Above is a VR-SIM image of prostate biopsy containing high-grade prostatic intraepithelial neoplasia (PIN). 205.5 megapixel raw image collected in 24.5 seconds, covering 82.81 millimeter square
Research in our laboratory focuses on the application and clinical translation of quantitative optical spectroscopy and imaging tools for the improvement of cancer management. We develop translatable optical methods to directly address gaps in clinical care, and carry those through to clinical validation in humans alongside our interdisciplinary collaborators. A major theme in this work is the use of novel imaging devices (and computational analysis tools) to improve patient outcomes in surgical tumor removal in organs such as the breast, prostate, and kidney. We also develop tools and strategies using optics to answer interesting biological questions in cell and animal models. To achieve these goals, we leverage new and existing technologies across multiple spatial scales such as quantitative diffuse reflectance spectroscopy and imaging (DRS, DRI), fluorescence lifetime imaging, structured-illumination microscopy (SIM), and light sheet microscopy (LSM).
RAPID POINT-OF-PROCEDURE MICROSCOPY OF DIAGNOSTIC BIOPSY
VR-SIM image of prostate biopsy containing adenocarcinoma. 134.2 megapixel raw image collected in 16 seconds, covering 54.08 millimeter square.
Diagnostic biopsy of organs such as the prostate is hindered by the inability to locate the lesion of interest using existing image guidance tools, and as a result cancer is often missed at the initial biopsy procedure, necessitating additional painful and expensive procedures and delaying treatment. We have developed video-rate structured illumination microscopy (VR-SIM) as a practical means to obtain high-resolution optically-sectioned mosaic images of fresh biopsies within seconds of removal, in time to enable a pathologist to quickly assess the tumor content of the biopsies in time to collect additional biopsies if necessary.
INTRAOPERATIVE MICROSCOPY OF ENTIRE TUMOR RESECTION MARGINS
Surgical removal of the tumor is the first and best treatment option for non-metastatic cancers. However, in many organ sites such as the prostate, breast, and kidney, it is challenging to determine the completeness of tumor removal during the first operation, due to lack of available intra-operative technologies to assist surgeons and pathologists in detection of residual tumor. We are developing ultra-high-throughput practical optical sectioning microscopy (VR-SIM) using fluorescence contrast to meet the clinical requirements for intra-operative assessment of tumor margins. We are validating this approach in IRB-approved clinical studies at Tulane University for prostate and kidney removal. Our mission is to help patients avoid unnecessary repeat surgeries or radiation therapy, and reduce worries about recurrent tumors.
DIGITAL FLUORESCENCE HISTOLOGY FOR EX VIVO MICROSCOPY
Comparison of a 10μm frozen prostate tissue section stained with H&E (A&C) and our novel dual-color fluroescent stain (B & D). A & C are traditional H&E collected with brightfield microscopy, whereas B & D are images collected with fluorescence microscopy and digitally recolored to simulate the appearance of H&E. C and D are zooms of the boxed areas in A and B, respectively.
Hematoxylin and eosin (H&E) staining is the gold standard by which pathologists evaluate tissue sections for diagnosis. Simple single color topical fluorescent stains have shown value for ex vivo optical sectioning microscopy of fresh tissues, but the staining mechanisms do not accurately recapitulate gold-standard H&E stains, which may hinder adoption by pathologists. We are developing dual-color staining strategies that accurately mimic H&E histology – allowing pseudo-H&E “sections” of intact fresh tissues to be obtained rapidly at the point-of-care, without lengthy tissue sectioning and staining steps.
LIGHT SHEET FLUORESCENCE MICROSCOPY