日本女性的乳腺癌发病率一直在增加。用于诊断和监测治疗反应的测量技术对于提高乳腺癌患者的生活质量 (QOL) 非常重要。近红外光谱法 (NIRS) 是一种无创测量技术,可以量化生物组织中的吸收和散射系数、血红蛋白浓度和组织氧饱和度,预期用于检测因乳腺癌生长或缩小而引起的参数变化。光学乳腺成像是一种专为乳腺测量设计的 NIRS 系统,将提供对乳腺癌的早期检测和更容易的监测。
用于 NIRS 测量的光是波长范围为 700 nm 至 1100 nm 的近红外光,与其他波长的光相比,相对更容易穿过生物组织。照射到生物组织的光主要被血红蛋白、水和脂质吸收。氧合血红蛋白 (O2Hb) 和脱氧血红蛋白 (HHb) 的浓度可根据其特定吸收特性进行量化。组织氧饱和度 (StO2) 为 O2Hb 与总血红蛋白 (tHb) 的比值。我们使用了一种利用脉冲激光的测量技术,称为时间分辨光谱测定 (TRS),与使用 CW 激光和强度调制激光的技术相比,该技术有望显示出更好的定量性和可再现性。
如图 1 所示,使用近红外脉冲激光照射生物组织,并检测通过组织的光。为了获得生物组织的吸收和散射系数,根据表达散射介质中的光子迁移的光子扩散理论来分析检测到的光的时间曲线。使用公式 (1),\(O_2Hb\)、\(HHb\)、\(tHb\) 和 \(StO_2\) 是通过几个波长的吸收系数确定的。
\( \mu_{a}^{\lambda} \) = \( \varepsilon_{O_{2}Hb}^{\lambda} \) \(C_{O_{2}Hb} \)+\( \varepsilon_{HHb}^{\lambda} \) \(C_{HHb} \)+\( \mu_{a,BG}^{\lambda} \) (1)
\(\varepsilon_{O_{2}Hb}^{\lambda} \):氧合血红蛋白摩尔消光系数 (\(cm^{-1}・\mu M^{-1}\))
\(\varepsilon_{HHb}^{\lambda} \):脱氧血红蛋白摩尔消光系数 (\(cm^{-1}・\mu M^{-1}\))
\(\mu_{a,BG}^{\lambda} \):背景介质吸收系数 (\(cm^{-1}\))
\(C_{O_{2}Hb} \)(\(\mu M\)):氧合血红蛋白浓度
\(C_{HHb}\)(\(\mu M\)):脱氧血红蛋白浓度
\(C_{tHb}\) = \(C_{O_{2}Hb}+C_{HHb}\)(\(\mu M\)):总血红蛋白浓度
\(StO_2\) =100\(\times\frac{C_{O2Hb}}{C_{tHb}}\)(\(%\)):组织氧饱和度
图 1. 反射几何中的时间分辨光谱测定概念图。
图 2 显示了光学乳腺成像,我们的目标是开发一套紧凑且便携的诊断成像系统,在床边即可获得功能图像。
图 2. 光学乳腺成像的图片。手持探头(左)用于在仰卧位(右)进行测量。
我们对一位在滨松大学医学院接受治疗的乳腺癌患者进行了初步的临床测量,以确认光学乳腺成像测量患者化疗期间反应的能力。在三个时间点进行测量,以测量化疗期间的反应:在开始化疗前进行基线测量,开始化疗 3 周和 6 周后分别进行第二次和第三次测量。图 3 所示的乳腺肿瘤超声图像表明,肿瘤在化疗期间逐渐减小。断层图像和 tHb 浓度重建区域内的最大值图如图 3 所示。这些结果表明,患病乳腺中的 tHb 浓度高于健康乳腺,并且在化疗期间降低。通过这些测量,我们确认了光学乳腺成像有潜力检测化疗期间的反应。测量血红蛋白浓度和组织氧饱和度有望用于检测化疗期间的反应,并在短时间内(1 至 10 天)评估治疗效果。
(a) 肿瘤位置
肿瘤位置
(b)
基线
26×28×21 mm
3 周后
26×22×17 mm
6 周后
18×16×10 mm
(c)
图 3. 肿瘤位置 (a),超声图像 (b),以及在乳腺癌患者化疗期间通过光学乳腺成像获得的重建图像和总血红蛋白浓度的最大值图。
我们打算修改测量程序和图像重建算法,以提高重建图像的质量和定量。
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