Structural Changes in Brain White Matter Tracts Associated With Overactive Bladder Revealed by Diffusion Tensor Magnetic Resonance Imaging: Findings From a Symptoms of Lower Urinary Tract Dysfunction Research Network Cross-Sectional Case-Control Study.

PURPOSE: Our objective was to investigate structural changes in brain white matter tracts using diffusion tensor imaging (DTI) in patients with overactive bladder (OAB). MATERIALS AND METHODS: Treatment-seeking OAB patients and matched controls enrolled in the cross-sectional case-control LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) Neuroimaging Study received a brain DTI scan. Microstructural integrity of brain white matter was assessed using fractional anisotropy (FA) and mean diffusivity. OAB and urgency urinary incontinence (UUI) symptoms were assessed using the OAB Questionnaire Short-Form and International Consultation on Incontinence Questionnaire-Urinary Incontinence. The Lower Urinary Tract Symptoms Tool UUI questions and responses were correlated with FA values. RESULTS: Among 221 participants with evaluable DTI data, 146 had OAB (66 urinary urgency-only without UUI, 80 with UUI); 75 were controls. Compared with controls, participants with OAB showed decreased FA and increased mean diffusivity, representing greater microstructural abnormalities of brain white matter tracts among OAB participants. These abnormalities occurred in the corpus callosum, bilateral anterior thalamic radiation and superior longitudinal fasciculus tracts, and bilateral insula and parahippocampal region. Among participants with OAB, higher OAB Questionnaire Short-Form scores were associated with decreased FA in the left inferior fronto-occipital fasciculus, P < .0001. DTI differences between OAB and controls were driven by the urinary urgency-only (OAB-dry) but not the UUI (OAB-wet) subgroup. CONCLUSIONS: Abnormalities in microstructural integrity in specific brain white matter tracts were more frequent in OAB patients. More severe OAB symptoms were correlated with greater degree of microstructural abnormalities in brain white matter tracts in patients with OAB. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02485808.

Microstructural white matter abnormalities in overactive bladder syndrome evaluation with diffusion kurtosis imaging tract-based spatial statistics analysis.

PURPOSE: This prospective study aimed to explore the microstructural alterations of the white matter in overactive bladder syndrome (OAB) using the Tract-based Spatial Statistics (TBSS) method of diffusion kurtosis imaging (DKI). METHODS: A total of 30 patients were enrolled and compared with 30 controls. White matter (WM) status was assessed using tract-based spatial statistics for DKI. The differences in DKI-derived parameters, including kurtosis fractional anisotropy (KFA), fractional anisotropy (FA), mean kurtosis (MK), mean diffusivity (MD), radial kurtosis (RK), axial kurtosis (AK), axial diffusivity (AD), and radial diffusivity (RD), were compared between the two groups using the TBSS method. The correlation between the altered DKI-derived parameters and the (OABSS) scores was analyzed. A receiver operating characteristic curve (ROC) was used to evaluate the diagnostic performance of different white matter parameters. RESULTS: As a result, compared with the HC group, the KFA, and FA values decreased significantly in the OAB group. Compared with the HC group, the MK and MD values increased significantly in the OAB group. The KFA values of the genu of corpus callosum (GCC) were significantly correlated with the OABSS scores (r = - 0.509; p = 0.004). The FA values of anterior corona radiata (ACR) were significantly correlated with OABSS scores (r = - 0.447; p = 0.013). The area under the ROC curve (AUC) for the genu of corpus callosum KFA values was higher than FA for the diagnosis of OAB patients. CONCLUSION: DKI is a promising approach to the investigation of the pathophysiology of OAB and a potential biomarker for clinical diagnosis of OAB.

Brain Response Induced by Peroneal Electrical Transcutaneous Neuromodulation Invented for Overactive Bladder Treatment, as Detected by Functional Magnetic Resonance Imaging.

OBJECTIVES: In this study, we aimed to investigate whether peroneal electrical Transcutaneous Neuromodulation invented for overactive bladder (OAB) treatment elicits activation in brain regions involved in neural regulation of the lower urinary tract. MATERIALS AND METHODS: Among 22 enrolled healthy female volunteers, 13 were eligible for the final analysis. Functional magnetic resonance imaging (fMRI) (Siemens VIDA 3T; Erlangen, Germany) was used to compare the brain region activation elicited by peroneal electrical Transcutaneous Neuromodulation with the activation elicited by sham stimulation. Each subject underwent brain fMRI recording during eight 30-second periods of rest, alternating with 30-second periods of passive feet movement using the sham device, mimicking the motor response to peroneal nerve stimulation. Subsequently, fMRI recording was performed during the analogic "off-on" stimulation paradigm using peroneal electrical transcutaneous neuromodulation. Magnetic resonance imaging data acquired during both paradigms were compared using individual and group statistics. RESULTS: During both peroneal electrical Transcutaneous Neuromodulation and sham feet movements, we observed activation of the primary motor cortex and supplementary motor area, corresponding to the cortical projection of lower limb movement. During peroneal electrical Transcutaneous Neuromodulation, we observed significant activations in the brain stem, cerebellum, cingulate gyrus, putamen, operculum, and anterior insula, which were not observed during the sham feet movement. CONCLUSIONS: Our study provides evidence that peroneal electrical Transcutaneous Neuromodulation elicits activation of brain structures that have been previously implicated in the perception of bladder fullness and that play a role in the ability to cope with urinary urgency. Our data suggest that neuromodulation at the level of supraspinal control of the lower urinary tract may contribute to the treatment effect of peroneal electrical Transcutaneous Neuromodulation in patients with OAB.

Association between voiding lower urinary tract symptoms and findings on dynamic magnetic resonance imaging with regard to pelvic organs and their supportive structures.

OBJECTIVES: Pelvic organ prolapse (POP) causes voiding lower urinary tract symptoms (vLUTS). In the present study, we investigated the association between vLUTS and pelvic organ mobility (POM), including relevant supportive structures, on dynamic magnetic resonance imaging (dMRI). METHODS: We included 118 patients who had POP of stage II or less before straining and stage III or more when straining during dMRI. The presence of vLUTS and overactive bladder (OAB) was determined by a voiding subscore of the International Prostate Symptom Score (vIPSS) ≥5 and the OAB symptom score, respectively. POM was measured by dMRI before and during straining, and patients with and without vLUTS as well as patients with and without vLUTS and/or OAB were compared. p < .05 was considered to be statistically significant. RESULTS: According to vIPSS, 42 patients (35.6%) had vLUTS. On dMRI, patients with vLUTS showed a significantly more ventral position and/or movement of the bladder and cervix. Moreover, patients with vLUTS and OAB had significantly more ventral movement of the uterine cervix and a larger strain on imaginary uterosacral and cardinal ligaments than those without these symptoms. In addition, patients with vLUTS and OAB had significantly higher vIPSS than those with vLUTS alone. CONCLUSIONS: vLUTS may be associated with the proximity of the bladder and cervix to the pubic bone and consequent compression of the urethra by the prolapsed organs. vLUTS with OAB might indicate more advanced lower urinary tract dysfunction than vLUTS alone.

Differences between brain responses to peroneal electrical transcutaneous neuromodulation and transcutaneous tibial nerve stimulation, two treatments for overactive bladder.

OBJECTIVES: To compare brain responses to peroneal electrical transcutaneous neuromodulation (peroneal eTNM®) and transcutaneous tibial nerve stimulation (TTNS), two methods for treating overactive bladder (OAB), using functional magnetic resonance imaging (fMRI). The present study was not designed to compare their clinical efficacy. MATERIALS AND METHODS: This study included 32 healthy adult female volunteers (average age 38.3 years (range 22-73)). Brain MRI using 3 T scanner was performed during three 8-min blocks of alternating sequences. During each 8-min block, the protocol alternated between sham stimulation (30 s) and rest (30 s) for 8 repeats; then peroneal eTNM® stimulation (30 s) and rest (30 s) for 8 repeats; then, TTNS stimulation (30 s) and rest (30 s) for 8 repeats. Statistical analysis was performed at the individual level with a threshold of p = 0.05, family-wise error (FWE)-corrected. The resulting individual statistical maps were analyzed in group statistics using a one-sample t-test, p = 0.05 threshold, false discovery rate (FDR)-corrected. RESULTS: During peroneal eTNM®, TTNS, and sham stimulations, we recorded activation in the brainstem, bilateral posterior insula, bilateral precentral gyrus, bilateral postcentral gyrus, left transverse temporal gyrus, and right supramarginal gyrus. During both peroneal eTNM® and TTNS stimulations, but not sham stimulations, we recorded activation in the left cerebellum, right transverse temporal gyrus, right middle frontal gyrus, and right inferior frontal gyrus. Exclusively during peroneal eTNM® stimulation, we observed activation in the right cerebellum, right thalamus, bilateral basal ganglia, bilateral cingulate gyrus, right anterior insula, right central operculum, bilateral supplementary motor cortex, bilateral superior temporal gyrus, and left inferior frontal gyrus. CONCLUSIONS: Peroneal eTNM®, but not TTNS, induces the activation of brain structures that were previously implicated in neural control of the of bladder filling and play an important role in the ability to cope with urgency. The therapeutic effect of peroneal eTNM® could be exerted, at least in part, at the supraspinal level of neural control.

The effect of oral medications on fMRI brain activation: A randomized, double blind, controlled pilot trial of older women with overactive bladder.

INTRODUCTION AND AIM: Observational studies have associated oral anticholinergic medications for overactive bladder (OAB) with cognitive impairment. This is the first pilot trial to compare the effects of two classes of OAB medications on brain activity in women. We evaluated the effect of anticholinergic versus non-anticholinergic (Non-Ach) interventions on regional brain activation during a cognitive task. METHODS: Twelve cognitively normal women seeking OAB therapy were recruited to a randomized, double-blind, parallel, controlled pilot trial. Whole-brain regional activity at baseline and 29 ± 1 days postintervention was assessed with functional magnetic resonance imaging during a working memory task. Average activation strength by region was compared after anticholinergic, beta-3 agonist, or placebo. Two-way ANOVA compared effects of group and time on average activation strength in anticholinergic versus Non-Ach (beta-3 agonists or placebo) groups. RESULTS: The mean (SD) age and body mass index of 12 women were 61 (7) years and 36 (7) kg/m2. Baseline depression and learning scores differed in the anticholinergic group (n = 3) versus the Non-Ach group (n = 9). Right mamillary body activation postintervention was higher after Non-Ach exposure (F 4.9, p < 0.04). In the full sample of participants at follow-up, there was less activation of the right middle frontal gyrus (p = 0.02), superior frontal gyrus (p < 0.01), and supramarginal (p < 0.01) gyrus. CONCLUSION: Activation strength in brain regions underlying working memory was lower over time, and recognition scores improved. A powered trial is needed to adequately evaluate for differential effects of OAB oral medications on regional brain activation.

Video-urodynamics efficacy of sacral neuromodulation for neurogenic bladder guided by three-dimensional imaging CT and C-arm fluoroscopy: a single-center prospective study.

To assess the efficacy of sacral neuromodulation (SNM) for neurogenic bladder (NB), guided by intraoperative three-dimensional imaging of sacral computed tomography (CT) and mobile C-arm fluoroscopy through video-urodynamics examination. We enrolled 52 patients with NB who underwent conservative treatment with poor results between September 2019 and June 2021 and prospectively underwent SNM guided by intraoperative three-dimensional imaging of sacral CT and mobile C-arm fluoroscopy. Video-urodynamics examination, voiding diary, quality of life questionnaire, overactive bladder symptom scale (OABSS) scoring, and bowel dysfunction exam were completed and recorded at baseline, at SNM testing, and at 6-month follow-up phases. Finally, we calculated the conversion rate from period I to period II, as well as the treatment efficiency and the occurrence of adverse events during the testing and follow-up phases. The testing phase of 52 NB patients was 18-60 days, with an average of (29.3 ± 8.0) days. Overall, 38 patients underwent SNM permanent electrode implantation, whose follow-up phase was 3-25 months, with an average of (11.9 ± 6.1) months. Compared with baseline, the voiding times, daily catheterization volume, quality of life score, OABSS score, bowel dysfunction score, maximum detrusor pressure before voiding, and residual urine volume decreased significantly in the testing phase. The daily voiding volume, functional bladder capacity, maximum urine flow rate, bladder compliance, and maximum cystometric capacity increased significantly in the testing phase. Besides, the voiding times, daily catheterization volume, quality of life score, OABSS score, bowel dysfunction score, maximum detrusor pressure before voiding, and residual urine volume decreased further from the testing to follow-up phase. Daily voiding volume, functional bladder capacity, maximum urine flow rate, bladder compliance, and maximum cystometric capacity increased further from testing to follow-up. At baseline, 10 ureteral units had vesicoureteral reflux (VUR), and 9 of them improved in the testing phase. Besides, there was 1 unit that further improved to no reflux during the follow-up phase. At baseline, 10 patients had detrusor overactivity (DO), and 8 of them improved in the testing phase. Besides, 1 patient's symptoms further improved during the follow-up phase. At baseline, there were 35 patients with detrusor-bladder neck dyssynergia (DBND); 14 (40.0%) of them disappeared during the testing phase. Among 13 cases who had DBND in the testing phase, 6 (46.2%) disappeared during the follow-up phase. Of the 47 patients with detrusor-external sphincter dyssynergia (DESD) at baseline, 8 (17.0%) disappeared during the testing phase. Among 26 cases who had DESD in the testing phase, 6 (23.1%) disappeared during the follow-up phase. The effective rate of this study was 88.5% (46/52), and the conversion rate from phase I to phase II was 73.1% (38/52). Additionally, the efficacy in a short-term follow-up was stable. SNM guided by intraoperative three-dimensional imaging of sacral CT and mobile C-arm fluoroscopy is an effective and safe treatment option for NB in short time follow-up. It would be well improved in the bladder storage function, sphincter synergetic function and emptying efficiency by video-urodynamics examination in this study.Trial registration: Chinese Clinical Trial Registry. ChiCTR2100050290. Registered August 25 2021. http://www.chictr.org.cn/index.aspx .

Evaluation of pelvic floor muscle elasticity in patients with overactive bladder syndrome using real-time tissue elastography.

INTRODUCTION AND HYPOTHESIS: The purpose of this study was to compare the muscle elasticity of the striated urethral sphincter (SUS) using real-time tissue elastography (RTE) as an evaluation of pelvic floor muscle (PFM) function between overactive bladder (OAB) patients and healthy women. METHODS: The subjects were 8 healthy middle-aged women (healthy group; age range 57-65 years) and 9 female OAB patients (OAB group; age range 42-80 years). The target sites of elastography were the striated urethral sphincter (SUS) and adipose tissue as the reference site; muscle elasticity was calculated as the strain ratio (SR) of the SUS to the reference site. Evaluations were performed at rest and during PFM contraction. The OAB group completed OAB symptom and quality of life questionnaires. The SUS SR was compared between the groups. The SUS SR at rest and during PFM contraction was compared within groups using the t-test and Wilcoxon's test. The relationship between the questionnaire results and the SUS SR was evaluated by correlation analysis. RESULTS: Intergroup comparisons between the healthy and OAB groups showed no significant differences in SUS SR at rest and during PFM contraction. On intragroup comparisons, the SUS SR was significantly higher during PFM contraction than at rest in the healthy group (p = 0.011); in the OAB group, there was no significant difference in the SUS SR between rest and PFM contraction. The SUS SR was not significantly correlated with questionnaire results for OAB symptoms. CONCLUSION: This study shows the potential to non-invasively confirm the inability of OAB patients to correctly perform PFM contraction using RTE.

OAB supraspinal control network, transition with age, and effect of treatment: A systematic review.

OBJECTIVE: In light of a better understanding of supraspinal control of nonneurogenic overactive bladder (OAB), the prevalence of which increases with age, functional imaging has gained significant momentum. The objective of this study was to perform a systematic review on the transition of supraspinal control of OAB with age, the effect of therapeutic modalities, and a coordinate-based meta-analysis of all neuroimaging evidence on supraspinal OAB control in response to bladder filling. METHODOLOGY: We performed a systematic literature search of all relevant libraries in November 2021. The coordinates of brain activity were extracted from eligible neuroimaging studies to perform an activation likelihood estimation (ALE) meta-analysis. RESULTS: A total of 16 studies out of 241 were selected for our systematic review. Coordinates were extracted from five experiments involving 70 patients. ALE meta-analysis showed activation of the insula, supplementary motor area, dorsolateral prefrontal cortex, anterior cingulate gyrus, and temporal gyrus with a transition of activation patterns with age, using a threshold of uncorrected p < 0.001. Among young patients, neuroplasticity allows the activation of accessory circuits to maintain continence, as in the cerebellum and temporoparietal lobes. Anticholinergics, pelvic floor muscle training, sacral neuromodulation, and hypnotherapy are correlated with supraspinal changes attributed to adaptability and possibly a substratum of an intrinsic supraspinal component. The latter is better demonstrated by a resting-state functional connectivity analysis, a promising tool to phenotype OAB with recent successful models of predicting severity and response to behavioral treatments. CONCLUSION: Future neuroimaging studies are necessary to better define an OAB neurosignature to allocate patients to successful treatments.

Signal abnormalities of the bladder wall detected by native T1 mapping in patients with overactive bladder.

OBJECT: Native T1 mapping provides tissue-specific T1 relaxation times, which can be used to identify structural changes in the various organs. The object of this article was to evaluate the bladder wall of patients with overactive bladder using native T1 mapping and compare the relaxation times of patients and healthy controls. MATERIAL AND METHODS: Seventeen patients with a diagnosis of overactive bladder and 15 healthy controls were enrolled in this prospective study. All participants underwent pelvic MRI and T1 maps were acquired. Native T1 relaxation times were calculated via regions of interest acquired from the anterosuperior wall of the bladder in all participants. Mean T1 relaxation times of the overactive bladder patients were compared with those of controls. RESULTS: Overactive bladder patients had statistically significantly higher T1 relaxation times compared with controls (p = 0.004). In the subgroup analysis, there was no statistically significant difference between males (1113.42 ± 62.4) and females (1176.70 ± 100.9) regarding the T1 relaxation times (p = 0.165). There were no correlations between age and T1 relaxation times in patient or control groups (r = 0.057, p = 0.825, and r = 0.052, p = 0.932, respectively). CONCLUSION: Native T1 mapping can identify structural changes in the bladder wall of patients with overactive bladder. This technique has a promising role in the diagnosis of patients with suspected overactive bladder.

Abnormal resting-state brain activity and connectivity of brain-bladder control network in overactive bladder syndrome.

BACKGROUND: Neuroimaging studies have shown that the brain is involved in the mechanism of overactive bladder disease (OAB). PURPOSE: To explorer spatial patterns of spontaneous neural activities and functional integration in patients with OAB. MATERIAL AND METHODS: In total, 28 patients with OAB and 28 matched healthy controls (HC) underwent resting-state functional magnetic resonance imaging and completed questionnaires to assess clinical symptoms. The amplitude of low-frequency fluctuation (ALFF) and ROI-based functional connectivity (FC) within the brain-bladder control network (BBCN) were calculated and compared between the two groups using a two-sample t-test. Pearson correlation analysis was performed to investigate the relationship between ALFF and the clinical score of patients with OAB. RESULTS: Compared with HCs, patients with OAB exhibited significantly decreased ALFF in the left superior medial middle gyrus (SFGmed) and superior dorsal frontal gyrus (SFGdor), and increased ALFF in the right hippocampus. Furthermore, ALFF values in the left SFGmed were negatively correlated with OABSS scores. FC in patients with OAB was significantly increased between the bilateral caudate nucleus (CAU) and bilateral SFGdor, the bilateral CAU and bilateral supplementary motor area (SMA), the bilateral thalamus and SMA; the left CAU and bilateral SFGmed, the left CAU and bilateral anterior cingulate gyrus, and the left CAU and left insula. Additionally, decreased FC was found between the bilateral amygdala and bilateral SFGmed and the left SMA and left insula. CONCLUSION: These abnormal activities and connectivities of BBCN may indicate impaired cortical control of micturition in OAB, suggesting a possible neural mechanism of OAB.

Detrusor overactivity assessment using ultrasound bladder vibrometry.

Objective. Detrusor overactivity (DO) is a urodynamic observation characterized by fluctuations in detrusor pressure (Pdet) of the bladder. Although detecting DO is important for the management of bladder symptoms, the invasive nature of urodynamic studies (UDS) makes it a source of discomfort and morbidity for patients. Ultrasound bladder vibrometry (UBV) could provide a direct and noninvasive means of detecting DO, due to its sensitivity to changes in elasticity and load in the bladder wall. In this study, we investigated the feasibility and applying UBV toward detecting DO.Approach. UBV and urodynamic study (UDS) measurements were collected in 76 neurogenic bladder patients (23 with DO). Timestamped group velocity squared (cg2) data series were collected from UBV measurements. ConcurrentPdetdata series were identically analyzed for comparison and validation. A processing approach is developed to separate transient fluctuations in the data series from the larger trend of the data and a DO index is proposed for characterizing the transient peaks observed in the data.Main Results.Applying the DO index as a classifier for DO produced sensitivities and specificities of 0.70 and 0.75 forcg2data series and 0.70 and 0.83 forPdetdata series respectively.Significance. It was found that DO can be feasibly detected from data series of timestamped UBV measurements. Collectively, these initial results are promising, and further refinement to the UBV measurement process is likely to improve and clarify its capabilities for noninvasive detection of DO.

Association between overactive bladder and pelvic organ mobility as evaluated by dynamic magnetic resonance imaging.

Overactive bladder (OAB) is a prevalent condition, which negatively impacts patients' quality of life. Pelvic organ prolapse (POP), also prevalent in women, has been recognized as an important etiology of female OAB, although the pathophysiological mechanisms remain controversial. In this study, we reviewed findings of dynamic magnetic resonance imaging (dMRI) in 118 patients with POP and investigated the association between dMRI findings, including positions and mobilities of pelvic organs as well as parameters of pelvic organ support and bladder outlet obstruction (urethral kinking), and OAB in order to elucidate the pathophysiology of OAB in patients with POP. Our results showed that compared with non-OAB patients, OAB patients had a significantly higher body mass index, more severe pelvic floor muscle impairment, and more profound supportive defects in the uterine cervix (apical compartment). On the other hand, dMRI parameters showed hardly any significant difference between patients with mild and moderate to severe OAB. These findings may imply that levator ani impairment and defective supports of the apical compartment could be associated with the presence of OAB and that the severity of OAB could be affected by factors other than those related to pelvic organ mobility and support or urethral kinking.

Considering non-bladder aetiologies of overactive bladder: a functional neuroimaging study.

OBJECTIVES: To better understand the neuropathophysiology of overactive bladder (OAB) in women by characterising supraspinal activity in response to bladder distention and cold stimulation. SUBJECTS/PATIENTS AND METHODS: We recruited 24 female participants, 12 with OAB (median [interquartile range, IQR] age 40 [32-42] years) and 12 healthy controls (HCs) without lower urinary tract (LUT) symptoms (median [IQR] age 34 [28-44] years), and assessed LUT and cognitive function through neuro-urological examination, 3-day bladder diary, urodynamic investigation, and questionnaires. Functional magnetic resonance (MR) imaging using a 3-T scanner was performed in all participants during automated, repetitive bladder filling and draining (block design) with 100 mL body temperature (37 °C) saline using a MR-compatible and MR-synchronised infusion-drainage device until strong desire to void (HIGH-FILLING/DRAINING) and bladder filling with cold saline (4 °C, i.e. COLD). Whole-brain and region-of-interest analyses were conducted using Statistical Parametric Mapping, version 12. RESULTS: Significant between-group differences were found for 3-day bladder diary variables (i.e. voiding frequency/24 h, P < 0.001; voided volume/void, P = 0.04; and urinary incontinence [UI] episodes/24 h, P = 0.007), questionnaire scores (International Consultation on Incontinence Questionnaire-Female LUT symptoms [overall, filling, and UI scores, all P < 0.001]; the Overactive Bladder Questionnaire short form [symptoms and quality-of-life scores, both P < 0.001]; the Hospital Anxiety and Depression Scale [anxiety P = 0.004 and depression P = 0.003 scores]), as well as urodynamic variables (strong desire to void, P = 0.02; maximum cystometric capacity, P = 0.007; and presence of detrusor overactivity, P = 0.002). Age, weight and cognitive function (i.e. Mini-Mental State Examination, P = 1.0) were similar between groups (P > 0.05). In patients with OAB, the HIGH task elicited activity in the superior temporal gyrus, ventrolateral prefrontal cortex (VLPFC), and mid-cingulate cortex; and the COLD task elicited activity in the VLPFC, cerebellum, and basal ganglia. Compared to HCs, patients with OAB showed significantly stronger cerebellar activity during HIGH-FILLING and significantly less activity in the insula and VLPFC during HIGH-DRAINING. CONCLUSIONS: The present findings suggest a sensory processing and modulation deficiency in our OAB group, probably as part of their underlying pathophysiology, as they lacked activity in essential sensory processing areas, such as the insula. Instead, accessory areas, such as the cerebellum, showed significantly stronger activation compared to HCs, presumably supporting pelvic-floor motor activity to prevent UI. The novel findings of the present study provide physiological evidence of the necessity to consider non-bladder aetiologies of bladder symptoms.

Excessive accumulation of visceral fat is associated with lower urinary symptoms including overactive bladder in female patients.

OBJECTIVE: To assess the relationship between visceral fat accumulation and lower urinary tract symptoms in female patients. METHODS: In this single-center study, we enrolled all women who underwent screening abdominal computed tomography 3 months before the study, irrespective of whether they experienced lower urinary tract symptoms. The Overactive Bladder Symptom Score was used to assess subjective symptoms. Uroflowmetry and ultrasound assessment of post-void residual urine were carried out to assess objective signs. We analyzed the relationship between lower urinary tract symptoms and various body fat accumulation parameters, including visceral fat area, visceral fat volume and total abdominal fat volume, assessed using computed tomography scans. RESULTS: A total of 182 patients were divided into the overactive bladder (n = 71, 39.0%) and the non-overactive bladder (n = 111, 61.0%) groups. The visceral fat area, visceral fat volume and visceral fat volume/total abdominal fat volume values were all significantly higher in the overactive bladder group than in the non-overactive bladder group (P < 0.001). Of these parameters, the visceral fat volume/total abdominal fat volume ratio showed the strongest correlation with the total Overactive Bladder Symptom Score (r = 0.394, P < 0.001). The maximum urine flow rate correlated negatively with the visceral fat volume/total abdominal fat volume value (visceral fat volume/total abdominal fat volume r = -0.289, P < 0.001). Subsequent multivariate analysis showed that a high visceral fat volume/total abdominal fat volume value, age and metabolic syndrome-related diseases were independent risk factors for the presence of overactive bladder. CONCLUSIONS: Excessive accumulation of visceral fat is independently associated with overactive bladder in females.

Chronic mirabegron treatment increases human brown fat, HDL cholesterol, and insulin sensitivity.

BACKGROUNDMirabegron is a ß3-adrenergic receptor (ß3-AR) agonist approved only for the treatment of overactive bladder. Encouraging preclinical results suggest that ß3-AR agonists could also improve obesity-related metabolic disease by increasing brown adipose tissue (BAT) thermogenesis, white adipose tissue (WAT) lipolysis, and insulin sensitivity.METHODSWe treated 14 healthy women of diverse ethnicities (27.5 ± 1.1 years of age, BMI of 25.4 ± 1.2 kg/m2) with 100 mg mirabegron (Myrbetriq extended-release tablet, Astellas Pharma) for 4 weeks in an open-label study. The primary endpoint was the change in BAT metabolic activity as measured by [18F]-2-fluoro-d-2-deoxy-d-glucose (18F-FDG) PET/CT. Secondary endpoints included resting energy expenditure (REE), plasma metabolites, and glucose and insulin metabolism as assessed by a frequently sampled intravenous glucose tolerance test.RESULTSChronic mirabegron therapy increased BAT metabolic activity. Whole-body REE was higher, without changes in body weight or composition. Additionally, there were elevations in plasma levels of the beneficial lipoprotein biomarkers HDL and ApoA1, as well as total bile acids. Adiponectin, a WAT-derived hormone that has antidiabetic and antiinflammatory capabilities, increased with acute treatment and was 35% higher upon completion of the study. Finally, an intravenous glucose tolerance test revealed higher insulin sensitivity, glucose effectiveness, and insulin secretion.CONCLUSIONThese findings indicate that human BAT metabolic activity can be increased after chronic pharmacological stimulation with mirabegron and support the investigation of ß3-AR agonists as a treatment for metabolic disease.TRIAL REGISTRATIONClinicaltrials.gov NCT03049462.FUNDINGThis work was supported by grants from the Intramural Research Program of the NIDDK, NIH (DK075112, DK075116, DK071013, and DK071014).

Intra- and inter-resting-state networks abnormalities in overactive bladder syndrome patients: an independent component analysis of resting-state fMRI.

PURPOSE: This study aims to determine whether intra-network and inter-network brain connectivities are altered using an independent component analysis (ICA). METHODS: Resting-state functional MRI (rs-fMRI) data were acquired from 26 patients with OAB and 28 healthy controls (HC). Eleven resting-state networks (RSNs) were identified via ICA. General linear model (GLM) was used to compare intra-network FC and inter-network FC of RSNs between the two groups. Pearson correlation analyses were performed to investigate the relationship between the identified RSNs and clinical variables. RESULTS: Compared with HC, the OAB group showed abnormal FC within the sensorimotor-related network (SMN), the dorsal attention network (DAN), the dorsal visual network (dVN), and the left frontoparietal network (LFPN). With respect to inter-network interactions, decreased FC was detected between the SMN and the anterior default mode network (aDMN). CONCLUSION: This study demonstrated that abnormal FC between RSNs may reflect the altered resting state of the brain-bladder network. The findings of this study provide complementary evidence that can help further understand the neural substrates of the overactive bladder.

Risk factors for febrile genito-urinary infection in the catheterized patients by with spinal cord injury-associated chronic neurogenic lower urinary tract dysfunction evaluated by urodynamic study and cystography: a retrospective study.

INTRODUCTION: To investigate the risk factors for febrile genito-urinary tract infection (GUTI) in spinal cord injury-associated neurogenic lower urinary tract dysfunction (NLUTD) patients who perform routine clean intermittent catheterization (CIC) evaluated by urodynamic study (UDS) and cystography. PATIENTS AND METHODS: Over a 3-year period, we retrospectively assessed risk factors for febrile UTI in 141 spinal cord injury patients diagnosed as NLUTD and performing routine CIC, regarding gender, UDS findings such as bladder compliance, maximum cystometric capacity, and cystography. RESULTS: A total of 41 patients had febrile GUTI in the follow-up period as along with 32 cases of pyelonephritis, 10 cases of epididymitis, and 1 case of prostatitis, including patients with multiple infectious diseases. The causative bacteria were Escherichia coli (14 cases) followed by Pseudomonas aeruginosa (n = 5), Klebsiella pneumoniae (n = 4), and Klebsiella oxytoca (n = 4). Antibiotic-resistant E. coli were seen, with 36.4% instances of extended-spectrum beta-lactamase production in whole of E. coli. Male gender (p = 0.018), ASIA Impairment Scale (AIS) C or more severe (p = 0.031), the number of CIC (p = 0.034), use of quinolones (p < 0.001) and severe bladder deformity (DG 2 or more, p = 0.004) were significantly associated with febrile GUTI occurrence. CONCLUSIONS: Our data demonstrated that male gender, severe bladder deformity (DG 2 or more), AIS C or more, the number of CIC, and use of quinolones were significantly associated with febrile GUTI occurrence in NLUTD patients employing routine CIC. Further prospective studies are necessary to define the full spectrum of possible risk factors for febrile GUTI in these patients.

Use of Ultrasound Urodynamics to Identify Differences in Bladder Shape Between Individuals With and Without Overactive Bladder.

OBJECTIVES: The objective of this study was to identify differences in bladder shape changes between individuals with overactive bladder (OAB) and unaffected individuals during ultrasound urodynamics. METHODS: A prospective urodynamic study was performed with concurrent transabdominal ultrasound (ultrasound urodynamics) on individuals with and without OAB based on validated International Consultation on Incontinence Questionnaire - OAB survey scores. Three-dimensional ultrasound images were acquired at 1-minute increments during filling and used to measure bladder diameters in the height, width, and depth orientations. The engineering strain for each diameter was compared between participants with OAB and controls during urodynamic filling. The height-to-width ratio at capacity was used to determine if individuals were shape outliers. RESULTS: A total of 22 subjects were enrolled, including 11 with OAB and 11 without OAB. During urodynamic filling in both groups, the greatest degree of geometric strain was found in the height orientation, indicating that bladders generally fill in a craniocaudal shape. The mean ± SD height-to-width ratio of the control group was 1.06 ± 0.12 yielding a 95% confidence interval of 0.82 to 1.30. Five (45.5%) of 11 OAB subjects had height-to-width ratios outside this interval as compared with none of the control subjects, identifying a potential shape-mediated subgroup of OAB. CONCLUSIONS: Three-dimensional ultrasound urodynamics can be used to identify differences in bladder shape comparing individuals with and without OAB. This method may be used to identify a subset of OAB patients with abnormal bladder shapes which may play a role in the pathophysiology of their OAB symptoms.