University of Notre Dame, Department of Electrical Engineering, Notre Dame, Indiana, United States.
University of Notre Dame, Department of Applied and Computational Mathematics and Statistics, Notre, United States.
J Biomed Opt. 2021 Jun;26(6). doi: 10.1117/1.JBO.26.6.065004.
Noninvasive diffuse optical spectroscopy (DOS) is a promising adjunct diagnostic imaging technique for distinguishing benign and malignant breast lesions. Most DOS approaches require normalizing lesion biomarkers to healthy tissue since major tissue constituents exhibit large interpatient variations. However, absolute optical biomarkers are desirable as it avoids reference measurements which may be difficult or impractical to acquire.
Our goal is to determine whether absolute measurements of minor absorbers such as collagen and methemoglobin (metHb) can successfully distinguish lesions. We hypothesize that metHb would exhibit less interpatient variability and be more suitable as an absolute metric for malignancy. However, we would expect collagen to exhibit more variability, because unlike metHb, collagen is also present in the healthy tissue.
In this retrospective clinical study, 30 lesions with breast imaging reporting and database system score ( BIRADS ) > = 3 (12 benign and 18 malignant) measured with broadband quantitative DOS were analyzed for their oxyhemoglobin (HbO), deoxyhemoglobin (HHb), water, lipids, collagen, metHb concentrations, and optical scattering characteristics. Wilcoxon rank sum test was used to compare benign and malignant lesions for all variables in both normalized and absolute forms.
Among all absolute DOS parameters considered, only absolute metHb was observed to be significant for lesion discrimination (0.43 ± 0.18 μM for benign versus 0.87 ± 0.32 μM for malignant, p = 0.0002). Absolute metHb concentration was also determined to be the best predictor of malignancy with an area under the curve of 0.89.
Our findings demonstrate that lesion metHb concentration measured by DOS can improve noninvasive optical diagnosis of breast malignancies. Since metHb concentration found in normal breast tissue is extremely low, metHb may be a more direct indicator of malignancy that does not depend on other biomarkers found in healthy tissue with significant variability. Furthermore, absolute parameters require reduced measurement time and can be utilized in cases where healthy reference tissue is not available.
非侵入性漫射光学光谱(DOS)是一种很有前途的辅助诊断成像技术,可用于区分良性和恶性乳腺病变。由于主要组织成分在患者间存在较大差异,大多数 DOS 方法都需要将病变生物标志物与健康组织进行归一化。然而,由于绝对光学生物标志物避免了可能难以或不切实际获得的参考测量,因此更可取。
我们的目标是确定是否可以使用诸如胶原蛋白和高铁血红蛋白(metHb)等次要吸收体的绝对测量值成功区分病变。我们假设 metHb 会表现出较小的患者间差异,并且更适合作为恶性肿瘤的绝对指标。但是,我们预计胶原蛋白会表现出更大的差异,因为与 metHb 不同,胶原蛋白也存在于健康组织中。
在这项回顾性临床研究中,分析了 30 个具有乳腺成像报告和数据库系统评分(BIRADS)≧3(12 个良性和 18 个恶性)的病变,使用宽带定量 DOS 进行了测量,分析了其氧合血红蛋白(HbO)、脱氧血红蛋白(HHb)、水、脂质、胶原蛋白、metHb 浓度和光散射特性。使用 Wilcoxon 秩和检验比较了所有变量在归一化和绝对形式下良性和恶性病变之间的差异。
在所考虑的所有绝对 DOS 参数中,只有绝对 metHb 被观察到对病变具有显著的区分能力(良性为 0.43±0.18μM,恶性为 0.87±0.32μM,p=0.0002)。绝对 metHb 浓度也被确定为恶性肿瘤的最佳预测指标,曲线下面积为 0.89。
我们的研究结果表明,DOS 测量的病变 metHb 浓度可以改善乳腺恶性肿瘤的无创光学诊断。由于正常乳腺组织中发现的 metHb 浓度极低,因此 metHb 可能是一种更直接的恶性肿瘤指标,它不依赖于健康组织中具有显著差异的其他生物标志物。此外,绝对参数需要更少的测量时间,并且可以在无法获得健康参考组织的情况下使用。