Instrumental validation of free water, peak‐width of skeletonized mean diffusivity, and white matter hyperintensities: MarkVCID neuroimaging kits

Maillard, Pauline; Lu, Hanzhang; Arfanakis, Konstantinos; Gold, Brian T.; Bauer, Christopher E.; Zachariou, Valentinos; Stables, Lara; Wang, Danny J.J.; Jann, Kay; Seshadri, Sudha; Duering, Marco; Hillmer, Laura J.; Rosenberg, Gary A.; Snoussi, Haykel; Sepehrband, Farshid; Habes, Mohamad; Singh, Baljeet; Kramer, Joel H.; Corriveau, Roderick A.; Singh, Herpreet; Schwab, Kristin; Helmer, Karl G.; Greenberg, Steven M.; Caprihan, Arvind; DeCarli, Charles

doi:10.1002/dad2.12261

Cited by 39 publications

(60 citation statements)

References 37 publications

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“…However, in our study FW was not associated with working memory performance even when it was entered as a sole model predictor ( Supplementary Table 5 ). Free water quantifies highly isotropic diffusion, which is thought to primarily reflect extracellular water content ( Pasternak et al, 2009 , 2012 ; Maillard et al, 2019 , 2022 ). Recent MRI studies further suggest that FW may be a biomarker of global cerebral injury, as elevated FW is associated with a variety of conditions including schizophrenia ( Pasternak et al, 2015 ; Lyall et al, 2018 ), Alzheimer’s disease ( Ji et al, 2017 ; Bergamino et al, 2021 ), Parkinson’s disease ( Ofori et al, 2015 ; Planetta et al, 2016 ), and cerebral small vessel disease/vascular pathology ( Ji et al, 2017 ; Maillard et al, 2017 , 2019 ; Duering et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…Strengths of our study include the mapping of the white matter connections between fMRI-defined working memory network regions using probabilistic tractography, the use of advanced multi-compartment modeling enabled by multi-shell diffusion imaging, and the consideration of previously validated diffusion metrics ( Chang et al, 2015 ; Albi et al, 2017 ; Lehmann et al, 2021 ; Maillard et al, 2022 ) as predictors of age and cognition. Of particular note, in contrast to most published studies, multiple diffusion metrics were included in the same linear regression models when appropriate (Model 2: FWE-FA and FW; Model 3: ICVF, ODI, and CSF Fraction) to account for shared variance between predictors.…”

Section: Discussionmentioning

confidence: 99%

“…These limitations have led to the development of multi-compartment models that make use of multiple diffusion weightings to separate the diffusion signal into tract-related and free water [or cerebrospinal fluid (CSF)] compartments ( Pasternak et al, 2009 ). Two compartment, free water elimination (FWE) models can yield metrics of free water (FW) and the more white matter tract-related metric of free water eliminated FA (FWE-FA) ( Ji et al, 2017 ; Duering et al, 2018 ; Maillard et al, 2019 , 2022 ; Bergamino et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

“…Results from these studies have suggested that metrics derived from multi-compartment models may be more sensitive predictors of age ( Billiet et al, 2015 ; Cox et al, 2016 ; Kodiweera et al, 2016 ; Chad et al, 2018 ; Beck et al, 2021 ) and/or cognitive performance in older adults ( Merluzzi et al, 2016 ; Ji et al, 2017 ; Duering et al, 2018 ; Maillard et al, 2019 ; Fu et al, 2020 ). Notably, most studies have focused on white matter across the brain ( Ji et al, 2017 ; Chad et al, 2018 ; Duering et al, 2018 ; Maillard et al, 2019 , 2022 ; Beck et al, 2021 ) and/or explored individual white matter tracts that form portions of multiple cognitive networks ( Cox et al, 2016 ; Ji et al, 2017 ; Chad et al, 2018 ; Beck et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Multi-compartment diffusion magnetic resonance imaging models link tract-related characteristics with working memory performance in healthy older adults

Bauer

Zachariou²,

Maillard³

et al. 2022

Front. Aging Neurosci.

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Multi-compartment diffusion MRI metrics [such as metrics from free water elimination diffusion tensor imaging (FWE-DTI) and neurite orientation dispersion and density imaging (NODDI)] may reflect more specific underlying white-matter tract characteristics than traditional, single-compartment metrics [i.e., metrics from Diffusion Tensor Imaging (DTI)]. However, it remains unclear if multi-compartment metrics are more closely associated with age and/or cognitive performance than single-compartment metrics. Here we compared the associations of single-compartment [Fractional Anisotropy (FA)] and multi-compartment diffusion MRI metrics [FWE-DTI metrics: Free Water Eliminated Fractional Anisotropy (FWE-FA) and Free Water (FW); NODDI metrics: Intracellular Volume Fraction (ICVF), Orientation Dispersion Index (ODI), and CSF-Fraction] with both age and working memory performance. A functional magnetic resonance imaging (fMRI) guided, white matter tractography approach was employed to compute diffusion metrics within a network of tracts connecting functional regions involved in working memory. Ninety-nine healthy older adults (aged 60–85) performed an in-scanner working memory task while fMRI was performed and also underwent multi-shell diffusion acquisition. The network of white matter tracts connecting functionally-activated regions was identified using probabilistic tractography. Diffusion metrics were extracted from skeletonized white matter tracts connecting fMRI activation peaks. Diffusion metrics derived from both single and multi-compartment models were associated with age (ps ≤ 0.011 for FA, FWE-FA, ICVF and ODI). However, only multi-compartment metrics, specifically FWE-FA (p = 0.045) and ICVF (p = 0.020), were associated with working memory performance. Our results suggest that while most current diffusion metrics are sensitive to age, several multi-compartment metrics (i.e., FWE-FA and ICVF) appear more sensitive to cognitive performance in healthy older adults.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Multi-compartment diffusion magnetic resonance imaging models link tract-related characteristics with working memory performance in healthy older adults

Bauer

Zachariou²,

Maillard³

et al. 2022

Front. Aging Neurosci.

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“…Image analyses were performed at the Imaging of Dementia and Aging (IDeA) laboratory at UC Davis, using established pipelines. 44 All images were analyzed by operators blinded to all participant characteristics, including cognitive performance on neuropsychological testing. Peak width of skeletonized mean diffusivity (PSMD) is a novel and fully automated MRI biomarker, which has shown clinical relevance in SVD, an essential contributor to VCI.…”

Section: Methodsmentioning

confidence: 99%

Cerebral Small Vessel Disease Burden is Associated with Decreased Abundance of Gut Barnesiella intestinihominis Bacterium in the Framingham Heart Study

Fongang

Kautz

Ngouongo³

et al. 2022

Preprint

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A bidirectional communication exists between the brain and the gut, in which the gut microbiota influences cognitive function and vice-versa. Gut dysbiosis has been linked to several diseases, including Alzheimer's disease and related dementias (ADRD). However, the relationship between gut dysbiosis and markers of cerebral small vessel disease (cSVD), a major contributor to ADRD, is unknown. In this cross-sectional study, we examined the connection between the gut microbiome, cognitive, and neuroimaging markers of cSVD in the Framingham Heart Study (FHS). Markers of cSVD included white matter hyperintensities (WMH), peak width of skeletonized mean diffusivity (PSMD), and executive function (EF), estimated as the difference between the trail-making tests B and A. We included 972 FHS participants with MRI scans, neurocognitive measures, and stool samples and quantified the gut microbiota composition using 16S rRNA sequencing. We used multivariable association and differential abundance analyses adjusting for age, sex, BMI, and education level to estimate the association between gut microbiota and WMH, PSMD, and EF measures. Our results suggest an increased abundance of Pseudobutyrivibrio and Ruminococcus genera was associated with lower WMH and PSMD (p-values < 0.001), as well as better executive function (p-values < 0.01). In addition, in both differential and multivariable analyses, we found that the gram-negative bacterium Barnesiella intestinihominis was strongly associated with markers indicating a higher cSVD burden. Finally, functional analyses using PICRUSt implicated various KEGG pathways, including microbial quorum sensing, AMP/GMP-activated protein kinase, phenylpyruvate, and β-hydroxybutyrate production previously associated with cognitive performance and dementia. Our study provides important insights into the association between the gut microbiome and cSVD, but further studies are needed to replicate the findings.

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Association of Early Adulthood Hypertension and Blood Pressure Change With Late-Life Neuroimaging Biomarkers

et al. 2023

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ImportanceThe association between hypertension developed before midlife and late-life brain health is understudied and, because of the cardioprotective benefits of estrogen before menopause, may differ by sex.ObjectiveTo assess the association of early adulthood hypertension and blood pressure (BP) change with late-life neuroimaging biomarkers and examine potential sex differences.Design, Setting, and ParticipantsThis cohort study used data from the Study of Healthy Aging in African Americans (STAR) and Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study, which were harmonized longitudinal cohorts of racially and ethnically diverse adults aged 50 years and older from the San Francisco Bay area and Sacramento Valley in California. The STAR was conducted from November 6, 2017, to November 5, 2021, and the KHANDLE study was conducted from April 27, 2017, to June 15, 2021. The current study included 427 participants from the KHANDLE and STAR studies who received health assessments between June 1, 1964, and March 31, 1985. Regional brain volumes and white matter (WM) integrity were measured via magnetic resonance imaging between June 1, 2017, and March 1, 2022.ExposuresHypertension status (normotension, transition to hypertension, and hypertension) and BP change (last measure minus first measure) were assessed at 2 multiphasic health checkups (MHCs; 1964-1985) in early adulthood (ages 30-40 years).Main Outcomes and MeasuresRegional brain volumes and WM integrity were measured using 3T magnetic resonance imaging and z standardized. General linear models adjusted for potential confounders (demographic characteristics and study [KHANDLE or STAR]) were used to assess the association of hypertension and BP change with neuroimaging biomarkers. Sex interactions were tested.ResultsAmong 427 participants, median (SD) ages were 28.9 (7.3) years at the first MHC, 40.3 (9.4) years at the last MHC, and 74.8 (8.0) years at neuroimaging. A total of 263 participants (61.6%) were female and 231 (54.1%) were Black. Overall, 191 participants (44.7%) had normotension, 68 (15.9%) transitioned to hypertension, and 168 (39.3%) had hypertension. Compared with participants who had normotension, those who had hypertension and those who transitioned to hypertension had smaller cerebral volumes (hypertension: β = −0.26 [95% CI, −0.41 to −0.10]; transition to hypertension: β = −0.23 [95% CI, −0.44 to −0.23]), with similar differences in cerebral gray matter volume (hypertension: β = −0.32 [95% CI, −0.52 to −0.13]; transition to hypertension: β = −0.30 [95% CI, −0.56 to −0.05]), frontal cortex volume (hypertension: β = −0.43 [95% CI, −0.63 to −0.23]; transition to hypertension: β = −0.27 [95% CI, −0.53 to 0]), and parietal cortex volume (hypertension: β = −0.22 [95% CI, −0.42 to −0.02]; transition to hypertension: β = −0.29 [95% CI, −0.56 to −0.02]). Participants with hypertension also had smaller hippocampal volume (β = −0.22; 95% CI, −0.42 to −0.02), greater ventricular volumes (lateral ventricle: β = 0.44 [95% CI, 0.25-0.63]; third ventricle: β = 0.20 [95% CI, 0.01-0.39]), larger free water volume (β = 0.35; 95% CI, 0.18-0.52), and lower fractional anisotropy (β = −0.26; 95% CI, −0.45 to −0.08) than those who had normotension. Holding hypertension status constant, a 5-mm Hg increase in systolic BP was associated with smaller temporal cortex volume (β = −0.03; 95% CI, −0.06 to −0.01), while a 5-mm Hg increase in diastolic BP was associated with smaller parietal cortex volume (β = −0.06; 95% CI, −0.10 to −0.02). The negative association of hypertension and BP change with regional brain volumes appeared stronger in men than women for some regions.Conclusions and RelevanceIn this cohort study, early adulthood hypertension and BP change were associated with late-life volumetric and WM differences implicated in neurodegeneration and dementia. Sex differences were observed for some brain regions whereby hypertension and increasing BP appeared more detrimental for men. These findings suggest that prevention and treatment of hypertension in early adulthood is important for late-life brain health, particularly among men.

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Instrumental validation of free water, peak‐width of skeletonized mean diffusivity, and white matter hyperintensities: MarkVCID neuroimaging kits

Cited by 39 publications

References 37 publications

Multi-compartment diffusion magnetic resonance imaging models link tract-related characteristics with working memory performance in healthy older adults

Multi-compartment diffusion magnetic resonance imaging models link tract-related characteristics with working memory performance in healthy older adults

Cerebral Small Vessel Disease Burden is Associated with Decreased Abundance of Gut Barnesiella intestinihominis Bacterium in the Framingham Heart Study

Association of Early Adulthood Hypertension and Blood Pressure Change With Late-Life Neuroimaging Biomarkers

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