AbstractIn this study, time domain diffuse optical spectroscopy is performed in the range 600–1100 nm on 11 healthy volunteers with a portable system for the quantitative characterization of breast tissue in terms of optical properties and optically-derived blood parameters, tissue constituent concentrations, and scattering parameters.

摘要在这项研究中，使用便携式系统在11名健康志愿者的600-1100 nm范围内进行时域漫反射光谱分析，以定量表征乳腺组织的光学特性和光学衍生的血液参数，组织成分浓度和散射参数。

A measurement protocol involving different geometries (reflectance and transmittance), subject’s positions (sitting and lying down), probing locations (outer, lower, and inner breast quadrants), and source-detector distances (2 and 3 cm) allowed us to investigate the effect of tissue heterogeneity and different measurement configurations on the results with the aim of identifying the best experimental conditions for the estimate of breast density (i.e., amount of fibro-glandular tissue in the breast) as a strong independent risk factor for breast cancer.

涉及不同几何形状（反射率和透射率），受试者位置（坐着和躺着），探测位置（乳房外象限，下象限和内象限）以及源探测器距离（2和3 cm）的测量协议使我们能够研究组织异质性和不同测量配置对结果的影响，目的是确定估计乳腺密度（即乳房中纤维腺体组织的数量）的最佳实验条件，作为乳腺癌的强烈独立危险因素。

Transmittance results, that in previous studies correlated strongly with mammographic density, are used as a reference for the initial test of the simpler and more comfortable reflectance measurement configuration. The higher source-detector distance, which probes deeper tissue, retrieves optical outcomes in agreement with higher average density tissue.

在先前的研究中，透射率结果与乳房X线照相密度密切相关，可作为更简单，更舒适的反射率测量配置初始测试的参考。探测更深组织的更高源-检测器距离可以获得与更高平均密度组织一致的光学结果。

Similarly, results on the outer quadrants indicate higher density than internal quadrants. These findings are coherent with breast anatomy since the concentration of dense fibro-glandular stroma is higher in deep tissue and towards the external portion of the breast, where the mammary gland is located.

同样，外部象限的结果表明密度高于内部象限。这些发现与乳房解剖结构相一致，因为致密的纤维腺体基质在深部组织中的浓度较高，并且朝向乳腺所在的乳房外部。

The dataset generated with this laboratory campaign is used to device an optimal measurement protocol for a future clinical trial, where optical results will be correlated with conventional mammographic density, allowing us to identify a sub.

通过这项实验室活动生成的数据集用于为未来的临床试验设计最佳的测量方案，其中光学结果将与常规乳房X线照相密度相关，从而使我们能够识别sub。

IntroductionBreast cancer is the neoplasia with the highest incidence and mortality among women and represents a significant strain for healthcare systems worldwide1. Early diagnosis increases therapeutical options and survival rates up to 99%1.Except for gender and age, breast density is the most relevant risk factor involved in the development of breast cancer2.

引言乳腺癌是女性发病率和死亡率最高的肿瘤，是全球医疗保健系统的重要压力1。早期诊断可增加治疗选择，生存率高达99%1。除性别和年龄外，乳腺密度是乳腺癌发展中最相关的危险因素2。

It is defined as the relative proportion between radio-opaque fibro-glandular tissue and transparent adipose tissue3. Nowadays breast density is estimated from the analysis of X-ray mammograms, which typically results in the assignment of the patient to one of the four BI-RADS categories4 (Breast Imaging Reporting and Data System), from category A, corresponding to the lowest density, to category D, corresponding to the highest density.

它被定义为不透射线的纤维腺组织和透明脂肪组织之间的相对比例3。。

Mammograms are most often acquired in the context of screening programs aimed at women not younger than 40 or 50 years old5, due to the ionizing nature of X-ray radiation and the lower sensitivity of mammography in the dense breast, more common in young women6. However, information on breast density could be useful earlier in life.

由于X射线辐射的电离性质以及乳腺X线照相术在致密乳房中的敏感性较低（在年轻女性中更常见），乳腺X线照片通常是在针对40岁或50岁以下女性的筛查计划中获得的。然而，有关乳房密度的信息可能在生命早期有用。

It would allow one to implement at a younger age targeted monitoring of subjects with higher risk of cancer, develop personalized prevention paths and possibly lead to early cancer detection. From this picture, the pressing need for a non-invasive and effective way to assess breast density emerges, especially in young woman.Diffuse optics (DO) investigates the absorption and scattering properties of tissue, which depend, respectively, on the chemical composition and on the size and density of scattering centers, that randomize the propagation direction of photons.

它将允许人们在年轻时对癌症风险较高的受试者进行有针对性的监测，开发个性化的预防途径，并可能导致早期癌症检测。从这张照片来看，迫切需要一种非侵入性和有效的方法来评估乳房密度，特别是在年轻女性中。漫反射光学（DO）研究组织的吸收和散射特性，这分别取决于化学成分以及散射中心的大小和密度，散射中心随机化光子的传播方向。

This information can be used to distinguish fibro-glandular stroma from adipose tissue,.

该信息可用于区分纤维腺基质和脂肪组织，。

1.

1.

The optimization and validation of the portable TD-DOS system for in vivo measurements of breast density, in view of its future clinical implementation.

鉴于其未来的临床实施，对用于体内测量乳房密度的便携式TD-DOS系统进行了优化和验证。

2.

2.

The identification of a subject’s and physician’s friendly measurement configuration in reflectance geometry (or more than one configuration) to be subsequently implemented in the clinical study.

。

3.

3.

The generation of an open dataset of in vivo data on the breast tissue, including broadband optical properties (absorption and reduced scattering coefficients), tissue composition (water, lipids, and collagen), blood parameters (total hemoglobin concentration and oxygen saturation), and scattering parameters (scattering amplitude and power providing) to investigate inter-subject and intra-subject variability..

生成乳房组织体内数据的开放数据集，包括宽带光学特性（吸收和减少的散射系数），组织组成（水，脂质和胶原蛋白），血液参数（总血红蛋白浓度和氧饱和度）和散射参数（散射幅度和功率提供），以调查受试者之间和受试者内部的变异性。。

The cohort of subjects involved in the study is relatively young (see Table 1 for demographics) and most of them are not of age for screening. For this reason, mammograms are not available for direct comparison of optical parameters with BIRADS categories. Transmittance acquisitions, that in previous were strongly correlated with mammographic breast density43,46,47,48, are used to validate the reflectance measurements in this preliminary study.

参与该研究的受试者队列相对年轻（人口统计学见表1），其中大多数未达到筛查年龄。因此，乳房X线照片无法直接比较光学参数与BIRADS类别。在这项初步研究中，透射率采集与乳腺X线摄影的乳房密度43,46,47,48密切相关，用于验证反射率测量结果。

In an upcoming clinical trial, recent mammograms will be available for the enrolled subjects, allowing us to correlate directly optical results from point-like, reflectance measurements with BI-RADS categories. The intent will then be to investigate the broadband optical properties of breast tissue and determine how much of this information is essential for a good estimate of breast composition and density, in order to identify a minimal set of wavelengths (and measurement points) that is sufficient for a good correlation with traditional mammography.

在即将进行的临床试验中，将为登记的受试者提供最新的乳房X线照片，使我们能够将点状反射率测量的光学结果与BI-RADS类别直接关联。然后，目的是研究乳房组织的宽带光学特性，并确定这些信息中有多少对于良好估计乳房组成和密度至关重要，以便确定一组最小的波长（和测量点），足以与传统乳房X线照相术形成良好的相关性。

The collection of this extensive set of measurements has involved a rather long measurement time of about 45 min (see “Measurement protocol” section). The study was approval by the Ethical Review Board of our Institution to be performed in our laboratory environment, where the length of the measurements is not a major issue.

收集这组广泛的测量涉及大约45分钟的相当长的测量时间（请参阅“测量协议”部分）。这项研究得到了我们机构伦理审查委员会的批准，将在我们的实验室环境中进行，在那里测量的长度不是一个主要问题。

On the other hand, it was not feasible to enroll a broad number of subjects, all with recent X-ray mammograms available. The latter would only be feasible in clinical settings, but in that case a long measurement time would not be acceptable as it would not fit in the screening/diagnostic workflow. This has motivated our choice to separate the work in the initial small laboratory study followed by the broader clinical study.Table 1 Age, BMI, and breast thickness.

另一方面，招募大量受试者是不可行的，所有受试者都有最近的X射线乳房X线照片。后者仅在临床环境中可行，但在这种情况下，长时间的测量时间是不可接受的，因为它不适合筛查/诊断工作流程。这促使我们选择在最初的小型实验室研究中分离工作，然后进行更广泛的临床研究。表1年龄，BMI和乳房厚度。

(1)

(1)

where \({\lambda }_{0}\) = 600 nm is a reference wavelength and \(a\) and \(b\) are called, respectively, scattering amplitude and power and are associated, respectively, to the density and size of scattering centers.Statistical analysisThe linear correlations among tissue components and scattering parameters are investigated through the Pearson linear correlation coefficient r.

其中（{λ}u0}）=600 nm是参考波长，\（a）和\（b）分别称为散射振幅和功率，并分别与散射中心的密度和大小相关。统计分析通过Pearson线性相关系数r研究组织成分和散射参数之间的线性相关性。

The same test was used to analyze the correlation between results from different measurement configurations (e.g., outer quadrants vs inner quadrant, or ρ = 2 cm vs ρ = 3 cm), while the significance of their difference is assessed using the Wilcoxon matched-pairs signed-rank test. Bonferroni correction is applied to adjust p-values for multiple testing53.

使用相同的测试来分析不同测量配置（例如，外象限与内象限，或ρ==2 cm与ρ==3 cm）的结果之间的相关性，同时使用Wilcoxon匹配对符号秩检验评估其差异的显着性。应用Bonferroni校正来调整多重测试的p值53。

This correction might be excessively strict since a relatively small sample size is involved and the tests we consider are expected to be not completely independent. Therefore, when statistical significance is lost due to Bonferroni multiplicity adjustment, the p-value before adjustment is also reported.

。因此，当由于Bonferroni多重性调整而失去统计显着性时，还报告了调整前的p值。

Tests are applied with a level of significance α = 0.05 and results are considered statistically significant when p < 0.05.Results and discussionOptical propertiesTo provide a general overview of the inter-subject variability of the optical properties of the breast in reflectance geometry, Fig. 3 shows the absorption and reduced scattering spectra of the 11 subjects, averaged over left and right breasts and the three different measurement locations on the breast (outer, lower and inner quadrants) in the supine-subject configuration, at inter-fiber distance \(\uprho =\) 3 cm.Figure 3Absorption (a) and reduced scattering (b) spectra of the 11 subjects (averaged over left and right breasts, and all measurement locations on the brea.

测试的显着性水平为α=0.05，当p<0.05时，结果被认为具有统计学意义。结果和讨论光学特性为了提供反射几何中乳房光学特性的受试者间变异性的一般概述，图3显示了11个受试者的吸收和减少的散射光谱，在仰卧受试者配置中，在纤维间距离为3厘米时，在左右乳房和乳房上的三个不同测量位置（外部，下部和内部象限）上平均。图3 11名受试者的吸收（a）和减少散射（b）光谱（左右乳房的平均值，以及brea上的所有测量位置）。

Data availability

数据可用性

The dataset gathered, analyzed, and discussed in this study is available in the Zenodo repository, https://doi.org/https://doi.org/10.5281/zenodo.10955509. For any additional information please contact the corresponding author.

本研究中收集、分析和讨论的数据集可在Zenodo存储库中找到，https://doi.org/https://doi.org/10.5281/zenodo.10955509.如需更多信息，请联系通讯作者。

ReferencesSiegel, R., Ward, E., Brawley, O. & Jemal, A. Cancer statistics, 2011. CA Cancer J. Clin. 61, 212–236 (2011).Article

参考Siegel，R.，Ward，E.，Brawley，O。＆Jemal，A。癌症统计，2011。CA Cancer J.Clin。61212-236（2011）。文章

PubMed

PubMed

Google Scholar

谷歌学者

McCormack, V. A. & dos Santos Silva, I. Breast density and parenchymal patterns as markers of breast cancer risk: A meta-analysis. Cancer Epidemiol. Biomark. Prevent. 15, 1159–1169 (2006).Article

McCormack，V.A。和dos Santos Silva，I。乳腺密度和实质模式作为乳腺癌风险标志物：荟萃分析。癌症流行病学。生物标志物。预防。151159-1169（2006）。文章

Google Scholar

谷歌学者

Wang, A. T., Vachon, C. M., Brandt, K. R. & Ghosh, K. Breast density and breast cancer risk: A practical review. Mayo Clin. Proc. 89, 548–557 (2014).Article

Wang，A.T.，Vachon，C.M.，Brandt，K.R。＆Ghosh，K。乳腺密度和乳腺癌风险：实践综述。梅奥临床。程序。89548-557（2014）。文章

PubMed

PubMed

Google Scholar

谷歌学者

D’Orsi, C. J., Sickles, E. A., Mendelson, E. B. & Morris, E. A. ACR BI-RADS® Atlas, Breast Imaging Reporting and Data System (Springer, 2013).Ren, W., Chen, M., Qiao, Y. & Zhao, F. Global guidelines for breast cancer screening: A systematic review. The Breast 64, 85–99 (2022).Article .

D'Orsi，C.J.，Sickles，E.A.，Mendelson，E.B。＆Morris，E.A。ACR BI-RADS®图谱，乳房成像报告和数据系统（Springer，2013）。Ren，W.，Chen，M.，Qiao，Y。＆Zhao，F。全球乳腺癌筛查指南：系统评价。乳房64,85-99（2022）。文章。

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Buist, D. S. M., Porter, P. L., Lehman, C., Taplin, S. H. & White, E. Factors contributing to mammography failure in women aged 40–49 years. JNCI J. Natl. Cancer Inst. 96, 1432–1440 (2004).Article

Buist，D.S.M.，Porter，P.L.，Lehman，C.，Taplin，S.H。＆White，E。导致40-49岁女性乳房X光检查失败的因素。JNCI J.Natl。癌症研究所961432-1440（2004）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Akbari-Sari, A., Mobinizadeh, M. & Azadbakht, M. A systematic review of the effects of diffuse optical imaging in breast diseases. Iran. J. Cancer Prev. 6, 44–51 (2013).PubMed

Akbari Sari，A.，Mobinizadeh，M。＆Azadbakht，M。扩散光学成像对乳腺疾病影响的系统评价。伊朗。J、 癌症预防。6，44-51（2013）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Leff, D. R. et al. Diffuse optical imaging of the healthy and diseased breast: A systematic review. Breast Cancer Res. Treatment 108, 9–22. https://doi.org/10.1007/s10549-007-9582-z (2008).Article

Leff，D.R.等人，《健康和患病乳腺的扩散光学成像：系统综述》。乳腺癌研究治疗108,9-22。https://doi.org/10.1007/s10549-007-9582-z（2008年）。文章

Google Scholar

谷歌学者

Moon, J. H. et al. Supplemental use of optical diffusion breast imaging for differentiation between benign and malignant breast lesions. Am. J. Roentgenol. 197, 732–739 (2011).Article

Moon，J.H.等人。光学扩散乳腺成像在乳腺良恶性病变鉴别中的补充应用。美国J·伦琴。197732-739（2011）。文章

Google Scholar

谷歌学者

Pal, U. M. et al. Optical spectroscopy-based imaging techniques for the diagnosis of breast cancer: A novel approach. Appl. Spectrosc. Rev. 55, 778–804 (2020).Article

Pal，U.M.等人。基于光谱的成像技术诊断乳腺癌：一种新方法。应用。光谱。第55778-804版（2020年）。文章

ADS

广告

CAS

中科院

Google Scholar

谷歌学者

Taroni, P. et al. Non-invasive optical estimate of tissue composition to differentiate malignant from benign breast lesions: A pilot study. Sci. Rep. 7, 40683 (2017).Article

Taroni，P.等人。组织成分的非侵入性光学估计，以区分乳腺良恶性病变：一项初步研究。科学。代表740683（2017）。文章

ADS

广告

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Tromberg, B. J. et al. Imaging in breast cancer: Diffuse optics in breast cancer: Detecting tumors in pre-menopausal women and monitoring neoadjuvant chemotherapy. Breast Cancer Res. 7, 279 (2005).Article

Tromberg，B.J.等人，《乳腺癌成像：乳腺癌的弥散光学：检测绝经前妇女的肿瘤和监测新辅助化疗》。乳腺癌研究7279（2005）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Maffeis, G. et al. The SOLUS instrument: Optical characterization of the first hand-held probe for multimodal imaging (ultrasound and multi-wavelength time-resolved diffuse optical tomography). Opt. Lasers Eng. 176, 108075 (2024).Article

Maffeis，G.等人，《SOLUS仪器：用于多模式成像（超声波和多波长时间分辨漫反射光学断层扫描）的第一个手持式探针的光学表征》。选择。激光工程176108075（2024）。文章

Google Scholar

谷歌学者

Quaresima, V., Matcher, S. J. & Ferrari, M. Identification and quantification of intrinsic optical contrast for near-infrared mammography. Photochem. Photobiol. 67, 4–14 (1998).CAS

Quaresima，V.，Matcher，S.J。和Ferrari，M。近红外乳房X光检查内在光学对比度的识别和量化。光化学。光生物。67，4-14（1998）。中科院

PubMed

PubMed

Google Scholar

谷歌学者

Choe, R. et al. Differentiation of benign and malignant breast tumors by in-vivo three-dimensional parallel-plate diffuse optical tomography. J. Biomed. Opt. 14, 024020 (2009).Article

Choe，R.等人。通过体内三维平行板扩散光学断层扫描区分乳腺良恶性肿瘤。J、 生物医学。选择。14024020（2009）。文章

ADS

广告

PubMed

PubMed

Google Scholar

谷歌学者

Zimmermann, B. B. et al. Multimodal breast cancer imaging using coregistered dynamic diffuse optical tomography and digital breast tomosynthesis. J. Biomed. Opt. 22, 046008 (2017).Article

Zimmermann，B.B.等人。使用共注册动态扩散光学断层扫描和数字乳腺断层合成的多模式乳腺癌成像。J、 生物医学。选择。22046008（2017）。文章

ADS

广告

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Li, S., Zhang, M., Xue, M. & Zhu, Q. Real-time breast lesion classification combining diffuse optical tomography frequency domain data and BI-RADS assessment. J. Biophoton. 17, 5 (2024).Article

Li，S.，Zhang，M.，Xue，M。＆Zhu，Q。结合扩散光学断层扫描频域数据和BI-RADS评估的实时乳腺病变分类。J、 生物光子。17，5（2024）。文章

CAS

中科院

Google Scholar

谷歌学者

Vasudevan, S., Campbell, C., Liu, F. & O’Sullivan, T. D. Broadband diffuse optical spectroscopy of absolute methemoglobin concentration can distinguish benign and malignant breast lesions. J. Biomed. Opt. 26, 458 (2021).Article

Vasudevan，S.，Campbell，C.，Liu，F。＆O'Sullivan，T.D。绝对高铁血红蛋白浓度的宽带漫反射光谱可以区分良性和恶性乳腺病变。J、 生物医学。选择。26458（2021）。文章

Google Scholar

谷歌学者

Feng, J. et al. Addition of T2-guided optical tomography improves noncontrast breast magnetic resonance imaging diagnosis. Breast Cancer Res. 19, 117 (2017).Article

Feng，J。等人。T2引导光学断层扫描的增加改善了非对比乳腺磁共振成像诊断。乳腺癌研究19117（2017）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Muldoon, A. et al. Method to improve the localization accuracy and contrast recovery of lesions in separately acquired X-ray and diffuse optical tomographic breast imaging. Biomed. Opt. Express 13, 5295 (2022).Article

Muldoon，A。等人。在分别获得的X射线和扩散光学断层摄影乳腺成像中提高病灶定位准确性和对比度恢复的方法。生物医学。选择。快递135295（2022）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Maffeis, G. et al. In vivo test-driven upgrade of a time domain multi-wavelength optical mammograph. Biomed. Opt. Express 12, 1105 (2021).Article

Maffeis，G.等人。时域多波长光学乳腺X线摄影仪的体内测试驱动升级。生物医学。选择。。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

O’Sullivan, T. D. et al. Optical imaging correlates with magnetic resonance imaging breast density and reveals composition changes during neoadjuvant chemotherapy. Breast Cancer Res. 15, R14 (2013).Article

光学成像与磁共振成像乳腺密度相关，并揭示新辅助化疗期间的成分变化。乳腺癌研究15，R14（2013）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Jakubowski, D. B. et al. Monitoring neoadjuvant chemotherapy in breast cancer using quantitative diffuse optical spectroscopy: A case study. J. Biomed. Opt. 9, 230 (2004).Article

Jakubowski，D.B.等人。使用定量漫反射光谱学监测乳腺癌新辅助化疗：案例研究。J、 生物医学。选择。9230（2004）。文章

ADS

广告

PubMed

PubMed

Google Scholar

谷歌学者

Schaafsma, B. E. et al. Optical mammography using diffuse optical spectroscopy for monitoring tumor response to neoadjuvant chemotherapy in women with locally advanced breast cancer. Clin. Cancer Res. 21, 577–584 (2015).Article

Schaafsma，B.E.等人。使用漫反射光谱学的光学乳房X线照相术用于监测局部晚期乳腺癌女性对新辅助化疗的肿瘤反应。临床。癌症研究21577-584（2015）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Gunther, J. E. et al. Dynamic diffuse optical tomography for monitoring neoadjuvant chemotherapy in patients with breast cancer. Radiology 287, 778–786 (2018).Article

Gunther，J.E.等人。动态扩散光学断层扫描用于监测乳腺癌患者的新辅助化疗。放射学287778-786（2018）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Cochran, J. M. et al. Tissue oxygen saturation predicts response to breast cancer neoadjuvant chemotherapy within 10 days of treatment. J. Biomed. Opt. 24, 1 (2018).Article

Cochran，J.M.等人，《组织氧饱和度预测治疗后10天内对乳腺癌新辅助化疗的反应》。J、 生物医学。选择。24,1（2018）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Tromberg, B. J. et al. Predicting responses to neoadjuvant chemotherapy in breast cancer: ACRIN 6691 trial of diffuse optical spectroscopic imaging. Cancer Res. 76, 5933–5944 (2016).Article

Tromberg，B.J.等人，《预测乳腺癌对新辅助化疗的反应：ACRIN 6691扩散光谱成像试验》。癌症研究765933-5944（2016）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Liu, Y. H. et al. Diffuse optical spectroscopy for monitoring the responses of patients with breast cancer to neoadjuvant chemotherapy. Medicine 97, e12683 (2018).Article

Liu，Y.H.等人。用于监测乳腺癌患者对新辅助化疗反应的漫反射光谱。医学97，e12683（2018）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Altoe, M. L. et al. Effects of neoadjuvant chemotherapy on the contralateral non-tumor-bearing breast assessed by diffuse optical tomography. Breast Cancer Res. 23, 16 (2021).Article

Altoe，M.L.等人。通过扩散光学断层扫描评估新辅助化疗对对侧非肿瘤乳腺的影响。乳腺癌研究23,16（2021）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Altoe, M. L. et al. Diffuse optical tomography of the breast: A potential modifiable biomarker of breast cancer risk with neoadjuvant chemotherapy. Biomed. Opt. Express 10, 4305 (2019).Article

Altoe，M.L.等人，《乳腺扩散光学断层扫描：新辅助化疗乳腺癌风险的潜在可改变生物标志物》。生物医学。选择。Express 104305（2019）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Taroni, P. et al. Optical identification of subjects at high risk for developing breast cancer. J. Biomed. Opt. 18, 060507 (2013).Article

Taroni，P.等人。乳腺癌高危人群的光学鉴定。J、 生物医学。选择。18060507（2013）。文章

ADS

广告

PubMed

PubMed

Google Scholar

谷歌学者

Lloyd, R. et al. Alternative methods to measure breast density in younger women. Br. J. Cancer 128, 1701–1709 (2023).Article

Lloyd，R.等人。测量年轻女性乳房密度的替代方法。《癌症杂志》1281701-1709（2023）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Michaelsen, K. E. et al. Effects of breast density and compression on normal breast tissue hemodynamics through breast tomosynthesis guided near-infrared spectral tomography. J. Biomed. Opt. 21, 091316 (2016).Article

Michaelsen，K.E.等人。通过乳房断层合成引导的近红外光谱断层扫描，乳房密度和压缩对正常乳房组织血流动力学的影响。J、 生物医学。选择。。文章

ADS

广告

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Grosenick, D., Rinneberg, H., Cubeddu, R. & Taroni, P. Review of optical breast imaging and spectroscopy. J. Biomed. Opt. 21, 091311 (2016).Article

Grosenick，D.，Rinneberg，H.，Cubeddu，R。＆Taroni，P。光学乳房成像和光谱学评论。J、 生物医学。选择。21091311（2016）。文章

ADS

广告

PubMed

PubMed

Google Scholar

谷歌学者

Durduran, T., Choe, R., Baker, W. B. & Yodh, A. G. Diffuse optics for tissue monitoring and tomography. Rep. Progress Phys. 73, 076701 (2010).Article

Durduran，T.，Choe，R.，Baker，W.B。＆Yodh，A.G。用于组织监测和断层扫描的漫反射光学。代表进步物理。73076701（2010）。文章

ADS

广告

Google Scholar

谷歌学者

Zhu, Q. & Poplack, S. A review of optical breast imaging: Multi-modality systems for breast cancer diagnosis. Eur. J. Radiol. 129, 109067 (2020).Article

Zhu，Q。＆Poplack，S。光学乳腺成像综述：乳腺癌诊断的多模态系统。欧洲放射杂志。129109067（2020）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Blackmore, K. M., Knight, J. A., Jong, R. & Lilge, L. Assessing breast tissue density by transillumination breast spectroscopy (TIBS): An intermediate indicator of cancer risk. Br. J. Radiol. 80, 545–556 (2007).Article

Blackmore，K.M.，Knight，J.A.，Jong，R。＆Lilge，L。通过透照乳腺光谱（TIBS）评估乳腺组织密度：癌症风险的中间指标。英国放射学会。80545-556（2007）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Blackmore, K. M., Knight, J. A., Walter, J. & Lilge, L. The association between breast tissue optical content and mammographic density in pre- and post-menopausal women. PLOS ONE 10, e0115851 (2015).Article

Blackmore，K.M.，Knight，J.A.，Walter，J。＆Lilge，L。绝经前后女性乳腺组织光学含量与乳房X线密度之间的关系。PLOS ONE 10，e0115851（2015）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Walter, E. J., Knight, J. A. & Lilge, L. A multi-wavelength, laser-based optical spectroscopy device for breast density and breast cancer risk pre-screening. J. Biophoton. 10, 565–576 (2017).Article

Walter，E.J.，Knight，J.A。＆Lilge，L。一种用于乳腺密度和乳腺癌风险预筛查的多波长激光光谱仪。J、 生物光子。10565-576（2017）。文章

CAS

中科院

Google Scholar

谷歌学者

Walter, E. J. & Lilge, L. Optical assessment of mammographic breast density by a 12-wavelength vs a continuous-spectrum optical spectroscopy device. J. Biophoton. 11, 145 (2018).Article

Walter，E.J。＆Lilge，L。通过12波长与连续光谱光谱仪对乳房X线照相密度进行光学评估。J、 生物光子。11145（2018）。文章

Google Scholar

谷歌学者

Brooksby, B. et al. Imaging breast adipose and fibroglandular tissue molecular signatures by using hybrid MRI-guided near-infrared spectral tomography. Proc. Natl. Acad. Sci. 103, 8828–8833 (2006).Article

。程序。纳特尔。阿卡德。科学。1038828-8833（2006）。文章

ADS

广告

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

El-Ghussein, F., Mastanduno, M. A., Jiang, S., Pogue, B. W. & Paulsen, K. D. Hybrid photomultiplier tube and photodiode parallel detection array for wideband optical spectroscopy of the breast guided by magnetic resonance imaging. J. Biomed. Opt. 19, 011010 (2013).Article

El Ghussein，F.，Mastanduno，M.A.，Jiang，S.，Pogue，B.W。＆Paulsen，K.D。混合光电倍增管和光电二极管平行检测阵列，用于磁共振成像引导的乳腺宽带光谱。J、 生物医学。选择。19011010（2013）。文章

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Taroni, P. et al. Noninvasive assessment of breast cancer risk using time-resolved diffuse optical spectroscopy. J. Biomed. Opt. 15, 060501 (2010).Article

Taroni，P。等人。使用时间分辨漫反射光谱学对乳腺癌风险进行无创评估。J、 生物医学。选择。1560501（2010）。文章

ADS

广告

PubMed

PubMed

Google Scholar

谷歌学者

Taroni, P. et al. Time domain diffuse optical spectroscopy: In vivo quantification of collagen in breast tissue. In Optical Methods for Inspection, Characterization, and Imaging of Biomaterials II, vol. 9529 (eds. Ferraro, P., et al.) 952910 (SPIE, 2015).Taroni, P., Bassi, A., Farina, A., Cubeddu, R.

Taroni，P。等人。时域漫反射光谱：乳腺组织中胶原蛋白的体内定量。在生物材料的检查，表征和成像的光学方法II中，第9529卷（编辑Ferraro，P。等人）952910（SPIE，2015）。塔罗尼，P.，巴西，A.，法里纳，A.，库贝杜，R。

& Pifferi, A. Role of collagen scattering for in vivo tissue characterization. In Biomedical Optics and 3-D Imaging (OSA, 2010). https://doi.org/10.1364/BIOMED.2010.BTuD107.Taroni, P. et al. Effects of tissue heterogeneity on the optical estimate of breast density. Biomed. Opt. Express 3, 2411 (2012).Article .

&Pifferi，A。胶原散射在体内组织表征中的作用。生物医学光学和三维成像（OSA，2010）。https://doi.org/10.1364/BIOMED.2010.BTuD107.Taroni，P。等人。组织异质性对乳房密度光学估计的影响。生物医学。选择。快报32411（2012）。文章。

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Perera, D. et al. The distribution of breast density in women aged 18 years and older. Breast Cancer Res. Treat. 205, 521–531 (2024).Article

Perera，D.等人，《18岁及以上女性乳房密度的分布》。乳腺癌研究治疗。205521-531（2024）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Kehm, R. D. et al. A comparison of various methods for measuring breast density and breast tissue composition in adolescent girls and women. Sci. Rep. 12, 13547 (2022).Article

Kehm，R.D.等人，《测量青春期女孩和女性乳房密度和乳房组织成分的各种方法的比较》。科学。代表1213547（2022）。文章

ADS

广告

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Martelli, F., Del-Bianco, S., Ismaelli, A. & Zaccanti, G. Light Propagation Through Biological Tissue and Other Diffusive Media: Theory, Solutions, and Software (SPIE Press, 2010).

Martelli，F.，Del Bianco，S.，Ismaelli，A。＆Zaccanti，G。通过生物组织和其他扩散介质的光传播：理论，解决方案和软件（SPIE Press，2010）。

Google Scholar

谷歌学者

D’Andrea, C. et al. Time-resolved spectrally constrained method for the quantification of chromophore concentrations and scattering parameters in diffusing media. Opt. Express 14, 1888 (2006).Article

D'Andrea，C.等人。扩散介质中发色团浓度和散射参数定量的时间分辨光谱约束方法。选择。。文章

ADS

广告

PubMed

PubMed

Google Scholar

谷歌学者

Mourant, J. R., Fuselier, T., Boyer, J., Johnson, T. M. & Bigio, I. J. Predictions and measurements of scattering and absorption over broad wavelength ranges in tissue phantoms. Appl. Opt. 36, 949 (1997).Article

Mourant，J.R.，Fuselier，T.，Boyer，J.，Johnson，T.M。＆Bigio，I.J。预测和测量组织模型中宽波长范围内的散射和吸收。应用。选择。36949（1997）。文章

ADS

广告

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Nilsson, A. M. K., Sturesson, C., Liu, D. L. & Andersson-Engels, S. Changes in spectral shape of tissue optical properties in conjunction with laser-induced thermotherapy. Appl. Opt. 37, 1256 (1998).Article

Nilsson，A.M.K.，Sturesson，C.，Liu，D.L。和Andersson-Engels，S。结合激光诱导热疗的组织光学性质光谱形状的变化。应用。选择。371256（1998）。文章

ADS

广告

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Armstrong, R. A. When to use the Bonferroni correction. Ophthalm. Physiol. Opt. 34, 502–508 (2014).Article

Armstrong，R.A。何时使用Bonferroni校正。眼科。生理学。选择。34502-508（2014）。文章

Google Scholar

谷歌学者

Ferocino, E. et al. High throughput detection chain for time domain optical mammography. Biomed. Opt. Express 9, 755 (2018).Article

Ferocino，E。等人。用于时域光学乳房X线照相术的高通量检测链。生物医学。选择。Express 9755（2018）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Carp, S. A. et al. Dynamic functional and mechanical response of breast tissue to compression. Opt. Express 16, 16064 (2008).Article

Carp，S.A.等人。乳房组织对压缩的动态功能和机械响应。选择。快报1616064（2008）。文章

ADS

广告

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Carp, S. A. et al. Compression-induced changes in the physiological state of the breast as observed through frequency domain photon migration measurements. J. Biomed. Opt. 11, 064016 (2006).Article

Carp，S.A.等人。通过频域光子迁移测量观察到压缩引起的乳房生理状态的变化。J、 生物医学。选择。11064016（2006）。文章

ADS

广告

PubMed

PubMed

Google Scholar

谷歌学者

Busch, D. R. et al. Blood flow reduction in breast tissue due to mammographic compression. Acad. Radiol. 21, 151–161 (2014).Article

Busch，D.R。等人。由于乳房X线照相压缩，乳房组织中的血流减少。阿卡德。放射性。21151-161（2014）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Pifferi, A. et al. Spectroscopic time-resolved diffuse reflectance and transmittance measurements of the female breast at different interfiber distances. J. Biomed. Opt. 9, 1143 (2004).Article

Pifferi，A。等人。不同纤维间距离下女性乳房的光谱时间分辨漫反射和透射测量。J、 生物医学。选择。91143（2004）。文章

ADS

广告

PubMed

PubMed

Google Scholar

谷歌学者

Cieśla, S., Wichtowski, M., Poźniak-Balicka, R. & Murawa, D. The surgical anatomy of the mammary gland (part 1). Nowotwory J. Oncol. 70, 211–219 (2020).Article

Cieśla，S.，Wichtowski，M.，Poźniak-Balicka，R。＆Murawa，D。乳腺的外科解剖学（第1部分）。Nowotwory J.Oncol。70211-219（2020）。文章

Google Scholar

谷歌学者

Lippi, G. et al. Postural change during venous blood collection is a major source of bias in clinical chemistry testing. Clin. Chim. Acta 440, 164–168 (2015).Article

Lippi，G。等人。静脉采血过程中的姿势变化是临床化学测试偏倚的主要来源。临床。奇姆。Acta 440164–168（2015）。文章

ADS

广告

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Derakhshan, A. et al. Supine-related pseudoanemia in hospitalized patients. J. Hosp. Med. 16, 219–222 (2021).Article

Derakhshan，A。等人。住院患者仰卧位相关性假性贫血。J、 医院医学杂志16219-222（2021）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Ardeshirpour, Y., Huang, M. & Zhu, Q. Effect of the chest wall on breast lesion reconstruction. J. Biomed. Opt. 14, 044005 (2009).Article

Ardeshirpour，Y.，Huang，M。＆Zhu，Q。胸壁对乳房病变重建的影响。J、 生物医学。选择。14044005（2009）。文章

ADS

广告

PubMed

PubMed

Google Scholar

谷歌学者

Zhang, M., Li, S., Zou, Y. & Zhu, Q. Deep learning-based method to accurately estimate breast tissue optical properties in the presence of the chest wall. J. Biomed. Opt. 26, 10 (2021).Article

Zhang，M.，Li，S.，Zou，Y。＆Zhu，Q。基于深度学习的方法，可以在胸壁存在的情况下准确估计乳腺组织的光学特性。J、 生物医学。选择。26，10（2021）。文章

ADS

广告

Google Scholar

谷歌学者

Pifferi, A., Torricelli, A., Taroni, P. & Cubeddu, R. Reconstruction of absorber concentrations in a two-layer structure by use of multidistance time-resolved reflectance spectroscopy. Opt. Lett. 26, 1963 (2001).Article

Pifferi，A.，Torricelli，A.，Taroni，P。＆Cubeddu，R。通过使用多距离时间分辨反射光谱重建双层结构中的吸收剂浓度。选择。利特。1963年（2001年）第26页。文章

ADS

广告

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Pifferi, A. et al. Collagen content as a risk factor in breast cancer? A pilot clinical study. In Diffuse Optical Imaging V 953813 (OSA, 2015). https://doi.org/10.1364/ECBO.2015.953813.Provenzano, P. P. et al. Collagen density promotes mammary tumor initiation and progression. BMC Med.

？一项初步临床研究。在漫反射光学成像V 953813（OSA，2015）中。https://doi.org/10.1364/ECBO.2015.953813.Provenzano，P.P。等人。胶原蛋白密度促进乳腺肿瘤的发生和发展。BMC医学。

6, 11 (2008).Article .

6、11（2008年）。文章。

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Guo, Y.-P. et al. Growth factors and stromal matrix proteins associated with mammographic densities. http://aacrjournals.org/cebp/article-pdf/10/3/243/3257576/ce030100243p.pdf (2001).Zheng, B. et al. Bilateral mammographic density asymmetry and breast cancer risk: A preliminary assessment.

Guo，Y.-P.等。与乳腺X线密度相关的生长因子和基质基质蛋白。http://aacrjournals.org/cebp/article-pdf/10/3/243/3257576/ce030100243p.pdf（2001年）。郑斌等。双侧乳腺X线密度不对称与乳腺癌风险：初步评估。

Eur. J. Radiol. 81, 3222–3228 (2012).Article .

欧洲无线电杂志。81, 3222-3228 (2012).第[UNK]条。

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Scutt, D., Lancaster, G. A. & Manning, J. T. Breast asymmetry and predisposition to breast cancer. Breast Cancer Res. 8, R14 (2006).Article

Scutt，D.，Lancaster，G.A。和Manning，J.T。乳腺不对称和乳腺癌易感性。乳腺癌研究8，R14（2006）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Download referencesAcknowledgementsThe authors acknowledge funding from the European Union’s Horizon 2020 research and innovation programme as part of the PHAST-ETN project under the Marie Sklodowska-Curie grant agreement No. 860185 and from the European Union’s NextGeneration EU programme “Integrated infrastructure initiative in Photonic and Quantum Sciences”—I-PHOQS (IR0000016, ID D2B8D520, CUP B53C22001750006).Author informationAuthors and AffiliationsDipartimento di Fisica, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133, Milan, ItalyNicola Serra, Rinaldo Cubeddu, Giulia Maffeis, Vamshi Damagatla, Antonio Pifferi & Paola TaroniIstituto di Fotonica e Nanotecnologie, Consiglio Nazionale delle Ricerche, Piazza Leonardo da Vinci 32, 20133, Milan, ItalyAntonio Pifferi & Paola TaroniAuthorsNicola SerraView author publicationsYou can also search for this author in.

下载参考文献致谢作者感谢欧盟地平线2020研究与创新计划（作为Marie Sklodowska-Curie第860185号赠款协议下PHAST-ETN项目的一部分）以及欧盟下一代欧盟计划“光子和量子科学综合基础设施倡议”-I-PHOQS（IR0000016，ID D2B8D520，CUP B53C22001750006）的资助。作者信息作者和附属机构Dipartmento di Fisica，Politecnico di Milano，Piazza Leonardo da Vinci 3220133，米兰，ItalyNicola Serra，Rinaldo Cubeddu，Giulia Maffeis，Vamshi Damagatla，Antonio Pifferi＆Paola Taronistituto di Fotonica e Nanotecnologie，Consiglio Nazionale delle Ricerche，Piazza Leonarda Vinci 3220133，Milan，Italyantononio Pifferi＆Paola TaroniAuthorsNicola SerraView作者出版物您也可以在中搜索这位作者。（笑声）。

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PubMed Google ScholarContributionsR.C., A.P. and P.T conceived and designed the study, N.S. and V.D. optimized and characterized the setup, G.M. recruited the volunteers, N.S., G.M. and R.C. conducted the experiments, N.S. analyzed the data, all authors contributed to the interpretation of the results, P.T.

PubMed谷歌学术贡献。C、 ，A.P.和P.T构思并设计了这项研究，N.S.和V.D.优化并表征了设置，G.M.招募了志愿者，N.S.，G.M.和R.C.进行了实验，N.S.分析了数据，所有作者都为结果的解释做出了贡献，P.T。

outlined the manuscript, N.S. wrote the final form of the manuscript. All authors reviewed the manuscript.Corresponding authorCorrespondence to.

概述了手稿，N.S.写了手稿的最终形式。所有作者都审阅了手稿。对应作者对应。

Nicola Serra.Ethics declarations

尼古拉·塞拉。道德宣言

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Reprints and permissionsAbout this articleCite this articleSerra, N., Cubeddu, R., Maffeis, G. et al. In vivo optimization of the experimental conditions for the non-invasive optical assessment of breast density.

转载和许可本文引用了这篇文章Serra，N.，Cubeddu，R.，Maffeis，G。等人。乳腺密度无创光学评估实验条件的体内优化。

Sci Rep 14, 19154 (2024). https://doi.org/10.1038/s41598-024-70099-xDownload citationReceived: 24 April 2024Accepted: 13 August 2024Published: 19 August 2024DOI: https://doi.org/10.1038/s41598-024-70099-xShare this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

Sci Rep 1419154（2024）。https://doi.org/10.1038/s41598-024-70099-xDownload引文接收日期：2024年4月24日接受日期：2024年8月13日发布日期：2024年8月19日OI：https://doi.org/10.1038/s41598-024-70099-xShare本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

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