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A preliminary assessment of the relationship of radial diffusivity of the fornix to future episodic memory performance in Multiple Sclerosis1Imaging Sciences, The Cleveland Clinic, Cleveland, OH, United States, 2Neurological Institute, The Cleveland Clinic, Cleveland, OH, United States, 3Schey Center for Cognitive Neuroimaging, The Cleveland Clinic, Cleveland, OH, United States
Synopsis
Here we present a preliminary report assessing the relationship of DTI measures of the fornix to future episodic memory in patients with multiple sclerosis (MS). We find that radial diffusivity of the fornix is longitudinally related to visual spatial episodic memory. This finding suggests this measure is appropriate to investigate as a potential predictive marker of cognitive decline.
Introduction
Approximately half of individuals affected by multiple sclerosis (MS) experience cognitive dysfunction,1 which can have a major impact on quality of life and is associated with increased depression and unemployment rate. There is currently no measure that can predict which patients are at risk of cognitive decline. Our previous work found that radial diffusivity (RD) of the fornix, as measured with diffusion tensor imaging (DTI) MRI, was related to cognitive performance in a cross-sectional sample of patients with MS, particularly to visual spatial episodic memory.2 Here we present preliminary results from a longitudinal study, the aim of which is to define neuroimaging markers related to future cognitive decline. We hypothesize that RD of the fornix at baseline will be related to future episodic memory performance in a longitudinal cohort of patients with MS.Methods
In an IRB-approved protocol, 56 participants with MS (age: 50.72 ± 8.4 years, 16 males, EDSS: 3.9 ± 1.5) were scanned on a Siemens 7T Magnetom with SC72 gradient (Siemens Medical Solutions, Erlangen) using a 32-channel head coil (Nova Medical). All participants completed the Selective Reminding Test (SRT), a measure of verbal episodic memory, and the Brief Visual Spatial Memory Test (BVMT-R), a measure of visual spatial episodic memory. Eighteen participants returned for a second scan and cognitive testing session after 1 year (time point 2; TP2).
MRI acquisition
A whole-brain anatomical MP2RAGE (voxel size = 0.75mm3) and a DTI scan were acquired. DTI acquisition parameters were as follows: 100-1mm thick axial slices; 60 directions with b=1000 sec/mm2, TE/TR=61.1/10600ms, matrix=192x192, FOV=192 x 192mm2; GRAPPA 3; readout BW = 1532 Hz/pixel, scan time 12 minutes.
Data analysis
Post-processing of DTI data included motion correction3, unwarping4, and the voxel-wise calculation of diffusion tensors5. The right and left fornix were manually drawn on the high-resolution MP2RAGE, starting at the separation of the crura and continuing to the fimbria. The fornix regions of interest (ROIs) were transformed to DTI space and checked for accuracy. Mean axial diffusivity (AD) and RD were calculated for each ROI. Pearson correlations were used to assess the relationship of diffusion and cognition.
Results
At baseline, BVMT was negatively related to RD of the left fornix (r = -0.38, p < 0.0004; Figure 1), though showed no relationship on the right. SRT performance was related to RD of both the right (r = -0.50, p < 8.9x10-5) and left (r = -0.44, p < 0.0006) fornix. There was no difference in RD of the fornix from TP1 to TP2. Lower RD of the left fornix at TP1 was related to better performance on the BVMT at TP2 (r = -0.50, p < 0.034; Figure 2). The relationship of the change in SRT performance to RD of the right fornix at TP1 trended toward significance (r = -0.33, p < 0.170).Discussion and Conclusion
Though our longitudinal sample is small, we are encouraged to find that MRI measures are related to later cognitive performance. We expect that the relationship of TP1 diffusion to the change in cognitive performance will become stronger as sample size increases. This suggests that imaging measures may be useful as a predictor of future cognitive decline. Additional visits are in progress, and as more longitudinal data is collected we will more fully assess the value of baseline DTI measures to predict future cognitive function.
Acknowledgements
This work was supported by the Department of Defense (MS150097). The authors acknowledge technical support by Siemens Medical Solutions.References
1. Achiron A, Chapman J, Magalashvili D, Dolev M, Lavie M, Bercovich E, et al. Modeling of Cognitive Impairment by Disease Duration in Multiple Sclerosis: A Cross-Sectional Study. PLoS One. 2013;8(8):e71058
2. Koenig, K.A., Sakaie, K.E., Lowe, M.J., Lin, J., Stone, L., Bermel, R.A., Beall, E.B., Rao, S.M., Trapp, B.D., Phillips, M.D. (2013) High spatial and angular resolution diffusion imaging reveals forniceal damage related to memory impairment. MRI, 31:5; 695-699.
3. Sakaie KE, Lowe MJ. Quantitative assessment of motion correction for high angular resolution diffusion imaging. Magn Reson Imaging. 2010;28(2):290-6.
4. Jenkinson M. A fast, automated, n-dimensional phase unwrapping algorithm. . Magnetic Resonance in Medicine. 2003;49(1):193-7.
5. Basser PJ, Mattiello J, LeBihan D. Estimation of the effective self-diffusion tensor from the NMR spin echo. J Magn Reson B. 1994;103(3):247-54.
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