Altered Bladder-Related Brain Network in Multiple Sclerosis Women With Voiding Dysfunction

Objectives: A number of neuro-urology imaging studies have mainly focused on investigating the brain activations during micturition in healthy and neuropathic patients. It is, however, also necessary to study brain functional connectivity (FC) within bladder-related regions in order to understand the brain organization during the execution of bladder function. This study aims to identify the altered brain network associated with bladder function in multiple sclerosis (MS) women with voiding dysfunction through comparisons with healthy subjects via concurrent urodynamics (UDS)/fMRI. Materials and Methods: Ten healthy adult women and nine adult ambulatory women with clinically stable MS for ≥ 6 months and symptomatic voiding phase Neurogenic Lower Urinary Tract Dysfunction (NLUTD) underwent UDS/fMRI evaluation with a task of bladder filling/emptying that was repeated three to five times. We quantitatively compared their FC within 17 bladder-related brain regions during two urodynamic phases: ‘strong desire to void’ and ‘(attempt at) voiding initiation’. Results: At ‘strong desire to void’, the healthy group showed significantly stronger FC in regions involved in bladder filling and suppression of voiding compared to the patient group. These regions included the bilateral anterior cingulate cortex, right supplementary motor area, and right middle frontal gyrus. During ‘(attempt at) voiding initiation’, healthy subjects exhibited stronger FC in the right inferior frontal gyrus compared to MS patients. Conclusion: Our study offers a new way to identify alterations in the neural mechanisms underlying NLUTD and provides potential targets for clinical interventions (such as cortical neuromodulation) aimed at restoring bladder functions in MS patients

Design, Development and Temporal Evaluation of an MRI-Compatible In-Vitro Circulation Model Using a Compliant AAA Phantom

Biomechanical characterization of abdominal aortic aneurysms (AAA) has become commonplace in rupture risk assessment studies. However, its translation to the clinic has been greatly limited due to the complexity associated with its tools and their implementation. The unattainability of patient-specific tissue properties leads to the use of generalized population-averaged material models in finite element analyses, which adds a degree of uncertainty to the wall mechanics quantification. In addition, computational fluid dynamics modeling of AAA typically lacks the patient-specific inflow and outflow boundary conditions that should be obtained by non-standard of care clinical imaging. An alternative approach for analyzing AAA flow and sac volume changes is to conduct in vitro experiments in a controlled laboratory environment. We designed, built, and characterized quantitatively a benchtop flow-loop using a deformable AAA silicone phantom representative of a patient-specific geometry. The impedance modules, which are essential components of the flow-loop, were fine-tuned to ensure typical intra-sac pressure conditions. The phantom was imaged with a magnetic resonance imaging (MRI) scanner to acquire time-resolved images of the moving wall and the velocity field inside the sac. Temporal AAA sac volume changes lead to a corresponding variation in compliance throughout the cardiac cycle. The primary outcome of this work was the design optimization of the impedance elements, the quantitative characterization of the resistive and capacitive attributes of a compliant AAA phantom, and the exemplary use of MRI for flow visualization and quantification of the deformed AAA geometry

ECG-triggered non-enhanced MR angiography of peripheral arteries in comparison to DSA in patients with peripheral artery occlusive disease

Object: The purpose of this study was to evaluate peripheral non-enhanced-MRA (NE-MRA) acquired with a 3D Turbo Spin Echo sequence with electrocardiographt (ECG) triggering in comparison to Digital Subtraction Angiography (DSA) as the gold standard in symptomatic peripheral artery occlusive disease (PAOD) patients. Materials and methods: This IRB approved prospective study included 23 PAOD patients from whom three patients had to be excluded. The remaining 20 subjects were included in the analysis (15 male; mean age 62.4±15.3years). The patients first underwent DSA followed by NE-MRA on a 1.5-T whole body scanner within 24h after the DSA study. A NATIVE (Non-contrast Angiography of the Arteries and Veins) SPACE (Sampling Perfection with Application Optimized Contrast by using different flip angle Evolution) sequence at four levels (pelvis, upper leg, knee region and lower leg) was acquired. For evaluation purposes, subtracted standardized MIP (maximum intensity projection) images were generated from the NE-MRA data sets. Qualitative assessment of NE-MRA images in reference to the corresponding DSA images, as well as blinded stenosis grading of preselected segments in NE-MRA images were performed by two experienced readers. Image quality in 95 corresponding arterial segments was rated from 1 (good) to 4 (inadequate) directly comparing the NE-MRA with the corresponding DSA segment as the gold standard. Blinded stenosis grading consisted of 66 preselected stenoses rated from 1 (90%) in NE-MRA which were compared to the grade in the corresponding DSA. Results: The mean image quality of NE-MRA in comparison to DSA was 2.7±1.1 (reader 1) and 3.0±1.0 (reader 2). The kappa value indicating interobserver agreement was 0.34; readers 1 and 2 rated the image quality as good in 21% and 3%, sufficient in 19% and 41%, limited in 29% and 14% and inadequate in 31% and 42%, respectively. Stenosis graduation revealed significantly higher grades in NE-MRA (reader 1: 3.0±0.7, p<0.001 and reader 2: 3.1+0.8, p<0.001) compared to DSA (mean value DSA 2.7±0.8). The kappa value indicating interobserver agreement concerning stenosis grading was 0.59. Conclusion: NE-MRA revealed a relatively high number of inadequate quality segments. This is in line with recently published comparable studies of the similar SPACE NE-MRA techniques. Further advance of NE-MRA techniques remains desirable for patients with PAO

Predictors for Outcomes of Noninvasive, Individualized Transcranial Magnetic Neuromodulation in Multiple Sclerosis Women With Neurogenic Voiding Dysfunction

Purpose: Multiple sclerosis (MS) is a multifocal demyelinating disease that affects the central nervous system (CNS) and commonly leads to neurogenic lower urinary tract dysfunction (NLUTD). Proper storage and release of urine relies on synchronized activity of the LUT, which is meticulously regulated by supraspinal circuits, making it vulnerable to diseases such as MS. NLUTD, characterized by voiding dysfunction (VD), storage issues, or a combination of both is a common occurrence in MS. Unfortunately, there are limited treatment options for NLUTD, making the search for alternative treatments such as transcranial rotating permanent magnet stimulation (TRPMS) of utmost importance. To assess effectiveness of treatment we also need to understand underlying factors that may affect outcomes, which we addressed here. Methods: Ten MS subjects with VD and median age of 54.5 years received daily TRPMS sessions for two weeks. Five pre-determined regions of interest (ROIs) known to be involved in the micturition cycle were modulated (stimulated or inhibited) using TRPMS. Clinical data (non-instrumented uroflow and urodynamics parameters, PVR, bladder symptom questionnaires) and neuro-imaging data were collected at baseline and following TRPMS via 7-Tesla Siemens MAGNETOM Terra magnetic resonance imaging (MRI) scanner. Each participant underwent functional MRI (fMRI) concurrently with a repeated urodynamic study (UDS). Baseline data of each arm was evaluated to determine any indicators of successful response to treatment

Evaluating Noninvasive Brain Stimulation to Treat Overactive Bladder in Individuals With Multiple Sclerosis: A Randomized Controlled Trial Protocol

Background Multiple Sclerosis (MS) is an often debilitating disease affecting the myelin sheath that encompasses neurons. It can be accompanied by a myriad of pathologies and adverse effects such as neurogenic lower urinary tract dysfunction (NLUTD). Current treatment modalities for resolving NLUTD focus mainly on alleviating symptoms while the source of the discomfort emanates from a disruption in brain to bladder neural circuitry. Here, we leverage functional magnetic resonance imaging (fMRI), repetitive transcranial magnetic stimulation (rTMS) protocols and the brains innate neural plasticity to aid in resolving overactive bladder (OAB) symptoms associated with NLUTD. Methods By employing an advanced neuro-navigation technique along with processed fMRI and diffusion tensor imaging data to help locate specific targets in each participant brain, we are able to deliver tailored neuromodulation protocols and affect either an excitatory (20 min @ 10 Hz, applied to the lateral and medial pre-frontal cortex) or inhibitory (20 min @ 1 Hz, applied to the pelvic supplemental motor area) signal on neural circuitry fundamental to the micturition cycle in humans to restore or reroute autonomic and sensorimotor activity between the brain and bladder. Through a regimen of questionnaires, bladder diaries, stimulation sessions and analysis, we aim to gauge rTMS effectiveness in women with clinically stable MS. Discussion Some limitations do exist with this study. In targeting the MS population, the stochastic nature of MS in general highlights difficulties in recruiting enough participants with similar symptomology to make meaningful comparisons. As well, for this neuromodulatory approach to achieve some rate of success, there must be enough intact white matter in specific brain regions to receive effective stimulation. While we understand that our results will represent only a subset of the MS community, we are confident that we will accomplish our goal of increasing the quality of life for those burdened with MS and NLUTD. Trial registration This trial is registered at ClinicalTrials.gov (NCT06072703), posted on Oct 10, 2023

Gold-silver alloy nanoshells: a new candidate for nanotherapeutics and diagnostics

We have developed novel gold-silver alloy nanoshells as magnetic resonance imaging (MRI) dual T1 (positive) and T2 (negative) contrast agents as an alternative to typical gadolinium (Gd)-based contrast agents. Specifically, we have doped iron oxide nanoparticles with Gd ions and sequestered the ions within the core by coating the nanoparticles with an alloy of gold and silver. Thus, these nanoparticles are very innovative and have the potential to overcome toxicities related to renal clearance of contrast agents such as nephrogenic systemic fibrosis. The morphology of the attained nanoparticles was characterized by XRD which demonstrated the successful incorporation of Gd(III) ions into the structure of the magnetite, with no major alterations of the spinel structure, as well as the growth of the gold-silver alloy shells. This was supported by TEM, ICP-AES, and SEM/EDS data. The nanoshells showed a saturation magnetization of 38 emu/g because of the presence of Gd ions within the crystalline structure with r1 and r2 values of 0.0119 and 0.9229 mL mg-1 s-1, respectively (Au:Ag alloy = 1:1). T1- and T2-weighted images of the nanoshells showed that these agents can both increase the surrounding water proton signals in the T1-weighted image and reduce the signal in T2-weighted images. The as-synthesized nanoparticles exhibited strong absorption in the range of 600-800 nm, their optical properties being strongly dependent upon the thickness of the gold-silver alloy shell. Thus, these nanoshells have the potential to be utilized for tumor cell ablation because of their absorption as well as an imaging agent

Disruption of Specific White Matter Tracts Is Associated With Neurogenic Lower Urinary Tract Dysfunction in Women With Multiple Sclerosis

Objective: To identify specific white matter tracts (WMTs) whose disruption is associated with the severity of Neurogenic Lower Urinary Tract Dysfunction (NLUTD) in two independent cohorts of women with MS and NLUTD. Methods: Cohort 1 consisted of twenty-eight women with MS and NLUTD. The validation cohort consisted of ten women with MS and NLUTD. Eleven healthy women served as controls. Participants of both MS cohorts had the same inclusion and exclusion criteria. Both MS cohorts and the healthy controls underwent the same clinical assessment and fMRI protocol, except that the validation MS cohort underwent 7-Tesla fMRI scan. Fifteen WMTs (six coursing to relevant brainstem areas) involved in bladder control were a priori regions of interest (ROI). Spearman’s correlation test was performed between each the Fractional Anisotropy (FA) and Mean Diffusivity (MD) of each WMT and the clinical parameters. Results: Overall, we found a very high degree of overlap (100% of a priori ROI) in the tracts identified by our correlation analysis as having the greatest contribution to NLUTD symptoms in MS women. The Right Inferior Cerebellar Peduncle, Left Posterior Limb of Internal Capsule, and Left Superior Cerebellar Peduncle displayed significant associations to the greatest number of clinical parameters. Conclusions: Our correlation analysis supports the role of specific WMT disruptions in the contribution of symptoms in women with MS and NLUTD, as confirmed in two independent MS cohorts

Disruption of Specific White Matter Tracts is Associated With Neurogenic Lower Urinary Tract Dysfunction in Women With Multiple Sclerosis

OBJECTIVE: To identify specific white matter tracts (WMTs) whose disruption is associated with the severity of neurogenic lower urinary tract dysfunction (NLUTD) in two independent cohorts of women with multiple sclerosis (MS) and NLUTD. METHODS: Cohort 1 consisted of twenty-eight women with MS and NLUTD. The validation cohort consisted of 10 women with MS and NLUTD. Eleven healthy women served as controls. Participants of both MS cohorts had the same inclusion and exclusion criteria. Both MS cohorts and the healthy controls underwent the same clinical assessment and functional MRI (fMRI) protocol, except that the validation MS cohort underwent 7-Tesla fMRI scan. Fifteen WMTs (six coursing to relevant brainstem areas) involved in bladder control were a priori regions of interest (ROI). Spearman\u27s correlation test was performed between each the Fractional Anisotropy (FA) and mean diffusivity (MD) of each WMT and the clinical parameters. RESULTS: Overall, we found a very high degree of overlap (100% of a priori ROI) in the tracts identified by our correlation analysis as having the greatest contribution to NLUTD symptoms in MS women. The right inferior cerebellar peduncle, left posterior limb of internal capsule, and left superior cerebellar peduncle displayed significant associations to the greatest number of clinical parameters. CONCLUSIONS: Our correlation analysis supports the role of specific WMT disruptions in the contribution of symptoms in women with MS and NLUTD, as confirmed in two independent MS cohorts