An animal experimental study on pubourethral ligament restoration with platelet rich plasma for the treatment of stress urinary incontinence.

Introduction: Minimally invasive methods for injured ligament and tendon restoration have been developed and gained popularity in recent years. Injury and relaxation of the pubourethral ligament (PUL) can lead to stress urinary incontinence (SUI). The aim of this study was to investigate the impact of injecting platelet rich plasma (PRP) into the PUL following its surgical transection resulting in SUI, confirmed by leak point pressure (LPP) measurements pre- and post-intervention in an experimental animal model. Material and methods: Twenty female adult Sprague-Dawley rats were assigned in 2 groups: 1) treatment group with transection of the PUL and application of PRP at the time of transection and at one month follow-up and 2) a control group, with transection of the PUL only. Leak point pressures (LPPs) were measured prior to transection, immediately following the transection and at 1 and 2 months in both groups. Results: The median LPPs for the control group were: LPP - preT: 35.6 (29.8-44.8) cmH2O, LPP - postT: 14.6 (5.8-19.0) cmH2O, LPP - 1 month: 27.3 (19.2-33.8) cmH2O, LPP - 2 months: 29.0 (27.0-34.0) cmH2O, whereas for the PRP group were: LPP-preT: 40.5 (33.2-46.3) cmH2O, LPP - postT: 15.7 (3.0-24.0) cmH2O, LPP - 1month: 31.6 (24.8-37.4) cmH2O, LPP - 2 months: 36.8 (32.5-45.4) cmH2O. PRP injections on transected PULs significantly increased LPPs at one month follow-up [31.6 cmH2O vs. 27.3 cmH2O, p = .043]. This effect was confirmed at two months [36.8 cmH2O vs. 29.0 cmH2O, p <.001]. Conclusions: Injection of PRP into transected PULs significantly improved LPPs at one and two months' follow-up. However, further experimental and clinical research is needed to evaluate the safety and efficacy of this treatment, in clinical practice

Label-driven weakly-supervised learning for multimodal deformable image registration

Spatially aligning medical images from different modalities remains a challenging task, especially for intraoperative applications that require fast and robust algorithms. We propose a weakly-supervised, label-driven formulation for learning 3D voxel correspondence from higher-level label correspondence, thereby bypassing classical intensity-based image similarity measures. During training, a convolutional neural network is optimised by outputting a dense displacement field (DDF) that warps a set of available anatomical labels from the moving image to match their corresponding counterparts in the fixed image. These label pairs, including solid organs, ducts, vessels, point landmarks and other ad hoc structures, are only required at training time and can be spatially aligned by minimising a cross-entropy function of the warped moving label and the fixed label. During inference, the trained network takes a new image pair to predict an optimal DDF, resulting in a fully-automatic, label-free, real-time and deformable registration. For interventional applications where large global transformation prevails, we also propose a neural network architecture to jointly optimise the global- and local displacements. Experiment results are presented based on cross-validating registrations of 111 pairs of T2-weighted magnetic resonance images and 3D transrectal ultrasound images from prostate cancer patients with a total of over 4000 anatomical labels, yielding a median target registration error of 4.2 mm on landmark centroids and a median Dice of 0.88 on prostate glands.Comment: Accepted to ISBI 201

Thermal dosimetry for bladder hyperthermia treatment. An overview.

The urinary bladder is a fluid-filled organ. This makes, on the one hand, the internal surface of the bladder wall relatively easy to heat and ensures in most cases a relatively homogeneous temperature distribution; on the other hand the variable volume, organ motion, and moving fluid cause artefacts for most non-invasive thermometry methods, and require additional efforts in planning accurate thermal treatment of bladder cancer. We give an overview of the thermometry methods currently used and investigated for hyperthermia treatments of bladder cancer, and discuss their advantages and disadvantages within the context of the specific disease (muscle-invasive or non-muscle-invasive bladder cancer) and the heating technique used. The role of treatment simulation to determine the thermal dose delivered is also discussed. Generally speaking, invasive measurement methods are more accurate than non-invasive methods, but provide more limited spatial information; therefore, a combination of both is desirable, preferably supplemented by simulations. Current efforts at research and clinical centres continue to improve non-invasive thermometry methods and the reliability of treatment planning and control software. Due to the challenges in measuring temperature across the non-stationary bladder wall and surrounding tissues, more research is needed to increase our knowledge about the penetration depth and typical heating pattern of the various hyperthermia devices, in order to further improve treatments. The ability to better determine the delivered thermal dose will enable clinicians to investigate the optimal treatment parameters, and consequentially, to give better controlled, thus even more reliable and effective, thermal treatments

BIOMECHANICS AND FUNCTION OF THE FEMALE RAT URETHRA IN STRESS URINARY INCONTINENCE INDUCED BY BIRTH TRAUMA

Stress urinary incontinence (SUI) is common in women after vaginal delivery (VD) in childbirth or pelvic trauma, and may be associated with altered biomechanical or functional properties of the urethra. The goal of this dissertation was to identify biomechanical and functional changes in the urethra in a rat model of VD, as well as to understand the role of longitudinal smooth muscle in the healthy urethra. Female rat urethras were isolated in a rat model of SUI induced by VD. Controls were urethras isolated from normal rats. Our established ex vivo urethral testing system was utilized for biomechanical and pharmacological assessments. In this system, outer diameter was measured via a laser micrometer, and recorded along with applied intraluminal pressure to a computer. Urethral thickness was assessed histologically.Biomechancial properties of the urethra were markedly altered by VD for the baseline, passive (via calcium chelation), and active (stimulation via adrenergic and muscarinic receptors) states, most notably in the proximal urethra. Additionally, contractile responses to phenylephrine and bethanechol increased in the proximal urethra in VD rats compared to controls. There were also changes in the VD mid urethral segment. Functional and biomechanical parameters indicated that basal activity was increased for VD compared to controls in the middle segment, as well as adrenergic active biomechanical properties at low strains. VD impaired the basal tone distally compared to controls, but this was the only difference observed. VD urethras had evidence of altered collagen and elastin. Additionally, there was a lack of PGP 9.5, tyrosine hydroxylase, and vesicular acetylcholine transferase in the urethras of the VD group. This suggests that VD has mechanically damaging effects on urethral innervation.Finally, the role of the longitudinal smooth muscle in the urethra was further clarified via a modified urethral testing system. Circumferential and longitudinal testing of baseline, active, and passive urethral properties and function supported the idea that the role of longitudinally-oriented components of the urethra was to lengthen or shorten to enable the circumferential muscle to fully contract and shorten as required. In summary, this dissertation has provided evidence of damaged muscular, neural, and matrix components of the urethra associated with VD. The combination of these changes may contribute to SUI induced by VD

EFFECTS OF DIABETES MELLITUS ON THE BIOMECHANICAL PROPERTIES AND PHARMACOLOGICAL FUNCTION OF THE FEMALE RAT URETHRA EX-VIVO

EFFECTS OF DIABETES MELLITUS ON THE BIOMECHANICAL PROPERTIES AND PHARMACOLOGICAL FUNCTION OF THE FEMALE RAT URETHRA EX-VIVORachelle Lynn Prantil, MSUniversity of Pittsburgh, 2004Diabetic cystopathy results in a grossly distended, hypomotile bladder due to inefficient voiding. While the bladder has been extensively studied, little effort has been made towards the understanding of the urethra and the effects of this devastating disease. The current study is aimed to evaluate the effects of diabetes mellitus (DM) on the biomechanical properties and the pharmacological function of the female rat urethra ex vivo. DM was induced in female rats by injection of streptozotocin. At 3, 5,and 10 weeks, the urethras were excised and mounted into an ex-vivo system at in vivo length. For mechanical testing, urethras were subjected to stepwise increases of static, intraurethral pressure from 0 to 20 mmHg in both a baseline and passive state. Continuous outer diameter measurements were made using a laser micrometer at proximal, middle, and distal portions of the urethra. Compliance and beta stiffness were calculated from measured data. Pharmacological experiments involved assessments of mid urethral outer diameter response to Nč Nitro-L-arginine, phenylephrine, and EDTA. Age matched normal urethras served as controls. Statistical comparisons were made via ANOVA. Tissue was then processed for immuno- and histochemical quantification of smooth muscle, collagen, and elastin. For baseline healthy tissue, results showed a proximal to distal compliance gradient (proximal most compliant and distal least compliant), and the passive state enhanced the observation. Baseline beta stiffness values showed an increased stiffness in proximal and middle urethral portions by 5 and 10 weeks, and baseline compliance values showed at low pressures showed an increase in proximal compliance at 3 weeks and a decrease in proximal compliance at 5 weeks at high pressures. Passive beta stiffness and compliance values indicated proximal urethral stiffening by 10 weeks DM. Pharmacological studies revealed that DM abolishes endogenous nitric oxide release and increases the time to reach maximal relaxation. In cases of severe DM, alpha 1 adrenergic contraction was minimized. Little or no differences were found in the amount collagen, smooth muscle, and elastin. From these findings, it can be concluded that DM causes urethral stiffening and impaired contractile and relaxation urethral mechanism. Damaged urethral properties and function have serious implications for outlet resistance; thus, contributing to diabetic cystopathy