Kimberly J Hemmerling

Numerous approaches have been used to denoise spinal cord functional magnetic resonance imaging (fMRI) data. Principal component analysis (PCA)-based techniques, which derive regressors from a noise region of interest (ROI), have been used in both brain (e.g., CompCor) and spinal cord fMRI. However, spinal cord fMRI denoising methods have yet to be systematically evaluated. Here, we formalize and evaluate a PCA-based technique for deriving nuisance regressors for spinal cord fMRI analysis (SpinalCompCor). In this method, regressors are derived with PCA from a noise ROI, an area defined outside of the spinal cord and cerebrospinal fluid. A parallel analysis is used to systematically determine how many components to retain as regressors for modeling; this designated a median of 9 regressors across four fMRI datasets: motor task (n=26), breathing task (n=27), and resting state (n=15 and n=10). First-level fMRI modeling demonstrated that principal component regressors did fit noise (e.g., physiological noise from blood vessels), though the effectiveness may be dependent upon the acquisition parameters. However, group-level activation maps did not show a clear benefit from including SpinalCompCor regressors. The potential for collinearity of principal component regressors with the task may be a concern, and this should be considered in future implementations for which task-correlated noise is anticipated. In general, denoising with SpinalCompCor regressors in place of physiological recording-derived regressors is only recommended when the latter are unavailable, as SpinalCompCor may not consistently reproduce recording-based denoising across datasets or acquisitions.

Impaired spinal cord vascular function contributes to numerous neurological pathologies, making it important to be able to noninvasively characterize these changes. Here, we propose a functional magnetic resonance imaging (fMRI)-based method to map spinal cord vascular reactivity (SCVR). We used a hypercapnic breath-holding task, monitored with end-tidal CO2 (PETCO2), to evoke a systemic vasodilatory response during concurrent blood oxygenation level-dependent (BOLD) fMRI. SCVR amplitude and hemodynamic delay were mapped at the group level in 27 healthy participants as proof-of-concept of the approach, and then in two highly-sampled participants to probe feasibility/stability of individual SCVR mapping. Across the group and the highly-sampled individuals, a strong ventral SCVR amplitude was initially observed without accounting for local regional variation in the timing of the vasodilatory response. Shifted breathing traces (PETCO2) were used to account for temporal differences in the vasodilatory response across the spinal cord, producing maps of SCVR delay. These delay maps reveal an earlier ventral and later dorsal response and demonstrate distinct gray matter regions concordant with territories of arterial supply. The SCVR fMRI methods described here enable robust mapping of spatiotemporal hemodynamic properties of the human spinal cord. This noninvasive approach has exciting potential to provide early insight into pathology-driven vascular changes in the cord, which may precede and predict future irreversible tissue damage and guide the treatment of several neurological pathologies involving the spine.

Upper extremity motor paradigms during spinal cord functional magnetic resonance imaging (fMRI) can provide insight into the functional organization of the cord. Hand-grasping is an important daily function with clinical significance, but previous studies of similar squeezing movements have not reported consistent areas of activity and are limited by sample size and simplistic analysis methods. Here, we study spinal cord fMRI activation using a unimanual isometric hand-grasping task that is calibrated to participant maximum voluntary contraction (MVC). Two task modeling methods were considered: (1) a task regressor derived from an idealized block design (Ideal) and (2) a task regressor based on the recorded force trace normalized to individual MVC (%MVC). Across these two methods, group motor activity was highly lateralized to the hemicord ipsilateral to the side of the task. Activation spanned C5–C8 and was primarily localized to the C7 spinal cord segment. Specific differences in spatial distribution are also observed, such as an increase in C8 and dorsal cord activity when using the %MVC regressor. Furthermore, we explored the impact of data quantity and spatial smoothing on sensitivity to hand-grasp motor task activation. This analysis shows a large increase in number of active voxels associated with the number of fMRI runs, sample size, and spatial smoothing, demonstrating the impact of experimental design choices on motor activation.