Isotropic Fractionator Research Articles

Effects of Diastolic Blood Pressure on Brain Structures and Cognitive Functions in Middle and Old Ages: Longitudinal Analyses.

Hypertension is a pervasive public health concern due to strong associations with cardiovascular diseases and stroke. Alternatively, the associations between hypertension and the risk of Alzheimer’s disease are complex and recent large sample studies reported positive associations. In this paper, we examine the associations between diastolic blood pressure (BP) and subsequent changes in brain structure and cognitive function over several years by multiple regression analyses (with adjustment for a wide range of potential confounding variables) among a large cohort from the UK Biobank. Higher baseline diastolic BP was associated with a slightly smaller relative increase (relative improvements) in reaction time and a slightly greater reduction in depression scores. Higher baseline diastolic BP was also associated with a greater total gray matter volume (GMV) retention, while aging alone was associated with GMV reduction. White matter microstructural analyses revealed that a greater diastolic BP was associated with reduced longitudinal mean and regional fractional anisotropy, greater increases in mean and regional mean diffusivity, radial diffusivity, and axial diffusivity, a greater decline in mean intracellular volume fraction, and greater increases in mean and regional isotropic volume fraction. These white matter microstructural changes were consistent with those seen in the aging process. Additional analyses revealed a greater cheese intake level at baseline, which is associated with a subsequent decline in diastolic BP and a relative subsequent increase in depressive tendency together with a relative increase in fluid intelligence and visuospatial memory performance. These results are congruent with the view that a higher BP in the aging brain has a complex role.

Application of Neurite Orientation Dispersion and Density Imaging to Evaluate and Predict the Surgical Outcome for Degenerative Cervical Myelopathy.

ObjectivesAlthough the neurite orientation dispersion and density imaging (NODDI) has been shown useful to evaluate the spinal cord dysfunction, there are few prospective studies on analyzing the operation recovery of degenerative cervical myelopathy (DCM) disease using NODDI. This study aims to investigate the preoperative evaluation and predictive ability of NODDI in DCM patients who received posterior cervical laminoplasty.MethodsThis prospective study included 55 patients with DCM from January to December 2017. NODDI metrics, including intracellular volume fraction (Vic), isotropic volume fraction (Viso), and orientation dispersion index (ODI) were measured at the maximally compressed (MC) level and the non‐compressed C2 level in each patient at the preoperative and the 3‐ and 6‐month postoperative follow‐up stages. Neurological function was assessed using the modified Japanese Orthopaedic Association (mJOA) scoring system at each stage. Spearman's correlation and Kendall's tau‐b correlation were used to analyze the relationship between NODDI metrics and mJOA scores. Wilcoxon signed rank test was used to examine the changes in the NODDI and mJOA scores between the preoperative and 6‐month follow‐up stages. ROC analysis was used to further evaluate the predictive capability.ResultsPreoperative Vic at the level of C2 has a significant correlation with the preoperative mJOA score (r = 0.278, p = 0.048). Vic and Viso at the MC level were significantly different between the preoperative period and 6‐month follow‐up. Viso at the MC level was correlated with the mJOA score at 6‐month follow‐up (r = −0.302, p = 0.044). Vic and ODI at the C2 level predicted the surgical prognosis, with areas under the receiver‐operating characteristic curve of 0.663 (p = 0.042) and 0.716 (p = 0.014).ConclusionsThe preoperative NODDI metrics at the C2 level are capable of evaluating the severity of spinal cord dysfunction and predict the surgical outcome.

Effects of Body Mass Index on Brain Structures in the Elderly: Longitudinal Analyses.

The relationship between obesity and neurocognitive consequences is complex. Here we investigated associations between body mass index (BMI) and subsequent changes in brain structures, cognitive changes, and the onset of dementia after adjustment of a wide range of potential confounding variables using a large prospective cohort data of UK Biobank. After correcting for confounding factors, higher BMI was associated with greater retention in visuospatial memory performance (decline in error numbers) [beta = -0.019 (CI:-0.027~-0.016), N = 39191], increase in depression tendency scores [beta = 0.036(0.027~0.045)] as well as decreased risk of incident dementia [increasing BMI by 1 is associated with HR of 0.981 (CI:0.969~0.992), N = 398782], but not changes in fluid intelligence or reaction time. Whole brain multiple regression analyses (volumetric analyses: N = 1253, other analyses: N = 1241) revealed positive associations between BMI and subsequent changes in regional gray matter volume (rGMV) in multiple areas, regional white matter volume changes in widespread white matter (WM) tracts, fractional anisotropy changes in several tracts, and intracellular volume fraction (ICVF) and orientation dispersion (OD) in widespread areas, and isotropic volume fraction (ISOVF) in a few areas, and negative associations between BMI and subsequent changes in rGMV in the bilateral medial temporal lobe areas, mean, axial and radial diffusivity, and ISOVF in widespread areas. These results are mostly consistent with the view that less BMI precedes greater neurocognitive aging or atrophy, with a few exceptions including OD findings and the rGMV finding of the medial temporal lobes as most of significant longitudinal associations of higher BMI were opposite to those seen in higher age and dementia. Future epidemiological studies should consider separating effects of higher BMI itself from potential confounders.

Diagnostic performance of gliomas grading and IDH status decoding A comparison between 3D amide proton transfer APT and four diffusion-weighted MRI models.

The focus of neuro-oncology research has changed from histopathologic grading to molecular characteristics, and medical imaging routinely follows this change. To compare the diagnostic performance of amide proton transfer (APT) and four diffusion models in gliomas grading and isocitrate dehydrogenase (IDH) genotype. Prospective. A total of 62 participants (37 males, 25 females; mean age, 52 ± 13 years) whose IDH genotypes were mutant in 6 of 14 grade II gliomas, 8 of 20 of grade III gliomas, and 4 of 28 grade IV gliomas. APT imaging using sampling perfection with application optimized contrasts by using different flip angle evolutions (SPACE) and DWI with q-space Cartesian grid sampling were acquired at 3T. The ability of diffusion kurtosis imaging, diffusion kurtosis imaging, neurite orientation dispersion and density imaging (NODDI), mean apparent propagator (MAP), and APT imaging for glioma grade and IDH status were assessed, with histopathological grade and genetic testing used as a reference standard. Regions of interest (ROIs) were drawn by two neuroradiologists after consensus. T-test and Mann-Whitney U test; one-way analysis of variance (ANOVA); receiver operating curve (ROC) and area under the curve (AUC); DeLong test. P value < 0.05 was considered statistically significant. Compared with IDH-mutant gliomas, IDH-wildtype gliomas showed a significantly higher mean, 5th-percentile (APT5 ), and 95th-percentile from APTw, the 95th-percentile value of axial, mean, and radial diffusivity from DKI, and 95th-percentile value of isotropic volume fraction from NODDI, and no significantly different parameters from DTI and MAP (P = 0.075-0.998). The combined APT model showed a significantly wider area under the curve (AUC 0.870) for IDH status, when compared with DKI and NODDI. APT5 was significantly different between two of the three groups (glioma II vs. glioma III vs. glioma IV: 1.35 ± 0.75 vs. 2.09 ± 0.93 vs. 2.71 ± 0.81). APT has higher diagnostic accuracy than DTI, DKI, MAP, and NODDI in glioma IDH genotype. APT5 can effectively identify both tumor grading and IDH genotyping, making it a promising biomarker for glioma classification. 1 TECHNICAL EFFICACY: Stage 2.

Altered regional brain white matter in dry eye patients: a brain imaging study.

This study aimed to investigate the regional changes of brain white matter (WM) in DE patients using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI). A total of 25 dry eye patients (PAT) and 25 healthy controls (HC) were recruited. All subjects underwent DTI and NODDI, fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), isotropic volume fraction (FISO), intra-cellular volume fraction (FICVF), and orientation dispersion index (ODI) were obtained respectively. Then complete Hospital Anxiety and Depression Scale (HADS), anxiety score (AS) or depression scores (DS) were obtained. Receiver operating characteristic (ROC) curve analysis was used to evaluate the reliability of DTI and NODDI in distinguishing the two groups. DTI revealed that PAT had lower FA in both the left superior longitudinal fasciculus (LSLF) and the corpus callosum (CC), and higher MD in the LSLF, the right posterior limb of the internal capsule and the right posterior thalamic radiation. PAT had significant AD changes in regions including the genu of the CC, the right posterior limb of internal capsule, and the right splenium of the CC. From NODDI, PAT showed increased ODI in the LSLF and increased FISO in the right splenium of the CC. FICVF showed a significant decrease in the LSLF while increased in the left anterior corona radiata and the CC. Furthermore, the average values of MD and FICVF were significantly correlated with DS and AS. Hence the results of this study suggest that there are regional changes in WM in DE patients which may contribute to further understanding of the pathological mechanism of DE.

Multimodal magnetic resonance imaging quantification of gray matter alterations in relapsing-remitting multiple sclerosis and neuromyelitis optica spectrum disorder.

Herein, we combined neurite orientation dispersion and density imaging (NODDI) and synthetic magnetic resonance imaging (SyMRI) to evaluate the spatial distribution and extent of gray matter (GM) microstructural alterations in patients with relapsing-remitting multiple sclerosis (RRMS) and neuromyelitis optica spectrum disorder (NMOSD). The NODDI (neurite density index [NDI], orientation dispersion index [ODI], and isotropic volume fraction [ISOVF]) and SyMRI (myelin volume fraction [MVF]) measures were compared between age- and sex-matched groups of 30 patients with RRMS (6 males and 24 females; mean age, 51.43±8.02years), 18 patients with anti-aquaporin-4 antibody-positive NMOSD (2 males and 16 females; mean age, 52.67±16.07years), and 19 healthy controls (6 males and 13 females; mean age, 51.47±9.25years) using GM-based spatial statistical analysis. Patients with RRMS showed reduced NDI and MVF and increased ODI and ISOVF, predominantly in the limbic and paralimbic regions, when compared with healthy controls, while only increases in ODI and ISOVF were observed when compared with NMOSD. Compared to NDI and MVF, the changes in ODI and ISOVF were observed more widely, including in the cerebellar cortex. These abnormalities were associated with disease progression and disability. In contrast, patients with NMOSD only showed reduced NDI mainly in the cerebellar, limbic, and paralimbic cortices when compared with healthy controls and patients with RRMS. Taken together, our study supports the notion that GM pathologies in RRMS are distinct from those of NMOSD. However, owing to the limitations of the study, the results should be cautiously interpreted.

Role of NODDI in the MRI Characterization of Hippocampal Abnormalities in Temporal Lobe Epilepsy: Clinico-histopathologic Correlations.

The identification of possible hippocampal alterations is a crucial point for the diagnosis and therapy of patients with unilateral temporal lobe epilepsy (TLE). This study aims to investigate the role of neurite orientation dispersion and density imaging (NODDI) compared to diffusion tensor imaging (DTI) in the comprehension of hippocampal microstructure in TLE. DTI and NODDI metrics were calculated in the hippocampi of adult patients with TLE, with and without histology-confirmed hippocampal sclerosis (HS), and in age/sex-matched healthy controls (HC). Diffusion metrics and hippocampal volumes of the pathologic side were compared within participants and between participants among the HS, non-HS, and HC groups. Diffusion metrics were also correlated with hippocampal volume and patients' clinical features. After surgery, hippocampal specimens were processed for neuropathology examinations. Fifteen patients with TLE (9 with and 6 without HS) and 11 HC were included. Hippocampal analyses resulted in a significant increase in fractional anisotropy (FA) and mean diffusivity (MD; mm2/s × 10-3) and decrease in orientation dispersion index (ODI) comparing the pathologic side of patients with HS and their relative nonpathologic side (0.203 vs 0.183, 0.825 vs 0.724, 0.366 vs 0.443, respectively), the pathologic side of patients without HS (0.203 vs 0.169, 0.825 vs 0.745, 0.366 vs 0.453, respectively), and HC (0.203 vs 0.172, 0.825 vs 0.729, 0.366 vs 0.447, respectively). Moreover, neurite density (ND) was significantly decreased comparing both hippocampi of patients with HS (0.416 vs 0.460). A significant increase in free-water isotropic volume fraction (fiso) was found in the comparison of pathologic hippocampi of patients with HS and nonpathologic hippocampi of patients with HS (0.323 vs 0.258) and HC (0.323 vs 0.226). Hippocampal volume of all patients with TLE negatively correlated with MD (r = -0.746, p = 0.0145) and positively correlated with ODI (r = 0.719, p = 0.0145). Fiso and ND of sclerotic hippocampi positively correlated with disease duration (r = 0.684, p = 0.0424 and r = 0.670, p = 0.0486, respectively). Immunohistochemistry in sclerotic hippocampal specimens revealed neuronal loss in the pyramidal layer and fiber reorganization at the level of stratum lacunosum-moleculare, confirming ODI and ND metrics. This study shows the capability of diffusion MRI metrics to detect hippocampal microstructural alterations. Among them, ODI seems to better highlight the fiber reorganization observed by neuropathology in sclerotic hippocampi.

The role of critical immune genes in brain disorders: insights from neuroimaging immunogenetics.

Genetic variants in the human leukocyte antigen and killer cell immunoglobulin-like receptor regions have been associated with many brain-related diseases, but how they shape brain structure and function remains unclear. To identify the genetic variants in HLA and KIR genes associated with human brain phenotypes, we performed a genetic association study of ∼30 000 European unrelated individuals using brain MRI phenotypes generated by the UK Biobank (UKB). We identified 15 HLA alleles in HLA class I and class II genes significantly associated with at least one brain MRI-based phenotypes (P < 5 × 10−8). These associations converged on several main haplotypes within the HLA. In particular, the human leukocyte antigen alleles within an ancestral haplotype 8.1 were associated with multiple MRI measures, including grey matter volume, cortical thickness (TH) and diffusion MRI (dMRI) metrics. These alleles have been strongly associated with schizophrenia. Additionally, associations were identified between HLA-DRB1*04∼DQA1*03:01∼DQB1*03:02 and isotropic volume fraction of diffusion MRI in multiple white matter tracts. This haplotype has been reported to be associated with Parkinson’s disease. These findings suggest shared genetic associations between brain MRI biomarkers and brain-related diseases. Additionally, we identified 169 associations between the complement component 4 (C4) gene and imaging phenotypes. We found that C4 gene copy number was associated with cortical TH and dMRI metrics. No KIR gene copy numbers were associated with image-derived phenotypes at genome-wide threshold. To address the multiple testing burden in the phenome-wide association study, we performed a multi-trait association analysis using trait-based association test that uses extended Simes procedure and identified MRI image-specific associations. This study contributes to insight into how critical immune genes affect brain-related traits as well as the development of neurological and neuropsychiatric disorders.

Multi-Contrast Magnetic Resonance Imaging of Visual White Matter Pathways in Patients With Glaucoma.

PurposeGlaucoma is a disorder that involves visual field loss caused by retinal ganglion cell damage. Previous diffusion magnetic resonance imaging (dMRI) studies have demonstrated that retinal ganglion cell damage affects tissues in the optic tract (OT) and optic radiation (OR). However, because previous studies have used a simple diffusion tensor model to analyze dMRI data, the microstructural interpretation of white matter tissue changes remains uncertain. In this study, we used a multi-contrast MRI approach to further clarify the type of microstructural damage that occurs in patients with glaucoma.MethodsWe collected dMRI data from 17 patients with glaucoma and 30 controls using 3-tesla (3T) MRI. Using the dMRI data, we estimated three types of tissue property metrics: intracellular volume fraction (ICVF), orientation dispersion index (ODI), and isotropic volume fraction (IsoV). Quantitative T1 (qT1) data, which may be relatively specific to myelin, were collected from all subjects.ResultsIn the OT, all four metrics showed significant differences between the glaucoma and control groups. In the OR, only the ICVF showed significant between-group differences. ICVF was significantly correlated with qT1 in the OR of the glaucoma group, although qT1 did not show any abnormality at the group level.ConclusionsOur results suggest that, at the group level, tissue changes in OR caused by glaucoma might be explained by axonal damage, which is reflected in the intracellular diffusion signals, rather than myelin damage. The significant correlation between ICVF and qT1 suggests that myelin damage might also occur in a smaller number of severe cases.

Abstract 9: Pervasive White Matter Microstructure Dysintegrity Related To High Blood Pressure Among Asymptomatic Population

Background: Blood pressure is the strongest contributor to clinically evident cerebrovascular disease. We investigated the role of blood pressure on white matter (WM) microstructure among asymptomatic individuals without clinically evident cerebrovascular disease. Methods: We conducted a nested study within the UK Biobank, restricting our analysis to participants without cerebrovascular disease or dementia and with available brain diffusion tensor imaging (DTI). We tested for association between systolic blood pressure (SBP) and six different DTI metrics: fractional anisotropy (FA), mean diffusivity (MD), tensor mode (MO), intra-cellular volume fraction (ICVF), isotropic or free water volume fraction (ISOVF), and orientation dispersion index (OD) across 48 WM tracts using multivariable linear regression adjusted for potential confounders. We used Bonferroni-corrected p-values (0.05/48) for statistical significance. Results: We analyzed 33,440 participants. Mean age was 63.0 (SD 7.7), and 17,688 (53%) were female. Higher SBP is independently associated with pervasive decrease in FA and ICVF and increase in MD (Figure), after adjustment for vascular risk-factors. SBP was also associated with lower neurite OD (a more specific metric of axonal damage) in bilateral posterior corona radiata, external capsule, medial lemniscus, and corticospinal tracs. FA and OD of external capsule and posterior corona radiata had the largest drop per 10 mmHg increase of SBP (steepest slope). Conclusions: Higher SBP is associated with pervasive WM microstructure dysintegrity in asymptomatic individuals without evident cerebrovascular disease. DTI metrics of the posterior corona radiata and external capsule are most reflective of variations in SBP and may provide a potential biomarker to assess subtle WM microstructural damage in hypertensive patients or monitor treatment response in clinical trials.

Severe Gestational Low-Protein Intake Impacts Hippocampal Cellularity, Tau, and Amyloid-β Levels, and Memory Performance in Male Adult Offspring: An Alzheimer-Simile Disease Model?

Background:Maternal undernutrition has been associated with psychiatric and neurological disorders characterized by learning and memory impairment.Objective:Considering the lack of evidence, we aimed to analyze the effects of gestational protein restriction on learning and memory function associated with hippocampal cell numbers and neurodegenerative protein content later in life.Methods:Experiments were conducted in gestational low- (LP, 6% casein) or regular-protein (NP, 17% casein) diet intake offspring. Behavioral tests, isolated hippocampal isotropic fractionator cell studies, immunoblotting, and survival lifetime were observed.Results:The birthweight of LP males is significantly reduced relative to NP male progeny, and hippocampal mass increased in 88-week-old LP compared to age-matched NP offspring. The results showed an increased proximity measure in 87-week-old LP compared to NP offspring. Also, LP rats exhibited anxiety-like behaviors compared to NP rats at 48 and 86-wk of life. The estimated neuron number was unaltered in LP rats; however, non-neuron cell numbers increased compared to NP progeny. Here, we showed unprecedented hippocampal deposition of brain-derived neurotrophic factor, amyloid-β peptide (Aβ), and tau protein in 88-week-old LP relative to age-matched NP offspring.Conclusion:To date, no predicted studies showed changes in hippocampal morphological structure in maternal protein-restricted elderly offspring. The current data suggest that gestational protein restriction may accelerate hippocampal function loss, impacting learning/memory performance, and supposedly developing diseases similar to Alzheimer’s disease (AD) in elderly offspring. Thus, we propose that maternal protein restriction could be an elegant and novel method for constructing an AD-like model in adult male offspring.

Developmental Lead Exposure in Rats Causes Sex-Dependent Changes in Neurobiological and Anxiety-Like Behaviors that Are Improved by Taurine Co-treatment.

Lead (Pb2+) is a developmental neurotoxicant that causes alterations in the brain's excitation-to-inhibition (E/I) balance by disrupting the development of the GABAergic systems. These GABAergic disruptions have persistent neurobiological and neurobehavioral structure-function relationships that can be examined using animal models of Pb2+ exposure. Further, taurine, a GABA-AR agonist, has been shown to offer neuroprotection against neurodevelopmental Pb2+ exposure and senescence. The present study evaluated the effects of Pb2+ exposure (i.e., at 150 ppm and 1,000 ppm doses) on Long Evans hooded rats during the perinatal period of development on locomotor activity in the open field (OF) and anxiety-like behaviors in the elevated plus maze (EPM). This was followed by an examination of brain mass using an encephalization quotient (EQ) and isotropic fractionation (ITF) of total cells and the number of neurons and non-neuronal cells in the prefrontal cortex, hippocampus, and diencephalon. The results suggest that neurodevelopmental Pb2+ exposure caused persistent anxiety-like behaviors in both the OF and EPM with associated changes in EQ, but not ITF-determined cell density. Further, taurine treatment was observed to compensate for Pb2+ exposure in the behavioral assessments although precise neurobiological mechanisms remain unknown. Thus, more work is required to evaluate the role of taurine and other anxiolytic compounds in the alleviation of neurotoxicant-induced neurobehavioral syndromes and their associated neurobiological correlates.

Longitudinal microstructural MRI markers of demyelination and neurodegeneration in early relapsing-remitting multiple sclerosis: Magnetisation transfer, water diffusion and g-ratio

IntroductionQuantitative microstructural MRI, such as myelin-sensitive magnetisation transfer ratio (MTR) or saturation (MTsat), axon-sensitive water diffusion Neurite Orientation Dispersion and Density Imaging (NODDI), and the aggregate g-ratio, may provide more specific markers of white matter integrity than conventional MRI for early patient stratification in relapsing-remitting multiple sclerosis (RRMS). The aim of this study was to determine the sensitivity of such markers to longitudinal pathological change within cerebral white matter lesions (WML) and normal-appearing white matter (NAWM) in recently diagnosed RRMS. MethodsSeventy-nine people with recently diagnosed RRMS, from the FutureMS longitudinal cohort, were recruited to an extended MRI protocol at baseline and one year later. Twelve healthy volunteers received the same MRI protocol, repeated within two weeks. Ethics approval and written informed consent were obtained.3T MRI included magnetisation transfer, and multi-shell diffusion-weighted imaging. NAWM and whole brain were segmented from 3D T1-weighted MPRAGE, and WML from T2-weighted FLAIR. MTR, MTsat, NODDI isotropic (ISOVF) and intracellular (ICVF) volume fractions, and g-ratio (calculated from MTsat and NODDI data) were measured within WML and NAWM. Brain parenchymal fraction (BPF) was also calculated.Longitudinal change in BPF and microstructural metrics was assessed with paired t-tests (α = 0.05) and linear mixed models, adjusted for confounding factors with False Discovery Rate (FDR) correction for multiple comparisons. Longitudinal changes were compared with test-retest Bland-Altman limits of agreement from healthy control white matter. The influence of longitudinal change on g-ratio was explored through post-hoc analysis in silico by computing g-ratio with realistic simulated MTsat and NODDI values. ResultsIn NAWM, g-ratio and ICVF increased, and MTsat decreased over one year (adjusted mean difference = 0.007, 0.005, and −0.057 respectively, all FDR-corrected p < 0.05). There was no significant change in MTR, ISOVF, or BPF. In WML, MTsat, NODDI ICVF and ISOVF increased over time (adjusted mean difference = 0.083, 0.024 and 0.016, respectively, all FDR-corrected p < 0.05). Group-level longitudinal changes exceeded test-retest limits of agreement for NODDI ISOVF and ICVF in WML only. In silico analysis showed g-ratio may increase due to a decrease in MTsat or ISOVF, or an increase in ICVF. DiscussionG-ratio and MTsat changes in NAWM over one year may indicate subtle myelin loss in early RRMS, which were not apparent with BPF or NAWM MTR. Increases in NAWM and WML NODDI ICVF were not anticipated, and raise the possibility of axonal swelling or morphological change. Increases in WML MTsat may reflect myelin repair. Changes in NODDI ISOVF are more likely to reflect alterations in water content. Competing MTsat and ICVF changes may account for the absence of g-ratio change in WML. Longitudinal changes in microstructural measures are significant at a group level, however detection in individual patients in early RRMS is limited by technique reproducibility. ConclusionMTsat and g-ratio are more sensitive than MTR to early pathological changes in RRMS, but complex dependence of g-ratio on NODDI parameters limit the interpretation of aggregate measures in isolation. Improvements in technique reproducibility and validation of MRI biophysical models across a range of pathological tissue states are needed.

White matter tracts that overlap with the thalamus and the putamen are protected against multiple sclerosis pathology

BackgroundThe thalamus and the putamen are highly connected hubs implicated in multiple sclerosis (MS) pathology. It remains unclear if white matter (WM) tracts, which pass through them, have a different susceptibility to MS pathology, and if so, if their impact on disability predominates over that exerted by disease in other WM tracts. We hypothesized that WM tracts connected to and passing through these hubs (subsequently termed hub+ tracts) would be more susceptible to MS-related pathology than tracts that do not pass through them (hub- tracts) due to retrograde and anterograde distant degeneration. Thus, we compared the lesion load and neurite orientation dispersion and density imaging (NODDI) derived metrics between hub+ and hub- tracts and assessed the relationship between these MRI metrics and those of physical impairment. MethodsEighteen patients (mean age of 45.5 years, 12 females) had 3 Tesla MRI consisting of T1-weighted and T2-weighted Fluid Attenuated Inversion Recovery (FLAIR), and NODDI from which the orientation dispersion index (ODI), neurite density index (NDI), and isotropic volume fraction (IVF) were derived. Forty-nine WM tracts, i.e., 12 hub+ and 37 hub- tracts, were segmented out. Exploratory analyses of the differences in lesion burden, whole tract and normal appearing WM (NAWM) NODDI metrics were carried out between the two types of tracts using a Mann-Whitney U test. Correlations with physical impairment, quantified using the expanded disability status scale (EDSS) and timed 25-foot walk (T25FW) test were assessed using Spearman correlation analyses. ResultsHub- tracts had larger T1- (p<0.001) and T2-lesion (p<0.001) volumes; lower ODI (p<0.001), NDI (p<0.001) and higher IVF (p = 0.020) in comparison to hub+ tracts. Measures of tissue injury in hub+ tracts correlated with those of clinical disability, though less strongly than in hub- tracts. ConclusionsContrary to our hypothesis, our exploratory pilot study results suggest that WM tracts that overlap with the thalamus and the putamen have a lower degree of lesional and non-lesional tissue injury, suggesting a protective role of the hubs against MS pathology or a higher degree of vulnerability of those not passing through hub stations. We also show a weaker association between disability impairment and hub+ pathology, compared to that in hub- tracts. Our findings point to a potential role of disease location in relation to hubs as guidance for treatment personalization in MS

Atrophy and partial volume related bias in cortical region of interest NODDI metrics

AbstractBackgroundNeurite Orientation Dispersion and Density Imaging (NODDI) provides in‐vivo indices of neurite density (NDI) and orientation dispersion (ODI) within the tissue compartment of each voxel. However, NDI and ODI are treated equally when calculating region of interest (ROI) means, despite tissue fraction (TF) varying within regions undergoing neurodegeneration. Covariation between TF and cortical NODDI measures bias these conventional means and we recommend using tissue‐weighted averages to address this.MethodIn this study, we included 22 healthy controls and 33 individuals affected by Young‐Onset Alzheimer’s disease (YOAD, see Table 1 for demographics) with suitable diffusion‐weighted and T1‐weighted 3T MR images. Diffusion data were corrected for eddy currents, motion and susceptibility artefacts before fitting the NODDI model to produce NDI, ODI, isotropic volume fraction (ISO) and TF maps (TF=1‐ISO). T1w images were parcellated into cortical ROIs using Geodesic Information Flow (Cardoso et al., IEEE Trans.Med.Im.; 34:1976‐1988, 2015). Five bilateral ROIs expected to undergo neurodegeneration were analysed (Precuneus, Fusiform Gyrus, Superior Parietal, Middle and Inferior Temporal cortex). ROIs were resampled into native diffusion space and two regional measures calculated: 1) conventional, unweighted NDI and ODI averages and 2) tissue‐weighted averages using voxel TF as weights. Within‐participant differences between conventional and tissue‐weighted measures were calculated. Spearman’s rank tested correlations and Wilcoxon tests evaluated within‐ and between‐participant differences (Bonferroni adjusted for multiple comparisons).ResultTF positively correlated with GM volume (rs range=0.33‐0.68,p&lt;0.05) in all ROIs except the left fusiform gyrus (rs=0.31,p=0.06) (Figure 1). YOAD individuals had lower TF than healthy controls in all ROIs (Figure 2a), and lower volumes in all ROIs except the right fusiform gyrus (W=475,p=0.27) (Figure 2b). NDI showed small positive/negative biases in six of the ten ROIs (Figure 3a), while ODI showed significant positive biases across all ROIs (Figure 3b). Biases decreased as TF increased towards its maximum of one (Figure 4a‐4b).ConclusionLower cortical volumes in YOAD were associated with lower TF and higher bias, suggesting a greater risk for misestimation of cortical region NODDI metrics in studies involving neurodegenerative disease. We recommend tissue‐weighted averages to account for varying intra‐regional TF in NODDI measures.

Single-shell NODDI using dictionary-learner-estimated isotropic volume fraction.

Neurite orientation dispersion and density imaging (NODDI) enables the assessment of intracellular, extracellular, and free water signals from multi-shell diffusion MRI data. It is an insightful approach to characterize brain tissue microstructure. Single-shell reconstruction for NODDI parameters has been discouraged in previous studies caused by failure when fitting, especially for the neurite density index (NDI). Here, we investigated the possibility of creating robust NODDI parameter maps with single-shell data, using the isotropic volume fraction (fISO ) as a prior. Prior estimation was made independent of the NODDI model constraint using a dictionary learning approach. First, we used a stochastic sparse dictionary-based network (DictNet), which is trained with data obtained from in vivo and simulated diffusion MRI data, to predict fISO . In single-shell cases, the mean diffusivity and raw T2 signal with no diffusion weighting (S0 ) was incorporated in the dictionary for the fISO estimation. Then, the NODDI framework was used with the known fISO to estimate the NDI and orientation dispersion index (ODI). The fISO estimated using our model was compared with other fISO estimators in the simulation. Further, using both synthetic data simulation and human data collected on a 3 T scanner (both high-quality HCP and clinical dataset), we compared the performance of our dictionary-based learning prior NODDI (DLpN) with the original NODDI for both single-shell and multi-shell data. Our results suggest that DLpN-derived NDI and ODI parameters for single-shell protocols are comparable with original multi-shell NODDI, and the protocol with b= 2000 s/mm2 performs the best (error ~ 5% in white and gray matter). This may allow NODDI evaluation of studies on single-shell data by multi-shell scanning of two subjects for DictNet fISO training.

Exploring Peritumoral Neural Tracts by Using Neurite Orientation Dispersion and Density Imaging.

Diffusion Tensor Imaging (DTI) tractography has been widely used in brain tumor surgery to ensure thorough resection and minimize functional damage. However, due to enhanced anisotropic uncertainty in the area with peritumoral edema, diffusion tractography is generally not practicable leading to high false-negative results in neural tracking. In this study, we evaluated the usefulness of the neurite orientation dispersion and density imaging (NODDI) derived tractography for investigating structural heterogeneity of the brain in patients with brain tumor. A total of 24 patients with brain tumors, characterized by peritumoral edema, and 10 healthy counterparts were recruited from 2014 to 2021. All participants underwent magnetic resonance imaging. Moreover, we used the images obtained from the healthy participants for calibrating the orientation dispersion threshold for NODDI-derived corticospinal tract (CST) reconstruction. Compared to DTI, NODDI-derived tractography has a great potential to improve the reconstruction of fiber tracking through regions of vasogenic edema. The regions with edematous CST in NODDI-derived tractography demonstrated a significant decrease in the intracellular volume fraction (VFic, p < 0.000) and an increase in the isotropic volume fraction (VFiso, p < 0.014). Notably, the percentage of the involved volume of the concealed CST and lesion-to-tract distance could reflect the motor function of the patients. After the tumor resection, four patients with 1–5 years follow-up were showed subsidence of the vasogenic edema and normal CST on DTI tractography. NODDI-derived tractography revealed tracts within the edematous area and could assist neurosurgeons to locate the neural tracts that are otherwise not visualized by conventional DTI tractography.

Enhancing Electrostrictive Actuation via Strong Electrostatic Repulsion among Field-Induced Nanodomains in a Relaxor Ferroelectric Poly(vinylidene fluoride-co-trifluoroethylene-co-chlorotrifluoroethylene) Random Terpolymer

Electrostrictive polymers having a large strain are desirable for actuation, sensing, and energy harvesting in wearable electronics and soft robotics. However, a high electric field (>100 MV/m) is usually required for current electrostrictive polymers. To realize large electrostriction at reduced electric fields, the fundamental electrostriction mechanism needs to be better understood. In response to this need, the structure and electrostrictive properties of relaxor ferroelectric (RFE) poly(vinylidene fluoride-co-trifluoroethylene-co-chlorotrifluoroethylene) [P(VDF-TrFE-CTFE)] random terpolymers films with different thermal annealing histories were studied in this work. First, the semicrystalline structure of the P(VDF-TrFE-CTFE) terpolymer films was studied by combined small-angle X-ray scattering and wide-angle X-ray diffraction analyses. A three-phase model was employed, namely, crystals and oriented and isotropic amorphous fractions (OAF and IAF). The bulky CTFE units generated taut-tie molecules (TTM) in the crystalline lamella, dividing it into many nanosized crystals (∼1.3 nm thick). It is this unique crystalline structure with nanocrystals and mobile TTM/OAF that enabled the RFE behavior for the P(VDF-TrFE)-based terpolymers. Through electrostriction measurements and nonlinear dielectric analysis, an inverse correlation was observed between the ferroelectric nonlinearity and the electrostrictive coefficient under a high poling electric field (>100 MV/m). This suggested that higher electrostriction performance could be achieved by decreasing the ferroelectric nonlinearity of the RFE terpolymer. Indeed, above the Curie temperature, the paraelectric terpolymer films achieved a high electrostrictive performance with the transverse strain being ∼5% at 200 MV/m. This was attributed to the strong electrostatic repulsion among electric field-induced ferroelectric nanodomains. The finding from this work provides a viable way to design new electrostrictive polymers with higher performance at low driving fields.

Utility of Advanced DWI in the Detection of Spinal Cord Microstructural Alterations and Assessment of Neurologic Function in Cervical Spondylotic Myelopathy Patients.

Diffusion-weighted imaging (DWI) can quantify the microstructural changes in the spinal cord. It might be a substitute for T2 increased signal intensity (ISI) for cervical spondylotic myelopathy (CSM) evaluation and prognosis. The purpose of the study is to investigate the relationship between DWI metrics and neurologic function of patients with CSM. Retrospective. Forty-eight patients with CSM (18.8% females) and 36 healthy controls (HCs, 25.0% females). 3 T; spin-echo echo-planar imaging-DWI; turbo spin-echo T1/T2; multi-echo gradient echo T2*. For patients, conventional MRI indicators (presence and grades of T2 ISI), DWI indicators (neurite orientation dispersion and density imaging [NODDI]-derived isotropic volume fraction [ISOVF], intracellular volume fraction, and orientation dispersion index [ODI], diffusion tensor imaging [DTI]-derived fractional anisotropy [FA] and mean diffusivity [MD], and diffusion kurtosis imaging [DKI]-derived FA, MD, and mean kurtosis), clinical conditions, and modified Japanese Orthopaedic Association (mJOA) were recorded before the surgery. Neurologic function improvement was measured by the 3-month follow-up recovery rate (RR). For HCs, DWI, and mJOA were measured as baseline comparison. Continuous (categorical) variables were compared between patients and HCs using Student's t-tests or Mann-Whitney U tests (chi-square or Fisher exact tests). The relationships between DWI metrics/conventional MRI findings, and the pre-operative mJOA/RR were assessed using correlation and multivariate analysis. P < 0.05 was considered statistically significant. Among patients, grades of T2 ISI were not correlated with pre-surgical mJOA/RR (P=0.717 and0.175, respectively). NODDI ODI correlated with pre-operative mJOA (r=-0.31). DTI FA, DKI FA, and NODDI ISOVF were correlated with the recovery rate (r=0.31, 0.41, and -0.34, respectively). In multivariate analysis, NODDI ODI (DTI FA, DKI FA, NODDI ISOVF) significantly contributed to the pre-operative mJOA (RR) after adjusting for age. DTI FA, DKI FA, and NODDI ISOVF are predictors for prognosis in patients with CSM. NODDI ODI can be used to evaluate CSM severity. 3 TECHNICAL EFFICACY STAGE: 5.

The MRi-Share database: brain imaging in a cross-sectional cohort of 1870 university students.

We report on MRi-Share, a multi-modal brain MRI database acquired in a unique sample of 1870 young healthy adults, aged 18-35years, while undergoing university-level education. MRi-Share contains structural (T1 and FLAIR), diffusion (multispectral), susceptibility-weighted (SWI), and resting-state functional imaging modalities. Here, we described the contents of these different neuroimaging datasets and the processing pipelines used to derive brain phenotypes, as well as how quality control was assessed. In addition, we present preliminary results on associations of some of these brain image-derived phenotypes at the whole brain level with both age and sex, in the subsample of 1722 individuals aged less than 26years. We demonstrate that the post-adolescence period is characterized by changes in both structural and microstructural brain phenotypes. Grey matter cortical thickness, surface area and volume were found to decrease with age, while white matter volume shows increase. Diffusivity, either radial or axial, was found to robustly decrease with age whereas fractional anisotropy only slightly increased. As for the neurite orientation dispersion and densities, both were found to increase with age. The isotropic volume fraction also showed a slight increase with age. These preliminary findings emphasize the complexity of changes in brain structure and function occurring in this critical period at the interface of late maturation and early ageing.