Aug 2026· NMR in Biomedicine· Vol 39· 0 citations· 37 references
Medicine
TL;DR
The results help to clarify the biophysical interpretation of dMRI microstructural parameters by determining how strongly they are influenced by myelin content and reinforces the use of DKI and FBWM.
Abstract
ABSTRACT Diffusion MRI (dMRI) methods including diffusion tensor imaging (DTI) and more advanced models including diffusional kurtosis imaging (DKI) and fiber ball white matter modeling (FBWM) probe various aspects of white matter (WM) microstructure. However, the associations between these variables and myelin content remain largely unknown. We examined this issue using ViSTa myelin water imaging (MWI), which estimates the proportion of tissue water associated with myelin using the apparent myelin water fraction (aMWF) and examined correlations with dMRI variables across heterogeneous deep WM regions. Four healthy adults underwent anatomical MRI, multishell dMRI, and ViSTa‐MWI. We computed DTI, DKI, FBWM, and aMWF metrics within a binarized deep WM atlas and callosal subregions (the genu and splenium) and evaluated associations between dMRI and aMWF using voxel‐wise block‐permutation Spearman correlations. Across WM regions, axonal water fraction (ρ = 0.68), mean kurtosis (ρ = 0.63), and radial kurtosis (ρ = 0.62) had stronger correlations with aMWF than conventional DTI metrics. Correlations for dMRI variables were consistently higher within the splenium (mean |ρ| = 0.68) compared to the genu (mean |ρ| = 0.56), reflecting stronger associations with aMWF in an earlier‐myelinating region with denser axonal packing and reduced fiber dispersion. DTI, DKI, and FBWM variables all correspond with aMWF. Select DKI and FBWM variables demonstrated the strongest associations with aMWF and were more sensitive than conventional DTI metrics. Correlations for all metric families were stronger within the splenium compared to the genu, presumably reflecting the high density of myelination in this region. These results help to clarify the biophysical interpretation of dMRI microstructural parameters by determining how strongly they are influenced by myelin content. This preliminary examination helps to clarify the roles of dMRI variables for future studies of WM integrity and reinforces the use of DKI and FBWM.
Diffusion kurtosis imaging (DKI) is typically applied to white matter, but it may provide insight into age‐related microstructural changes in gray matter tissue like the hippocampus. The goal was to assess neurodevelopment and aging changes in hippocampal subfields using 1 mm isotropic DKI across the healthy lifespan (5–90 years). Multi‐shell, 1 mm3, diffusion imaging focused on the hippocampus, was acquired at 3 T in 363 healthy participants (5–90 years, 206 females). Automatic hippocampal subfield segmentation and unfolded maps were obtained using HippUnfold. Nonlinear lifespan trajectories, sex differences, and age‐corrected residual correlations with cognitive scores and other demographics were assessed for volume, mean diffusivity (MD), fractional anisotropy (FA), mean kurtosis (MK), and kurtosis FA (KFA). Whole hippocampus yielded distinct age trajectories for the volume, diffusion tensor, and diffusion kurtosis parameters: volume—quadratic fit (maximum ~35–42 years); MD—negative Gamma variate (minimum ~35 years); FA—positive Gamma variate fit (maximum ~25 years); MK—exponential fit (steep increase during development that plateaus after ~25 years); and KFA—negative linear across the lifespan. There were sex differences in age trajectories for volume and MK that were not evident with DTI metrics. Males exhibited larger volume and larger MK than females. The subfields showed similar age trajectories as whole hippocampus albeit with regional variations in the values. The subiculum showed dramatically higher MK after age 20, with males exhibiting higher values than females. MK residuals in whole hippocampus correlated positively with body mass index residuals in three age groups (young, middle age, and older). In conclusion, high‐resolution 1 mm isotropic DKI of hippocampus revealed linear and nonlinear patterns with development and aging over a wide age range of 5–90 years that differ from DTI. These results suggest that DKI can provide novel insight into age‐related microstructural changes at the sub‐hippocampal level.
P. Stack-Sanchez, Donald W. Gross, Ali R. Khan et al.· NMR in Biomedicine· 0 citations
Objective To investigate white matter microstructural alterations in amyotrophic lateral sclerosis (ALS) using free-water-corrected diffusion tensor imaging (FW-DTI), compare its findings with those of conventional DTI, and examine the clinical correlations and preliminary diagnostic value of these metrics. Methods 44 ALS patients and 42 healthy controls underwent multi-b-value diffusion MRI. Conventional DTI metrics (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity [AxD], radial diffusivity [RD]), free-water-corrected metrics (FW-FA, FW-MD, FW-AxD, FW-RD), and the free-water fraction (FWF) were calculated. Tract-based spatial statistics (TBSS) was used for voxelwise group comparisons. Correlations between clinical parameters, including disease progression rate (ΔFS) and the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score, and DTI metrics were examined. A diagnostic nomogram was constructed using logistic regression based on imaging markers that showed significant differences between groups. Results Conventional DTI identified white matter abnormalities in ALS-related regions, including corticospinal tract-related regions, the corpus callosum, and the cingulate gyrus. FW-DTI showed additional and partially distinct alterations, including changes in the fornix, bilateral superior corona radiata, anterior and posterior corona radiata, and the posterior limb of the internal capsule. The free-water fraction did not differ between groups. Correlation analysis revealed that ΔFS was negatively associated with FA in the left posterior limb of the internal capsule (r = −0.432), and the ALSFRS-R score was positively associated with FW-FA in the right anterior corona radiata (r = 0.389). A diagnostic nomogram combining FA in the right cerebral peduncle and FW-FA in the right anterior corona radiata showed preliminary discriminative performance (area under the curve [AUC] = 0.860). Conclusion FW-DTI may provide complementary model-derived information for characterizing ALS-related white matter alterations beyond conventional DTI. Specific regional metrics were associated with ΔFS and the ALSFRS-R score, and the preliminary diagnostic nomogram yielded an AUC of 0.860.
Zelin Liu, Haiqing Yang, J. Cui et al.· Frontiers in Neuroscience· 0 citations
ABSTRACT
AIM: To determine hemispheric asymmetries in major white matter tracts using diffusion tensor imaging (DTI) metrics and morphometric measurements, as comprehensive multitract analyses remain limited. MATERIAL and METHODS: Diffusion MRI data from 102 healthy adults enrolled in the Human Connectome Project (HCP) were analyzed using DSI Studio to reconstruct 17 major white- matter tracts bilaterally. For each tract, diffusion metrics (fractional anisotropy [FA], mean diffusivity [MD], radial diffusivity [RD], axial diffusivity [AD], quantitative anisotropy [QA], isotropic value [ISO], restricted diffusion imaging [RDI], and normalized RDI [nrdı]) and morphometric parameters (fiber count, mean length, trunk volume, branch volume, total volume, and termination region areas) were quantified. Paired t-tests compared left-right hemispheric differences. Multiple comparison corrections were performed with the Benjamini-Krieger-Yekutieli procedure, and effect sizes were reported as Cohen's d. RESULTS: Significant hemispheric asymmetries were observed in most tracts. FA was significantly higher in the left hemisphere (p<0.001) for the arcuate fasciculus (AF), inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), and uncinate fasciculus (UF). Mean diffusivity (MD) demonstrated left dominance in the UF and SLF2-3 (p=0.009). QA was predominantly left- lateralized across multiple tracts, including AF, IFOF, ILF, and frontal aslant tract (FAT) (p<0.01, Cohen's d: 0.42 to 1.17), except for the vertical occipital fasciculus (VOF), where rightward dominance was noted (Cohen's d: -0.55). Tract-trunk-branch volumes were predominantly left-lateralized in frontal lobe pathways such as AF, SLF1, SLF2, FAT, and UF (p<0.01). Rightward dominance was observed in SLF3, parietal aslant tract (PAT), IFOF, ILF, and middle longitudinal fasciculus (MLF) (p<0.05). Similar asymmetries were observed in termination region areas, fiber counts, and fiber lengths (p<0.001). CONCLUSION: Widespread hemispheric asymmetries were observed across multiple pathways. Such asymmetry may reflect distinct hemispheric functional specialization and the neurological basis of lateralized functions.
Taghi Khaniyev, Efecan Çekiç, Muhammed Yakup Altug et al.· Turkish Neurosurgery· 0 citations
Background Essential hypertension (HTN) is an established risk factor for cerebral small vessel disease and cognitive decline. Although conventional diffusion tensor imaging (DTI) has identified white matter (WM) abnormalities in HTN, these metrics are often confounded by extracellular free-water (FW) contamination and cannot distinguish tissue microstructural abnormalities from extracellular fluid shifts. This study applied a free-water elimination (FWE) model in combination with the diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index to investigate tissue-specific microstructural alterations, extracellular fluid shifts, and glymphatic function in both WM and cortical gray matter (GM). Methods Single-shell diffusion magnetic resonance imaging (MRI) data were acquired from 30 patients with HTN and 30 age- and sex-matched healthy controls (HCs). Tissue-specific DTI metrics, including free-water-corrected fractional anisotropy (FAt) and free-water-corrected mean diffusivity (MDt), as well as FW fractional volume maps, were derived. The DTI-ALPS index was calculated to assess glymphatic clearance. Tract-based spatial statistics (TBSS) and gray matter-based spatial statistics (GBSS) were used to evaluate between-group differences. Results The HTN group showed no statistically significant difference in the DTI-ALPS index compared with the HC group (p > 0.05). However, alongside conventional diffusion abnormalities, patients with HTN exhibited widespread reductions in FAt and increases in MDt across both WM and GM skeletons. In addition, HTN patients showed a localized reduction in FW fractional volume, predominantly in the corpus callosum. Systolic blood pressure (SBP) was negatively correlated with conventional FA in white matter, and with both FA and FAt in cortical GM across extensive regions. No significant correlations were found with Mini-Mental State Examination (MMSE) scores. Conclusions These cross-sectional findings suggest that, in HTN, tissue-specific diffusion abnormalities and localized fluid shifts are detectable even in the absence of statistically significant group differences in the DTI-ALPS index. This divergence indicates that FWE metrics may serve as sensitive neuroimaging indicators for evaluating hypertensive brain involvement.
Taipeng Zeng, Xiaoyang Wang, Wen-Hui Xu et al.· Frontiers in Medicine· 0 citations
PURPOSE
To investigate relationships among relaxation, susceptibility, and diffusion parameters in healthy white matter (WM) and to characterize WM MRI feature organization using an integrative multimodal quantitative MRI framework.
METHODS
Twenty-two healthy volunteers underwent 3T MRI. Quantitative parameter mapping provided R1, R2*, R1·R2*, and quantitative susceptibility mapping, while diffusion kurtosis imaging provided fractional anisotropy (FA), mean kurtosis, axial kurtosis (AK), and radial kurtosis. All maps were spatially normalized to Montreal Neurological Institute (MNI) space, and mean values were extracted from WM tracts defined by the Johns Hopkins University (JHU) White Matter Atlas. Pearson correlation analysis with false discovery rate correction, principal component analysis (PCA), hierarchical clustering, and bootstrap stability analysis were performed.
RESULTS
The first 2 principal components explained 77.7% of the total variance. The first principal component (PC1) was mainly associated with relaxation-related parameters and diffusion kurtosis metrics, whereas the second principal component (PC2) was characterized by opposing contributions from AK and FA. Quantitative susceptibility mapping showed weak correlations with other parameters (r = -0.37 to -0.08), suggesting relatively independent susceptibility-related information. The PCA structure was preserved after excluding R1·R2*, and bootstrap analysis supported loading stability, with mean loading correlations of 0.94 for PC1 and 0.90 for PC2. WM tracts formed 4 major cluster-like groups and showed tract-specific multimodal fingerprints.
CONCLUSION
Multimodal quantitative MRI provides a concise tract-level MRI feature representation of WM by integrating relaxation, susceptibility, and diffusion information. This exploratory framework may support future studies investigating subtle WM alterations, although validation in pathological cohorts is required.
Emi Sato, Yuki Kanazawa, Masafumi Harada et al.· Magnetic Resonance in Medica...· 0 citations
BACKGROUND: White matter hyperintensities (WMH) are widely used to assess cerebral small vessel disease but reflect late-stage injury. Diffusion magnetic resonance imaging (MRI) biomarkers have been proposed to capture earlier small vessel disease-related microstructural damage but their temporal progression relative to WMH and risk factors associated with progression remain unexplored. METHODS: We identified 2077 participants from the population-based cohort study of the Mayo Clinic Study of Aging in Olmsted County, Minnesota (aged 50–101 years) collected between 05/2005 and 09/2024 with longitudinal neuroimaging. Using multioutput nonlinear mixed-effects models in those with at least 2 fluid-attenuated inversion recovery-MRI and diffusion MRI scans, we characterized the temporal progression of WMH and 4 diffusion MRI biomarkers: fractional anisotropy of the genu of the corpus callosum, peak width of skeletonized mean diffusivity, free water, and Arteriolosclerosis-score, which were automatically estimated. Models incorporated participant-specific time shifts, correlations between biomarkers, and effects of risk factors (sex, education, APOE ε4 status, cardiometabolic conditions). RESULTS: The study population had a mean age of 78 years, 47% were women, 28% were APOE ε4 allele carriers, and 80% were cognitively unimpaired, with an average follow-up of 5.2 years (SD, 4.3 years) for fluid-attenuated inversion recovery-MRI and 4.3 years (SD, 3.9 years) for diffusion MRI. Arteriolosclerosis-score, fractional anisotropy of the genu of the corpus callosum, free water, and peak width of skeletonized mean diffusivity became abnormal in 50% of the study population 16, 12, 10, and 7 years before WMH become abnormal (half-width of CI <1 year), respectively. Global markers (Arteriolosclerosis-score, free water, peak width of skeletonized mean diffusivity, and WMH) were correlated, indicating shared substrates of widespread white matter injury. Fractional anisotropy of the genu of the corpus callosum, a vascular risk microstructural injury biomarker, was weakly coupled with WMH and had an earlier but more linear worsening across adulthood. Cardiometabolic conditions predicted earlier worsening of all biomarkers. Female participants showed earlier WMH, fractional anisotropy of the genu of the corpus callosum, and Arteriolosclerosis-score abnormalities, whereas male participants exhibited earlier peak width of skeletonized mean diffusivity and free water abnormalities. CONCLUSIONS: Diffusion MRI biomarkers were abnormal at least a decade before WMH become abnormal in the population, revealing a prolonged phase of early small vessel disease and highlighting their potential for small vessel disease prevention.
P. Vemuri, Mingzhao Hu, Emily S. Lundt et al.· Stroke· 0 citations
