Macroscopic-imaging technique for subsurface quantification of near-infrared markers during surgery

Abstract

Obtaining accurate quantitative information on the concentration and distribution of fluorescent markers lying at a depth below the surface of optically turbid media, such as tissue, is a significant challenge. Here, we introduce a fluorescence reconstruction technique based on a diffusion light transport model that can be used during surgery, including guiding resection of brain tumors, for depth-resolved quantitative imaging of near-infrared fluorescent markers. Hyperspectral fluorescence images are used to compute a topographic map of the fluorophore distribution, which yields structural and optical constraints for a three-dimensional subsequent hyperspectral diffuse fluorescence reconstruction algorithm. Using the model fluorophore Alexa Fluor 647 and brain-like tissue phantoms, the technique yielded estimates of fluorophore concentration within ±25% of the true value to depths of 5 to 9 mm, depending on the concentration. The approach is practical for integration into a neurosurgical fluorescence microscope and has potential to further extend fluorescence-guided resection using objective and quantified metrics of the presence of residual tumor tissue.

Intraoperative Fluorescence Imaging for Personalized Brain Tumor Resection: Current State and Future Directions

“…Wide-field, fluorescence-guided surgery limitations include ( 184 ) ambiguity at the margins where fluorescence intensity decays and difficulty of visualization on the sides of a resection cavity and shaded areas in the surgical wound. Further limitations include fluorescence absorbance by blood and tissue layers ( 197 ), insufficient fluorescence intensity in >95% of low-grade gliomas ( 107 , 198 , 199 ), and lack of quantitative assessment of fluorescence intensity. In PpIX fluorescence visualization, PpIX is quantitatively related at the microscopic level to increasing malignancy in both low- and high-grade gliomas ( 117 ).…”

Red-light excitation of protoporphyrin IX fluorescence for subsurface tumor detection

“…Previous studies exploring the ability of red-light–excited fluorescence to detect subsurface PpIX in tissue-simulation phantoms have demonstrated PpIX detection at depths of up to 5 mm, with either a fiber optic point-spectroscopy probe or a wide-field imaging system. 4,10 Fluorophore visualization at such a depth may well have practical benefit, countering the common obscuration of parts of the resection surface by blood or necrotic tissue. Strategies, instrumentation, and algorithms capable of assessing the depth and quantity of subsurface fluorophore are under development.…”

Depth-Resolved Multispectral Sub-Surface Imaging Using Multifunctional Upconversion Phosphors with Paramagnetic Properties

“…It has been demonstrated that this model can be used not only in pointlike fluorescence depth estimation but also in topographic mapping of subsurface fluorescence depth. 23 This depth retrieval technique requires reduced scattering and absorption coefficients of the tissue to be known a priori. Table 1 demonstrates optical properties of chicken breast tissue for two different wavelengths.…”

“…Interestingly, eq is of the linear form, in which the logarithm of fluorescence ratio at two wavelengths linearly depends on the depth of fluorescent source under the tissue. It has been demonstrated that this model can be used not only in pointlike fluorescence depth estimation but also in topographic mapping of subsurface fluorescence depth . This depth retrieval technique requires reduced scattering and absorption coefficients of the tissue to be known a priori.…”