Sheng-Kwei (Victor) Song
Washington University School of Medicine
Biomedical Magnetic Resonance Laboratory
Campus Box 8227
4525 Scott Avenue
St. Louis, MO 63110
Professor of Radiology
The development of diffusion MRI derived biomarker of white matter injury and function has been the primary research goal of Song lab.
- Diffusion Basis Spectrum Imaging (DBSI): Over the years, we have observed the insufficiency of diffusion tensor imaging (DTI) to detect white matter injury in the presence of inflammation associated cellular infiltration and edema, in addition to the previously known crossing-fiber and cerebrospinal fluid contamination. To quantitatively address these confounding factors affecting DTI sensitivity and specificity to the white matter pathologies, a novel diffusion basis spectrum imaging (DBSI) has been developed. In brief, DBSI models diffusion weighted MR signals as a linear combination of anisotropic (representing crossing fiber tracts) and isotropic (reflecting extra-axonal environment associated with inflammation and tissue loss) tensors. Preliminary findings in optic nerves and spinal cord from experimental autoimmune encephalomyelitis (EAE) mice, spinal cord from mouse model of contusion spinal cord injury, corpus callosum from cuprizone treated mice, and brain of stroke rats support that DBSI indeed resolved and quantified extra-axonal structural and pathological complications accurately estimating increased cellularity and vasogenic edema associated with inflammation. Currently, we have translated DBSI to human imaging brain, optic nerve, and spinal cord pathologies in patients of multiple sclerosis. In addition, DBSI has also been applied to image spinal cord damages in patients with spinal cord injury (SCI) or cervical spondylotic myelopathy (CSM) patients assessing the extent of irreversible axonal loss noninvasively. Other human translation of DBSI including brain tumor, stroke, traumatic brain injury (TBI), prostate cancer (PCa), and Alzheimer’s disease.
- Diffusion functional MRI (diffusion fMRI): Standard blood-oxygen-level-dependent (BOLD) fMRI studies have been applied to examine brain plasticity in patients and provide valuable information about gray-matter function. However, the lower fractional blood volumes and the limited capacity for physiological modulation of white-matter blood volume prevents application of BOLD fMRI to assess white-matter function. Thus white-matter MRI is, at present, largely limited to probing structural integrity of fiber tracts. In preliminary investigations we observed, for the first time, a visual stimulus-induced 27% decrease in the apparent diffusion coefficient of water perpendicular to the axonal fibers (ADC⊥) for C57BL/6 mouse optic nerve in vivo. No change in ADC|| (diffusion parallel to the optic nerve fibers) was observed during visual stimulation. The stimulus-induced changes are completely reversible. A possible vascular contribution was definitively ruled out since the stimulus-induced ADC⊥ change was reproduced in hypercapnic mice while resting ADC⊥ was indistinguishable from that in room-air-mice. Further application of diffusion fMRI to EAE mice detected a significantly reduced extent of optic nerve function in EAE mice, correlating with immunohistochemistry quantified axonal injury, demyelination and inflammation; positively correlating with visual.
- Simultaneously imaging nerve function and pathologies: DBSI detects and differentiates optic nerve axonal injury, demyelination, and inflammation and can be used to quantify axon number. Diffusion fMRI measures visual-stimulation-induced decreases in the apparent diffusion coefficient (ADC), a sensitive indicator of optic nerve function. We will combine these technologies to deliver a new, diffusion MRI-based method to assess optic nerve anatomy, function and pathology simultaneously in both mice and human. We will validate this approach by monitoring the progression and/or regression of axonal damage in glaucoma and optic neuritis. Both in vivo MRI measurements and in silico Monte-Carlo simulation will be pursued to establish the clinically usable diffusion MRI protocol to image nerve function and pathology simultaneously.
- Y. Wang, Q. Wang, S.K. Song, “Diagnosis of Central Nervous System White Matter Pathology Using Diffusion MRI” USA Patent. Serial No. 61/345,367.
- Ze-Zhong Ye and Sheng-Kwei Song, “Quantitative Differentiation of Inflammation from Solid Tumors, Heart and Nerve Injury” Provisional patent filed on 8/30/2016.
- Song SK, Sun SW, Ramsbottom MJ, Chang C, Russell J, Cross AH. Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water. Neuroimage. 2002 Nov; 17 (3):1429-36. PubMed PMID: 12414282.
- Song SK, Qu Z, Garabedian EM, Gordon JI, Milbrandt J, Ackerman JJ. Improved magnetic resonance imaging detection of prostate cancer in a transgenic mouse model. Cancer Res. 2002 Mar 1;62(5):1555-8. PubMed PMID: 11888935.
- Song SK, Sun SW, Ju WK, Lin SJ, Cross AH, Neufeld AH. Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia. Neuroimage. 2003 Nov;20(3):1714-22. PubMed PMID: 14642481.
- Song SK, Yoshino J, Le TQ, Lin SJ, Sun SW, Cross AH, Armstrong RC. Demyelination increases radial diffusivity in corpus callosum of mouse brain. Neuroimage. 2005 May 15;26(1):132-40. PubMed PMID: 15862213.
- Xu J, Humphrey PA, Kibel AS, Snyder AZ, Narra VR, Ackerman JJ, Song SK. Magnetic resonance diffusion characteristics of histologically defined prostate cancer in humans. Magn Reson Med. 2009 Apr;61(4):842-50. PubMed PMID: 19215051; PubMed Central PMCID: PMC3080096.
- Wang Y, Wang Q, Haldar JP, Yeh FC, Xie M, Sun P, Tu TW, Trinkaus K, Klein RS, Cross AH, Song SK. Quantification of increased cellularity during inflammatory demyelination. Brain. 2011 Dec;134(Pt 12):3590-601. PubMed PMID: 22171354; PubMed Central PMCID: PMC3235568.
- Spees WM, Lin TH, Song SK. White-matter diffusion fMRI of mouse optic nerve. Neuroimage. 2013 Jan 15;65:209-15. PubMed PMID: 23085108; PubMed Central PMCID: PMC3513522.
- Chiang CW, Wang Y, Sun P, Lin TH, Trinkaus K, Cross AH, Song SK. Quantifying white matter tract diffusion parameters in the presence of increased extra-fiber cellularity and vasogenic edema. Neuroimage. 2014 Nov 1;101:310-9. PubMed PMID: 25017446; PubMed Central PMCID: PMC4165711.
- Lin TH, Spees WM, Chiang CW, Trinkaus K, Cross AH, Song SK. Diffusion fMRI detects white-matter dysfunction in mice with acute optic neuritis. Neurobiol Dis. 2014 Jul;67:1-8. PubMed PMID: 24632420; PubMed Central PMCID: PMC4035476.
- Wang Y, Sun P, Wang Q, Trinkaus K, Schmidt RE, et al. Differentiation and quantification of inflammation, demyelination and axon injury or loss in multiple sclerosis. Brain. 2015 Feb 26;PubMed PMID: 25724201.
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