Myelin water imaging in multiple sclerosis: quantitative correlations with histopathology

Abstract

Various magnetic resonance (MR) techniques are used to study the pathological evolution of demyelinating diseases, such as multiple sclerosis (MS). However, few studies have validated MR derived measurements with histopathology. Here, we determine the correlation of myelin water imaging, an MR measure of myelin content, with quantitative histopathologic measures of myelin density. The multi-component T2 distribution of water was determined from 25 formalin-fixed MS brain samples using a multi-echo T2 relaxation MR experiment. The myelin water fraction (MWF), defined as T2 signal below 30 milliseconds divided by the total signal, was determined for various regions of interest and compared to Luxol fast blue (myelin stain) mean optical density (OD) for each sample. MWF had a strong correlation with myelin stain [mean (range) R2 = 0.67 (0.45-0.92)], validating MWF as a measure of myelin density. This quantitative technique has many practical applications for the in vivo monitoring of demyelination and remyelination in a variety of disorders of myelin.

Improved myelin water quantification using spatially regularized non‐negative least squares algorithm

“…Despite its improved performance compared with the original NNLS algorithm, the rNNLS algorithm is still sensitive to noise in the data. Therefore, to achieve reasonable SNR before the rNNLS algorithm is applied, four CPMG acquisitions at 1.5 Tesla (T) are typically averaged, which makes the total acquisition time as long as 26 minutes for a single slice (3,4,6,18).In this study, we expanded the regularization of the rNNLS algorithm into the spatial domain in addition to the spectral domain for robust MWF measurements with reduced sensitivity to noise. A similar spatial regularization concept was used in the analysis of longitudinal relaxation data for the inverse Laplace transform to obtain the fractional contributions of WM, gray mat-…”

“…QUANTITATIVE MEASUREMENTS of myelin content can substantially improve our understanding of the pathological progress of several white matter (WM) diseases, such as multiple sclerosis (MS) (1)(2)(3)(4). A technique that provides specific and sensitive information about the myelin content was developed based on an analysis of T 2 relaxation times (5,6).…”

“…A technique that provides specific and sensitive information about the myelin content was developed based on an analysis of T 2 relaxation times (5,6). It has been reported that the T 2 spectrum of WM and several myelinated tissue samples consists of multiple components (7)(8)(9)(10)(11)(12)(13) and that the short component with T 2 between 10 ms and 50 ms corresponds to the water pool within the myelin sheath (2)(3)(4)(5)(6). Myelin content can therefore be quantitated using the fraction of this short T 2 component.…”

Computationale Neuroanatomie und Mikrostrukturbildgebung mit der Magnetresonanztomographie

“…T1, T2, T2*, PD und MT hängen unter anderem vom makromolekularen Gehalt ab und werden daher als Biomarker für Myelinisierung verwendet [12][13][14][15]. Die Diffusionsbildgebung [16,17] Abb.…”

Neuroimaging in Multiple Sclerosis: Neurotherapeutic Implications

“…Diffusion tensor imaging can be used to monitor tract-specific changes that may be more closely linked to clinical measures [105,106] and may be particularly powerful when combined with functional measures, such as functional MRI [107]. T1/T2 relaxation is another quantitative approach that may provide a better metric for diffuse brain changes occurring beyond traditional white matter regions [108] and to quantify myelin content [109]. Quantification of brain iron levels is an area attracting intense interest [110].…”