Hierarchical microimaging for multiscale analysis of large vascular networks

Heinzer, Stefan; Krucker, Thomas; Stampanoni, Marco; Meyer, Éric P.; Schuler, Alexandra; Schneider, Philipp; Müller, Ralph

doi:10.1016/j.neuroimage.2006.03.043

Cited by 161 publications

(156 citation statements)

References 33 publications

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“…Recently, a hierarchical imaging method was developed that involved using synchrotron radiation mCT (SRmCT) to image corrosion casts of 3D capillary networks at 1.4 mm resolution in select regions of interest (ROIs) 1 mm 3 in size (Heinzer et al, 2006). However, constructing an intact corrosion cast without damaging microvessels remains technically challenging, and any complementary information is lost during tissue maceration (Hossler and Douglas, 2001).…”

Section: Introductionmentioning

confidence: 99%

Vascular phenotyping of brain tumors using magnetic resonance microscopy (μMRI)

Kim

Zhang

Hong

et al. 2011

J Cereb Blood Flow Metab

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Abnormal vascular phenotypes have been implicated in neuropathologies ranging from Alzheimer's disease to brain tumors. The development of transgenic mouse models of such diseases has created a crucial need for characterizing the murine neurovasculature. Although histologic techniques are excellent for imaging the microvasculature at submicron resolutions, they offer only limited coverage. It is also challenging to reconstruct the three-dimensional (3D) vasculature and other structures, such as white matter tracts, after tissue sectioning. Here, we describe a novel method for 3D whole-brain mapping of the murine vasculature using magnetic resonance microscopy (lMRI), and its application to a preclinical brain tumor model. The 3D vascular architecture was characterized by six morphologic parameters: vessel length, vessel radius, microvessel density, length per unit volume, fractional blood volume, and tortuosity. Region-of-interest analysis showed significant differences in the vascular phenotype between the tumor and the contralateral brain, as well as between postinoculation day 12 and day 17 tumors. These results unequivocally show the feasibility of using lMRI to characterize the vascular phenotype of brain tumors. Finally, we show that combining these vascular data with coregistered images acquired with diffusion-weighted MRI provides a new tool for investigating the relationship between angiogenesis and concomitant changes in the brain tumor microenvironment.

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Section: Introductionmentioning

confidence: 99%

Vascular phenotyping of brain tumors using magnetic resonance microscopy (μMRI)

Kim

Zhang

Hong

et al. 2011

J Cereb Blood Flow Metab

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“…This does not appear to be from failure to fill (and thus detect) small capillary-like interconnections in the normal pia that then remodel into collaterals after MCAO, for several reasons: (1) have repeatedly been unable to find such vessels using different filling or staining methods in the present (e.g., Figure 1) or earlier studies (Clayton et al, 2008;; (2) pressure and infusion time are adjusted during filling, while viewing the pial circulation with a stereomicroscope, to make sure that the penetrating arterioles (including those in the collateral zone) and beginning of their capillaries are filled; (3) the adult pial circulation in humans lacks capillaries (Duvernoy, 1999). Inspection of high resolution images in Heinzer et al (2006) appear to extend this absence to the mouse. And we confirmed this in this study-no capillaries were detected in the pia of any of the 15 strains.…”

Section: Discussionmentioning

confidence: 97%

Wide Genetic Variation in the Native Pial Collateral Circulation is a Major Determinant of Variation in Severity of Stroke

Zhang

Prabhakar

Sealock

et al. 2010

J Cereb Blood Flow Metab

228

383

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Severity of stroke varies widely among individuals. Whether differences in the extent of the native (preexisting) pial collateral circulation exist and contribute to this variability is unknown. We addressed these questions and probed for potential genetic contributions using morphometric analysis of the collateral circulation in 15 inbred mouse strains recently shown to exhibit wide differences in infarct volume. Morphometrics were determined in the unligated left hemisphere (for native collaterals) and ligated right hemisphere (for remodeled collaterals) 6 days after permanent middle cerebral artery (MCA) occlusion. Variation among strains in native collateral number, diameter, MCA, anterior cerebral artery (ACA), and posterior cerebral artery (PCA) tree territories were, respectively: 56-fold, 3-fold, 42%, 56%, and 61%. Collateral length (P < 0.001) and the number of penetrating arterioles branching from them also varied (P < 0.05). Infarct volume correlated inversely with collateral number (P < 0.0001), diameter (P < 0.0001), and penetrating arteriole number (P < 0.05) and directly with MCA territory (P < 0.05). Relative collateral conductance and MCA territory, when factored together, strongly predicted infarct volume (P < 0.0001). Outward remodeling of collaterals in the ligated hemisphere varied B3-fold. These data show that the extent of the native pial collateral circulation and collateral remodeling after obstruction vary widely with genetic background, and suggest that this variability, due to natural polymorphisms, is a major contributor to variability in infarct volume.

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“…1D). The details of the intricate features of normal cerebral vasculature using corrosion casts have been described by our group (21,24,25). …”

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confidence: 99%

Altered morphology and 3D architecture of brain vasculature in a mouse model for Alzheimer's disease

Meyer

Ulmann-Schuler

Staufenbiel

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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239

215

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Substantial evidence from epidemiological, pathological, and clinical reports suggests that vascular factors are critical in the pathogenesis of Alzheimer's disease (AD), and changes in blood flow are currently the most reliable indicators of the disease. We previously reported that older APP23 transgenic (tg) mice have significant blood flow alterations correlated with structural modifications of blood vessels. For the present study, our objective was to analyze the age-dependent morphological and architectural changes of the cerebral vasculature of APP23 tg mice. To visualize the 3D arrangement of the entire brain vasculature, we used vascular corrosion casts. Already at young ages, when typically parenchymal amyloid plaques are not yet present, APP23 tg mice had significant alterations, particularly of the microvasculature, often accompanied by small deposits attached to the vessels. In older animals, vasculature abruptly ended at amyloid plaques, resulting in holes. Often, small deposits were sitting near or at the end of truncated vessels. Between such holes, the surrounding vascular array appeared more dense and showed features typical for angiogenesis. We propose that small amyloid aggregates associated with the microvasculature lead to morphological and architectural alterations of the vasculature, resulting in altered local blood flow. The characteristic early onset of vascular alterations suggests that imaging blood flow and/or vasculature architecture could be used as a tool for early diagnosis of the disease and to monitor therapies. amyloid precursor protein ͉ cerebral blood flow ͉ scanning electron microscopy ͉ vascular corrosion casting T he typical clinical picture of Alzheimer's disease (AD) includes a progressive decline of memory function, often accompanied by other clinical signs such as agitation, aggression, sleep disturbances, and social withdrawal. Nonetheless, brain autopsy is needed to positively confirm the diagnosis (1). A high density of neuritic plaques, neurofibrillary tangles, and vascular amyloid (A␤) is a characteristic neuropathological marker of AD (2, 3). Plaques and tangles in the neuropil may affect neuronal function and also contribute to the neuronal damage; however, it is unclear whether their incidence correlates with the clinical signs and symptoms of cognitive impairment characteristic of the disease (4). Evidence suggests that cerebrovascular pathologies, such as structural alterations (5), atherosclerotic lesions (6), and impaired hemodynamic responses (7), are early features of AD (for review, see ref. 8). Reduced blood flow has been reported as one of the most consistent physiological deficits in AD (9, 10); however, it remains unclear whether the reduced cerebral blood flow is a response to neuronal damage or a factor initiating the characteristic neuropathology. In vivo studies showed the effect of A␤ on cerebral blood flow and vessel architecture in a mouse model for AD (11,12). In other models, cerebrovascular regulatory mechanisms, such as endothelium-depende...

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Hierarchical microimaging for multiscale analysis of large vascular networks

Cited by 161 publications

References 33 publications

Vascular phenotyping of brain tumors using magnetic resonance microscopy (μMRI)

Vascular phenotyping of brain tumors using magnetic resonance microscopy (μMRI)

Wide Genetic Variation in the Native Pial Collateral Circulation is a Major Determinant of Variation in Severity of Stroke

Altered morphology and 3D architecture of brain vasculature in a mouse model for Alzheimer's disease

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