Mean Diffusivity Research Articles

Heterogeneity and convergence across seven neuroimaging modalities: a review of the autism spectrum disorder literature.

A growing body of literature classifies autism spectrum disorder (ASD) as a heterogeneous, complex neurodevelopmental disorder that often is identified prior to three years of age. We aim to provide a narrative review of key structural and functional properties that differentiate the neuroimaging profile of autistic youth from their typically developing (TD) peers across different neuroimaging modalities. Relevant studies were identified by searching for key terms in PubMed, with the most recent search conducted on September 1, 2023. Original research papers were included if they applied at least one of seven neuroimaging modalities (structural MRI, functional MRI, DTI, MRS, fNIRS, MEG, EEG) to compare autistic children or those with a family history of ASD to TD youth or those without ASD family history; included only participants <18 years; and were published from 2013 to 2023. In total, 172 papers were considered for qualitative synthesis. When comparing ASD to TD groups, structural MRI-based papers (n = 26) indicated larger subcortical gray matter volume in ASD groups. DTI-based papers (n = 14) reported higher mean and radial diffusivity in ASD participants. Functional MRI-based papers (n = 41) reported a substantial number of between-network functional connectivity findings in both directions. MRS-based papers (n = 19) demonstrated higher metabolite markers of excitatory neurotransmission and lower inhibitory markers in ASD groups. fNIRS-based papers (n = 20) reported lower oxygenated hemoglobin signals in ASD. Converging findings in MEG- (n = 20) and EEG-based (n = 32) papers indicated lower event-related potential and field amplitudes in ASD groups. Findings in the anterior cingulate cortex, insula, prefrontal cortex, amygdala, thalamus, cerebellum, corpus callosum, and default mode network appeared numerous times across modalities and provided opportunities for multimodal qualitative analysis. Comparing across neuroimaging modalities, we found significant differences between the ASD and TD neuroimaging profile in addition to substantial heterogeneity. Inconsistent results are frequently seen within imaging modalities, comparable study populations and research designs. Still, converging patterns across imaging modalities support various existing theories on ASD.

Characterization of dynamic changes in cardiac microstructure after reperfused ST-elevation myocardial infarction by biphasic diffusion tensor cardiovascular magnetic resonance.

Microstructural disturbances underlie dysfunctional contraction and adverse left ventricular (LV) remodelling after ST-elevation myocardial infarction (STEMI). Biphasic diffusion tensor cardiovascular magnetic resonance (DT-CMR) quantifies dynamic reorientation of sheetlets (E2A) from diastole to systole during myocardial thickening, and markers of tissue integrity [mean diffusivity (MD) and fractional anisotropy (FA)]. This study investigated whether microstructural alterations identified by biphasic DT-CMR: (i) enable contrast-free detection of acute myocardial infarction (MI); (ii) associate with severity of myocardial injury and contractile dysfunction; and (iii) predict adverse LV remodelling. Biphasic DT-CMR was acquired 4 days (n = 70) and 4 months (n = 66) after reperfused STEMI and in healthy volunteers (HVOLs) (n = 22). Adverse LV remodelling was defined as an increase in LV end-diastolic volume ≥ 20% at 4 months. MD and FA maps were compared with late gadolinium enhancement images. Widespread microstructural disturbances were detected post-STEMI. In the acute MI zone, diastolic E2A was raised and systolic E2A reduced, resulting in reduced E2A mobility (all P < .001 vs. adjacent and remote zones and HVOLs). Acute global E2A mobility was the only independent predictor of adverse LV remodelling (odds ratio .77; 95% confidence interval .63-.94; P = .010). MD and FA maps had excellent sensitivity and specificity (all > 90%) and interobserver agreement for detecting MI presence and location. Biphasic DT-CMR identifies microstructural alterations in both diastole and systole after STEMI, enabling detection of MI presence and location as well as predicting adverse LV remodelling. DT-CMR has potential to provide a single contrast-free modality for MI detection and prognostication of patients after acute STEMI.

DTI fiber-tracking parameters adjacent to gliomas: the role of tract irregularity value in operative planning, resection, and outcome.

The goal of glioma surgery is maximal tumor resection associated with minimal post-operative morbidity. Diffusion tensor imaging-tractography/fiber tracking (DTI-FT) is a valuable white-matter (WM) visualization tool for diagnosis and surgical planning. Still, it assumes a descriptive role since the main DTI metrics and parameters showed several limitations in clinical use. New applications and quantitative measurements were recently applied to describe WM architecture that surround the tumor area. The brain adjacent tumor area (BAT) is defined as the region adjacent to the gross tumor volume, which contains signal abnormalities on T2-weighted or FLAIR sequences. The DTI-FT analysis of the BAT can be adopted as predictive values and a guide for safe tumor resection. This is an observational prospective study on an extensive series of glioma patients who performed magnetic resonance imaging (MRI) with pre-operative DTI-FT analyzed on the BAT by two different software. We examined DTI parameters of Fractional anisotropy (FA mean, min-max), Mean diffusivity (MD), and the shape-metric "tract irregularity" (TI) grade, comparing it with the surgical series' clinical, radiological, and outcome data. The population consisted of 118 patients, with a mean age of 60.6 years. 82 patients suffering from high-grade gliomas (69.5%), and 36 from low-grade gliomas (30.5%). A significant inverse relationship exists between the FA mean value and grading (p = 0.001). The relationship appears directly proportional regarding MD values (p = 0.003) and TI values (p = 0.005). FA mean and MD values are susceptible to significant variations with tumor and edema volume (p = 0.05). TI showed an independent relationship with grading regardless of tumor radiological features and dimensions, with a direct relationship with grading, ki67% (p = 0,05), PFS (p < 0.001), and EOR (p < 0.01). FA, MD, and TI are useful predictive measures of the clinical behavior of glioma, and TI could be helpful for tumor grading identification and surgical planning.

Differentiation between high-grade gliomas and solitary brain metastases based on multidiffusion MRI model quantitative analysis.

Differentiating high-grade gliomas (HGGs) from solitary brain metastases (SBMs) using conventional magnetic resonance imaging (MRI) remains challenging due to their similar imaging features. This study aimed to evaluate the diagnostic performance of advanced diffusion models, such as neurite orientation dispersion and density imaging (NODDI) and mean apparent propagator magnetic resonance imaging (MAP-MRI), incomparison to traditional techniques like diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI), and diffusion kurtosis imaging (DKI) for distinguishing HGGs from SBMs. In total, 17 patients with HGGs and 26 patients with SBMs were prospectively recruited based on the established inclusion and exclusion criteria. Structural MRI sequences and diffusion spectrum imaging (DSI) were utilized to assess quantitative parameter models, including NODDI, MAP-MRI, DWI, DTI, and DKI. Quantitative parameters were measured for both the tumor parenchymal area and the peritumoral edema area. The quantitative parameters of the two patient groups were compared using either the independent Student's t-test or the Mann-Whitney U test. The effectiveness of each model was evaluated using receiver operating characteristic (ROC) curves and calculating the area under the curve (AUC). Finally, the DeLong test was employed to compare the diagnostic performance of each model through pairwise comparisons of ROC curves. Isotropic volume fraction (Viso) based on NODDI; mean squared displacement (MSD) and the return to plane probabilities (RTPP) based on MAP-MRI; radial diffusivity (RDk) and mean diffusivity (MDk) based on DKI; and axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) based on DTI of the peritumoral edema tumor were significantly different between HGGs and SBMs (p < 0.05). The optimal single discriminant parameters for each model are NODDI_Viso, MAP-MRI_MSD, DKI_MDk, and DTI_AD. Among these, the AUC of Viso (0.809) exceeds that of MSD (0.733), MDk (0.718), and AD (0.779). The combined model, which incorporates DTI_AD, DKI_RD, and NODDI_Viso, demonstrated superior diagnostic performance (0.897). Advanced diffusion MRI quantitative parameters derived from NODDI, such as Viso, have the potential to enhance the differentiation between HGGs and SBMs. The integrated utilization of these models is anticipated to enhance diagnostic accuracy and refine MRI protocols for brain tumor assessment.

Diffusion and functional MRI reveal microstructural and network connectivity impairment in adult-onset neuronal intranuclear inclusion disease.

Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder lacking reliable neuroimaging biomarkers. This study aimed to evaluate microstructural and functional connectivity alterations using diffusion kurtosis imaging (DKI) and resting-state fMRI (rs-fMRI), and to investigate their diagnostic potential as biomarkers. Twenty-three patients with NIID and 40 matched healthy controls (HCs) were recruited. Firstly, gray matter (GM) and white matter (WM) changes were assessed by voxel-based analysis (VBA) and tract-based spatial statistics (TBSS). Then we explored modifications in brain functional networks connectivity by independent component analysis. And the relationship between the altered DKI parameters and neuropsychological evaluation was analyzed. Finally, a receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of different gray matter and white matter parameters. Compared with the HCs, NIID patients showed reduced mean kurtosis (MK), radial kurtosis (RK), axial kurtosis (AK), and kurtosis fractional anisotropy (KFA) values in deep gray matter regions. Significantly decreased MK, RK, AK, KFA and fractional anisotropy (FA), and increased mean diffusivity (MD) values were observed in extensive white matter fiber tracts. Notable alterations in functional connectivity were also detected. Among all DKI parameters, the diagnostic efficiency of AK in GM and FA in WM regions was the highest. Adult-onset NIID patients exhibited altered microstructure and functional network connectivity. Our findings suggest that DKI parameters may serve as potential imaging biomarkers for diagnosing adult-onset NIID.

Application of preoperative advanced diffusion magnetic resonance imaging in evaluating the postoperative recurrence of lower grade gliomas

BackgroundRecurrence of lower grade glioma (LrGG) appeared to be unavoidable despite considerable research performed in last decades. Thus, we evaluated the postoperative recurrence within two years after the surgery in patients with LrGG by preoperative advanced diffusion magnetic resonance imaging (dMRI).Materials and methods48 patients with lower-grade gliomas (23 recurrence, 25 nonrecurrence) were recruited into this study. Different models of dMRI were reconstructed, including apparent fiber density (AFD), white matter tract integrity (WMTI), diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), neurite orientation dispersion and density imaging (NODDI), Bingham NODDI and standard model imaging (SMI). Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) was used to construct a multiparametric prediction model for the diagnosis of postoperative recurrence.ResultsThe parameters derived from each dMRI model, including AFD, axon water fraction (AWF), mean diffusivity (MD), mean kurtosis (MK), fractional anisotropy (FA), intracellular volume fraction (ICVF), extra-axonal perpendicular diffusivity (De⊥), extra-axonal parallel diffusivity (De∥) and free water fraction (fw), showed significant differences between nonrecurrence group and recurrence group. The extra-axonal perpendicular diffusivity (De⊥) had the highest area under curve (AUC = 0.885), which was significantly higher than others. The variable importance for the projection (VIP) value of De⊥ was also the highest. The AUC value of the multiparametric prediction model merging AFD, WMTI, DTI, DKI, NODDI, Bingham NODDI and SMI was up to 0.96.ConclusionPreoperative advanced dMRI showed great efficacy in evaluating postoperative recurrence of LrGG and De⊥ of SMI might be a valuable marker.

Evidence of small vessel disease in patients with transient global amnesia based on the peak width of skeletonized mean diffusivity.

The peak width of skeletonized mean diffusivity (PSMD) is a novel marker of small vessel disease. In this study, we aimed to investigate the presence of small vessel disease in patients with transient global amnesia (TGA) using the PSMD. We enrolled 75 patients newly diagnosed with TGA and included 65 age-and sex-matched healthy controls. Diffusion tensor imaging (DTI) was performed using a 3T magnetic resonance imaging scanner. We measured the PSMD based on DTI using the FSL program. This measure was compared between patients with TGA and healthy controls. Additionally, we conducted a correlation analysis to explore the relationship between PSMD and clinical factors. A significant difference in the PSMD between patients with TGA and healthy controls was observed. Patients with TGA exhibited higher a PSMD compared to healthy controls (2.297±0.232 vs. 2.188±0.216 ×10-4 mm2/s, p=0.005). Additionally, patients with TGA but without any vascular risk factors, such as diabetes, hypertension or dyslipidemia, also exhibited higher a PSMD compared to healthy controls (2.278±0.253 vs. 2.188±0.216 ×10-4 mm2/s, p=0.036). The PSMD positively correlated with age (r=0.248, p=0.032); however, it was not associated with duration of amnesia. This finding underscores the feasibility of using PSMD as a marker for detecting small vessel diseases in patients with neurological disorders. Furthermore, our study also implies the presence of small vessel disease may be present in patients with TGA. TGA=transient global amnesia; TIA= transient ischemic attack; PSMD= peak width of skeletonized mean diffusivity; DTI= diffusion tensor imaging.

Cluster-Based White Matter Signatures and the Risk of Dementia, Stroke, and Mortality in Community-Dwelling Adults.

Markers of white matter (WM) injury on brain MRI are important indicators of brain health. Different patterns of WM atrophy, WM hyperintensities (WMHs), and microstructural integrity could reflect distinct pathologies and disease risks, but large-scale imaging studies investigating WM signatures are lacking. This study aims to identify distinct WM signatures using brain MRI in community-dwelling adults, determine underlying risk factor profiles, and assess risks of dementia, stroke, and mortality associated with each signature. Between 2005 and 2016, we measured WMH volume, WM volume, fractional anisotropy (FA), and mean diffusivity (MD) using automated pipelines on structural and diffusion MRI in community-dwelling adults aged older than 45 years of the Rotterdam study. Continuous surveillance was conducted for dementia, stroke, and mortality. We applied hierarchical clustering to identify separate WM injury clusters and Cox proportional hazard models to determine their risk of dementia, stroke, and mortality. We included 5,279 participants (mean age 65.0 years, 56.0% women) and identified 4 distinct data-driven WM signatures: (1) above-average microstructural integrity and little WM atrophy and WMH; (2) above-average microstructural integrity and little WMH, but substantial WM atrophy; (3) poor microstructural integrity and substantial WMH, but little WM atrophy; and (4) poor microstructural integrity with substantial WMH and WM atrophy. Prevalence of cardiovascular risk factors, lacunes, and cerebral microbleeds was higher in clusters 3 and 4 than in clusters 1 and 2. During a median 10.7 years of follow-up, 291 participants developed dementia, 220 had a stroke, and 910 died. Compared with cluster 1, dementia risk was increased for all clusters, notably cluster 3 (hazard ratio [HR] 3.06, 95% CI 2.12-4.42), followed by cluster 4 (HR 2.31, 95% CI 1.58-3.37) and cluster 2 (HR 1.67, 95% CI 1.17-2.38). Compared with cluster 1, risk of stroke was higher only for clusters 3 (HR 1.55, 95% CI 1.02-2.37) and 4 (HR 1.94, 95% CI 1.30-2.89), whereas mortality risk was increased in all clusters (cluster 2: HR 1.27, 95% CI 1.06-1.53, cluster 3: HR 1.65, 95% CI 1.35-2.03, cluster 4: HR 1.76, 95% CI 1.44-2.15), compared with cluster 1. Models including clusters instead of an individual imaging marker showed a superior goodness of fit for dementia and mortality, but not for stroke. Clustering can derive WM signatures that are differentially associated with dementia, stroke, and mortality risk. Future research should incorporate spatial information of imaging markers.

White matter microstructure damage measured by automated fiber quantification correlates with pain symptoms in lung cancer patients.

To investigative the white matter (WM) alterations in lung cancer patients with cancer pain (CP+), and explore the correlations between damaged WM fiber tracts and clinical indicators. Twenty-six CP+, 26 lung cancer patients without CP (CP-), and 31 healthy controls (HC) were recruited. All participants underwent diffusion tensor imaging (DTI) and clinical assessments. Automated fiber quantification (AFQ) technique was performed to identify the 20 WM fiber bundles, and the fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were extracted. Intergroup comparisons of these diffusion metrics were conducted based on the entire fiber bundle level and 100 node levels along each tract. The associations between altered diffusion metrics and the numeric rating scale (NRS) scores, as well as the pain duration, were analyzed. At the entire level, the CP + group showed impaired WM structure in the right cingulum hippocampus (CH_R). At the pointwise level, the CP + group exhibited extensive nodal FA reduction or MD, RD, and AD elevation. In addition, the AD of the posterior portion of the right inferior longitudinal fasciculus (ILF_R, nodes 71-75) in the CP + group was positively correlated with the pain duration, and the FA of CH_R (nodes 22-38) was negatively correlated with NRS score. Extensive WM microstructural damage may be a pattern of brain abnormalities in lung cancer patients with CP, and in particular, specific nodal disruption along pain-related fiber tracts may be a sensitive imaging biomarker to characterize the severity and duration of CP.

Cardiac diffusion-weighted and tensor imaging: a Society for Cardiovascular Magnetic Resonance (SCMR) special interest group consensus statement

Thanks to recent developments in Cardiovascular magnetic resonance (CMR), cardiac diffusion-weighted magnetic resonance is fast emerging in a range of clinical applications. Cardiac diffusion-weighted imaging (cDWI) and diffusion tensor imaging (cDTI) now enable investigators and clinicians to assess and quantify the 3D microstructure of the heart. Free-contrast DWI is uniquely sensitized to the presence and displacement of water molecules within the myocardial tissue, including the intra-cellular, extra-cellular and intra-vascular spaces. CMR can determine changes in microstructure by quantifying: a) mean diffusivity (MD) –measuring the magnitude of diffusion; b) fractional anisotropy (FA) – specifying the directionality of diffusion; c) helix angle (HA) and transverse angle (TA) –indicating the orientation of the cardiomyocytes; d) E2A and E2A mobility – measuring the alignment and systolic-diastolic mobility of the sheetlets, respectively.This document provides recommendations for both clinical and research cDWI and cDTI, based on published evidence when available and expert consensus when not. It introduces the cardiac microstructure focusing on the cardiomyocytes and their role in cardiac physiology and pathophysiology. It highlights methods, observations and recommendations in terminology, acquisition schemes, post-processing pipelines, data analysis and interpretation of the different biomarkers. Despite the ongoing challenges discussed in the document and the need for ongoing technical improvements, it is clear that cDTI is indeed feasible, can be accurately and reproducibly performed and, most importantly, can provide unique insights into myocardial pathophysiology.

Measuring the impact of treatment on memory functions in pediatric posterior fossa tumor survivors using diffusion tensor imaging

Background and purposeThe aim of the present prospective exploratory study was to investigate the long-term impact of treatment on brain structure integrity and memory functions in pediatric posterior fossa tumor (PFT) survivors using diffusion tensor imaging (DTI), to determine whether the latter could provide useful biomarkers of memory impairment. Material and MethodsSixty participants were included in this study, divided into three groups: 22 irradiated PFT, 17 non-irradiated PFT, and 21 healthy controls. All underwent memory tests and multimodal MRI, including a DTI sequence. Mean diffusivity and fractional anisotropy values were extracted for bilateral brain structures involved in memory, in order to carry out between-group comparisons and calculate correlations with memory test scores and radiotherapy doses. Statistical tests were two-sided, and p values < 0.05 were considered statistically significant. ResultsDTI metrics were significantly higher for irradiated PFT survivors than in non-irradiated PFT survivors and controls (p < 0.05). Memory test scores were significantly lower for PFT survivors, particularly irradiated patients (p < 0.02), and were correlated with DTI metrics.(−0.27 < r < -0.62, p < 0.04). DTI metrics were correlated with either total or maximum dose for some structures. ConclusionPreliminary results of this study point to microstructural damage in memory-related brain areas in PFT survivors, particularly in irradiated patients, and identify DTI metrics as potential biomarkers of memory deficit.

White matter integrity upon progesterone antagonism in individuals with premenstrual dysphoric disorder: A randomized placebo-controlled diffusion tensor imaging study

BackgroundPremenstrual dysphoric disorder (PMDD) is a depressive disorder triggered by fluctuations of progesterone and estradiol during the luteal phase of the menstrual cycle. Selective progesterone receptor modulation (SPRM), while exerting an antagonistic effect on progesterone and maintaining estradiol on moderate levels, has shown beneficial effects on the mental symptoms of PMDD. Progesterone is also known for its neuroprotective effects, while synthetic progestins have been suggested to promote myelination. However, the impact of SPRM treatment on white matter microstructure is unexplored. MethodsDiffusion tensor imaging was employed to collect data on white matter integrity in patients with PMDD, before and after treatment with ulipristal acetate (an SPRM) or placebo, as part of a double-blind randomized controlled-trial. Tract based spatial statistics were performed to investigate SPRM treatment vs. placebo longitudinal effects on fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), on the whole white matter skeleton. ResultsVoxel-wise analyses indicated no change over time in any white matter microstructure metrics in individuals treated with SPRM versus placebo. Improvement in PMDD symptoms did not correlate with changes in white matter microstructure. In secondary, exploratory, cross-sectional comparisons during treatment, the SPRM group displayed lower FA and higher MD, RD, and AD in several tracts. ConclusionThe main findings suggest that SPRM treatment did not impact white matter microstructure compared with placebo. However, secondary exploratory analyses yielded between-group differences after treatment, which call for further investigation on the tracts potentially impacted by progesterone antagonism. Clinical trial registrationEUDRA-CT 2016–001719-19; “Selective progesterone receptor modulators for treatment of premenstrual dysphoric disorder. A randomized, double-blind, placebo-controlled study.”; https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001719-19/SE

Symptoms Do Not Predict White Matter Injury in the Watershed Regions in Children with Moyamoya

ObjectiveTo assess if white matter injuries differ in symptomatic versus asymptomatic moyamoya-affected hemispheres using diffusion magnetic resonance imaging (dMRI) since there is controversy on when or if to revascularize children with asymptomatic moyamoya. Study designWe conducted a cross-sectional study of children with moyamoya who underwent dMRI prior to revascularization surgery as well as controls without moyamoya. We measured the fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) of white matter tracts in the watershed regions. Moyamoya-affected hemispheres were included if they did not have any visible stroke or infarct. Moyamoya-affected hemispheres were labeled “symptomatic” if transient ischemic attack (TIA), seizure, or movement disorder were localizable to that hemisphere, or if the child had headaches. Moyamoya-affected hemispheres were “asymptomatic” if the child did not have symptoms attributable to that hemisphere. Asymptomatic and symptomatic hemispheres were compared with each other and control children using ANOVA. ResultsWe included 17 children with moyamoya with 26 moyamoya-affected hemispheres and 27 control children. Compared with controls MD, RD, and AD were higher in both symptomatic and asymptomatic moyamoya-affected hemispheres but were not significantly different from each other. ConclusionChildren with moyamoya without stroke or silent infarct have unrecognized white matter injury that is similar in both symptomatic and asymptomatic moyamoya-affected hemispheres, suggesting that symptoms do not accurately reflect moyamoya severity.

Effect of metacognitive interpersonal therapy on brain structural connectivity in borderline personality disorder: Results from the CLIMAMITHE randomized clinical trial

BackgroundRecently, we showed that Metacognitive Interpersonal Therapy (MIT) is effective in improving clinical symptoms in borderline personality disorder (BPD). Here, we investigated whether the effect of MIT on clinical features is associated to microstructural changes in brain circuits supporting core BPD symptoms. MethodsForty-seven BPD were randomized to MIT or structured clinical management, and underwent a clinical assessment and diffusion-weighted imaging before and after the intervention. Fractional anisotropy (FA), mean, radial, and axial diffusivities maps were computed using FSL toolbox. Microstructural changes were assessed (i) voxel-wise, with tract based spatial statistics (TBSS) and (ii) ROI-wise, in the triple network system (default mode, salience, and executive control networks). The effect of MIT on brain microstructure was assessed with paired tests using FSL PALM (voxel-wise), Linear Mixed-Effect Models or Generalized Linear Mixed Models (ROI-wise). Associations between microstructural and clinical changes were explored with linear regression (voxel-wise) and correlations (ROI-wise). ResultsThe voxel-wise analysis showed that MIT was associated with increased FA in the bilateral thalamic radiation and left associative tracts (p < .050, family-wise error rate corrected). At network system level, MIT increased FA and both interventions reduced AD in the executive control network (p = .05, uncorrected). LimitationsThe DTI metrics can't clarify the nature of axonal changes. ConclusionsOur results indicate that MIT modulates brain structural connectivity in circuits related to associative and executive control functions. These microstructural changes may denote activity-dependent plasticity, possibly representing a neurobiological mechanism underlying MIT effects. Trial registrationClinicalTrials.govNCT02370316 (https://clinicaltrials.gov/study/NCT02370316).

A Diffusion Model Account of Cognitive Variability in Healthy Aging and Mild Cognitive Impairment

ABSTRACT Within-person variation in cognitive performance is linked to pathological aging. Cognitive fluctuations have not been analyzed using cognitive process models, such as the diffusion model, to characterize which cognitive processes contribute to variability in cognition. We collected 21 daily assessments of attention and personality in younger adults, healthy older adults, and those with mild cognitive impairment. We employed mixed-effects location scale models to analyze group differences on mean diffusion parameters and daily variability. Discussion focuses on how these methods extend our understanding of how cognitive deficits might appear in aging and disease and the moderating influence of daily personality.

Small-Vessel Disease in Patients with ESKD Evidenced by Elevated Peak Width of Skeletonized Mean Diffusivity

Small-Vessel Disease in Patients with ESKD Evidenced by Elevated Peak Width of Skeletonized Mean Diffusivity

Unveiling the Exquisite Microstructural Details in Zebrafish Brain Non-Invasively Using Magnetic Resonance Imaging at 28.2 T

Zebrafish (Danio rerio) is an important animal model for a wide range of neurodegenerative diseases. However, obtaining the cellular resolution that is essential for studying the zebrafish brain remains challenging as it requires high spatial resolution and signal-to-noise ratios (SNR). In the current study, we present the first MRI results of the zebrafish brain at the state-of-the-art magnetic field strength of 28.2 T. The performance of MRI at 28.2 T was compared to 17.6 T. A 20% improvement in SNR was observed at 28.2 T as compared to 17.6 T. Excellent contrast, resolution, and SNR allowed the identification of several brain structures. The normative T1 and T2 relaxation values were established over different zebrafish brain structures at 28.2 T. To zoom into the white matter structures, we applied diffusion tensor imaging (DTI) and obtained axial, radial, and mean diffusivity, as well as fractional anisotropy, at a very high spatial resolution. Visualisation of white matter structures was achieved by short-track track-density imaging by applying the constrained spherical deconvolution method (stTDI CSD). For the first time, an algorithm for stTDI with multi-shell multi-tissue (msmt) CSD was tested on zebrafish brain data. A significant reduction in false-positive tracks from grey matter signals was observed compared to stTDI with single-shell single-tissue (ssst) CSD. This allowed the non-invasive identification of white matter structures at high resolution and contrast. Our results show that ultra-high field DTI and tractography provide reproducible and quantitative maps of fibre organisation from tiny zebrafish brains, which can be implemented in the future for a mechanistic understanding of disease-related microstructural changes in zebrafish models of various brain diseases.

Cognitive impairment mediates the white matter injury load and gait disorders in subcortical ischemic vascular disease.

Gait disorders are common in patients with subcortical ischemic vascular disease (SIVD). We aim to explore the impact of white matter (WM) damage on gait disorders in SIVD. 21 SIVD patients and 20 normal controls (NC) were included in the study. Montreal Cognitive Assessment (MoCA) was used to evaluate general cognition, while Speed-Accuracy Trade-Off (SAT) was used to assess executive function. Gait velocity, cadence, and stride length were measured. Diffusion Tensor Imaging (DTI) data were analyzed using Tract-Based Spatial Statistics (TBSS) and Peak Width of Skeletonized Mean Diffusivity (PSMD). The relationships among WM damage, gait disorders, and cognitive function were examined through mediation analysis. SIVD scored lower than NC in MoCA and SAT tests (P < 0.001). Gait velocity and stride length were decreased in SIVD. SIVD had lower PSMD (P < 0.001). PSMD correlated with gait parameters, which were totally mediated by MoCA and partially mediated by SAT. The fractional anisotropy (FA) and mean diffusivity (MD) of the genu of the corpus callosum (GCC) and body of CC (BCC) were correlated with gait parameters. The FA of the bilateral anterior corona radiata (ACR) was positively correlated with gait parameters, while the MD of the bilateral superior corona radiata (SCR), bilateral superior longitudinal fasciculus (SLF), and left external capsule (EC) were negatively correlated with them (P < 0.05). Gait impairments in SIVD were associated with cognitive deficits. Cognitive impairment mediated the WM damage and gait disorders. The microstructural alterations of CC, SLF, EC, and CR may be related to changes in gait.

Baseline and Longitudinal MRI Markers Associated With 16-Year Mortality in Patients With Cerebral Small Vessel Disease.

Information on whether small vessel disease (SVD) reduces life expectancy is limited. Moreover, the excess mortality risk attributed specifically to SVD compared with controls from the general population has not been evaluated. This study aimed to investigate the baseline and progression of MRI markers of SVD associated with mortality in a 16-year follow-up cohort study and to determine the excess long-term mortality risk of patients with SVD. Participants with SVD from the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort (RUN DMC) study (with MRI assessments in 2006, 2011, 2015, and 2020) were followed until their death or December 1, 2021. Adjusted Cox regression analyses and linear mixed-effect regression models were used to investigate the association between MRI markers of SVD and mortality. The excess mortality risk of SVD was calculated by comparing mortality data of the RUN DMC study with the general population matched by sex, age, and calendar year. 200 of 503 (39.9%) participants died during a follow-up period of 15.9 years. Cause of death was available for 182 (91%) participants. Baseline white matter hyperintensity volume (HR 1.3 per 1-SD increase [95% CI 1.1-1.5], p = 0.010), presence of lacunes (1.5 [95% CI 1.1-2.0], p = 0.008), mean diffusivity (HR 1.1 per 1-SD increase [95% CI 1.1-1.2], p = 0.001), and total brain volume (HR 1.5 per 1-SD decrease [95% CI 1.3-1.9], p < 0.001) were associated with all-cause mortality after adjusting for age, sex, and vascular risk factors. Total brain volume decrease over time was associated with all-cause mortality after adjusting for age, sex, and vascular risk factors (HR 1.3 per 1-SD decrease [95% CI 1.1-1.7], p = 0.035), and gray matter volume decrease remained significant after additionally adjusting for its baseline volume (1.3 per 1-SD decrease [1.1-1.6], p = 0.019). Participants with a Fazekas score of 3, presence of lacunes, or lower microstructural integrity had an excess long-term mortality risk (21.8, 15.7, 10.1 per 1,000 person-years, respectively) compared with the general population. Excess long-term mortality risk only exists in patients with severe SVD (Fazekas score of 3, presence of lacunes, or lower microstructural integrity). This could help in assisting clinicians to predict the clinical outcomes of patients with SVD by severity.

In vivo cardiac diffusion tensor imaging on an MR system featuring ultrahigh performance gradients with 200 mT/m maximum gradient strength.

Our aim is to assess the potential of an MR system with ultrahigh performance gradients (200 mT/m maximum gradient strength) to address two interrelated challenges in cardiac DTI: low SNR and sensitivity to bulk motion. Imaging was performed in 20 healthy volunteers, two patients, and one swine post-myocardial infarction. The impact of maximum gradient strength was assessed with spin echo cardiac DTI featuring second-order motion compensation and varying maximum system gradient strengths (40, 80, 200 mT/m). Motion compensation requirements at 200 mT/m were assessed with sequences featuring zeroth-, first-, and second-order motion compensation. SNR, mean diffusivity, fractional anisotropy, helix angle transmurality, and secondary eigenvector angle in the left ventricle were compared. Increasing maximum system gradient strength from 40 and 80 mT/m to 200 mT/m increased SNR of b = 500 s/mm2 images by 150% and 40% due to reductions in TE. Observed improvements in DTI metrics included reduction in variance in mean diffusivity and helix angle transmurality across healthy volunteers, improved visualization of myocardial borders and delineation of suspected scar. Whereas second-order motion compensation acquisitions were robust to motion-induced signal dropout, zeroth- and first-order motion compensation acquisitions suffered from severe signal loss and localized signal voids, respectively. Ultrahigh performance gradients (200 mT/m) enable high SNR DWIs of the heart and resultant improvements in diffusion tensor metrics. Despite reduced diffusion-encoding duration, second-order motion compensation is required to overcome sensitivity to cardiac motion.