Cancers are often impossible to visually distinguish from normal tissue. This is critical for brain cancer where residual invasive cancer cells frequently remain after surgery, leading to disease recurrence and a negative impact on overall survival. No preoperative or intraoperative technology exists to identify all cancer cells that have invaded normal brain. To address this problem, we developed a handheld contact Raman spectroscopy probe technique for live, local detection of cancer cells in the human brain. Using this probe intraoperatively, we were able to accurately differentiate normal brain from dense cancer and normal brain invaded by cancer cells, with a sensitivity of 93% and a specificity of 91%. This Raman-based probe enabled detection of the previously undetectable diffusely invasive brain cancer cells at cellular resolution in patients with grade 2 to 4 gliomas. This intraoperative technology may therefore be able to classify cell populations in real time, making it an ideal guide for surgical resection and decision-making.

Intraoperative video-rate hemodynamic response assessment in human cortex using snapshot hyperspectral optical imaging," Neurophoton. Abstract. 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.

We present a non-contact diffuse optical tomography (DOT) scanner with multi-view detection (over 360°) for localizing fluorescent markers in scattering and absorbing media, in particular small animals. It relies on time-domain detection after short pulse laser excitation. Ultrafast time-correlated single photon counting and photomultiplier tubes are used for time-domain measurements. For light collection, seven free-space optics non-contact dual wavelength detection channels comprising 14 detectors overall are placed around the subject, allowing the measurement of time point-spread functions at both excitation and fluorescence wavelengths. The scanner is endowed with a stereo camera pair for measuring the outer shape of the subject in 3D. Surface and DOT measurements are acquired simultaneously with the same laser beam. The hardware and software architecture of the scanner are discussed. Phantoms are used to validate the instrument. Results on the localization of fluorescent point-like inclusions immersed in a scattering and absorbing object are presented. The localization algorithm relies on distance ranging based on the measurement of early photons arrival times at different positions around the subject. This requires exquisite timing accuracy from the scanner. Further exploiting this capability, we show results on the effect of a scattering hetereogenity on the arrival time of early photons. These results demonstrate that our scanner provides all that is necessary for reconstructing images of small animals using full tomographic reconstruction algorithms, which will be the next step. Through its free-space optics design and the short pulse laser used, our scanner shows unprecedented timing resolution compared to other multi-view time-domain scanners.

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A brain needle biopsy procedure is performed for suspected brain lesions in order to sample tissue that is subsequently analysed using standard histopathology techniques. A common complication resulting from this procedure is brain hemorrhaging from blood vessels clipped off during tissue extraction. Interstitial optical tomography (iOT) has recently been introduced by our group as a mean to assess the presence of blood vessels in the vicinity of the needle. The clinical need to improve safety requires the detection of blood vessels within 2 mm from the outer surface of the needle, since this distance is representative of the volume of tissue that is aspirated durirng tissue extraction. Here, a sensitivity analysis is presented to establish the intrinsic detection limits of iOT based on simulations and experiments using brain tissue phantoms. It is demonstrated that absorbers can be detected with diameters >300 μm located up to >2 mm from the biopsy needle core for bulk optical properties consistent with brain tissue.