publications

2024

1. bioRxiv

   MRI mapping of hemodynamics in the human spinal cord

   Kimberly J. Hemmerling, Mark A. Hoggarth, Milap S. Sandhu, Todd B. Parrish, and Molly G. Bright

   Human Brain Mapping, Feb 2024

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   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.

2023

1. Hum Brain Mapp

   Spatial distribution of hand-grasp motor task activity in spinal cord functional magnetic resonance imaging

   Kimberly J. Hemmerling, Mark A. Hoggarth, Milap S. Sandhu, Todd B. Parrish, and Molly G. Bright

   Human Brain Mapping, Aug 2023

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   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.

2022

1. Front Neurol

   Effects of variability in manually contoured spinal cord masks on fMRI co-registration and interpretation

   Mark A. Hoggarth, Max C. Wang, Kimberly J. Hemmerling, Andrew D. Vigotsky, Zachary A. Smith, and 3 more authors

   Frontiers in Neurology, Oct 2022

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   Functional magnetic resonance imaging (fMRI) of the human spinal cord (SC) is a unique non-invasive method for characterizing neurovascular responses to stimuli. Group-analysis of SC fMRI data involves co-registration of subject-level data to standard space, which requires manual masking of the cord and may result in bias of group-level SC fMRI results. To test this, we examined variability in SC masks drawn in fMRI data from 21 healthy participants from a completed study mapping responses to sensory stimuli of the C7 dermatome. Masks were drawn on temporal mean functional image by eight raters with varying levels of neuroimaging experience, and the rater from the original study acted as a reference. Spatial agreement between rater and reference masks was measured using the Dice Similarity Coefficient, and the influence of rater and dataset was examined using ANOVA. Each rater’s masks were used to register functional data to the PAM50 template. Gray matter-white matter signal contrast of registered functional data was used to evaluate the spatial normalization accuracy across raters. Subject- and group-level analyses of activation during left- and right-sided sensory stimuli were performed for each rater’s co-registered data. Agreement with the reference SC mask was associated with both rater (F_{(7, 140)} = 32.12, P < 2 × 10⁻¹⁶, η² = 0.29) and dataset (F_{(20, 140)} = 20.58, P < 2 × 10⁻¹⁶, η² = 0.53). Dataset variations may reflect image quality metrics: the ratio between the signal intensity of spinal cord voxels and surrounding cerebrospinal fluid was correlated with DSC results (p < 0.001). As predicted, variability in the manually-drawn masks influenced spatial normalization, and GM:WM contrast in the registered data showed significant effects of rater and dataset (rater: F_{(8, 160)} = 23.57, P < 2 × 10⁻¹⁶, η² = 0.24; dataset: F_{(20, 160)} = 22.00, P < 2 × 10⁻¹⁶, η² = 0.56). Registration differences propagated into subject-level activation maps which showed rater-dependent agreement with the reference. Although group-level activation maps differed between raters, no systematic bias was identified. Increasing consistency in manual contouring of spinal cord fMRI data improved co-registration and inter-rater agreement in activation mapping, however our results suggest that improvements in image acquisition and post-processing are also critical to address.

2021

1. IEEE EMBC

   A visualization tool for assessment of spinal cord functional magnetic resonance imaging data quality

   Kimberly J. Hemmerling, and Molly G. Bright

   In 2021 43rd Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), Dec 2021

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   Functional magnetic resonance imaging (fMRI) is an extensively used neuroimaging technique to non-invasively detect neural activity. Data quality is highly variable, and fMRI analysis typically consists of a number of complex processing steps. It is crucial to visually assess images throughout analysis to ensure that data quality at each step is satisfactory. For fMRI analysis of the brain, there is a simple tool to visualize four-dimensional data on a two-dimensional plot for qualitative analysis. Despite the practicality of this method, it cannot be directly applied to fMRI data of the spinal cord, and a comparable approach does not exist for spinal cord fMRI analysis. The additional challenges encountered in spinal cord imaging, including the small size of the cord and the influence of physiological noise sources, drive the importance of developing a similar visualization technique for spinal cord fMRI. Here, we introduce a highly versatile image analysis tool to visualize spinal cord fMRI data as a simple heatmap and to co-visualize relevant traces such as physiological or motion timeseries. We present multiple variations of the plot, data features that can be identified with the heatmap, and examples of the useful qualitative analyses that can be performed using this method. The spinal cord plot can be easily integrated into an fMRI analysis pipeline and can streamline visual inspection and qualitative analysis of functional imaging data.Clinical Relevance— Implementation of this data visualization method is a simple addition to spinal cord fMRI analysis that could be used to identify normal vs. abnormal signal variation in pathologies that impact the cord, such as spinal cord injury or multiple sclerosis.

2. Bone Joint J

   Fretting and corrosion of metal liners from modular dual mobility constructs

   Kimberly J. Hemmerling, Lydia Weitzler, Thomas W. Bauer, Douglas E. Padgett, and Timothy M. Wright

   The Bone & Joint Journal, Jul 2021

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3. J Bone Miner Res

   Bone Tissue Composition in Postmenopausal Women Varies With Glycemic Control From Normal Glucose Tolerance to Type 2 Diabetes Mellitus

   Heather B Hunt, Nicholas A Miller, Kimberly J Hemmerling, Maho Koga, Kelsie A Lopez, and 4 more authors

   Journal of Bone and Mineral Research, Feb 2021

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   The risk of fragility fracture increases for people with type 2 diabetes mellitus (T2DM), even after controlling for bone mineral density, body mass index, visual impairment, and falls. We hypothesize that progressive glycemic derangement alters microscale bone tissue composition. We used Fourier-transform infrared (FTIR) imaging to analyze the composition of iliac crest biopsies from cohorts of postmenopausal women characterized by oral glucose tolerance testing: normal glucose tolerance (NGT; n = 35, age = 65 ± 7 years, HbA1c = 5.8 ± 0.3%), impaired glucose tolerance (IGT; n = 26, age = 64 ± 5 years, HbA1c = 6.0 ± 0.4%), and overt T2DM on insulin (n = 25, age = 64 ± 6 years, HbA1c = 9.13 ± 0.6). The distributions of cortical bone mineral content had greater mean values (+7%) and were narrower (−10%) in T2DM versus NGT groups (p < 0.05). The distributions of acid phosphate, an indicator of new mineral, were narrower in cortical T2DM versus NGT and IGT groups (−14% and −14%, respectively) and in trabecular NGT and IGT versus T2DM groups (−11% and −10%, respectively) (all p < 0.05). The distributions of crystallinity were wider in cortical NGT versus T2DM groups (+16%) and in trabecular NGT versus T2DM groups (+14%) (all p < 0.05). Additionally, bone turnover was lower in T2DM versus NGT groups (P1NP: −25%, CTx: −30%, ucOC: −24%). Serum pentosidine was similar across groups. The FTIR compositional and biochemical marker values of the IGT group typically fell between the NGT and T2DM group values, although the differences were not always statistically significant. In summary, worsening glycemic control was associated with greater mineral content and narrower distributions of acid phosphate, an indicator of new mineral, which together are consistent with observations of lower turnover; however, wider distributions of mineral crystallinity were also observed. A more mineralized, less heterogeneous tissue may affect tissue-level mechanical properties and in turn degrade macroscale skeletal integrity. In conclusion, these data are the first evidence of progressive alteration of bone tissue composition with worsening glycemic control in humans. © 2020 American Society for Bone and Mineral Research (ASBMR).