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）是世界上五种最常见的恶性肿瘤之一，其分期是膀胱肿瘤渗透到膀胱壁的不同层进行治疗目前是一种昂贵的治疗方案。建议进行常规膀胱镜检查、经尿道肿瘤切除术 (TURBT) 和影像学监测尽管根治性膀胱切除术是分期的金标准，但仍可应对高达 80% 的 BCa 复发率。由于 TURBT 和可用的成像方式存在一定的准确性，因此对于指导治疗来说并不实用。检测肌肉侵袭的失败率约为 50%，对安全放射学措施的需求尚未得到满足区分惰性 BCa 和侵袭性 BCa 进行监测，以选择患者进行适当的膀胱治疗方案节省新辅助治疗并尽量减少侵袭性 BCa 治愈性膀胱切除术的延迟。静脉注射钆后动态对比增强磁共振成像（DCE-MRI）基于造影剂 (GBCA) 的 BCa 肿瘤分期明显优于计算机断层扫描， MRI 发展相对较差，MRI 应用于 BCa 诊断和治疗仍存在主要障碍。此外，注射 GBCA 还存在过敏反应、健康风险和增加医疗保健的风险。这项探索性研究的科学前提是基于我们最近的高分辨率 MRI 报告。直接膀胱灌注（通过导尿管）新型对比后的啮齿动物和人类膀胱壁由钆布醇 (GBCA) 和 Ferumoxytol 组成的混合物 (NCM) 在无菌水中用于阳性对比膀胱壁通过 GBCA 扩散，同时通过保留膀胱腔内的负对比 Ferumoxytol（分子大小是 GBCA 的 10 倍）因此，NCM 增强 T1 加权 MRI 可以利用膀胱壁中癌细胞和正常细胞的不同GBCA渗透性以实现三维 (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。旨在确定 NCM-MRI 对于 BCa 分期的技术和科学价值，然后再进行未来的随机临床试验旨在实现高分辨率 3D MRI（BCa 的临床标准）目标 1 将评估组织病理学分期之间的多模式一致性。 21 例 BCA 患者的 TURBT 标本和术前简化 NCM-MRI 临床分期目标 2 将至少评估一例膀胱镜确诊的乳头状膀胱肿瘤。用于 BCa 分期的术前 NCM-MRI 与整体病理学检查的金标准之间的比较 21 例经组织学证实的肌肉侵袭性 BCa 患者的膀胱切除标本的联合治疗的强度。 NCM-MRI 和组织病理学之间的一致性将通过 Kappa (κ) 统计数据和相对值进行评估基于 MRI 的配对 t 检验的两种技术的差异已经改变了对患者的护理。前列腺癌，这项探索性研究旨在通过像素方式实现虚拟组织学的目标 T1 映射展示了 NCM 增强 MRI 作为 BCa 分期微创工具的潜力。

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：

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

DOI：
10.3390/curroncol30050350
发表时间：
2023-04-30
期刊：
Current oncology (Toronto, Ont.)
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

NSAUA 2022 Annual Meeting Abstracts - Oncology II.

NSAUA 2022 年会摘要 - 肿瘤学 II。