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Evaluation of Intravoxel Incoherent Motion in the Spinal Cord of Multiple Sclerosis Patients1Philips, Cleveland, OH, United States, 2Radiology, University of Texas Southwestern Medical Center, Dallas, TX, United States, 33Department of Health and Care Professions, University of Exeter, Exeter, United Kingdom
Synopsis
Keywords: Spinal Cord, Spinal Cord
Motivation: Previous perfusion-weighted imaging studies in multiple sclerosis (MS) have revealed alterations of cerebral perfusion, yet these types of studies have not been translated to studying MS in the spinal cord.
Goal(s): Evaluate the use of intravoxel incoherent motion (IVIM) as a non-contrast MRI technique to assess perfusion in the spinal cord of MS.
Approach: A cross-sectional analysis was conducted to determine spinal cord, white matter, and gray matter differences in IVIM-derived indices between the healthy and MS cohorts.
Results: Spinal cord white matter perfusion fraction (p=0.082) and pseudo-diffusion (p=0.055) measurements came close to statistical significance between MS patients and healthy controls.
Impact: This is the first study utilizing IVIM in the spinal cord and the findings suggest that IVIM has potential as a tool for assessing the microcirculation of the human spinal cord in MS.
Introduction:
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system which leads to demyelination and neurodegeneration1. Early and accurate diagnosis of MS is critical and is done through a combination of reported clinical symptoms and positive radiological findings on MRI. The pathogenesis of MS is not completely understood, however, there is growing evidence that a vascular component may contribute to the progression of the disease2. Advanced MRI techniques, including perfusion weighted imaging (PWI), have been used to better characterize and understand MS3. Previous PWI studies in MS have revealed alterations of cerebral perfusion compared with healthy controls. In MS patients, the spinal cord is often affected by inflammation and demyelination. Spinal cord abnormalities are also visible on up to 90% of MS patients MRI’s4. However, all of the PWI work in MS has been done in the brain leaving a gap of information in regards to perfusion changes in the spinal cord caused by the progression of MS5. Intravoxel incoherent motion (IVIM) offers a non-contrast way to study the microcirculatory blood and provide in-vivo perfusion information6. Here we evaluate the ability of IVIM to differentiate microcirculation changes in the spinal cord of MS patients.Methods:
Fifteen healthy controls with a mean age of 29.0 ± 5.0 years (10 males, and 5 females), and fifteen MS patients with a mean age of 39.3 ± 6.1 years, (15 females) were enrolled and underwent MR imaging. All MRI experiments were performed on a 3T scanner (Philips Achieva, Best, Netherlands) using a 16-channel phased array neurovascular coil. Multi-echo T2* GRE (0.65 × 0.65 × 5 mm3, TE = 7.1ms, TR = 753ms, flip angle = 28°) scans were acquired to obtain high-resolution anatomical images for visualization of the spinal cord white matter, gray matter, and MS Lesions (Figure 1). Fat suppressed multi-shell DWI (1.25 × 1.25 × 10 mm3, TE = 65ms, TR = 3000ms, 96 directions, b-values = 0 – 2855 s/mm2) were used to perform IVIM calculations. T2* and DWI were acquired axially with slice prescriptions centered at the C3/C4 intervertebral disc level. Analysis (Figure 2) consisting of segmentation, co-registration, and metric extraction was performed using the open-source spinal cord toolbox (https://github.com/spinalcordtoolbox). IVIM metrics (Figure 3) for perfusion fraction (fIVIM), pseudo-diffusion coefficient (D*) and water diffusion coefficient in tissue (D) were computed using the open source IVIM-tool box (https://github.com/slevyrosetti/ivim-toolbox). Two-sample T-test was performed using MiniTab (Minitab 18 Statistical Software, State College, PA) on the mean fIVIM, D*, D values in the spinal cord, white matter (WM), and gray matter (GM) between healthy controls and MS patients. Significance threshold was set at p<0.05.Results:
No significant differences were found (Figure 4) between the healthy controls and MS patient groups in the s[inal cord, WM, or GM ROIs for any of the IVIM indices (fIVIM, D*, D). However, the WM ROI perfusion fraction (fIVIM) and pseudo-diffusion (D*) measurements came close to statistical significance with p-values of 0.082 and 0.055 respectively (Table 1). The WM ROI reached the highest significance for all three IVIM metrics analyzed whereas the GM ROI showed the lowest. Looking at all the ROIs the GM showed the highest perfusion fraction (fIVIM) with the WM ROI being the lowest. This relationship was also seen for the pseudo-diffusion coefficient (D*) with WM showing the lowest followed by the SC and the GM exhibiting the highest value.Discussion:
In this study, we investigated IVIM to assess microvascular perfusion and diffusion in the spinal cord of MS patients. Although not reaching the level of significance there are several findings of interest in this study. The SC, WM, and GM in the MS cohort showed reduced perfusion fraction and pseudo-diffusion coefficient compared to the healthy controls. Overall, our findings are consistent with the current PWI literature focused on MS in the brain. MS PWI findings have shown decreased cerebral blood flow and cerebral blood volume in chronic MS lesions when compared to NAWM and controls7. Gray matter in MS patients also showed reduced perfusion when compared to healthy controls3. Limitations of this study include the small number of subjects and that the MS patient cohort was entirely female.Conclusion:
IVIM is a promising technique for the evaluation of the spinal cord in MS patients. It has the potential to provide valuable information on the microvascular perfusion and diffusion, which may be related to the disease progression and response to treatment. Further research is needed to improve the technical and methodological aspects of IVIM and to better understand the underlying microstructural changes and the potential confounding factors.Acknowledgements
This research was supported by a grant from the American Society of Radiological Technologists Foundation.References
1. Dendrou CA, Fugger L, Friese MA. Immunopathology of multiple sclerosis. Nature Reviews Immunology. 2015;15(9):545.
2. Grigoriadis N, Van Pesch V. A basic overview of multiple sclerosis immunopathology. European journal of neurology. 2015;22:3-13.
3. Lapointe E, Li D, Traboulsee A, Rauscher A. What have we learned from perfusion MRI in multiple sclerosis? American Journal of Neuroradiology. 2018;39(6):994-1000.
4. Bot JC, Barkhof F, Polman C, et al. Spinal cord abnormalities in recently diagnosed MS patients: added value of spinal MRI examination. Neurology. 2004;62(2):226-233.
5. Kearney H, Miller DH, Ciccarelli O. Spinal cord MRI in multiple sclerosis—diagnostic, prognostic and clinical value. Nature Reviews Neurology. 2015;11(6):327-338.
6. Federau C. Intravoxel incoherent motion MRI as a means to measure in vivo perfusion: A review of the evidence. NMR in Biomedicine. 2017;30(11):e3780.
7. Boxerman JL, Hamberg LM, Rosen BR, Weisskoff RM. MR contrast due to intravascular magnetic susceptibility perturbations. Magnetic resonance in medicine. 1995;34(4):555-566.
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