Study of white matter at the centrum semiovale level with magnetic resonance spectroscopy and diffusion tensor imaging in cerebral small vessel disease

Background and Purpose: Chronic hypoxia-ischemia is a putative mechanism underlying the development of white matter hyperintensities (WMH) and microstructural disruption in cerebral small vessel disease. WMH fall primarily within deep white matter (WM) watershed regions. We hypothesized that elevated oxygen extraction fraction (OEF), a signature of hypoxia-ischemia, would be detected in the watershed where WMH density is highest. We further hypothesized that OEF would be elevated in regions immediately surrounding WMH, at the leading edge of growth. Methods: In this cross-sectional study conducted from 2016 to 2019 at an academic medical center in St Louis, MO, participants (age >50) with a range of cerebrovascular risk factors underwent brain magnetic resonance imaging using pseudocontinuous arterial spin labeling, asymmetric spin echo, fluid-attenuated inversion recovery and diffusion tensor imaging to measure cerebral blood flow (CBF), OEF, WMH, and WM integrity, respectively. We defined the physiologic watershed as a region where CBF was below the 10th percentile of mean WM CBF in a young healthy cohort. We conducted linear regression to evaluate the relationship between CBF and OEF with structural and microstructural WM injury defined by fluid-attenuated inversion recovery WMH and diffusion tensor imaging, respectively. We conducted ANOVA to determine if OEF was increased in proximity to WMH lesions. Results: In a cohort of 42 participants (age 50–80), the physiologic watershed region spatially overlapped with regions of highest WMH lesion density. As CBF decreased and OEF increased, WMH density increased. Elevated watershed OEF was associated with greater WMH burden and microstructural disruption, after adjusting for vascular risk factors. In contrast, WM and watershed CBF were not associated with WMH burden or microstructural disruption. Moreover, OEF progressively increased while CBF decreased, in concentric contours approaching WMH lesions. Conclusions: Chronic hypoxia-ischemia in the watershed region may contribute to cerebral small vessel disease pathogenesis and development of WMH. Watershed OEF may hold promise as an imaging biomarker to identify individuals at risk for cerebral small vessel disease progression.

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PRESERVE: Randomized Trial of Intensive Versus Standard Blood Pressure Control in Small Vessel Disease

Stroke ◽

10.1161/strokeaha.120.032054 ◽

2021 ◽

Author(s):

Hugh S. Markus ◽

Marco Egle ◽

Iain D. Croall ◽

Hasan Sari ◽

Usman Khan ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Blood Pressure ◽

Diffusion Tensor Imaging ◽

White Matter ◽

Magnetic Resonance ◽

Diffusion Tensor ◽

Small Vessel Disease ◽

Small Vessel ◽

Resonance Imaging ◽

Vessel Disease

Background and Purpose: In cerebral small vessel disease, cerebral blood flow and autoregulation are impaired and therefore excessive blood pressure reduction could possibly accelerate white matter damage and worsen outcome. The trial determined, in severe symptomatic cerebral small vessel disease, whether intensive blood pressure lowering resulted in progression of white matter damage assessed using diffusion tensor imaging. Methods: Randomized, parallel, multicenter controlled, blinded-outcomes clinical trial. One hundred eleven participants with magnetic resonance imaging confirmed symptomatic lacunar infarct and confluent white matter hyperintensities and were recruited and randomized to standard (systolic=130–140 mmHg) (N=56) or intensive (systolic<125 mmHg) (N=55) blood pressure targets. The primary end point was change in diffusion tensor imaging white matter mean diffusivity peak height between baseline and 24 months. Secondary end points were other magnetic resonance imaging markers and cognition. Results: Patients were mean 68 years and 60% male. Mean (SD) blood pressure reduced by −15.3 (15.4) and −23.1 (22.04) mm Hg in the standard/intensive groups, respectively ( P <0.001). There was no difference between treatment groups for the primary end point: standard, adjusted mean (SE)=12.5×10 −3 (0.2×10 −3 ); intensive, 12.5×10 −3 (0.2×10 −3 ), P =0.92. In the whole population over 24 months follow-up, there was a significant deterioration in white matter microstructure but no detectable decrease in cognition. Conclusions: Intensive blood pressure lowering in severe cerebral small vessel disease was not associated with progression of white matter damage on diffusion tensor imaging or magnetic resonance imaging. In a multicentre study setting over 2 years, multimodal diffusion tensor imaging-magnetic resonance imaging was more sensitive to detecting change than cognitive testing. REGISTRATION: URL: https://www.isrctn.com ; Unique identifier: ISRCTN37694103.

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Cognitive Function in Small Vessel Disease: The Additional Value of Diffusion Tensor Imaging to Conventional Magnetic Resonance Imaging: The RUN DMC Study

Journal of Alzheimer s Disease ◽

10.3233/jad-2012-120784 ◽

2012 ◽

Vol 32 (3) ◽

pp. 667-676 ◽

Cited By ~ 14

Author(s):

Anouk G.W. van Norden ◽

Inge W.M. van Uden ◽

Karlijn F. de Laat ◽

Ewoud J. van Dijk ◽

Frank-Erik de Leeuw

Keyword(s):

Magnetic Resonance Imaging ◽

Diffusion Tensor Imaging ◽

Cognitive Function ◽

Magnetic Resonance ◽

Diffusion Tensor ◽

Small Vessel Disease ◽

Conventional Magnetic Resonance Imaging ◽

Resonance Imaging ◽

Vessel Disease ◽

Additional Value

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Microstructural Predictors of Cognitive Impairment in Cerebral Small Vessel Disease and the Conditions of Their Formation

Diagnostics ◽

10.3390/diagnostics10090720 ◽

2020 ◽

Vol 10 (9) ◽

pp. 720

Author(s):

Larisa A. Dobrynina ◽

Zukhra Sh. Gadzhieva ◽

Kamila V. Shamtieva ◽

Elena I. Kremneva ◽

Bulat M. Akhmetzyanov ◽

...

Keyword(s):

Blood Flow ◽

Cognitive Impairment ◽

White Matter ◽

Diffusion Tensor ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Venous Blood Flow ◽

Csf Flow ◽

Vessel Disease

Introduction: Cerebral small vessel disease (CSVD) is the leading cause of vascular and mixed degenerative cognitive impairment (CI). The variability in the rate of progression of CSVD justifies the search for sensitive predictors of CI. Materials: A total of 74 patients (48 women, average age 60.6 ± 6.9 years) with CSVD and CI of varying severity were examined using 3T MRI. The results of diffusion tensor imaging with a region of interest (ROI) analysis were used to construct a predictive model of CI using binary logistic regression, while phase-contrast magnetic resonance imaging and voxel-based morphometry were used to clarify the conditions for the formation of CI predictors. Results: According to the constructed model, the predictors of CI are axial diffusivity (AD) of the posterior frontal periventricular normal-appearing white matter (pvNAWM), right middle cingulum bundle (CB), and mid-posterior corpus callosum (CC). These predictors showed a significant correlation with the volume of white matter hyperintensity; arterial and venous blood flow, pulsatility index, and aqueduct cerebrospinal fluid (CSF) flow; and surface area of the aqueduct, volume of the lateral ventricles and CSF, and gray matter volume. Conclusion: Disturbances in the AD of pvNAWM, CB, and CC, associated with axonal damage, are a predominant factor in the development of CI in CSVD. The relationship between AD predictors and both blood flow and CSF flow indicates a disturbance in their relationship, while their location near the floor of the lateral ventricle and their link with indicators of internal atrophy, CSF volume, and aqueduct CSF flow suggest the importance of transependymal CSF transudation when these regions are damaged.

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Impact of fluoxetine on the human brain in multiple sclerosis as quantified by proton magnetic resonance spectroscopy and diffusion tensor imaging

Psychiatry Research Neuroimaging ◽

10.1016/j.pscychresns.2007.12.014 ◽

2008 ◽

Vol 164 (3) ◽

pp. 274-282 ◽

Cited By ~ 36

Author(s):

Paul E. Sijens ◽

Jop P. Mostert ◽

Roy Irwan ◽

Jan Hendrik Potze ◽

Matthijs Oudkerk ◽

...

Keyword(s):

Multiple Sclerosis ◽

Diffusion Tensor Imaging ◽

Magnetic Resonance ◽

Magnetic Resonance Spectroscopy ◽

Human Brain ◽

Proton Magnetic Resonance ◽

Proton Magnetic Resonance Spectroscopy ◽

Diffusion Tensor ◽

Resonance Spectroscopy ◽

And Diffusion

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Diffusion tensor imaging and MR spectroscopy in hypertension and presumed cerebral small vessel disease

Magnetic Resonance in Medicine ◽

10.1002/mrm.21461 ◽

2008 ◽

Vol 59 (3) ◽

pp. 528-534 ◽

Cited By ~ 48

Author(s):

Arani Nitkunan ◽

Rebecca A. Charlton ◽

Dominick J.O. McIntyre ◽

Thomas R. Barrick ◽

Franklyn A. Howe ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

Mr Spectroscopy ◽

Diffusion Tensor ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Vessel Disease

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Affective status in cerebral small vessel disease

Medicinski pregled ◽

10.2298/mpns1910280s ◽

2019 ◽

Vol 72 (9-10) ◽

pp. 280-285

Author(s):

Aleksandar Stevanovic ◽

Anja Stefanovic ◽

Natasa Stojanovski ◽

Gordana Tomic ◽

Jasna Zidverc-Trajkovic ◽

...

Keyword(s):

White Matter ◽

Magnetic Resonance ◽

Affective Disorders ◽

Small Vessel Disease ◽

Statistical Tests ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Screening Tests ◽

White Matter Changes ◽

Vessel Disease

Introduction. Cerebral small vessel disease is a neurological condition characterized by motor, cognitive and affective disorders, often found on brain magnetic resonance imaging scans in patients with vascular risk factors. Affective disorders may have a major impact on patients? quality of life, although they are often ignored as an entity in cerebrovascular pathology. Material and Methods. This prospective study included 80 patients with the diagnosis of cerebral small vessel disease admitted at the Clinic of Neurology, Clinical Center of Serbia in the period from January 1, 2017 to January 1, 2019. Baseline demographic data and brain magnetic resonance findings were obtained along with the results of cognitive function and affective status tests. Data were analyzed using standard statistical tests. Results. Standard screening tests revealed that 51.25% and 33.75% of our patients with cerebral small vessel disease suffer from apathy and depression, respectively. A significant correlation was found between the severity of white matter changes on magnetic resonance scans and apathy (p = 0.0092). Additionally, white matter changes were also significantly associated with depression (p = 0.021). Conclusion. Affective disorders are not uncommon in cerebral small vessel disease and apathy was the leading phenomenon among our patients. Since a strong correlation was detected between affective disorders and severity of vascular changes on magnetic resonance scans, we may conclude that both apathy and depression are key features of an underlying brain injury, rather than just comorbidity.

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White matter differences in euthymic bipolar I disorder: a combined magnetic resonance imaging and diffusion tensor imaging voxel-based study

Bipolar Disorders ◽

10.1111/bdi.12073 ◽

2013 ◽

Vol 15 (4) ◽

pp. 365-376 ◽

Cited By ~ 32

Author(s):

Louise Emsell ◽

Camilla Langan ◽

Wim Van Hecke ◽

Gareth J Barker ◽

Alexander Leemans ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Diffusion Tensor Imaging ◽

White Matter ◽

Magnetic Resonance ◽

Diffusion Tensor ◽

Resonance Imaging ◽

Bipolar I Disorder ◽

And Diffusion

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Using DTI to assess white matter microstructure in cerebral small vessel disease (SVD) in multicentre studies

Clinical Science ◽

10.1042/cs20170146 ◽

2017 ◽

Vol 131 (12) ◽

pp. 1361-1373 ◽

Cited By ~ 32

Author(s):

Iain D. Croall ◽

Valerie Lohner ◽

Barry Moynihan ◽

Usman Khan ◽

Ahamad Hassan ◽

...

Keyword(s):

White Matter ◽

Diffusion Tensor ◽

Small Vessel Disease ◽

Mean Diffusivity ◽

Peak Height ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Single Centre ◽

Vessel Disease ◽

Multicentre Studies

Diffusion tensor imaging (DTI) metrics such as fractional anisotropy (FA) and mean diffusivity (MD) have been proposed as clinical trial markers of cerebral small vessel disease (SVD) due to their associations with outcomes such as cognition. However, studies investigating this have been predominantly single-centre. As clinical trials are likely to be multisite, further studies are required to determine whether associations with cognition of similar strengths can be detected in a multicentre setting. One hundred and nine patients (mean age =68 years) with symptomatic lacunar infarction and confluent white matter hyperintensities (WMH) on MRI was recruited across six sites as part of the PRESERVE DTI substudy. After handling missing data, 3T-MRI scanning was available from five sites on five scanner models (Siemens and Philips), alongside neuropsychological and quality of life (QoL) assessments. FA median and MD peak height were extracted from DTI histogram analysis. Multiple linear regressions were performed, including normalized brain volume, WMH lesion load, and n° lacunes as covariates, to investigate the association of FA and MD with cognition and QoL. DTI metrics from all white matter were significantly associated with global cognition (standardized β =0.268), mental flexibility (β =0.306), verbal fluency (β =0.376), and Montreal Cognitive Assessment (MoCA) (β =0.273). The magnitudes of these associations were comparable with those previously reported from single-centre studies found in a systematic literature review. In this multicentre study, we confirmed associations between DTI parameters and cognition, which were similar in strength to those found in previous single-centre studies. The present study supports the use of DTI metrics as biomarkers of disease progression in multicentre studies.

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