Dynamic Optical Imaging Biomarkers of Tumor Response to Therapy

肿瘤治疗反应的动态光学成像生物标志物

• 批准号: 8888513
• 负责人: Stefan Alexandru Carp
• 金额: $ 52.14万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-03 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8888513
• 关键词: Area Under Curve; Behavior; Biological Markers; Biomechanics; Biopsy; Blood Vessels; Blood flow; Breast; Breast Cancer Patient; Breast Cancer Treatment; Breast-Conserving Surgery; Cicatrix; Clinical; Clinical Research; Contrast Media; Coupling; Custom; Data; Data Quality; Development; Diagnosis; Diffuse; Digital Breast Tomosynthesis; Disease; Drug Delivery Systems; Drug Kinetics; ERBB2 gene; Early treatment; Enrollment; Exhibits; Functional Imaging; Gadolinium DTPA; Goals; Healed; Hemoglobin; Image; In complete remission; Individual; Intercellular Fluid; Lead; Lesion; Magnetic Resonance Imaging; Malignant - descriptor; Mammary Gland Parenchyma; Mammography; Mechanics; Methods; Monitor; Neoadjuvant Therapy; Neoplasm Metastasis; Optics; Outcome; Oxygen; PET/CT scan; Participant; Pathologic; Pathway interactions; Patient Schedules; Patients; Performance; Pharmaceutical Preparations; Phase; Physiological; Physiology; Positioning Attribute; Positron-Emission Tomography; Premenopause; Primary Neoplasm; Procedures; Property; Protocols documentation; ROC Curve; Relaxation; Reperfusion Therapy; Research; Roentgen Rays; Scanning; Staging; Stimulus; Stress; Survival Rate; System; Techniques; Testing; TimeLine; Tissues; Translations; Treatment outcome; Tumor Tissue; Validation; Variant; Work; base; cancer therapy; chemotherapy; contrast enhanced; cost; diffuse optical tomography; drug development; effective therapy; elastography; experience; healing; hemodynamics; imaging biomarker; imaging modality; improved; in vivo; individualized medicine; instrumentation; malignant breast neoplasm; meetings; metabolic rate; molecular imaging; optical imaging; pressure; public health relevance; radiologist; response; spectroscopic imaging; therapy development; tool; triple-negative invasive breast carcinoma; tumor; tumor microenvironment; volunteer

 DESCRIPTION (provided by applicant): Neoadjuvant chemotherapy (NACT) is often used in the management of patients with locally advanced breast cancer. It can improve outcomes by early treatment of micro-metastases, downstaging the disease, and increasing breast conserving surgery rates. However, NACT is met with heterogeneous outcomes. While 70- 80% of the patients demonstrate some degree of response, only approximately 25% achieve a pathologic complete response, the only outcome shown to correlate with improved survival. Such variability has motivated the development of therapy monitoring techniques to identify ineffective treatments, especially given recent data showing response guided NACT may lead to increased survival. Monitoring may be particularly important for triple negative breast cancer, and with the increasing use of targeted agents. The best sensitivity to early response is provided by functional imaging methods, because changes in tumor physiology occur before actual tumor shrinkage. Near infrared diffuse optical spectroscopy and imaging (NIR-DOSI) is emerging as a promising non-invasive tool for probing the tumor microenvironment. Our group has been one of the pioneers of dynamic optical imaging, which is able to probe the response of breast tissue to external stimuli, in addition to quantifying baseline hemoglobin concentration and oxygenation. In particular, we have recently shown that, prior to treatment, breast cancer tumors exhibit delayed reperfusion and a persistent reduction in hemoglobin oxygen saturation (SO2) vs. the surrounding healthy tissue during the viscoelastic relaxation phase following fractional mammographic like compression. This response is likely determined by the interplay of the increased stiffness and interstitial fluid pressure, and the higher metabolic rate of malignant lesions. Preliminary data indicates these differences nearly disappear by 30 days into NACT for responding tumors, while persisting for non-responding ones, suggesting dynamic optical imaging could be used to probe the tumor biomechanical properties. Tumor stiffness and increased IFP have been shown to cause poor drug delivery and correlate with an increased likelihood of metastasis. Improved blood flow through vascular normalization, and reduction of internal stresses using anti-fibrotic agents are promising new avenues of cancer therapy development. Dynamic optical imaging can help this endeavor as a versatile non-invasive tool that probes both the vascular (through total hemoglobin concentration (HbT) and SO2) and biomechanical tumor properties (through monitoring the hemodynamic response to compression). The goal of this project is to validate the variation of tissue HbT and SO2 due to breast compression as biomarkers for guiding breast cancer neoadjuvant chemotherapy. Our main approach is to develop a combined optical+x-ray mammography scanner for ease of clinical translation, but we will also employ Magnetic Resonance Imaging and MR Elastography to investigate the physiological basis of the compression response.

 描述（由适用提供）：新辅助化疗（NACT）经常用于局部晚期乳腺癌患者的管理。它可以通过早期治疗微焦点，使疾病降低并增加乳房保存手术率来改善预后。但是，裸露的结果遇到了异质的结果。尽管70-80％的患者表现出一定程度的反应，但只有大约25％的患者达到了病理完全反应，这是与提高生存率相关的唯一结果。这种变异性融合了治疗监测技术以识别无效治疗方法的发展，尤其是考虑到最近的数据表明响应引导的NACT可能导致生存率增加。监测对于三重阴性乳腺癌以及靶向剂的使用越来越大。功能成像方法提供了对早期反应的最佳敏感性，因为肿瘤生理的变化发生在实际肿瘤收缩之前。近红外弥散光谱和成像（NIR-DOSI）正在成为一种有希望的非侵入性工具，用于探测肿瘤微环境。我们的组是动态光学成像的先驱之一，除了量化基线血红蛋白浓度和氧合化外，还能够探测乳腺组织对外部刺激的反应。特别是，我们最近表明，在治疗之前，乳腺癌肿瘤暴露了延迟再灌注，并且在分数乳腺摄影类似压缩后，在粘弹性松弛阶段与周围健康组织的血红蛋白氧安全性（SO2）相对于周围的健康组织。这种反应可能取决于增加刚度和间质液压的相互作用，以及更高的恶性病变代谢率。初步数据表明，对于反应肿瘤，裸露的肿瘤几乎消失了30天，同时持续进行无反应的肿瘤，这表明可以使用动态光学成像来探测肿瘤生物力学特性。肿瘤僵硬和IFP的增加已显示导致药物输送不良，并与转移的可能性增加相关。通过抗纤维化剂的血液流动改善了血管归一化，并减少了内部应力，这是癌症治疗发展的新途径。动态光学成像可以帮助这项努力作为一种多功能的非侵入性工具，该工具可以使血管（通过总血红蛋白浓度（HBT）和SO2）和生物力学肿瘤特性（通过监测血液动力学对压缩的反应）。该项目的目的是验证组织HBT和SO2的变化，因为乳房压缩是指导乳腺癌新辅助化学疗法的生物标志物。我们的主要方法是开发一种合并的光学+X射线X线X线摄影扫描仪，以便于临床翻译，但是我们还将采用磁共振成像和MR弹性图来研究压缩反应的物理基础。