Bladder outlet obstruction (BOO) is known to obstruct urine outflow through lower urinary tract, but chronic BOO can also induce tissue remodeling of upper urinary tract which can be detrimental to ureteral peristalsis and to vesicoureteric junction (VUJ) competency.  Superior soft tissue resolution of magnetic resonance imaging (MRI) at 1.5-3T enables non-invasive, post-operative monitoring of ~ 5mm wide human ureter function (1) but higher spatial resolution is a prerequisite for MR urography (MRU) of ten times smaller ureters of rodents. We performed MRU of partial BOO (pBOO) in male rats at 9.4T to inform computational modeling (digital twin) of BOO mechanobiology,

Under isoflurane anesthesia, pelvis incision was made in male Sprague Dawley rats (n=6) to tie 4-0 silk ligature around prostatic urethra of pBOO rat and untied for sham. 4-weeks post-surgery, T2 weighted Turbo spin echo scans were acquired in multiple planes with or without acute diuresis in Bruker Biospin 9.4T system at the resolution of 400micron and 6-17frame rate per min (fpm).

High spatial resolution of 0.4mm at 9.4T for MRU of 4-week-old pBOO male rat displayed an intact anti-reflux mechanism with the absence of bright urine backflow from bladder to ureter. Although ureter orifice diameter doubled in pBOO relative to sham (Fig.1), orifice enlargement did not violate Paquin's 1:5 ratio with intravesical ureter tunnel length of 4.1mm.  Pre-diuresis scans at 17fpm (Fig.2) portrayed 3-4 peristaltic waves per minute in both cohorts but urine bolus propagation in pBOO required significant dilation of distal ureters to 1.85±0.24 mm vs 1.01±0.16 mm in sham (p<0.05). The sequential dilation and contraction of distal ureters propagated 3.6mm long urine bolus (4microliter) at the speed of ~1mm/s in pBOO rat. The peristalsis of small urine bolus transiently deformed bladder shape but bladder deformation was minimal in presence of diuresis, which caused coalescence of boluses into urine columns in ureter. High spatial resolution of MRU at 9.4T is authenticated by the visualization of 0.15mm thick, 4-0 silk ligature below the bladder neck of pBOO rats (Fig.2) in post-diuresis scans, with ligature analogous to a needle in the haystack of lower pelvic organs.

MRU at 9.4T enables incision-free, longitudinal imaging of ureter structure and function without the catheterization of ureters or dye injection (2). Laplace’s equation asserts intraluminal pressure decline and inefficient urine peristalsis following pBOO induced ureter dilation for bladder–kidney differential pressures of 10 and 30 cmH2O for storage and voiding phase, respectively. Fig.1 illustrates that the conservation of fluid momentum from larger lumen of distal ureter to narrower lumen of intravesical ureter tunnel running from UVJ to the ureteral orifice raises intraluminal pressure and enable intravesical ureter to act as nozzle for ejection of urine boluses as jets into bladder lumen. Accordingly, the widening of intravesical ureter due to long-standing BOO can compromise the anti-reflux mechanism of UVJ.  While ureteral peristalsis of smaller urine boluses produced at 37% lower GFR under anesthesia is portrayed in pre-diuresis scans, the obfuscation of pBOO induced ureter dilation by diuresis is consistent with the positive impact of diuresis on bladder compliance of BOO patients.

MRU at 9.4T is capable of non-invasive longitudinal assessment of BOO induced remodeling of ureter morphology and function. The recapitulation of benign prostatic enlargement (BPE) induced ureter dilation by a ligature tied around male rat urethra affirms the advantage of this model to construct a digital twin of BOO mechanobiology over extrapolating female rat BOO to understand male LUTS. A digital twin of BPE induced BOO can predict the delayed improvement of storage vs voiding symptoms after de-obstruction surgery as well as the amelioration of ureter dilation by Tadalafil in BPE patients (3).

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