PhD Thesis Defense: Jaime Bravo

Thursday, May 17, 2018, 11:00am–1:00pm

Auditorium H, Williamson Translational Research Building, DHMC

“Intraoperative Fluorescence Quantification to Enhance Contrast During Fluorescence-Guided Neurosurgery”


Fluorescence-guided surgery (FGS) is a technique for providing intraoperative contrast to aid in localizing tumor. FGS has demonstrated potential in neurosurgery, which suffers from low normal tissue to tumor contrast, by showing beneficial diagnostic value for high-grade gliomas, meningiomas, and metastases. Of the available methods to achieve this contrast 5-aminolevulinic acid (ALA) mediated protoporphyrin IX (PpIX) FGS has shown the most promise with its high tumor specificity and recent approval by the U.S. Food & Drug Administration (ALA had already received approval in Europe). Fluorescein sodium (FS) has been used as an alternative to ALA due to its low cost and higher excitation (485 nm), allowing for a more natural looking field under filtered illumination, but sacrifices tumor specificity.

Current clinical methods of FGS rely on raw fluorescence emissions, which are known to contain contributions from other sources (e.g. background autofluorescence and photoproducts). Additionally, tissue optical properties, namely absorption and scattering, are capable of substantially distorting measured/perceived fluorescence limiting the surgeon to qualitative assessment of visual fluorescence. We utilized spectral processing methods based on coupled measurements of reflectance and fluorescence to decouple target fluorescence from the background and correct for optical property based attenuation. This thesis focuses on modifications made to our spectral processing methods to improve accuracy and adapt to new challenges experienced in the clinical arena. We demonstrated increased accuracy in estimation of tissue optical properties from reflectance in the presence FS, a small Stokes' shift fluorophore, and developed a novel subdiffuse reflectance model well suited for probes with small fiber optics. For fluorescence, we defined a confidence interval based approach for filtering wide-field maps of quantitative fluorescence and generated the first optical property corrected estimates of FS. Further, new challenges stemming from spectral anomalies observed clinically were addressed, potentially paving the way for novel clinical insights. 

The work presented here serves to further improve quantitative techniques by developing more accurate models of light transport, accounting for unexpected spectral distortions, improving the visualization of target biomarkers, and expanding to cover multiple fluorophores, including the first optical property correction for FS.

Thesis Committee

For more information, contact Daryl Laware at