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David R. Jacobs

Possible papers associated with this exact author name in Arrow. This page groups case-insensitive exact name matches and is not a full identity disambiguation profile.

4 papers

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YNICL Journal 2025 Journal Article

Spatial and signal features of white matter integrity and associations with clinical factors: A CARDIA brain MRI study

Faezeh Vedaei
Dhivya Srinivasan
Drew Parker
Guray Erus
Sudipto Dolui
Farzaneh A. Sorond
David R. Jacobs
Lenore J. Launer

White matter hyperintensities (WMH) may be indicative of age-related cerebrovascular diseases and contribute to cognitive and functional decline. Normal appearing WM (NAWM) adjacent to WMH, termed "penumbra," is known to be vulnerable to future WMH pathology. WM integrity can be evaluated using multiple magnetic resonance imaging (MRI) modalities. We aimed to identify MRI features predictive of WMH growth and to compare the implications of these features based on spatial proximity to existing WMH versus signal features in baseline NAWM. We used baseline and 5-year follow-up MRI scans in 485 middle-aged participants form the Coronary Artery Risk Development in Young Adults (CARDIA). Multimodal MRI at baseline, including fluid attenuated inversion recovery (FLAIR), diffusion tensor imaging (DTI), and cerebral blood flow (CBF), was measured within WM ROIs including baseline WMH and regions that later developed into new WMH, within and external to the baseline penumbra. Overall, we found that 80% of new WMH appeared within the baseline penumbra. We also found lower fractional anisotropy (FA) and CBF and higher FLAIR and median diffusivity (MD) in NAWM at baseline in regions with subsequent WMH growth compared to those without WMH growth. For NAWM regions defined by signal features, subthreshold FA and suprathreshold MD and FLAIR abnormality at baseline were the most robust predictors of WMH growth. Baseline systolic blood pressure had significant associations with baseline abnormalities in NAWM and subsequently with cognitive decline, particularly for FA and MD measures. The findings support the use of DTI as the predictor of WMH growth, which is correlated with subtle, adverse WM alterations and cognitive function years before developing to WMH. The results may contribute to future clinical trials aimed at preserving WM integrity.

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YNICL Journal 2019 Journal Article

Characterizing a perfusion-based periventricular small vessel region of interest

Sudipto Dolui
Dylan Tisdall
Marta Vidorreta
David R. Jacobs
Ilya M. Nasrallah
R. Nick Bryan
David A. Wolk
John A. Detre

The periventricular white matter (PVWM) is supplied by terminal distributions of small vessels and is particularly susceptible to developing white matter lesions (WML) associated with cerebral small vessel disease (CSVD). We obtained group-averaged cerebral blood flow (CBF) maps from Arterial Spin Labeled (ASL) perfusion MRI data obtained in 436 middle-aged (50.4 ± 3.5 years) subjects in the NHLBI CARDIA study and in 61 elderly (73.3 ± 6.9 years) cognitively normal subjects recruited from the Penn Alzheimer's Disease Center (ADC) and found that the lowest perfused brain voxels are located within the PVWM. We constructed a white matter periventricular small vessel (PSV) region of interest (ROI) by empirically thresholding the group averaged CARDIA CBF map at CBF < 15 ml/100 g/min. Thereafter we compared CBF in the PSV ROI and in the remaining white matter (RWM) with the location and volume of WML measured with Fluid Attenuated Inversion Recovery (FLAIR) MRI. WM CBF was lower within WML than outside WML voxels (p < <0.0001) in both the PSV and RWM ROIs, however this difference was much smaller (p < <0.0001) in the PSV ROI than in the RWM suggesting a more homogenous reduction of CBF in the PSV region. Normalized WML volumes were significantly higher in the PSV ROI than in the RWM and in the elderly cohort as compared to the middle-aged cohort (p < <0.0001). Additionally, the PSV ROI showed a significantly (p = .001) greater increase in lesion volume than the RWM in the elderly ADC cohort than the younger CARDIA cohort. Considerable intersubject variability in PSV CBF observed in both study cohorts likely represents biological variability that may be predictive of future WML and/or cognitive decline. In conclusion, a data-driven PSV ROI defined by voxels with low perfusion in middle age defines a region with homogeneously reduced CBF that is particularly susceptible to progressive ischemic injury in elderly controls. PSV CBF may provide a mechanistically specific biomarker of CSVD.

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YNICL Journal 2018 Journal Article

White matter microstructure, white matter lesions, and hypertension: An examination of early surrogate markers of vascular-related brain change in midlife

Thaddeus Haight
R. Nick Bryan
Guray Erus
Meng-Kang Hsieh
Christos Davatzikos
Ilya Nasrallah
Mark D'Esposito
David R. Jacobs

Objective: We examined imaging surrogates of white matter microstructural abnormalities which may precede white matter lesions (WML) and represent a relevant marker of cerebrovascular injury in adults in midlife. Methods: In 698 community-dwelling adults (mean age 50 years ±3.5 SD) from the Coronary Artery Risk Development in Young Adults (CARDIA) Brain MRI sub-study, WML were identified on structural MR and fractional anisotropy (FA), representing WM microstructural integrity, was derived using Diffusion Tensor Imaging. FA and WML maps were overlaid on a parcellated T1-template, based on an expert-delineated brain atlas, which included 42 WM tract ROIs. Analyses occurred in stages: 1) WML were quantified for the different tracts (i.e., frequency, volume, volume relative to tract size); 2) the interdependence of FA in normal appearing WM (NAWM) and WML was examined across tracts; 3) associations of NAWM FA and hypertension status were assessed controlling for WML volume. In the latter analysis, both overall hypertension (i.e. hypertension vs. normotension and prehypertension vs. normotension) and hypertension categorized by antihypertensive treatment status (yes/no) and blood pressure control (e.g., diastolic <90 mmHg, systolic <140 mmHg), were assessed. Results: WML were widely distributed across different WM tracts, however, WML volume was small. Mean NAWM FA was lower in participants with vs. participants without WML in given tracts. Hypertension was significantly associated with lower mean NAWM FA globally across tracts, both before and after adjustment for WML volume. Moreover, the magnitude of this association differed by treatment status and the level of control of the hypertension. Conclusions: In middle-aged adults, NAWM FA could represent a relevant marker of cerebrovascular injury when WML are minimally present.

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YNIMG Journal 2015 Journal Article

Vascular risk factors, cerebrovascular reactivity, and the default-mode brain network

Thaddeus J. Haight
R. Nick Bryan
Guray Erus
Christos Davatzikos
David R. Jacobs
Mark D'Esposito
Cora E. Lewis
Lenore J. Launer

Cumulating evidence from epidemiologic studies implicates cardiovascular health and cerebrovascular function in several brain diseases in late life. We examined vascular risk factors with respect to a cerebrovascular measure of brain functioning in subjects in mid-life, which could represent a marker of brain changes in later life. Breath-hold functional MRI (fMRI) was performed in 541 women and men (mean age 50. 4years) from the Coronary Artery Risk Development in Young Adults (CARDIA) Brain MRI sub-study. Cerebrovascular reactivity (CVR) was quantified as percentage change in blood-oxygen level dependent (BOLD) signal in activated voxels, which was mapped to a common brain template and log-transformed. Mean CVR was calculated for anatomic regions underlying the default-mode network (DMN) – a network implicated in AD and other brain disorders – in addition to areas considered to be relatively spared in the disease (e. g. occipital lobe), which were utilized as reference regions. Mean CVR was significantly reduced in the posterior cingulate/precuneus (β=−0. 063, 95% CI: −0. 106, −0. 020), anterior cingulate (β=−0. 055, 95% CI: −0. 101, −0. 010), and medial frontal lobe (β=−0. 050, 95% CI: −0. 092, −0. 008) relative to mean CVR in the occipital lobe, after adjustment for age, sex, race, education, and smoking status, in subjects with pre-hypertension/hypertension compared to normotensive subjects. By contrast, mean CVR was lower, but not significantly, in the inferior parietal lobe (β=−0. 024, 95% CI: −0. 062, 0. 014) and the hippocampus (β=−0. 006, 95% CI: −0. 062, 0. 050) relative to mean CVR in the occipital lobe. Similar results were observed in subjects with diabetes and dyslipidemia compared to those without these conditions, though the differences were non-significant. Reduced CVR may represent diminished vascular functionality for the DMN for individuals with prehypertension/hypertension in mid-life, and may serve as a preclinical marker for brain dysfunction in later life.

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