Mapping of the Human Brainstem During Continence and Micturition: Noninvasive 7-T fMRI Study

NCT04846387 | Completed

• 1 other identifier: PRO00026967
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The lower urinary tract (bladder, bladder neck, urethra and urethral sphincter) has two functions: Storage (Continence) and voiding (micturition). Lower urinary tract dysfunction (LUTD) includes symptoms in the storage phase (such as urinary frequency, urgency, incontinence) or micturition phase (such as voiding dysfunction, hesitancy and urinary retention), or both. Proper urinary tract function is controlled by a complex network of peripheral and central nervous system. A delicate and complex switch exists between storage of urine and elimination of urine and in humans, the control over this switch is located in brain stem. Although significant research efforts have been utilized to understand supraspinal neural control of LUTs in humans, our understanding of the brainstem in humans is very limited, mainly due to the small size of nuclei. The extensive involvement of the brainstem in LUTS control has urged us to look into a better way to investigate and identify the brainstem nuclei involved throughout the entire bladder cycle, especially in neurogenic patients. To our knowledge, there has been no published study using high-resolution MRI (7 Tesla) to study the role of brainstem specifically in LUT. Brainstem evaluation in regards to LUT function in a thorough and accurate manner using high-resolution techniques is of high priority for benign urology and National Institute of Health. The findings from this proposal will lay the foundation to study of brainstem control in the bladder cycle in neurogenic patients with high-resolution neuroimaging, and will be seminal research in the field. The investigators hypothesize that Grey matter (blood-oxygen-level-dependent BOLD) signals and functional connectivity (FC) evaluation of the brainstem regions involved in continence and micturition are superior in 7T when compared to 3T in humans allowing assessment of the variations between men and women. Brainstem Regions of Interest (ROIs) include Pontine Storage Center (PSC) ("L region of the pons) and PAG are expected to be activated during the storage (continence) phase and Pontine Micturition Center (PMC) ("M" region of the pons) are expected to be activated during the voiding (micturition) phase.

Conditions

Healthy

Keywords

Pontine Storage Center (PSC); Functional Magnetic Resonance Imaging (fMRI); Lower Urinary Tract Symptoms (LUTS); Pontine Micturition Center (PMC); Neuroimaging; Periaqueductal Gray (PAG); Micturition; Bladder; Incontinence; Overactive Bladder

Outcome Measures

Primary Outcomes (1)

• Blood Oxygen Level Dependent (BOLD) signals intensity

  BOLD signal intensity in the regions of interest during empty bladder, full bladder, and micturition in healthy males and females

  2 years

Secondary Outcomes (6)

• Blood Oxygen Level Dependent (BOLD) signals

  2 years

• Uroflow measure

  2 years

• Postvoid Residual

  2 years

• Urinary symptoms scores

  2 years

• Mean Diffusivity (MD)

  2 years

Study Arms (2)

Females with Normal Bladder Function

Diagnostic Tests: functional MRI and urodynamic studies. During screening, subject will be asked to come to their appointment with a full bladder. For the uroflow, they will urinate into a special funnel connected to a measuring instrument in a private bathroom followed by measuring Post void residual volume through PVR scanner. This is to ensure that they do not have any urological issue which can disqualify them from the study. At this visit, we will also instruct them about the urine voiding-holding task, our noninvasive fMRI paradigm, which the subjects will be performing during the fMRI portion of the study at visit 2. A 7-Tesla Siemens MAGNETOM scanner will be used. A urinary pouch will be used to collect the participant's urine while in the scanner.

Diagnostic Test: Magnetic Resonance Imaging (MRI); Diagnostic Test: Post-Void Residual; Diagnostic Test: Uroflowmetry; Behavioral: Questionaire - AUA Symptom Score

Males with Normal Bladder Function

Diagnostic Tests: functional MRI and urodynamic studies. During screening, subject will be asked to come to their appointment with a full bladder. For the uroflow, they will urinate into a special funnel connected to a measuring instrument in a private bathroom followed by measuring Post void residual volume through PVR scanner. This is to ensure that they do not have any urological issue which can disqualify them from the study. At this visit, we will also instruct them about the urine voiding-holding task, our noninvasive fMRI paradigm, which the subjects will be performing during the fMRI portion of the study at visit 2. A 7-Tesla Siemens MAGNETOM scanner will be used. A condom catheter will be used to collect the participant's urine while in the scanner.

Diagnostic Test: Magnetic Resonance Imaging (MRI); Diagnostic Test: Post-Void Residual; Diagnostic Test: Uroflowmetry; Behavioral: Questionaire - AUA Symptom Score

Interventions

Magnetic Resonance Imaging (MRI) DIAGNOSTIC_TEST

A T1-weighted Anatomical Image, Diffusion Weighted Image, and functional MRI (fMRI) of "empty bladder" image will be obtained. Additionally, fMRI image during "full bladder" state and voiding/holding tasks will be obtained.

Females with Normal Bladder Function; Males with Normal Bladder Function

Post-Void Residual DIAGNOSTIC_TEST

The patient's post-void residual is determined using a portable ultrasound machine after emptying the bladder just prior to entering the MRI scanner and immediately after the MRI scan.

Also known as: PVR

Females with Normal Bladder Function; Males with Normal Bladder Function

Uroflowmetry DIAGNOSTIC_TEST

Patients will urinate into a funnel connected to an electric flow meter to record urine flow rates in mililters per second. This is used as part of the screening process.

Females with Normal Bladder Function; Males with Normal Bladder Function

Questionaire - AUA Symptom Score BEHAVIORAL

Subjects will fill out questionnaire asking about urinary symptoms. The range is 0-35.

Also known as: AUASS

Females with Normal Bladder Function; Males with Normal Bladder Function

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

We will recruit healthy male and female volunteers \> 18 years of age with no neurological disease and urinary issues at Houston Methodist Hospital. We anticipate an equal gender distribution (10 men and 10 women) among study participants. Once screened for inclusion and exclusion criteria, volunteers will be approached and asked if they would like to participate in this study. They will then be given study material and allowed sufficient time to make an informed decision regarding participation.

You may qualify if:

• Healthy adult male and female volunteers ≥18 years of age with no neurological disease and genitourinary abnormalities will be screened:
• Post-Void Residual (PVR) \< 20% of their bladder capacity OR
• Above 10 percentile of Liverpool nomogram
• AND
• AUASS score \< 7 will be eligible to participate in the study.

You may not qualify if:

• history of clinically relevant genitourinary malignancy or surgery such as:
• anti-incontinence procedures
• urethral strictures
• advanced pelvic organ prolapse
• any neurological disorders
• history of seizures,
• pregnancy or planning to become pregnant,
• and contraindications to MRI will be excluded.
• Research team members who are involved with the data collection and the data analysis for this study.

Sponsors & Collaborators

• The Methodist Hospital Research Institute: lead

Study Sites (1)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Lower Urinary Tract Symptoms; Urinary Bladder, Overactive

Interventions

Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Rose Khavari, MD

  The Methodist Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Houston Methodist Hospital Urologist and Research Director

Study Record Dates

• First Submitted: April 12, 2021
• First Posted: April 15, 2021
• Study Start: January 18, 2021
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: April 10, 2025

Record last verified: 2025-04

Locations

US (1)