Cerebrovascular reactivity measurement in cerebral small vessel disease: Rationale and reproducibility of a protocol for MRI acquisition and image processing

Thrippleton, Michael J.; Shi, Yulu; Blair, Gordon W.; Hamilton, I.; Waiter, Gordon D.; Schwarzbauer, Christian; Pernet, Cyril; Andrews, Peter; Marshall, Ian; Doubal, Fergus; Wardlaw, Joanna M.

doi:10.1177/1747493017730740

Cited by 51 publications

(112 citation statements)

References 39 publications

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“…Studies report reduced cortical CVR in those with WMH; however, there remains poor consensus on this relationship . Our results indicate no difference in GM CVR and VTF‐AUC between groups.…”

Section: Discussioncontrasting

confidence: 65%

“…We also found it was imprudent to conduct a VTF‐CVR analysis in the absence of exogenous CO 2 manipulation. Despite the appeal of resting‐state CVR for ease of implementation, recent work shows that a boxcar CVR protocol is well tolerated among adults with CSVD …”

Section: Discussionmentioning

confidence: 99%

“…46 BOLD-CVR in WM can inform vascular-specific deficits that reflect reduced modulation by metabolic demands 47 and temporal kinetics, 48 which is particularly important given that the CSVD pathological features are of presumed vascular origin. 1,2 Studies report reduced cortical CVR in those with WMH 14,49,50 ; however, there remains poor consensus on this relationship. 3 Our results indicate no difference in GM CVR and VTF-AUC between groups.…”

Section: Figurementioning

confidence: 99%

“…Findings from BOLD‐based CVR studies of sporadic CSVD are more mixed . Some report no association of whole brain CVR with white matter hyperintensities (WMHs), while others show reduced CVR in grey and white matter (GM and WM), whereas in CADASIL, a severe autosomal dominant phenotype, reduced CVR at initial assessment predicts larger increases in WMH lesions at follow‐up . Despite the recognized clinical utility of CVR, there are still opportunities to make protocols and assessment measures more robust, and more amenable to within‐brain and between‐session comparisons …”

Section: Introductionmentioning

confidence: 99%

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BOLD‐based cerebrovascular reactivity vascular transfer function isolates amplitude and timing responses to better characterize cerebral small vessel disease

et al. 2019

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Cerebrovascular reactivity (CVR) is a dynamic measure of the cerebral blood vessel response to vasoactive stimulus. Conventional CVR measures amplitude changes in the blood‐oxygenation‐level‐dependent (BOLD) signal per unit change in end‐tidal CO2 (PETCO2), effectively discarding potential timing information. This study proposes a deconvolution procedure to characterize CVR responses based on a vascular transfer function (VTF) that separates amplitude and timing CVR effects. We implemented the CVR‐VTF to primarily evaluate normal‐appearing white matter (WM) responses in those with a range of small vessel disease. Comparisons between simulations of PETCO2 input models revealed that boxcar and ramp hypercapnia paradigms had the lowest relative deconvolution error. We used a T2* BOLD‐MRI sequence on a 3 T MRI scanner, with a boxcar delivery model of CO2, to test the CVR‐VTF approach in 18 healthy adults and three white matter hyperintensity (WMH) groups: 20 adults with moderate WMH, 12 adults with severe WMH, and 10 adults with genetic WMH (CADASIL). A subset of participants performed a second CVR session at a one‐year follow‐up. Conventional CVR, area under the curve of VTF (VTF‐AUC), and VTF time‐to‐peak (VTF‐TTP) were assessed in WM and grey matter (GM) at baseline and one‐year follow‐up. WMH groups had lower WM VTF‐AUC compared with the healthy group (p < 0.0001), whereas GM CVR did not differ between groups (p > 0.1). WM VTF‐TTP of the healthy group was less than that in the moderate WMH group (p = 0.016). Baseline VTF‐AUC was lower than follow‐up VTF‐AUC in WM (p = 0.013) and GM (p = 0.026). The intraclass correlation for VTF‐AUC in WM was 0.39 and coefficient of repeatability was 0.08 [%BOLD/mm Hg]. This study assessed CVR timing and amplitude information without applying model assumptions to the CVR response; this approach may be useful in the development of robust clinical biomarkers of CSVD.

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Section: Discussioncontrasting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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BOLD‐based cerebrovascular reactivity vascular transfer function isolates amplitude and timing responses to better characterize cerebral small vessel disease

et al. 2019

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“…(9,10) Magnetic resonance imaging (MRI) techniques measure CVR in all brain tissues, including the subcortical areas commonly affected by SVD. (11) So far, MRI-based CVR has been assessed in relatively few small studies in SVD, but used different CVR challenges,(12-16) and did not account for clinically-relevant variables (e.g. age, blood pressure [BP], gender) that could confound CVR associations with SVD features.…”

Section: Introductionmentioning

confidence: 99%

Intracranial functional haemodynamic relationships in patients with cerebral small vessel disease

Blair

Thrippleton

Shi

et al. 2019

Preprint

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BackgroundCerebral small vessel disease (SVD) is a major cause of stroke and dementia. The underlying cerebrovascular dysfunction is poorly understood. We investigated cerebrovascular reactivity, blood flow, vascular and cerebrospinal fluid (CSF) pulsatility, and their independent relationship to SVD features, in patients with minor ischaemic stroke and MRI evidence of SVD.MethodsWe recruited patients with minor ischaemic stroke and assessed CVR using Blood Oxygen Level Dependent (BOLD) MRI during a hypercapnic challenge, cerebral blood flow, vascular and CSF pulsatility using phase contrast MRI, and structural MR brain imaging to quantify white matter hyperintensities (WMH) and perivascular spaces (PVS). We quantified CVR in seven white matter and six subcortical grey matter regions, measured blood flow in carotid and vertebral arteries, intracranial venous sinuses, internal jugular veins and CSF flow at the aqueduct and foramen magnum. We used multiple regression to identify SVD features, blood flow and pulsatility parameters associated with CVR, controlling for patient characteristics.ResultsIn 53 of 60 patients with complete data (age 68.0±8.8, 74% male, 75% hypertensive), CVR in grey and white matter decreased with increasing blood pressure (BP, respectively −0.001%/mmHg, p=0.01 and −0.006%/mmHg, p=0.01, per mmHg increase in BP). After controlling for age, gender and systolic BP, white matter CVR decreased with increasing WMF volume (−0.01%/mmHg per log10 increase in WMH volume, p=0.02) and basal ganglia PVS (−0.01%/mmHg per point increase in PVS score, p=0.02). White matter CVR decreased with increasing venous pulsatility (superior sagittal sinus −0.03%/mmHg, p=0.02, per unit increase in pulsatility index) but not with cerebral blood flow (p=0.58). Lower foramen magnum CSF stroke volume was associated with worse white matter CVR (0.04%/mmHg per ml increase in stroke volume, p=0.04) and increased basal ganglia PVS.ConclusionsContemporaneous assessment of CVR, intracranial vascular and CSF pulsatility demonstrates important interrelationships of these vascular functions in humans. Decreased CVR, increased venous pulsatility and reduced foramen magnum CSF stroke volume suggests that dynamic vascular dysfunctions underpin PVS dysfunction and WMH development. Improved understanding of microvascular dysfunction and CSF dynamics offers new intervention targets to reduce SVD lesion development and their impact on cognitive dysfunction and stroke.

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CADASIL Affects Multiple Aspects of Cerebral Small Vessel Function on 7T‐MRI

Brink

Kopczak²,

Arts

et al. 2022

Annals of Neurology

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the SVDs@target group Objective: Cerebral small vessel diseases (cSVDs) are a major cause of stroke and dementia. We used cutting-edge 7T-MRI techniques in patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), to establish which aspects of cerebral small vessel function are affected by this monogenic form of cSVD. Methods: We recruited 23 CADASIL patients (age 51.1 AE 10.1 years, 52% women) and 13 age-and sex-matched controls (46.1 AE 12.6, 46% women). Small vessel function measures included: basal ganglia and centrum semiovale perforating artery blood flow velocity and pulsatility, vascular reactivity to a visual stimulus in the occipital cortex and reactivity to hypercapnia in the cortex, subcortical gray matter, white matter, and white matter hyperintensities. Results: Compared with controls, CADASIL patients showed lower blood flow velocity and higher pulsatility index within perforating arteries of the centrum semiovale (mean difference À 0.09 cm/s, p = 0.03 and 0.20, p = 0.009) and basal ganglia (mean difference À 0.98 cm/s, p = 0.003 and 0.17, p = 0.06). Small vessel reactivity to a short visual stimulus was decreased (blood-oxygen-level dependent [BOLD] mean difference À0.21%, p = 0.04) in patients, while reactivity to hypercapnia was preserved in the cortex, subcortical gray matter, and normal appearing white matter. Among patients, reactivity to hypercapnia was decreased in white matter hyperintensities compared to normal appearing white matter (BOLD mean difference À0.29%, p = 0.02). Interpretation: Multiple aspects of cerebral small vessel function on 7T-MRI were abnormal in CADASIL patients, indicative of increased arteriolar stiffness and regional abnormalities in reactivity, locally also in relation to white matter injury. These observations provide novel markers of cSVD for mechanistic and intervention studies.

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Cerebrovascular reactivity measurement in cerebral small vessel disease: Rationale and reproducibility of a protocol for MRI acquisition and image processing

Cited by 51 publications

References 39 publications

BOLD‐based cerebrovascular reactivity vascular transfer function isolates amplitude and timing responses to better characterize cerebral small vessel disease

BOLD‐based cerebrovascular reactivity vascular transfer function isolates amplitude and timing responses to better characterize cerebral small vessel disease

Intracranial functional haemodynamic relationships in patients with cerebral small vessel disease

CADASIL Affects Multiple Aspects of Cerebral Small Vessel Function on 7T‐MRI

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