Laparoscopic optical coherence tomography imaging of human ovarian cancer
Introduction
Ovarian cancer is the most lethal of all gynecological cancer, partially attributed to a lack of distinctive early symptom manifestation and screening tests with adequate resolution and specificity. As a result, ovarian cancer is often diagnosed at advanced stages, after invasion of adjacent structures or metastasis to a distant site. Women with regional and distant disease have a 5-year survival rate of 71% and 30% (at best), respectively. If diagnosed at the localized stage, the 5-year survival rate is 92%; however, only about 19% of all cases are detected at this stage, typically identified incidentally during another medical procedure [1].
Currently, routine screening for asymptomatic women without an elevated risk for ovarian cancer is not recommended because screening tests with sufficient resolution are not available to date; the pelvic exam is the sole avenue for detection for women of average risk, occasionally aiding in the identification of disease which has often progressed to the more advanced stages. In women at high risk of ovarian cancer based on their personal or family history of other cancers, screening includes a combination of the pelvic exam, transvaginal ultrasound, and blood tests for tumor marker CA125 [1]. However, the sensitivity and specificity of these screening tools even in combination have been described as insufficient [2], [3], [4], [5], [6].
Ovarian neoplasms are classified based on their origination from surface epithelium, germ cell, or stromal tissue, with the vast majority of malignant neoplasms arising from the epithelium [7]. The current hypothesis in epithelial ovarian cancer pathogenesis is that ovarian neoplasms can be divided into two types [8]. Type I neoplasms (including low-grade micropapillary serous carcinoma, mucinous, endometrioid, and clear cell carcinomas) consist of slow growing neoplasms often confined to the ovary at diagnosis and develop from well-established precursor lesions. Type II neoplasms are aggressive, rapidly growing neoplasms thought to arise from surface epithelium or subsurface epithelial inclusion cysts, including high-grade serous carcinoma [8]. Conventional white light laparoscopy allows for the identification of larger surface abnormalities, but does not provide subsurface information and thus may not be capable of visualizing the earlier stages of Type II neoplasms. The ability to visualize lesions not grossly visible and/or subsurface lesions either laparoscopically or transvaginally may potentially improve diagnostic capabilities for these more aggressive Type II lesions.
Optical coherence tomography is a recently emerging non-destructive imaging technology, using a near-infrared broad-bandwidth light source to achieve subsurface imaging with high axial resolution (10–20 μm) at imaging depths up to 2 mm. Contrast is generated from light backscattered at index of refraction mismatches to create high-resolution cross-sectional images without requiring application of exogenous dyes. OCT can be adapted for fiber based endoscopic applications with relative ease, including miniaturization for small diameter applications, and has been evaluated in a wide array of in vivo applications, including human eye [9], [10], gastrointestinal tract [11], [12], and coronary artery [13], [14].
OCT has also been used to study the structural features of gynecological tissues, including ex vivo ovary [15], [16], [17], in vivo ovary during laparoscopy [18], and endometrium and uterine cervix [16], [18], [19], [20], [21], [22], [23], [24]. Previously, we studied ex vivo OCT imaging in normal and diseased human ovary and found OCT capable of resolving tissue level changes, including inclusion cysts, endometrial implants, and superficial tumor masses. Changes in stromal organization and directionality of collagen fibers thought to be associated with malignancy were suggested in several of the images of cancer. Areas of necrosis and blood vessels were also visualized, which were indicative of an underlying abnormality in the tissue [17].
We recently developed the first custom laparoscopic OCT device fabricated specifically for laparoscopic procedures. In this study, we utilized laparoscopic OCT to image the ovaries of patients undergoing oophorectomy to determine the feasibility and safety of laparoscopic OCT imaging and evaluate the tissue microstructural features of ovarian tissue in vivo.
Section snippets
Patients
Patients undergoing exploratory laparotomy or transabdominal endoscopy and oophorectomy at University Medical Center in Tucson, AZ were asked to participate in this in vivo imaging study. Patients were excluded from the study if they were under 18 years of age or pregnant. The study was approved by the Institutional Review Board of the University of Arizona and informed consent was obtained from each patient who participated.
Laparoscopic OCT
The OCT system uses a superluminescent diode light source with a
Results
Thirty ovaries of seventeen patients (ages: 39–85 years, average age: 60.7 years) were imaged with laparoscopic OCT successfully during laparoscopy or laparotomy without any known complications. In four patients, only unilateral ovarian imaging was performed at the surgeon's discretion. Images from both ovaries of one patient were removed from analysis due to imaging artifacts precluding analysis of the data. Of the remaining twenty-eight ovaries, sixteen were diagnosed as normal (Figs. 2a–b),
Discussion
Laparoscopy provides a method of external visualization of the ovaries, but is limited to surface topography. OCT provides cross-sectional, depth-resolved information, providing the ability to interrogate tissues with micrometer-scale resolution without destruction or required excision of the tissue. We present the development of the first OCT probe fabricated specifically for laparoscopic procedures. The successful implementation of laparoscopic OCT for in vivo human ovarian imaging
Conflict of interest statement
The authors declare that there are no conflicts of interest.
Acknowledgments
The authors would like to thank Dr. Urs Utzinger for his contributions to this study.
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