Assessing Cortical Cerebral Microinfarcts on High Resolution MR Images

Summary

A high resolution ex vivo 7T MR imaging protocol is presented, to perform MR-guided histopathological validation of microvascular pathology in post-mortem human brain tissue. Furthermore, guidelines are provided for the assessment of cortical microinfarcts on in vivo 7T as well as 3T MR images.

Abstract

Cerebral microinfarcts are frequent findings in the post-mortem human brain, and are related to cognitive decline and dementia. Due to their small sizes it is challenging to study them on clinical MRI scans. It was recently demonstrated that cortical microinfarcts can be depicted with MRI scanners using high magnetic field strengths (7T). Based on this experience, a proportion of these lesions is also visible on lower resolution 3T MRI. These findings were corroborated with ex vivo imaging of post-mortem human brain tissue, accompanied by histopathological verification of possible cortical microinfarcts.

Here an ex vivo imaging protocol is presented, for the purpose of validating MR observed cerebral microvascular pathology with histological evaluation. Furthermore, guidelines are provided for the assessment of cortical microinfarcts on both in vivo 7T and 3T MR images. These guidelines provide researchers with a tool to rate cortical microinfarcts on in vivo images of larger patient samples, to further unravel their clinical relevance in cognitive decline and dementia, and establish these lesions as a novel biomarker of cerebral small vessel disease.

Introduction

The application of ultra-high field 7 Tesla (T) MRI in patient studies is rapidly progressing¹. This paper introduces a representative application of 7T MRI in the context of cerebrovascular disease in the aging human brain. Cerebrovascular disease is a major cause of cognitive decline and dementia. This vascular contribution to dementia frequently involves the small vessels of the brain, such as arterioles, small veins, and capillaries. Hence, it is referred to as cerebral small vessel disease (SVD)². Because the cerebral small vessels are too small to capture with conventional MRI, only the consequences of SVD - i.e., the resulting tis....

Protocol

The use of the autopsy samples and in vivo MR images for this protocol was in accordance with local regulations and approved by the local institutional review board of the University Medical Center Utrecht (UMCU).

1. MR-guided Histopathological Validation of Cortical Microinfarcts

1. Ex vivo MRI
   1. When handling brain tissue, always wear gloves and suitable protective clothing.
   2. Based on the research question, select appropriate, preferably 10-mm thick, formalin-fixed brain slabs. The brain slabs for this paper were derived from the neuropathology department of the UMCU, and VU University Medica....

Results

An impression of the high resolution and high image quality of an ex vivo sequence acquired at 7T is provided here (Figure 4). This is a 3D T2* weighted ex vivo scan, with an isotropic resolution of 0.18 mm. Tissue was derived from an 84-year old demented female with pathologically proven Alzheimer’s disease and severe cerebral amyloid angiopathy (CAA). The detail of the image allows the identification of cortical mi.......

Discussion

CMIs have attracted increasing attention over the last few years. A growing body of evidence derived from autopsy studies has identified CMIs as important contributors to age-related cognitive decline and dementia^4,5. CMIs are now detectable on 7T and also 3T MRI. Optimization and standardization of assessment protocols for these lesions will support rapid implementation of robust and valid CMI detection in cohort studies throughout the world. This will enable a widespread evaluation of the clinical relevance .......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Fomblin / Galden PFPE	Solvay Solexis, Bollate, Italy
7T MR system	Philips Healthcare, Cleveland, OH, USA
32-channel receive head coil	Nova Medical, Wilmington, MA, USA
MeVisLab	MeVis Medical Solutions AG, Bremen, Germany