Diffusion Tensor Imaging Indices Research Articles

Multifocal alterations of white matter accompany the transition from normal cognition to dementia in Parkinson's disease patients.

The purpose of the present study was to investigate the pattern of white matter (WM) changes associated with Parkinson's disease (PD)-related cognitive impairment by using fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) measures. Diffusion Tensor Imaging (DTI) was performed in 21 PD-patients with dementia (PDD) and in an age-matched control group including 40 PD-patients without dementia (PD-CTRL). The Parkinson's disease-Cognitive Rating Scale (PD-CRS) was used for patients' neuropsychological assessment. Local microstructural WM differences associated with the presence of cognitive impairment were tested using tract-based spatial statistics analysis. Multiple regression models investigated the association of DTI indices with total PD-CRS score, PD-CRS raw items and other clinical measures across the whole study sample. Significant FA decreases were found in PDD compared to PD-CTRL patients mainly in the body of corpus callosum, corona radiata and cingulum. Lower PD-CRS score was significantly associated with decreased FA, MD and AD values in multiple WM tracts primarily located in prefrontal and limbic areas as well as across the corpus callosum. Lower performance in specific PD-CRS raw items was also associated with FA decreases in major WM tracts. The results suggest that multifocal microstructural changes of WM accompany the transition from normal to demented cognitive state in PD-patients. The corpus callosum, the corona radiata and the cingulum are among the regions mostly affected during this course. A progressive axonal degeneration is proposed as a key underlying mechanism.

Progressive Assessment of Ischemic Injury to White Matter Using Diffusion Tensor Imaging: A Preliminary Study of a Macaque Model of Stroke.

Background:Previous Diffusion Tensor Imaging (DTI) studies have demonstrated the temporal evolution of stroke injury in grey matter and white matter can be characterized by DTI indices. However, it still remains not fully understood how the DTI indices of white matter are altered progressively during the hyperacute (first 6 hours) and acute stage of stroke (≤ 1 week). In the present study, DTI was employed to characterize the temporal evolution of infarction and white matter injury after stroke insult using a macaque model with permanent ischemic occlusion.Methods and materials:Permanent middle cerebral artery (MCA) occlusion was induced in rhesus monkeys (n=4, 10-21 years old). The brain lesion was examined longitudinally with DTI during the hyperacute phase (2-6 hours, n=4), 48 hours (n=4) and 96 hours (n=3) post-occlusion.Results:Cortical infarction was seen in all animals. The Mean Diffusivity (MD) in lesion regions decreased substantially at the first time point (2 hours post stroke) (35%, p <0.05, compared to the contralateral side) and became pseudo-normalized at 96 hours. In contrast, evident FA reduction was seen at 48 hours (39%, p <0.10) post-stroke. MD reduction in white matter bundles of the lesion area was much less than that in the grey matter during the hyper-acute phase but significant change was observed 4 hours (4.2%, p < 0.05) post stroke . Also, MD pseudonormalisation was seen at 96 hours post stroke. There was a significant correlation between the temporal changes of MD in white matter bundles and those in whole lesion areas during the entire study period. Meanwhile, no obvious fractional anisotropy (FA) changes were seen during the hyper-acute phase in either the entire infarct region or white matter bundles. Significant FA alteration was observed in entire lesion areas and injured white matter bundles 48 and 96 hours post stroke. The stroke lesion in grey matter and white matter was validated by pathological findings.Conclusion: The temporal evolution of ischemic injury to the grey matter and white matter from 2 to 96 hours after stroke onset was characterized using a macaque model and DTI. Progressive MD changes in white matter bundles are seen from hyperacute phase to acute phase after permanent MCA occlusion and temporally correlated with the MD changes in entire infarction regions. MD reduction in white matter bundles is mild in comparison with that in the grey matter but significant and progressive, indicating it may be useful to detect early white matter degeneration after stroke.

Exploration of male urethral sphincter complex using diffusion tensor imaging (DTI)-based fiber-tracking.

Urinary incontinence is a major clinical problem arising primarily from age-related degenerative changes to the sphincter muscles. However, the precise anatomy of the normal male sphincter muscles has yet to be established. Diffusion tensor imaging (DTI) may offer a unique insight into muscle microstructure and fiber architecture. To explore the anatomy of the urethral sphincter muscles pertinent to urinary continence function using DT-MRI. Prospective cohort study. Eleven normal male subjects (mean age: 25.4 years); two subjects were scanned in three separate sessions to assess reproducibility. 3T; using a diffusion-weighted spin echo planar sequence. DT parameters including fractional anisotropy (FA), primary (λ1 ), secondary (λ2 ), and tertiary (λ3 ) eigenvalues, Apparent diffusion coefficient and radial diffusivity were analyzed statistically, while tracked muscle fibers were assessed visually. Regional differences (sphincters and longitudinal muscle of the urethra) in the DTI indices were assessed by one-way analysis of variance. A Tukey post-hoc test was used to identify significant differences between muscle regions. Two sphincter muscles, one proximal near the base of the bladder, corresponding to the lisso-sphincter, and the other distal to the end of the prostate corresponding to the rhabdo-sphincter, surrounding a central urethral muscle fiber bundle, were clearly identified. FA was higher and λ3 lower in the proximal sphincter muscle compared to the central urethral muscle and the distal sphincter (P < 0.05). The average coefficient of variation ranged from 5-12% for the DTI indices. Since DTI values are known to reflect underlying tissue microarchitecture, significant differences in DTI indices identified here between the muscles of the urethral complex may potentially arise from differences in tissue microarchitecture that may in turn be related to the specific function of the sphincter and other muscles. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1002-1011.

Longitudinal microstructural changes of cerebral white matter and their association with mobility performance in older persons.

Mobility impairment in older persons is associated with brain white matter hyperintensities (WMH), a common finding in magnetic resonance images and one established imaging biomarker of small vessel disease. The contribution of possible microstructural abnormalities within normal-appearing white matter (NAWM) to mobility, however, remains unclear. We used diffusion tensor imaging (DTI) measures, i.e. fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), to assess microstructural changes within supratentorial NAWM and WMH sub-compartments, and to investigate their association with changes in mobility performance, i.e. Tinetti assessment and the 2.5-meters walk time test. We analyzed baseline (N = 86, age ≥75 years) and 4-year (N = 41) follow-up data. Results from cross-sectional analysis on baseline data showed significant correlation between WMH volume and NAWM-FA (r = -0.33, p = 0.002), NAWM-AD (r = 0.32, p = 0.003) and NAWM-RD (r = 0.39, p = 0.0002). Our longitudinal analysis showed that after 4-years, FA and AD decreased and RD increased within NAWM. In regional tract-based analysis decrease in NAWM-FA and increase in NAWM-RD within the genu of the corpus callosum correlated with slower walk time independent of age, gender and WMH burden. In conclusion, global DTI indices of microstructural integrity indicate that significant changes occur in the supratentorial NAWM over four years. The observed changes likely reflect white matter deterioration resulting from aging as well as accrual of cerebrovascular injury associated with small vessel disease. The observed association between mobility scores and regional measures of NAWM microstructural integrity within the corpus callosum suggests that subtle changes within this structure may contribute to mobility impairment.

A combined diffusion tensor imaging and Ki-67 labeling index study for evaluating the extent of tumor infiltration using the F98 rat glioma model.

Diffusion tensor imaging (DTI) has been proven to be a sophisticated and useful tool for the delineation of tumors. In the present study, we investigated the predictive role of DTI compared to other magnetic resonance imaging (MRI) techniques in combination with Ki-67 labeling index in defining tumor cell infiltration in the peritumoral regions of F98 glioma-bearing rats. A total of 29 tumor-bearing Fischer rats underwent T2-weighted imaging, contrast-enhanced T1-weighted imaging, and DTI of their brain using a 7.0-T MRI scanner. The fractional anisotropy (FA) ratios were correlated to the Ki-67 labeling index using the Spearman correlation analysis. A receiver operating characteristic curve (ROC) analysis was established to evaluate parameters with sensitivity and specificity in order to identify the threshold values for predicting tumor infiltration. Significant correlations were observed between the FA ratios and Ki-67 labeling index (r = - 0.865, p < 0.001). The ROC analysis demonstrated that the apparent diffusion coefficient (ADC) and FA ratios could predict 50% of the proliferating cells in the regions of interest (ROI), with a sensitivity of 88.1 and 81.3%, and a specificity of 86.2 and 90.2%, respectively (p < 0.001). Meanwhile, the two ratios could also predict 10% of the proliferating cells in the ROI, with a sensitivity of 82.5 and 94.9%, and a specificity of 100 and 88.9%, respectively (p < 0.001). The present study demonstrated that the FA ratios are closely correlated with the Ki-67 labeling index. Furthermore, both ADC and FA ratios, derived from DTI, were useful for quantitatively predicting the Ki-67 labeling of glioma cells.

Age related diffusion and tractography changes in typically developing pediatric cervical and thoracic spinal cord.

Background and objectiveDiffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) are two techniques that can measure white matter integrity of the spinal cord. Recently, DTI indices have been shown to change with age. The purpose of this study is (a) to evaluate the maturational states of the entire pediatric spinal cord using DTI and DTT indices including fractional anisotropy (FA), mean diffusivity (MD), mean length of white matter fiber tracts and tract density and (b) to analyze the DTI and DTT parameters along the entire spinal cord as a function of spinal cord levels and age.MethodA total of 23 typically developing (TD) pediatric subjects ranging in age from 6 to 16 years old (11.94 ± 3.26 (mean ± standard deviation), 13 females and 10 males) were recruited, and scanned using 3.0 T MR scanner. Reduced FOV diffusion tensor images were acquired axially in the same anatomical location prescribed for the T2-weighted images to cover the entire spinal cord (C1-mid L1 levels). To mitigate motion induced artifacts, diffusion directional images were aligned with the reference image (b0) using a rigid body registration algorithm performed by in-house software developed in Matlab (MathWorks, Natick, Massachusetts). Diffusion tensor maps (FA and MD) and streamline deterministic tractography were then generated from the motion corrected DTI dataset. DTI and DTT parameters were calculated by using ROIs drawn to encapsulate the whole cord along the entire spinal cord by an independent board certified neuroradiologist. These indices then were compared between two age groups (age group A = 6–11 years (n = 11) and age group B = 12–16 years (n = 12)) based on similar standards and age definitions used for reporting spinal cord injury in the pediatric population. Standard least squared linear regression based on a restricted maximum likelihood (REML) method was used to evaluate the relationship between age and DTI and DTT parameters.ResultsAn increase in FA (group A = 0.42 ± 0.097, group B = 0.49 ± 0.116), white matter tract density (group A = 368.01 ± 236.88, group B = 440.13 ± 245.24) and mean length of fiber tracts (group A = 48.16 ± 20.48 mm, group B = 60.28 ± 23.87 mm) and a decrease in MD (group A = 1.06 ± 0.23 × 10−3 mm2/s, group B = 0.82 ± 0.24 × 10−3 mm2/s) were observed with age along the entire spinal cord. Statistically significant increases have been shown in FA (p = 0.004, R2 = 0.57), tract density (p = 0.0004, R2 = 0.58), mean length of fiber tracts (p < 0.001, R2 = 0.5) and a significant decrease has been shown in MD (p = 0.002, R2 = 0.59) between group A and group B. Also, it has been shown DTI and DTT parameters vary along the spinal cord as a function of intervertebral disk and mid-vertebral body level.ConclusionThis study provides an initial understanding of age related changes of DTI values as well as DTT metrics of the spinal cord. The results show significant differences in DTI and DTT parameters which may result from decreasing water content, myelination of fiber tracts, and the thickening diameter of fiber tracts during the maturation process. Consequently, when quantitative DTI and DTT of the spinal cord is undertaken in the pediatric population an age and level matched normative dataset should be used to accurately interpret the quantitative results.

Diffusion Tensor Imaging of Rotator Cuff: Influence of Arm Position

Diffusion tensor imaging (DTI) of skeletal muscles has been reported as capable to characterize physiological properties, tissue microstructure and architectural organization. However, the DTI indices may vary with the contractile state of the muscles, and in the rotator cuff muscles, a change in forearm position can result in variation of the DTI indices. The purpose of this study was to examine the influence of forearm position on the major DTI indices of the rotator cuff muscles. The DTI of right rotator cuff was acquired under the neutral position and external and internal rotation of the forearm in nine healthy volunteers. Fractional anisotropy (FA) and mean diffusivity (MD) of each muscle were calculated and compared among the three forearm positions. FA and MD were significantly different between external and internal rotation in infraspinatus, teres minor and subscapularis (p<0.05). We considered that this difference was due to the change in cross-sectional area of muscle fibers based on their contractile state. That is, when the muscle is contracted, its cross-sectional area is increased and the muscle fiber density in the short axis direction becomes less. This causes a change in FA and MD due to increase in λ2 and λ3 through increased diffusion of intercellular water in the short axis direction. In conclusion, the DTI indices of the rotator cuff muscles are affected by the forearm position.

Disability in progressive MS is associated with T2 lesion changes

BackgroundProgressive multiple sclerosis (MS) is characterised by diffuse changes on brain magnetic resonance imaging (MRI), which complicates the use of MRI as a diagnostic and prognostic marker. The relationship between MRI measures (conventional and non-conventional) and clinical disability in progressive MS therefore warrants further investigation. ObjectiveTo investigate the relationship between clinical disability and MRI measures in patients with progressive MS. MethodsData from 93 primary and secondary progressive MS patients who had participated in 3 phase 2 clinical trials were included in this cross-sectional study. From 3T MRI baseline scans we calculated total T2 lesion volume and analysed magnetisation transfer ratio (MTR) and the diffusion tensor imaging indices fractional anisotropy (FA) and mean diffusivity (MD) in T2 lesions, normal-appearing white matter (NAWM) and cortical grey matter. Disability was assessed by the Expanded Disability Status Scale (EDSS) and the MS functional composite. ResultsT2 lesion volume was associated with impairment by all clinical measures. MD and MTR in T2 lesions were significantly related to disability, and lower FA values correlated with worse hand function in NAWM. In multivariable analyses, increasing clinical disability was independently correlated with increasing T2 lesion volumes and MTR in T2 lesions. ConclusionIn progressive MS, clinical disability is related to lesion volume and microstructure.

Diffusion tensor tractography in cerebral small vessel disease: correlation with cognitive function.

Background Patients with cerebral small vessel disease may suffer from varying levels of cognitive deficit and may progress on to vascular dementia. The extent of involvement, as seen on conventional magnetic resonance (MR) measures, correlates poorly with the level of cognitive decline. The purpose of this study was to investigate the utility of diffusion tensor imaging (DTI) as a marker for white matter damage in small vessel disease and to assess its correlation with cognitive function. Methods Thirty consecutive patients with cerebral small vessel disease underwent conventional MR imaging, DTI, and neuropsychological assessment. Results On tractographic analysis, fractional anisotropy was significantly reduced while mean diffusivity significantly increased in several white matter tracts. The alteration in DTI indices correlated well with cognitive function. No significant correlation was identified between T2 lesion load and cognitive performance. Conclusions Tractographic analysis of white matter integrity is a useful measure of disease severity and correlates well with cognitive function. It may have a significant potential in monitoring disease progression and may serve as a surrogate marker for treatment trials.

Developmental trajectory of the prefrontal cortex: a systematic review of diffusion tensor imaging studies.

Fluctuations in gray and white matter volumes in addition to the fibers' reorganization and refinement of synaptic connectivity apparently happen in a particular temporo-spatial sequence during the dynamic and prolonged process of cerebral maturation. These developmental events are associated with regional modifications of brain tissues and neural circuits, contributing to networks' specialization and enhanced cognitive processing. According to several studies, improvements in cognitive processes are possibly myelin-dependent and associated to white matter maturation. Of particular interest is the developmental pattern of the prefrontal cortex (PFC), more specifically the PFC white matter, due to its role in high-level executive processes such as attention, working memory and inhibitory control. A systematic review of the literature was conducted using the Web of Science, PubMed and Embase databases to analyze the development of PFC white matter using Diffusion Tensor Imaging (DTI), a widely used non-invasive technique to assess white matter maturation. Both the research and reporting of results were based on Cochrane's recommendations and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. Information extracted from 27 published studies revealed an increased myelination, organization and integrity of frontal white matter with age, as revealed by DTI indexes (fractional anisotropy [FA], mean diffusivity [MD], radial diffusivity [RD] and axial diffusivity [AD]). These patterns highlight the extended developmental course of the frontal structural connectivity, which parallels the improvements in higher-level cognitive functions observed between adolescence and early adulthood.

White matter microstructure within the superior longitudinal fasciculus modulates the degree of response conflict indexed by N2 in healthy adults

Response conflict can be induced by priming multiple responses competing for control of action in trials. The N2 is one functionally-related cognitive control index for response conflict. And yet the underlying whiter matter neural substrates of inter-individual difference in conflict N2 remain unclear. So the aim of present study was to address the white matter microstructure of the N2 responsible for conflict by directly relating the amplitude cost of the event-related potential (ERP) N2 component to diffusion tensor imaging (DTI) indices in healthy subjects. Thirty healthy subjects underwent DTI scanning and electrophysiology recording during a modified Flanker task. N2 was a stimulus-locked negative ERP component. Fractional anisotropy (FA) was calculated based on DTI measures and was assumed to reflect the integrity of myelinate fiber bundles. Therefore, we tested the relationship between N2 amplitude and FA in brain white matter. Results showed that FA, an index for white matter characteristics, in the right superior longitudinal fasciculus (SLF) was significantly positively associated with N2 amplitude cost. The N2 amplitude cost also predicted response time (RT) cost in the Flanker task. Higher FA was associated with larger N2 amplitude cost, suggesting that changes in white matter integrity in the SLF may account for changes in efficient transmission of fronto-parietal modulatory conflict signals.

Disease stage-dependent relationship between diffusion tensor imaging and electrophysiology of the visual system in a murine model of multiple sclerosis.

Diffusion tensor imaging (DTI) is commonly used to evaluate white matter integrity in multiple sclerosis (MS), but the relationship between DTI measures and functional changes during disease remains ambiguous. Using a mouse model of MS, we tested the hypothesis that DTI measures would correlate to the visual evoked potential (VEPs) dynamically at different disease stages. In vivo DTI, gadolinium-enhanced T1WI (Gd-T1WI) and VEPs were performed in 5 control and 25 mice after 2-12weeks of experimental autoimmune encephalomyelitis (EAE). DTI indices, including fractional anisotropy (FA), axial and radial diffusivities (AD and RD), and Gd-T1WI enhancement, were measured in the optic nerve and tract (ON and OT), which were compared with measured VEPs. Gd-T1WI showed a 3- to 4-fold enhancement over controls beginning after 2weeks of EAE. Across the time course, we found progressive reductions in FA and increases in RD with increases in VEP latency and reductions in amplitude. Significant correlations between DTI (FA and RD) and VEP evolved; in control/early asymptomatic EAE mice, both FA and RD were highly correlated with VEP latency (but not amplitude), while in late EAE, both DTI indices were highly correlated with VEP amplitude (but not latency). DTI measures FA and RD are associated to VEP latency in early stages of EAE but associated to VEP amplitude in later stages, suggesting that the patterns of DTI related to the functional decline may depend on the stage of disease progression.

Neurite dispersion: a new marker of multiple sclerosis spinal cord pathology?

ObjectiveConventional magnetic resonance imaging (MRI) of the multiple sclerosis spinal cord is limited by low specificity regarding the underlying pathological processes, and new MRI metrics assessing microscopic damage are required. We aim to show for the first time that neurite orientation dispersion (i.e., variability in axon/dendrite orientations) is a new biomarker that uncovers previously undetected layers of complexity of multiple sclerosis spinal cord pathology. Also, we validate against histology a clinically viable MRI technique for dispersion measurement (neurite orientation dispersion and density imaging, NODDI), to demonstrate the strong potential of the new marker.MethodsWe related quantitative metrics from histology and MRI in four post mortem spinal cord specimens (two controls; two progressive multiple sclerosis cases). The samples were scanned at high field, obtaining maps of neurite density and orientation dispersion from NODDI and routine diffusion tensor imaging (DTI) indices. Histological procedures provided markers of astrocyte, microglia, myelin and neurofilament density, as well as neurite dispersion.ResultsWe report from both NODDI and histology a trend toward lower neurite dispersion in demyelinated lesions, indicative of reduced neurite architecture complexity. Also, we provide unequivocal evidence that NODDI‐derived dispersion matches its histological counterpart (P < 0.001), while DTI metrics are less specific and influenced by several biophysical substrates.InterpretationNeurite orientation dispersion detects a previously undescribed and potentially relevant layer of microstructural complexity of multiple sclerosis spinal cord pathology. Clinically feasible techniques such as NODDI may play a key role in clinical trial and practice settings, as they provide histologically meaningful dispersion indices.

Structural and Neuronal Integrity Measures of Fatigue Severity in Multiple Sclerosis.

Fatigue is a common and disabling symptom in Multiple Sclerosis (MS). However, consistent neuroimaging correlates of its severity are not fully elucidated. In this article, we study the neuronal correlates of fatigue severity in MS. Forty-three Relapsing Remitting MS (RRMS) patients with MS-related fatigue (Fatigue Severity Scale (FSS) range: 1–7) and Expanded Disability Status Scale (EDSS) ≤ 4, were divided into high fatigue (HF, FSS ≥ 5.1) and low fatigue groups (LF, FSS ≤ 3). We measured T2 lesion load using a semi-automated technique. Cortical thickness, volume of sub-cortical nuclei, and brainstem structures were measured using Freesurfer. Cortical Diffusion Tensor Imaging (DTI) parameters were extracted using a cross modality technique. A correlation analysis was performed between FSS, volumetric, and DTI indices across all patients. HF patients showed significantly lower volume of thalamus, (p = 0.02), pallidum (p = 0.01), and superior cerebellar peduncle ((SCP), p = 0.002). The inverse correlation between the FSS score and the above volumes was significant in the total study population. In the right temporal cortex (RTC), the Radial Diffusivity ((RD), p = 0.01) and Fractional Anisotropy ((FA), p = 0.01) was significantly higher and lower, respectively, in the HF group. After Bonferroni correction, thalamic volume, FA-RTC, and RD-RTC remained statistically significant. Multivariate regression analysis identified FA-RTC as the best predictor of fatigue severity. Our data suggest an association between fatigue severity and volumetric changes of thalamus, pallidum, and SCP. Early neuronal injury in the RTC is implicated in the pathogenesis of MS-related fatigue.

Correlation between diffusion tensor imaging and histological brain injury in ventilated preterm lambs

Objective: Inflammation and mechanical ventilation contribute additively to white matter injury in the preterm infant. We examined whether in vivo diffusion tensor imaging (DTI) indices correlate with immunohistochemical analyses of brain inflammation and injury caused by injurious ventilation at birth, in the presence or absence of intrauterine inflammation. Methods: Twin-bearing ewes received an ultrasound guided injection of lipopolysaccharide (LPS; n=11) or saline (n=12) 7 days prior to delivery at ~125 days gestation. Immediately after delivery, lambs received either an injurious (LPS+INJ; n=5 and INJ; n=6) or protective (LPS+PROT; n=6 and PROT; n=5) ventilation strategy for 90 min, after which DTI was assessed. Following imaging, neuronal density (NeuN antibody) in the thalamus (Th) and myelin density (myelin basic protein, MBP) in the internal capsule (IC) and periventricular white matter (PVWM) were assessed. Results: LPS exposure significantly increased axial diffusivity (P=0.01) and decreased myelin density in the IC (P=0.02) compared to saline groups. Moreover, there was a strong inverse correlation between fractional anisotropy values and myelin density in PVWM (P=0.01), and a trend in the IC (P=0.07) in all lambs. Injurious ventilation tended to reduce radial and mean diffusivity in the Th (P=0.07 and P=0.08). Conclusion: DTI was able to detect microstructural changes associated with a reduction in myelination due to inflammation in the short term. However, DTI indices were not sensitive enough to consistently detect the microstructural changes induced by injurious ventilation immediately after birth.

USEFULNESS AND STABILITY OF MULTICENTER DIFFUSION TENSOR IMAGING AS AN EARLY MARKER FOR SUBJECTIVE COGNITIVE DECLINE AND AMNESTIC MILD COGNITIVE IMPAIRMENT: FIRST RESULTS FROM THE PROSPECTIVE DZNE DELCODE STUDY

Diffusion tensor imaging (DTI) is a useful diagnostic marker for differentiating patients with mild cognitive impairment (MCI) and Alzheimer's disease dementia (AD) from cognitively normal controls, as reported in various monocentric studies. Few monocentric studies performed DTI in individuals with subjective cognitive decline (SCD), who may be at risk of future AD. Compared to normal controls, most of these studies showed decreased fractional anisotropy (FA) and increased mean diffusivity (MD). However, multicenter studies using retrospective data reported a high vulnerability of DTI indices to nuisance variance, introduced by differences in acquisition parameters and study procedures. In the present study, we examined the stability of DTI in a large prospective multicenter cohort using identical scanning protocols and high-level standardized procedures. Furthermore, we assessed the usefulness of multicenter DTI to differentiate between individuals with SCD, MCI patients, AD patients and normal controls. N = 198 subjects from the DZNE Longitudinal Cognitive Impairment and Dementia (DELCODE) study were included in the analysis. We calculated the FA and MD indices for the baseline DTI data that was acquired across seven sites and analyzed them using tract-based spatial statistics (TBSS) and voxel-based analysis. For the latter approach, we applied partial volume correction to reduce the effect of cerebrospinal fluid contamination on grey matter MD estimates. Results will be presented at the conference. We expect to find reduced inter-site variability compared to a multicenter DTI study without harmonized acquisition parameters (European DTI study on Dementia; EDSD). Comparing the diagnostic groups, we expect to find decreased FA and increased MD indices in SCD subjects compared to normal controls, as well as in MCI and AD patients compared to SCD subjects and normal controls. The results from this study will contribute to the evaluation of DTI as a diagnostic marker at prodromal and at-risk stages of AD.

The efficiency of retrospective artifact correction methods in improving the statistical power of between-group differences in spinal cord DTI

Diffusion tensor imaging (DTI) is a promising approach for investigating the white matter microstructure of the spinal cord. However, it suffers from severe susceptibility, physiological, and instrumental artifacts present in the cord. Retrospective correction techniques are popular approaches to reduce these artifacts, because they are widely applicable and do not increase scan time.In this paper, we present a novel outlier rejection approach (reliability masking) which is designed to supplement existing correction approaches by excluding irreversibly corrupted and thus unreliable data points from the DTI index maps. Then, we investigate how chains of retrospective correction techniques including (i) registration, (ii) registration and robust fitting, and (iii) registration, robust fitting, and reliability masking affect the statistical power of a previously reported finding of lower fractional anisotropy values in the posterior column and lateral corticospinal tracts in cervical spondylotic myelopathy (CSM) patients.While established post-processing steps had small effect on the statistical power of the clinical finding (slice-wise registration: −0.5%, robust fitting: +0.6%), adding reliability masking to the post-processing chain increased it by 4.7%. Interestingly, reliability masking and registration affected the t-score metric differently: while the gain in statistical power due to reliability masking was mainly driven by decreased variability in both groups, registration slightly increased variability. In conclusion, reliability masking is particularly attractive for neuroscience and clinical research studies, as it increases statistical power by reducing group variability and thus provides a cost-efficient alternative to increasing the group size.

Subject-specific regional measures of water diffusion are associated with impairment in chronic spinal cord injury.

We aimed to identify non-invasive imaging parameters that can serve as biomarkers for the integrity of the spinal cord, which is paramount to neurological function. Diffusion tensor imaging (DTI) indices are sensitive to axonal and myelin damage, and have strong potential to serve as such biomarkers. However, averaging DTI indices over large regions of interest (ROIs), a common approach to analyzing the images of injured spinal cord, leads to loss of subject-specific information. We investigated if DTI-tractography-driven, subject-specific demarcation approach can yield measures that are more specific to impairment. In 18 individuals with chronic spinal cord injury (SCI), subject-specific demarcation of the injury region was performed using DTI tractography, which yielded three regions relative to injury (RRI; regions superior to, at, and below injury epicenter). DTI indices averaged over each RRI were correlated with measures of residual motor and sensory function, obtained using the International Standard of Neurological Classification for Spinal Cord Injury (ISNCSCI). Total ISNCSCI score (ISNCSCI-tot; sum of ISNCSCI motor and sensory scores) was significantly (p<0.05) correlated with fractional anisotropy and axial and radial diffusivities. ISNCSCI-tot showed strongest correlation with indices measured from the region inferior to the injury epicenter (IRRI), the degree of which exceeded that of those measured from the entire cervical cord-suggesting contribution from Wallerian degeneration. DTI tractography-driven, subject-specific injury demarcation approach provided measures that were more specific to impairment. Notably, DTI indices obtained from the IRRI region showed the highest specificity to impairment, demonstrating their strong potential as biomarkers for the SCI severity.

White matter damage and systemic inflammation in Parkinson\u2019s disease

BackgroundSystemic inflammation and white matter (WM) alterations have been noted as effects of Parkinson’s disease (PD). This study sought to evaluate WM integrity in PD patients using diffusion tensor imaging (DTI) and to assess its relationship with systemic inflammation.MethodsSixty-six patients with PD (23 men and 43 women) and 67 healthy volunteers (29 men and 38 women) underwent blood sampling to quantify inflammatory markers and DTI scans to determine fiber integrity. The inflammatory markers included leukocyte apoptosis, as well as cellular and serum adhesion molecules, in each peripheral blood sample. DTI-related indices [including fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD)] were derived from DTI scans. The resulting FA maps were compared using voxel-based statistics to determine differences between the PD and control groups. The differences in the DTI indices, clinical severity, and inflammatory markers were correlated.ResultsExploratory group-wise comparison between the two groups revealed that the PD patients exhibited extensive DTI index differences. Low FA accompanied by high RD and MD, without significant differences in AD, suggesting a demyelination process, were found in the parietal, occipital, cerebellar, and insular WM of the PD patients. The declined DTI indices were significantly correlated with increased clinical disease severity, adhesion molecules, and leukocyte apoptosis.ConclusionsPatients with PD experience WM integrity damage in vulnerable regions, and these impairments are associated with increased disease severity and systemic inflammation. The possible interactions among them may represent variant neuronal injuries and their consequent processes in PD.

The rapid development of structural plasticity through short water maze training: A DTI study

Diffusion MRI is sensitive to the microstructure of tissue and allows the study of structural plasticity over short time scales of only hours. The initial temporal and spatial progression of this process, however, has yet to be elucidated. With the aim of examining early temporal progression of structural plasticity, we subjected rats to short training periods on a task in the Morris water maze (MWM), a paradigm previously shown to induce rapid changes in diffusion tensor imaging (DTI) indices. Two groups of rats were each divided into subgroups that consecutively completed 1, 2 or 3 sets of short trials (up to 60s) in the MWM. Each set comprised 4 trials (1 from each quadrant of the WMW), with a specific time interval between sets. To assess the effect of the duration of the task on the evolving changes in DTI indices, we allowed a rest of 45min between sets in one group of rats and a 2-h rest in the other. All rats were scanned with a DTI protocol before and 45min after their last trial. We found that a few minutes of training in a new task sufficed to generate changes in diffusion indices. The earliest changes in DTI (measured after one set of trials) progressed with further training (measured after two sets), but within a few more minutes (after three sets) they reached a plateau. Lengthening the duration of the overall task by prolonging the time interval between sessions did not alter this pattern of change, suggesting that at least within this short time scale such changes are task-dependent, but not time dependent. Our results demonstrate the progression of structural neuroplasticity at different stages of exposure to a novel experience, and show that DTI can be used to trace, in vivo, the localization of structural plasticity induced by training.