Changes In Diffusion Metrics Research Articles

Diffusion tensor imaging changes of the cortico-thalamic-striatal tracts correlate with fatigue and disability in people with relapsing-remitting MS

PurposeTo investigate how the microstructural neural integrity of cortico-thalamic-striatal (CTS) tracts correlate with fatigue and disability over time. The primary outcome was diffusion tensor imaging (DTI) metrics change over time, and the secondary outcome was correlations with fatigue and disability in people with RRMS (pw-RRMS). Methods76 clinically stable pw-RRMS and 43 matched healthy controls (HCs). The pw-RRMS cohort consisted of three different treatment subgroups. All participants underwent disability, cognitive, fatigue and mental health assessments. Structural and diffusion scans were performed at baseline (BL) and 2-year follow-up (2-YFU) for all participants. Fractional anisotropy (FA), mean, radial and axial diffusivities (MD, RD, AD) of normal-appearing white matter (NAWM) and white matter lesion (WML) in nine tracts-of-interests (TOIs) were estimated using our MRtrix3 in-house pipeline. ResultsWe found significant BL and 2-YFU differences in most diffusion metrics in TOIs in pw-RRMS compared to HCs (pFDR ≤ 0.001; false-detection-rate (FDR)-corrected). There was a significant decrease in WML diffusivities and an increase in FA over the follow-up period in most TOIs (pFDR ≤ 0.001). Additionally, there were no differences in DTI parameters across treatment groups. AD and MD were positively correlated with fatigue scores (r ≤ 0.33, p ≤ 0.01) in NAWM-TOIs, while disability (EDSS) was negatively correlated with FA in most NAWM-TOIs (|r|≤0.31, p ≤ 0.01) at both time points. Disability scores correlated with all diffusivity parameters (r ≤ 0.29, p ≤ 0.01) in most WML-TOIs at both time points. ConclusionStatistically significant changes in diffusion metrics in WML might be indicative of integrity improvement over two years in CTS tracts in clinically stable pw-RRMS. This finding represents structural changes within lesioned tracts. Measuring diffusivity in pw-RRMS affected tracts might be a relevant measure for future remyelination clinical trials.

Multimodal MRI improves diagnostic accuracy and sensitivity to longitudinal change in amyotrophic lateral sclerosis

BackgroundRecent advances in MRI acquisitions and image analysis have increased the utility of neuroimaging in understanding disease-related changes. In this work, we aim to demonstrate increased sensitivity to disease progression as well as improved diagnostic accuracy in Amyotrophic lateral sclerosis (ALS) with multimodal MRI of the brain and cervical spinal cord.MethodsWe acquired diffusion MRI data from the brain and cervical cord, and T1 data from the brain, of 20 participants with ALS and 20 healthy control participants. Ten ALS and 14 control participants, and 11 ALS and 13 control participants were re-scanned at 6-month and 12-month follow-ups respectively. We estimated cross-sectional differences and longitudinal changes in diffusion metrics, cortical thickness, and fixel-based microstructure measures, i.e. fiber density and fiber cross-section.ResultsWe demonstrate improved disease diagnostic accuracy and sensitivity through multimodal analysis of brain and spinal cord metrics. The brain metrics also distinguished lower motor neuron-predominant ALS participants from control participants. Fiber density and cross-section provided the greatest sensitivity to longitudinal change. We demonstrate evidence of progression in a cohort of 11 participants with slowly progressive ALS, including in participants with very slow change in ALSFRS-R. More importantly, we demonstrate that longitudinal change is detectable at a six-month follow-up visit. We also report correlations between ALSFRS-R and the fiber density and cross-section metrics.ConclusionsOur findings suggest that multimodal MRI is useful in improving disease diagnosis, and fixel-based measures may serve as potential biomarkers of disease progression in ALS clinical trials.

Mapping early tumor response to radiotherapy using diffusion kurtosis imaging*.

In this pilot study, DKI measures of diffusivity and kurtosis were compared in active tumor regions and correlated to radiologic response to radiotherapy after completion of 2weeks of treatment to derive potential early measures of tumor response. MRI and Magnetic Resonance Spectroscopic Imaging (MRSI) data were acquired before the beginning of RT (pre-RT) and 2weeks after the initiation of treatment (during-RT) in 14 glioblastoma patients. The active tumor region was outlined as the union of the residual contrast-enhancing region and metabolically active tumor region. Average and standard deviation of mean, axial, and radial diffusivity (MD, AD, RD) and mean, axial, and radial kurtosis (MK, AK, RK) values were calculated for the active tumor VOI from images acquired pre-RT and during-RT and paired t-tests were executed to estimate pairwise differences. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive capabilities of changes in diffusion metrics for progression-free survival (PFS). Analysis showed significant pairwise differences for AD (p = 0.035; Cohen's d of 0.659) and AK (p = 0.019; Cohen's d of 0.753) in diffusion measures after 2weeks of RT. ROC curve analysis showed that percentage change differences in AD and AK between pre-RT and during-RT scans provided an Area Under the Curve (AUC) of 0.524 and 0.762, respectively, in discriminating responders (PFS>180 days) and non-responders (PFS<180days). This pilot study, although preliminary in nature, showed significant changes in AD and AK maps, with kurtosis derived AK maps showing an increased sensitivity in mapping early changes in the active tumor regions.

Longitudinal monitoring of amyotrophic lateral sclerosis by diffusion tensor imaging: Power calculations for group studies.

IntroductionDiffusion tensor imaging (DTI) can be used to map disease progression in amyotrophic lateral sclerosis (ALS) and therefore is a promising candidate for a biomarker in ALS. To this end, longitudinal study protocols need to be optimized and validated regarding group sizes and time intervals between visits. The objective of this study was to assess the influences of sample size, the schedule of follow-up measurements, and measurement uncertainties on the statistical power to optimize longitudinal DTI study protocols in ALS.Patients and methodsTo estimate the measurement uncertainty of a tract-of–interest-based DTI approach, longitudinal test-retest measurements were applied first to a normal data set. Then, DTI data sets of 80 patients with ALS and 50 healthy participants were analyzed in the simulation of longitudinal trajectories, that is, longitudinal fractional anisotropy (FA) values for follow-up sessions were simulated for synthetic patient and control groups with different rates of FA decrease in the corticospinal tract. Monte Carlo simulations of synthetic longitudinal study groups were used to estimate the statistical power and thus the potentially needed sample sizes for a various number of scans at one visit, different time intervals between baseline and follow-up measurements, and measurement uncertainties.ResultsFrom the simulation for different longitudinal FA decrease rates, it was found that two scans per session increased the statistical power in the investigated settings unless sample sizes were sufficiently large and time intervals were appropriately long. The positive effect of a second scan per session on the statistical power was particularly pronounced for FA values with high measurement uncertainty, for which the third scan per session increased the statistical power even further.ConclusionWith more than one scan per session, the statistical power of longitudinal DTI studies can be increased in patients with ALS. Consequently, sufficient statistical power can be achieved even with limited sample sizes. An improved longitudinal DTI study protocol contributes to the detection of small changes in diffusion metrics and thereby supports DTI as an applicable and reliable non-invasive biomarker in ALS.

Implications of DTI in mild traumatic brain injury for detecting neurological recovery and predicting long-term behavioural outcome in paediatric and young population-a systematic review.

This systematic review was done with the aim to answer these three questions: 1) Is there any change in diffusion metrics in MRI-DTI sequences after mildtraumatic brain injury in paediatric and young population?, 2) Is there any correlation of these changes in diffusion metrics with severity of post concussionsymptoms?, 3) Is the change in diffusion metrics predictive of neurocognitive function or neurological recovery? Eligibility criteria- Mild TBI patients upto 22 years of age, MRI- DTI sequence done post injury, Outcome measurement with follow up at least for onemonth and articles published in English language only.Data sources- PubMed, EMBASE, CINAHL, Scopus and Cochrane RESULTS: Some studies show increased FA and some studies show decrease FA and few showed no change in white matter microstructure in mTBI patients and thisdepends on the duration of injury. Prediction of PCSs severity on the basis of changes in white matter microstructure showed inconsistent results.Radiological recovery in contrast to clinical recovery, is often delayed ranging from 6 months to 2-3 years. But change in diffusion metrics after mTBI isnot definite predictive of neurocognitive outcomes. Large, properly designed, multicentric studies with appropriate extracranial or orthopedic control and long follow up are needed to establish the use of DTIin mTBI for predicting behavioral outcome.

Multi-shot echo-planar diffusion tensor imaging in cervical spondylotic myelopathy.

The aim of this study was to use diffusion tensor imaging (DTI) to investigate changes in diffusion metrics in patients with cervical spondylotic myelopathy (CSM) up to five years after decompressive surgery. We correlated these changes with clinical outcomes as scored by the Modified Japanese Orthopedic Association (mJOA) method, Neck Disability Index (NDI), and Visual Analogue Scale (VAS). We used multi-shot, high-resolution, diffusion tensor imaging (ms-DTI) in patients with cervical spondylotic myelopathy (CSM) to investigate the change in diffusion metrics and clinical outcomes up to five years after anterior cervical interbody discectomy and fusion (ACDF). High signal intensity was identified on T2-weighted imaging, along with DTI metrics such as fractional anisotropy (FA). MJOA, NDI, and VAS scores were also collected and compared at each follow-up point. Spearman correlations identified correspondence between FA and clinical outcome scores. Significant differences in mJOA scores and FA values were found between preoperative and postoperative timepoints up to two years after surgery. FA at the level of maximum cord compression (MCL) preoperatively was significantly correlated with the preoperative mJOA score. FA postoperatively was also significantly correlated with the postoperative mJOA score. There was no statistical relationship between NDI and mJOA or VAS. ms-DTI can detect microstructural changes in affected cord segments and reflect functional improvement. Both FA values and mJOA scores showed maximum recovery two years after surgery. The DTI metrics are significantly associated with pre- and postoperative mJOA scores. DTI metrics are a more sensitive, timely, and quantifiable surrogate for evaluating patients with CSM and a potential quantifiable biomarker for spinal cord dysfunction. Cite this article: Bone Joint J 2020;102-B(9):1210-1218.

Tract-specific analysis improves sensitivity of spinal cord diffusion MRI to cross-sectional and longitudinal changes in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a late-onset fatal neurodegenerative disease that causes progressive degeneration of motor neurons in the brain and the spinal cord. Corticospinal tract degeneration is a defining feature of ALS. However, there have been very few longitudinal, controlled studies assessing diffusion MRI (dMRI) metrics in different fiber tracts along the spinal cord in general or the corticospinal tract in particular. Here we demonstrate that a tract-specific analysis, with segmentation of ascending and descending tracts in the spinal cord white matter, substantially increases the sensitivity of dMRI to disease-related changes in ALS. Our work also identifies the tracts and spinal levels affected in ALS, supporting electrophysiologic and pathologic evidence of involvement of sensory pathways in ALS. We note changes in diffusion metrics and cord cross-sectional area, with enhanced sensitivity to disease effects through a multimodal analysis, and with strong correlations between these metrics and spinal components of ALSFRS-R.

Diffusion Tensor Imaging Detects Acute and Subacute Changes in Corpus Callosum in Blast-Induced Traumatic Brain Injury.

There is a critical need for understanding the progression of neuropathology in blast-induced traumatic brain injury using valid animal models to develop diagnostic approaches. In the present study, we used diffusion imaging and magnetic resonance (MR) morphometry to characterize axonal injury in white matter structures of the rat brain following a blast applied via blast tube to one side of the brain. Diffusion tensor imaging was performed on acute and subacute phases of pathology from which fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were calculated for corpus callosum (CC), cingulum bundle, and fimbria. Ventricular volume and CC thickness were measured. Blast-injured rats showed temporally varying bilateral changes in diffusion metrics indicating persistent axonal pathology. Diffusion changes in the CC suggested vasogenic edema secondary to axonal injury in the acute phase. Axonal pathology persisted in the subacute phase marked by cytotoxic edema and demyelination which was confirmed by ultrastructural analysis. The evolution of pathology followed a different pattern in the cingulum bundle: axonal injury and demyelination in the acute phase followed by cytotoxic edema in the subacute phase. Spatially, structures close to midline were most affected. Changes in the genu were greater than in the body and splenium; the caudal cingulum bundle was more affected than the rostral cingulum. Thinning of CC and ventriculomegaly were greater only in the acute phase. Our results reveal the persistent nature of blast-induced axonal pathology and suggest that diffusion imaging may have potential for detecting the temporal evolution of blast injury.

Development of anisotropic phantoms using wood and fiber materials for diffusion tensor imaging and diffusion kurtosis imaging

ObjectiveSeveral studies have demonstrated that anisotropic phantoms can be utilized for diffusion magnetic resonance imaging. The purpose of our study was to examine whether wood is suitable as an anisotropic phantom material from the viewpoints of affordability and availability. In the current study, wood was used for restricted diffusion, and fibers were used for hindered diffusion.Materials and methodsWood and fiber phantoms were made. Diffusion kurtosis images were acquired with three magnetic resonance scanners. Fractional anisotropy, radial diffusivity, axial diffusivity, radial kurtosis and axial kurtosis values were measured. The wood phantom was imaged, and its durability was confirmed. The phantoms were imaged in varying orientations within the magnetic field. The wood was observed using an optical microscope.ResultsTen kinds of wood and the fiber had a diffusion metrics. The wood diffusion metrics suggested low variation over a period of 9 months. Changing the orientation of the phantoms within the magnetic field resulted in changes in diffusion metrics. Observation of wood vessels and fibers was conducted.DiscussionWood and fibers have anisotropy and are promising as phantom materials. The development of anisotropic phantoms that anyone can use is useful for diffusion magnetic resonance imaging research and clinical applications.

Changes in Diffusion Metrics of the Red Nucleus in Chronic Stroke Patients With Severe Corticospinal Tract Injury: A Preliminary Study.

ObjectiveTo explore plastic changes in the red nucleus (RN) of stroke patients with severe corticospinal tract (CST) injury as a compensatory mechanism for recovery of hand function.MethodsThe moderate group (MG) comprised 5 patients with synergistic hand grasp movement combined with limited extension, and the severe group (SG) included 5 patients with synergistic hand grasp movement alone. The control group (CG) included 5 healthy subjects. Motor assessment was measured by Motricity Index (MI). Diffusion tensor imaging was analyzed using fractional anisotropy (FA) and radial diffusivity (RD) in the individual regions of interest (ROIs)—bilateral internal capsule and anterior pons for CST injury and bilateral RN for rubrospinal tract (RST) injury.ResultsThe SG showed a significantly lower MI score than the MG mainly due to differences in hand subscores. Significantly reduced FA was observed in both MG and SG compared with CG, while SG showed increased MD and RD in the affected ROIs of CST, and increased FA on the unaffected side compared with CG. However, in the RN ROI, a significantly increased FA and decreased RD on the unaffected side similar to the affected side were found only in the SG. The relative index of FA was lower and RD in SG was higher than in CG in RST. ConclusionThe diffusion metrics of RST showed changes in patients with severe CST injury, suggesting that RST may play a role in the recovery of hand function in patients with severe CST injury.

Analyses of regional radiosensitivity of white matter structures along tract axes using novel white matter segmentation and diffusion imaging biomarkers.

Background and purposeBrain radiotherapy (RT) can cause white matter damage and downstream neurocognitive decline. We developed a computational neuroimaging tool to regionally partition individual white matter tracts, then analyze regional changes in diffusion metrics of white matter damage following brain RT.Materials and methodsRT dose, diffusion metrics and white matter tract structures were extracted and mapped to a reference brain for 49 patients who received brain RT, and underwent diffusion tensor imaging pre- and 9–12 months post-RT. Based on their elongation, 23 of 48 white matter tracts were selected. The Tract-Crawler software was developed in MATLAB to create cross-sectional slice planes normal to a tract’s computed medial axis. We then performed slice- and voxel-wise analysis of radiosensitivity, defined as percent change in mean diffusivity (MD) and fractional anisotropy (FA) as a function of dose relative to baseline.ResultsDistinct patterns of FA/MD radiosensitivity were seen for specific tracts, including the corticospinal tract, medial lemniscus, and inferior cerebellar peduncle, in particular at terminal ends. These patterns persisted for corresponding tracts in left and right hemispheres. Local sensitivities were as high as 40%/Gy (e.g., voxel-wise: −39 ± 31%/Gy in right corticospinal tract FA, −45 ± 25%/Gy in right inferior cerebellar peduncle FA), p < 0.05.ConclusionsTract-Crawler, a novel tool to visualize and analyze cuts of white matter structures normal to medial axes, was used to demonstrate that particular white matter tracts exhibit significant regional variations in radiosensitivity based on diffusion biomarkers.

Longitudinal DTI changes following cognitive training therapy in a mild traumatic brain injury rat model

Longitudinal DTI changes following cognitive training therapy in a mild traumatic brain injury rat model

Diffusion Tensor Imaging of Central Auditory Pathways in Patients with Sensorineural Hearing Loss: A Systematic Review.

Objective The radiologic evaluation of patients with hearing loss includes computed tomography and magnetic resonance imaging (MRI) to highlight temporal bone and cochlear nerve anatomy. The central auditory pathways are often not studied for routine clinical evaluation. Diffusion tensor imaging (DTI) is an emerging MRI-based modality that can reveal microstructural changes in white matter. In this systematic review, we summarize the value of DTI in the detection of structural changes of the central auditory pathways in patients with sensorineural hearing loss. Data Sources PubMed, Embase, and Cochrane. Review Methods We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement checklist for study design. All studies that included at least 1 sensorineural hearing loss patient with DTI outcome data were included. Results After inclusion and exclusion criteria were met, 20 articles were analyzed. Patients with bilateral hearing loss comprised 60.8% of all subjects. Patients with unilateral or progressive hearing loss and tinnitus made up the remaining studies. The auditory cortex and inferior colliculus (IC) were the most commonly studied regions using DTI, and most cases were found to have changes in diffusion metrics, such as fractional anisotropy, compared to normal hearing controls. Detectable changes in other auditory regions were reported, but there was a higher degree of variability. Conclusion White matter changes based on DTI metrics can be seen in patients with sensorineural hearing loss, but studies are few in number with modest sample sizes. Further standardization of DTI using a prospective study design with larger sample sizes is needed.

Short-term white matter alterations in Alzheimer's disease characterized by diffusion tensor imaging.

To investigate whether there are any white matter changes in a 6-month follow-up of mild-moderate Alzheimer's patients using diffusion tensor imaging (DTI). We recruited 18 mild-moderate Alzheimer's disease patients and they underwent magnetic resonance imaging (MRI) at recruitment and at 6-month follow-up. Diffusion MRI images were processed using DTI-ToolKit to create a population-based tensor template. This template was integrated with a voxel-wise and atlas-based analysis in FSL to determine the magnitude and location of change in diffusion metrics over the 6-month follow-up period. There were significant widespread changes in diffusion metrics across the entire white matter skeleton (P < 0.001), 95% confidence interval (CI) difference in fractional anisotropy: -0.007 (-0.011, -0.002), mean diffusivity: 0.040 (0.023, 0.058), axial diffusivity: 0.015 (0.008, 0.022), radial diffusivity: 0.012 (0.006, 0.019), as well as regions of interest in the splenium and superior longitudinal fasciculus. Our findings show that diffusion metrics are altered in a 6-month follow-up period of mild-moderate Alzheimer's patients, supporting the potential of DTI metrics to act as sensitive biomarkers for disease progression even over a relatively short time interval, and the potential utility to be applied to clinical trials of putative disease-modifying therapies.

Imaging Findings Associated with Cognitive Performance in Primary Lateral Sclerosis and Amyotrophic Lateral Sclerosis

Introduction: Executive dysfunction occurs in many patients with amyotrophic lateral sclerosis (ALS), but it has not been well studied in primary lateral sclerosis (PLS). The aims of this study were to (1) compare cognitive function in PLS to that in ALS patients, (2) explore the relationship between performance on specific cognitive tests and diffusion tensor imaging (DTI) metrics of white matter tracts and gray matter volumes, and (3) compare DTI metrics in patients with and without cognitive and behavioral changes. Methods: The Delis-Kaplan Executive Function System (D-KEFS), the Mattis Dementia Rating Scale (DRS-2), and other behavior and mood scales were administered to 25 ALS patients and 25 PLS patients. Seventeen of the PLS patients, 13 of the ALS patients, and 17 healthy controls underwent structural magnetic resonance imaging (MRI) and DTI. Atlas-based analysis using MRI Studio software was used to measure fractional anisotropy, and axial and radial diffusivity of selected white matter tracts. Voxel-based morphometry was used to assess gray matter volumes. The relationship between diffusion properties of selected association and commissural white matter and performance on executive function and memory tests was explored using a linear regression model. Results: More ALS than PLS patients had abnormal scores on the DRS-2. DRS-2 and D-KEFS scores were related to DTI metrics in several long association tracts and the callosum. Reduced gray matter volumes in motor and perirolandic areas were not associated with cognitive scores. Conclusion: The changes in diffusion metrics of white matter long association tracts suggest that the loss of integrity of the networks connecting fronto-temporal areas to parietal and occipital areas contributes to cognitive impairment.