Revealing the uterine blood vessel network via virtual pathology

GRAPHICAL ABSTRACT: [Image: see text] ABSTRACT: BACKGROUND: The distribution of the blood vessel network at any point in time in any body tissue may provide valuable information with regard to the tissue condition, whether it is in a growth, declining or recovery phase as well as giving insights as to its angiogenesis functionality. The blood vessel three-dimensional network of the endometrium goes through a process of change over a relatively short period of 4 weeks on average. It is well accepted that angiogenesis within the endometrium is closely related to the success or failure of the implantation of the embryo. OBJECTIVE AND RATIONALE: Our study aims to present a method to follow the three-dimensional evolution of the superficial blood vessel distribution in the endometrium throughout the uterine cycle. METHOD: This method utilizes differences in the observed broadband colors of the blood vessels in order to assess their depth coordinate below the endometrial tissue surface. We implemented the method using microscopic images of fresh, ex vivo, endometrial samples of different cycle days to obtain the statistical evolution track of the superficial blood vessel population in both human and animal (swine) samples. OUTCOMES: In human samples, we observed a systematic and consistent trend in the blood vessel diameter distribution at different tissue depths. We demonstrate that the magnitude of this trend evolves throughout the course of the female cycle. WIDER IMPLICATIONS: This method has the potential to further our understanding of the mechanisms of angiogenesis in tissues other than the endometrium. We propose that this method may also contribute to more precise endometrial dating and may assist in more accurate determination of embryo transfer timing within in vitro fertilization treatments. LAY SUMMARY: The inner lining tissue of the womb (uterus) is called the endometrium, and it undergoes significant changes during the menstrual cycle. The endometrium blood vessel network goes through rapid changes during the cycle. We have developed a new method to measure this through surface imaging of the endometrium. We use samples of endometrial tissues collected at different dates in the cycle to show how useful this method is in evaluating the development of the endometrium. The method may also be used to investigate different processes of generating new blood vessels and may help to support dating the development of the endometrium. Our work offers a non-invasive or minimally invasive method which reveals the three-dimensional blood vessel network and may be used to help in a variety of diagnoses. For example, this method may be used to see how receptive the uterus is during in vitro fertilization treatment.