Phase I Amount
$1,218,888
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.
Public Health Relevance Statement: Public Health Relevance: Brain surgery is the cornerstone for the treatment of most of 20,000 primary brain tumors and many of the 250,000 brain metastases diagnosed in the US each year. Survival and quality of life depend strongly on the extent of tumor resection, but brain surgeons tend to err on the side of lesser resection to avoid neurologic deficits, leaving some tumor behind, because tumor is not readily distinguished from uninvolved tissue by the bare eye. This proposal aims to develop a novel microscope and an associated consumable that together will allow brain surgeons to accurately access the completeness of resection in real-time during brain surgery and, if successful, will improve survival and quality of life for patient with this devastating disease.
Project Terms: Area; base; Biological; biomaterial compatibility; Biopsy; Biopsy Specimen; blind; Brain; Brain Neoplasms; brain surgery; brain tissue; brain tumor resection; Characteristics; Clinical; Collaborations; Color; Custom; Data; design; Development; Devices; Diagnosis; diagnostic accuracy; Disease; Dyes; Effectiveness; Engineering; Excision; experience; Eye; Feedback; Fiber; Glioma; Goals; Gold; Grant; graphical user interface; Head; Hematoxylin and Eosin Staining Method; Histology; Histopathology; Image; Imaging Device; imaging system; improved; Infiltration; innovation; instrument; Investigation; Label; Laboratories; Lasers; Lead; Left; Medical; Medical Device; meetings; Metastatic malignant neoplasm to brain; Microscope; Microscopic; microscopic imaging; Microscopy; Molecular; Neurologic Deficit; new technology; novel; Operative Surgical Procedures; Outcome; Patients; Phase; Preparation; Primary Brain Neoplasms; Process; Prognostic Factor; prototype; public health relevance; Quality of life; Reading; Recurrence; Regulation; Resectable; Resolution; Safety; Sampling; Scheme; Science; Sensitivity and Specificity; Side; Silicon; Slide; Specimen; Spectrum Analysis; Speed; Staining method; Stains; Sterility; Suction; Surgeon; Surgically-Created Resection Cavity; System; Techniques; Testing; Time; Tissue imaging; Tissues; translational medicine; Translations; tumor; Validation; Work
