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Three-dimensional microanatomy of human nipple visualized by X-ray dark-field computed tomography

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The three-dimensional (3D) structure of the human nipple has not been fully clarified. However, its importance has increased in recent years because it has become common practice to preoperatively explore the spread of breast cancer to the nipple with needle biopsy, ductoscopy, and/or ductal lavage for nipple-sparing mastectomy. Here, we demonstrated that X-ray dark-field computed tomography (XDFI-CT) is a powerful tool for reconstructing the 3D distribution pattern of human lactiferous ducts non-destructively, without contrast agent, and with high tissue contrast.


Nipples amputated from mastectomy specimens of 51 patients with breast cancer were visualized three-dimensionally by XDFI-CT. First, CT images and conventionally stained tissue sections were compared to demonstrate that XDFI-CT provides 3D anatomical information. Next, the number of ducts in the nipple and the number of ducts sharing an ostium near the tip of the nipple were measured from the volume set of XDFI-CT. Finally, the 3D distribution pattern of the ducts was determined.


XDFI-CT can provide images almost equivalent to those of low-magnification light microscopy of conventional hematoxylin–eosin-stained histological sections. The mean number of ducts in all cases was 28.0. The total number of ducts sharing an ostium near the tip of the nipple was 525 of 1428. The 3D distribution patterns of the ducts were classified into three types that we defined as convergent (22%), straight (39%), or divergent (39%).


XDFI-CT is useful for exploring the microanatomy of the human nipple and might be used for non-invasive nipple diagnosis in the future.

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Data availability

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.


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The Si crystal with the imaging optics was manufactured at the Photon Factory Crystal Optics Processing Laboratory within KEK, Tsukuba, Japan by Dr. H. Sugiyama and Mr. T. Sasaya. The X-ray cameras for the XDFI-CT system were borrowed from Dr. K. Hirano and Dr. K. Hyodo. The experiments were performed as part of four research projects (2008S2002, 2016G0625, 2012G562, and 2015G597) funded by the KEK. This research was partially supported by a Grant-in-Aid for Scientific Research (grant numbers 16K01369, 16K08654, 22591353, 15H01129, 26286079, and 18K13765) from the Japanese Ministry of Education, Culture, Sports, Science and Technology.

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Authors and Affiliations



NS, DS, RO, AW, and KN obtained the duct positions from the CT data. NS performed the subjective classification of the duct structure. NS developed the mathematical method to classify the types of 3D duct structures. SI and RN prepared all nipple samples used in this research. NS reconstructed the CT images of all samples. SI prepared the histological sections of each nipple sample. NS wrote the main text of the manuscript, and SI, SD, RN, TY, and MA reviewed the manuscript.

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Correspondence to Naoki Sunaguchi.

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The authors declare that they have no conflict of interest.

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All procedures used in this research were approved by the Ethical Committee of Nagoya University and Nagoya Medical Center.

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With regard to the appropriate procedure for collecting data from existing tissue samples, we adopted an opt-out system instead of informed consent. Our website and bulletin boards announced that we were collecting data from existing tissue samples for scientific research in the present study. The patients’ personal information is protected, but the data will be used automatically unless the patients actively dissent.

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Sunaguchi, N., Shimao, D., Yuasa, T. et al. Three-dimensional microanatomy of human nipple visualized by X-ray dark-field computed tomography. Breast Cancer Res Treat 180, 397–405 (2020).

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