Ovarian cancer has the highest mortality of all the gynecologic cancers and the overall survival rate is poor due to the early metastasis prior to the onset of distinctive early symptoms as well as the lack of efficacious screening and diagnostic techniques. In 2002, two landmark studies were published on the benefit of prophylactic oophorectomy (PO), which reduces the risk of ovarian cancer by more than 50% and has become accepted as the standard of care for high risk women [1
]. However, PO has been found in recent years to increase mortality of women undergoing oophorectomy prior to the age of 45 [3
] or even before the age of 55-60 [4
]. Moreover, these high risk women are not candidates for hormone replacement therapy because of their increased risk of breast cancer [3
]. Thus, new intraoperative devices capable of reliably diagnosing ovarian cancer in earlier stages during minimally invasive surgery could minimize the use of PO, and reduce the high mortality of this deadly disease, particularly in high risk women.
Optical coherence tomography (OCT), a high resolution imaging technique [5
], measures back-scattered light generated from an infrared light source directed to the tissues being examined. OCT typically obtains a resolution on the scale of several to tens of microns and a penetration depth of 1-3 mm. OCT has been used to image tissues in the body that can be accessed either directly or via an endoscope or catheter, including eye [6
], coronary blood vessels [9
], and GI tract [11
]. The morphological features of pre-neoplastic or early neoplastic changes have prompted development of this high-resolution imaging modality for early-stage ovarian cancer detection [14
]. OCT is sensitive to changes in collagen that are seen when malignancy develops [17
]. OCT can also detect areas of necrosis that are indicative of an underlying abnormality in the tissue not detected by the surgeon [18
Photoacoustic imaging (PAI) is an emerging biomedical imaging modality that has the advantage of providing optical absorption contrast at ultrasound resolution [19
]. It uses an ultrasound transducer to measure the ultrasonic waves generated from thermoelastic expansion resulting from a transient temperature rise due to the short pulse light absorption of biological tissue. The acquired ultrasonic waves are used to reconstruct the light absorption distribution which directly relates to vasculature of tumors or tumor angiogenesis [21
]. Tumor angiogenesis is a fundamental step in tumor growth and metastasis [21
]. In addition, if two optical wavelengths are used, the measured photoacoustic signals can be used to reconstruct the distribution of tumor oxygenation, which is an important indicator of tumor metabolism and therapeutic response. Pulse-echo ultrasound (US), a conventional imaging modality, can be readily achieved with a PAI system and provides tissue structure information at deeper depth than OCT with resolutions that are scalable with the transducer frequency and bandwidth. Co-registered ultrasound and PAI for non-invasive transvaginal imaging has been investigated for ovarian cancer detection by our group [23
Combining OCT, US and PAI would further provide complementary tissue optical absorption, scattering information, and deep tissue structures. Previously, Yang et al.
developed a photoacoustic endoscopy [24
]; Yin et al.
reported an integrated intravascular OCT and ultrasound imaging probe [25
]; Wang et al.
demonstrated an ultrasound guided spectroscopic intravascular photoacoustic imaging system [27
]; Li et al.
] and Jiao et al.
] both introduced the integrated OCT and photoacoustic microscopy. For the above referenced studies, either one or two imaging modalities were investigated, although some were not suitable for endoscopy applications. This study, to the best of our knowledge, reports the first prototype system that integrates OCT, US and PAI modalities for endoscopy applications. The performance of the system in ovarian tissue characterization has been demonstrated using ex vivo
porcine and human ovaries.