imaging studies

Abstract This meta-analysis and systematic review synthesized data from 30 longitudinal diffusion tensor imaging (DTI) studies on the magnitude, direction, spatial patterns, and modifiers of naturally occurring within-person changes in healthy adult white matter (WM) microstructure. Results revealed: (1) significant within-person declines in fractional anisotropy (FA) in the whole WM (d = -0.12), genu (d = -0.16), and splenium (d = -0.13); (2) greater declines in FA associated with older age, longer follow-up times, and female sex; (3) a possible yet inconclusive vulnerability of late-myelinating WM (the “development-to-degeneration” gradient); and (4) factors decelerating (e.g., physical activity and social activities) and accelerating (e.g., vascular risk factors, biomarkers for Alzheimer’s disease, and alcohol consumption) age-related FA changes. Our findings encourage the consideration of WM as a new target for treatments and interventions against cognitive decline and lay the foundation for studying the plastic and regenerative potential of adult WM in clinical trials. Individual differences in WM changes could aid in the preclinical diagnosis of dementia, opening a window for earlier, more effective treatments.

The effect of polygenic risk on white matter microstructural degeneration in Parkinson's disease: A longitudinal Diffusion Tensor Imaging study.

This study was undertaken to investigate the effect of genetic risk on whole brain white matter (WM) integrity in patients with Parkinson disease (PD). Data were acquired from the Parkinson's Progression Markers Initiative (PPMI) database. Polygenic load was estimated by calculating weighted polygenic risk scores (PRS) using (i) all available 26 PD-risk single nucleotide polymorphisms (SNPs) (PRS1) and (ii) 23 SNPs with minor allele frequency (MAF) >0.05 (PRS2). According to the PRS2, and combined with clinical and diffusion tensor imaging (DTI) data over 3-year follow-up, 60 PD patients were screened and assigned to the low-PRS group (n=30) and high-PRS group (n=30) to investigate intergroup differences in clinical profiles and WM microstructure measured by DTI cross-sectionally and longitudinally. PRS were associated with younger age at onset in patients with PD (PRS1, Spearman ρ=-0.190, p=0.003; PRS2, Spearman ρ=-0.189, p=0.003). The high-PRS group showed more extensive WM microstructural degeneration compared with the low-PRS group, mainly involving the anterior thalamic radiation (AThR) and inferior fronto-occipital fasciculus (IFOF) (p<0.05). Furthermore, WM microstructural changes in AThR correlated with declining cognitive function (r=-0.401, p=0.028) and increasing dopaminergic deficits in caudate (r=-0.405, p=0.030). These findings suggest that PD-associated polygenic load aggravates the WM microstructural degeneration and these changes may lead to poor cognition with continuous dopamine depletion. This study provides advanced evidence that combined with a cumulative PRS and DTI methods may predict disease progression in PD patients.

Temporal Dynamics of Brain White Matter Plasticity in Sighted Subjects during Tactile Braille Learning: A Longitudinal Diffusion Tensor Imaging Study.

The white matter (WM) architecture of the human brain changes in response to training, though fine-grained temporal characteristics of training-induced white matter plasticity remain unexplored. We investigated white matter microstructural changes using diffusion tensor imaging at five different time points in 26 sighted female adults during 8 months of training on tactile braille reading. Our results show that training-induced white matter plasticity occurs both within and beyond the trained sensory modality, as reflected by fractional anisotropy (FA) increases in somatosensory and visual cortex, respectively. The observed changes followed distinct time courses, with gradual linear FA increase along the training in the somatosensory cortex and sudden visual cortex cross-modal plasticity occurring after braille input became linguistically meaningful. WM changes observed in these areas returned to baseline after the cessation of learning in line with the supply-demand model of plasticity. These results also indicate that the temporal dynamics of microstructural plasticity in different cortical regions might be modulated by the nature of computational demands. We provide additional evidence that observed FA training-induced changes are behaviorally relevant to tactile reading. Together, these results demonstrate that WM plasticity is a highly dynamic process modulated by the introduction of novel experiences.SIGNIFICANCE STATEMENT Throughout the lifetime the human brain is shaped by various experiences. Training-induced reorganization in white matter (WM) microstructure has been reported, but we know little about its temporal dynamics. To fill this gap, we scanned sighted subjects five times during tactile braille reading training. We observed different dynamics of WM plasticity in the somatosensory and visual cortices implicated in braille reading. The former showed a continuous increase in WM tissue anisotropy along with tactile training, while microstructural changes in the latter were observed only after the participants learned to read braille words. Our results confirm the supply-demand model of brain plasticity and provide evidence that WM reorganization depends on distinct computational demands and functional roles of regions involved in the trained skill.

Working Memory Training Effects on White Matter Integrity in Young and Older Adults.

ObjectivesWorking memory is essential for daily life skills like reading comprehension, reasoning, and problem-solving. Healthy aging of the brain goes along with working memory decline that can affect older people’s independence in everyday life. Interventions in the form of cognitive training are a promising tool for delaying age-related working memory decline, yet the underlying structural plasticity of white matter is hardly studied.MethodsWe conducted a longitudinal diffusion tensor imaging study to investigate the effects of an intensive four-week adaptive working memory training on white matter integrity quantified by global and tract-wise mean diffusivity. We compared diffusivity measures of fiber tracts that are associated with working memory of 32 young and 20 older participants that were randomly assigned to a working memory training group or an active control group.ResultsThe behavioral analysis showed an increase in working memory performance after the four-week adaptive working memory training. The neuroanatomical analysis revealed a decrease in mean diffusivity in the working memory training group after the training intervention in the right inferior longitudinal fasciculus for the older adults. There was also a decrease in mean diffusivity in the working memory training group in the right superior longitudinal fasciculus for the older and young participants after the intervention.ConclusionThis study shows that older people can benefit from working memory training by improving their working memory performance that is also reflected in terms of improved white matter integrity in the superior longitudinal fasciculus and the inferior longitudinal fasciculus, where the first is an essential component of the frontoparietal network known to be essential in working memory.

Time heals all wounds? A 2-year longitudinal diffusion tensor imaging study in major depressive disorder

Cross-sectional studies have repeatedly shown impaired white matter integrity in patients with major depressive disorder. Longitudinal analyses are missing from the current research and are crucial to elucidating the impact of disease trajectories on white matter impairment in major depressive disorder. Fifty-nine patients with major depressive disorder receiving inpatient treatment, as well as 49 healthy controls, took part in a prospective study. Participants were scanned twice (baseline and follow-up), approximately 2.25 years apart, using diffusion tensor imaging. We analyzed diffusion metrics using tract-based spatial statistics. At baseline, patients had higher mean diffusivity in a large bilateral frontal cluster comprising the body and genu of the corpus callosum, the anterior and superior corona radiata, and the superior longitudinal fasciculus. A significant group × time interaction revealed a decrease of mean diffusivity in patients with major depressive disorder over time, abolishing group differences at follow-up. This effect was observed irrespective of disease course in the follow-up period. Analyzing the course of illness is challenging because of recollection biases in patients with major depressive disorder. This study reports follow-up diffusion tensor imaging data in patients with major depressive disorder after an acute depressive episode. We demonstrated impaired prefrontal white matter microstructure (higher mean diffusivity) at baseline in patients with major depressive disorder, which normalized at follow-up after 2 years, irrespective of disease course. This might have been due to a general treatment effect and might have reflected recovery of white matter integrity.

Tracking the Re-organization of Motor Functions After Disconnective Surgery: A Longitudinal fMRI and DTI Study.

Objective: Mechanisms of motor plasticity are critical to maintain motor functions after cerebral damage. This study explores the mechanisms of motor reorganization occurring before and after surgery in four patients with drug-refractory epilepsy candidate to disconnective surgery.Methods: We studied four patients with early damage, who underwent tailored hemispheric surgery in adulthood, removing the cortical motor areas and disconnecting the corticospinal tract (CST) from the affected hemisphere. Motor functions were assessed clinically, with functional MRI (fMRI) tasks of arm and leg movement and Diffusion Tensor Imaging (DTI) before and after surgery with assessments of up to 3 years. Quantifications of fMRI motor activations and DTI fractional anisotropy (FA) color maps were performed to assess the lateralization of motor network. We hypothesized that lateralization of motor circuits assessed preoperatively with fMRI and DTI was useful to evaluate the motor outcome in these patients.Results: In two cases preoperative DTI-tractography did not reconstruct the CST, and FA-maps were strongly asymmetric. In the other two cases, the affected CST appeared reduced compared to the contralateral one, with modest asymmetry in the FA-maps. fMRI showed different degrees of lateralization of the motor network and the SMA of the intact hemisphere was mostly engaged in all cases. After surgery, patients with a strongly lateralized motor network showed a stable performance. By contrast, a patient with a more bilateral pattern showed worsening of the upper limb function. For all cases, fMRI activations shifted to the intact hemisphere. Structural alterations of motor circuits, observed with FA values, continued beyond 1 year after surgery.Conclusion: In our case series fMRI and DTI could track the longitudinal reorganization of motor functions. In these four patients the more the paretic limbs recruited the intact hemisphere in primary motor and associative areas, the greater the chances were of maintaining elementary motor functions after adult surgery. In particular, DTI-tractography and quantification of FA-maps were useful to assess the lateralization of motor network. In these cases reorganization of motor connectivity continued for long time periods after surgery.

Development of white matter microstructure in relation to verbal and visuospatial working memory-A longitudinal study.

Working memory capacity is pivotal for a broad specter of cognitive tasks and develops throughout childhood. This must in part rely on development of neural connections and white matter microstructure maturation, but there is scarce knowledge of specific relations between this and different aspects of working memory. Diffusion tensor imaging (DTI) enables us to study development of brain white matter microstructure. In a longitudinal DTI study of 148 healthy children between 4 and 11 years scanned twice with an on average 1.6 years interval, we characterized change in fractional anisotropy (FA), mean (MD), radial (RD) and axial diffusivity (AD) in 10 major white matter tracts hypothesized to be of importance for working memory. The results showed relationships between change in several tracts and change in visuospatial working memory. Specifically, improvement in visuospatial working memory capacity was significantly associated with decreased MD, RD and AD in inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF) and uncinate fasciculus (UF) in the right hemisphere, as well as forceps major (FMaj). No significant relationships were found between change in DTI metrics and change in verbal working memory capacity. These findings yield new knowledge about brain development and corresponding working memory improvements in childhood.

Effect of switching from glatiramer acetate 20 mg/daily to glatiramer acetate 40 mg three times a week on gray and white matter pathology in subjects with relapsing multiple sclerosis: A longitudinal DTI study

BackgroundGlatiramer acetate (GA) 40 mg × 3/weekly was approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). While the beneficial effect of GA 20 mg/daily in MS patients on non-conventional MRI measures has been demonstrated, the effect of GA 40 mg × 3/weekly at the microstructural tissue level has yet to be explored. ObjectiveTo investigate the effect of switching from GA 20 mg/daily to GA 40 mg × 3/weekly on the evolution of microstructural changes in the thalamus and normal appearing white matter (NAWM), using diffusion tensor imaging (DTI). MethodsIn this observational, longitudinal, cross-over, 34-month MRI study, we recruited 150 RRMS patients that underwent MRI 12–18 months before switching (pre-index), during the switch (index) and 12–18 months after switching (post-index) from GA 20 mg/daily to GA 40 mg × 3/weekly. Regional DTI metrics and tract-based spatial statistics (TBSS) analyses were performed. Mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD) and fractional anisotropy (FA) were measured in thalamus and NAWM. ResultsRegional DTI measures, measures of whole brain, white and gray matter, and thalamus volumes, as well as lesion volume, showed no significant changes. However, the voxel-wise TBSS analysis showed increased FA both in the NAWM and thalamus, as well as increased MD and AD in NAWM, and decreased RD in NAWM (p < .05). Areas of increased FA and MD as well as decreased RD in the NAWM, and increased AD both in the NAWM and thalamus were detected between index to post-index (p < .05). ConclusionsThis study confirms a comparable effect of GA 40 mg × 3/weekly to GA 20 mg/daily on DTI measures over 34 months.

Cytotoxic edema at onset in West syndrome of unknown etiology: A longitudinal diffusion tensor imaging study.

To clarify longitudinal changes in white matter microstructures from the onset of disease in patients with West syndrome (WS) of unknown etiology. Diffusion tensor imaging (DTI) was prospectively performed at onset and at 12 and 24 months old in 17 children with WS of unknown etiology. DTI was analyzed using tract-based spatial statistics (TBSS) and tract-specific analysis (TSA) of 13 fiber tracts, and fractional anisotropy (FA) and mean diffusivity (MD) were compared with those of 42 age-matched controls. Correlations of FA and MD with developmental quotient (DQ) at age 24 months were analyzed. Multiple comparisons were adjusted for using the false discovery rate (q-value). TBSS analysis at onset showed higher FA and lower MD in the corpus callosum and brainstem in patients. TSA showed lower MD in bilateral uncinate fasciculi (UF) (right: q < 0.001; left: q = 0.03) at onset in patients. TBSS showed a negative correlation between FA at onset and DQ in the right frontal lobe, whereas FA at 24 months old exhibited a positive correlation with DQ in the diffuse white matter. MD for bilateral UF at 24 months old on TSA correlated positively with DQ (q = 0.04, both). These findings may indicate the existence of cytotoxic edema in the immature white matter and dorsal brainstem at onset, and subsequent alterations in the diffuse white matter in WS of unknown etiology. Microstructural development in the UF might play important roles in cognitive development in WS.

Evidence of progressive tissue loss in the core of chronic MS lesions: A longitudinal DTI study.

ObjectiveUsing diffusion tensor imaging (DTI), we examined chronic stable MS lesions, peri-lesional white matter (PLWM) and normal appearing white matter (NAWM) in patients with relapsing-remitting multiple sclerosis (RRMS) for evidence of progressive tissue destruction and evaluated whether diffusivity change is associated with conventional MRI parameters and clinical findings.MethodPre- and post-gadolinium T1, T2 and DTI images were acquired from 55 consecutive RRMS patients at baseline and 42.3 ± 9.7 months later. Chronic stable T2 lesions of sufficient size were identified in 43 patients (total of 134 lesions). Diffusivity parameters such as axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD) and fractional anisotropy (FA) were compared at baseline and follow-up. MRI was also performed in 20 normal subjects of similar age and gender.ResultsWithin the core of chronic MS lesions the diffusion of water molecules significantly increased over the follow-up period, while in NAWM all diffusivity indices remained stable. Since increase of AD and RD in lesional core was highly concordant, indicating isotropic nature of diffusivity change, and considering potential effect of crossing fibers on directionally-selective indices, only MD, a directionally-independent measure, was used for further analysis. The significant increase of MD in the lesion core during the follow-up period (1.29 ± 0.19 μm2/ms and 1.34 ± 0.20 μm2/ms at baseline and follow-up respectively, P < 0.0001) was independent of age or disease duration, total brain lesion volume or new lesion activity, lesion size or location and baseline tissue damage (T1 hypointensity). Change of MD in the lesion core, however, was associated with progressive brain atrophy (r = 0.47, P = 0.002). A significant gender difference was also observed: the MD change in male patients was almost twice that of female patients (0.030 ± 0.04 μm2/ms and 0.058 ± 0.03 μm2/ms in female and male respectively, P = 0.01). Sub-analysis of lesions with lesion-free surrounding revealed the largest MD increase in the lesion core, while MD progression gradually declined towards PLWM. MD in NAWM remained stable over the follow-up period.ConclusionThe significant increase of isotropic water diffusion in the core of chronic stable MS lesions likely reflects gradual, self-sustained tissue destruction in demyelinated white matter that is more aggressive in males.

White matter alterations over the course of two consecutive high-school football seasons and the effect of a jugular compression collar: A preliminary longitudinal diffusion tensor imaging study.

The cumulative effects of repetitive subclinical head impacts during sports may result in chronic white matter (WM) changes and possibly, neurodegenerative sequelae. In this pilot study, we investigated the longitudinal WM changes over the course of two consecutive high-school football seasons and explored the long-term effects of a jugular vein compression collar on these WM alterations. Diffusion tensor imaging data were prospectively collected both pre- and postseason in the two consecutive seasons. Participants were assigned into either collar or noncollar groups. Tract-based spatial statistics (TBSS) approach and region of interest-based approach were used to quantify changes in WM diffusion properties. Despite comparable exposure to repetitive head impacts, significant reductions in mean, axial, and/or radial diffusivity were identified in Season 1 in multiple WM regions in the noncollar group but not in the collar group. After an 8- to 9-month long off-season, these changes observed in the noncollar group partially and significantly reversed but also remained significantly different from the baseline. In Season 2, trend level WM alterations in the noncollar group were found but located in spatially different regions than Season 1. Last, the WM integrity in the collar group remained unchanged throughout the four time points. In conclusion, we quantitatively assessed the WM structural changes and partial reversal over the course of two consecutive high-school football seasons. In addition, the mitigated WM alterations in athletes in the collar group might indicate potential effect of the collar in ameliorating the changes against repetitive head impacts. Hum Brain Mapp 39:491-508, 2018. © 2017 Wiley Periodicals, Inc.

Spatiotemporal microstructural white matter changes in diffusion tensor imaging after transient focal ischemic stroke in rats.

Structural reorganization in white matter (WM) after stroke is a potential contributor to substitute or to newly establish the functional field on the injured brain in nature. Diffusion tensor imaging (DTI) is an imaging modality that can be used to evaluate damage and recovery within the brain. This method of imaging allows for in vivo assessment of the restricted movements of water molecules in WM and provides a detailed look at structural connectivity in the brain. For longitudinal DTI studies after a stroke, the conventional region of interest method and voxel-based analysis are highly dependent on the user-hypothesis and parameter settings for implementation. In contrast, tract-based spatial statistics (TBSS) allows for reliable voxel-wise analysis via the projection of diffusion-derived parameters onto an alignment-invariant WM skeleton. In this study, spatiotemporal WM changes were examined with DTI-derived parameters (fractional anisotropy, FA; mean diffusivity, MD; axial diffusivity, DA; radial diffusivity, RD) using TBSS 2h to 6weeks after experimental focal ischemic stroke in rats (N=6). FA values remained unchanged 2-4h after the stroke, followed by a continuous decrease in the ipsilesional hemisphere from 24h to 2weeks post-stroke and gradual recovery from the ipsilesional corpus callosum to the external capsule until 6weeks post-stroke. In particular, the fibers in these areas were extended toward the striatum of the ischemic boundary region at 6weeks on tractography. The alterations of the other parameters in the ipsilesional hemisphere showed patterns of a decrease at the early stage, a subsequent pseudo-normalization of MD and DA, a rapid reduction of RD, and a progressive increase in MD, DA and RD with a decreased extent in the injured area at later stages. The findings of this study may reflect the ongoing processes on tissue damage and spontaneous recovery after stroke.

A preliminary longitudinal study of white matter alteration in cocaine use disorder subjects

BackgroundPrevious diffusion tensor imaging (DTI) studies have consistently shown that subjects with cocaine use disorder (CocUD) had altered white matter microstructure in the corpus callosum. It is believed that these alterations are due to preexisting factors, chronic cocaine use, or both. However, there is no published longitudinal DTI study on human cocaine users yet which could shed light on the relationship between cocaine use and DTI findings. MethodsThis study used a longitudinal design and DTI to test if the white matter microstructure shows quicker alteration in CocUD subjects than controls. DTI data were acquired from eleven CocUD subjects who participated a treatment study and eleven non-drug-using controls at baseline (Scan 1) and after ten weeks (Scan 2). The baseline fractional anisotropy (FA), a general measure of white matter microstucture, and the change in FA (ΔFA, equals Scan 1 FA minus Scan 2 FA) were both compared between groups. ResultsThe two groups did not show a difference in FA at baseline. The CocUD subjects had significantly greater ΔFA than the controls in the left splenium of the corpus callosum. In CocUD subjects, greater ΔFA in this region was associated with shorter lifetime cocaine use and greater number of positive cocaine urine samples collected during the treatment. ConclusionThe finding in the left splenium is consistent with previous animal studies and provide indirect evidence about the effects of chronic cocaine use on white matter alterations. The subject sample size is small, therefore the results should be treated as preliminary.

White matter alterations in college football players: a longitudinal diffusion tensor imaging study.

The aim of this study was to evaluate longitudinal changes in the diffusion characteristics of brain white matter (WM) in collegiate athletes at three time points: prior to the start of the football season (T1), after one season of football (T2), followed by six months of no-contact rest (T3). Fifteen male collegiate football players and 5 male non-athlete student controls underwent diffusion MR imaging and computerized cognitive testing at all three timepoints. Whole-brain tract-based spatial statistics (TBSS) were used to compare fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD), and trace between all timepoints. Average diffusion values were obtained from statistically significant clusters for each individual. No athlete suffered a concussion during the study period. After one season of play (T1 to T2), we observed a significant increase in trace in a cluster located in the brainstem and left temporal lobe, and a significant increase in FA in the left parietal lobe. After six months of no-contact rest (T2 to T3), there was a significant decrease in trace and FA in clusters that were partially overlapping or in close proximity with the initial clusters (T1 to T2), with no significant changes from T1 to T3. Repetitive head impacts (RHI) sustained during a single football season may result in alterations of the brain's WM in collegiate football players. These changes appear to return to baseline after 6months of no-contact rest, suggesting remission of WM alterations. Our preliminary results suggest that collegiate football players might benefit from periods without exposure to RHI.

The Impact of Cognitive Training on Cerebral White Matter in Community-Dwelling Elderly: One-Year Prospective Longitudinal Diffusion Tensor Imaging Study.

It has been shown that cognitive training (CogTr) is effective and recuperative for older adults, and can be used to fight against cognitive decline. In this study, we investigated whether behavioural gains from CogTr would extend to white matter (WM) microstructure, and whether training-induced changes in WM integrity would be associated with improvements in cognitive function, using diffusion tensor imaging (DTI). 48 healthy community elderly were either assigned to multi-domain or single-domain CogTr groups to receive 24 sessions over 12 weeks, or to a control group. DTI was performed at both baseline and 12-month follow-up. Positive effects of multi-domain CogTr on long-term changes in DTI indices were found in posterior parietal WM. Participants in the multi-domain group showed a trend of long-term decrease in axial diffusivity (AD) without significant change in fractional anisotropy (FA), mean diffusivity (MD) or radial diffusivity (RD), while those in the control group displayed a significant FA decrease, and an increase in MD and RD. In addition, significant relationships between an improvement in processing speed and changes in RD, MD and AD were found in the multi-domain group. These findings support the hypothesis that plasticity of WM can be modified by CogTr, even in late adulthood.

Risperidone-induced topological alterations of anatomical brain network in first-episode drug-naive schizophrenia patients: a longitudinal diffusion tensor imaging study.

It remains unclear whether the topological deficits of the white matter network documented in cross-sectional studies of chronic schizophrenia patients are due to chronic illness or to other factors such as antipsychotic treatment effects. To answer this question, we evaluated the white matter network in medication-naive first-episode schizophrenia patients (FESP) before and after a course of treatment. We performed a longitudinal diffusion tensor imaging study in 42 drug-naive FESP at baseline and then after 8 weeks of risperidone monotherapy, and compared them with 38 healthy volunteers. Graph theory was utilized to calculate the topological characteristics of brain anatomical network. Patients' clinical state was evaluated using the Positive and Negative Syndrome Scale (PANSS) before and after treatment. Pretreatment, patients had relatively intact overall topological organizations, and deficient nodal topological properties primarily in prefrontal gyrus and limbic system components such as the bilateral anterior and posterior cingulate. Treatment with risperidone normalized topological parameters in the limbic system, and the enhancement positively correlated with the reduction in PANSS-positive symptoms. Prefrontal topological impairments persisted following treatment and negative symptoms did not improve. During the early phase of antipsychotic medication treatment there are region-specific alterations in white matter topological measures. Limbic white matter topological dysfunction improves with positive symptom reduction. Prefrontal deficits and negative symptoms are unresponsive to medication intervention, and prefrontal deficits are potential trait biomarkers and targets for negative symptom treatment development.

Aberrant nigral diffusion in Parkinson's disease: A longitudinal diffusion tensor imaging study.

Measuring microstructure alterations with diffusion tensor imaging in PD is potentially a valuable tool to use as a biomarker for early diagnosis and to track disease progression. Previous studies have reported a specific decrease of nigral fractional anisotropy in PD. However, to date the effect of disease progression on nigral or striatal diffusion indices has not been fully explored. We have conducted a cross-sectional and longitudinal diffusion tensor imaging study in 18 early stage, treated PD patients and 14 age-matched controls. PD patients were scanned on 2 occasions OFF medication, 19.3 months apart (standard deviation = 3.1 months). Longitudinal change of regional nigral and striatal measures of fractional anisotropy and mean diffusivity were calculated using a region-of-interest approach. Region-of-interest analysis demonstrated that at baseline, PD patients and controls did not differ in regard to diffusion indices in any region assessed. A significant difference of nigral fractional anisotropy and mean diffusivity between controls and PD patients at follow-up was detected and confirmed with longitudinal analysis within PD patients. Alterations in striatal regions were not detected in either group or over time. Our findings indicate that nigral diffusion measure may be a valuable measure of disease progression. In the future, larger longitudinal studies will confirm whether diffusion indices may serve as sensitive and clinically meaningful measures of disease progression in PD. © 2016 International Parkinson and Movement Disorder Society.