The independent prognostic value of brain diffusion tensor imaging in comatose patients after cardiac arrest

ObjectiveCognitive impairment in patients with cerebral small vessel disease (CSVD) is closely associated with white matter injury. This study aims to evaluate whether diffusion tensor imaging (DTI) metrics can predict the risk of cognitive impairment in CSVD patients.MethodsWe retrospectively analyzed data from 54 CSVD patients, classified into a cognitive impairment group (CI, n = 25) and a non-cognitive impairment group (NCI, n = 29). Using tract-based spatial statistics (TBSS), we computed fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) across 48 major white matter tracts. Significant DTI metrics identified by univariate logistic regression were used to construct a multivariate logistic regression model. Model performance was evaluated via 5-fold cross-validation based on the area under the ROC curve (AUC), calibration curves, and decision curve analysis.ResultsSeveral DTI metrics showed significant correlations with cognitive impairment, including FA (fornix, left corticospinal tract, bilateral medial lemniscus/inferior cerebellar peduncle, left cerebral peduncle, right cingulum hippocampus), MD (right superior cerebellar peduncle, left cerebral peduncle), and RD (bilateral medial lemniscus, right inferior/superior cerebellar peduncle, left cerebral peduncle, right external capsule, cingulum hippocampus). The multivariate model constructed based on these metrics demonstrated the best predictive performance, with a mean training AUC of 0.940 and testing AUC of 0.809. The calibration curves showed good agreement between predicted and observed outcomes, and decision curve analysis confirmed the clinical utility of the model.ConclusionThe multivariate logistic regression model incorporating DTI metrics can effectively identify cognitive impairment in CSVD patients. This study establishes a link between damage in specific white matter tracts and cognitive dysfunction, providing a practical tool for assessing the risk of cognitive impairment in clinical settings.

Microstructural abnormalities found in uncinate fasciculus and superior cerebellar tracts in children with global developmental delay: a feasibility study

Item does not contain fulltext

Throughout adulthood, the brain undergoes an array of structural and functional changes during the typical aging process. These changes involve decreased brain volume, reduced synaptic density, and alterations in white matter (WM). Although there have been some previous neuroimaging studies that have measured the ability of adult language production and its correlations to brain function, structural gray matter volume, and functional differences between young and old adults, the structural role of WM in adult language production in individuals across the life span remains to be thoroughly elucidated. This study selected 38 young adults and 35 old adults for diffusion tensor imaging (DTI) and performed the Controlled Oral Word Association Test to assess verbal fluency (VF). Tract-Based Spatial Statistics were employed to evaluate the voxel-based group differences of diffusion metrics for the values of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and local diffusion homogeneity (LDH) in 12 WM regions of interest associated with language production. To investigate group differences on each DTI metric, an analysis of covariance (ANCOVA) controlling for sex and education level was performed, and the statistical threshold was considered at p < 0.00083 (0.05/60 labels) after Bonferroni correction for multiple comparisons. Significant differences in DTI metrics identified in the ANCOVA were used to perform correlation analyses with VF scores. Compared to the old adults, the young adults had significantly (1) increased FA values on the bilateral anterior corona radiata (ACR); (2) decreased MD values on the right ACR, but increased MD on the left uncinate fasciculus (UF); and (3) decreased RD on the bilateral ACR. There were no significant differences between the groups for AD or LDH. Moreover, the old adults had only a significant correlation between the VF score and the MD on the left UF. There were no significant correlations between VF score and DTI metrics in the young adults. This study adds to the growing body of research that WM areas involved in language production are sensitive to aging.

Diffusion tensor imaging (DTI) metrics such as fractional anisotropy (FA) and mean diffusivity (MD) have been proposed as clinical trial markers of cerebral small vessel disease (SVD) due to their associations with outcomes such as cognition. However, studies investigating this have been predominantly single-centre. As clinical trials are likely to be multisite, further studies are required to determine whether associations with cognition of similar strengths can be detected in a multicentre setting. One hundred and nine patients (mean age =68 years) with symptomatic lacunar infarction and confluent white matter hyperintensities (WMH) on MRI was recruited across six sites as part of the PRESERVE DTI substudy. After handling missing data, 3T-MRI scanning was available from five sites on five scanner models (Siemens and Philips), alongside neuropsychological and quality of life (QoL) assessments. FA median and MD peak height were extracted from DTI histogram analysis. Multiple linear regressions were performed, including normalized brain volume, WMH lesion load, and n° lacunes as covariates, to investigate the association of FA and MD with cognition and QoL. DTI metrics from all white matter were significantly associated with global cognition (standardized β =0.268), mental flexibility (β =0.306), verbal fluency (β =0.376), and Montreal Cognitive Assessment (MoCA) (β =0.273). The magnitudes of these associations were comparable with those previously reported from single-centre studies found in a systematic literature review. In this multicentre study, we confirmed associations between DTI parameters and cognition, which were similar in strength to those found in previous single-centre studies. The present study supports the use of DTI metrics as biomarkers of disease progression in multicentre studies.

This study aimed to investigate the effectiveness of tract-specific diffusion tensor imaging (DTI) metrics in identifying the responsible segments for neurological dysfunction in cervical spondylotic myelopathy (CSM). The study encompassed nineteen participants diagnosed with CSM, including 10 males and 9 females. Additionally, a control group consisting of ten healthy caregivers (5 males and 5 females) were recruited with no symptoms and no compressions on magnetic resonance imaging (MRI). All participants underwent a comprehensive physical examination, MRI assessment, and DTI examination conducted by a senior chief physician. Several parameters were collected from the MR images, including the aspect ratio (defined as the anteroposterior diameter / the transverse diameter of the corresponding segment's spinal cord), transverse ratio (defined as the transverse diameter of the corresponding segment's spinal cord / the transverse diameter of the spinal cord at C2/3), and T2 high signal of the spinal cord. Furthermore, quantitative DTI metrics, such as axial diffusivity (AD), mean diffusivity (MD), radial diffusivity (RD), and fractional anisotropy (FA), were calculated using automatic region-of-interest (ROI) analysis for both whole spinal cord column and dorsal column. Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic efficacy of the aspect ratio, transverse ratio, and DTI parameters. The area under the curve (AUC), sensitivity, and specificity were calculated. Intraoperative spinal cord electrophysiological examination was performed as the objective measure of spinal cord function during surgery. As determined by electrophysiological examination, neurological dysfunction was found in 2 patients due to C3/4 compression, in 10 patients due to C4/5 compression, in 6 patients due to C5/6 compression, and in 1 patient due to C6/7 compression. The modified Japanese Orthopedic Association scale (mJOA) was 12.71 ± 1.55 in the CSM group, with 4.87 ± 0.72 for sensory nerve function and 5.05 ± 1.35 for motor nerve function. For the control group, none of the volunteers had neurological dysfunction. T2 high signal was found at the most stenotic segment in 13 patients of the CSM group. Considering all the cervical segments, the aspect ratio (AUC = 0.823, P = 0.001, Sensitivity = 68.42%, Specificity = 82.47%) was more capable of determining the responsible segment than transverse ratio (AUC = 0.661, P = 0.027, Sensitivity = 68.42%, Specificity = 67.01%). AD, MD, and RD were significantly higher while FA was significantly lower in the responsible segment than in the irresponsible segment (P < 0.05). The AUC of DTI-Dorsal column parameters (AD, MD, RD, FA) was larger than the corresponding parameters of the DTI (Whole spinal cord). AD of DTI-Dorsal Column possessed the greatest efficacy (AUC = 0.823, sensitivity = 84.21%, specificity = 77.32%) to determine the responsible segment, larger than AD of DTI-Whole spinal cord (AUC = 0.822, P = 0.001, Sensitivity = 89.47%, Specificity = 77.32%), aspect ratio (AUC = 0.823, P = 0.001, Sensitivity = 68.42%, Specificity = 82.47%) and transverse ratio (AUC = 0.661, P = 0.027, Sensitivity = 68.42%, Specificity = 67.01%). Subgroup analysis revealed that the diagnostic efficacy of DTI and MRI parameters was influenced by cervical spine segment. When considering all cervical segments, AD from the DTI-Dorsal Column exhibited the most significant potential in identifying responsible segments. This potential was found to be superior to that of DTI-Whole spinal cord, aspect ratio, the most stenotic segment, T2 high signals, transverse ratio, motor nerve dysfunction, and sensory nerve dysfunction. The diagnostic effectiveness of both DTI and MRI parameters was notably influenced by the specific cervical spine segment.

BackgroundNumerous studies have reported correlations between diffusion tensor imaging (DTI) metrics and cerebrospinal (CSF) biomarkers of Alzheimer’s disease (AD) pathology. However, the assumption of Gaussian diffusion in DTI limits the ability to characterize white matter (WM) microstructural changes. Mean apparent propagator (MAP) MRI is a model that attempts to overcome this limitation by allowing for the estimation of parameters that convey more precise information about WM microstructure.To investigate MAP MRI’s sensitivity to early WM degeneration associated with preclinical, asymptomatic AD pathology, we examined the relationship between CSF biomarkers and MAP MRI microstructural parameters in 92 cognitively unimpaired adults.Method92 cognitively unimpaired controls from the Wisconsin Registry for Alzheimer’s Prevention and the Wisconsin Alzheimer’s Disease Research Center were imaged with multi‐shell diffusion‐weighted MRI. DTI metrics (FA, MD, RD, AxD) were computed and the MAP MRI model was employed to calculate various microstructural parameters: Return to origin probability (RTOP), return to axis probability (RTAP), return to plane probability (RTPP), mean squared displacement (MSD), Non‐Gaussianity (NG), and q‐space inverse variance (QIV). DTI and MAP parameter values were extracted from the cingulum and correlated to Aβ42, P‐Tau, P‐Tau/Aβ42, YKL‐40, and neurofilament light chain (NFL) levels in lumbar cerebrospinal fluid samples.ResultMAP parameters were moderately and significantly correlated to most CSF measures. RTPP was significantly correlated to all 5 CSF measures, while MSD, NG, and QIV were significantly correlated to 4 of 5 CSF measures. NFL, a known marker for axonal degeneration, was significantly related to 5 of the 6 MAP parameters assessed. Meanwhile, correlations between DTI and CSF measures were weak and non‐significant.ConclusionThese preliminary results highlight the potential of MAP MRI to detect early WM deterioration indicative of preclinical, asymptomatic AD and associated neurodegeneration. MAP metrics extracted from a commonly affected WM tract in AD were more strongly and significantly correlated with CSF measures than DTI metrics were, suggesting that MAP MRI may be more useful than DTI for identifying the earliest WM microstructural changes associated with AD. Future work will incorporate longitudinal data and assess the effects of CSF and molecular imaging markers on MAP age trajectories.

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor and extra-motor systems. Diffusion tensor imaging (DTI) can be used to assess white matter (WM) tracts and has potential to be a marker of disease progression. Aims: This study aims to assess the abnormalities in brain white and gray matter in patients with amyotrophic lateral sclerosis (ALS) using MRI. It focuses on the white matter changes associated with cognitive change and serial studies in patients with ALS. Methods: MRI data were acquired in a total of 30 patients and 19 healthy controls. Patients were scanned up to three times with 6–month intervals on a 3T MRI. ALSFRS-R and cognitive testing were administered at each clinical visit. The MRI included a T1-weighted image and diffusion weighted MRI along 64 directions. MRI data were analyzed using voxel-based morphometry (VBM), and tract-based spatial statistics (TBSS) for all DTI metrics, sub-grouping ALS patients based on their cognitive performance. For the serial studies, TBSS and region-of-interest (ROI) methods were applied to the longitudinal datasets. In the 6–month follow-up study, total number of ALS subjects was 23, FA and MD were measured for the motor and extra-motor pathways and correlated with the revised ALS functional rating scale (ALSFRS–R) and disease duration. TBSS and ROI methods, both manual and atlas-based approaches, were used for the 12–month follow-up study which included only 15 subjects. Results for both ROI approaches were compared. Results: There was variability in clinical presentation among patients, with a mixture of site of onset and presence/absence of cognitive changes. At the first time-point study, all DTI measures and GM volume differed significantly between ALS subjects and controls in motor and extra-motor regions. Comparing each ALS subgroup to controls, greater DTI changes were present in ALS with cognitive impairment (ALScog) than ALS subjects without cognitive impairment (ALSnon-cog) subjects. In ALS compared to controls, there were changes on the right side and in a small region in the left middle frontal gyrus. Comparing ALS sub-groups, GM results showed reduction in the caudate nucleus volume in ALScog subjects. In the serial scans, when comparing all ALS time-points, the TBSS showed no significant changes between the first two scans or at three time-points. Using ROI method for 6-month follow-up, the average changes in FA and MD in the selected ROIs were small and not significant after correcting for multiple com parisons. The FA correlated with ALSFRS-R in the genu of corpus callosum (gCC) and bilaterally in the forceps minor and inferior longitudinal fasciculus (ILF) at first scan but not at the second scan. The MD in the hippocampus WM tracts (Hpc), the association fibers and anterior limb of internal capsule (ALIC), gCC and corona radiata (CR) correlated with disease duration and ALSFRS-R. Over 12-month follow-up, when TBSS group comparison were performed for each time-point compared to controls, the changes in serial three time-points were mainly along the cortico-spinal tract (CST) and the whole corpus callosum (CC). ROI methods showed no significant differences in the average FA in the posterior limb of internal capsule (PLIC) or CST at the pons between time-point. There was a significant correlation of the values for the rate of loss in the left PLIC with survival and the correlation approached significance for the right PLIC. Linear regression analysis showed a significant relationship between the manual and atlas based methods for the PLIC but not the pons. However, this study found that manual ROI (mROI) is correlated with the atlas-based ROI (aROI). Conclusion: The combined DTI and VBM study at the first time point showed changes in motor and extra-motor regions in patients with ALS compared to controls. The DTI changes were more extensive in ALS with cognitive impairment than pure ALS subjects. It is likely that the inclusion of ALS subjects with cognitive impairment in previous studies resulted in extra-motor WM abnormalities being reported in ALS subjects. Our study finds that there was little change in the DTI over time in patients with ALS. However, there was variability in clinical features among patients. For individuals there is some correlation with disease progression, measured by ALSFRS-R and survival. Our results would suggest that better results are obtained from the PLIC than the CST in the pons.

Background and purposePatients with transient ischemic attack (TIA) show evidence of cognitive impairment but the reason is not clear. Measurement of microstructural changes in white matter (WM) using diffusion tensor imaging (DTI) may be a useful outcome measure. We report WM changes using DTI and the relationship with neuropsychological performance in a cohort of transient ischemic attack (TIA) and non-TIA subjects.MethodsNinety-five TIA subjects and 51 non-TIA subjects were assessed using DTI and neuropsychological batteries. Fractional anisotropy (FA) and mean diffusivity (MD) maps were generated and measurements were collected from WM tracts. Adjusted mixed effects regression modelled the relationship between groups and DTI metrics.ResultsTransient ischemic attack subjects had a mean age of 67.9 ± 9.4 years, and non-TIA subjects had a mean age 64.9 ± 9.9 years. The TIA group exhibited higher MD values in the fornix (0.36 units, P < 0.001) and lower FA in the superior longitudinal fasciculus (SLF) (-0.29 units, P = 0.001), genu (-0.22 units, P = 0.016), and uncinate fasciculus (UF) (-0.26 units, P = 0.004). Compared to non-TIA subjects, subjects with TIA scored lower on the Addenbrooke’s Cognitive Assessment-Revised (median score 95 vs 91, P = 0.01) but showed no differences in scores on the Montreal Cognitive Assessment (median 27 vs 26) or the Mini-Mental State Examination (median 30). TIA subjects had lower scores in memory (median 44 vs 52, P < 0.01) and processing speed (median 45 vs 62, P < 0.01) but not executive function, when compared to non-TIA subjects. Lower FA and higher MD in the fornix, SLF, and UF were associated with poorer performance on tests of visual memory and executive function but not verbal memory. Lower FA in the UF and fornix were related to higher timed scores on the TMT-B (P < 0.01), and higher SLF MD was related to higher scores on TMT-B (P < 0.01), confirming worse executive performance in the TIA group.ConclusionsDTI scans may be useful for detecting microstructural disease in TIA subjects before cognitive symptoms develop. DTI parameters, white matter hyperintensities, and vascular risk factors underly some of the altered neuropsychological measures in TIA subjects.

AimCurrent multimodal approaches leave approximately half of the comatose patients after cardiac arrest with an indeterminate prognosis. Here we investigated whether early MRI markers of brain network integrity can distinguish between comatose patients with a good versus poor neurological outcome six months later. MethodsWe performed a prospective cohort study in 48 patients after cardiac arrest submitted in a comatose state to the Intensive Care Unit of two Dutch hospitals. MRI was performed at three days after cardiac arrest, including resting state functional MRI and diffusion-tensor imaging (DTI). Resting state fMRI was used to quantify functional connectivity within ten resting-state networks, and DTI to assess mean diffusivity (MD) in these same networks. We contrasted two groups of patients, those with good (n = 29, cerebral performance category 1–2) versus poor (n = 19, cerebral performance category 3–5) outcome at six months. Mutual associations between functional connectivity, MD, and clinical outcome were studied. ResultsPatients with good outcome show higher within-network functional connectivity (fMRI) and higher MD (DTI) than patients with poor outcome across 8/10 networks, most prominent in the default mode network, salience network, and visual network. While the anatomical distribution of outcome-related changes was similar for functional connectivity and MD, the pattern of inter-individual differences was very different: functional connectivity showed larger inter-individual variability in good versus poor outcome, while the opposite was observed for MD. Exploratory analyses suggested that it is possible to define network-specific cut-off values that could help in outcome prediction: (1) high functional connectivity and high MD, associated with good outcome; (2) low functional connectivity and low MD, associated with poor outcome; (3) low functional connectivity and high MD, associated with uncertain outcome. DiscussionResting-state functional connectivity and mean diffusivity-three days after cardiac arrest are strongly associated with neurological recovery-six months later in a complementary fashion. The combination of fMRI and MD holds potential to improve prediction of outcome.

Usefulness of different DTI parameters in identifying neurodegenerative process: Evidence from amyotrophic lateral sclerosis

Tractography is a procedure that can track and demonstrate the 3D neural tracts of the white matter of the brain. The images of the brain are obtained by analyzing the diffusion tensor, identification of which can provide the anatomical connections of the brain. Studying these connections is integral to the understanding of the brain function. Specifically, the uncinate fasciculus and fornix, which are the white matter in the human brain, are said to be related to cognitive function. The tractography is calculated using diffusion tensor imaging (DTI) parameter. Studies have shown that the DTI parameter of dementia patients is lower than that of healthy individuals. It is also suggested that the DTI parameter of healthy individuals decreases with age. In addition, Proton MR Spectroscopy ((1)H-MRS) is indicative of neuronal damage and has been used for decades as a noninvasive technique for assessing the biochemistry of the human brain. This is reflected by the increasing number of clinical MRS investigations of neurological disorders. Thus, MRS and DTI can provide complementary images on white matter in brain and it is important to investigate the white matter brain changes by simultaneously acquiring DTI and MRS in health control subjects. In this research, we have calculated the correlation coefficient between the DTI parameter of uncinate fasciculus, fornix and (1)H-MRS. Our result shows that the correlation coefficient of DTI parameter and (1)H-MRS of a left fornix is 0.65 at the maximum. Correlation between DTI measurement and (1)H-MRS suggests the relationships between the uncinate fasciculus, fornix and cognitive neuronal function. Our finding matches previous reports on the correlation between DTI parameters and (1)H-MRS.

White matter abnormalities in 22q11.2 deletion syndrome: Preliminary associations with the Nogo-66 receptor gene and symptoms of psychosis

BackgroundBrain aging is associated with cerebral small vessel disease (SVD). Recently, it was suggested that SVD is mainly driven by increases of extracellular free water (FW). The aim of the present study was to examine the association of FW, conventional and FW‐corrected diffusion tensor imaging (DTI) parameters (fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD)) with aging. The second aim was to determine if differences in FW and DTI parameters exist between individuals with first signs of pathology and healthy elderly controls regarding metrics that are not associated with age.MethodWe examined 87 healthy elderly (age: M = 66.34, SD = 9.82) and 87 individuals with first signs of cerebral pathology (age: M = 68.14, SD = 9.18) of the Austrian Stroke Prevention Family Study. Individuals with first signs of cerebral pathology were defined as having WMH score &gt;1, presence of lacunes and/or microbleeds. FW in global normal appearing white matter (NAWM) as well as conventional and FW‐corrected DTI parameters were used in correlation analyses to assess their association with age. ANOVA adjusted for multiple comparison was used to determine the differences in FW and FW‐corrected DTI metrics between individuals with initial signs of SVD and healthy controls.ResultFW in NAWM as well as non‐FW‐corrected DTI were significantly associated with age in the total sample and both stratified groups (range of |r|: 0.24‐0.49). No correlation between FW‐corrected DTI measures and age were found. Differences between individuals with and without first signs of pathology were only identified for FW in NAWM.ConclusionThe association between uncorrected conventional DTI parameters and age is mainly driven by the amount of FW, calling for caution when interpreting uncorrected DTI scores. In contrast, FW appears to be a sensitive marker at very early, clinically silent, signs of SVD.

Application of data harmonization and tract-based spatial statistics reveals white matter structural abnormalities in pediatric patients with focal cortical dysplasia