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To evaluate the effects of PFA on tissue fluorescence, we imaged brain tissue samples using MSFI from two cohorts of mice: the SOX10 Cre; R26R-Brainbow 2.1/Confetti mice (expressing four exogenous fluorophores), and wild type Cre-negative controls. Specimens from each were immersed in 10 ml of PFA or phosphate buffer saline (PBS) as a control. The fluorescence intensity was captured using MFSI every 15 minutes over three hours. Analysis was performed on the resulting images to produce quantitative metrics of the resulting fluorescence signal. The results show that exogenous fluorophores are dramatically quenched within the first half hour when fixed in PFA, whereas endogenous fluorescence increased slightly in the same time period. These results are valuable to understand how fixation can influence fluorescence properties and can inform optimal fixation protocols.
Gastrinomas are gastrin-producing neuroendocrine tumors (NETs) located in the gastroenteropancreatic system. Gastrinomas are often small, multifocal, and found at late stages. Their unpredictable behavior and metastatic potential make it extremely challenging to develop therapeutic strategies. Surgery is the only potentially curative treatment for gastrinoma, but current tumor localization techniques such as intraoperative ultrasound and manual palpitation have poor sensitivity for small tumors, resulting in higher rates of recurrence and metastasis. Therefore, there is a strong clinical need for developing advanced intraoperative imaging technologies for tumor localization in treating gastrinoma. Polarized light imaging (PLI) is a promising method for label-free tissue characterization due to its sensitivity to micro and nanoscale structures, which are often influenced with the onset of cancer, but no works have yet investigated the application of PLI for gastrinoma localization.
To assess the suitability of PLI for gastrinoma localization, we imaged 11 formalin-fixed paraffin embedded (FFPE) specimens of gastrinoma using a five-wavelength Mueller Matrix Polarization Microscope. The Lu-Chipman decomposition was applied to spatial maps of the sixteen Mueller matrix parameters. Values for depolarization, diattenuation, and retardance were compared for regions of interest corresponding to tumor and adjacent tissues. There was significant difference between the average depolarization of the Brunner’s gland and tumors when imaged with light at 442, 543, and 632 nm (p<0.05), and the average diattenuation values of the two at 405 nm (p<0.05), suggesting that these properties could be used for label-free localization. These results motivate further study of the use of PLI for NET localization. Future steps include broadening the sample pool to other NETs and validating results in fresh tissue studies.
Mouse models are essential tools for understanding cancer growth and accelerating the development of therapeutic and diagnostic technologies. Xenografts, generated by implanting tumor cells directly into mice through injection, are frequently used to study cancer biology and therapeutics. In these models, assessment of tumor growth and development is necessary to support the study of disease progression and model validation. Unfortunately, such measurements often require sacrificing the animal to create organ explants or tissue cultures, resulting in increased animal use and hampering longitudinal measurements of individual tumors. A tool enabling in vivo tumor monitoring for xenograft models could improve the efficiency of these animal models and provide more robust growth measurements through true longitudinal measurement.
One method of optical tumor assessment involves tagging biomolecules of interest with fluorescent species to enable detection with minimally invasive fluorescence imaging, implemented endoscopically or laparoscopically. However, utilizing fluorescence imaging in vivo in murine models poses challenges due to both tortuous anatomy and small gastrointestinal lumen caliber.
This work reports a miniature fluorescence imaging probe equipped with a multiband filter and biopsy device to image and sample fluorescently-tagged, xenografted tumors as they develop in mouse models. We present the design and characterization of the device and report measurements of the modulation transfer function and ex vivo imaging performance, demonstrating its promise as a valuable research tool to advance cancer research in xenograft models, enabling the development of imaging biomarkers for cancer detection in a clinical setting without the need for exogenous contrast.
Phase and polarization of coherent light are highly perturbed by interaction with microstructural changes in premalignant tissue, holding promise for label-free detection of early tumors in endoscopically accessible tissues such as the gastrointestinal tract. Flexible optical multicore fiber (MCF) bundles used in conventional diagnostic endoscopy and endomicroscopy scramble phase and polarization, restricting clinicians instead to low-contrast amplitude-only imaging. We apply a transmission matrix characterization approach to produce full-field
Ovarian cancer is the deadliest gynecologic cancer due predominantly to late diagnosis. Early detection of ovarian cancer can increase 5-year survival rates from 40% up to 92%, yet no reliable early detection techniques exist. Multiphoton microscopy (MPM) is a relatively new imaging technique sensitive to endogenous fluorophores, which has tremendous potential for clinical diagnosis, though it is limited in its application to the ovaries. Wide-field fluorescence imaging (WFI) has been proposed as a complementary technique to MPM, as it offers high-resolution imagery of the entire organ and can be tailored to target specific biomarkers that are not captured by MPM imaging. We applied texture analysis to MPM images of a mouse model of ovarian cancer. We also conducted WFI targeting the folate receptor and matrix metalloproteinases. We find that texture analysis of MPM images of the ovary can differentiate between genotypes, which is a proxy for disease, with high statistical significance (
While MPM has shown favorable results in a research environment, it has not yet found broad success in a clinical setting. One major obstacle is the quantitative analysis of the image content. Recently, the application of texture analysis to MPM images has shown success for characterizing the collagen content of the tissue, making it a prime candidate for disease screening. Unfortunately, existing work is limited in its application to ovarian tissue and few texture analysis approaches have been evaluated in this context.
To address these challenges, we applied texture analysis to second harmonic generation (SHG) and two-photon excited fluorescence (TPEF) images of a mouse model (TgMISIIR-TAg) of ovarian cancer. Using features from the grey-level co-occurrence matrix, we find that texture analysis of TPEF images of the ovary can differentiate between genotype with high statistical significance (p<0.001), whereas TPEF and SHG images of the oviducts (fallopian tubes) are most sensitive to age, and SHG images of the ovaries are most sensitive to reproductive status. While these results suggest that texture analysis is suitable for characterizing ovarian tissue health, further work is focused on developing a classification algorithm based on these features, and also to couple the results with a histopathological analysis.
Wide-field phase imaging for the endoscopic detection of dysplasia and early-stage esophageal cancer
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