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BOLD signal within and around white matter lesions distinguishes multiple sclerosis and non-specific white matter disease: a three-dimensional approach

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Abstract

Multiple sclerosis (MS) diagnostic criteria are based upon clinical presentation and presence of white matter hyperintensities on two-dimensional magnetic resonance imaging (MRI) views. Such criteria, however, are prone to false-positive interpretations due to the presence of similar MRI findings in non-specific white matter disease (NSWMD) states such as migraine and microvascular disease. The coexistence of age-related changes has also been recognized in MS patients, and this comorbidity further poses a diagnostic challenge. In this study, we investigated the physiologic profiles within and around MS and NSWMD lesions and their ability to distinguish the two disease states. MS and NSWMD lesions were identified using three-dimensional (3D) T2-FLAIR images and segmented using geodesic active contouring. A dual-echo functional MRI sequence permitted near-simultaneous measurement of blood-oxygen-level-dependent signal (BOLD) and cerebral blood flow (CBF). BOLD and CBF were calculated within lesions and in 3D concentric layers surrounding each lesion. BOLD slope, an indicator of lesion metabolic capacity, was calculated as the change in BOLD from a lesion through its surrounding perimeters. We observed sequential BOLD signal reductions from the lesion towards the perimeters for MS, while no such decreases were observed for NSWMD lesions. BOLD slope was significantly lower in MS compared to NSWM lesions, suggesting decreased metabolic activity in MS lesions. Furthermore, BOLD signal within and around lesions significantly distinguished MS and NSWMD lesions. These results suggest that this technique shows promise for clinical utility in distinguishing NSWMD or MS disease states and identifying NSWMD lesions occurring in MS patients.

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Acknowledgements

We thank all the patients and volunteers who participated in this research efforts. We thank our lab research interns and coordinators for their help in recruiting patients and volunteering for the study. Special thanks to Jeffery Spence, and Hanzhang Lu for their scientific input regarding the study. Funding: This work was supported by a National Multiple Sclerosis Society Research Grant (RG-1507-04951) to BR and DO.

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Authors and Affiliations

  1. School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, USA

    Dinesh K. Sivakolundu, Kathryn L. West, Mark D. Zuppichini & Bart Rypma

  2. Neuroinnovation Program, Multiple Sclerosis & Neuroimmunology Imaging Program, Department of Neurology & Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX, USA

    Tatum M. Moog, Aiden P. Blinn & Darin T. Okuda

  3. Department of Computer Science, University of Texas at Dallas, Dallas, TX, USA

    Andrew Wilson, Yeqi Wang, Thomas Stanley & Xiaohu Guo

  4. Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX, USA

    Bart Rypma

  5. Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

    Braeden D. Newton

  6. Department of Biological Sciences, University of Texas at Dallas, Dallas, TX, USA

    Dinesh K. Sivakolundu

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  1. Dinesh K. Sivakolundu
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Correspondence to Darin T. Okuda.

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Conflicts of interest

KW, MZ, AW, XG, TM, AB, YW, TS, and BR report no disclosures. DO received advisory and consulting fees from Celgene, EMD Serono, Genentech, Genzyme, and Novartis and research support from Biogen. DS, BN, and DO have a patent pending related to the submitted work.

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This study was approved by the University of Texas Southwestern Medical Center Institution Review Board. Written informed consent was obtained from all participants prior to study participation.

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Sivakolundu, D.K., West, K.L., Zuppichini, M.D. et al. BOLD signal within and around white matter lesions distinguishes multiple sclerosis and non-specific white matter disease: a three-dimensional approach. J Neurol 267, 2888–2896 (2020). https://doi.org/10.1007/s00415-020-09923-z

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  • DOI: https://doi.org/10.1007/s00415-020-09923-z

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