Contrast-Enhanced Magnetic Resonance Microangiography Reveals Remodeling of the Cerebral Microvasculature in Transgenic ArcA Mice

Institute for Biomedical Engineering, Swiss Federal Institute of Technology and University of Zurich, CH-8093 Zurich, Switzerland.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 02/2012; 32(5):1705-13. DOI: 10.1523/JNEUROSCI.5626-11.2012
Source: PubMed


Amyloid-β (Aβ) deposition in the cerebral vasculature is accompanied by remodeling which has a profound influence on vascular integrity and function. In the current study we have quantitatively assessed the age-dependent changes of the cortical vasculature in the arcAβ model of cerebral amyloidosis. To estimate the density of the cortical microvasculature in vivo, we used contrast-enhanced magnetic resonance microangiography (CE-μMRA). Three-dimensional gradient echo datasets with 60 μm isotropic resolution were acquired in 4- and 24-month-old arcAβ mice and compared with wild-type (wt) control mice of the same age before and after administration of superparamagnetic iron oxide nanoparticles. After segmentation of the cortical vasculature from difference images, an automated algorithm was applied for assessing the number and size distribution of intracortical vessels. With CE-μMRA, cerebral arteries and veins with a diameter of less than the nominal pixel resolution (60 μm) can be visualized. A significant age-dependent reduction in the number of functional intracortical microvessels (radii of 20-80 μm) has been observed in 24-month-old arcAβ mice compared with age-matched wt mice, whereas there was no difference between transgenic and wt mice of 4 months of age. Immunohistochemistry demonstrated strong fibrinogen and Aβ deposition in small- and medium-sized vessels, but not in large cerebral arteries, of 24-month-old arcAβ mice. The reduced density of transcortical vessels may thus be attributed to impaired perfusion and vascular occlusion caused by deposition of Aβ and fibrin. The study demonstrated that remodeling of the cerebrovasculature can be monitored noninvasively with CE-μMRA in mice.

Download full-text


Available from: Jan Klohs, Aug 19, 2015
20 Reads
  • Source
    • "Many diseases affect general properties of the cerebrovascular network, examples are arteriosclerosis and dilative vascular malformations changing vessel shape and diameter, but also Alzheimer's and related neuro-degenerative diseases are suspected to affect the general vascularity and global network proper- 5 ties [1] [2]. Studies investigating such diseases frequently use mouse models for experiments and commonly acquire in-vivo cerebrovascular imagery by means of magnetic resonance microangiography (µMRA). "
    [Show abstract] [Hide abstract]
    ABSTRACT: We introduce a probabilistic approach to vessel network extraction that enforces physiological constraints on the vessel structure. The method accounts for both image evidence and geometric relationships between vessels by solving an integer program, which is shown to yield the maximum a posteriori (MAP) estimate to a probabilistic model. Starting from an overconnected network, it is pruning vessel stumps and spurious connections by evaluating the local geometry and the global connectivity of the graph. We utilize a high-resolution micro computed tomography (μCT) dataset of a cerebrovascular corrosion cast to obtain a reference network and learn the prior distributions of our probabilistic model and we perform experiments on in-vivo magnetic resonance microangiography (μMRA) images of mouse brains. We finally discuss properties of the networks obtained under different tracking and pruning approaches. Copyright © 2015 Elsevier B.V. All rights reserved.
    Medical Image Analysis 04/2015; 25(1). DOI:10.1016/ · 3.65 Impact Factor
  • Source
    • "Dorr et al. identified and marked the major vessels in the CBA mouse using Microfil perfusion and Micro-CT imaging [4], [5]. MRI techniques can also visualize the macro vessels in the whole mouse brain [6], [7]. To observe the smaller, more complex micro vessels, ex vivo two-photon laser scanning microscopy is used to image the capillary network in the cortex to a depth of 1 mm using fluorescent gelatin vessel perfusion [8]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The topology of the cerebral vasculature, which is the energy transport corridor of the brain, can be used to study cerebral circulatory pathways. Limited by the restrictions of the vascular markers and imaging methods, studies on cerebral vascular structure now mainly focus on either observation of the macro vessels in a whole brain or imaging of the micro vessels in a small region. Simultaneous vascular studies of arteries, veins and capillaries have not been achieved in the whole brain of mammals. Here, we have combined the improved gelatin-Indian ink vessel perfusion process with Micro-Optical Sectioning Tomography for imaging the vessel network of an entire mouse brain. With 17 days of work, an integral dataset for the entire cerebral vessels was acquired. The voxel resolution is 0.35×0.4×2.0 µm(3) for the whole brain. Besides the observations of fine and complex vascular networks in the reconstructed slices and entire brain views, a representative continuous vascular tracking has been demonstrated in the deep thalamus. This study provided an effective method for studying the entire macro and micro vascular networks of mouse brain simultaneously.
    PLoS ONE 01/2014; 9(1):e88067. DOI:10.1371/journal.pone.0088067 · 3.23 Impact Factor
  • Source
    • "Modern imaging is surely the second approach for directly visualizing early vascular changes. Contrast-enhanced magnetic resonance microangiography (CE-μMRA; [40]) opens the avenue for new MRI sequences having the capacity to detect tiny vascular events like stases, vessel-wall-adherent coagulation or plasma leakage. A better diagnostic will give the basis for a specifically adapted treatment of patients developing dementia and stroke-like symptoms from CSVD. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cerebral small vessel disease (CSVD, cerebral microangiopathy) leads to dementia and stroke-like symptoms. Lacunes, white matter lesions (WML) and microbleeds are the main pathological correlates depicted in in-vivo imaging diagnostics. Early studies described segmental arterial wall disorganizations of small penetrating cerebral arteries as the most pronounced underlying histopathology of lacunes. Luminal narrowing caused by arteriolosclerosis was supposed to result in hypoperfusion with WML and infarcts. We have used the model of spontaneously hypertensive stroke-prone rats (SHRSP) for a longitudinal study to elucidate early histological changes in small cerebral vessels. We suggest that endothelial injuries lead to multiple sites with blood brain barrier (BBB) leakage which cause an ongoing damage of the vessel wall and finally resulting in vessel ruptures and microbleeds. These microbleeds together with reactive small vessel occlusions induce overt cystic infarcts of the surrounding parenchyma. Thus, multiple endothelial leakage sites seem to be the starting point of cerebral microangiopathy. The vascular system reacts with an activated coagulatory state to these early endothelial injuries and by this induces the formation of stases, accumulations of erythrocytes, which represent the earliest detectable histological peculiarity of small vessel disease in SHRSP. In this review we focus on the meaning of the BBB breakdown in CSVD and finally discuss possible consequences for clinicians.
    Experimental and Translational Stroke Medicine 03/2013; 5(1):4. DOI:10.1186/2040-7378-5-4
Show more