For the first time we demonstrate the ability to detect innate lumbosacral spinal cord activity in humans within regions involved in regulating lower urinary tract (LUT) function [1]. While there have been notable progressions in functional magnetic resonance imaging (fMRI) research that have deepened our comprehension of how the brain regulates bladder function in humans, there remains a significant void in the investigation of real-time spinal cord involvement [2]. The aim of this pilot feasibility study was to develop an imaging protocol that effectively captured spinal activation in healthy adults during both task and resting state fMRI sessions by utilizing a natural bladder filling paradigm.

Healthy adult men and women (≥18 years old) without prior history of urinary symptoms or genitourinary abnormalities, post-void residual (PVR) <100mL, PVR/bladder capacity (PVR/BC) <20% and American Urologic Association Symptom Score (AUASS) <7 were recruited for this study. During neuroimaging sessions participants were asked to consume 250mL of water within a 5-minute span prior to entering a 3-Tesla Siemens Vida scanner. Initial anatomical scans were conducted, succeeded by two sets of alternating resting-state and task-oriented fMRI evaluations during states of both full and empty bladders (Figure 1A). Task-based stimulation was carried out through the use of a novel device to elicit a simulated bulbocavernosus reflex (sBCR), which can be seen in figure 1B[3]. The functional spinal neuroimaging data were processed and analyzed using a tailored pipeline that included Spinal Cord Toolbox (SCT), FSL’s FEAT module, and MATLAB scripting for preprocessing and analysis. Time-series (first-level) statistical analysis was conducted utilizing FMRIB's Improved Linear Model (FILM) and Z (Gaussianised T/F) statistic images were thresholded using clusters determined by Z>3.1, with a (corrected) cluster significance threshold set at P=0.05.

Twenty healthy individuals (9 men and 11 women) who met the eligibility criteria consented to participate in the study and were prospectively enrolled between November 2022 and August 2023. Five participants were later excluded (men n=2, women n=3) from analysis because of imaging artifacts intersecting the spinal cord during functional scans (n=2) or due to issues with physiological data acquisition (n=3). First level BOLD analysis of task-based fMRI (sBCR stimulation) conducted during both full and empty bladder states, displayed diverse patterns of spinal activation in 15 healthy adults (7 men, 8 women) spanning the T10-L1 vertebral level. Notably, 71% of the male participants exhibited more focal areas of activation during sBCR in both full and empty bladder states. In contrast, 63% of the female participants demonstrated less pronounced areas of activation during sBCR (Figure 2).

The activated regions seen during full and empty bladder states encompassed sympathetic (T10-L2), parasympathetic (S2-S4), and somatic nuclei (S2-S4) known for their involvement in regulating LUT function. Furthermore, activation around the S2-S4 spinal levels during both bladder states (full and empty) aligns with anticipated outcomes during sBCR elicitation. The observed activation between T10-L2 can be attributed to sympathetic innervation, which plays a role during the storage phase of the micturition reflex. Lastly, our preliminary findings suggest that sex differences may influence these activation patterns, though further investigation and second-level analysis are warranted to confirm this observation.

Results of this novel spinal fMRI study demonstrate the efficacy of our protocol in detecting activation of the lumbosacral spinal cord in real-time and advances our understanding of its involvement in coordinating bladder function in humans. Moreover, this study serves as a platform to investigate changes in activity associated with different neurological pathologies in the future so that targeted treatments can be developed based on this information.

1.	Drake MJ, Fowler CJ, Griffiths D, Mayer E, Paton JF, Birder L. Neural control of the lower urinary and gastrointestinal tracts: supraspinal CNS mechanisms. Neurourol Urodyn. 2010;29(1):119-27. doi:10.1002/nau.20841
2.	Figley CR, Yau D, Stroman PW. Attenuation of lower-thoracic, lumbar, and sacral spinal cord motion: implications for imaging human spinal cord structure and function. AJNR Am J Neuroradiol. Sep 2008;29(8):1450-4. doi:10.3174/ajnr.A1154
3.	Hoffman KA, Mazeaud C, Salazar BH, et al. Conception and implementation of an MRI-compatible device to elicit the bulbocavernosus reflex for an open spinal cord study. Neurourol Urodyn. 2024; 1-8. doi:10.1002/nau.25461

Continence 12S (2024) 101493
DOI: 10.1016/j.cont.2024.101493