Peak width of skeletonized mean diffusivity as a neuroimaging biomarker in first-episode schizophrenia.

Background and objective: Peak width of skeletonized mean diffusivity (PSMD), a fully automated diffusion tensor imaging (DTI) biomarker of white matter (WM) microstructure damage, has been shown to be associated with cognition in various WM pathologies. However, its application in schizophrenic disease remains unexplored. This study aims to investigate PSMD along with other DTI markers in first-episode schizophrenia patients compared to healthy controls (HCs), and explore the correlations between these metrics and clinical characteristics. Methods: A total of 56 first-episode drug-naive schizophrenia patients and 64 HCs were recruited for this study. Participants underwent structural imaging and DTI, followed by comprehensive clinical assessments, including the Positive and Negative Syndrome Scale (PANSS) for patients and cognitive function tests for all participants. We calculated PSMD, peak width of skeletonized fractional anisotropy (PSFA), axial diffusivity (PSAD), radial diffusivity (PSRD) values, skeletonized average mean diffusivity (MD), average fractional anisotropy (FA), average axial diffusivity (AD), and average radial diffusivity (RD) values as well as structural network global topological parameters, and examined between-group differences in these WM metrics. Furthermore, we investigated associations between abnormal metrics and clinical characteristics. Results: Compared to HCs, patients exhibited significantly increased PSMD values (t = 2.467, p = 0.015), decreased global efficiency (Z = -2.188, p = 0.029), and increased normalized characteristic path length (lambda) (t = 2.270, p = 0.025). No significant differences were observed between the groups in the remaining metrics, including PSFA, PSAD, PSRD, average MD, FA, AD, RD, local efficiency, normalized cluster coefficient, small-worldness, assortativity, modularity, or hierarchy (p > 0.05). After adjusting for relevant variables, both PSMD and lambda values exhibited a significant negative correlation with reasoning and problem-solving scores (PSMD: r = -0.409, p = 0.038; lambda: r = -0.520, p = 0.006). No statistically significant correlations were observed between each PANSS score and the aforementioned metrics in the patient group (p > 0.05). Multivariate linear regression analysis revealed that increased PSMD (ß = -0.426, t = -2.260, p = 0.034) and increased lambda (ß = -0.490, t = -2.994, p = 0.007) were independently associated with decreased reasoning and problem-solving scores respectively ( R a d j 2 = 0.295, F = 2.951, p = 0.029). But these significant correlations did not withstand FDR correction (p_FDR > 0.05). Conclusion: PSMD can be considered as a valuable neuroimaging biomarker that complements conventional diffusion measurements for investigating abnormalities in WM microstructural integrity and cognitive functions in schizophrenia.

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

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Lateral thinking: Neurodegeneration of the cortical cholinergic system in Alzheimer's disease.

INTRODUCTION: Atrophy of the nucleus basalis of Meynert (NBM) is an early indicator of Alzheimer's disease (AD). However, reduced integrity of the NBM white matter tracts may be more relevant for cognitive impairment and progression to dementia than NBM volume. Research is needed to compare differences in NBM volume and integrity of the lateral and medial NBM tracts across early and later stages of AD progression. METHODS: 187 participants were included in this study who were either healthy controls (HC; n = 50) or had early mild cognitive impairment (EMCI; n = 50), late MCI (LMCI; n = 37), or AD (n = 50). NBM volume was calculated using voxel-based morphometry and mean diffusivity (MD) of the lateral and medial NBM tracts were extracted using probabilistic tractography. Between group differences in NBM volume and tract MD were compared using linear mixed models controlling for age, sex, and either total intracranial volume or MD of a control mask, respectively. Associations between NBM volume and tract MD with executive function, memory, language, and visuospatial function were also analysed. RESULTS: NBM volume was smallest in AD followed by LMCI (p < 0.0001), with no difference between EMCI and HC. AD had highest MD for both tracts compared to all other groups (p < 0.01). Both MCI groups had higher lateral tract MD compared to HC (p < 0.05). Medial tract MD was higher in LMCI (p = 0.008), but not EMCI (p = 0.09) compared to HC. Higher lateral tract MD was associated with executive function (p = 0.001) and language (p = 0.02). DISCUSSION: Integrity of the lateral NBM tract is most sensitive to the earliest stages of AD and should be considered an important therapeutic target for early detection and intervention.

Alterations in the Glymphatic System and Association with Brain Structure and Cognitive Function in Moyamoya Disease.

The glymphatic system is crucial for clearing metabolic waste from the brain, maintaining neural health and cognitive function. This study explores the glymphatic system's role in Moyamoya disease (MMD), characterized by progressive cerebral artery stenosis and brain structural lesions. We assessed 33 MMD patients and 21 healthy controls using diffusion tensor imaging along the perivascular space (DTI-ALPS) and global cortical gray matter-cerebrospinal fluid (CSF) coupling indices (gBOLD-CSF), which are indirect measurements of the glymphatic system. Cerebral perfusion in patients was evaluated via computed tomography perfusion imaging. We also measured the peak width of skeletonized mean diffusivity (PSMD), white matter hyperintensity (WMH) burden, and cognitive function. MMD patients exhibited lower ALPS and gBOLD-CSF coupling indices compared to controls (P < 0.01), indicating disrupted glymphatic function. Significant cognitive impairment was also observed in MMD patients (P < 0.01). ALPS indices varied with cerebral perfusion stages, being higher in earlier ischemic stages (P < 0.05). Analysis of brain structure showed increased CSF volume, PSMD index, and higher WMH burden in MMD patients (P < 0.01). The ALPS index positively correlated with white matter volume and cognitive scores, and negatively correlated with CSF volume, PSMD, and WMH burden (P < 0.05). Mediation analysis revealed the number of periventricular WMH significantly mediated the relationship between glymphatic dysfunction and cognitive impairment. In summary, MMD patients exhibit significant glymphatic system impairments, associated with brain structural changes and cognitive deficits.

Spatial and temporal patterns of cortical mean diffusivity in Alzheimer's disease and suspected non-Alzheimer's disease pathophysiology.

INTRODUCTION: The spatial and temporal patterns of cortical mean diffusivity (cMD), as well as its association with Alzheimer's disease (AD) and suspected non-Alzheimer's pathophysiology (SNAP), are not yet fully understood. METHODS: We compared baseline (n = 617) and longitudinal changes (n = 421) of cMD, cortical thickness, and gray matter volume and their relations to vascular risk factors, amyloid beta (Aß), and tau positron emission tomography (PET), and longitudinal cognitive decline in Aß PET negative and positive older adults. RESULTS: cMD increases were more sensitive to detecting brain structural alterations than cortical thinning and gray matter atrophy. Tau-related cMD increases partially mediated Aß-related cognitive decline in AD, whereas vascular disease-related increased cMD levels substantially mediated age-related cognitive decline in SNAP. DISCUSSION: These findings revealed the dynamic changes of microstructural and macrostructural indicators and their associations with AD and SNAP, providing novel insights into understanding upstream and downstream events of cMD in neurodegenerative disease. HIGHLIGHTS: Cortical mean diffusivity (cMD) was more sensitive to detecting structural changes than macrostructural factors. Tau-related cMD increases partially mediated amyloid beta-related cognitive decline in Alzheimer's disease (AD). White matter hyperintensity-related higher cMD mainly explained the age-related cognitive decline in suspected non-Alzheimer's pathophysiology (SNAP). cMD may assist in tracking earlier neurodegenerative signs in AD and SNAP.

Unveiling the link between glymphatic function and cortical microstructures in post-traumatic stress disorder.

PURPOSE: The discovery of the glymphatic system, crucial for cerebrospinal and interstitial fluid exchange, has enhanced our grasp of brain protein balance and its potential role in neurodegenerative disease prevention and therapy. Detecting early neurodegenerative shifts via noninvasive biomarkers could be key in identifying at-risk individuals for Alzheimer's disease (AD). Our research explores a diffusion tensor imaging (DTI) method that measures cortical mean diffusivity (cMD), potentially a more sensitive indicator of neurodegeneration than traditional macrostructural methods. MATERIALS AND METHODS: We analyzed 67 post-traumatic stress disorder (PTSD)-diagnosed veterans from the Alzheimer's Disease Neuroimaging Initiative database. Participants underwent structural MRI, DTI, Aß PET imaging, and cognitive testing. We focused on the DTI-ALPS technique to assess glymphatic function and its relation to cMD, cortical Aß accumulation, and thickness, accounting for age and APOE ε4 allele variations. RESULTS: The cohort, all male with an average age of 68.1 (SD 3.4), showed a strong inverse correlation between DTI-ALPS and cMD in AD-affected regions, especially in the entorhinal, parahippocampal, and fusiform areas. Higher DTI-ALPS readings were consistently linked with greater cortical thickness, independent of Aß deposits and genetic risk factors. Age and cMD emerged as inversely proportional predictors of DTI-ALPS, indicating a complex interaction with age. CONCLUSION: The study confirms a meaningful association between glymphatic efficiency and cMD in AD-sensitive zones, accentuating cortical microstructural alterations in PTSD. It positions DTI-ALPS as a viable biomarker for assessing glymphatic function in PTSD, implicating changes in DTI-ALPS as indicative of glymphatic impairment.

Assessment the Impact of IDH Mutation Status on MRI Assessments of White Matter Integrity in Glioma Patients: Insights From Peak Width of Skeletonized Mean Diffusivity and Free Water Metrics.

BACKGROUND: Gliomas are highly invasive brain tumors that evade accurate geographic assessment by conventional MRI due to microscopic invasion along white matter (WM) tracts. Advanced diffusion MRI techniques are needed to assess occult WM involvement. PURPOSE: To evaluate peak width of skeletonized mean diffusivity (PSMD) and peak width of skeletonized free water (PSFW), and axonal water fraction (AWF) for assessing glioma-induced alterations in normal-appearing WM and their relationship with isocitrate dehydrogenase 1 (IDH1) mutation. STUDY TYPE: Retrospective. POPULATION: One hundred five glioma patients (46 ± 13 years), 53 healthy controls (HCs) (46 ± 9 years). FIELD STRENGTH/SEQUENCE: 3.0 T, T1WI, T1-CE, T2WI, T2FLAIR, and DKI. ASSESSMENT: PSMD and PSFW were compared between lesion and contralateral sides in glioma patients and between patients and HCs. The associations between these metrics and clinical variables, including IDH1 mutation, was assessed. Corpus callosum (CC) injury, quantified by the AWF, was evaluated for its mediated effect of IDH1 mutation on contralesional PSMD and PSFW. STATISTICAL TESTS: Paired-t tests, ANCOVA, univariate and multivariate linear regression, and mediation analysis with significance set at P < 0.05. RESULTS: Contralateral PSMD and PSFW were significantly higher in left-sided gliomas (PSMD: 0.206 ± 0.027 vs. 0.193 ± 0.023; PSFW: 0.119 ± 0.019 vs. 0.106 ± 0.020) than in HCs, with similar increases in right-sided gliomas (PSMD: 0.219 ± 0.036 vs. 0.195 ± 0.023; PSFW: 0.129 ± 0.031 vs. 0.109 ± 0.020). IDH1 wild-type gliomas were associated with higher contralateral PSMD and PSFW (ß = -0.302 and -0.412). AWF of CC mediated the impact of IDH1 mutations on contralesional PSMD and PSFW (mediated proportion: 42.7% and 53.7%). DATA CONCLUSION: PSMD and PSFW are effective biomarkers for assessing WM integrity in gliomas, significantly associated with IDH1 mutation status. AWF of CC mediates the relationship between IDH1 mutation and contralesional PSMD and PSFW. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Diffusion tensor metrics, motor and non-motor symptoms in de novo Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neurons' degeneration of the substantia nigra, presenting with motor and non-motor symptoms. We hypothesized that altered diffusion metrics are associated with clinical symptoms in de novo PD patients. METHODS: Fractional Anisotropy (FA) and Mean (MD), Axial (AD), and Radial Diffusivity (RD) were assessed in 55 de novo PD patients (58.62 ± 9.85 years, 37 men) and 55 age-matched healthy controls (59.92 ± 11.25 years, 34 men). Diffusion-weighted images and clinical variables were collected from the Parkinson's Progression Markers Initiative study. Tract-based spatial statistics were used to identify white matter (WM) changes, and fiber tracts were localized using the JHU-WM tractography atlas. Motor and non-motor symptoms were evaluated in patients. RESULTS: We observed higher FA values and lower RD values in patients than controls in various fiber tracts (p-TFCE < 0.05). No significant MD or AD difference was observed between groups. Diffusion metrics of several regions significantly correlated with non-motor (state and trait anxiety and daytime sleepiness) and axial motor symptoms in the de novo PD group. No correlations were observed between diffusion metrics and other clinical symptoms evaluated. CONCLUSION: Our findings suggest microstructural changes in de novo PD fiber tracts; however, limited associations with clinical symptoms reveal the complexity of PD pathology. They may contribute to understanding the neurobiological changes underlying PD and have implications for developing targeted interventions. However, further longitudinal research with larger cohorts and consideration of confounding factors are necessary to elucidate the underlying mechanisms of these diffusion alterations in de novo PD.

Leptin bioavailability and markers of brain atrophy and vascular injury in the middle age.

INTRODUCTION: We investigated the associations of leptin markers with cognitive function and magnetic resonance imaging (MRI) measures of brain atrophy and vascular injury in healthy middle-aged adults. METHODS: We included 2262 cognitively healthy participants from the Framingham Heart Study with neuropsychological evaluation; of these, 2028 also had available brain MRI. Concentrations of leptin, soluble leptin receptor (sOB-R), and their ratio (free leptin index [FLI]), indicating leptin bioavailability, were measured using enzyme-linked immunosorbent assays. Cognitive and MRI measures were derived using standardized protocols. RESULTS: Higher sOB-R was associated with lower fractional anisotropy (FA, ß = -0.114 ± 0.02, p < 0.001), and higher free water (FW, ß = 0.091 ± 0.022, p < 0.001) and peak-width skeletonized mean diffusivity (PSMD, ß = 0.078 ± 0.021, p < 0.001). Correspondingly, higher FLI was associated with higher FA (ß = 0.115 ± 0.027, p < 0.001) and lower FW (ß = -0.096 ± 0.029, p = 0.001) and PSMD (ß = -0.085 ± 0.028, p = 0.002). DISCUSSION: Higher leptin bioavailability was associated with better white matter (WM) integrity in healthy middle-aged adults, supporting the putative neuroprotective role of leptin in late-life dementia risk. HIGHLIGHTS: Higher leptin bioavailability was related to better preservation of white matter microstructure. Higher leptin bioavailability during midlife might confer protection against dementia. Potential benefits might be even stronger for individuals with visceral obesity. DTI measures might be sensitive surrogate markers of subclinical neuropathology.

A data-driven intravoxel mean diffusivities distribution approach for molecular classifications and MIB-1 prediction of gliomas.

BACKGROUND: Measuring non-parametric intravoxel mean diffusivity distributions (MDDs) using magnetic resonance imaging (MRI) is a sensitive method for detecting intracellular diffusivity changes during physiological alterations. Histological and molecular glioma classifications are essential for prognosis and treatment, with distinct water diffusion dynamics among subtypes. PURPOSE: We developed a data-driven approach using a fully connected network (FCN) to enhance the speed and stability of calculating MDDs across varying SNRs, enable tumor microstructural mapping, and test its reliability in identifying MIB-1 labeling index (LI) levels and molecular status of gliomas. METHODS: An FCN was trained to learn the mapping between the simulated diffusion decay curves and the ground truth MDDs. We performed 5 000 000 simulation curves with various diffusivity components and random SNR ∈ [ 30 , 300 ] $ \in [ {30,\ 300} ]$ . Eighty percent of simulation curves were used for the FCN training, 10% for validation, and the others were external tests for the FCN performance evaluation. In vivo data were collected to evaluate its clinical reliability. One hundred one patients (44 years ± $ \pm $ 14, 67 men) with gliomas and six healthy controls underwent a 3.0 T MRI examination with a spin echo-echo planar imaging (SE-EPI) diffusion-weighted imaging (DWI) sequence. The trained FCN was employed to calculate MDDs of each brain voxel by voxel. We used the Fuzzy C-means algorithm to cluster the MDDs of tumor voxels, facilitating the characterization of distinct glioma tissues. Quantitative assessments were conducted through sectional integrals of the MDDs, demarcated by six bands to derive signal fractions ( f n , n = 1 - 6 ${{f}_n},\ n = 1 -6$ ) and diffusivities of the maximum peaks ( D p e a k ${{D}_{peak}}$ ). Cosine similarity scores (CSS) were used for MDD similarity. ANOVA and Mann-Whitney U test were used for difference analysis. Logistic regression and area under the receiver operator characteristic curve (AUC) were used for classification evaluation. RESULTS: The simulation results showed that the FCN-based MDD approach (FCN-MDD) achieved higher CSS than non-negative least squares-based MDD (NNLS-MDD). For in vivo data, the spectra of ET and NET obtained by FCN-MDD are more distinguishable than NNLS-MDD. Fraction maps delineate the characteristics of different tumor tissues (enhancing and non-enhancing tumor, edema, and necrosis). f 3 , f 4 , D p e a k ${{f}_3},\ {{f}_4},{{D}_{peak}}$ showed a positive and negative correlation with MIB-1 respectively ( r = 0.568 , r = - 0.521 , r = - 0.654 $r = 0.568,\ r = - 0.521,\ r = - 0.654$ , all p < 0.001 $p < 0.001$ ). The AUC of D p e a k ${{D}_{peak}}$ for predicting MIB-1 LI levels was 0.900 (95% CI, 0.826-0.974), versus 0.781 (0.677-0.886) of ADC. The highest AUC of isocitrate dehydrogenase (IDH) mutation status, assessed by a logistic regression model ( f 1 + f 3 ${{f}_1} + {{f}_3}$ ) was 0.873 (95% CI, 0.802-0.944). CONCLUSION: The proposed FCN-MDD method was more robust to variations in SNR and less reliant on empirically set regularization values than the NNLS-MDD method. FCN-MDD also enabled qualitative and quantitative evaluation of the composition of gliomas.

Comparative Analysis of the Apparent Diffusion Coefficient and Diffusion Tensor Imaging in the Diagnosis of Prostate Cancer.

OBJECTIVE: The aim of this work was to demonstrate capabilities of diffusion tensor imaging as a diagnostic tool for prostate cancer in comparison with the apparent diffusion coefficient. METHODS: 364 patients with suspected prostate cancer underwent multiparametric magnetic resonance imaging including diffusion tensor imaging. RESULTS: The anatomical structure of the prostate obtained on T2-weighted imaging was compared with the apparent diffusion coefficient and diffusion tensor imaging maps. The rest of the gland (central and peripheral regions) were used as healthy areas. The apparent diffusion coefficient at diffusion-weighted imaging, fractional anisotropy and mean diffusivity at diffusion tensor imaging were evaluated in pathological zones. Cancer-suspicious areas of the prostate had high fractional anisotropy fractional anisotropy and low mean diffusivity compared to unaltered areas. Fractional anisotropy values were significantly elevated in central gland cancer, compared to normal tissue, and slightly elevated in peripheral zone cancer. CONCLUSION: Diffusion tensor imaging has the potential to identify prostate cancer with high accuracy and specificity. The combination of standard magnetic resonance imaging and diffusion tensor imaging can significantly improve the prognosis of the disease during active surveillance. The fractional anisotropy and mean diffusivity values can be useful in assessing the grade of malignancy and the radiolopathological correlation of the lesion.

Major brain injuries at term continue to influence DTI parameters in adolescents born very preterm: a 13-year follow-up study.

BACKGROUND: Major brain injuries in structural brain magnetic resonance imaging (MRI) at term affect concurrent diffusion tensor imaging (DTI) parameters in very preterm infants. White matter is known to gradually maturate along with increasing gestational age, which is characterized by increasing fractional anisotropy (FA) and decreasing mean diffusivity (MD). PURPOSE: To study the difference between DTI parameters at term and 13 years in adolescents born very preterm with and without major pathologies in structural brain MRI at term. MATERIAL AND METHODS: Adolescents born very preterm (gestational age <32 weeks and/or birth weight ≤1500 g) in 2004-2006 at Turku University Hospital, Finland were included. We evaluated FA and MD at term and 13 years in 18 regions of interest using the JHU-neonate-SS atlas to compare the differences in these parameters between adolescents with and without major injuries identified on MRI at term. RESULTS: A total of 24 adolescents underwent brain MRI including DTI both at term and 13 years. Adolescents with major brain injury pathologies (n = 6) in structural MRI at term had decreased FA in the left corpus callosum and right cingulate gyrus part, and increased MD in the left corpus callosum, right anterior limb of internal capsule, and right posterior limb of the internal capsule at 13 years, in comparison with adolescents without major brain injuries (n = 18) in structural MRI at term. CONCLUSION: Our findings suggest that major brain injuries identified on structural MRI at term affect brain maturation, with adverse effects in FA and MD still during adolescence.

Feasibility of diffusion tensor imaging in cervical spondylotic myelopathy using MUSE sequence.

BACKGROUND CONTEXT: The most frequent type of spinal cord injury is cervical spondylotic myelopathy (CSM). Conventional structural magnetic resonance imaging (MRI) is the gold diagnosis standard for CSM. Diffusion tensor imaging (DTI) could reflect microstructural changes in the spinal cord by tracing water molecular diffusion in early stages of CSM. However, due to the complex local anatomical structure and small field of view of the spinal cord, the imaging effect of traditional DTI imaging on the spinal cord is limited. MUSE (MUltiplexed Sensitivity-Encoding) -DTI is a novel diffusion-weighted imaging (DWI) sequence that achieves higher signal intensity through multiple excitation acquisition. MUSE sequence may improve the quality of spinal cord DTI imaging. STUDY DESIGN: Prospective study. PURPOSE: This study aimed to investigate the clinical diagnosis value of a novel protocol of MUSE-DTI in patients with cervical spondylotic myelopathy (CSM). PATIENT SAMPLE: From August 2021 to March 2022, a total of 60 subjects (22-71 years) were enrolled, including 51 CSM patients (22 males, 29 females) and 9 healthy subjects (4 males and 5 females). Each subject underwent a MUSE-DTI examination and a clinical Japanese Orthopedic Association (JOA) scale. OUTCOME MEASURES: We measured values of FA (Fractional Anisotropy), MD (Mean Diffusivity), AD (Axial Diffusivity), and RD (Radial Diffusivity), and collected the clinical JOA scores of each subject before the MR examination. METHODS: A 3.0T MR scanner (Signa Architect, GE Healthcare) performed the MUSE-DTI sequence on each subject. The cervical canal stenosis of subjects was classified from grade 0 to grade Ⅲ according to the method of an MRI grading system. FA, MD, AD, and RD maps were generated by postprocessing MUSE-DTI data on the GE workstation. Regions of interest (ROIs) were manually drawn at the C2 vertebral body level and C2/3-C6/7 intervertebral disc levels by covering the whole spinal cord. The clinical severity of myelopathy of subjects was assessed by the clinical Japanese Orthopedic Association scale (JOA). RESULTS: MUSE-DTI can acquire a high-resolution diffusion image compared to traditional DTI. The FAMCL values showed a decreasing trend from grade 0 to grade Ⅲ, while the MDMCL, ADMCL, and RDMCL values showed an overall increasing trend. Significant differences in MDMCL, ADMCL, and RDMCL values were found between adjacent groups among grades Ⅰ-Ⅲ (p<.05). The ADC2 values in CSM patients (grade I-Ⅲ) were significantly lower than in healthy individuals (grade 0) (p=.019). The clinical JOA score has a significant correlation with FAMCL (p=.035), MDMCL (p<.001), ADMCL (p<.001), and RDMCL (p<.001) values. CONCLUSIONS: MUSE-DTI displayed a better image quality compared to traditional DTI. MUSE-DTI parameters displayed a grade-dependent trend. All the MUSE-DTI parameters at MCL were correlated with the clinical JOA scores. The ADC2 values can reflect the secondary damage of distal spinal cord. Therefore, MUSE-DTI could be a reliable biomarker for clinical auxiliary diagnosis of spinal cord injury severity in cervical spondylotic myelopathy.

Diffusion tensor imaging within the healthy cervical spinal cord: Within- participants reliability and measurement error.

BACKGROUND: Diffusion tensor imaging (DTI) is a promising technique for the visualization of the cervical spinal cord (CSC) in vivo. It provides information about the tissue structure of axonal white matter, and it is thought to be more sensitive than other MR imaging techniques for the evaluation of damage to tracts in the spinal cord. AIM: The purpose of this study was to determine the within-participants reliability and error magnitude of measurements of DTI metrics in healthy human CSC. METHODS: A total of twenty healthy controls (10 male, mean age: 33.9 ± 3.5 years, 10 females, mean age: 47.5 ± 14.4 years), with no family history of any neurological disorders or a contraindication to MRI scanning were recruited over a period of two months. Each participant was scanned twice with an MRI 3 T scanner using standard DTI sequences. Spinal Cord Toolbox (SCT) software was used for image post-processing. Data were first corrected for motion artefact, then segmented, registered to a template, and then the DTI metrics were computed. The within-participants coefficients of variation (CV%), the single and average within-participants intraclass correlation coefficients (ICC) and Bland-Altman plots for WM, VC, DC and LC fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were determined for the cervical spinal cord (between the 2nd and 5th cervical vertebrae). RESULTS: DTI metrics showed poor to excellent within-participants reliability for both single and average ICC and moderate to high reproducibility for CV%, all variation dependent on the location of the ROI. The BA plots showed good within-participants agreement between the scan-rescan values. CONCLUSION: Results from this reliability study demonstrate that clinical trials using the DTI technique are feasible and that DTI, in particular regions of the cord is suitable for use for the monitoring of degenerative WM changes.

The bidirectional relationship between brain structure and physical activity: A longitudinal analysis in the UK Biobank.

Physical activity is a protective factor against brain atrophy, while loss of brain volume could also be a determinant of physical activity. Therefore, we aimed to explore the bidirectional association of physical activity with brain structures in middle-aged and older adults from the UK Biobank. Overall, 3027 participants (62.45 ± 7.27 years old, 51.3% females) had data at two time points. Hippocampal volume was associated with total (ß=0.048, pFDR=0.016) and household (ß=0.075, pFDR<0.001) physical activity. Global fractional anisotropy (ß=0.042, pFDR=0.028) was also associated with household physical activity. In the opposite direction, walking was negatively associated with white matter volume (ß=-0.026, pFDR=0.008). All these associations were confirmed by the linear mixed models. Interestingly, sports at baseline were linked to hippocampal and frontal cortex volumes at follow-up but these associations disappeared after adjusting for multiple comparisons (pall>0.104). In conclusion, we found more consistent evidence that a healthier brain structure predicted higher physical activity levels than for the inverse, more established relationship.

Cortical Macro- and Microstructural Changes in Parkinson's Disease with Probable Rapid Eye Movement Sleep Behavior Disorder.

BACKGROUND: Evidence regarding cortical atrophy patterns in Parkinson's disease (PD) with probable rapid eye movement sleep behavior disorder (RBD) (PD-pRBD) remains scarce. Cortical mean diffusivity (cMD), as a novel imaging biomarker highly sensitive to detecting cortical microstructural changes in different neurodegenerative diseases, has not been investigated in PD-pRBD yet. OBJECTIVES: The aim was to investigate cMD as a sensitive measure to identify subtle cortical microstructural changes in PD-pRBD and its relationship with cortical thickness (CTh). METHODS: Twenty-two PD-pRBD, 31 PD without probable RBD (PD-nonpRBD), and 28 healthy controls (HC) were assessed using 3D T1-weighted and diffusion-weighted magnetic resonance imaging on a 3-T scanner and neuropsychological testing. Measures of cortical brain changes were obtained through cMD and CTh. Two-class group comparisons of a general linear model were performed (P < 0.05). Cohen's d effect size for both approaches was computed. RESULTS: PD-pRBD patients showed higher cMD than PD-nonpRBD patients in the left superior temporal, superior frontal, and precentral gyri, precuneus cortex, as well as in the right middle frontal and postcentral gyri and paracentral lobule (d > 0.8), whereas CTh did not detect significant differences. PD-pRBD patients also showed increased bilateral posterior cMD in comparison with HCs (d > 0.8). These results partially overlapped with CTh results (0.5 < d < 0.8). PD-nonpRBD patients showed no differences in cMD when compared with HCs but showed cortical thinning in the left fusiform gyrus and lateral occipital cortex bilaterally (d > 0.5). CONCLUSIONS: cMD may be more sensitive than CTh displaying significant cortico-structural differences between PD subgroups, indicating this imaging biomarker's utility in studying early cortical changes in PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Associations between maternal pre-pregnancy BMI and infant striatal mean diffusivity.

BACKGROUND: It is well-established that parental obesity is a strong risk factor for offspring obesity. Further, a converging body of evidence now suggests that maternal weight profiles may affect the developing offspring's brain in a manner that confers future obesity risk. Here, we investigated how pre-pregnancy maternal weight status influences the reward-related striatal areas of the offspring's brain during in utero development. METHODS: We used diffusion tensor imaging to quantify the microstructure of the striatal brain regions of interest in neonates (N = 116 [66 males, 50 females], mean gestational weeks at birth [39.88], SD = 1.14; at scan [43.56], SD = 1.05). Linear regression was used to test the associations between maternal pre-pregnancy body mass index (BMI) and infant striatal mean diffusivity. RESULTS: High maternal pre-pregnancy BMI was associated with higher mean MD values in the infant's left caudate nucleus. Results remained unchanged after the adjustment for covariates. CONCLUSIONS: In utero exposure to maternal adiposity might have a growth-impairing impact on the mean diffusivity of the infant's left caudate nucleus. Considering the involvement of the caudate nucleus in regulating eating behavior and food-related reward processing later in life, this finding calls for further investigations to define the prognostic relevance of early-life caudate nucleus development and weight trajectories of the offspring.

Presenilin-1 mutation position influences amyloidosis, small vessel disease, and dementia with disease stage.

INTRODUCTION: Amyloidosis, including cerebral amyloid angiopathy, and markers of small vessel disease (SVD) vary across dominantly inherited Alzheimer's disease (DIAD) presenilin-1 (PSEN1) mutation carriers. We investigated how mutation position relative to codon 200 (pre-/postcodon 200) influences these pathologic features and dementia at different stages. METHODS: Individuals from families with known PSEN1 mutations (n = 393) underwent neuroimaging and clinical assessments. We cross-sectionally evaluated regional Pittsburgh compound B-positron emission tomography uptake, magnetic resonance imaging markers of SVD (diffusion tensor imaging-based white matter injury, white matter hyperintensity volumes, and microhemorrhages), and cognition. RESULTS: Postcodon 200 carriers had lower amyloid burden in all regions but worse markers of SVD and worse Clinical Dementia Rating® scores compared to precodon 200 carriers as a function of estimated years to symptom onset. Markers of SVD partially mediated the mutation position effects on clinical measures. DISCUSSION: We demonstrated the genotypic variability behind spatiotemporal amyloidosis, SVD, and clinical presentation in DIAD, which may inform patient prognosis and clinical trials. HIGHLIGHTS: Mutation position influences Aß burden, SVD, and dementia. PSEN1 pre-200 group had stronger associations between Aß burden and disease stage. PSEN1 post-200 group had stronger associations between SVD markers and disease stage. PSEN1 post-200 group had worse dementia score than pre-200 in late disease stage. Diffusion tensor imaging-based SVD markers mediated mutation position effects on dementia in the late stage.

Superficial white matter integrity in neuromyelitis optica spectrum disorder and multiple sclerosis.

Background: Superficial white matter (SWM) is a particularly vulnerable area of white matter adjacent to cerebral cortex that was shown to be a sensitive marker of disease severity in several neurological and psychiatric disorders, including multiple sclerosis (MS), but has not been studied in neuromyelitis optica spectrum disorder (NMOSD). Objective: To compare the integrity of SWM between MS patients, NMOSD patients and healthy controls, and explore the correlation of SWM integrity with cognitive performance and overall disability. Methods: Forty NMOSD patients, 48 MS patients and 52 healthy controls were included in the study. Mean diffusivity (MD) values obtained by diffusion tensor imaging were used as a measure of SWM integrity. Cognitive performance and overall disability were assessed with standardized tests. Results: Superficial white matter MD was increased in MS patients compared to healthy controls. Higher MD was associated with poorer spatial memory (most prominently in right temporal and right limbic lobe) and poorer information processing speed in MS patients. After adjusting for age, no significant differences of SWM MD were observed between NMOSD patients and healthy controls. Conclusion: Integrity of SWM is compromised in MS, but not in NMOSD, and can serve as a sensitive marker of disease severity.