Abstract P59: Peak Width of Skeletonized Mean Diffusivity Outperforms Other Diffusion Tensor Imaging Metrics as Biomarker for Cognition in Memory-Clinic Subjects With Cerebral Amyloid Angiopathy

Introduction: Peak width of skeletonized mean diffusivity (PSMD) is a novel fully automated diffusion tensor imaging (DTI) marker that has been consistently associated with cognition in cerebral small vessel disease (SVD) cohorts, including cerebral amyloid angiopathy (CAA). We hypothesized that PSMD would be more strongly associated with cognitive performance compared to other conventional DTI metrics in our CAA sample. Methods: We recruited non-demented subjects with probable-CAA from a single-center memory-clinic cohort. We analyzed structural MRIs to compute a validated CAA burden score (0-6 points scale, based on the following MRI features: lobar microbleeds, superficial siderosis, perivascular spaces in centrum semiovale, and white matter hyperintensities). PSMD was obtained using a freely available script ( www.psmd-marker.com ). We used the same skeleton-mask to compute: mean of skeletonized mean diffusivity (mean MD) and mean of skeletonized fractional anisotropy (mean FA). We used linear regression analyses to explore relationships with CAA burden score and cognitive composite scores (processing speed, executive function, memory, and language - z-scores adjusted for age, sex and education level). Results: We included 43 subjects (mean age 74.4 ± 5.9 years; 48.8% female; PSMD median [IQR]: 4.05 [3.58 - 4.80] x 10 -4 mm 2 /s). In linear regression models adjusting for age, DTI metrics were significantly associated with CAA burden score (mean FA: β = -0.563, Adj. R 2 : 0.27; p < 0.001; mean MD: β = 0.581; Adj. R 2 : 0.32; p < 0.001; PSMD: β = 0.364, Adj. R 2 : 0.12; p = 0.018). PSMD was significantly associated with cognitive performance, specifically in the domains of executive function ( β = -0.568; Adj. R 2 : 0.25; p < 0.001) and processing speed ( β = -0.447; Adj. R 2 : 0.19; p = 0.004). Other DTI metrics were not significantly associated with cognitive scores. Conclusion: In this CAA sample, all DTI metrics were associated with CAA burden scores, however, only PSMD was significantly associated with cognition, in domains that are commonly affected in vascular cognitive impairment. Our results warrant confirmation in larger samples, but support PSMD as biomarker for cognition in CAA, outperforming other conventional DTI metrics.

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Abstract 9: Peak Width of Skeletonized Mean Diffusivity and Cognition in Cerebral Amyloid Angiopathy

Stroke ◽

10.1161/str.52.suppl_1.9 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Mitchell J Horn ◽

Elif Gokcal ◽

J. A Becker ◽

Alvin S Das ◽

Kristin Schwab ◽

...

Keyword(s):

White Matter ◽

Regression Model ◽

Cerebral Amyloid Angiopathy ◽

Mean Diffusivity ◽

Multiple Regression Model ◽

Amyloid Angiopathy ◽

Peak Width ◽

Symbol Substitution ◽

Relevant Variables ◽

Cerebral Amyloid

Background: We hypothesized that Peak Width of Skeletonized Mean Diffusivity (PSMD), an automated marker of cerebral microangiopathy representing microstructural disruption of white matter (WM), would be increased in patients with cerebral amyloid angiopathy (CAA) compared to healthy controls (HCs) and increased PSMD would be associated with lower processing speed scores (PSSs) in patients with CAA. Methods: Seventy-two nondemented probable CAA patients and 23 HCs prospectively underwent high-resolution brain MRIs and cognitive tests. PSMD scores were quantified from a probabilistic skeleton of the WM tracts as previously validated (http://www.psmd-marker.com). In subjects with intracerebral hemorrhage (ICH, n=27), ICH regions were masked and removed from the PSMD pipeline. The analyses were repeated in the non-ICH hemisphere. Raw scores of Trail Making Test-B and Symbol Substitution Test were transformed into standardized z -scores and averaged to obtain PSSs. Results: The mean age (p=0.366) and sex (p=0.811) were similar between CAA patients and HCs. PSMD was higher in the CAA group [(3.95±0.9) х 10 –4 mm 2 /s] compared to HCs [(3.32±0.6) х 10 –4 mm 2 /s] (p=0.003). This association remained significant in a linear regression model corrected for age and sex (β=0.700, 95%CI 0.3-1, p=0.001). Within the CAA cohort, higher PSMD was associated with higher WM hyperintensity volume in a multiple regression model adjusted for all relevant variables (β=0.890, 95%CI 0.7-1, p<0.001). In a regression model corrected for age, sex, years of education and presence of ICH, a lower PSS was independently associated with increased PSMD (β=-0.405, 95%CI {-0.6}-{-0.2}, p<0.001). These results did not change when the non-ICH hemisphere was used for PSMD processing. Conclusion: PSMD is increased in CAA and is associated with worse PSSs supporting the view that disruption of white matter has a significant role in cognitive impairment in CAA.

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Changes in language white matter tract microarchitecture associated with cognitive deficits in patients with presumed low-grade glioma

Journal of Neurosurgery ◽

10.3171/2017.12.jns171681 ◽

2019 ◽

Vol 130 (5) ◽

pp. 1538-1546 ◽

Cited By ~ 6

Author(s):

Fatih Incekara ◽

Djaina Satoer ◽

Evy Visch-Brink ◽

Arnaud Vincent ◽

Marion Smits

Keyword(s):

Executive Function ◽

Diffusion Tensor Imaging ◽

White Matter ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Low Grade Glioma ◽

Cognitive Domain ◽

Awake Surgery ◽

Low Grade ◽

Linear Regression Models

OBJECTIVEThe authors conducted a study to determine whether cognitive functioning of patients with presumed low-grade glioma is associated with white matter (WM) tract changes.METHODSThe authors included 77 patients with presumed low-grade glioma who underwent awake surgery between 2005 and 2013. Diffusion tensor imaging with deterministic tractography was performed preoperatively to identify the arcuate, inferior frontooccipital, and uncinate fasciculi and to obtain the mean fractional anisotropy (FA) and mean diffusivity per tract. All patients were evaluated preoperatively using an extensive neuropsychological protocol that included assessments of the language, memory, and attention/executive function domains. Linear regression models were used to analyze each cognitive domain and each diffusion tensor imaging metric of the 3 WM tracts.RESULTSSignificant correlations (corrected for multiple testing) were found between FA of the arcuate fasciculus and results of the repetition test for the language domain (β = 0.59, p < 0.0001) and between FA of the inferior frontooccipital fasciculus and results of the imprinting test for the memory domain (β = −0.55, p = 0.002) and the attention test for the attention and executive function domain (β = −0.62, p = 0.006).CONCLUSIONSIn patients with glioma, language deficits in repetition of speech, imprinting, and attention deficits are associated with changes in the microarchitecture of the arcuate and inferior frontooccipital fasciculi.

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A pilot study of diffusion tensor imaging metrics and cognitive performance pre and post repetitive, intentional sub-concussive heading in soccer practice

Journal of Concussion ◽

10.1177/2059700219885503 ◽

2019 ◽

Vol 3 ◽

pp. 205970021988550 ◽

Cited By ~ 1

Author(s):

Rebecca A Kenny ◽

Chantel D Mayo ◽

Samantha Kennedy ◽

Aaron A Varga ◽

Lynneth Stuart-Hill ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Executive Function ◽

Diffusion Tensor Imaging ◽

Assessment Tool ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Soccer Players ◽

Resonance Imaging ◽

Sport Concussion ◽

Within Subjects

Background Although soccer players routinely head the ball in practice and games, recent research has suggested that cumulative effects of repetitive heading may cause sub-concussive injury with accompanying effects on brain and behavior. The current study aimed to prospectively investigate the effects of repetitive, intentional heading in soccer practice on brain structure and cognitive function, using a within-subjects design. Methods Participants included 10 soccer players (mean age 20.09 years ± 2.88) who were examined immediately pre- and post-heading practice. An accelerometer was used to measure the force of the impact during soccer heading. Magnetic resonance imaging data were acquired on a 3 T GE Scanner with diffusion tensor imaging. Diffusion tensor imaging analyses were completed using functional magnetic resonance imaging of the brain software library’s Tract-Based Spatial Statistics to examine changes in both fractional anisotropy and mean diffusivity due to heading the soccer ball. Behavioral measures were also completed pre- and post-soccer heading and included the Sport Concussion Assessment Tool and three short-computerized executive function tasks; R studio was used to compare behavioral data within subjects. Results Accelerometer data revealed that none of the heading impacts were >10 g. At this level of impact, there were no significant pre–post heading differences in either fractional anisotropy or mean diffusivity. Additionally, aside from minimal practice effects, there were no significant differences in Sport Concussion Assessment Tool scores and no significant differences in the performance of the three executive function tasks pre–post heading. Conclusions The results provide initial evidence that repetitive heading in soccer practice, at a g force of 10, does not cause changes in brain structure or executive function. Future research should investigate heading in the context of games and with a greater sample size that would allow for sex-based comparisons.

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White Matter Alterations in Cerebral Amyloid Angiopathy Measured by Diffusion Tensor Imaging

Stroke ◽

10.1161/01.str.0000227328.86353.a7 ◽

2006 ◽

Vol 37 (7) ◽

pp. 1759-1764 ◽

Cited By ~ 40

Author(s):

David H. Salat ◽

Eric E. Smith ◽

David S. Tuch ◽

Thomas Benner ◽

Vasanth Pappu ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

White Matter ◽

Cerebral Amyloid Angiopathy ◽

Diffusion Tensor ◽

Amyloid Angiopathy ◽

Cerebral Amyloid

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Peak Width of Skeletonized Mean Diffusivity as Neuroimaging Biomarker in Cerebral Amyloid Angiopathy

American Journal of Neuroradiology ◽

10.3174/ajnr.a7042 ◽

2021 ◽

Author(s):

N. Raposo ◽

M.C. Zanon Zotin ◽

D. Schoemaker ◽

L. Xiong ◽

P. Fotiadis ◽

...

Keyword(s):

Cerebral Amyloid Angiopathy ◽

Mean Diffusivity ◽

Amyloid Angiopathy ◽

Peak Width ◽

Cerebral Amyloid

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Is There a Relationship between the Elasticity of Brain Tumors, Changes in Diffusion Tensor Imaging, and Histological Findings? A Pilot Study Using Intraoperative Ultrasound Elastography

Brain Sciences ◽

10.3390/brainsci11020271 ◽

2021 ◽

Vol 11 (2) ◽

pp. 271

Author(s):

Santiago Cepeda ◽

Sergio García-García ◽

María Velasco-Casares ◽

Gabriel Fernández-Pérez ◽

Tomás Zamora ◽

...

Keyword(s):

Brain Tumor ◽

Diffusion Tensor Imaging ◽

Linear Regression ◽

Brain Tumors ◽

Diffusion Tensor ◽

Intraoperative Ultrasound ◽

Ultrasound Elastography ◽

Proliferation Index ◽

Strong Positive Correlation ◽

Non Linear

Intraoperative ultrasound elastography (IOUS-E) is a novel image modality applied in brain tumor assessment. However, the potential links between elastographic findings and other histological and neuroimaging features are unknown. This study aims to find associations between brain tumor elasticity, diffusion tensor imaging (DTI) metrics, and cell proliferation. A retrospective study was conducted to analyze consecutively admitted patients who underwent craniotomy for supratentorial brain tumors between March 2018 and February 2020. Patients evaluated by IOUS-E and preoperative DTI were included. A semi-quantitative analysis was performed to calculate the mean tissue elasticity (MTE). Diffusion coefficients and the tumor proliferation index by Ki-67 were registered. Relationships between the continuous variables were determined using the Spearman ρ test. A predictive model was developed based on non-linear regression using the MTE as the dependent variable. Forty patients were evaluated. The pathologic diagnoses were as follows: 21 high-grade gliomas (HGG); 9 low-grade gliomas (LGG); and 10 meningiomas. Cases with a proliferation index of less than 10% had significantly higher medians of MTE (110.34 vs. 79.99, p < 0.001) and fractional anisotropy (FA) (0.24 vs. 0.19, p = 0.020). We found a strong positive correlation between MTE and FA (rs (38) = 0.91, p < 0.001). A cubic spline non-linear regression model was obtained to predict tumoral MTE from FA (R2 = 0.78, p < 0.001). According to our results, tumor elasticity is associated with histopathological and DTI-derived metrics. These findings support the usefulness of IOUS-E as a complementary tool in brain tumor surgery.

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White Matter Integrity Predicts Delay Discounting Behavior in 9- to 23-Year-Olds: A Diffusion Tensor Imaging Study

Journal of Cognitive Neuroscience ◽

10.1162/jocn.2009.21107 ◽

2009 ◽

Vol 21 (7) ◽

pp. 1406-1421 ◽

Cited By ~ 119

Author(s):

Elizabeth A. Olson ◽

Paul F. Collins ◽

Catalina J. Hooper ◽

Ryan Muetzel ◽

Kelvin O. Lim ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

White Matter ◽

Delay Discounting ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Imaging Study ◽

Temporal Lobes ◽

Brain White Matter ◽

Independent Effects ◽

Age Range

Healthy participants (n = 79), ages 9–23, completed a delay discounting task assessing the extent to which the value of a monetary reward declines as the delay to its receipt increases. Diffusion tensor imaging (DTI) was used to evaluate how individual differences in delay discounting relate to variation in fractional anisotropy (FA) and mean diffusivity (MD) within whole-brain white matter using voxel-based regressions. Given that rapid prefrontal lobe development is occurring during this age range and that functional imaging studies have implicated the prefrontal cortex in discounting behavior, we hypothesized that differences in FA and MD would be associated with alterations in the discounting rate. The analyses revealed a number of clusters where less impulsive performance on the delay discounting task was associated with higher FA and lower MD. The clusters were located primarily in bilateral frontal and temporal lobes and were localized within white matter tracts, including portions of the inferior and superior longitudinal fasciculi, anterior thalamic radiation, uncinate fasciculus, inferior fronto-occipital fasciculus, corticospinal tract, and splenium of the corpus callosum. FA increased and MD decreased with age in the majority of these regions. Some, but not all, of the discounting/DTI associations remained significant after controlling for age. Findings are discussed in terms of both developmental and age-independent effects of white matter organization on discounting behavior.

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Structural brain changes after 4 wk of unilateral strength training of the lower limb

Journal of Applied Physiology ◽

10.1152/japplphysiol.00277.2012 ◽

2013 ◽

Vol 115 (2) ◽

pp. 167-175 ◽

Cited By ~ 23

Author(s):

H. S. Palmer ◽

A. K. Håberg ◽

M. S. Fimland ◽

G. M. Solstad ◽

V. Moe Iversen ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

Strength Training ◽

Isometric Contraction ◽

Healthy Adult ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Cortical Activation ◽

Maximum Voluntary Isometric Contraction ◽

The Right ◽

Unilateral Strength Training

Strength training enhances muscular strength and neural drive, but the underlying neuronal mechanisms remain unclear. This study used magnetic resonance imaging (MRI) to identify possible changes in corticospinal tract (CST) microstructure, cortical activation, and subcortical structure volumes following unilateral strength training of the plantar flexors. Mechanisms underlying cross-education of strength in the untrained leg were also investigated. Young, healthy adult volunteers were assigned to training ( n = 12) or control ( n = 9) groups. The 4 wk of training consisted of 16 sessions of 36 unilateral isometric plantar flexions. Maximum voluntary isometric contraction torque was tested pre- and posttraining. MRI investigation included a T1-weighted scan, diffusion tensor imaging and functional MRI. Probabilistic fiber tracking of the CST was performed on the diffusion tensor imaging images using a two-regions-of-interest approach. Fractional anisotropy and mean diffusivity were calculated for the left and right CST in each individual before and after training. Standard functional MRI analyses and volumetric analyses of subcortical structures were also performed. Maximum voluntary isometric contraction significantly increased in both the trained and untrained legs of the training group, but not the control group. A significant decrease in mean diffusivity was found in the left CST following strength training of the right leg. No significant changes were detected in the right CST. No significant changes in cortical activation were observed following training. A significant reduction in left putamen volume was found after training. This study provides the first evidence for strength training-related changes in white matter and putamen in the healthy adult brain.

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White matter atrophy in cerebral amyloid angiopathy

Neurology ◽

10.1212/wnl.0000000000010017 ◽

2020 ◽

Vol 95 (5) ◽

pp. e554-e562 ◽

Cited By ~ 1

Author(s):

Panagiotis Fotiadis ◽

Yael D. Reijmer ◽

Susanne J. Van Veluw ◽

Sergi Martinez-Ramirez ◽

Fikret Isik Karahanoglu ◽

...

Keyword(s):

Executive Function ◽

White Matter ◽

Cerebral Amyloid Angiopathy ◽

Amyloid Angiopathy ◽

Intracranial Volume ◽

White Matter Volume ◽

Cognitive Changes ◽

Important Mediator ◽

Multivariable Analyses ◽

Cerebral Amyloid

ObjectiveWe postulated that cerebral amyloid angiopathy (CAA) is associated with white matter atrophy (WMA) and that WMA can be related to cognitive changes in CAA.MethodsWhite matter volume expressed as percent of intracranial volume (pWMV) of prospectively enrolled patients without dementia diagnosed with probable CAA was compared to age-matched healthy controls (HC) and patients with Alzheimer disease (AD). Cognitive scores were also sought to understand the potential effects of WMA on cognitive function.ResultsPatients with CAA (n = 72) had significantly lower pWMV (27.97% ± 2.63) when compared to age-matched HC (n = 72; mean difference [MD], 2.38%; p < 0.0001) and patients with AD (n = 72; MD, 1.57%; p < 0.0001). Differences were most pronounced in the posterior occipital regions in both comparisons. When comparisons were restricted to groups of patients with CAA but no intracerebral hemorrhage (n = 32) or hypertension (n = 32), and age-matched HC and AD, the significant differences were unaltered. Within the CAA cohort, higher age, lobar microbleed counts, and presence of hypertension were associated with lower pWMV (p = 0.0007, p = 0.031, and p = 0.003, respectively). All associations remained independent in multivariable analyses. Within the CAA cohort, higher pWMV independently correlated with better scores of executive function.ConclusionsPatients with CAA show WMA when compared to age-matched HC and patients with AD. WMA independently correlates with the number of lobar microbleeds, a marker of CAA severity. Consistent spatial patterns of WMA especially in posterior regions might be related to CAA. The association between WMA and measures of executive function suggests that WMA might represent an important mediator of CAA-related neurologic dysfunction.

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