Bridging macroscopic and microscopic methods for the measurements of cerebral blood flow

Kanno, Iwao; Masamoto, Kazuto

doi:10.1016/bs.pbr.2016.03.002

Cited by 3 publications

(3 citation statements)

References 61 publications

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“…Tissue blood flow is provided by the pressure gradient across the microcirculatory bed vascular resistance, which is largely determined by the vascular diameter and blood viscosity (6). The focal brain activity is highly variable; hence, regional metabolic requirements change fast and continuously.…”

Section: Capillary Dysfunctionmentioning

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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Section: Capillary Dysfunctionmentioning

confidence: 99%

Small Vessels Are a Big Problem in Neurodegeneration and Neuroprotection

Erdener

Dalkara

2019

Front. Neurol.

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“…In addition, 2PLSM angiography is limited to the regions where the large vessels are not densely distributed because of a signal loss by absorption effects (i.e., shadowing of light due to surface vessels). Future studies with complementary mesoscopic imaging may facilitate more precise characterization of regional variations in cerebrovascular volumes, leading to further translation to clinical applications by linking with cerebral perfusion data in the clinical practice 50 …”

Section: Discussionmentioning

confidence: 99%

“…Future studies with complementary mesoscopic imaging may facilitate more precise characterization of regional variations in cerebrovascular volumes, leading to further translation to clinical applications by linking with cerebral perfusion data in the clinical practice. 50…”

Section: Automated Measurements Of the Vascular Volumesmentioning

confidence: 99%

Three‐dimensional microvascular network reconstruction from in vivo images with adaptation of the regional inhomogeneity in the signal‐to‐noise ratio

et al. 2021

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Objective: Quantification of angiographic images with two-photon laser scanning fluorescence microscopy (2PLSM) relies on proper segmentation of the vascular images. However, the images contain inhomogeneities in the signal-to-noise ratio (SNR) arising from regional effects of light scattering and absorption. The present study developed a semiautomated quantification method for volume images of 2PLSM angiography by adjusting the binarization threshold according to local SNR along the vessel centerlines.Methods: A phantom model made with fluorescent microbeads was used to incorporate a region-dependent binarization threshold. Results:The recommended SNR for imaging was found to be 4.2-10.6 that provide the true size of imaged objects if the binarization threshold was fixed at 50% of SNR.However, angiographic images in the mouse cortex showed variable SNR up to 45 over the depths. To minimize the errors caused by variable SNR and a spatial extent of the imaged objects in an axial direction, the microvascular networks were threedimensionally reconstructed based on the cross-sectional diameters measured along the vessel centerline from the XY-plane images with adapted binarization threshold.The arterial volume was relatively constant over depths of 0-500 µm, and the capillary volume (1.7% relative to the scanned volume) showed the larger volumes than the artery (0.8%) and vein (0.6%). Conclusions:The present methods allow consistent segmentation of microvasculature by adapting the local inhomogeneity in the SNR, which will be useful for quantitative comparison of the microvascular networks, such as under disease conditions where SNR in the 2PLSM images varies over space and time.

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Vascular contributions to cognitive impairment and dementia: the emerging role of 20-HETE

et al. 2021

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The accumulation of extracellular amyloid-β (Aβ) and intracellular hyperphosphorylated τ proteins in the brain are the hallmarks of Alzheimer’s disease (AD). Much of the research into the pathogenesis of AD has focused on the amyloid or τ hypothesis. These hypotheses propose that Aβ or τ aggregation is the inciting event in AD that leads to downstream neurodegeneration, inflammation, brain atrophy and cognitive impairment. Multiple drugs have been developed and are effective in preventing the accumulation and/or clearing of Aβ or τ proteins. However, clinical trials examining these therapeutic agents have failed to show efficacy in preventing or slowing the progression of the disease. Thus, there is a need for fresh perspectives and the evaluation of alternative therapeutic targets in this field. Epidemiology studies have revealed significant overlap between cardiovascular and cerebrovascular risk factors such as hypertension, diabetes, atherosclerosis and stroke to the development of cognitive impairment. This strong correlation has given birth to a renewed focus on vascular contributions to AD and related dementias. However, few genes and mechanisms have been identified. 20-Hydroxyeicosatetraenoic acid (20-HETE) is a potent vasoconstrictor that plays a complex role in hypertension, autoregulation of cerebral blood flow and blood–brain barrier (BBB) integrity. Multiple human genome-wide association studies have linked mutations in the cytochrome P450 (CYP) 4A (CYP4A) genes that produce 20-HETE to hypertension and stroke. Most recently, genetic variants in the enzymes that produce 20-HETE have also been linked to AD in human population studies. This review examines the emerging role of 20-HETE in AD and related dementias.

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Bridging macroscopic and microscopic methods for the measurements of cerebral blood flow

Cited by 3 publications

References 61 publications

Small Vessels Are a Big Problem in Neurodegeneration and Neuroprotection

Small Vessels Are a Big Problem in Neurodegeneration and Neuroprotection

Three‐dimensional microvascular network reconstruction from in vivo images with adaptation of the regional inhomogeneity in the signal‐to‐noise ratio

Vascular contributions to cognitive impairment and dementia: the emerging role of 20-HETE

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