Clinical trial NCT04846387: Mapping of the Human Brainstem During Continence and Micturition: Noninvasive 7-T fMRI Study
Official title: High-resolution Mapping of the Human Brainstem During Continence and Micturition: in Vivo Noninvasive 7 Tesla fMRI Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
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
Lead sponsor: The Methodist Hospital Research Institute
Sponsor class: OTHER
First posted: 2021-04-15
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Detailed description: The current proposal will be the first 7-Tesla study evaluating brain and specifically brainstem control over LUT. The study will utilize a noninvasive functional MRI (fMRI) protocol that allows for evaluation of brainstem activity during continence and micturition in real-time, using high-resolution neuroimaging techniques (7T fMRI) in both men and women. The study will recruit 20 healthy subjects (10 male and 10 female) for participation in this study. The participants for this study will undergo a few tests including a uroflow, PVR and a protocol training session during screening at visit 1, and a fMRI at visit 2.

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 will involve having the participant drink 500-750 mL of water approximately 20 minutes prior to the start of their scan, which the subjects will be performing during the fMRI portion of the study at visit 2.

The subsequent Grey matter (BOLD) signals and functional connectivity (FC) analysis will allow investigators to further the current understanding of brainstem control of the LUT and bladder cycle.

Eligibility criteria: Inclusion Criteria:

• 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Blood Oxygen Level Dependent (BOLD) signals intensity
timeFrame: 2 years
Secondary outcomes:
measure: Blood Oxygen Level Dependent (BOLD) signals
timeFrame: 2 years
measure: Uroflow measure
timeFrame: 2 years
measure: Postvoid Residual
timeFrame: 2 years
measure: Urinary symptoms scores
timeFrame: 2 years
measure: Mean Diffusivity (MD)
timeFrame: 2 years
measure: Fractional Anisotropy (FA)
timeFrame: 2 years
Other outcomes:
Locations:
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
Study officials:
affiliation: The Methodist Hospital Research Institute
name: Rose Khavari, MD
role: PRINCIPAL_INVESTIGATOR
References: