Optically Monitoring Colon Microcirculation in Precancer

光学监测癌前病变的结肠微循环

基本信息

批准号：
7446560
负责人：
Vadim Backman
金额：
$ 25.95万
依托单位：
NORTHWESTERN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-07-01 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7446560
关键词：
Aberrant crypt foci Address Adenomatous Polyps Adjuvant Adopted Advocate Age American Animal Model Animals Area Attention Azoxymethane Benefits and Risks Biological Biomedical Engineering Blood Blood capillaries Cancer Detection Cancer Etiology Carcinogens Carcinoma Cessation of life Characteristics Chronology Clinical Clinical Medicine Clinical Trials Colitis Colon Colon Carcinoma Colonoscopes Colonoscopy Colorectal Cancer Communities Compatible Complication Control Animal Data Depth Development Diagnosis Disease Distant Metastasis Drug Formulations Epithelium Evaluation Event Excision Fiber Optics Frequencies Future Gastroenterologist Gastroenterology Genetic Genus Cola Goals Gold Grant Guidelines Hand Human Imagery Incidence Lead Legal Lesion Life Light-Scattering Spectroscopy Location Malignant - descriptor Malignant Neoplasms Maps Measurement Measures Microcirculation Modeling Molecular Monitor Mucous Membrane Mus Nature Neoplasms Neoplastic Cell Transformation Numbers Optics Outcome Patients Performance Personal Satisfaction Polyps Population Premalignant Prevention strategy Price Principal Investigator Procedures Prospective Studies Publishing Range Rate Rattus Risk Saline Sampling Screening procedure Societies Spectrum Analysis Staging Standards of Weights and Measures Stratification Techniques Technology Testing Time Treatment Protocols Vascular blood supply Visible Radiation adenoma base cancer prevention cancer risk capillary carcinogenesis clinically significant cohort colon carcinogenesis colorectal cancer prevention colorectal cancer screening cost improved in vivo insight instrument interest multidisciplinary neoplastic novel programs prospective tumor tumorigenesis tumorigenic

项目摘要

DESCRIPTION (provided by applicant): Colorectal cancer (CRC) remains the second leading cause of cancer of deaths underscoring the need for more effective preventive strategies. Indeed, while colonoscopy is effective in reducing CRC, it suffers from up to 30% polyp miss rate even among expert endoscopists and marginal ability to determine frequency of colonoscopy. Thus, technological advances are necessary to allow more effective implementation of colonoscopy into primary population screening. Our multidisciplinary CRC prevention group has been interested in bridging biomedical optics to clinical medicine. With the aid of an R21 grant from the NCI, we have recently developed polarization-gated visible light spectroscopy for accurate quantitation of microvascular blood content. Using this approach we have recently published our novel observation that early increase in blood supply (EIBS) in the colonic microcirculation occurs early during neoplastic transformation and precedes formation of adenomas, aberrant crypt foci and other currently known markers of CRC. We envision that, in the long-term, concomitantly measuring EIBS could guide colonoscopy by allowing a colonoscopist to identify colonic segments that require more intensive scrutiny and, since in humans EIBS is expected to precede tumorigenesis by at least a decade, also enable accurate determination of optimal colonoscopic frequency. In order for EIBS assessment to achieve clinical fruition it is critical to demonstrate the ability of this approach to predict concurrent and future neoplastic lesions. We plan to assess this using serial measurement of EIBS in the azoxymethane-treated rat model. We will use the carcinogen treatment regimen that repeatedly induces adenomas or carcinomas in ~50% of animals. To enable EIBS measurements in vivo, we will develop a rat colonoscope-compatible fiber-optic polarization- gated spectroscopy probe. We will perform rat colonoscopies and measure EIBS at various premalignant and malignant time-points in order to formulate and then prospectively validate prediction rules for future adenomas based on microvascular blood content. Thus, this project will allow development of a technique that will validate EIBS for CRC detection/screening paving the way for future clinical trials.

描述（由申请人提供）：结直肠癌（CRC）仍然是癌症死亡的第二大原因，这凸显了对更有效的预防策略的需要。事实上，虽然结肠镜检查可有效减少结直肠癌，但即使是专家内窥镜医师，其息肉漏诊率也高达 30%，且确定结肠镜检查频率的能力有限。因此，技术进步对于更有效地将结肠镜检查应用于初级人群筛查是必要的。我们的多学科结直肠癌预防小组一直对将生物医学光学与临床医学联系起来很感兴趣。在 NCI 的 R21 资助的帮助下，我们最近开发了偏振门控可见光谱，用于精确定量微血管血液含量。利用这种方法，我们最近发表了我们的新观察结果，即结肠微循环中的早期血液供应 (EIBS) 增加发生在肿瘤转化的早期，并且先于腺瘤、异常隐窝病灶和其他目前已知的 CRC 标志物的形成。我们设想，从长远来看，同时测量 EIBS 可以指导结肠镜检查，让结肠镜检查医师识别需要更深入检查的结肠段，并且由于在人类中 EIBS 预计会比肿瘤发生至少提前十年，因此也能够准确确定最佳结肠镜检查频率。为了使 EIBS 评估取得临床成果，证明这种方法预测并发和未来肿瘤病变的能力至关重要。我们计划使用氧化偶氮甲烷处理的大鼠模型中的 EIBS 连续测量来评估这一点。我们将使用致癌物治疗方案，在约 50% 的动物中反复诱发腺瘤或癌。为了实现体内 EIBS 测量，我们将开发一种与大鼠结肠镜兼容的光纤偏振门控光谱探头。我们将在不同的癌前和恶性时间点进行大鼠结肠镜检查并测量 EIBS，以便根据微血管血液含量制定并前瞻性验证未来腺瘤的预测规则。因此，该项目将允许开发一种技术，验证 EIBS 用于 CRC 检测/筛查的能力，为未来的临床试验铺平道路。