Detecting sub-voxel microvasculature with USPIO-enhanced susceptibility-weighted MRI at 7 T

Shen, Yimin; Hu, Jiani; Eteer, Khalid; Chen, Yongsheng; Buch, Sagar; Alhourani, Hani; Shah, Kamran; Jiang, Quan; Ge, Yulin; Haacke, E. Mark

doi:10.1016/j.mri.2019.12.010

Cited by 18 publications

(15 citation statements)

References 25 publications

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“…We use Ferumoxytol with a dose of 4 mg/kg to increase the susceptibility of the veins and add susceptibility to the arteries so that all vessels are visible with SWI (see Figure 1). The increased susceptibility induces a major signal loss for the small vessels that are less than a voxel in size (128,129). By using a resolution of 220 microns we can see vessels smaller than 100 microns at 3T, demonstrating the pitchfork (candelabra) behavior of the vessels that matches with the illustrations from the earlier cadaver brain work (Figure 2).…”

Section: Imaging the Microvasculature Using A Uspio Contrast Agentsupporting

confidence: 67%

“…The hypothesis was that using MICRO imaging it will be possible to see the complete venous vascular tree and, hence, be able to study the MS lesions for the presence of vascular abnormalities much better than has ever been done before in vivo . MICRO imaging has the potential to study the microvasculature of MS lesions and to follow vascular changes longitudinally over time similar to previous studies ( 133 ) to determine which comes first: abnormal vessel structure and flow or inflammation that then affects the vessel wall ( 129 , 134 , 135 ). Or, perhaps both contain some level of guilt and they create a destructive feedback loop exacerbating the disease.…”

Section: Introductionmentioning

confidence: 94%

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An Overview of Venous Abnormalities Related to the Development of Lesions in Multiple Sclerosis

Haacke

Sethi

et al. 2021

Front. Neurol.

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The etiology of multiple sclerosis (MS) is currently understood to be autoimmune. However, there is a long history and growing evidence for disrupted vasculature and flow within the disease pathology. A broad review of the literature related to vascular effects in MS revealed a suggestive role for abnormal flow in the medullary vein system. Evidence for venous involvement in multiple sclerosis dates back to the early pathological work by Charcot and Bourneville, in the mid-nineteenth century. Pioneering work by Adams in the 1980s demonstrated vasculitis within the walls of veins and venules proximal to active MS lesions. And more recently, magnetic resonance imaging (MRI) has been used to show manifestations of the central vein as a precursor to the development of new MS lesions, and high-resolution MRI using Ferumoxytol has been used to reveal the microvasculature that has previously only been demonstrated in cadaver brains. Both approaches may shed new light into the structural changes occurring in MS lesions. The material covered in this review shows that multiple pathophysiological events may occur sequentially, in parallel, or in a vicious circle which include: endothelial damage, venous collagenosis and fibrin deposition, loss of vessel compliance, venous hypertension, perfusion reduction followed by ischemia, medullary vein dilation and local vascular remodeling. We come to the conclusion that a potential source of MS lesions is due to locally disrupted flow which in turn leads to remodeling of the medullary veins followed by endothelial damage with the subsequent escape of glial cells, cytokines, etc. These ultimately lead to the cascade of inflammatory and demyelinating events which ensue in the course of the disease.

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Section: Imaging the Microvasculature Using A Uspio Contrast Agentsupporting

confidence: 67%

Section: Introductionmentioning

confidence: 94%

An Overview of Venous Abnormalities Related to the Development of Lesions in Multiple Sclerosis

Haacke

Sethi

et al. 2021

Front. Neurol.

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“…Previously, we developed a novel microvascular imaging approach using an ultrasmall superparamagnetic iron oxide (USPIO) contrast agent, Ferumoxytol. This method is referred to as: ‘Microvascular In-vivo Contrast Revealed Origins (MICRO)’ imaging ( Buch et al, 2020 , Liu et al, 2018 , Shen et al, 2020 ). MICRO imaging, which takes advantage of the susceptibility weighted imaging (SWI) sequence, has shown potential in studying small vessels that previously could only be seen in cadaver brain studies ( Buch et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Revealing vascular abnormalities and measuring small vessel density in multiple sclerosis lesions using USPIO

Buch

Subramanian

Jella

et al. 2021

NeuroImage: Clinical

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Highlights Ferumoxytol, a USPIO agent, was used to reveal microvasculature in six RRMS patients. Lesion pertaining vascular abnormalities were identified using SWI-FLAIR data. Detection of vascular signs increased from 54% to 93% in the presence of USPIO. Lesional vessel density was higher than the perilesional vessel density in all patients.

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“…Alternative emerging approaches to quantify ferumoxytol enhanced vasculature are susceptibility weighted imaging (SWI) and quantitative susceptibility mapping (QSM), which even enabled us to distinguish between vessel diameters (Liu et al, 2018;Buch et al, 2020;Shen et al, 2020). However, none of the studies performed histological validation and to our best knowledge, no SWI/QSM protocol for the mouse has been published in the context of cerebral microangiography.…”

Section: Discussionmentioning

confidence: 99%

Three-Dimensional Iron Oxide Nanoparticle-Based Contrast-Enhanced Magnetic Resonance Imaging for Characterization of Cerebral Arteriogenesis in the Mouse Neocortex

et al. 2021

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Purpose: Subsurface blood vessels in the cerebral cortex have been identified as a bottleneck in cerebral perfusion with the potential for collateral remodeling. However, valid techniques for non-invasive, longitudinal characterization of neocortical microvessels are still lacking. In this study, we validated contrast-enhanced magnetic resonance imaging (CE-MRI) for in vivo characterization of vascular changes in a model of spontaneous collateral outgrowth following chronic cerebral hypoperfusion.Methods: C57BL/6J mice were randomly assigned to unilateral internal carotid artery occlusion or sham surgery and after 21 days, CE-MRI based on T2*-weighted imaging was performed using ultra-small superparamagnetic iron oxide nanoparticles to obtain subtraction angiographies and steady-state cerebral blood volume (ss-CBV) maps. First pass dynamic susceptibility contrast MRI (DSC-MRI) was performed for internal validation of ss-CBV. Further validation at the histological level was provided by ex vivo serial two-photon tomography (STP).Results: Qualitatively, an increase in vessel density was observed on CE-MRI subtraction angiographies following occlusion; however, a quantitative vessel tracing analysis was prone to errors in our model. Measurements of ss-CBV reliably identified an increase in cortical vasculature, validated by DSC-MRI and STP.Conclusion: Iron oxide nanoparticle-based ss-CBV serves as a robust, non-invasive imaging surrogate marker for neocortical vessels, with the potential to reduce and refine preclinical models targeting the development and outgrowth of cerebral collateralization.

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Detecting sub-voxel microvasculature with USPIO-enhanced susceptibility-weighted MRI at 7 T

Cited by 18 publications

References 25 publications

An Overview of Venous Abnormalities Related to the Development of Lesions in Multiple Sclerosis

An Overview of Venous Abnormalities Related to the Development of Lesions in Multiple Sclerosis

Revealing vascular abnormalities and measuring small vessel density in multiple sclerosis lesions using USPIO

Three-Dimensional Iron Oxide Nanoparticle-Based Contrast-Enhanced Magnetic Resonance Imaging for Characterization of Cerebral Arteriogenesis in the Mouse Neocortex

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