Imaging of the Ovary

Abstract

Epithelial ovarian cancer has the highest mortality rate among the gynecologic cancers and spreads beyond the ovary in 90% of the women diagnosed with ovarian cancer. Detection before the disease has spread beyond the ovary would significantly improve the survival from ovarian cancer, which is currently only 30% over 5 years, despite extensive efforts to improve the survival. This study describes initial investigation of the use of optical technologies to improve the outcome for this disease by detecting cancers at an earlier and more treatable stage. Women undergoing oophorectomy were recruited for this study. Ovaries were harvested for fluorescence spectroscopy, confocal microscopy, and optical coherence tomography. Fluorescence spectroscopy showed large diagnostic differences between normal and abnormal tissue at 270 and 340 nm excitation. Optical coherence tomography was able to image up to 2mm deep into the ovary with particular patterns of backscattered intensity observed in normal versus abnormal tissue. Fluorescence confocal microscopy was able to visualize sub-cellular structures of the surface epithelium and underlying cell layers.Optical imaging and/or spectroscopy has the potential to improve the diagnostic capability in the ovary, but extended systematic investigations are needed to identify the unique signatures of disease. The combination of optical technologies supported by modern molecular biology may lead to an instrument that can accurately detect early carcinogenesis.Key word: Ovarian cancer imaging. IntroductionOvarian cancer goes undetected in both developed and developing countries because adequate technology does not exist to detect preinvasive or early stage disease. There are approximately 25,600 new cases of ovarian cancer in the United States per year, and an estimated 16,000 deaths from ovarian cancer in 2004 (1, 2). Although ovarian cancer accounts for only 4% of all new cancer cases, it is the fifth leading cause of cancer-related mortality in women, and the leading cause of death from gynecologic malignancies (3). High prevalence of late-stage disease and the poor prognosis associated with these later stages are the major factors that give ovarian cancer patients such a dismal prognosis. Women with disease localized to the ovary have a 5-year survival of 80-90%, while women with Stage III disease have a 5-year survival of 30% or less. With our current screening and diagnostic abilities, 70% of women will continue to be diagnosed with FIGO Stage III or IV disease (widespread intra-abdominal disease) and the majority of them will die of their disease (3). The conservative cost of treatment for ovarian cancer is estimated at least $15 billion dollars/year (4-6), due primarily to the late stage of diagnosis, the high morbidity associated with treatment, and the high rate of recurrence.Large cancers are easily detected at the time of surgery. However, occult cancers, which are only seen when ovaries are carefully sectioned and cannot be detected by visual assessment at the time of surg...

Confocal laser scanning microscopy of whole mouse ovaries: Excellent morphology, apoptosis detection, and spectroscopy

“…This technical note described a protocol that was useful to observe the morphology of whole ovaries. The existence of cell death marker, LT, may be able to be applied to other studies involving the ovary (44,45).…”

Simultaneous optical coherence tomography and laser induced fluorescence imaging in rat model of ovarian carcinogenesis

“…Optical coherence tomography is an emerging, non-destructive imaging modality using near-infrared light to create cross-sectional images of tissue structure with near histological resolution (2-20 µm) with the advantage of up to 2 mm penetration depth compared to other optical technologies which may only have 100 micron or less penetration. OCT has previously been used in a variety of applications, including human eye, 11,12 gastrointestinal neoplasms, 13,14 and gynecologic neoplasms such as ovary, [15][16][17][18][19] endometrium [18][19][20] and cervix. 18,19,[21][22][23][24][25][26] Prior studies evaluating OCT imaging of human ovarian tissue have shown promising results as a diagnostic tool for ovarian cancer, demonstrating the ability to visualize fine architectural features of both normal ovaries and ovarian malignancies ex vivo [16][17][18] and in vivo via laparoscopic imaging.…”

“…Peak emission intensities from collagen, NADH and FAD are typically seen at emission wavelengths of 390, 450 and 550 nm, respectively. LIF has been studied in multiple pathologies, 27 including gynecologic applications such as human cervical neoplasia, [26][27][28][29][30][31] human ovarian malignancies 16,32 and primate models for ovarian cancer chemopreventative studies. 33,34 Both OCT and LIF have shown promise in ovarian cancer diagnostics independently.…”

“…Comparison of OCT images and histopathology demonstrated that OCT could provide information on the microstructural features of cyclic, acyclic and malignant ovary consistent with features described in previous studies of both rat 35 and human ovary. [15][16][17][18][19] LIF was able to characterize spectral differences in fluorescence emission attributed to collagen, NADH/FAD and hemoglobin absorption among cyclic, acyclic and neoplastic ovaries. These findings support the potential application of OCT-LIF to distinguish a benign from a malignant ovary.…”

“…The successful application of OCT-LIF to a rodent model of ovarian cancer providing preliminary imaging criteria to differentiate cyclic ovaries mimicking pre-menopausal human females, acyclic ovaries mimicking postmenopausal human females, and stromal neoplasms is encouraging and should also be applicable to other types of ovarian tumors as it has been evaluated in previous imaging of human epithelial ovarian carcinoma. 2,16 Future studies will evaluate additional animal models with the intent to develop a model for epithelial ovarian cancer. Additionally, as this was a pilot study, the bilateral ovaries of a single animal were included in a given treatment group despite the fact that only the right ovary was treated with saline or DMBA, unless the ovary was found to be neoplastic, in which case it was assigned to the neoplasm group.…”