White matter lesion burden correlates with the free water distribution surrounding the lateral ventricle

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AbstractBackgroundThe clearance function is considered playing significant role in the neurodegeneration and neuroinflammation diseases, such as Alzheimer's disease (AD), Parkinson disease (PD) and multiple sclerosis (MS), etc. The enlarged perivascular space (EPVS) is believed to be a main pathway for the clearance of metabolic wastes. The free water in the PVS helps to clear the waste. The dysfunction of clearance function may accelerate the progression of diseases. We propose to use a T2 relaxometry based free water mapping to investigate the free water distribution in MS subjects. We call the free water mapping as cerebrospinal fluid water fraction (CSFF).MethodMulti‐echo T2 image was acquired with 7 echoes (TE = 0, 7.5, 17.5, 67.5, 147.5, 307.5, 1000 ms). Then the T2 data was fitted to three‐compartment water model (myelin water, intro‐extracellular water, and free water) by the T2 relaxometry of different tissue type. The CSFF in the white matter region is extracted from the FreeSurfer processed white matter mask. For each subject, the extracted WM CSFF was organized into a column vector and then fed in the k‐means algorithm. The number of categories is set to k = 8, which is sufficient to categorize the WM CSFF pattern into detailed tissue structure. We are interested in the distribution pattern of smallest CSFF values in WM, i.e., the category that has smallest mean CSFF.We then check the correspondence between the smallest CSFF pattern with the anatomic structure. If the distribution of the smallest CSFF is continuous region near the posterior of ventricle CSF, then we call the subject CSFF‐negative (Fig. 1a), otherwise it’s CSF‐positive (Fig. 1b).ResultThe distribution of the smallest WM CSFF in the MS cohort is significantly related to the severity of the disease. CSFF‐positive subjects have light MS lesion load, while the CSFF‐negative subjects have heavy MS lesion load (Fig.2).ConclusionThe results show that the T2 relaxometry based free water mapping could be treated as a biomarker of MS load. This finding might be helpful for the understanding of development of MS disease.