Non-Invasive Evaluation of Cerebral Microvasculature Using Pre-Clinical MRI: Principles, Advantages and Limitations

Abstract

Alterations to the cerebral microcirculation have been recognized to play a crucial role in the development of neurodegenerative disorders. However, the exact role of the microvascular alterations in the pathophysiological mechanisms often remains poorly understood. The early detection of changes in microcirculation and cerebral blood flow (CBF) can be used to get a better understanding of underlying disease mechanisms. This could be an important step towards the development of new treatment approaches. Animal models allow for the study of the disease mechanism at several stages of development, before the onset of clinical symptoms, and the verification with invasive imaging techniques. Specifically, pre-clinical magnetic resonance imaging (MRI) is an important tool for the development and validation of MRI sequences under clinically relevant conditions. This article reviews MRI strategies providing indirect non-invasive measurements of microvascular changes in the rodent brain that can be used for early detection and characterization of neurodegenerative disorders. The perfusion MRI techniques: Dynamic Contrast Enhanced (DCE), Dynamic Susceptibility Contrast Enhanced (DSC) and Arterial Spin Labeling (ASL), will be discussed, followed by less established imaging strategies used to analyze the cerebral microcirculation: Intravoxel Incoherent Motion (IVIM), Vascular Space Occupancy (VASO), Steady-State Susceptibility Contrast (SSC), Vessel size imaging, SAGE-based DSC, Phase Contrast Flow (PC) Quantitative Susceptibility Mapping (QSM) and quantitative Blood-Oxygenation-Level-Dependent (qBOLD). We will emphasize the advantages and limitations of each strategy, in particular on applications for high-field MRI in the rodent’s brain.

The Problem of Wound Healing in Diabetes—From Molecular Pathways to the Design of an Animal Model

“…This is extremely important when the changes in small arteries are potentially reversible, before significant thickening of the basement membrane and thrombotic and embolic occlusions occur. New MRI-based techniques used in preclinical studies on cerebral microcirculation in rodents might also be useful in diabetic wound studies [ 6 ]. Secondly, searching for microvascular revascularization methods and/or molecules and drugs preventing the occurrence of thrombotic and embolic changes and basal membrane thickening should be independent research directions [ 7 , 8 ].…”

“…Obese ob/ob mice 4 db/db mice 5 NONcNZO mice 6 Zucker fa/fa rats 7 In an established pig model (streptozotocin-injected Yorkshire pigs) of diabetic wound, the wounds healed within 18 days, which makes this model incoherent with the analogous process in humans [117]. Streptozotocin-induced models did not mimic type 1 DM because this disease is not caused by xenobiotic-mediated destruction of beta cells [118].…”

Intravoxel Incoherent Motion Magnetic Resonance Imaging Used in Preoperative Screening of High-Risk Patients With Moyamoya Disease Who May Develop Postoperative Cerebral Hyperperfusion Syndrome

“…Various imaging modalities such as single-photon emission computed tomography (SPECT), computed tomography (CT), and magnetic resonance imaging (MRI) can determine the cerebral perfusion status. SPECT and CT perfusion are radiative, whereas MRI techniques, including dynamic contrast-enhanced MRI, dynamic susceptibility contrast-enhanced (DSC) MRI, arterial spin labeling (ASL) MRI, and methods used to analyze cerebral microcirculation, such as intravoxel incoherent motion (IVIM) MRI, and vascular space occupancy are non-radiative ( Callewaert et al, 2021 ). Brain IVIM technique is advantageous over other technique, such as positron emission tomography, CT, DSC MRI, and ASL MRI, because it does not require contrast media injection or radiation exposure and is not affected by the arterial input ( Hara et al, 2019 ).…”

“…Microvessels are below the currently achievable spatial resolution of MRI and other clinically applicable imaging methods, making the direct non-invasive measurement of microvascular density impossible to be performed. Nonetheless, MRI can be applied to measure microvascular perfusion, providing indirect readouts of the underlying microvasculature alteration ( Federau et al, 2012 ; Callewaert et al, 2021 ).…”

Non-Invasive Evaluation of Cerebral Hemodynamic Changes After Surgery in Adult Patients With Moyamoya Using 2D Phase-Contrast and Intravoxel Incoherent Motion MRI

“…Conversely, IVIM imaging, a new perfusion evaluation modality, is designed to determine microvascular perfusion and microstructural integrity simultaneously ( 8 ) and may be better for detecting the changes in microvascular perfusion and microstructural integrity in patients with MMD after surgery. It has been proven to provide essential information on microperfusion in the tissue; therefore, it is a promising tool for applications in neurological and neurovascular diseases ( 9 , 10 ).…”