scholarly journals 18F-AV1451 PET imaging and white matter changes in progressive supranuclear palsy

2019 ◽  
Author(s):  
Nicolas Nicastro ◽  
Patricia Vazquez Rodriguez ◽  
Maura Malpetti ◽  
William Richard Bevan-Jones ◽  
P. Simon Jones ◽  
...  

ABSTRACTIntroductionProgressive supranuclear palsy (PSP) is characterized by deposition of straight filament tau aggregates in the grey matter of deep nuclei and cerebellum. White matter changes are increasingly documented as a feature of degenerative parkinsonism. We therefore examined the relationship between tau pathology (assessed via 18F-AV1451 positron emission tomography) and white matter integrity (using diffusion tensor imaging, DTI) in PSP.MethodsTwenty-three people with clinically probable PSP-Richardson’s syndrome (age 68.8 ± 5.8 years, 39% female) and 23 controls underwent structural 3T brain MRI including DTI. Twenty-one patients also underwent 18F-AV145 PET imaging. DTI group comparisons were performed using Fractional Anisotropy (FA), Mean Diffusivity (MD) and Radial Diffusivity (RD). Voxel-wise white matter integrity was correlated with 18F-AV1451 binding in typical subcortical PSP regions of interest (i.e. putamen, pallidum, thalamus and midbrain). DTI and 18F-AV1451 imaging measures were correlated with clinical impairment.ResultsWidespread DTI changes in PSP subjects relative to controls (family-wise error FWE p<0.01) were observed. In PSP, higher 18F-AV1451 binding correlated with reduced white matter integrity in the bilateral internal capsule, corona radiata, and superior longitudinal fasciculus (FWE p<0.05). Association between cognitive impairment (ACER score) and white matter deficits were found in the genu of corpus callosum and cingulum (p<0.005).ConclusionThis cross-sectional study demonstrates an association between in vivo proxy measures of tau pathology and white matter degeneration in PSP. Longitudinal studies and more specific PET probes for non-Alzheimer tauopathies are warranted to assess the complex interplay between microstructural changes and protein deposition in PSP.

2021 ◽  
Vol 80 (2) ◽  
pp. 567-576
Author(s):  
Fei Han ◽  
Fei-Fei Zhai ◽  
Ming-Li Li ◽  
Li-Xin Zhou ◽  
Jun Ni ◽  
...  

Background: Mechanisms through which arterial stiffness impacts cognitive function are crucial for devising better strategies to prevent cognitive decline. Objective: To examine the associations of arterial stiffness with white matter integrity and cognition in community dwellings, and to investigate whether white matter injury was the intermediate of the associations between arterial stiffness and cognition. Methods: This study was a cross-sectional analysis on 952 subjects (aged 55.5±9.1 years) who underwent diffusion tensor imaging and measurement of brachial-ankle pulse wave velocity (baPWV). Both linear regression and tract-based spatial statistics were used to investigate the association between baPWV and white matter integrity. The association between baPWV and global cognitive function, measured as the mini-mental state examination (MMSE) was evaluated. Mediation analysis was performed to assess the influence of white matter integrity on the association of baPWV with MMSE. Results: Increased baPWV was significantly associated with lower mean global fractional anisotropy (β= –0.118, p < 0.001), higher mean diffusivity (β= 0.161, p < 0.001), axial diffusivity (β= 0.160, p < 0.001), and radial diffusivity (β= 0.147, p < 0.001) after adjustment of age, sex, and hypertension, which were measures having a direct effect on arterial stiffness and white matter integrity. After adjustment of age, sex, education, apolipoprotein E ɛ4, cardiovascular risk factors, and brain atrophy, we found an association of increased baPWV with worse performance on MMSE (β= –0.093, p = 0.011). White matter disruption partially mediated the effect of baPWV on MMSE. Conclusion: Arterial stiffness is associated with white matter disruption and cognitive decline. Reduced white matter integrity partially explained the effect of arterial stiffness on cognition.


2019 ◽  
Vol 267 (2) ◽  
pp. 341-349 ◽  
Author(s):  
Nicolas Nicastro ◽  
Patricia Vazquez Rodriguez ◽  
Maura Malpetti ◽  
William Richard Bevan-Jones ◽  
P. Simon Jones ◽  
...  

Abstract Objectives Progressive supranuclear palsy (PSP) is characterized by deposition of straight filament tau aggregates in the grey matter (GM) of deep nuclei and cerebellum. We examined the relationship between tau pathology (assessed via 18F-AV1451 PET) and multimodal MRI imaging using GM volume, cortical thickness (CTh), and diffusion tensor imaging (DTI). Methods Twenty-three people with clinically probable PSP-Richardson’s syndrome (age 68.8 ± 5.8 years, 39% female) and 23 controls underwent structural 3 T brain MRI including DTI. Twenty-one patients also had 18F-AV1451 PET imaging. Voxelwise volume-based morphometry, surface-based morphometry, and DTI correlations were performed with 18F-AV1451 binding in typical PSP regions of interest (putamen, thalamus and dentate cerebellum). Clinical impairment was also assessed in relation to the different imaging modalities. Results PSP subjects showed GM volume loss in frontotemporal regions, basal ganglia, midbrain, and cerebellum (FDR-corrected p < 0.05), reduced CTh in the left entorhinal and fusiform gyrus (p < 0.001) as well as DTI changes in the corpus callosum, internal capsule, and superior longitudinal fasciculus (FWE-corrected p < 0.05). In PSP, higher 18F-AV1451 binding correlated with GM volume loss in frontal regions, DTI changes in motor tracts, and cortical thinning in parietooccipital areas. Cognitive impairment was related to decreased GM volume in frontotemporal regions, thalamus and pallidum, as well as DTI alteration in corpus callosum and cingulum. Conclusion This cross-sectional study demonstrates an association between in vivo proxy measures of tau pathology and grey and white matter degeneration in PSP. This adds to the present literature about the complex interplay between structural changes and protein deposition.


2021 ◽  
Vol 13 ◽  
Author(s):  
Stephanie Matijevic ◽  
Lee Ryan

Well-established literature indicates that older adults have poorer cerebral white matter integrity, as measured through diffusion tensor imaging (DTI). Age differences in DTI have been observed widely across white matter, although some tracts appear more sensitive to the effects of aging than others. Factors like APOE ε4 status and sex may contribute to individual differences in white matter integrity that also selectively impact certain tracts, and could influence DTI changes in aging. The present study explored the degree to which age, APOE ε4, and sex exerted global vs. tract specific effects on DTI metrics in cognitively healthy late middle-aged to older adults. Data from 49 older adults (ages 54–92) at two time-points separated by approximately 2.7 years were collected. DTI metrics, including fractional anisotropy (FA) and mean diffusivity (MD), were extracted from nine white matter tracts and global white matter. Results showed that across timepoints, FA and MD increased globally, with no tract-specific changes observed. Baseline age had a global influence on both measures, with increasing age associated with lower FA and higher MD. After controlling for global white matter FA, age additionally predicted FA for the genu, callosum body, inferior fronto-occipital fasciculus (IFOF), and both anterior and posterior cingulum. Females exhibited lower global FA on average compared to males. In contrast, MD was selectively elevated in the anterior cingulum and superior longitudinal fasciculus (SLF), for females compared to males. APOE ε4 status was not predictive of either measure. In summary, these results indicate that age and sex are associated with both global and tract-specific alterations to DTI metrics among a healthy older adult cohort. Older women have poorer white matter integrity compared to older men, perhaps related to menopause-induced metabolic changes. While age-related alterations to white matter integrity are global, there is substantial variation in the degree to which tracts are impacted, possibly as a consequence of tract anatomical variability. The present study highlights the importance of accounting for global sources of variation in DTI metrics when attempting to investigate individual differences (due to age, sex, or other factors) in specific white matter tracts.


2021 ◽  
Vol 15 ◽  
Author(s):  
Ami Tsuchida ◽  
Alexandre Laurent ◽  
Fabrice Crivello ◽  
Laurent Petit ◽  
Antonietta Pepe ◽  
...  

Human brain white matter undergoes a protracted maturation that continues well into adulthood. Recent advances in diffusion-weighted imaging (DWI) methods allow detailed characterizations of the microstructural architecture of white matter, and they are increasingly utilized to study white matter changes during development and aging. However, relatively little is known about the late maturational changes in the microstructural architecture of white matter during post-adolescence. Here we report on regional changes in white matter volume and microstructure in young adults undergoing university-level education. As part of the MRi-Share multi-modal brain MRI database, multi-shell, high angular resolution DWI data were acquired in a unique sample of 1,713 university students aged 18–26. We assessed the age and sex dependence of diffusion metrics derived from diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) in the white matter regions as defined in the John Hopkins University (JHU) white matter labels atlas. We demonstrate that while regional white matter volume is relatively stable over the age range of our sample, the white matter microstructural properties show clear age-related variations. Globally, it is characterized by a robust increase in neurite density index (NDI), and to a lesser extent, orientation dispersion index (ODI). These changes are accompanied by a decrease in diffusivity. In contrast, there is minimal age-related variation in fractional anisotropy. There are regional variations in these microstructural changes: some tracts, most notably cingulum bundles, show a strong age-related increase in NDI coupled with decreases in radial and mean diffusivity, while others, mainly cortico-spinal projection tracts, primarily show an ODI increase and axial diffusivity decrease. These age-related variations are not different between males and females, but males show higher NDI and ODI and lower diffusivity than females across many tracts. These findings emphasize the complexity of changes in white matter structure occurring in this critical period of late maturation in early adulthood.


Neurology ◽  
2019 ◽  
Vol 92 (19) ◽  
pp. e2221-e2231 ◽  
Author(s):  
Pauline Maillard ◽  
Evan Fletcher ◽  
Baljeet Singh ◽  
Oliver Martinez ◽  
David K. Johnson ◽  
...  

ObjectiveTo determine whether free water (FW) content, initially developed to correct metrics derived from diffusion tensor imaging and recently found to be strongly associated with vascular risk factors, may constitute a sensitive biomarker of white matter (WM) microstructural differences associated with cognitive performance but remains unknown.MethodsFive hundred thirty-six cognitively diverse individuals, aged 77 ± 8 years, received yearly comprehensive clinical evaluations and a baseline MRI examination of whom 224 underwent follow-up MRI. WM microstructural measures, including FW, fractional anisotropy, and mean diffusivity corrected for FW and WM hyperintensity burden were computed within WM voxels of each individual. Baseline and change in MRI metrics were then used as independent variables to explain baseline and change in episodic memory (EM), executive function (EF), and Clinical Dementia Rating (CDR) scores using linear, logistic, and Cox proportional-hazards regressions.ResultsHigher baseline FW and WM hyperintensity were associated with lower baseline EM and EF, higher baseline CDR, accelerated EF and EM decline, and higher probability to transition to a more severe CDR stage (p values <0.01). Annual change in FW was also found to be associated with concomitant change in cognitive and functional performance (p values <0.01).ConclusionsThis study finds cross-sectional and longitudinal associations between FW content and trajectory of cognitive and functional performance in a large sample of cognitively diverse individuals. It supports the need to investigate the pathophysiologic process that manifests increased FW, potentially leading to more severe WM territory injury and promoting cognitive and functional decline.


2021 ◽  
Author(s):  
Yiming Xiao ◽  
Terry M. Peters ◽  
Ali R. Khan

AbstractParkinson’s disease (PD) is a progressive neurodegenerative disorder that is characterized by a range of motor and non-motor symptoms, often with the motor dysfunction initiated unilaterally. Knowledge regarding disease-related alterations in white matter pathways can effectively help improve the understanding of the disease and propose targeted treatment strategies. Microstructural imaging techniques, including diffusion tensor imaging (DTI), allows inspection of white matter integrity to study the pathogenesis of various neurological conditions. Previous voxel-based analyses with DTI measures, such as fractional anisotropy and mean diffusivity have uncovered changes in brain regions that are associated with PD, but the conclusions were inconsistent, partially due to small patient cohorts and the lack of consideration for clinical laterality onset, particularly in early PD. Fixel-based analysis (FBA) is a recent framework that offers tract-specific insights regarding white matter health, but very few FBA studies on PD exist. We present a study that reveals strengthened and weakened white matter integrity that is subject to symptom laterality in a large drug-naïve de novo PD cohort using complementary DTI and FBA measures. The findings suggest that the disease gives rise to both functional degeneration and the creation of compensatory networks in the early stage.


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Kyle C Kern ◽  
Clinton B Wright ◽  
Richard Leigh

Background: Stroke causes focal and diffuse structural brain changes that may contribute to subsequent cognitive decline and dementia. We hypothesize that MRI structural measures can detect continued cerebral degeneration over the first year after stroke. We identify predictors for progression of brain atrophy, leukoaraiosis and diffusion tensor imaging (DTI) metrics. Methods: Patients with ischemic stroke were enrolled prospectively in an observational study that included serial brain MRI. Patients underwent MRI FLAIR and DTI at the time of acute stroke and were followed for at least 9 months with multiple MRIs between 30 days and 15 months post-stroke. We used FLAIR to measure brain atrophy as the percent brain parenchymal fraction (BPF) of the total intracranial volume (TICV) and white matter hyperintensity volume (WMHV) as a percentage of TICV. DTI was used to calculate Peak Skeletonized Mean Diffusivity (PSMD), a global measure of white matter integrity previously validated in cerebral small vessel disease. Longitudinal changes in BPF, WMHV or PSMD were measured from 30 days post-stroke onward using linear regression models that included age, stroke volume, baseline BPF and WMHV as predictors. Results: Twenty-six patients had a median of 4 follow-ups over 9-15 months. Median age was 74 years (range 51-84) and 38% were women. Mean stroke volume was 4.5cc (0 - 30cc). Mean BPF was 78% (72 - 86%) and mean baseline WMHV was 1.1% (0.1 - 3.9%). BPF was associated with age and declined by 0.7% per year (t(111) = 2.7, p = 0.007). Progression was associated with baseline BPF (t(111) = -3.4, p < 0.001). WMHV in the non-stroke hemisphere was associated with age and increased by 0.10% per year (t(87) = -5.8, p < 0.001). Accumulation was associated with age (t(87) = 5.8, p < 0.001). PSMD was associated with baseline WMHV and had a relative increase of 1.9% per year in the non-stroke hemisphere and 4.5% in the stroke hemisphere (t(174) = -2.1, p = 0.03). Progression was associated with age (t(174) = 2.3, p = 0.03) and stroke volume (t(174) = 2.4, p = 0.02). Conclusions: During the months after ischemic stroke, BPF, WMHV and PSMD can detect persistent structural changes that may reflect later phases of stroke injury or ongoing contributions of aging, silent ischemia, or neurodegeneration.


2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S249-S250
Author(s):  
Seda Arslan ◽  
Tuba Şahin ◽  
Didenur Şahin ◽  
Timothea Toulopoulou

Abstract Background Psychotic disorders are characterized by neurobiological deviations, including in the macro and microstructure of white matter. White matter alterations are also seen in psychosis-proneness and in individuals who have a high risk of psychosis. For example, studies have indicated decreases in white matter integrity in the genu/forceps minor of corpus callosum (CC) in the latter populations. Anterior corona radiata (ACR) is one crucial white-matter tract connecting the anterior cingulate cortex to the striatum. Indeed, reductions in the white matter structure of anterior genu of CC significantly predict the transition from ultra-high risk to psychosis. However, there is a gap in the literature related to observing the psychosis-proneness by applying both micro and macrostructural brain analyses, and most of the microstructural white matter studies in psychosis focus on fractional anisotropy (FA) and not include mean diffusivity (MD). Thus, the current study aims to assess whether white matter deviations in CG, ACR, and CC, are associated with psychosis proneness by combining both tract-based spatial statistics (TBSS) and voxel-based morphometry (VBM) analyses in a sample of participants with psychosis proneness (PP) and without psychosis proneness (NPP). Methods The study included 53 participants (29 PP vs. 24 NPP) whose ages were between 17 and 24 years. Participants were split into two groups based on their scores on Structured Interview for Schizotypy assessment, a well-validated instrument of psychosis proneness. White matter integrity was analyzed via diffusion tensor imaging (DTI) and white matter volume (WMV) via VBM. Two sample t-test was used in GLM for both DTI and VBM analyses. FA, MD, and VMV were compared between two groups to observe micro and macro white matter structure alterations in the region of interest. Results DTI analysis revealed decreased FA values in the right ACR and right genu of the CC in the psychosis-proneness group (F(1,52)= 7.37, p= 0.009). Moreover, VBM showed a significant WMV decreases in the right CG, Brodmann areas 8, 9, and 32 in the PP group (F(1,52)= 50.85, uncorrected p&lt;0.01). However, MD did not differ between the two groups (F(1,51)= 3.65, p=0.06) Discussion These findings suggest that PP associated with decreased white matter integrity in ACR, genu of CC, and also reduced white matter volumes in the right CG, Brodmann areas 8, 9, and 32. Significant FA decreases might result from alterations in radial or axial diffusivity since we did not observe significant MD differences between two groups. The current findings suggested that participants with PP had both macro and micro white matter structure disruptions, mostly in frontal parts of the right cerebrum, compared to no PP group.


2013 ◽  
Vol 19 (8) ◽  
pp. 925-937 ◽  
Author(s):  
Nikki H. Stricker ◽  
David H. Salat ◽  
Jessica M. Foley ◽  
Tyler A. Zink ◽  
Ida L. Kellison ◽  
...  

AbstractImproved understanding of the pattern of white matter changes in early and prodromal Alzheimer's disease (AD) states such as mild cognitive impairment (MCI) is necessary to support earlier preclinical detection of AD, and debate remains whether white matter changes in MCI are secondary to gray matter changes. We applied neuropsychologically based MCI criteria to a sample of normally aging older adults; 32 participants met criteria for MCI and 81 participants were classified as normal control (NC) subjects. Whole-head high resolution T1 and diffusion tensor imaging scans were completed. Tract-Based Spatial Statistics was applied and a priori selected regions of interest were extracted. Hippocampal volume and cortical thickness averaged across regions with known vulnerability to AD were derived. Controlling for cortical thickness, the MCI group showed decreased average fractional anisotropy (FA) and decreased FA in parietal white matter and in white matter underlying the entorhinal and posterior cingulate cortices relative to the NC group. Statistically controlling for cortical thickness, medial temporal FA was related to memory and parietal FA was related to executive functioning. These results provide further support for the potential role of white matter integrity as an early biomarker for individuals at risk for AD and highlight that changes in white matter may be independent of gray matter changes. (JINS, 2013, 19, 1–13)


2020 ◽  
Vol 35 (1) ◽  
pp. 44-57
Author(s):  
Yi Zhao ◽  
Bronte Ficek ◽  
Kimberly Webster ◽  
Constantine Frangakis ◽  
Brian Caffo ◽  
...  

Background Transcranial direct current stimulation (tDCS), in conjunction with language therapy, improves language therapy outcomes in primary progressive aphasia (PPA). However, no studies show whether white matter integrity predicts language therapy or tDCS effects in PPA. Objective We aimed to determine whether white matter integrity, measured by diffusion tensor imaging (DTI), predicts written naming/spelling language therapy effects (letter accuracy on trained and untrained words) with and without tDCS over the left inferior frontal gyrus (IFG) in PPA. Methods Thirty-nine participants with PPA were randomly assigned to tDCS or sham condition, coupled with language therapy for 15 daily sessions. White matter integrity was measured by mean diffusivity (MD) and fractional anisotropy (FA) in DTI scans before therapy. Written naming outcomes were evaluated before, immediately after, 2 weeks, and 2 months posttherapy. To assess tDCS treatment effect, we used a mixed-effects model with treatment evaluation and time interaction. We considered a forward model selection approach to identify brain regions/fasciculi of which white matter integrity can predict improvement in performance of word naming. Results Both sham and tDCS groups significantly improved in trained items immediately after and at 2 months posttherapy. Improvement in the tDCS group was greater and generalized to untrained words. White matter integrity of ventral language pathways predicted tDCS effects in trained items whereas white matter integrity of dorsal language pathways predicted tDCS effects in untrained items. Conclusions White matter integrity influences both language therapy and tDCS effects. Thus, it holds promise as a biomarker for deciding which patients will benefit from language therapy and tDCS.


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