Login to Access Video or Poster Abstract: MP85-07
Sources of Funding: P20 DK108276

Introduction

Lower urinary tract symptoms (LUTS) are common and poorly understood; treatment is often ineffective. Failure of neural control of bladder function likely contributes to LUTS symptoms in many patients. Mice are continent and serve as excellent models of LUTS, in part because they can be manipulated genetically. To relate what is learned in mice to humans, we have developed functional MRI methods for mice which mirror those in humans. Such methods will allow us to compare directly the activation patterns of mouse and human brains during bladder filling and voiding, in normal and disease states.

Methods

Mice are anesthetized with urethane and a catheter is implanted in the bladder dome. Blood Oxygen Level Detection Magnetic Resonance Imaging (BOLD-MRI) is carried out in a Bruker 9.4T magnet with a 4 element mouse brain phased array coil. A series of 2D multislice gradient echo-planar images are acquired every 2s, while the mouse undergoes cystometry. 25 slices are acquired with slices of 500µm, interslice distance 600µm and in-plane resolution of 250µm. Imaging occurs over a 45 minute time frame during which the mouse undergoes 10-15 voiding cycles (CMG). Data are analyzed with Statistical Parameter Mapping (SPM12) software using mouse brain adaptations. Linear modeling proceeds in 2 stages; first by providing a statistical map of the brain of individual animals and second by combining results across all animals in a group.

Results

Preliminary results on female C57BL6/J (n =5) with a fixed effects analysis identified candidate regions across the brain with clear activation in the right Pontine Micturition Center (PMC) observed, which was confirmed by a region based random effects analysis. Negative contrast identified more extensive regions such as the periaqueductal gray and inferior colliculus with an indication that these regions are &[Prime]switched off&[Prime] during the transition to voiding.

Conclusions

Although technically challenging due to the small size, BOLD-MRI on mice is feasible and reveals regions of brain activation related to voiding cycles. Development of this technique along with fine mapping of brain circuits related to voiding will help define mechanisms of LUTS in mouse models that should be translatable to human disease.

Funding

P20 DK108276