Diagnostic Imaging of Blood in Breast Tumor Angiogenesis

描述(由申请人提供)： 激光光声成像系统(LOIS)是一种新型的高灵敏度高成像系统 分辨率数字成像设备在乳腺癌检测中的应用 激光感生声的光学组织对比和超声检测 海浪。目前应用于乳腺的非侵入性活体成像方法 癌症检测不能区分良性和恶性病变。目标是 该项目的主要目的是开发光声成像的诊断能力 定量光谱技术在乳腺癌检测中的应用 肿瘤血管生成中的血红蛋白氧合测定。作为一个系统 早期肿瘤不发达或肿瘤需要增强检查 在抑制血管生成的情况下，我们建议使用纳米颗粒 吸收近红外激光脉冲并与抗体偶联 靶向乳腺肿瘤血管生成。我们的初步研究 在NCI的支持下实现了记录在案的里程碑 可行性和概念论证。正常人的光声对比度 组织和癌症肿瘤显示明显更大(2-6倍) 而不是传统模式提供的对比度。它的主要来源是 对比度及其变化来自于血红蛋白的强光吸收 血液在肿瘤血管中的生成。医学支持的活体数据 文献提示氧合血红蛋白在血管生成中的浓度 与良性肿瘤相比，恶性肿瘤的发病率大大降低。 初步研究揭示了近红外光谱中的最佳激光波长 可以优先在恶性疾病中诱发声源的范围 肿瘤(h=760 nm，脱氧血红蛋白)或良性肿瘤(h=1064 nm， 氧合血红蛋白)。两幅光声图像的组合及其比值 将提供乳癌与良性纤维腺瘤的鉴别 非凡的灵敏度(由于高光学对比度)和卓越 分辨率(归因于超宽带压电检测 超声波)。具体目标集中在(1)将LOIS修改为(I) 将Nd：YAG激光器和紫翠宝石激光器集成到一个光纤光源中 传输系统和(Ii)构造先进的超宽带双焦点阵列 超高分辨率的二维图像超声换能器， (2)用乳胶模体对血色“肿瘤”进行初步测试 类似于恶性和良性肿块的光学和机械特性， (3)临床应用LOIS的敏感性和特异性评价 24例患者的临床试验，(4)敏感度增强的评价和 纳米造影剂对LOIS小鼠模型的特异性研究 基于(I)检测到的来自 超过光声非线性阈值的纳米粒子和(Ii) 纳米粒子在乳腺癌中的选择性积聚 与抗血管内皮生长因子抗体的偶联。

DESCRIPTION (provided by applicant): Laser Optoacoustic Imaging System (LOIS) is a novel highly sensitive high resolution digital imaging modality for breast cancer detection utilizing optical tissue contrast and ultrasonic detection of laser-induced acoustic waves. Noninvasive in vivo imaging modalities presently applied for breast cancer detection cannot differentiate benign from malignant lesions. The goal of this project is to develop diagnostic capability for optoacoustic imaging applied in breast cancer detection based on quantitative spectroscopic measurement of hemoglobin oxygenation in tumor angiogenesis. As the system enhancement needed for detection of early tumors with underdeveloped or tumors with suppressed angiogenesis, we propose utilization of nanoparticles absorbing near-infrared laser pulses and conjugated with antibodies that target specifically breast tumor angiogenesis. Our preliminary studies supported by NCI resulted in accomplishment of milestones that documented feasibility and the proof of concept. Optoacoustic contrast between normal tissues and cancerous tumors was shown to be significantly greater (2-6 fold) than contrast provided by conventional modalities. The primary source of this contrast and its variation comes from strong optical absorption in hemoglobin of blood in the tumor angiogenesis. In vivo data supported by medical literature suggest that concentration of oxyhemoglobin in angiogenesis of malignant tumors is substantially reduced relative to that in benign tumors. Pilot studies revealed optimal laser wavelengths in the near-infrared spectral range that can preferentially induce acoustic sources either in malignant tumors (h=760-nm, deoxyhemoglobin) or in benign tumors (h=1064-nm, oxyhemoglobin). Combination of the two optoacoustic images and their ratio will provide differentiation of breast carcinoma from benign fibroadenoma with exceptional sensitivity (owed to high optical contrast) and superior resolution (owed to ultrawide-band piezoelectric detection of resulting ultrasonic waves). Specific aims focus on (1) modification of LOIS to (I) incorporate Nd:YAG laser and Alexandrite lasers into one fiberoptic light delivery system and (ii) construct an advanced bifocal array of ulrawideband ultrasonic transducers for exceptional resolution of two-dimensional images, (2) initial tests using milk-gel phantoms with blood-colored "tumors" resembling optical and mechanical properties of malignant and benign masses, and cysts, (3) evaluation of the LOIS sensitivity and specificity in clinical trials on 24 patients, (4) evaluation of enhancement of sensitivity and specificity of LOIS in mouse model utilizing nanoparticulate contrast agent based on (I) two-orders of magnitude increase in detected signal from nanoparticles hated above the threshold of optoacoustic nonlinearity and (ii) selective accumulation of nanoparticles in breast cancer owed to their conjugation with antibodies against vascular endothelial growth factor.