Non-contact time-resolved diffuse reflectance imaging at null source-detector separation

We report results of the proof-of-principle tests of a novel non-contact tissue imaging system. The system utilizes a quasi-null source-detector separation approach for time-domain near-infrared spectroscopy, taking advantage of an innovative state-of-the-art fast-gated single photon counting detector. Measurements on phantoms demonstrate the feasibility of the non-contact approach for the detection of optically absorbing perturbations buried up to a few centimeters beneath the surface of a tissue-like turbid medium. The measured depth sensitivity and spatial resolution of the new system are close to the values predicted by Monte Carlo simulations for the inhomogeneous medium and an ideal fast-gated detector, thus proving the feasibility of the non-contact approach for high density diffuse reflectance measurements on tissue. Potential applications of the system are also discussed. © 2011 Optical Society of America

Optimal estimation reconstruction of the optical properties of a two-layered tissue phantom from time-resolved single-distance measurements

In this work, we have tested the optimal estimation (OE) algorithm for the reconstruction of the optical properties of a two-layered liquid tissue phantom from time-resolved single-distance measurements. The OE allows a priori information, in particular on the range of variation of fit parameters, to be included. The purpose of the present investigations was to compare the performance of OE with the Levenberg–Marquardt method for a geometry and real experimental conditions typically used to reconstruct the optical properties of biological tissues such as muscle and brain. The absorption coefficient of the layers was varied in a range of values typical for biological tissues. The reconstructions performed demonstrate the substantial improvements achievable with the OE provided a priori information is available. We note the extreme reliability, robustness, and accuracy of the retrieved absorption coefficient of the second layer obtained with the OE that was found for up to six fit parameters, with an error in the retrieved values of less than 10%. A priori information on fit parameters and fixed forward model parameters clearly improves robustness and accuracy of the inversion procedure

Performance assessment of time-domain optical brain imagers, part 1: basic instrumental performance protocol

open21siAbstract.  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.H. Wabnitz; D. R. Taubert; M. Mazurenka; O. Steinkellner; A. Jelzow;R. Macdonald;D. Milej;P. Sawosz;M. Kacprzak;A. Liebert;R. Cooper;J. Hebden;A. Pifferi;A. Farina;I. Bargigia;D. Contini;M. Caffini;L. Zucchelli;L. Spinelli;R. Cubeddu;A. TorricelliH., Wabnitz; D. R., Taubert; M., Mazurenka; O., Steinkellner; A., Jelzow; R., Macdonald; D., Milej; P., Sawosz; M., Kacprzak; A., Liebert; R., Cooper; J., Hebden; Pifferi, ANTONIO GIOVANNI; Farina, Andrea; Bargigia, Ilaria; Contini, Davide; Caffini, Matteo; Zucchelli, LUCIA MARIA GRAZIA; Spinelli, Lorenzo; Cubeddu, Rinaldo; Torricelli, Alessandr

Performance assessment of time-domain optical brain imagers, part 2: nEUROPt protocol

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

Quantifizierung von Absorptionsänderungen im menschlichen Gehirn in vivo mittels zeitaufgelöster Nahinfrarotspektroskopie

Das Vermessen der Gehirnaktivität ist essentiell für das Verständnis von Hirnfunktion und potentiell auch für die Diagnose von Hirnerkrankungen. Die Hirnaktivität wird begleitet von zerebralen hämodynamischen Prozessen, die durch lokale Konzentrationsänderungen von Oxy- und Desoxyhämoglobin in Erscheinung treten. Mittels der funktionellen Nahinfrarotspektroskopie (fNIRS) können diese Änderungen, und damit indirekt die Hirnaktivität, in vivo und nicht-invasiv gemessen werden. Jedoch wird eine genaue Quantifizierung der Konzentrationsänderungen durch die starke Lichtstreuung im Gewebe, die heterogene Kopfstruktur und das tiefliegende Gehirn erschwert. Darüber hinaus überlagern nicht-zerebrale hämodynamische Prozesse das zerebrale Signal und können die eigentliche Hirnaktivierung verschleiern. In dieser Arbeit wurde die Quantifizierung der Konzentrationsänderungen mit Hilfe der zeitaufgelösten Nahinfrarotspektroskopie in Verbindung mit der Momentenmethode zur Analyse von Photonen-Laufzeit-Verteilungen verbessert. Zur Berechnung von Hämoglobinkonzentrationsänderungen wurde basierend auf einem Schichtmodel des Kopfes eine Rekonstruktionsmethode entwickelt, bei der die Rekonstruktionsparameter individuell anhand der experimentellen Daten anpasst werden. Diese Methode wurde mit Hilfe eines Zwei-Schicht-Phantoms validiert und auf Messdaten angewendet, die in vivo an gesunden Probanden gewonnen wurden. Die Ergebnisse der Rekonstruktion wurden auch mit denen aus einer Rechnung verglichen, die auf einem Modell des homogenen semiinfiniten Mediums basiert und ausschließlich von der intrinsischen Tiefenselektivität der Momente höherer Ordnung profitiert. Außerdem wurde die zeitaufgelöste fNIRS-Technik mit anderen Neuroimaging-Techniken und Aufzeichnungen von systematisch-physiologischen Signalen bei in vivo-Messungen kombiniert. Die unterschiedlichen Modalitäten lieferten komplementäre Informationen, die zur Validierung von fNIRS benutzt wurden. Am heterogenen Zwei-Schicht-Phantom konnten mit Hilfe der auf dem Schichtmodel basierenden Methode Absorptionsänderungen mit einer Genauigkeit von ± 10 % rekonstruiert werden. In Falle von in vivo-Daten war es damit möglich, die oberflächlichen und zerebralen hämodynamischen Verläufe zu trennen. Während der homogene Ansatz Absorptionsänderungen immanent unterschätzt, ist die schichtbasierte Methode in der Lage dies zu kompensieren. Das resultiert in bis zu zehnfach größeren Werten von Hämoglobinkonzentrationsänderungen. Die hier vorgeschlagene schichtbasierte Methode ermöglicht, die Quantifizierung zerebraler hämodynamischer Verläufe zu verbessern. Die Abtrennung der oberflächlichen Signalanteile führt zur zuverlässigeren Detektion der Hirnaktivität.Measurement of the brain activity is essential for the understanding of brain function and potentially for the diagnosis of brain pathologies. Human brain activity is accompanied by cerebral haemodynamics, i.e. local concentration changes of oxy- and deoxyhaemoglobin. These changes can be measured non-invasively and in vivo by functional near-infrared spectroscopy (fNIRS) which thereby provides an indirect measure of the brain activity. However, accurate quantification of haemoglobin concentrations is hampered by the strong light scattering of tissue, the heterogeneous structure of the head and the depth of the brain cortex. Moreover, non-cerebral haemodynamics overlay the desired cerebral signals and can mask the actual brain activity. In this thesis a time-domain NIRS technique together with data analysis based on moments of distributions of time of flight of photons was employed to improve the quantification. For retrieval of haemoglobin concentration changes an improved method was developed. It is based on an approximation of the head by a layered structure and uses experimental data to adapt reconstruction related parameters to the individual measurement. This method was validated on a two-layered phantom and applied to data obtained on healthy subjects in vivo. The results were also compared to data from a reconstruction based on a homogeneous semi-infinite medium. This method benefits from the intrinsic depth selectivity of the higher order moments only. In addition, time-domain fNIRS in vivo measurements were performed in combination with other neuroimaging modalities and the recording of systemic physiological signals. The obtained data was used for validation based on the complimentary information provided by the different modalities. With a two-layered heterogeneous phantom absorption changes were retrieved using the approach based on the layered medium with an accuracy of ± 10%. In the in vivo case it was possible to separate superficial and cerebral haemodynamics. Furthermore, the intrinsic underestimation of the cerebral absorption changes obtained using the model of the homogeneous medium was strongly reduced if the new approach based the layered structure was used. In the in vivo case this results in up to tenfold higher haemoglobin concentration changes. The approach presented here allows for improved quantification of cerebral haemodynamics in fNIRS studies. The separation of the superficial signal contribution leads to more reliable detection of the brain activation

Optimal estimation reconstruction of the optical properties of a two-layered tissue phantom from time-resolved single-distance measurements

In this work, we have tested the optimal estimation (OE) algorithm for the reconstruction of the optical properties of a two-layered liquid tissue phantom from time-resolved single-distance measurements. The OE allows a priori information, in particular on the range of variation of fit parameters, to be included. The purpose of the present investigations was to compare the performance of OE with the Levenberg–Marquardt method for a geometry and real experimental conditions typically used to reconstruct the optical properties of biological tissues such as muscle and brain. The absorption coefficient of the layers was varied in a range of values typical for biological tissues. The reconstructions performed demonstrate the substantial improvements achievable with the OE provided a priori information is available. We note the extreme reliability, robustness, and accuracy of the retrieved absorption coefficient of the second layer obtained with the OE that was found for up to six fit parameters, with an error in the retrieved values of less than 10%. A priori information on fit parameters and fixed forward model parameters clearly improves robustness and accuracy of the inversion procedure