| BackgroundEndometriosis, which is estimated to affect6%-10%of women of reproductive age, is usually underdiagnosed and associated with an over-6-year mean latency from onset of symptoms to definitive diagnosis, usually with the requirement of an invasive procedure such as a laparoscopy. Thus, there is an obvious requirement for the development of reliable and sensitive nonsurgical methods, such as new imaging modalities, for the diagnosis of this highly prevalent disease. Photoacoustic tomography (PAT) is one of the fastest growing and exciting noninvasive biomedical imaging technologies, which uniquely combines the absorption contrast of light or radio frequency waves and the acoustic detection. This results in a hybrid imaging system that can produce high-contrast images possessing high spatial resolution. It has been broadly used to study animal and human tissues, providing comprehensive anatomical and functional imaging, even molecular and genetic imaging. This is the first study on endometriosis in PAT, in order to find out the predominant optical absorption for endometriosis and estimate its diagnostic utility..MethodsThe eutopic endometrium from patients with and without endometriosis was collected and transplanted into nude mice by subcutaneous injection to establish the models of endometriosis. Human endometrium in vitro was photoacoustically imaged using multiple wavelengths from720nm to850nm and a wavelength of532nm. Absorption intensity was calculated and the signal-to-noise ratio could be shown in the images. Using the appropriate wavelength found in the in vitro PAT scan, in vivo nude mice models were imaged, and one, two and three-dimensional images were obtained. Statistical analysis was used to assess the sensitivity, specificity and accuracy of PAT on endometriosis. Finally, histopathological evidence was assayed by hematoxylin-eosin-staining and immunohistochemical staining.ResultsEither with or without endometriosis, the eutopic endometrium could be successfully transplanted into the nude mice to establish the models of endometriosis, while the positive rate was38.4%and55.0%respectively, and48.4%overall. During in vitro scanning, the predominant absorption of endometrium was found at the wavelength of532nm, that was ten times the intensity of other wavelengths and high signal-to-noise ratio has been shown in the one-dimensional images. PAT for nude mice models of endometriosis in vivo showed high sensitivity of0.9375(SE=0.0605) and higher specificity of1(SE=O). The Youden index was0.9375(SE=0.0605). Quantitative data on maximum diameter also show great accuracy. Furthermore, simultaneous imaging of the lesions and the surrounding vessels was achieved at532nm. Finally, all the specimens in these experiments were proved to be human endometrium.ConclusionThe nude mouse model of subcutaneous endometriosis is the ideal model for human endometriosis, as it is perfect for the research of understanding its pathogenesis and pathophysiology and the development of sensitive nonsurgical diagnostic assays and effective treatments. At the wavelength of532nm, PAT shows its splendid sensitivity, specificity and accuracy for endometriosis. Simultaneous imaging of the lesions and the surrounding vessels provides an unprecedented opportunity for understanding the interactions between a focus of endometriosis its microenvironment and for noninvasively detecting endometriosis. Not only for nosurgical diagnosis of EM but for endometrium related disseases PAT is a potential and exciting imaging technology. |