Near Infrared Diffused Light Imaging with Ultrasound Guidance

描述（由申请人提供）：超声引导下的近红外漫射光成像：我们建议探索一种新型混合成像技术的应用：1)准确诊断乳房病变，从而减少良性活检；2)评价化疗反应，评价治疗效果。该混合技术通过在手持探头上同时部署近红外（NIR）光学传感器和商用超声换能器来实现，并利用超声提供的共注册病变结构信息来改进逆光学层析成像重建。因此，光学断层扫描克服了与强光散射相关的问题，并提供了可靠的肿瘤血管生成分布。一组活检患者的初步结果表明，与纤维腺瘤和其他良性病变相比，早期浸润性癌症的总血红蛋白浓度平均高两倍。从晚期癌症中获得的早期结果表明，血管生成分布高度扭曲和不均匀，扭曲分布与组织学微血管计数相关，可用于评估化疗反应。在本次续期申请中，我们建议进行更大规模的临床研究，以进一步验证这些初步结果。本应用的具体目标是：1)估计和纠正胸壁引起的近红外漫反射波畸变，这种畸变常发生在乳房组织体积较小的患者中，并通过结合数字信号处理模块实现在线光学成像重建；2)将原型近红外系统升级为成像平台；3)验证光学断层扫描/超声鉴别乳腺良性肿瘤和早期恶性肿瘤的初始敏感性、特异性、阳性预测值和阴性预测值。大约300名将接受超声引导活检的患者将从康涅狄格大学健康中心和哈特福德医院招募到这项研究；在两所院校进行初步的诊断研究；4)验证光学断层扫描/超声作为评估化疗反应和评估治疗疗效的有价值的成像工具。大约40名将接受化疗的患者将从这两个机构招募到这项试点研究中。

DESCRIPTION (provided by applicant): Near Infrared Diffused Light Imaging with Ultrasound Guidance: We propose to explore the utility of a novel hybrid imaging technique for: 1) Accurate diagnosis of breast lesions and therefore reduction of benign biopsies; and 2) Assessing chemotherapy response and evaluating treatment efficacy. The hybrid technique is implemented by simultaneously deploying near infrared (NIR) optical sensors and a commercial ultrasound transducer mounted on a hand-held probe, and utilizing coregistered lesion structure information provided by ultrasound to improve the inverse optical tomography reconstruction. As a result, the optical tomography has overcome problems associated with the intense light scattering and has provided reliable tumor angiogenesis distributions. Preliminary results with a group of biopsied patients have shown that early-stage invasive cancers may be distinguished by an average of twofold greater total hemoglobin concentration when compared to fibroadenomas and other benign lesions. Early results obtained from advanced cancers have shown that the angiogenesis distribution is highly distorted and heterogeneous, and the distorted distributions correlate with histological microvessel counts and can be used to assess chemotherapy response. In this renewal application, we propose larger-scale clinical studies to further validate these initial results. The proposed specific aims in this application are: 1) To estimate and correct chest-wall induced NIR diffusive wave distortion, which often occurs in patients with a smaller volume of breast tissue, and to implement on-line optical imaging reconstruction by incorporating a digital signal processing module; 2) To upgrade prototype NIR systems to imaging platforms; 3) To validate the initial sensitivity, specificity, positive predictive value and negative predictive value obtained from optical tomography/ultrasound in distinguishing benign and early-stage malignant breast tumors from a larger patient pool. Approximately 300 patients who will undergo ultrasound-guided biopsy will be recruited to this study from the University of Connecticut Health Center and Hartford Hospital; To perform a pilot study in diagnostic setting at both institutions; and 4) To validate the optical tomography/ultrasound as a valuable imaging tool in assessing chemotherapy response and evaluating treatment efficacy. Approximately 40 patients who will undergo chemotherapy treatments will be recruited to this pilot study from both institutions.