Outer Bladder Wall Research Articles

EDIT Software: A tool for the semi-automatic 3D reconstruction of bladder cancer and urinary bladder of animal models

Background and objectiveThis study presents the EDIT software, a tool for the visualization of the urinary bladder anatomy in the 3D space and for its semi-automatic 3D reconstruction. Methods: The inner bladder wall was computed by applying a Region of Interest (ROI) feedback-based active contour algorithm on the ultrasound images while the outer bladder wall was calculated by expanding the inner borders to approach the vascularization area on the photoacoustic images. The validation strategy of the proposed software was divided into two processes. Initially, the 3D automated reconstruction was performed on 6 phantom objects of different volume in order to compare the software computed volumes of the models with the true volumes of phantoms. Secondly, the in-vivo 3D reconstruction of the urinary bladder for 10 animals with orthotopic bladder cancer, which range in different stages of tumor progression was performed. Results: The results showed that the minimum volume similarity of the proposed 3D reconstruction method applied on phantoms is 95.59%. It is noteworthy to mention that the EDIT software enables the user to reconstruct the 3D bladder wall with high precision, even if the bladder silhouette has been significantly deformed by the tumor. Indeed, by taking into account the dataset of the 2251 in-vivo ultrasound and photoacoustic images, the presented software performs segmentation with dice similarity 96.96% and 90.91% for the inner and the outer borders of the bladder wall, respectively. Conclusions: This study delivers the EDIT software, a novel software tool that uses ultrasound and photoacoustic images to extract different 3D components of the bladder.

The impact of intra-fractional bladder filling on "Plan of the day" adaptive bladder radiotherapy.

A retrospective audit on the "Plan of the day" (POD) selection and intra-fractional bladder fillings were carried out on twenty adaptive bladder radiotherapy patients at a single institution. Treatment time, differences in bladder volume and displacement of outer bladder wall expansion over the treatment fraction were analysed. Average treatment time was 8.9 min. The mean percentage difference in bladder volume pre and post treatment was 13.7%, resulting in expansion of the bladder predominately in the superior and anterior directions. This audit confirmed that the institution's POD process sufficed without being significantly affected by the intra-fractional bladder filings.

Deep-learning convolutional neural network: Inner and outer bladder wall segmentation in CT urography.

We are developing a computerized segmentation tool for the inner and outer bladder wall as a part of an image analysis pipeline for CT urography (CTU). A data set of 172 CTU cases was collected retrospectively with Institutional Review Board (IRB) approval. The data set was randomly split into two independent sets of training (81 cases) and testing (92 cases) which were manually outlined for both the inner and outer wall. We trained a deep-learning convolutional neural network (DL-CNN) to distinguish the bladder wall from the inside and outside of the bladder using neighborhood information. Approximately, 240000 regions of interest (ROIs) of 16×16 pixels in size were extracted from regions in the training cases identified by the manually outlined inner and outer bladder walls to form a training set for the DL-CNN; half of the ROIs were selected to include the bladder wall and the other half were selected to exclude the bladder wall with some of these ROIs being inside the bladder and the rest outside the bladder entirely. The DL-CNN trained on these ROIs was applied to the cases in the test set slice-by-slice to generate a bladder wall likelihood map where the gray level of a given pixel represents the likelihood that a given pixel would belong to the bladder wall. We then used the DL-CNN likelihood map as an energy term in the energy equationof a cascaded level sets method to segment the inner and outer bladder wall. The DL-CNN segmentation with level sets was compared to the three-dimensional (3D) hand-segmented contours as a reference standard. For the inner wall contour, the training set achieved the average volume intersection, average volume error, average absolute volume error, and average distance of 90.0±8.7%, -4.2±18.4%, 12.9±13.9%, and 3.0±1.6mm, respectively. The corresponding values for the test set were 86.9±9.6%, -8.3±37.7%, 18.4±33.8%, and 3.4±1.8mm, respectively. For the outer wall contour, the training set achieved the values of 93.7±3.9%, -7.8±11.4%, 10.3±9.3%, and 3.0±1.2mm, respectively. The corresponding values for the test set were 87.5±9.9%, -1.2±20.8%, 11.9±17.0%, and 3.5±2.3mm, respectively. Our study demonstrates that DL-CNN-assisted level sets can effectively segment bladder walls from the inner bladder and outer structures despite a lack of consistent distinctions along the inner wall. However, even with the addition of level sets, the inner and outer walls may still be over-segmented and the DL-CNN-assisted level sets may incorrectly segment parts of the prostate that overlap with the outer bladder wall. The outer wall segmentation was improved compared to our previous method and the DL-CNN-assisted level sets were also able to segment the inner bladder wall with similar performance. This study shows the DL-CNN-assisted level set segmentation tool can effectively segment the inner and outer wall of the bladder.

91. Functional sub-structures of lower urinary tract in cervix cancer: Contouring and dose distribution

Purpose Radiotherapy related urinary morbidity includes various clinical endpoints (i.e. frequency, cystitis, incontinence, bleeding, fistula) that may be related to various anatomical sub-structures. Nowadays, reporting of bladder dose is based on the contouring of the outer bladder wall. This study aims to investigate contouring and dose evaluation of sub-structures potentially responsible for urinary morbidity after radiochemotherapy and Image Guided Adaptive Brachytherapy (IGABT) in locally advanced cervical cancer (LACC). Methods The study hypothesis is that different bladder sub-structures (trigone, bladder neck, urethra) are related to different morbidity endpoints. Structures were contoured for all BT fractions extracting the DVH parameters: outer bladder wall ( D 2cm3 , D 0.1cm3 ) , ICRU Bladder point, trigone ( D 2cm3 , D 0.1cm3 ) , bladder neck ( D 0.1cm3 ) , and urethra ( D 0.1cm3 , D 2cm3 ) . Doses to the Posterior-Inferior Border of the Pubic Symphysis (PIBS) points were also extracted as urethral sphincters surrogate. Finally, the Vaginal Reference Length (VRL), defined as the PIBS point-source distance, was measured. A total of 110 LACC [FIGO Stage: IB(8), IIA(3), IIB(78), IIIA(2), IIIB(9), IVA(1), IVB(9)] patients according to the EMBRACE protocol was selected. Results The reported values represent the cumulative EBRT+BT dose in EQD2. Median D 2cm3 values were 71.7[56.0–81.8] and 55.2[46.3–75.6] Gy for bladder wall and trigone, respectively. Bladder wall dose was systematically higher, and hotspots often placed outside the trigone. Median ICRU Bladder point dose was 63.6[48.4–90.7] Gy, Median D 0.1cm3 values for bladder wall, trigone, bladder neck and urethra were 82.0[68.2–109.8], 66.8[48.3–105.6], 59.5[46.5–88.3], and 50.4[44.8–88.3] Gy, respectively. Median PIBS and PIBS+2 cm point doses were 40.5[3.6–60.5] and 50.9[40–78.5] Gy, while median VRL was 5.9[1.9–8.2] cm. Conclusions The study showed that the parameters currently used for IGABT bladder dose reporting ( D 2cm3 , ICRU Bladder point) do not fully describe the dose distribution in the lower urinary. D 2cm3 for the outer bladder wall is often higher than trigone dose, while the ICRU bladder point better represents the trigone D 2cm3 and D 0.1cm3 , as shown in Fig. 1. PIBS point does not seem good surrogates for urethral sphincters, whereas VRL is a good indicator for bladder base dose sparing. Further understanding of dose-effect relationships for the bladder may be gained by future systematic delineation of bladder sub-structures. Download : Download high-res image (351KB) Download : Download full-size image

OA039] Contouring and dose reporting for lower urinary tract sub-structures in cervix cancer

Purpose Radiotherapy related bladder morbidity include various clinical endpoints (i.e. frequency, cystitis, incontinence, bleeding, fistula) that may be related to various anatomical sub-structures. Evaluation and reporting of bladder dose is currently based on the total bladder volume with contouring of the outer wall. This study aims to investigate contouring and dose evaluation of several bladder sub-structures potentially responsible for urinary morbidity after radiochemotherapy and Image Guided Adaptive Brachytherapy (IGABT) in locally advanced cervical cancer (LACC). Methods The study hypothesis is that different bladder structures are related to different morbidity endpoints. Therefore, a methodology for contouring subvolumes (trigone, bladder neck, urethra) was established. Structures were contoured for all BT fraction extracting DVH parameters: outer bladder wall ( D 2 cm 3 , D 0.1 cm 3 ) , ICRU Bladder point, trigone ( D 2 cm 3 , D 0.1 cm 3 ) , bladder neck ( D 0.1 cm 3 ) , and urethra (volume, D 0.1 cm 3 , D 2 cm 3 . A total of 40 LACC [FIGO Stage: IB(3), IIB(30), IIIA(1), IIIB(1), IVB(5)] patients according to the EMBRACE protocol was selected. Results The reported values represent the cumulative EBRT+BT dose in EQD2. Median D 2 cm 3 values were 71.7 [59.2–81.8] and 56.2 [47.8–69.3] Gy for bladder wall and trigone, respectively. Bladder wall dose was systematically higher, and hotspots often placed outside the trigone. Median ICRU point dose was 63.0 [49.8–80.5] Gy, Median D 0.1 cm 3 values for bladder wall, trigone, bladder neck and urethra were 85.6 [68.2–109.8], 70.9 [48.3–105.6], 61.7 [46.5–76.9], and 50.6 [45.6–64.7] Gy, respectively. Median urethra volume and D 2 cm 3 dose were 3.2 [1.4–6.5] cm3 and 47.9 [44.8–58.7] Gy, respectively. Conclusion The study showed that the parameters currently used for IGABT bladder dose reporting ( D 2 cm 3 , ICRU point) do not fully and accurately describe the dose distribution in the lower urinary tract sub-structures. D2cm3 for the outer bladder wall is often higher than trigone dose and in many cases the ICRU bladder point is not a good indicator. It is interesting to note that urethra volume may be relevant for endpoints such as incontinence varied across patients. Further understanding of dose-effect relationships for the bladder may be gained by future systematic delineation of bladder sub-structures.

EP-1845: The impact of intra-fractional bladder filling on adaptive bladder radiotherapy

A retrospective audit on the “Plan of the day” (POD) selection and intra-fractional bladder fillings were carried out on twenty adaptive bladder radiotherapy patients at a single institution. Treatment time, differences in bladder volume and displacement of outer bladder wall expansion over the treatment fraction were analysed. Average treatment time was 8.9 minutes. The mean percentage difference in bladder volume pre and post treatment was 13.7%, resulting in expansion of the bladder predominately in the superior and anterior directions. This audit confirmed that the institution’s POD process sufficed without being significantly affected by the intra-fractional bladder filings.

Assessment of Cystitis Glandularis by Transvaginal Sonography in Women

The aims of this retrospective study were to determine the accuracy of transvaginal sonography for diagnosing cystitis glandularis in women and to describe the sonographic features of cystitis glandularis masses in confirmed cases. For 90 patients with clinically or sonographically suspected cystitis glandularis, we retrospectively reviewed the imaging files. Twenty-one cases were confirmed by histopathologic examination. All patients had undergone transvaginal sonography to evaluate bladder masses in a standardized manner no more than 1 week before histopathologic examination. Findings from preoperative transvaginal sonography of the masses were described and compared with histopathologic findings. Cystitis glandularis masses were correctly identified on transvaginal sonography in 15 of 21 cases (71.4%), whereas 6 of 21 (28.6%) had negative preoperative sonographic findings. The sensitivity, specificity, and positive and negative predictive values of transvaginal sonography for diagnosing cystitis glandularis were 71.4% (15 of 21), 92.8% (64 of 69), 75.0% (15 of 20), and 91.4% (64 of 70), respectively, and the total accuracy was 87.8% (79 of 90). Detection of cystitis glandularis masses by transvaginal sonography depends on the mucosal surface roughness, bladder wall thickness, outer bladder wall continuity, mixed echoes, sparse vessels, and mobility of the cervix. Transvaginal sonography is a promising modality for identifying cystitis glandularis masses.

High Incidence of Vesicoureteral Reflux in Mice With Fgfr2 Deletion in Kidney Mesenchyma

Mice with Fgfr2 conditional deletion in metanephric mesenchyma (Fgfr2(Mes-/-)) have ureteral bud induction abnormalities. We determined whether Fgfr2(Mes-/-) mutants developed abnormally positioned ureters predisposing to vesicoureteral reflux. We measured common nephric duct length and assayed for apoptosis in embryonic day 11.5 mice. We performed 3-dimensional reconstruction of, and real-time polymerase chain reaction and whole mount in situ hybridization for Fgfr2 in urinary tracts in embryonic day 15.5 embryos. We also performed cystograms followed by 3-dimensional reconstruction in postnatal animals. Compared with controls Fgfr2(Mes-/-) embryos had increased common nephric duct length with no difference in apoptosis, indicating cranially displaced ureteral buds. Three-dimensional reconstruction at embryonic day 15.5 showed low ureteral insertion into the bladder near the bladder neck in Fgfr2(Mes-/-) mice. Postnatal Fgfr2(Mes-/-) mutants had a high rate of vesicoureteral reflux compared with controls (47.4% vs 4.0%, p = 0.00006). In postnatal mutants with unilateral reflux the refluxing ureters inserted closer to the bladder neck than nonrefluxing ureters. External ureteral insertional angles at the outer bladder wall formed by the ureteral insertion points and the bladder neck were greater in mutant refluxing ureters than in contralateral nonrefluxing ureters or control ureters. At embryonic day 15.5 Fgfr2 was decreased in Fgfr2(Mes-/-) kidneys compared with that in controls but not statistically different in ureters or bladders. Fgfr2(Mes-/-) mice have ureteral induction abnormalities associated with abnormal ureteral insertion in the bladder and subsequent vesicoureteral reflux, consistent with the Mackie and Stephens hypothesis.

Defining the Clinical Target Volume for Bladder Cancer Radiotherapy Treatment Planning

There are currently no data for the expansion margin required to define the clinical target volume (CTV) around bladder tumors. This information is particularly relevant when perivesical soft tissue changes are seen on the planning scan. While this appearance may reflect extravesical extension (EVE), it may also be an artifact of previous transurethral resection (TUR). Eighty patients with muscle-invasive bladder cancer who had undergone radical cystectomy were studied. All patients underwent preoperative TUR and staging computed tomography (CT) scans. The presence and extent of tumor growth beyond the outer bladder wall was measured radiologically and histopathologically. Forty one (51%) patients had histologically confirmed tumor extension into perivesical fat. The median and mean extensions beyond the outer bladder wall were 1.7 and 3.1 mm, respectively. Thirty five (44%) patients had EVE, as seen on CT scans. The sensitivity and specificity of CT scans for EVE were 56% and 79%, respectively. False-positive results were infrequent and not affected by either the timing or the amount of tissue resected at TUR. CT scans consistently tended to overestimate the extent of EVE. Tumor size and the presence of either lymphovascular invasion or squamoid differentiation predict a greater extent of EVE. In patients with radiological evidence of extravesical disease, the CTV should comprise the outer bladder wall plus a 10-mm margin. In patients with no evidence of extravesical disease on CT scans, the CTV should be restricted to the outer bladder wall plus a 6-mm margin. These recommendations would encompass microscopic disease extension in 90% of cases.

A model to predict bladder shapes from changes in bladder and rectal filling.

The purpose of this study is to develop a model that quantifies in three dimensions changes in bladder shape due to changes in bladder and/or rectal volume. The new technique enables us to predict changes in bladder shape over a short period of time, based on known urinary inflow. Shortly prior to the treatment, the patient will be scanned using a cone beam CT scanner (x-ray volume imager) that is integrated with the linear accelerator. After (automated) delineation of the bladder, the model will be used to predict the short-term shape changes of the bladder for the time interval between image acquisition and dose delivery. The model was developed using multiple daily CT scans of the pelvic area of 19 patients. For each patient, the rigid bony structure in follow-up scans was matched to that of the planning CT scan, and the outer bladder and rectal wall were delineated. Each bladder wall was subdivided in 2500 domains. A fixed reference point inside the bladder was used to calculate for each bladder structure a "Mercator-like" 2D scalar map (similar to a height map of the globe), containing the distances from this reference point to each domain on the bladder wall. Subsequently, for all bladder shapes of a patient and for all domains on the wall individually, the distance to the reference point was fitted by a linear function of both bladder and rectal volume. The model uses an existing bladder structure to create a new structure via expansion (or contraction), until the expressed volume is reached. To evaluate the predictive power of the model, the jack-knife method was used. The errors in the fitting procedure depended on the part of the bladder and range from 0 to 0.5 cm (0.2 cm on average). It was found that a volume increase of 150 cc can lead to a displacement up to about 2.5 cm of the cranial part of the bladder. With the model, the uncertainty in the position of the bladder wall can be reduced down to a maximum value of about 0.5 cm in case the bladder volume increase is known. Furthermore, it was found that a change in rectal filling causes a shift of the bladder, while its shape is hardly influenced. In conclusion, we developed a model that describes the bladder shape and position as a function of the bladder volume and the rectal filling. The model accurately describes the complex shape of the bladder as it works on each domain of the bladder separately.

Effects of hyperthermia on the rat bladder: a pre-clinical study on thermometry and functional damage after treatment

The rat bladder was heated using a microwave applicator which was equipped with a system of circulating deionized water. The applicator was operated at 434 MHz and was placed at the ventral side with the rats in supine position. Temperatures in the bladder and adjacent were monitored using thermocouples with single or multiple sensors. One thermocouple located most centrally in the bladder served as reference. The rats were treated at intravesical reference temperature of 41, 42, 43, 44 and 45°C for 1 h. The heating time to reach the reference temperature was ~5 min. Temperatures inside the bladder varied within 0.5°C from the reference value, while the temperatures in the urethra were ~1.0°C lower. At the left and the right side of the outer bladder wall, temperatures were ~0.5°C lower than the reference value, while the temperature on the dorsal and ventral sides of the bladder wall were 1.0-1.5°C lower. In the rectum, located in the treatment field, the temperature reached 39.1, 40.5, 42.4 and 42.5°C after 1 h of hyperthermia at intravesical reference temperatures of 41, 42, 43, 44 and 45°C, respectively. Body core temperature measured in the esophagus behind the pericardium never exceeded 40.0°C. The capacity of the bladder was assessed after 1 h at 43, 44 and 45°C at various intervals after heat treatment. In the sham treated control group and in the animals treated at 43°C, no reduction in bladder capacity was observed. The treatment group where the bladder was kept at 44°C for 1 h showed a clear reduction in bladder capacity at days 1 and 3 after hyperthermia. In the 45°C treatment group, four out of seven rats died, this within a few days after treatment. The three surviving rats were tested for bladder capacity and all had a reduced capacity at days 3 and 7 post-treatment. Four weeks after 44°C hyperthermia, all rats had recovered. After hyperthermia, depending on the heat-dose, an increase in blood urea nitrogen (BUN) was observed. After treatment at 42, 43 and 44°C, peak values were observed after ~1 day (16 or 24 h) followed by recovery; after 42°C, BUN levels were almost back to normal after 1 week; after 43°C, the level was still twice as high as control levels; and after 44°C, recovery of BUN levels to normal seemed slow, 1 week after treatment it was still five times as high as control. From these results, it is concluded that temperatures in the bladder below 44°C are well tolerated. After 1 h at 44°C, a transient decrease in bladder capacity was observed, as well as a high level of azotemia. After 1 h at 45°C, a high mortality rate was observed. These observations agree with early clinical observations and may be used as guidelines for further clinical work.

Ureteral Tumors

<h3>To the Editor:—</h3> Robards and his associates in the March 7, 1964, issue ofThe Journal(<b>187</b>:778) in writing on "Primary Tumors of the Ureter" made several statements with which I take issue: I question calling papilloma a benign tumor. Recently, I did radical bladder surgery for a low ureteral metastasis from a previously "benign" mid-ureteral papilloma. In this case a nephrectomy and ureterectomy to the outer bladder wall had been performed. Careful analysis of the initial lesion had failed to reveal any submucosal infiltration, yet, metastasis did occur five years later. The goblet sign is mentioned in the urographic diagnosis of ureteral carcinoma, but no mention is made of the "coiled-catheter" sign. This was originally described by Drs. Friedenberg, Sayegh, and myself in the American Journal of Roentgenology, Radium Therapy and Nuclear Medicine (86:707 [Oct] 1961) and later corroborated by others as being of value. The statement that