Magnetic resonance imaging of brain angiogenesis after stroke

Abstract

Stroke is a major cause of mortality and long-term disability worldwide. The initial changes in local perfusion and tissue status underlying loss of brain function are increasingly investigated with noninvasive imaging methods. In addition, there is a growing interest in imaging of processes that contribute to post-stroke recovery. In this review, we discuss the application of magnetic resonance imaging (MRI) to assess the formation of new vessels by angiogenesis, which is hypothesized to participate in brain plasticity and functional recovery after stroke. The excellent soft tissue contrast, high spatial and temporal resolution, and versatility render MRI particularly suitable to monitor the dynamic processes involved in vascular remodeling after stroke. Here we review recent advances in the field of MR imaging that are aimed at assessment of tissue perfusion and microvascular characteristics, including cerebral blood flow and volume, vascular density, size and integrity. The potential of MRI to noninvasively monitor the evolution of post-ischemic angiogenic processes is demonstrated from a variety of in vivo studies in experimental stroke models. Finally, we discuss some pitfalls and limitations that may critically affect the accuracy and interpretation of MRI-based measures of (neo)vascularization after stroke.

Axon guidance factor netrin-1 and its receptors regulate angiogenesis after cerebral ischemia

“…Migrating neuroblasts pass through areas of vascular remodeling and regeneration, suggesting that angiogenesis assists neurogenesis, and that both processes promote functional recovery after ischemic stroke. Taken together, angiogenesis helps to restore neuronal function after ischemic stroke, which may offer useful insights into new treatment approaches for the condition [62,68,69] .…”

“…Gradually, the newly-formed vessels grow and increase the cerebral blood volume. However, whether angiogenesis leads to the formation of an intact and functional vessel network in the ischemic zone after stroke needs to be determined [62] .…”

Monitoring Brain Repair in Stroke Using Advanced Magnetic Resonance Imaging

“…25 DSC-MRI calculates cerebral hemodynamic parameters from the time course of signal changes induced by the first passage of an intravenously injected paramagnetic contrast agent. 26 DSC-MRI has demonstrated significantly increased CBV in the recovering ipsilesional cortex of rodent stroke models, which correlated well with increased vascular density on histology.…”

“…28,30 The low specificity of DSC-MRI or ASL for angiogenesis may be overcome by steady-state susceptibility contrast-enhanced MRI, which allows estimation of blood volume, vessel size, and microvessel density. 25 The ratio of changes in gradient-echo to spin-echo relaxation rate (ΔR 2 */ΔR 2 ) induced by a high-molecular-weight intravascular contrast agent provides an estimate of average vessel size after accounting for echo time, contrast concentration, and the main magnetic field. 31 The ratio Q≡ΔR 2 /(ΔR 2 *) 2/3 characterizes Yes ADC indicates apparent diffusion coefficient; ASL, arterial spin labelling; BOLD, blood oxygenation level-dependent imaging; CBF, cerebral blood flow; CBV, cerebral blood volume; DCE-MRI, dynamic contrast-enhanced magnetic resonance imaging; DSC-MRI, dynamic susceptibility contrast-enhanced magnetic resonance imaging; DTI, diffusion tensor imaging; FA, fractional anisotropy; HARDI, high-angular resolution diffusion imaging; K i , blood-brain barrier transfer constant; MEMRI, manganese-enhanced magnetic resonance imaging; MRI, magnetic resonance imaging; MRS, magnetic resonance spectroscopy; MVD, microvascular density; SSCE-MRI, steady-state susceptibility contrast-enhanced magnetic resonance imaging; SWI, susceptibility-weighted imaging.…”

“…MRI measurement algorithms also are based on relatively basic biophysical and mathematical models that may be inaccurate under complex or altered conditions seen with stroke. 25 DSC-MRI is arguably the most widely available perfusion MRI technique in the clinical setting, but DSC-MRI methods are not fully quantitative, and thus provide information with regard to the relative CBF and CBV. 39 Blood oxygenation level-dependent methods also are widely available and easily implemented but are again able to provide only a qualitative assessment of deoxyhemoglobin concentration or T2*.…”