Three-Dimensional Imaging of the Mouse Neurovasculature with Magnetic Resonance Microscopy

Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
PLoS ONE (Impact Factor: 3.23). 07/2011; 6(7):e22643. DOI: 10.1371/journal.pone.0022643
Source: PubMed


Knowledge of the three-dimensional (3D) architecture of blood vessels in the brain is crucial because the progression of various neuropathologies ranging from Alzheimer's disease to brain tumors involves anomalous blood vessels. The challenges in obtaining such data from patients, in conjunction with development of mouse models of neuropathology, have made the murine brain indispensable for investigating disease induced neurovascular changes. Here we describe a novel method for "whole brain" 3D mapping of murine neurovasculature using magnetic resonance microscopy (μMRI). This approach preserves the vascular and white matter tract architecture, and can be combined with complementary MRI contrast mechanisms such as diffusion tensor imaging (DTI) to examine the interplay between the vasculature and white matter reorganization that often characterizes neuropathologies. Following validation with micro computed tomography (μCT) and optical microscopy, we demonstrate the utility of this method by: (i) combined 3D imaging of angiogenesis and white matter reorganization in both, invasive and non-invasive brain tumor models; (ii) characterizing the morphological heterogeneity of the vascular phenotype in the murine brain; and (iii) conducting "multi-scale" imaging of brain tumor angiogenesis, wherein we directly compared in vivo MRI blood volume measurements with ex vivo vasculature data.

Download full-text


Available from: Jiangyang Zhang, Feb 13, 2014
  • Source
    • "Angiome: The Brain's Plumbing Schematic The focus of this review is the neuronal connectome; however, the brain's angiome or distribution of vascular elements can also be considered a connectome of sorts. In contrast to the brain's electrical circuit diagram, which is far from complete in any mammalian model organism, recent breakthroughs in imaging and sectioning technology have resulted in high-resolution capillary-level reconstructions of the rodent brain angiome (Blinder et al., 2013; Mayerich et al., 2011; Pathak et al., 2011; Tsai et al., 2009; Xue et al., 2014). Tracing blood vessels is "
    [Show abstract] [Hide abstract]
    ABSTRACT: Connections between neurons are affected within 3 min of stroke onset by massive ischemic depolarization and then delayed cell death. Some connections can recover with prompt reperfusion; others associated with the dying infarct do not. Disruption in functional connectivity is due to direct tissue loss and indirect disconnections of remote areas known as diaschisis. Stroke is devastating, yet given the brain's redundant design, collateral surviving networks and their connections are well-positioned to compensate. Our perspective is that new treatments for stroke may involve a rational functional and structural connections-based approach. Surviving, affected, and at-risk networks can be identified and targeted with scenario-specific treatments. Strategies for recovery may include functional inhibition of the intact hemisphere, rerouting of connections, or setpoint-mediated network plasticity. These approaches may be guided by brain imaging and enabled by patient- and injury-specific brain stimulation, rehabilitation, and potential molecule-based strategies to enable new connections.
    Neuron 09/2014; 83(6):1354-1368. DOI:10.1016/j.neuron.2014.08.052 · 15.05 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
    • "The rate constant, k in, 3D , is obtained from a single measurement of Q br /c pl at a fixed infusion time t. The assumption of unidirectional transport can be confirmed by performing multiple perfusion experiments as a function of infusion time and determining the slope (k in, 3D ) of a linear regression to a plot of Q br /c pl vs. time (Pathak et al., 2011). While k in, 3D can be used to compare the in vivo transport kinetics of different solutes (Youdim et al., 2003), it cannot be compared directly to in vitro measurements k in, 2D . "
    [Show abstract] [Hide abstract]
    ABSTRACT: It has been more than 100 years since Paul Ehrlich reported that various water-soluble dyes injected into the circulation did not enter the brain. Since Ehrlich's first experiments, only a small number of molecules, such as alcohol and caffeine have been found to cross the blood-brain barrier, and this selective permeability remains the major roadblock to treatment of many central nervous system diseases. At the same time, many central nervous system diseases are associated with disruption of the blood-brain barrier that can lead to changes in permeability, modulation of immune cell transport, and trafficking of pathogens into the brain. Therefore, advances in our understanding of the structure and function of the blood-brain barrier are key to developing effective treatments for a wide range of central nervous system diseases. Over the past 10 years it has become recognized that the blood-brain barrier is a complex, dynamic system that involves biomechanical and biochemical signaling between the vascular system and the brain. Here we reconstruct the structure, function, and transport properties of the blood-brain barrier from an engineering perspective. New insight into the physics of the blood-brain barrier could ultimately lead to clinical advances in the treatment of central nervous system diseases.
    Frontiers in Neuroengineering 08/2013; 6:7. DOI:10.3389/fneng.2013.00007
Show more