Near Infrared Diffused Light Imaging with Ultrasound Guidance

描述(申请人提供)：超声引导下的近红外扩散光成像：我们建议探索一种新的混合成像技术的用途：1)准确诊断乳腺病变，从而减少良性活检；2)评估化疗反应和评估治疗效果。该混合技术是通过同时部署近红外(NIR)光学传感器和安装在手持探头上的商用超声换能器来实现的，并利用超声提供的共配准病变结构信息来改进反向光学层析成像重建。因此，光学层析成像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。对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，早期侵袭性癌症的平均总血红蛋白浓度高出两倍。晚期癌症的早期研究结果表明，血管生成的分布是高度扭曲和不均匀的，这种扭曲的分布与组织学微血管计数相关，可以用来评估化疗疗效。在这次更新申请中，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。本应用中提议的具体目标是：1)估计和纠正胸壁引起的近红外扩散波失真，这种失真通常发生在较小体积的乳腺组织中，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到成像平台；3)验证光学断层扫描/超声在区分较大患者池中的早期乳腺良恶性肿瘤方面的初始灵敏度、特异度、阳性预测价值和阴性预测价值。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中；在这两家机构的诊断环境中进行一项试点研究；以及4)验证光学断层扫描/超声作为评估化疗反应和疗效的宝贵成像工具。将从这两个机构招募大约40名将接受化疗的患者参加这项试点研究。

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.