Multispectral fluorescence imaging of human ovarian and Fallopian tube tissue for early stage cancer detection

Abstract

With early detection, five year survival rates for ovarian cancer are over 90%, yet no effective early screening method exists. Emerging consensus suggests that perhaps over 50% of the most lethal form of the disease, high grade serous ovarian cancer, originates in the Fallopian tube. Cancer changes molecular concentrations of various endogenous fluorophores. Using specific excitation wavelengths and emissions bands on a Multispectral Fluorescence Imaging (MFI) system, spatial and spectral data over a wide field of view can be collected from endogenous fluorophores. Wavelength specific reflectance images provide additional information to normalize for tissue geometry and blood absorption. Ratiometric combination of the images may create high contrast between neighboring normal and abnormal tissue. Twenty-six women undergoing oophorectomy or debulking surgery consented the use of surgical discard tissue samples for MFI imaging. Forty-nine pieces of ovarian tissue and thirty-two pieces of Fallopian tube tissue were collected and imaged with excitation wavelengths between 280 nm and 550 nm. After imaging, each tissue sample was fixed, sectioned and H&E stained for pathological evaluation. Comparison of mean intensity values between normal, benign, and cancerous tissue demonstrate a general trend of increased fluorescence of benign tissue and decreased fluorescence of cancerous tissue when compared to normal tissue. The predictive capabilities of the mean intensity measurements are tested using multinomial logistic regression and quadratic discriminant analysis. Adaption of the system for in vivo Fallopian tube and ovary endoscopic imaging is possible and is briefly described.

Intraoperative multispectral and hyperspectral label‐free imaging: A systematic review of in vivo clinical studies

“…The second clinical focus of using intraoperative HSI has been to guide tumour resection. The feasibility of using HSI as a diagnostic technique for cancer has been comprehensively evaluated in multiple preclinical animal models and several recent studies have also demonstrated its use in assessing tumour margins in ex vivo tissue in the operating room . Fewer studies have reported the in vivo use of HSI during surgery but several groups have used HSI to highlight subtle changes in exogenous fluorescence .…”

“…The ability to quantitatively measure oxygenation levels in tissue has been tested in various pathologies and clinical contexts, including; peripheral vascular disease , retinal eye disease , diabetic foot disease and wound healing . Numerous groups have also published work demonstrating the effectiveness of using HSI for cancer detection . With the development of high‐resolution and fast frame rate multispectral and HSI cameras, enabling the capture of a rich imaging dataset at a video rate, these imaging methods offer great potential for real‐time non‐invasive tissue characterization and surgical guidance .…”

Sub-millimeter endoscope demonstrates feasibility of in vivo reflectance imaging, fluorescence imaging, and cell collection in the fallopian tubes

“… 22 , 24 , 25 Therefore, the optical (reflectance and autofluorescence) signature of STIC lesions is expected to be altered. 22 , 27 Changes in the abundance and accessibility of cell surface receptors and extracellular proteins also occur in STIC and subsequent ovarian cancer, including folate receptors and laminin-C1 proteins, which may be targeted with fluorescence-tagged ligands. 28 , 29 STIC lesions are also characterized by unique cellular and molecular features, and thus could be identified with the use of various cytological or omics analyses.…”

“… 30 Optical imaging is a relatively inexpensive, non-ionizing alternative to whole-body imaging and ultrasound that can detect either endogenous changes in reflectance and autofluorescence or the presence of contrast agents and fluorophores targeted to disease-related biomarkers. 22 , 27 , 28 , 31 – 33 An optical system using reflectance and fluorescence imaging achieved high sensitivity, specificity, and negative predictive value for the detection of clinically occult and cancer-related lesions within ex vivo fallopian tube tissue. However, it had high false-positive rates and therefore low PPV.…”

Fluorescence and Multiphoton Imaging for Tissue Characterization of a Model of Postmenopausal Ovarian Cancer

“…Optical imaging techniques that have shown promise for detection of ovarian cancer include fluorescence imaging [5], multispectral imaging [6], confocal imaging [7], MPM [8,9], photoacoustic imaging (PAI) [10], and optical coherence tomography (OCT) [11], among others. Reflectance and fluorescence spectroscopy can differentiate normal and neoplastic ovarian tissue but typically has poor resolution [12]. OCT visualizes details of tissue microstructure such as surface epithelium, follicles, cysts, collagen bundles, and vessels as well as potentially abnormal changes such as invaginations and changes in tissue density, but has inadequate resolution for cellular changes [13,14].…”