Real-time histopathology for intra-operative tumor margin delineation

Period of Performance: 05/01/2017 - 04/30/2018

$281K

Phase 2 SBIR

Recipient Firm

Invenio Imaging Inc.
SANTA CLARA, CA 95051
Principal Investigator
Principal Investigator

Abstract

? DESCRIPTION (provided by applicant): Surgical resection is the cornerstone treatment for the majority of the 20,000 primary brain tumors and 250,000 brain metastases diagnosed each year in the US. Extent of resection is an important prognostic factor, as most tumor recurrence is in or near the resection cavity. Unfortunately, safely maximizing the extent of resection remains a challenge, in part due to the difficulty of differentiating tumor from normal brain tissue. Consequently, suboptimal surgical outcomes are common for brain tumor patients. A recent study showed that among patients with safely resectable tumors, complete resection was achieved in only 23.5% of patients. Stimulated Raman Scattering (SRS) microscopy, co-developed by the technical Co-PI Dr. Freudiger, allows label- free imaging of biological tissues based on the intrinsic vibrational spectroscopy of their molecular components (Science 322, 1857 (2008)). In collaboration with clinical Co-PI Dr. Orringer we recently demonstrated SRS microscopy enables rapid histology with image quality and diagnostic accuracy comparable to gold-standard H&E staining but without the time delay caused by tissue sectioning and dye staining (Science Translational Medicine 5, 201 (2013)). Compared to other techniques under investigation, SRS produces the best image quality, and, consequently the highest sensitivity and specificity for detecting tumor infiltration. The overall goal for this Phase 2 grant is to develop the first FDA cleared clinical SRS instrument, based on the validated prototype incorporating our custom fiber-laser. This innovation will lead to the introduction of a novel technology to improve the safety and accuracy of brain tumor surgery. Specifically, we will establish quality systems for design and assembly according to federal regulations (21CRF820). We will then design the clinical SRS instrument to overcome the limitations of the prototype, i.e. improve the imaging speed for multi-color mosaic imaging, automate the sample loading scheme, modify the form factor, include design controls for compliance with electrical and laser safety standards, develop a simple graphical user interface, and develop a sterile consumable. We will work with an independent test laboratory to demonstrate safety according to the IEC60601 standard for medical devices and the IEC60825 standard for laser products. The clinical Co-PI will validate the effectiveness by performing a blind-read study comparing SRS imaging to the gold- standard H&E histopathology. Biocompatibility of the consumable will be demonstrated by compliance with ISO10993. As the final goal, we will work with an experienced regulatory consultant to obtain FDA clearance for the product.