Virtual Histology of the Bladder Wall for Bladder Cancer Staging

膀胱癌(BCA)是世界上最常见的五种恶性肿瘤之一，由 膀胱癌在膀胱壁不同层面的穿透治疗效果最佳。目前，一种昂贵的养生法 建议常规膀胱镜检查、经尿道肿瘤电切术(TURBT)和影像监视 以对抗高达80%的BCA复发率。尽管根治性膀胱切除术是分期的黄金标准 准确性，这对于指导治疗是不现实的。由于TURBT和现有的成像设备受到 ~50%的肌肉侵犯检测失败率，对安全的放射措施的需求尚未得到满足 区分惰性和侵袭性BCA进行监测，选择合适的膀胱治疗方案 避免新辅助治疗，最大限度地减少侵袭性BCA根治性膀胱切除术的延迟。虽然 静脉注射Gd后的动态增强磁共振成像(DCE-MRI) 基础造影剂(GBCA)在BCA的肿瘤分期方面明显优于CT， MRI相对落后，在BCA诊断和临床应用中仍存在主要障碍。 预后。此外，注射GBCA有过敏反应、健康风险和增加医疗保健的风险 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磁共振成像的报告 一种新型造影剂(经导尿管)直接膀胱灌注后的啮齿动物和人膀胱壁 无菌水中加多布洛尔(GBCA)和阿魏酸甲酯混合物(NCM)的阳性对照 通过GBCA扩散的膀胱壁和通过滞留在膀胱腔内的同时负对比 阿魏酸甘油(分子尺寸是GBCA的10倍)。因此，NCM增强的T1加权MRI可以利用 膀胱壁癌细胞与正常细胞GBCA通透性差异的三维实现 (3D)膀胱壁成像，以改进肿瘤检测和非手术BCA分期。遵循特定目标 旨在建立NCM-MRI用于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的目标是制作高分辨率的3D MRI，这是BCA的临床标准 诊断和治疗。Aim 1将评估不同组织病理学分期之间的一致性 21例BCA患者TURBT标本与NCM-MRI术前临床分期 至少一例膀胱镜检查证实为乳头状膀胱瘤。AIM 2将评估多式联运协议 BCA术前NCM-MRI分期与整体病理金标准的比较 21例经组织学证实的肌肉侵袭性BCA患者的膀胱切除标本。多式联运的优势 NCM-MRI与组织病理学的符合性将通过Kappa(κ)统计和相关的 两种技术的差异通过配对t检验。基于MRI的主动监控已经改变了对 前列腺癌和这项探索性研究试图通过像素级实现虚拟组织学的目标 T1标测显示NCM增强MRI作为BCA分期的微创工具的潜力。

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.