Abstract
Mapping the optical absorption and scattering properties of tissues using spatial frequency-domain imaging (SFDI) enhances quantitative fluorescence imaging of protoporphyrin IX (PpIX) in gliomas in the preclinical setting. The feasibility of using SFDI in the operating room was investigated here. A benchtop SFDI system was modified to mount directly to a commercial operating microscope. A digital light processing module imposed a selectable spatial light pattern from a broad-band xenon arc lamp to illuminate the surgical field. White light excitation and a liquid crystal-tunable filter allowed the diffuse reflectance images to be recorded at discrete wavelengths from 450 to 720nm on a sCMOS camera. The performance was first tested in tissue-simulating phantoms, and data were then acquired intraoperatively during brain tumor resection surgery. The optical absorption and transport scattering coefficients could be estimated with average errors of 3.2% and 4.5% for the benchtop and clinical systems, respectively, with spatial resolution of better than 0.7mm. These findings suggest that SFDI can be implemented in a clinically relevant configuration to achieve accurate mapping of the optical properties in the surgical field that can then be applied to achieve quantitative imaging of the fluorophore.
Highlights
Due to their infiltrative nature, primary brain tumors, even lowgrade cancers, often progress rapidly and present with poor prognosis
The US Food and Drug Administration (FDA) recently approved fluorescence guidance with ALA-PpIX (5-aminolevulinic acid that leads to selective endogenous synthesis of the fluorescent photosensitizer protoporphyrin IX) for human use in high-grade glioma resection
8 We have previously shown that quantification of ALA-PpIX fluorescence, i.e., determination of the absolute concentration of PpIX in the tissue, over a wide field yields diagnostic information about the surgical bed that extends beyond visual fluorescence for guiding brain tumor resection by detecting unresected tumor tissue that is not otherwise visible.[9,10]
Summary
Due to their infiltrative nature, primary brain tumors, even lowgrade cancers, often progress rapidly and present with poor prognosis. Completeness of resection in combination with preservation of maximal neurocognitive function has been shown to coincide with increased survival and better quality of life.[1,2] While standard of care involves coregistration of preoperative magnetic resonance imaging (MRI) for navigational guidance, fluorescence techniques are being widely adopted[3,4] for intraoperative guidance, as brain shift can cause deviation from the preoperative MRI.[5] Fluorescence imaging is useful for interrogating biological tissues as it provides information on underlying microstructure that can be obtained through a variety of optical imaging modalities.[6,7] the US Food and Drug Administration (FDA) recently approved fluorescence guidance with ALA-PpIX (5-aminolevulinic acid that leads to selective endogenous synthesis of the fluorescent photosensitizer protoporphyrin IX) for human use in high-grade glioma resection. Fluorescence imaging is useful for interrogating biological tissues as it provides information on underlying microstructure that can be obtained through a variety of optical imaging modalities.[6,7] the US Food and Drug Administration (FDA) recently approved fluorescence guidance with ALA-PpIX (5-aminolevulinic acid that leads to selective endogenous synthesis of the fluorescent photosensitizer protoporphyrin IX) for human use in high-grade glioma resection. 8 We have previously shown that quantification of ALA-PpIX fluorescence, i.e., determination of the absolute concentration of PpIX in the tissue, over a wide field (up to ∼5 cm) yields diagnostic information about the surgical bed that extends beyond visual fluorescence for guiding brain tumor resection by detecting unresected tumor tissue that is not otherwise visible.[9,10] by comparing fluorescence signals measured at two wavelengths within the emission spectra of PpIX, we developed a technique to estimate the depth of the fluorescence emissions as well as to distinguish between
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