Non-contact scanning at small source-detector separation enables imaging of cerebral and extracranial signals at high spatial resolution and their separation based on early and late photons accounting for the related spatio-temporal characteristics.
Melanoma skin cancer has one of the highest mortality rates of all types of cancer if not detected at an early stage. The survival rate is highly dependent on its penetration depth, which is commonly determined by histopathology. In this work, we aim at combining optical coherence tomography and optoacoustic as a non-invasive all-optical method to measure the penetration depth of melanoma. We present our recent achievements to setup a handheld multimodal device and also results from first in vivo measurements on healthy and cancerous skin tissue, which are compared to measurements obtained by ultrasound and histopathology.
We propose a simple and reliable solid phantom for mimicking realistic localized absorption changes within a diffusive medium. The phantom is based on a solid matrix holding a movable black inclusion embedded in a rod. Translating the rod parallel to the phantom surface, the inhomogeneity can be positioned beneath the source-detector pair (perturbed case) or far from it (unperturbed case). Examples of time-resolved transmittance measurements and time-resolved reflectance scans are shown to demonstrate the properties and the versatility of the phantom.
We developed a novel scanning system that relies on gated detection of late photons at short source-detector separation, enabling the recording of absorption changes in deep tissue compartments. The tissue was scanned by a galvanometer scanner from a distance of more than 10 cm, with a fixed separation of the illumination and the detection spot of a few mm. The light source was a supercontinuum laser with an acousto-optic tunable filter that was used to rapidly switch between two wavelength bands centered at 760 nm and 860 nm. A fast-gated single-photon avalanche diode was employed to eliminate the intense early part of the diffusely remitted signal and to detect photons with long times of flight with improved signal-to-noise ratio. A second detection channel contained a non-gated detector. The gated and non-gated time-of-flight distributions of photons were recorded by imaging time-correlated single photon counting synchronized with the movement of the scanner. A tissue area with dimensions of several cm was scanned with 32×32 pixels within a frame time of 1 s. Sensitivity and spatial resolution of the system were characterized by phantom measurements. In-vivo tests included functional brain activation by various tasks and demonstrated the feasibility of non-contact imaging of hemodynamic changes in the cerebral cortex.
The nEUROPt protocol is one of two new protocols developed within the European project nEUROPt to characterize the performances of time-domain systems for optical imaging of the brain. It was applied in joint measurement campaigns to compare the various instruments and to assess the impact of technical improvements. This protocol addresses the characteristic of optical brain imaging to detect, localize, and quantify absorption changes in the brain. It was implemented with two types of inhomogeneous liquid phantoms based on Intralipid and India ink with well-defined optical properties. First, small black inclusions were used to mimic localized changes of the absorption coefficient. The position of the inclusions was varied in depth and lateral direction to investigate contrast and spatial resolution. Second, two-layered liquid phantoms with variable absorption coefficients were employed to study the quantification of layer-wide changes and, in particular, to determine depth selectivity, i.e., the ratio of sensitivities for deep and superficial absorption changes. We introduce the tests of the nEUROPt protocol and present examples of results obtained with different instruments and methods of data analysis. This protocol could be a useful step toward performance tests for future standards in diffuse optical imaging.
Performance assessment of instruments devised for clinical applications is of key importance for validation and quality assurance. Two new protocols were developed and applied to facilitate the design and optimization of instruments for time-domain optical brain imaging within the European project nEUROPt. Here, we present the “Basic Instrumental Performance” protocol for direct measurement of relevant characteristics. Two tests are discussed in detail. First, the responsivity of the detection system is a measure of the overall efficiency to detect light emerging from tissue. For the related test, dedicated solid slab phantoms were developed and quantitatively spectrally characterized to provide sources of known radiance with nearly Lambertian angular characteristics. The responsivity of four time-domain optical brain imagers was found to be of the order of 0.1 m2 sr. The relevance of the responsivity measure is demonstrated by simulations of diffuse reflectance as a function of source-detector separation and optical properties. Second, the temporal instrument response function (IRF) is a critically important factor in determining the performance of time-domain systems. Measurements of the IRF for various instruments were combined with simulations to illustrate the impact of the width and shape of the IRF on contrast for a deep absorption change mimicking brain activation.
We present the experimental implementation and validation of a phantom for diffuse optical imaging based on totally absorbing objects for which, in the previous paper [J. Biomed. Opt.18(6), 066014, (2013)], we have provided the basic theory. Totally absorbing objects have been manufactured as black polyvinyl chloride (PVC) cylinders and the phantom is a water dilution of intralipid-20% as the diffusive medium and India ink as the absorber, filled into a black scattering cell made of PVC. By means of time-domain measurements and of Monte Carlo simulations, we have shown the reliability, the accuracy, and the robustness of such a phantom in mimicking typical absorbing perturbations of diffuse optical imaging. In particular, we show that such a phantom can be used to generate any absorption perturbation by changing the volume and position of the totally absorbing inclusion.
Using Monte Carlo simulations we demonstrate that a realistic absorption inhomogeneity embedded in a diffusive medium can be effectively mimicked by a small black object of a proper volume (Equivalence Relation). Applying this concept we propose the construction of simple and well reproducible inhomogeneous phantoms.
We present results of first in-vivo tests of an optical non-contact scanning imaging system, intended to study oxidative metabolism related processes in biological tissue by means of time-resolved near-infrared spectroscopy. Our method is a novel realization of the short source-detector separation approach and based on a fast-gated single-photon avalanche diode to detect late photons only. The scanning system is built in quasi-confocal configuration and utilizes polarizationsensitive detection. It scans an area of 4×4 cm2, recording images with 32×32 pixels, thus creating a high density of source-detector pairs. To test the system we performed a range of in vivo measurements of hemodynamic changes in several types of biological tissues, i.e. skin (Valsalva maneuver), muscle (venous and arterial occlusions) and brain (motor and cognitive tasks). Task-related changes in hemoglobin concentrations were clearly detected in skin and muscle. The brain activation shows weaker, but yet detectable changes. These changes were localized in pixels near the motor cortex area (C3). However, it was found that even very short hair substantially impairs the measurement. Thus the applicability of the scanner is limited to hairless parts of body. The results of our first in-vivo tests prove the feasibility of non-contact scanning imaging as a first step towards development of a prototype for biological tissue imaging for various medical applications.
Novel protocols were developed and applied in the European project “nEUROPt” to assess and compare the performance
of instruments for time-domain optical brain imaging and of related methods of data analysis. The objective of the first
protocol, “Basic Instrumental Performance”, was to record relevant basic instrumental characteristics in a direct way.
The present paper focuses on the second novel protocol (“nEUROPt” protocol) that was devoted to the assessment of
sensitivity, spatial resolution and quantification of absorption changes within inhomogeneous media. It was implemented
with liquid phantoms based on Intralipid and ink, with black inclusions and, alternatively, in two-layered geometry.
Small black cylinders of various sizes were used to mimic small localized changes of the absorption coefficient. Their
position was varied in depth and lateral direction to address contrast and spatial resolution. Two-layered liquid phantoms
were used, in particular, to determine depth selectivity, i.e. the ratio of contrasts due to a deep and a superficial
absorption change of the same magnitude. We introduce the tests of the “nEUROPt” protocol and present exemplary
results obtained with various instruments. The results are related to measurements with both types of phantoms and to
the analysis of measured time-resolved reflectance based on time windows and moments. Results are compared for the
different instruments or instrumental configurations as well as for the methods of data analysis. The nEUROPt protocol
is also applicable to cw or frequency-domain instruments and could be useful for designing performance tests in future
standards in diffuse optical imaging.
We report on the development of a scanning non-contact brain imager, based on a novel technique in time-resolved nearinfrared
spectroscopy, i.e. the null source-detector distance approach. Our concept is designed to image an area of about
10 cm2 with small adjustable scanning steps, i.e. a high density of mapping points can be realized. The feasibility of the
proposed method was tested with a single-point confocal optical setup without beam scanning so far. A set of test
measurements was performed on a liquid phantom with a small black polyvinyl chloride (PVC) cylinder as a target,
which was translated in X direction to emulate the optical scanning and estimate lateral spatial resolution, and in Z
direction to estimate the depth sensitivity of the instrument. The problem of dominance of early photons at null sourcedetector
separation was solved by applying a fast time-gated detector to detect late only photons. Two fast-gated
detectors, a newly developed state-of-art time-gated single-photon avalanche photodiode (tgSPAD) and commercially
available fast-gated intensified CCD (iCCD) camera, were compared against each other. It was shown that, due to its
better dynamic range, the tgSPAD is capable to detect later photons than the iCCD camera, and hence, a scanning system
equipped with the time-gated SPAD has better depth sensitivity. Thus the time-gated SPAD is the detector of choice for
further development of the non-contact confocal brain scanner.
To facilitate the design and optimization of instruments for time-domain optical brain imaging within the European
project "nEUROPt", the performance of various instruments is assessed and compared. This type of instruments relies on
picosecond lasers with high repetition rates, fast detectors and time-correlated single photon counting. The first step of
the assessment included a number of basic tests that are related to parameters of the source, to the differential
nonlinearity of the timing electronics and to the temporal instrument response function (IRF). An additional test has been
devised to measure the responsivity of the detection system, i.e. the overall efficiency to collect and detect light
emerging from tissue. Dedicated solid slab phantoms have been developed and quantitatively spectrally characterized to
provide sources of known radiance with nearly Lambertian angular characteristics. The wavelength-dependent
transmittance factor of these phantoms was of the order of 1020/(W s m2sr). Measurements of the responsivity of the
detection systems of three time-domain optical brain imagers tested yielded similar values of the order of 0.1 mm2sr.
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