Virtual Histology of the Bladder Wall for Bladder Cancer Staging

用于膀胱癌分期的膀胱壁虚拟组织学

基本信息

批准号：
10044470
负责人：
JODI Kathleen MARANCHIE
金额：
$ 32.65万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10044470
关键词：
3-Dimensional Agreement Allergic Reaction Anxiety Bladder Bladder Neoplasm Cancer Patient Cancer Prognosis Cancerous Caring Catheters Cessation of life Claustrophobias Clinical Clinical/Radiologic Contrast Media Cystectomy Cystoscopy Detection Diagnosis Diagnostic Neoplasm Staging Diagnostic Procedure Diagnostic tests Diffusion Disease Excision Failure Future Gadolinium Goals Gold Health Health Care Costs Healthcare Healthcare Systems Histologic Histology Histopathology Human Image Imaging Techniques Indolent Intravenous Intravesical Instillation Invaded Kidney Failure Magnetic Resonance Imaging Malignant Neoplasms Malignant neoplasm of prostate Malignant neoplasm of urinary bladder Measures Methods Morbidity - disease rate Muscle Neoadjuvant Therapy Normal Cell Papillary Pathologic Patients Penetration Permeability Pilot Projects Radial Radical Cystectomy Radiology Specialty Randomized Clinical Trials Recurrence Regimen Reporting Residual Tumors Resolution Risk Rodent Safety Schedule Specimen Staging Sterility Students Techniques Testing Three-Dimensional Image Tight Junctions Tissues Transurethral Resection Tumor Cell Invasion Tumor stage Urethra Water X-Ray Computed Tomography base cancer cell cancer diagnosis cancer imaging cancer recurrence cancer therapy chemotherapy contrast enhanced cost design ferumoxytol gadobutrol imaging modality improved intravenous injection minimally invasive molecular size muscle invasive bladder cancer novel optimal treatments overtreatment radiologist statistics surveillance imaging tool tumor tumor specificity urinary tract obstruction virtual

项目摘要

Bladder cancer (BCa) is one the five most common malignancies worldwide, which is staged by the penetration of bladder tumor in different layers of bladder wall for optimal treatment. Currently, a costly regimen of routine cystoscopy, transurethral resection of the tumor (TURBT) and imaging surveillance is recommended to counter the high BCa recurrence rate of 80%. Although radical cystectomy is the gold standard for staging accuracy, it is not practical for directing treatment. Since TURBT and available imaging modalities suffer from a ~50% failure rate in detecting muscle invasion, there is an unmet need for safe, radiologic measures to distinguish indolent from aggressive BCa for surveillance, to select patients for appropriate regimens of bladder sparing neoadjuvant therapy and to minimize the delay in curative cystectomy of aggressive BCa. Although dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) after intravenous injection of gadolinium- based contrast agent (GBCA) was dramatically superior to computed tomography for tumor staging of BCa, MRI is relatively poorly developed and major barriers still exist in the adaption of MRI for BCa diagnosis and prognosis. Besides, injected GBCA carries the risk of allergic reaction, health risk and increased healthcare cost. The scientific premise of this exploratory study is based on our recent report of high-resolution MRI of rodent and human bladder wall following direct bladder instillation (via urethral catheter) of a novel contrast mixture (NCM) composed of Gadobutrol (GBCA) and Ferumoxytol in sterile water for positive contrast in bladder wall via diffusion of GBCA and simultaneous negative contrast in bladder lumen via retention of Ferumoxytol (molecular size 10 fold of GBCA). Thus, NCM enhanced T1 weighted MRI can leverage the differential GBCA permeability of cancerous and normal cells in bladder wall to accomplish three-dimensional (3D) bladder wall imaging for improved tumor detection and non-surgical BCa staging. Following specific aims are designed to establish the technical and scientific merit of NCM-MRI for BCa staging, before pursuing a future randomized clinical trial towards the goal of making high resolution 3D MRI, a clinical standard in BCa diagnosis and treatment. Aim 1 will evaluate the intermodality agreement between histopathologic staging of TURBT specimens and the pre-operative clinical staging of BCa by abbreviated NCM-MRI in 21 patients with at least one cystoscopically confirmed papillary bladder tumor. Aim 2 will evaluate the intermodality agreement between preoperative NCM-MRI for BCa staging with the gold standard of whole-mount pathologic review of cystectomy specimen in 21 histologically proven muscle invasive BCa patients. The strength of intermodality agreement between NCM-MRI and the histopathology will be assessed by Kappa (κ) statistics and the relative differences of two techniques by paired t test. MRI based active surveillance has transformed the care of prostate cancer and this exploratory study seeks to accomplish the goal of virtual histology through pixel-wise T1 mapping to demonstrate the potential of NCM enhanced MRI as minimally invasive tool for BCa staging.

膀胱癌（BCA）是全球五个最常见的疟疾，这是由膀胱肿瘤在不同层的膀胱壁中渗透以进行最佳处理。目前，一种昂贵的方案建议进行常规膀胱镜检查，肿瘤（TURBT）的转直肌切除术和成像监视应对80％的高BCA复发率。尽管自由基膀胱切除术是分期的金标准准确性，指导治疗是不切实际的。由于Turbt和可用的成像方式遭受了〜50％的失败率在检测肌肉侵袭时，对安全，放射学措施的需求未满足区分监视的积极BCA，以选择适当的膀胱治疗方案的患者保留新辅助治疗，以最大程度地减少侵袭性BCA治愈性膀胱切除术的延迟。虽然静脉注射Gadolinium- 基于BCA的肿瘤分期，基于造影剂（GBCA）高于计算机断层摄影术高于计算机断层扫描 MRI相对较差，并且在MRI适应BCA诊断和预后。此外，注射的GBCA具有过敏反应，健康风险和医疗保健增加的风险成本。这项探索性研究的科学前提是基于我们最近关于高分辨率MRI的报告啮齿动物和人类的膀胱壁直接在直接膀胱滴注（通过尿道导管）的新型对比度由gadobutrol（GBCA）和无菌水中的铁氧托醇组成的混合物（NCM），在无菌水中，以呈阳性对比度通过GBCA的扩散和膀胱腔中的简单负面对比度，膀胱壁是通过保留的铁氧基二醇（分子大小10倍的GBCA）。那就是NCM增强的T1加权MRI可以利用取消和正常细胞在膀胱壁中的差异GBCA渗透性完成三维（3D）膀胱壁成像，用于改善肿瘤检测和非手术BCA分期。遵循特定目标旨在建立NCM-MRI在BCA分期的技术和科学价值，然后追求未来的随机临床试验，目的是制作高分辨率3D MRI，这是BCA的临床标准诊断和治疗。 AIM 1将评估组织病理学分期之间的模式间一致性缩写的NCM-MRI在21例患者中，TURBT标本和BCA的术前临床分期至少有一个膀胱镜面确认的乳头状膀胱肿瘤。 AIM 2将评估模式交易协议在BCA分期的术前NCM-MRI之间，具有整体病理学的金标准 21种组织学证明的肌肉侵入性BCA患者的膀胱切除术标本。跨模式的强度 NCM-MRI与组织病理学之间的一致性将由KAPPA（κ）统计和相对评估通过配对t检验的两种技术的差异。基于MRI的主动监视已改变了护理前列腺癌和这项探索性研究旨在通过像素来实现虚拟组织学的目标 T1映射以证明NCM增强MRI的潜力，作为BCA分期的最小侵入性工具。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Re: Mandhani A. The paradox of why and how in urology! Indian J Urol 2022;38:247-8.

DOI：
10.4103/iju.iju_354_22
发表时间：
2023-01
期刊：
Indian journal of urology : IJU : journal of the Urological Society of India
影响因子：
0
作者：
Tyagi P
通讯作者：
Tyagi P

NS-AUA 2023 Annual Meeting Abstracts - Female Urology, Incontinence.

NS-AUA 2023 年会摘要 - 女性泌尿科、失禁。

DOI：
10.5489/cuaj.8583
发表时间：
2023
期刊：
Canadian Urological Association journal = Journal de l'Association des urologues du Canada
影响因子：
0
作者：
通讯作者：

Does large volume of distribution of lidocaine masks its systemic uptake from bladder?

利多卡因的大量分布是否掩盖了其从膀胱的全身摄取？

DOI：
发表时间：
2023
期刊：
American journal of clinical and experimental urology
影响因子：
1.2
作者：
Tyagi,Pradeep;Ganguly,Anirban;Chermansky,Christopher;Tarin,TatumV;Yoshimura,Naoki;Maranchie,Jodi
通讯作者：
Maranchie,Jodi

Intravesical Contrast-Enhanced MRI: A Potential Tool for Bladder Cancer Surveillance and Staging.