A porcine bladder model of pre-clinical urodynamics demonstrates increased afferent nerve activity during filling.

INTRODUCTION AND OBJECTIVES: Urodynamics are the accepted gold standard for the evaluation of multiple forms of voiding dysfunction. However, the tests are expensive, invasive, poorly reproducible, and often prone to artifacts. Therefore, there is a pressing need to develop next-generation urodynamics. The purpose of this study was to develop a novel ex vivo porcine bladder urodynamics model with afferent pelvic nerve signaling that can be used as a preclinical surrogate for bladder sensation. METHODS: Porcine bladders including the ureters and vascular supply were harvested from local abattoirs using an established protocol in both male and female animals. Ex vivo bladder perfusion was performed using physiologic MOPS (3-(N-morpholino) propanesulfonic acid) buffer solution. The pelvic nerve adjacent to the bladder was grasped with micro-hook electrodes and electroneurogram (ENG) signals recorded at 20 kHz. Bladders were filled with saline at a nonphysiologic rate (100 mL/min) to a volume of 1 L using standard urodynamics equipment to simultaneously record intravesical pressure. ENG amplitude was calculated as the area under the curve for each minute, and ENG firing rate was calculated as number of spikes (above baseline threshold) per minute. At the conclusion of the experiment, representative nerve samples were removed and processed for nerve histology by a pathologist (hematoxylin and eosin and S100 stains). RESULTS: A total of 10 pig bladders were used, and nerve histology confirmed the presence of nerve in all adequately processed samples. Vesical pressure, ENG firing rate, and ENG amplitude all increased as a function of filling. During filling tertiles (low fill: min 1-3, med fill: min 4-6, and high fill: min 7-10), normalized pressures were 0.22 ± 0.04, 0.38 ± 0.05, and 0.72 ± 0.07 (cmH2O). Similarly, normalized ENG firing rates were 0.08 ± 0.03, 0.31 ± 0.06, and 0.43 ± 0.04 spikes/minute, respectively, and normalized nerve amplitudes were 0.11 ± 0.06, 0.39 ± 0.06, and 0.56 ± 0.14) µV, respectively. Strong relationships between average normalized pressure values and averaged normalized ENG firing rate (r2 = 0.66) and average normalized ENG amplitude (r2 = 0.8) were identified. CONCLUSIONS: The ex vivo perfused porcine bladder can be used as a preclinical model for the development of next-generation urodynamics technologies. Importantly, the model includes a reproducible method to measure afferent nerve activity that directly correlates with intravesical pressure during filling and could potentially be used as a surrogate measure of bladder sensation.

Prediction of Distal Femur and Proximal Tibia Bone Mineral Density From Total Body Dual Energy X-Ray Absorptiometry Scans in Persons with Spinal Cord Injury.

Bone density decreases rapidly after spinal cord injury (SCI), increasing fracture risk. The most common fracture sites are at the knee (i.e., distal femur or proximal tibia). Despite this high fracture incidence, knee-specific scans for bone density using dual x-ray absorptiometry (DXA) were not available until 2014 and are still not routinely used in clinical practice today. This has made it difficult to determine the rehabilitation efficacy and hindered understanding of the long-term changes in knee areal bone density. The purpose of this investigation was to compare areal bone mineral density values for the knee from both total-body and knee-specific DXA scans in persons with SCI. A total of 20 participants (16 males) >1 yr-post spinal cord injury received two DXA scans; a total-body scan and a knee-specific scan. Standardized methods were used to create regions of interest to determine bone density of four regions - the epiphysis and metaphysis of the distal femur and proximal tibia - from the total-body scan. Linear regressions and Bland-Altman analyses were conducted to determine the correlation (r2) and agreement (mean bias ± 95% level of agreement) respectively between the two scan types for each region. Linear regression analyses showed strong significant (p < 0.001) relationships between the two scan types for the distal femur epiphysis (r2 = 0.88) and metaphysis (r2 = 0.98) and the proximal tibia epiphysis (r2 = 0.88) and metaphysis (r2 = 0.99). The mean bias ± 95% level of agreement were distal femur epiphysis (0.05 ± 0.1 g/cm2) and metaphysis (0.02 ± 0.04 g/cm2); proximal tibia epiphysis (-0.02 ± 0.1 g/cm2) and metaphysis (0.02 ± 0.03 g/cm2). Results suggest knee-specific bone density can be assessed using a total-body DXA scan. This may allow for more comprehensive use of DXA scans which would reduce the burden of multiple site-specific scans for persons with SCI and enable more widespread adoption of knee bone density assessment in this population.

Measurement of Visceral Adipose Tissue in Persons With Spinal Cord Injury by Magnetic Resonance Imaging and Dual X-Ray Absorptiometry: Generation and Application of a Predictive Equation.

PURPOSE: Dual energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI) permits quantification of visceral adipose tissue (VAT). However, DXA has not been validated against MRI in persons with chronic spinal cord injury (SCI). A predictive equation was generated from the measurement of VAT by MRI, a "gold" standard to quantitate VAT, compared to that of DXA, a method with several practical advantages. METHOD: DXA and MRI scans were performed in 27 participants with SCI. MRI multiaxial images were captured for VAT analysis. DXA-VAT was quantified at the android region (DXA-VATANDROID-VOL) using enCore software. Android regions of DXA and MRI were matched using android height. Volumes of multiaxial MRI-VAT and subcutaneous adipose tissue (SAT) were quantified for the android region (MRI-VATANDROID-VOL, MRI-SATANDROID-VOL) and total trunk (MRI-VATANDROID-VOL). Linear regression analysis was used to establish the proposed predication equations. The prediction equations were then applied to an independent sample that consisted of 98 participants with SCI. Bland-Altman analysis was used to determine the limits of agreement. RESULTS: DXA-VATANDROID-VOL predicted 92% of the variance in MRI-VATANDROID-VOL (SEE = 252.5, p < 0.0005) and 85% of the variance in MRI-VATTRUNK-VOL (SEE = 1526.9, p < 0.0005). DXA-SATANDROID-VOL predicted 81.5% of the variance in MRI-SATANDROID-VOL (SEE = 458.2, p < 0.0005). Bland-Altman analysis revealed a high level of agreement between MRI-VATANDROID-VOL and DXA-VATANDROID-VOL (mean bias = 58.45 cm3). A predicted mean DXA-VATANDROID-VOL of 995.2 cm3 was estimated as the population-specific cut-off point for high levels of VAT. CONCLUSION: DXA-VATANDROID-VOL may accurately predict MRI-VATANDROID-VOL in persons with SCI. The ability of DXA to detect VAT changes in longitudinal studies in persons with SCI should be performed.

Race and Age-Related PSA Testing Disparities in Spinal Cord Injured Men: Analysis of National Veterans Health Administration Data.

Background: Prostate-specific antigen (PSA) testing remains controversial due to the debate about overdetection and overtreatment. Given the lack of published data regarding PSA testing rates in the population with spinal cord injury (SCI) within the US Department of Veterans Affairs (VA), there is concern for potential disparities and overtesting in this patient population. In this study, we sought to identify and evaluate national PSA testing rates in veterans with SCI. Methods: Using the VA Informatics and Computing Infrastructure Corporate Data Warehouse, we extracted PSA testing data for all individuals with a diagnosis of SCI. Testing rates were calculated, analyzed by race and age, and stratified according to published American Urological Association guideline groupings for PSA testing. Results: We identified 45,274 veterans at 129 VA medical centers with a diagnosis of SCI who had records of PSA testing in 2000 through 2017. Veterans who were only tested prior to SCI diagnosis were excluded. Final cohort data analysis included 37,243 veterans who cumulatively underwent 261,125 post-SCI PSA tests during the given time frame. Significant differences were found between African American veterans and other races veterans for all age groups (0.47 vs 0.46 tests per year, respectively, aged ≤ 39 years; 0.83 vs 0.77 tests per year, respectively, aged 40-54 years; 1.04 vs 1.00 tests per year, respectively, aged 55-69 years; and 1.08 vs 0.90 tests per year, respectively, aged ≥ 70 years; P < .001). Conclusions: Significant differences exist in rates of PSA testing in persons with SCI based on age and race. High rates of testing were found in all age groups, especially for African American veterans aged ≥ 70 years.

A stepwise approach for functional near infrared spectroscopy measurement during natural bladder filling.

Background: Functional near infrared spectroscopy (fNIRS) is a versatile, noninvasive, and inexpensive tool that can be used to measure oxyhemoglobin (O2Hb) changes in the cortical brain caused by increasing bladder sensation during filling in upright posture. This study's purpose is to provide a rigorous methodologic template that can be implemented for comparative studies of fNIRS in the diagnosis and management of lower urinary tract symptoms including overactive bladder (OAB) and other forms of lower urinary tract dysfunction. Methods: Participants without any urologic conditions completed a validated oral hydration protocol facilitating and equilibrating natural bladder filling. First desire to void and real time bladder sensation (0-100%) were recorded using a Sensation Meter. A 24-channel fNIRS template simultaneously recorded prefrontal cortical O2Hb. Each channel was analyzed between "first desire" to void and 100% sensation, defined in this study as the period of "high sensation". Channels were sub-divided by cortical regions: right (nine channels), left (nine channels), middle (six channels). Results: A total of eight participants (male: n=4, female: n=4) were enrolled with mean age 39±19.9 years and body mass index (BMI) of 25±3.93 kg/m2. There were no differences in age, BMI, race, or OAB survey scores based on biological sex. Signal acquisition improved with power bank use, postural head support for motion reduction, and head cap optimization. Acceleration-based concurrent motion measurement was effectively utilized to remove motion artifacts. O2Hb concentration patterns appeared irregular during low sensation and increased during high sensation after first desire across the frontal cortex. Conclusions: Employing a stepwise approach, this study defined a methodological guide for improved prefrontal fNIRS signal acquisition and analysis during bladder filling. The technique demonstrated that prefrontal fNIRS cortical O2Hb increases with elevated bladder sensation in normal subjects and sets the stage for comparative studies in individuals with OAB and other forms of lower urinary tract dysfunction.

Exoskeleton Training and Trans-Spinal Stimulation for Physical Activity Enhancement After Spinal Cord Injury (EXTra-SCI): An Exploratory Study.

After spinal cord injury (SCI) physical activity levels decrease drastically, leading to numerous secondary health complications. Exoskeleton-assisted walking (EAW) may be one way to improve physical activity for adults with SCI and potentially alleviate secondary health complications. The effects of EAW may be limited, however, since exoskeletons induce passive movement for users who cannot volitionally contribute to walking. Trans-spinal stimulation (TSS) has shown the potential to enable those with even the most severe SCI to actively contribute to movements during EAW. To explore the effects of EAW training on improving secondary health complications in persons with SCI, participants with chronic (n = 8) were enrolled in an EAW program 2-3 times per week for 12 weeks. Anthropometrics (seated and supine waist and abdominal circumferences (WC and AC), body composition assessment (dual exposure x-ray absorptiometry-derived body fat percent, lean mass and total mass for the total body, legs, and trunk), and peak oxygen consumption (VO2 during a 6-minute walk test [6MWT]) were assessed before and after 12 weeks of EAW training. A subset of participants (n = 3) completed EAW training with concurrent TSS, and neuromuscular activity of locomotor muscles was assessed during a 10-m walk test (10MWT) with and without TSS following 12 weeks of EAW training. Upon completion of 12 weeks of training, reductions from baseline (BL) were found in seated WC (-2.2%, P = 0.036), seated AC (-2.9%, P = 0.05), and supine AC (-3.9%, P = 0.017). Percent fat was also reduced from BL for the total body (-1.4%, P = 0.018), leg (-1.3%, P = 0.018), and trunk (-2%, P = 0.036) regions. No effects were found for peak VO2. The addition of TSS for three individuals yielded individualized responses but generally increased knee extensor activity during EAW. Two of three participants who received TSS were also able to initiate more steps without additional assistance from the exoskeleton during a 10MWT. In summary, 12 weeks of EAW training significantly attenuated markers of obesity relevant to cardiometabolic health in eight men with chronic SCI. Changes in VO2 and neuromuscular activity with vs. without TSS were highly individualized and yielded no overall group effects.

Skeletal muscle stiffness as measured by magnetic resonance elastography after chronic spinal cord injury: a cross-sectional pilot study.

Skeletal muscle stiffness is altered after spinal cord injury (SCI). Assessing muscle stiffness is essential for rehabilitation and pharmaceutical interventions design after SCI. The study used magnetic resonance elastography to assess the changes in stiffness after chronic SCI compared to matched able-bodied controls and determine its association with muscle size, spasticity, and peak torque in persons with SCI. Previous studies examined the association between muscle stiffness and spasticity, however, we are unaware of other studies that examined the effects of muscle composition on stiffness after SCI. Ten participants (one female) with chronic SCI and eight (one female) matched able-bodied controls participated in this cross-sectional study. Magnetic resonance elastography was utilized to monitor stiffness derived from shear waves propagation. Modified Ashworth scale was used to evaluate spasticity scores in a blinded fashion. Peak isometric and isokinetic torques were measured using a biodex dynamometer. Stiffness values were non-significantly lower (12.5%; P = 0.3) in the SCI group compared to able-bodied controls. Moreover, stiffness was positively related to vastus lateralis whole muscle cross-sectional area (CSA) (r2 = 0.64, P < 0.005) and vastus lateralis absolute muscle CSA after accounting for intramuscular fat (r2 = 0.78, P < 0.0007). Stiffness was also positively correlated to both isometric (r2= 0.55-0.57, P < 0.05) and isokinetic peak (r2= 0.46-0.48, P < 0.05) torques. Our results suggest that larger clinical trial is warranted to confirm the preliminary findings that muscle stiffness is altered after SCI compared to healthy controls. Stiffness appeared to be influenced by infiltration of intramuscular fat and modestly by the spasticity of the paralyzed muscles. The preliminary data indicated that the relationship between muscle stiffness and peak torque is not altered with changing the frequency of pulses or angular velocities. All study procedures were approved by the Institutional Review Board at the Hunter Holmes McGuire VA Medical Center, USA (IRB #: 02314) on May 3, 2017.

Methodological considerations for near-infrared spectroscopy to assess mitochondrial capacity after spinal cord injury.

Background: Skeletal muscle mitochondrial activity is reduced by ∼ 50-60% after SCI, resulting in impaired energy expenditure, glucose utilization and insulin sensitivity. Near infra-red spectroscopy (NIRS) is a non-invasive tool that can be used to assess mitochondrial capacity. Objectives: (1) Highlight methodological limitations impacting data acquisition and analysis such as subcutaneous adipose tissue (SAT) thickness, movement artifacts, inadequate muscle stimulation, light interference, and ischemic discomfort. (2) Provide technical considerations to improve data acquisition and analysis. This may serve as guidance to other researchers and clinicians using NIRS. Study Design: cross-sectional observational design. Settings: Clinical research medical center. Participants: Sixteen men with 1 > year post motor complete SCI. Methods: NIRS signals were obtained from right vastus lateralis muscle utilizing a portable system. Signals were fit to a mono-exponential curve. Outcome Measures: Rate constant and r2 values for the fit curve, indirectly measures mitochondrial capacity. Results: Only four participants produced data with accepted rate constants of 0.002-0.013 s-1 and r2 of 0.71-0.87. Applications of studentized residuals ≥2.5 resulted in sparing data from another four participants with rate constants of 0.010-0.018 s-1and r2 values ranging from 0.86-0.99. Conclusions: Several limitations may challenge the use of NIRS to assess mitochondrial capacity after SCI. Acknowledging these limitations and applying additional data processing techniques may overcome the discussed limitations and facilitate data sparing.

Long-term effect of intrathecal baclofen treatment on bone health and body composition after spinal cord injury: A case matched report.

BACKGROUND: Severe spasticity may negatively impact functionality and quality of life after spinal cord injury (SCI). Intrathecal baclofen treatment (IBT) is effectively used to manage severe spasticity and reduce comorbidities. However, long-term IBT may have a negative effect on bone mineral content (BMC), bone mineral density (BMD) and body composition (such as percentage fat mass and lean body mass). We demonstrated the negative effects of long-term IBT use in a single case compared with two non-IBT users. CASE SUMMARY: A 46-year old Caucasian male Veteran (case) with a 21 year history of complete tetraplegia (complete C6 SCI) was implanted with IBT for 20 years. The case was matched to two participants with different time since injuries [2 (match 1) and 13 (match 2) years] without IBT. Knee BMC and BMD at the epiphysis and metaphysis of the distal femur and proximal tibia were evaluated using dual knee and the dual femur modules of GE Lunar iDXA software. Total and leg body composition assessments were also conducted for the three participants. Potential effect of long-term IBT was demonstrated by changes in BMD, consistent with bone demineralization, at the distal femur and proximal tibia and changes in percentage fat mass and lean mass of legs. The case showed 113% lower BMD at the distal femur, and 78.1% lower at the proximal tibia compared to match 1, moreover the case showed 45% lower BMD at the distal femur, and no observed changes at the proximal tibia compared to match 2. The case had 27.1% and 16.5% greater leg %fat mass compared to match 1 and match 2, respectively. Furthermore, the case had 17.4% and 11.8% lower % leg lean mass compared to match 1 and match 2, respectively. CONCLUSION: Long-term IBT may impact bone health and body composition parameters in persons with complete SCI. It may be prudent to encourage regular screening of individuals on long-term IBT considering the prevalence of osteoporosis related fractures, cardiovascular diseases, and metabolic disorders in this population.

Prediction of thigh skeletal muscle mass using dual energy x-ray absorptiometry compared to magnetic resonance imaging after spinal cord injury.

Objectives: A rapid decline in lean mass (LM), fat-free mass (FFM) and increased intramuscular fat (IMF) predispose persons with spinal cord injury (SCI) to chronic medical conditions including dyslipidemia, insulin resistance, type 2 diabetes mellitus and cardiovascular disease. (1) To determine the relationship between dual energy x ray absorptiometry (DXA) and gold standard magnetic resonance imaging (MRI) LM values; (2) to develop predictive equations based on this relationship for assessing thigh LM in persons with chronic SCI. Study Design: Cross-sectional predicational design. Settings: Clinical research medical center. Participants: Thirty-two men with chronic (>1 y post-injury) motor complete SCI. Methods: Participants completed total body DXA scans to determine thigh LM and were compared to measurements acquired from trans-axial MRI. Outcome measures: MRI was used to measure whole muscle mass (MMMRI-WM), absolute muscle mass (MMMRI-ABS) after excluding IMF, and knee extensor muscle mass (MMMRI-KE). DXA was used to measure thigh LM (LMDXA) and (FFMDXA). To predict MMMRI-KE, LMDXA was multiplied by 0.52 and yielded LMDXA-KE. Results: LMDXA predicted MMMRI-WM [r2 = 0.90, standard error of the estimate (SEE) = 0.23 kg, P < 0.0001] and MMMRI-ABS (r2 = 0.82, SEE = 0.28 kg, P < 0.0001). LMDXA-KE predicted MMMRI-KE (r2 = 0.78, SEE = 0.16 kg, P < 0.0001). Conclusion: DXA measurements revealed an acceptable agreement with the gold standard MRI and may be a viable alternative for assessing thigh skeletal muscle mass after SCI.

Dietary manipulation and testosterone replacement therapy may explain changes in body composition after spinal cord injury: A retrospective case report.

BACKGROUND: Reduced level of physical activity, high-fat diet and skeletal muscle atrophy are key factors that are likely to contribute to deleterious changes in body composition and metabolic following spinal cord injury (SCI). Reduced caloric intake with lowering percentage macronutrients of fat and increasing protein intake may likely to improve body composition parameters and decrease ectopic adiposity after SCI. AIM: To highlight the effects of dietary manipulation and testosterone replacement therapy (TRT) on body composition after SCI. METHODS: A 31-year-old male with T5 SCI was administered transdermal TRT daily for 16 wk. Caloric intake and percentage macronutrients were analyzed using dietary recalls. Magnetic resonance imaging and dual-energy x-ray absorptiometry were used to measure changes in body composition. RESULTS: Caloric intake and fat percentage were reduced by 445 kcal/d and 6.5%, respectively. Total body weight decreased by 8%, body fat decreased by 29%, and lean mass increased by 7%. Thigh subcutaneous adipose tissue cross-sectional area was reduced by 31%. CONCLUSION: Manipulation of caloric intake, fat percentage, and protein percentage may have influenced body composition after SCI.

Semi-automated segmentation of magnetic resonance images for thigh skeletal muscle and fat using threshold technique after spinal cord injury.

Magnetic resonance imaging is considered the "gold standard" technique for quantifying thigh muscle and fat cross-sectional area. We have developed a semi-automated technique to segment seven thigh compartments in persons with spinal cord injury. Thigh magnetic resonance images from 18 men (18-50 years old) with traumatic motor-complete spinal cord injury were analyzed in a blinded fashion using the threshold technique. The cross-sectional area values acquired by thresholding were compared to the manual tracing technique. The percentage errors for thigh circumference were (threshold: 170.71 ± 38.67; manual: 169.45 ± 38.27 cm2) 0.74%, subcutaneous adipose tissue (threshold: 65.99±30.79; manual: 62.68 ± 30.22) 5.2%, whole muscle (threshold: 98.18 ± 20.19; manual: 98.20 ± 20.08 cm2) 0.13%, femoral bone (threshold: 6.53 ± 1.09; manual: 6.53 ± 1.09 cm2) 0.64%, bone marrow fat (threshold: 3.12 ± 1.12; manual: 3.1 ± 1.11 cm2) 0.36%, knee extensor (threshold: 43.98 ± 7.66; manual: 44.61 ± 7.81 cm2) 1.78% and % intramuscular fat (threshold: 10.45 ± 4.29; manual: 10.92 ± 8.35%) 0.47%. Collectively, these results suggest that the threshold technique provided a robust accuracy in measuring the seven main thigh compartments, while greatly reducing the analysis time.