The LURN Research Network Neuroimaging and Sensory Testing (NIST) Study: Design, protocols, and operations

Abstract

The Neuroimaging and Sensory Testing (NIST) Study of the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) is a cross-sectional, case-control study designed to investigate whether disrupted brain connectivity and sensory processing are associated with abnormal lower urinary tract symptoms (LUTS) in patients with overactive bladder syndrome (OAB). The NIST Study tests the hypotheses that patients with urinary urgency will demonstrate: (1) abnormal functional and structural connectivity of brain regions involved in urinary sensation on magnetic resonance imaging (MRI), and (2) hypersensitivity to painful (pressure) and non-painful (auditory) sensory stimuli on quantitative sensory testing (QST), compared to controls. Male and female adults (18 years or older) who present at one of the six participating LURN clinical centers for clinical care of their LUTS, with symptoms of urinary urgency with or without urgency urinary incontinence, are eligible to participate. The NIST Study is the largest MRI and QST study of its kind, yielding a neuroimaging and sensory testing dataset unprecedented in OAB research. Advanced multi-modal techniques are used to understand brain functional and structural connectivity, including gray matter volume, and sensory function. Unlike previous MRI studies which involved invasive catheterization and repeated cycles of non-physiologic bladder filling and emptying via a catheter, we use a water ingestion protocol to mimic more physiological bladder filling through natural diuresis. Furthermore, these data will be used in concert with other phenotyping data to improve our understanding of clinically meaningful subtypes of patients with LUTS in order to improve patient care and management outcomes.

Reflex voiding in rat occurs at consistent bladder volume regardless of pressure or infusion rate

“…We observed that increasing infusion rate had a significant effect on the pressure to evoke the micturition reflex, which was similar to Andersson and colleague's observation in humans, where for the majority of filling a higher infusion rate resulted in higher filling pressures 38 . Consequently, infusion rate has been termed a confound in urodynamics, 39 such that noninvasive techniques are being developed to circumvent the need for infusing volume into the bladder for urodynamic research 40 …”

Naturalistic Bladder Filling Reveals Subtypes in Overactive Bladder Syndrome That Differentially Engages Urinary Urgency-Related Brain Circuits: Results From the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN)

“…13 A cross-sectional assessment of brain and sensory differences between participants with OAB and CONs was performed. The full protocol has been described 13 : Eligible participants underwent experimental sensory testing 14 and noninvasive MRI, whereby high-resolution structural (T1), functional MRI (fMRI) during 2 different bladder fullness states and diffusion tensor imaging were acquired from brains of OAB patients and CONs. Data from different scanners were harmonized through phantom imaging and consistent image acquisition parameters (done prior to data collection) and image quality control and statistical stratification (done after collection and in postprocessing).…”

“…Various clinical measures assessing urinary (eg, OAB Questionnaire [OAB-q], International Consultation on Incontinence Questionnaire, LUTS Tool), pain (eg, Brief Pain Inventory), and psychosocial symptoms (eg, Complex Multi-Symptom Inventory, Patient-Reported Outcomes Measurement Information System) were collected, along with demographic measures (eg, age, sex, and race; Table 1). 13 Institutional review boards reviewed and approved study protocols (IRB No. 00007807); informed consent was obtained; all relevant ethical guidelines were followed; all research was conducted according to the Declaration of Helsinki.…”

“…The Neuroimaging and Sensory Testing substudy of the broader LURN Study examined men and women with symptoms consistent with OAB patients and CONs, recruited from 6 US university urology and urogynecology clinics. 13 A cross-sectional assessment of brain and sensory differences between participants with OAB and CONs was performed. The full protocol has been described 13 : Eligible participants underwent experimental sensory testing 14 and noninvasive MRI, whereby high-resolution structural (T1), functional MRI (fMRI) during 2 different bladder fullness states and diffusion tensor imaging were acquired from brains of OAB patients and CONs.…”

“…16 Those with a history of pelvic malignancy, neurogenic bladder, urinary tract infection, sling complication, radiation cystitis, or contraindication to MRI were excluded. 13 Urinary symptoms-free CONs must have no diagnosis of OAB and no/minimal LUTS (never/rarely had urgency or incontinence, frequency 1-7/d, nocturia 0-1/night).…”