Time Resolved Breast Imaging Using a Combined MRI and Optical Tomography Approach

描述（由申请方提供）：原发性全身（新辅助）治疗通常用于手术前的局部晚期乳腺癌患者，以降低疾病分期并增加成功结局的机会。然而，许多患者对新辅助治疗没有反应，并且可能更好地切换到不同的治疗方案，或立即进行手术。然而，治疗监测是困难的，因为目前的临床检查和X射线/超声乳腺摄影随访与最终治疗病理结果的相关性很差。磁共振成像（MRI）和正电子发射断层扫描（PET）都已被评估为反应的早期预测因子，研究表明，18F-FDG PET以及扩散加权（DW）MRI和胆碱化合物MR波谱（tCho-MRS）测量结果与治疗开始后几周内的治疗成功率相当。不幸的是，可用性（PET），复杂性（tCho-MRS）和特异性（MRI）限制了这些方法的适用性。因此，需要开发更容易整合到医疗实践中的非侵入性特异性早期预测方法。一个潜在的答案可能是近红外光谱和断层扫描（NIRS-DOT）。NIRS-DOT是一种新型的功能成像技术，可以提供组织发色团的图像，如氧合血红蛋白（HbO）和脱氧血红蛋白（HbR），水和脂质，小型研究表明，它有可能在治疗开始后一周内预测治疗结果。此外，最近的技术进步已经允许DOT达到高时间分辨率（> 1Hz），允许通过动态成像探测新类型的功能信息。特别是，我们的小组已经获得了有希望的初步结果，监测乳腺组织对外部压缩的反应。组织对压缩的粘弹性反应导致血流动力学（血容量）变化，具有双相时间曲线，可能区分健康组织和乳腺病变。此外，血液动力学和组织氧代谢的相互作用导致血红蛋白氧合瞬变，这提供了从时间分辨光学数据估计组织氧耗（OC）和血流量（BF）的机会。 该提案的总体目标是将联合收割机MRI和NIRS-DOT结合起来，以表征组织血流动力学、血流量和耗氧量的压缩使能测量的预测价值，作为对治疗进展敏感的新生物标志物，并量化它们与最终病理结果的关系。来自MRI扫描的结构信息将用作光学重建的先验信息，同时采集动态光学和HbR相关MR血氧水平依赖（BOLD）图像，从而能够采用融合方法重建时间分辨血流动力学图和BF/OC分布。将根据相应的HbR图交叉验证差异BOLD图像。这项工作将以临床试验结束，以评估新生物标志物的早期治疗结果预测能力。 公共卫生相关性：我们建议在乳房压迫期间使用快速光学断层扫描来研究正常和病变组织的生物力学和代谢特征，目的是提高癌症诊断的特异性和非侵入性监测化疗进展。

DESCRIPTION (provided by applicant): Primary systemic (neoadjuvant) therapy is routinely used for locally advanced breast cancer patients before surgery to down-stage the disease and increase the chances of a successful outcome. Many patients though do not respond to neoadjuvant therapy, and may be better off switching to a different treatment regime, or progressing to surgery immediately. However, therapy monitoring is difficult because current clinical examination and x-ray/ultrasound mammography follow-ups correlate poorly with final therapy pathological outcome. Both magnetic resonance imaging (MRI) and positron emission tomography (PET) have been evaluated as early predictors of response, with studies showing that 18F-FDG PET as well as diffusion weighted (DW) MRI and choline-compounds MR spectroscopy (tCho-MRS) measurements correspond well with therapy success within a few weeks from the beginning of treatment. Unfortunately, availability (PET), complexity (tCho-MRS), and specificity (MRI) limit the applicability of these methods. Consequently, there is a need to develop non-invasive specific early prediction approaches that more easily integrate into medical practice. A potential answer may be offered by near infrared spectroscopy and tomography (NIRS-DOT). NIRS-DOT is a novel functional imaging technique that can offer images of tissue chromophores such as oxy (HbO) and deoxy hemoglobin (HbR), water and lipids, and small studies have hinted at its potential to predict therapy outcome with high accuracy as early as one week after the start of treatment. Further, recent technological advancements have permitted DOT to reach high time resolution (> 1Hz), allowing new types of functional information to be probed by dynamic imaging. In particular, our group has obtained promising initial results monitoring the response of breast tissue to external compression. Tissue viscoelastic response to compression causes hemodynamic (blood volume) changes with bi-phasic temporal profiles likely to differentiate healthy tissues from breast lesions. Further, the interplay of hemodynamics and tissue oxygen metabolism leads to hemoglobin oxygenation transients that offer the opportunity to estimate tissue oxygen consumption (OC) and blood flow (BF) from time-resolved optical data. The overall goal of this proposal is to combine MRI and NIRS-DOT to characterize the predictive value of compression-enabled measurements of tissue hemodynamics, blood flow and oxygen consumption as new biomarkers sensitive to therapy progress and quantify their relationship to final pathological outcome. Structural information from the MRI scans will be used as prior information for the optical reconstructions and dynamic optical and HbR-related MR blood oxygen level dependent (BOLD) images will be simultaneously acquired enabling a fusion approach for reconstructing time-resolved hemodynamic maps and BF/OC distributions. Difference BOLD images will be cross-validated against corresponding HbR maps. The work will culminate with a clinical trial to assess the early therapy outcome predictive ability of the new biomarkers. PUBLIC HEALTH RELEVANCE: We propose to use fast optical tomography during breast compression to investigate biomechanical and metabolic characteristics of normal and lesion tissues, with the goal of improving specificity for cancer diagnosis and non-invasively monitoring chemotherapy progress.