The Bladder and the Brain - Investigation of the Supraspinal Neural Control of Lower Urinary Tract Function in Healthy Subjects and Patients With Neurogenic and Non-neurogenic Bladder Dysfunction Using Advanced Neuroimaging Techniques
The Bladder and the Brain - Investigation of the Supraspinal Neural Control of Lower Urinary Tract Function in Healthy Subjects and Patients With Neurogenic and Non-neurogenic Bladder Dysfunction Using Advanced Neuroimaging Techniques
The purpose of this study is to provide profound insight into the supraspinal neuronal mechanisms and networks responsible for lower urinary tract (LUT) control and to verify, amend or adjust neuronal circuitry models established from findings in healthy subjects in the context of neurogenic and non-neurogenic LUT dysfunction.
The subject recruitment will be performed within the Neuro-Urology outpatient clinic at the Balgrist University Hospital and in collaboration with the Departments of Neurology, Urology and Gynecology at the University Hospital Zürich.
The following subject groups will be recruited: 1) healthy controls (n=22), Non-neurogenic overactive bladder (NNOAB) patients (n=20), multiple sclerosis (MS) patients with OAB (n=15), MS patients without OAB (n=15), spinal cord injury (SCI) patients with neurogenic detrusor overactivity (n=24).
After inclusion, all subjects and patients will undergo one to two functional magnetic resonance imaging (fMRI) sessions. NNOAB patients might undergo an additional fMRI session after receiving overactive bladder (OAB) treatment (such as antimuscarinics, intradetrusor injections of botulinum toxin type A). Spinal cord injury (SCI) patients with neurogenic detrusor overactivity will undergo an additional fMRI session 5-7 weeks after intradetrusor injections of botulinum toxin type A.
High-resolution anatomical images and functional blood-oxygen-level-dependent (BOLD)-signal sensitive images will be acquired. In addition to the fMRI, diffusion tensor imaging (DTI) sequences will be recorded after the anatomical scans to provide information about the structural supraspinal connectivity.
Study endpoints are changes of the BOLD signal in regard to location and intensity, structural and functional connectivity (FC) between previously described supraspinal centers involved in LUT control, and statistical differences of changes in BOLD signals, structural and functional connectivity between patients and healthy controls.
All acquired fMRI data will be transferred to an off-line workstation running BrainVoyager QX or Statistical Parametric Mapping (SPM) Version 8. The functional data will be pre-processed for motion correction, spatial smoothing, linear trend removal, and temporal high-pass filtering. With both programs statistical analysis and graphical presentation of the results can be performed.
The DTI records will be evaluated with SPM8, BrainVoyager QX or other programs like Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (FSL) and DTI-Studio. To estimate FC we will use SPM8 or the brain connectivity toolbox. Both softwares allow the estimation of rest- and task-related connectivity on single subject and group level with corrected statistical threshold.
Overall, 96 subjects for the main study are estimated to be sufficient to demonstrate significant differences between groups.
Inclusion Criteria:
Healthy controls
MS patients with OAB
Right handed
MR suitability
Written informed consent
diagnosis of MS according to the McDonald criteria
Expanded Disability Status Scale (EDSS) ≤ 6
OAB symptoms since > 6 months
with or without detrusor overactivity
MS patients without OAB
Patients with NNOAB
Right handed
MR suitability
Written informed consent
idiopathic OAB symptoms since > 6 months
refractory to antimuscarinic treatment for ≥ 1 month
indication for intradetrusor injections of Botulinumtoxin Type A
willingness and ability to perform self-catheterization
SCI patients with neurogenic detrusor overactivity
Exclusion Criteria:
Healthy controls
impaired LUT function
pregnancy or breast feeding
no informed consent
any craniocerebral injury or surgery
any permanent ferromagnetic implant
any previous surgery of the LUT or genitalia
any anatomical anomaly of the LUT or genitalia
any LUT malignancy
postvoid residual urine volume (PVR) > 150ml
current urinary tract infection
any LUT symptoms
MS patients with OAB
MS patients without OAB
pregnancy or breast feeding
any permanent ferromagnetic implant
any neurological or psychological disease despite MS
any craniocerebral injury or surgery
any previous surgery of the LUT or genitalia
any anatomical anomaly or malignancy of the LUT or genitalia
any metabolic disease
PVR > 150ml
any concomitant treatment for the LUT (e.g. neuromodulation)
Stress urinary incontinence
any LUT symptoms
indwelling catheters or the necessity to perform self-catheterization
detrusor overactivity
current urinary tract infection
Patients with NNOAB
SCI patients with neurogenic detrusor overactivity