Capillary Transit Time Heterogeneity Is Associated with Modified Rankin Scale Score at Discharge in Patients with Bilateral High Grade Internal Carotid Artery Stenosis

Mundiyanapurath, Sibu; Ringleb, Peter A.; Diatschuk, Sascha; Hansen, Mikkel Bo; Mouridsen, Kim; Østergaard, Leif; Wick, Wolfgang; Bendszus, Martin; Radbruch, Alexander

doi:10.1371/journal.pone.0158148

Cited by 17 publications

(66 citation statements)

References 33 publications

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“…A possible physiological explanation might be that TTP is more sensitive to macrovascular perfusion, 74 while CTH is assumed to be particularly sensitive to capillary flow. 30 Lateralization of CTH outside-iWSA was stronger than for any other parameter (%16% outside iWSAs). This result points to a more widespread microvascular pathology beyond areas that are obviously affected by perfusion deficits.…”

Section: Capillary Transit Time Heterogeneity and Dysfunctionmentioning

confidence: 84%

Hemodynamic impairments within individual watershed areas in asymptomatic carotid artery stenosis by multimodal MRI

Kaczmarz

Göttler

Petr

et al. 2020

J Cereb Blood Flow Metab

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Improved understanding of complex hemodynamic impairments in asymptomatic internal carotid artery stenosis (ICAS) is crucial to better assess stroke risks. Multimodal MRI is ideal for measuring brain hemodynamics and has the potential to improve diagnostics and treatment selections. We applied MRI-based perfusion and oxygenation-sensitive imaging in ICAS with the hypothesis that the sensitivity to hemodynamic impairments will improve within individual watershed areas (iWSA). We studied cerebral blood flow (CBF), cerebrovascular reactivity (CVR), relative cerebral blood volume (rCBV), relative oxygen extraction fraction (rOEF), oxygen extraction capacity (OEC) and capillary transit-time heterogeneity (CTH) in 29 patients with asymptomatic, unilateral ICAS (age 70.3 ± 7.0 y) and 30 age-matched healthy controls. In ICAS, we found significant impairments of CBF, CVR, rCBV, OEC, and CTH (strongest lateralization ΔCVR = –24%), but not of rOEF. Although the spatial overlap of compromised hemodynamic parameters within each patient varied in a complex manner, most pronounced changes of CBF, CVR and rCBV were detected within iWSAs (strongest effect ΔCVR = +117%). At the same time, CTH impairments were iWSA independent, indicating widespread dysfunction of capillary-level oxygen diffusivity. In summary, complementary MRI-based perfusion and oxygenation parameters offer deeper perspectives on complex microvascular impairments in individual patients. Furthermore, knowledge about iWSAs improves the sensitivity to hemodynamic impairments.

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Section: Capillary Transit Time Heterogeneity and Dysfunctionmentioning

confidence: 84%

Hemodynamic impairments within individual watershed areas in asymptomatic carotid artery stenosis by multimodal MRI

Kaczmarz

Göttler

Petr

et al. 2020

J Cereb Blood Flow Metab

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“…Recently, severity of carotid stenosis have been associated with accumulation of cortical cerebral microinfarcts and poor cognitive performance, even in patients who did not experience acute ischemic stroke (160). Preoperative capillary transit time heterogeneity measured by MRI, an indicator for capillary dysfunction, predicts the functional independency (i.e., Modified Rankin Scale) following endovascular treatment in patients with symptomatic bilateral high-grade carotid stenosis (161).…”

Section: Microcirculatory Dysfunction In Neurodegenerationmentioning

confidence: 99%

Small Vessels Are a Big Problem in Neurodegeneration and Neuroprotection

Erdener

Dalkara

2019

Front. Neurol.

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The cerebral microcirculation holds a critical position to match the high metabolic demand by neuronal activity. Functionally, microcirculation is virtually inseparable from other nervous system cells under both physiological and pathological conditions. For successful bench-to-bedside translation of neuroprotection research, the role of microcirculation in acute and chronic neurodegenerative disorders appears to be under-recognized, which may have contributed to clinical trial failures with some neuroprotectants. Increasing data over the last decade suggest that microcirculatory impairments such as endothelial or pericyte dysfunction, morphological irregularities in capillaries or frequent dynamic stalls in blood cell flux resulting in excessive heterogeneity in capillary transit may significantly compromise tissue oxygen availability. We now know that ischemia-induced persistent abnormalities in capillary flow negatively impact restoration of reperfusion after recanalization of occluded cerebral arteries. Similarly, microcirculatory impairments can accompany or even precede neural loss in animal models of several neurodegenerative disorders including Alzheimer's disease. Macrovessels are relatively easy to evaluate with radiological or experimental imaging methods but they cannot faithfully reflect the downstream microcirculatory disturbances, which may be quite heterogeneous across the tissue at microscopic scale and/or happen fast and transiently. The complexity and size of the elements of microcirculation, therefore, require utilization of cutting-edge imaging techniques with high spatiotemporal resolution as well as multidisciplinary team effort to disclose microvascular-neurodegenerative connection and to test treatment approaches to advance the field. Developments in two photon microscopy, ultrafast ultrasound, and optical coherence tomography provide valuable experimental tools to reveal those microscopic events with high resolution. Here, we review the up-to-date advances in understanding of the primary microcirculatory abnormalities that can result in neurodegenerative processes and the combined neurovascular protection approaches that can prevent acute as well as chronic neurodegeneration.

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“…9,10 This approach has proved robust across realistic signalto-noise ratios [9][10][11] and demonstrated usefulness in patients with glioma, 10,12,13 acute stroke, 9 and bilateral high-grade internal carotid artery stenosis. 14 These studies, however, used a gradient-echo (GE) echo-planar imaging (EPI) DSC-MRI perfusion sequence. The GE-EPI DSC-MRI technique is the method of choice for routine clinical applications of DSC because of its relatively high contrast-to-noise ratio.…”

Section: Introductionmentioning

confidence: 99%

Recurrence of glioblastoma is associated with elevated microvascular transit time heterogeneity and increased hypoxia

Stadlbauer

Mouridsen

Doerfler

et al. 2017

J Cereb Blood Flow Metab

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Dynamic susceptibility contrast (DSC) perfusion MRI provide information about differences in macro- and microvasculature when executed with gradient-echo (GE; sensitive to macrovasculature) and spin-echo (SE; sensitive to microvasculature) contrast. This study investigated whether there are differences between macro- and microvascular transit time heterogeneity (MVTH and µVTH) and tissue oxygen tension (PO2) in newly-diagnosed and recurrent glioblastoma. Fifty-seven patients with glioblastoma (25 newly-diagnosed/32 recurrent) were examined with GE- and SE-DSC perfusion sequences, and a quantitative blood-oxygen-level-dependent (qBOLD) approach. Maps of MVTH, µVTH and coefficient of variation (MCOV and µCOV) were calculated from GE- and SE-DSC data, respectively, using an extended flow-diffusion equation. PO2 maps were calculated from qBOLD data. Newly-diagnosed and recurrent glioblastoma showed significantly lower ( P ≤ 0.001) µCOV values compared to both normal brain and macrovasculature (MCOV) of the lesions. Recurrent glioblastoma had significantly higher µVTH ( P = 0.014) and µCOV ( P = 0.039) as well as significantly lower PO2 values ( P = 0.008) compared to newly-diagnosed glioblastoma. The macrovasculature, however, showed no significant differences. Our findings provide evidence of microvascular adaption in the disorganized tumor vasculature for retaining the metabolic demands in stress response of therapeutically-uncontrolled glioblastomas. Thus, µVTH and PO2 mapping gives insight into the tumor microenvironment (vascular and hypoxic niches) responsible for therapy resistance.

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Capillary Transit Time Heterogeneity Is Associated with Modified Rankin Scale Score at Discharge in Patients with Bilateral High Grade Internal Carotid Artery Stenosis

Cited by 17 publications

References 33 publications

Hemodynamic impairments within individual watershed areas in asymptomatic carotid artery stenosis by multimodal MRI

Hemodynamic impairments within individual watershed areas in asymptomatic carotid artery stenosis by multimodal MRI

Small Vessels Are a Big Problem in Neurodegeneration and Neuroprotection

Recurrence of glioblastoma is associated with elevated microvascular transit time heterogeneity and increased hypoxia

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