Significance: The practicality of optical methods detecting tissue optical contrast (absorption, elastic and inelastic scattering, fluorescence) for surgical guidance is limited by interferences from blood pooling and the resulting partial or complete inability to interrogate cortex and blood vessels.
Aim: A multispectral diffuse reflectance technique was developed for intraoperative brain imaging of hemodynamic activity to automatically discriminate blood vessels, cortex, and bleeding at the brain surface.
Approach: A manual segmentation of blood pooling, cortex, and vessels allowed the identification of a frequency range in hemoglobin concentration variations associated with high optical signal in blood vessels and cortex but not in bleeding. Reflectance spectra were then used to automatically segment areas with and without hemodynamic activity as well as to discriminate blood from cortical areas.
Results: The frequency range associated with low-frequency hemodynamics and respiratory rate (0.03 to 0.3 Hz) exhibits the largest differences in signal amplitudes for bleeding, blood vessels, and cortex. A segmentation technique based on simulated reflectance spectra initially allowed discrimination of blood (bleeding and vessels) from cortical tissue. Then, a threshold applied to the low-frequency components from deoxyhemoglobin allowed the segmentation of bleeding from vessels. A study on the minimum acquisition time needed to discriminate all three components determined that ∼25 s was necessary to detect changes in the low-frequency range. Other frequency ranges such as heartbeat (1 to 1.7 Hz) can be used to reduce the acquisition time to few seconds but would necessitate optimizing instrumentation to ensure larger signal-to-noise ratios are achieved.
Conclusions: A method based on multispectral reflectance signals and low-frequency hemoglobin concentration changes can be used to distinguish bleeding, blood vessels, and cortex. This could be integrated into fiber optic probes to enhance signal specificity by providing users an indication of whether measurements are corrupted by blood pooling, an important confounding factor in biomedical optics applied to surgery.
Epilepsy is a neurological disorder characterized by chronic excessive neuronal discharges. Epilepsy surgery may be considered in patients who are resistant to drug treatment, and several tests are used during pre-operative planning to locate the epileptic focus to be resected (MRI, PET, SPECT, EEG, MEG). In some cases, intracranial EEG monitoring or intraoperative electrocorticography is required to confirm and better delineate the area to be resected. Despite available tests, epilepsy surgery outcome remains modest. We present a multimodal imaging platform connected to a neurosurgical microscope allowing intraoperative detection of intrinsic optical brain biomarkers for surgical guidance during epilepsy surgery. Hyperspectral imaging (HSI) allows detection of the hemodynamic response associated with epileptic activity, spatial frequency domain imaging (SFDI) is used for optical properties reconstruction (absorption and reduced scattering), and auto-fluorescence imaging (AFI) allows metabolic markers identification. Validation of SFDI and AFI systems was performed on optical phantoms. Acquisitions on ex vivo tissue samples demonstrate the capabilities of the system to produce fluorescence intensity maps, calibrated with optical properties obtained from SFDI to account for tissue attenuation. In vivo acquisition during epilepsy surgery with HSI allows characterization of the hemodynamic response associated with epileptic spikes.
Prostate cancer is the most diagnosed form of cancer among American men and, in vast proportion, the standard of care treatment includes radical prostatectomy. Important risk factors associated with prostatectomies are the presence of post-surgery residual prostate tissue and positive cancer margins, potentially leading to recurrences. Prostate histopathology analysis following the procedure is used to determine follow-up treatment. However, only a limited fraction of the prostate margins can be sampled, which can lead to suboptimal evaluation and treatment. Here we present the development of a wide-field multimodal imaging system designed to quantify intrinsic tissue fluorescence and map scattering and absorption coefficients using spatial frequency domain imaging (SFDI). The system allows targeting of suspicious prostate regions to guide histopathology analysis, aiming to improve diagnostic accuracy and treatment planning. Tissue excitation for endogenous fluorescence is achieved with a 405 nm laser diode and, for SFDI, a digital light projector transmits structured white light used to reconstruct tissue optical properties (absorption, scattering) between 420 and 720 nm. A light transport model-based quantification algorithm then corrects the fluorescence spectra for tissue attenuation, lending a biomarker that correlates with local fluorophore concentrations. Spectral and spatial calibration of both modalities was done on optical phantoms and validation of the fluorescence quantification on biological tissue. Finally, imaging results are presented for 5 human prostates interrogated with the system, along with spatially-registered histopathology analyses. Future work involves massive data acquisition and development of artificial intelligence models for tissue classification (prostate, non-prostate; healthy, cancerous) and adaptation for intraoperative use.
Using light, we are able to visualize the hemodynamic behavior of the brain to better understand neurovascular coupling and cerebral metabolism. In vivo optical imaging of tissue using endogenous chromophores necessitates spectroscopic detection to ensure molecular specificity as well as sufficiently high imaging speed and signal-to-noise ratio, to allow dynamic physiological changes to be captured, isolated, and used as surrogate of pathophysiological processes. An optical imaging system is introduced using a 16-bands on-chip hyperspectral camera. Using this system, we show that up to three dyes can be imaged and quantified in a tissue phantom at video-rate through the optics of a surgical microscope. In vivo human patient data are presented demonstrating brain hemodynamic response can be measured intraoperatively with molecular specificity at high speed.
Following normal neuronal activity, there is an increase in cerebral blood flow and cerebral blood volume to provide oxygenated hemoglobin to active neurons. For abnormal activity such as epileptiform discharges, this hemodynamic response may be inadequate to meet the high metabolic demands. To verify this hypothesis, we developed a novel hyperspectral imaging system able to monitor real-time cortical hemodynamic changes during brain surgery. The imaging system is directly integrated into a surgical microscope, using the white-light source for illumination. A snapshot hyperspectral camera is used for detection (4x4 mosaic filter array detecting 16 wavelengths simultaneously). We present calibration experiments where phantoms made of intralipid and food dyes were imaged. Relative concentrations of three dyes were recovered at a video rate of 30 frames per second. We also present hyperspectral recordings during brain surgery of epileptic patients with concurrent electrocorticography recordings. Relative concentration maps of oxygenated and deoxygenated hemoglobin were extracted from the data, allowing real-time studies of hemodynamic changes with a good spatial resolution. Finally, we present preliminary results on phantoms obtained with an integrated spatial frequency domain imaging system to recover tissue optical properties. This additional module, used together with the hyperspectral imaging system, will allow quantification of hemoglobin concentrations maps. Our hyperspectral imaging system offers a new tool to analyze hemodynamic changes, especially in the case of epileptiform discharges. It also offers an opportunity to study brain connectivity by analyzing correlations between hemodynamic responses of different tissue regions.
Cancer tissue often remains after brain tumor resection due to the inability to detect the full extent of cancer during surgery, particularly near tumor boundaries. Commercial systems are available for intra-operative real-time aminolevulenic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence imaging. These are standard white-light neurosurgical microscopes adapted with optical components for fluorescence excitation and detection. However, these instruments lack sensitivity and specificity, which limits the ability to detect low levels of PpIX and distinguish it from tissue auto-fluorescence. Current systems also cannot provide repeatable and un-biased quantitative fluorophore concentration values because of the unknown and highly variable light attenuation by tissue. We present a highly sensitive spectroscopic fluorescence imaging system that is seamlessly integrated onto a neurosurgical microscope. Hardware and software were developed to achieve through-microscope spatially-modulated illumination for 3D profilometry and to use this information to extract tissue optical properties to correct for the effects of tissue light attenuation. This gives pixel-by-pixel quantified fluorescence values and improves detection of low PpIX concentrations. This is achieved using a high-sensitivity Electron Multiplying Charge Coupled Device (EMCCD) with a Liquid Crystal Tunable Filter (LCTF) whereby spectral bands are acquired sequentially; and a snapshot camera system with simultaneous acquisition of all bands is used for profilometry and optical property recovery. Sensitivity and specificity to PpIX is demonstrated using brain tissue phantoms and intraoperative human data acquired in an on-going clinical study using PpIX fluorescence to guide glioma resection.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.