Recently, optical spectroscopy has shown considerable promise to be used as a potential clinical tool for human brain
tumor detection and therapeutic guidance. Our group showed for the first time the possibility of using combined
autofluorescence and diffuse reflectance spectroscopy and established its applicability for human brain tumor
demarcation in previous in vitro and in vivo studies. We report in this paper the results of a clinical study designed to
further evaluate the efficacy of the approach for demarcation of brain tumors and tumor margins from normal brain
tissues in intra-operative clinical setting. Using a portable system, optical spectra were collected from the brain of 110
patients undergoing craniotomy at the Vanderbilt University Medical Center. Spectral measurements were taken from
multiple sites of tumor core, tumor margin and normal areas of brain tissues and the resulting spectra were correlated
with the corresponding histopathologic diagnosis. Using histology as the gold standard, a probabilistic multi-class
diagnostic algorithm was developed to simultaneously distinguish tumor core and tumor margin from normal brain tissue
sites using independent training and validation sets of data. An unbiased estimate of the accuracy of the model indicates
that combined autofluorescence and diffuse reflectance spectroscopy was able to distinguish tumor core and tumor
margin from normal brain tissues with an average predictive accuracy of ~88%.
Past studies have demonstrated that combined fluorescence and diffuse reflectance spectroscopy can successfully discriminate between normal, tumor core, and tumor margin tissues in the brain. To achieve efficient surgical resection guidance with optical biopsy, probe-based spectroscopy must be extended to spectral imaging to spatially demarcate the tumor margins. This paper describes the design and testing of a combined fluorescence and diffuse reflectance imaging system which uses liquid-crystal tunable filter technology. Experiments were conducted to quantitatively determine its linearity, field of view, spatial and spectral resolution, and wavelength sensitivity. For functional testing, spectral images were acquired from tissue phantoms, mouse brain in vitro, and rat brain cortex in vivo. The spectral imaging system is characterized by measured intensities which are linear with sample emission intensity and integration time, a one-inch field of view for a seven-inch object distance, spectral resolution which is linear with wavelength, spatial resolution which is pixel-limited, and sensitivity functions which provide a guide for the distribution of total image integration time between wavelengths. Functional testing demonstrated good spatial and spectral constrast between brain tissue types, the capability to acquire adequate fluorescence and diffuse reflectance intensities within a one-minute imaging timeframe, and the importance of hemostasis to acquired signal strengths and imaging speed.
Multiple methodologies exist to implement spectral imaging for tissue demarcation and disease diagnosis. In this paper, benchtop acousto-optic tunable filter (AOTF), liquid-crystal tunable filter (LCTF) and Fourier interferometric spectral imaging systems were quantitatively compared in terms of imaging speed of soft tissue autofluorescence. Optical throughput, image signal-to-noise ratio (SNR), and collagen autofluorescence imaging in chicken breast were assessed. Within this comparison, the Fourier system possessed the largest optical throughput (~50%) relative to the tunable-filter imaging systems; however, its throughput advantage failed to correlate to improved image SNR over the LCTF system. Further, while the autofluorescence imaging capability of the Fourier system exceeded that of the LCTF system for comparable total image integration times, the LCTF is capable of producing equivalent autofluorescence SNR with superior SNR when interrogations at only a few wavelengths are required and the random access filter tuning of the LCTF can be exploited. Therefore, the simple, rugged design and random-access filter-tuning capability of LCTF-based spectral imaging makes it best-suited for clinical development of soft tissue autofluorescence imaging.
The primary treatment for brain tumors with infiltrating margins is surgical resection. However at the present time this method is limited by visual discrimination between normal and neoplastic marginal tissues during surgery. Imaging modalities such as CT, MRI, PET, and optical imaging techniques can accurately localize tumor margins. We hypothesize that coupling the fine resolution of current imaging techniques with the precise cutting of mid-infrared lasers through image-guided neurosurgery has the potential to enhance tumor margin resection. This paper describes a feasibility study designed to optically track in three-dimensional space the articulated arm delivery of a non-contact ablative laser beam.
Infrared-emitting diodes (IRED's) were attached to the handheld probe of an articulated arm to enable optical tracking of the laser beam focus in the operating room. Crosstalk between the infrared laser beam and the tracking diodes was measured. The geometry of the adapted laser probe was characterized to allow tracking the laser beam focus projected in front of the articulated arm. The target localization accuracy was assessed.
Stray laser light did not affect optical tracking accuracy. The mean target registration errors while optically tracking the laser beam focus was 3.16 ∓ 1.04 mm. Analysis of target localization errors indicated that precise optical tracking of a laser beam focus in three-dimensional space is feasible. However, since the projected beam focus is spatially defined relative to the tracking diodes, tracking accuracy is highly sensitive to laser beam delivery geometry and beam trajectory/alignment out of the articulated arm.
Complete infiltrating brain tumor margin resection continually eludes neurosurgeons due to inherent limitations of current margin localization techniques. A need exists for an objective, on-site, real-time imaging system which can accurately localize brain tumor margins and therefore be used as a basis for image-guided surgery. Optical biopsy methods are a proven means for successful brain tissue discrimination, indicating promise for spectral imaging to fill such a need. Before testing spectral imaging for surgical guidance, various spectral imaging modalities must be systematically compared to determine the modality most conducive to the clinical setting. A liquid crystal tunable filter spectral imaging system was characterized for field of view, spatial and spectral resolution, and ability to retain spectral features acquired from a clinical single-pixel spectroscopy system. For a 35-mm diameter field of view, the system possessed a spatial resolution of 50 μm in both image dimensions and a spectral resolution which monotonically increased from 10 to 30 nm over the tuning range of the filter. Differences between imaging and single-pixel spectra for location and FWHM of fluorescence peaks from two fluorescent dye targets were summarily less than 3 nm. However, two remediable artifacts were introduced to imaging system spectra during spectral sensitivity correction.
Surgical resection remains the treatment of choice for brain tumors with infiltrating margins but is limited by visual discrimination between normal and neoplastic marginal tissues during surgery. Imaging modalities such as CT, MRI, PET, and optical biopsy techniques can accurately localize tumor margins. We believe coupling the fine resolution of current imaging techniques with the precise cutting of mid-infrared lasers through image-guided neurosurgery can greatly enhance tumor margin resection. This paper describes a feasibility study designed to optically track in three-dimensional space the articulated arm delivery of a non-contact ablative laser beam. Infrared-emitting diodes were attached to the handheld probe of an articulated arm to enable optical tracking of the laser beam focus in the operating room. Crosstalk between the infrared laser beam and the tracking diodes was measured. The geometry of the adapted laser probe was characterized for tracking a makeshift passive tip and laser beam focus. The target localization accuracies for both probe configurations were assessed. Stray laser light did not affect optical tracking accuracy. The mean target registration errors while optically tracking the laser probe with a passive tip and tracking the laser beam focus were 9.24 ± 5.14 and 3.16 ± 1.04 mm, respectively. Analysis of target localization errors indicated that precise optical tracking of a laser beam focus in three-dimensional space is feasible. However, since the projected beam focus is spatially defined relative to the tracking diodes, tracking accuracy is highly sensitive to laser beam delivery geometry and beam trajectory/alignment out of the articulated arm.
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