MRI Visualization of Whole Brain Macro- and Microvascular Remodeling in a Rat Model of Ischemic Stroke: A Pilot Study

Abstract

Using superparamagnetic iron oxide nanoparticles (Spion) as a single contrast agent, we investigated dual contrast cerebrovascular magnetic resonance imaging (MRi) for simultaneously monitoring macro-and microvasculature and their association with ischemic edema status (via apparent diffusion coefficient [ADC]) in transient middle cerebral artery occlusion (tMCAO) rat models. High-resolution t 1 -contrast based ultra-short echo time MR angiography (Ute-MRA) visualized size remodeling of pial arteries and veins whose mutual association with cortical ischemic edema status is rarely reported. ΔR 2 -ΔR 2 * -MRi-derived vessel size index (VSi) and density indices (Q and MVD) mapped morphological changes of microvessels occurring in subcortical ischemic edema lesions. In cortical ischemic edema lesions, significantly dilated pial veins (p = 0.0051) and thinned pial arteries (p = 0.0096) of ipsilateral brains compared to those of contralateral brains were observed from UTE-MRAs. In subcortical regions, ischemic edema lesions had a significantly decreased Q and MVD values (p < 0.001), as well as increased VSi values (p < 0.001) than normal subcortical tissues in contralateral brains. This pilot study suggests that MR-based morphological vessel changes, including but not limited to venous blood vessels, are directly related to corresponding tissue edema status in ischemic stroke rat models.www.nature.com/scientificreports www.nature.com/scientificreports/ On the other hand, the spatial changes of MR signals can be measured with the administration of a blood-pool contrast agent, enabling morphological mapping of the macro-and microvasculature. To obtain morphological information regarding the entire macrovasculature, high-resolution 3-dimensional T 1 -contrast-based ultra-short echo time (UTE) MRA can be used 18,19 . To obtain morphological information about the microvasculature, vessel size index (VSI) and microvessel density indices (Q and MVD) can be measured. VSI, Q, and MVD values obtained through alteration of transverse relaxation rates (ΔR 2 and ΔR 2 * ) due to the administration of contrast agent 20-23 can be used to map morphological microvascular alterations after ischemic stroke [24][25][26][27][28][29][30] . As arteriogenesis and angiogenesis are likely to correlate with recovery after ischemic stroke, the association between vessel morphology and corresponding tissue ischemic edema status (via apparent diffusion coefficient [ADC]) can be verified by simultaneous assessment of total macro-and microvascular remodeling in the ischemic brain.In this pilot study, we performed dual contrast MRI using superparamagnetic iron oxide nanoparticles (SPION) as a single contrast agent 18,19 . We used Monte Carlo simulation to optimize the dose of SPION by correlating ΔR 2 and ΔR 2 * values at various vessel sizes/volumes at 7-T. High-resolution (59 μm 3 ) 3-dimensional UTE-MRA was combined with ΔR 2 -ΔR 2 * -MRI derived VSI/Q/MVD maps on tMCAO rat models. Such dual contrast MRI acquisition enabled simultaneous morphologica...

Magnetic Nanoparticles in Biology and Medicine: Past, Present, and Future Trends

“…PEG-IONCs demonstrated no significant toxicity and they were successfully used for full-body MRA; notably they were able to identify ischemia in cerebral angiograms. More recently, Kang et al used similar USPION in rats to monitor the remodeling of cerebral vasculature after ischemic stroke [91]. Cellular tracking and labeling are another common trend in preclinical and clinical IOP-based MRI [80,91].…”

“…More recently, Kang et al used similar USPION in rats to monitor the remodeling of cerebral vasculature after ischemic stroke [91]. Cellular tracking and labeling are another common trend in preclinical and clinical IOP-based MRI [80,91]. Because T1 imaging can be significantly impacted by compartmentalization of nanoparticles in cells, applications usually use T2-weighted MRI [66].…”

“…Cellular tracking and labeling are another common trend in preclinical and clinical IOP-based MRI [ 80 , 91 ]. Because T 1 imaging can be significantly impacted by compartmentalization of nanoparticles in cells, applications usually use T 2 -weighted MRI [ 66 ].…”

“…(A-C) Reproduced with permission from Wei et al, Proceedings of the National Academy of Sciences of the United States of America; published by National Academy of Science, 2017. (D-G) Reproduced with permission from Lu Y. et al, Nature Biomedical Engineering; published by Springer Nature, 2017.Cellular tracking and labeling are another common trend in preclinical and clinical IOP-based MRI[80,91]. Because T 1 imaging can be significantly impacted by compartmentalization of nanoparticles in cells, applications usually use T 2 -weighted MRI[66].…”

MRI investigation of vascular remodeling for heterogeneous edema lesions in subacute ischemic stroke rat models: Correspondence between cerebral vessel structure and function

“…[20][21][22] Microvascular remodeling in the inner brain region can be visualized by morphological mapping of the vessel size index (VSI) and microvessel density (MVD and Q), overcoming the spatial resolution limitation of MRA. [23][24][25][26][27][28] Dynamic susceptibility contrast MRI (DSC-MRI) can be used to estimate functional microvascular status, such as the cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) in lesions. [29][30][31] In this study, longitudinal morphological and functional vascular remodeling were investigated differentially between early and typical pseudo-normalization lesions to assess contrasting vascular conditions in a transient middle cerebral artery occlusion (tMCAO) rat model using dual contrast superparamagnetic iron oxide nanoparticles (SPION).…”