Detrusor Pressure Estimation from Single-Channel Urodynamics.

Urodynamics is the current gold-standard for diagnosing lower urinary tract dysfunction, but uses non-physiologically fast, retrograde cystometric filling to obtain a brief snapshot of bladder function. Ambulatory urodynamics allows physicians to evaluate bladder function during natural filling over longer periods of time, but artifacts generated from patient movement necessitate the use of an abdominal pressure sensor, which makes long-term monitoring and feedback for closed-loop treatment impractical. In this paper, we analyze the characteristics of single-channel bladder pressure signals from human and feline datasets, and present an algorithm designed to estimate detrusor pressure, which is useful for diagnosis and treatment. We utilize multiresolution analysis techniques to maximize the attenuation of probable abdominal pressure components in the vesical pressure signal. Results indicate a strong correlation, averaging 0.895 ± 0.121 (N = 40) and 0.812 ± 0.113 (N = 16) between the estimated detrusor pressure obtained by the proposed method and recorded urodynamic data from human and feline subjects, respectively. Clinical Relevance- This work establishes that signal pro-cessing techniques may be applied to vesical pressure alone to accurately reconstruct pressures generated independently by the detrusor muscle. This is relevant for emerging sensors that measure vesical pressure alone or for data analysis of bladder pressure in ambulatory subjects which contains significant abdominal pressure artifacts.

Closed-loop sacral neuromodulation for bladder function using dorsal root ganglia sensory feedback in an anesthetized feline model.

Overactive bladder patients suffer from a frequent, uncontrollable urge to urinate, which can lead to a poor quality of life. We aim to improve open-loop sacral neuromodulation therapy by developing a conditional stimulation paradigm using neural recordings from dorsal root ganglia (DRG) as sensory feedback. Experiments were performed in 5 anesthetized felines. We implemented a Kalman filter-based algorithm to estimate the bladder pressure in real-time using sacral-level DRG neural recordings and initiated sacral root electrical stimulation when the algorithm detected an increase in bladder pressure. Closed-loop neuromodulation was performed during continuous cystometry and compared to bladder fills with continuous and no stimulation. Overall, closed-loop stimulation increased bladder capacity by 13.8% over no stimulation (p < 0.001) and reduced stimulation time versus continuous stimulation by 57.7%. High-confidence bladder single units had a reduced sensitivity during stimulation, with lower linear trendline fits and higher pressure thresholds for firing observed during stimulation trials. This study demonstrates the utility of decoding bladder pressure from neural activity for closed-loop control of sacral neuromodulation. An underlying mechanism for sacral neuromodulation may be a reduction in bladder sensory neuron activity during stimulation. Real-time validation during behavioral studies is necessary prior to clinical translation of closed-loop sacral neuromodulation.

Tibial nerve stimulation increases vaginal blood perfusion and bone mineral density and yield load in ovariectomized rat menopause model.

INTRODUCTION AND HYPOTHESIS: Human menopause transition and post-menopausal syndrome, driven by reduced ovarian activity and estrogen levels, are associated with an increased risk for symptoms including but not limited to sexual dysfunction, metabolic disease, and osteoporosis. Current treatments are limited in efficacy and may have adverse consequences, so investigation for additional treatment options is necessary. Previous studies have demonstrated that percutaneous tibial nerve stimulation (PTNS) and electro-acupuncture near the tibial nerve are minimally invasive treatments that increase vaginal blood perfusion or serum estrogen in the rat model. We hypothesized that PTNS would protect against harmful reproductive and systemic changes associated with menopause. METHODS: We examined the effects of twice-weekly PTNS (0.2 ms pulse width, 20 Hz, 2× motor threshold) under ketamine-xylazine anesthesia in ovariectomized (OVX) female Sprague-Dawley rats on menopause-associated physiological parameters including serum estradiol, body weight, blood glucose, bone health, and vaginal blood perfusion. Rats were split into three groups (n = 10 per group): (1) intact control (no stimulation), (2) OVX control (no stimulation), and (3) OVX stimulation (treatment group). RESULTS: PTNS did not affect serum estradiol levels, body weight, or blood glucose. PTNS transiently increased vaginal blood perfusion during stimulation for up to 5 weeks after OVX and increased areal bone mineral density and yield load of the right femur (side of stimulation) compared to the unstimulated OVX control. CONCLUSIONS: PTNS may ameliorate some symptoms associated with menopause. Additional studies to elucidate the full potential of PTNS on menopause-associated symptoms under different experimental conditions are warranted.

Anesthetic agents affect urodynamic parameters and anesthetic depth at doses necessary to facilitate preclinical testing in felines.

Urodynamic studies, used to understand bladder function, diagnose bladder disease, and develop treatments for dysfunctions, are ideally performed with awake subjects. However, in small and medium-sized animal models, anesthesia is often required for these procedures and can be a research confounder. This study compared the effects of select survival agents (dexmedetomidine, alfaxalone, and propofol) on urodynamic (Δpressure, bladder capacity, bladder compliance, non-voiding contractions, bladder pressure slopes) and anesthetic (change in heart rate [∆HR], average heart rate [HR], reflexes, induction/recovery times) parameters in repeated cystometrograms across five adult male cats. The urodynamic parameters under isoflurane and α-chloralose were also examined in terminal procedures for four cats. Δpressure was greatest with propofol, bladder capacity was highest with α-chloralose, non-voiding contractions were greatest with α-chloralose. Propofol and dexmedetomidine had the highest bladder pressure slopes during the initial and final portions of the cystometrograms respectively. Cats progressed to a deeper plane of anesthesia (lower HR, smaller ΔHR, decreased reflexes) under dexmedetomidine, compared to propofol and alfaxalone. Time to induction was shortest with propofol, and time to recovery was shortest with dexmedetomidine. These agent-specific differences in urodynamic and anesthetic parameters in cats will facilitate appropriate study-specific anesthetic choices.

Hysteretic behavior of bladder afferent neurons in response to changes in bladder pressure.

BACKGROUND: Mechanosensitive afferents innervating the bladder increase their firing rate as the bladder fills and pressure rises. However, the relationship between afferent firing rates and intravesical pressure is not a simple linear one. Firing rate responses to pressure can differ depending on prior activity, demonstrating hysteresis in the system. Though this hysteresis has been commented on in published literature, it has not been quantified. RESULTS: Sixty-six bladder afferents recorded from sacral dorsal root ganglia in five alpha-chloralose anesthetized felines were identified based on their characteristic responses to pressure (correlation coefficient ≥ 0.2) during saline infusion (2 ml/min). For saline infusion trials, we calculated a maximum hysteresis ratio between the firing rate difference at each pressure and the overall firing rate range (or Hmax) of 0.86 ± 0.09 (mean ± standard deviation) and mean hysteresis ratio (or Hmean) of 0.52 ± 0.13 (n = 46 afferents). For isovolumetric trials in two experiments (n = 33 afferents) Hmax was 0.72 ± 0.14 and Hmean was 0.40 ± 0.14. CONCLUSIONS: A comprehensive state model that integrates these hysteresis parameters to determine the bladder state may improve upon existing neuroprostheses for bladder control.

Functional priorities, assistive technology, and brain-computer interfaces after spinal cord injury.

Spinal cord injury (SCI) often affects a person's ability to perform critical activities of daily living and can negatively affect his or her quality of life. Assistive technology aims to bridge this gap in order to augment function and increase independence. It is critical to involve consumers in the design and evaluation process as new technologies such as brain-computer interfaces (BCIs) are developed. In a survey study of 57 veterans with SCI participating in the 2010 National Veterans Wheelchair Games, we found that restoration of bladder and bowel control, walking, and arm and hand function (tetraplegia only) were all high priorities for improving quality of life. Many of the participants had not used or heard of some currently available technologies designed to improve function or the ability to interact with their environment. The majority of participants in this study were interested in using a BCI, particularly for controlling functional electrical stimulation to restore lost function. Independent operation was considered to be the most important design criteria. Interestingly, many participants reported that they would consider surgery to implant a BCI even though noninvasiveness was a high-priority design requirement. This survey demonstrates the interest of individuals with SCI in receiving and contributing to the design of BCIs.