Finite aperture correction for spectral cameras with integrated thin-film Fabry-Perot filters.

Spectral cameras with integrated thin-film Fabry-Perot filters enable many different applications. Some applications require the detection of spectral features that are only visible at specific wavelengths, and some need to quantify small spectral differences that are undetectable with RGB color cameras. One factor that influences the central wavelength of thin-film filters is the angle of incidence. Therefore, when light is focused from an imaging lens onto the filter array, undesirable shifts in the measured spectra are observed. These shifts limit the use of the sensor in applications that require fast lenses or lenses with large chief ray angles. To increase flexibility and enable new applications, we derive an analytical model that explains and can correct the observed shifts in measured spectra. The model includes the size of the aperture and physical position of each filter on the sensor. We experimentally validate the model with two spectral cameras: one in the visible and near-infrared region and one in the short wave infrared region.

Sub-diffuse interstitial optical tomography to improve the safety of brain needle biopsies: a proof-of-concept study.

The extraction of tissue samples during brain needle biopsy can cause life-threatening hemorrhage because of significant blood vessel injury during the procedure. Vessel rupture can have significant consequences for patient health, ranging from transient neurological deficits to death. Here, we present a sub-diffuse optical tomography technique that can be integrated into neurosurgical workflow to detect the presence of blood vessels. A proof-of-concept study performed on a realistic brain tissue phantom is presented and demonstrates that interstitial optical tomography (iOT) can detect several 1 mm diameter high-contrast absorbing objects located <2 mm from the needle.

Diffuse photon density wavefront speed as a contrast for tomographic imaging of heterogeneous diffusive media.

An imaging algorithm is implemented for tomographically reconstructing contrast maps of the space variant speed of diffuse photon density wavefronts (DPDWFs) propagating in biological tissue-like diffusing media. This speed serves as a novel contrast not previously exploited in the literature. The algorithm employs early photon arrival times (EPATs) extracted from a set of time domain measurements. A relationship between EPATs and the speed of DPDWFs is exploited as the forward model. The forward model and its use in an inverse problem are supported by experimental results. These are carried out for 3D media with tissue-like optical properties. The resulting inverse problem is formulated as a set of algebraic equations and solved within a constrained linear least squares framework. The results indicate that the algorithm provides tomographic information on heterogeneities locations and distributions.

Time-domain geometrical localization of point-like fluorescence inclusions in turbid media with early photon arrival times.

We introduce a novel approach for localizing a plurality of discrete point-like fluorescent inclusions embedded in a thick turbid medium using time-domain measurements. The approach uses early photon information contained in measured time-of-flight distributions originating from fluorescence emission. Fluorescence time point-spread functions (FTPSFs) are acquired with ultrafast time-correlated single photon counting after short pulse laser excitation. Early photon arrival times are extracted from the FTPSFs obtained from several source-detector positions. Each source-detector measurement allows defining a geometrical locus where an inclusion is to be found. These loci take the form of ovals in 2D or ovoids in 3D. From these loci a map can be built, with the maxima thereof corresponding to positions of inclusions. This geometrical approach is supported by Monte Carlo simulations performed for biological tissue-like media with embedded fluorescent inclusions. To validate the approach, several experiments are conducted with a homogeneous phantom mimicking tissue optical properties. In the experiments, inclusions filled with indocyanine green are embedded in the phantom and the fluorescence response to a short pulse of excitation laser is recorded. With our approach, several inclusions can be localized with low millimeter positional error. Our results support the approach as an accurate, efficient, and fast method for localizing fluorescent inclusions embedded in highly turbid media mimicking biological tissues. Further Monte Carlo simulations on a realistic mouse model show the feasibility of the technique for small animal imaging.

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

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.

Sensitivity analysis aimed at blood vessels detection using interstitial optical tomography during brain needle biopsy procedures.

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.

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

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 brain cancer detection with Raman spectroscopy in humans.

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.

A multi-view time-domain non-contact diffuse optical tomography scanner with dual wavelength detection for intrinsic and fluorescence small animal imaging.

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.