Label-Free Imaging of Cerebral β-Amyloidosis with Extended-Focus Optical Coherence Microscopy

Bolmont, Tristan; Bouwens, Arno; Pache, Christophe; Dimitrov, Milen; Berclaz, Corinne; Villiger, Martin; Wegenast‐Braun, Bettina M.; Lasser, Theo; Fraering, Patrick C.

doi:10.1523/jneurosci.0925-12.2012

Cited by 53 publications

(49 citation statements)

References 25 publications

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“…Cerebral amyloid-β (Aβ) amyloidosis, an early and critical biomarker for Alzheimer’s disease, has been visualized ex vivo and in vivo in Alzheimeric mouse models with OCM [115]. Amyloid plaques were detected up to 500 µm below the cortical surface.…”

Section: Oct In Brain Imagingmentioning

confidence: 99%

Optical Coherence Tomography for Brain Imaging and Developmental Biology

Men

Huang

Solanki

et al. 2016

IEEE J. Select. Topics Quantum Electron.

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Optical coherence tomography (OCT) is a promising research tool for brain imaging and developmental biology. Serving as a three-dimensional optical biopsy technique, OCT provides volumetric reconstruction of brain tissues and embryonic structures with micrometer resolution and video rate imaging speed. Functional OCT enables label-free monitoring of hemodynamic and metabolic changes in the brain in vitro and in vivo in animal models. Due to its non-invasiveness nature, OCT enables longitudinal imaging of developing specimens in vivo without potential damage from surgical operation, tissue fixation and processing, and staining with exogenous contrast agents. In this paper, various OCT applications in brain imaging and developmental biology are reviewed, with a particular focus on imaging heart development. In addition, we report findings on the effects of a circadian gene (Clock) and high-fat-diet on heart development in Drosophila melanogaster. These findings contribute to our understanding of the fundamental mechanisms connecting circadian genes and obesity to heart development and cardiac diseases.

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Section: Oct In Brain Imagingmentioning

confidence: 99%

Optical Coherence Tomography for Brain Imaging and Developmental Biology

Men

Huang

Solanki

et al. 2016

IEEE J. Select. Topics Quantum Electron.

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“…Similar methods were used to study microischemia because of repeated cocaine administration 15 and to generate images of vasculature for longitudinal image registration in a mouse model of cerebral β-amyloidosis. 16 In this paper, we present an OCT platform that enables longitudinal and quantitative monitoring of both global flow and microvascular flow patterns during chronic cerebral hypoperfusion, imaged for up to nine time points in the same animal over 1 month. In particular, the system parameters, animal model, and scanning protocols were optimized to enable selective imaging of red blood cell (RBC)-perfused capillaries.…”

Section: Introductionmentioning

confidence: 99%

Micro-Heterogeneity of Flow in a Mouse Model of Chronic Cerebral Hypoperfusion Revealed by Longitudinal Doppler Optical Coherence Tomography and Angiography

Srinivasan

Radhakrishnan

et al. 2015

J Cereb Blood Flow Metab

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Although microvascular dysfunction accompanies cognitive decline in aging, vascular dementia, and Alzheimer's disease, tools to study microvasculature longitudinally in vivo are lacking. Here, we use Doppler optical coherence tomography (OCT) and angiography for noninvasive, longitudinal imaging of mice with chronic cerebral hypoperfusion for up to 1 month. In particular, we optimized the OCT angiography method to selectively image red blood cell (RBC)-perfused capillaries, leading to a novel way of assessing capillary supply heterogeneity in vivo. After bilateral common carotid artery stenosis (BCAS), cortical blood flow measured by Doppler OCT dropped to half of baseline throughout the imaged tissue acutely. Microscopic imaging of the capillary bed with OCT angiography further revealed local heterogeneities in cortical flow supply during hypoperfusion. The number of RBC-perfused capillaries decreased, leading to increased oxygen diffusion distances in the days immediately after BCAS. Linear regression showed that RBC-perfused capillary density declined by 0.3% for a drop in flow of 1 mL/100 g per minute, and decreases in RBC-perfused capillary density as high as 25% were observed. Taken together, these results demonstrate the existence of local supply heterogeneity at the capillary level even at nonischemic global flow levels, and demonstrate a novel imaging method to assess this heterogeneity. Keywords: angiography; capillary recruitment; Doppler optical coherence tomography; hypoperfusion; vascular dementia INTRODUCTION Chronic cerebral hypoperfusion induced by small-artery occlusion or critical arterial stenosis is a pathophysiologic hallmark of vascular dementia. Histologically characterized by white matter changes and multifocal infarctions, chronic cerebral hypoperfusion is associated with cognitive decline. 1-3 Rodent models of chronic cerebral hypoperfusion that use common carotid artery stenosis or occlusion mimic many aspects of vascular cognitive impairment in patients, including decreased cerebral blood flow, inflammation and blood-brain barrier abnormalities, brain atrophy, white matter degeneration, decreased metabolism, as well as impaired working memory. 4 Bilateral common carotid artery occlusion has been widely used in the rat to model chronic cerebral hypoperfusion. 5 Recently, mouse bilateral common carotid artery stenosis (BCAS) models have emerged. 6 In these models, although the degree of hypoperfusion is correlated with the extent of ischemic lesions and neurologic impairment, 7 the magnitude of flow reductions after BCAS were moderate at best (~30 to 40%), 8 at least relative to classic ischemic thresholds of 80 to 85%, 9-11 and lasted only a few days before collateral development and recovery of flow. The lack of classic ischemia raises questions about the precise mechanism of tissue loss and cognitive impairment. Previous studies have used laser Doppler Journal of Cerebral Blood

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“…The OCM was used to image individual axons and unveil the myeloarchitecture in the cortex (Srinivasan et al, 2012; Leahy et al, 2013). Previous studies on brain and peripheral nerves using OCM have reported close correlations with histology (Arous et al, 2011; Bolmont et al, 2012; Magnain et al, 2013). Therefore, the method we propose (SOCS) has the potential to bridge multi-modality investigations on the central and peripheral nervous systems to construct a hierarchal view of neuroanatomical connections from molecular to system levels, thus opening important opportunities for systematic studies on brain mapping and neural disorders.…”

Section: Discussionmentioning

confidence: 72%

Cross-validation of serial optical coherence scanning and diffusion tensor imaging: A study on neural fiber maps in human medulla oblongata

et al. 2014

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We established a strategy to perform cross-validation of serial optical coherence scanner imaging (SOCS) and diffusion tensor imaging (DTI) on a postmortem human medulla. Following DTI, the sample was serially scanned by SOCS, which integrates a vibratome slicer and a multi-contrast optical coherence tomography rig for large-scale three-dimensional imaging at microscopic resolution. The DTI dataset was registered to the SOCS space. An average correlation coefficient of 0.9 was found between the co-registered fiber maps constructed by fractional anisotropy and retardance contrasts. Pixelwise comparison of fiber orientations demonstrated good agreement between the DTI and SOCS measures. Details of the comparison were studied in regions exhibiting a variety of fiber organizations. DTI estimated the preferential orientation of small fiber tracts; however, it didn’t capture their complex patterns as SOCS did. In terms of resolution and imaging depth, SOCS and DTI complement each other, and open new avenues for cross-modality investigations of the brain.

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Label-Free Imaging of Cerebral β-Amyloidosis with Extended-Focus Optical Coherence Microscopy

Cited by 53 publications

References 25 publications

Optical Coherence Tomography for Brain Imaging and Developmental Biology

Optical Coherence Tomography for Brain Imaging and Developmental Biology

Micro-Heterogeneity of Flow in a Mouse Model of Chronic Cerebral Hypoperfusion Revealed by Longitudinal Doppler Optical Coherence Tomography and Angiography

Cross-validation of serial optical coherence scanning and diffusion tensor imaging: A study on neural fiber maps in human medulla oblongata

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