Faculty of Science and Technology
Biomedical Photonic Imaging
P.O. Box 217
7500 AE Enschede
Telephone: +31 53 489 3112
Fax: +31 53 489 1105
Towards non-invasive acousto-optic, quantitative monitoring of chemical species in human blood or tissue. STW-project TGT.6656
Exploration of the possibilities and limitations of the acousto-optic method; development of instrument prototype for quantization of chemical components
An instrument that can non-invasively quantify parameters as total hemoglobin concentration and oxygen saturation locally and deep in tissue would have numerous applications in clinical medicine. Pulse oximetry, which is a standard technique for oxygenation measurements, has certain limitations connected with a low perfusion state. Moreover, it is not applicable for localized measurements deep in tissue. Diffuse optical tomography can measure deep within tissue, but the resolution decreases severely with increasing depth. One way to overcome this difficulty is to combine optics with ultrasound (US) as is done in photo-acoustic and acousto-optic (AO) imaging. It has been shown that photoacoustics has the capability to provide quantitative data on local absorbances, but always a mathematical model is required to estimate the local fluence. In AO, the local fluence can be measured in a more direct manner, because at the site(s) of interest the local light intensity is acoustically labeled.
Currently, we are investigating the feasibility to apply AO for millimeter-resolution measurements of the ratios of concentrations of optical absorbers in a model system mimicking a blood vessel embedded in tissue at different positions.
Previously we have shown that the use of microsecond US bursts combined with a gated optical excitation enabled the measurement of the absorption coefficient of an embedded dye in a scattering solution with a high spatial resolution. Consequently, the absorbing cylinder can be positioned perpendicularly to both the light path and the US-path, which results in a more practical geometry for in vivo measurements.
Schematics of the acousto-optical setup in transmission geometry. FG: two-channel programmable function generator (Tektronix AFG3102). D: delay line. P: MOSFET pulser to drive transducer. UST: 2.25 MHz US transducer (Panametrics V306). L: He-Ne laser, 35 mW at 633 nm and Argon-Ion laser, 260 mW at 514 nm. M: acousto optical modulator (Isomet 1201E-1). A1: aperture to block non-deflected light. A2: aperture for speckle selection system. B: IL-based phantom. CCD: camera. In the center of the phantom the cross-section of an absorber containing tube is depicted. The US-propagation is along the Z direction.
We extended our approach to multiple wavelengths and determined the concentration ratio of one component to the other and total concentration of a bi-component absorber inside a silicone rubber tube placed in an Intralipid-based phantom. We first calibrated the instrument by measuring the experimental response to the known absorption coefficient of a single component absorber embedded in the scattering phantom. The response to a single component absorber with absorption coefficient equal to that of the surrounding medium was taken as a baseline. Experimental data were normalized to this baseline and fitted to a Lambert-Beer type model. Subsequently, we used the obtained fitting coefficients to determine the absorption coefficient from measured data for an unknown bi-component absorber. With these established absorption coefficients and the molar extinction coefficients for pure dye components which are known for each wavelength, we can calculate the fraction of a single component in the mixture of absorbers and the total concentration of these absorbers:
S, the fraction of in the mixture, for the various prepared absorber combinations in dependence of set data in the single vessel phantom. The dotted line corresponds to a perfect match between set and measured S.
In addition, we demonstrated the feasibility to measure a 3D absorption map of the phantom:
The X axis cross-section of the map of values. X, Y are the coordinates of the US transducer. Light is entering the phantom from the right. The outer vessels within the phantom contain the absorbing dye. The figure was constructed from datasets containing 186 Z-scans which took ~286 minutes to complete. Scanning step size: 0.375mm in the Z direction and 0.5mm in the X-Y directions. Scanning range: 35mm in the Z direction, 15mm in X direction and 2.5mm in the Y direction. For these data the maximum SNR is ~96.
Publications in peer-reviewed journals:
“Feasibility of quantitative determination of local optical absorbances in tissue-mimicking phantoms using acousto-optic sensing,” by A. Bratchenia, R. Molenaar, and R. P. H. Kooyman, Appl. Phys. Lett. 92, 113901-(1-3) (2008).
“Millimeter-resolution acousto-optic quantitative imaging in a tissue model system,” by A. Bratchenia, R. Molenaar, T.G. van Leeuwen, and R. P. H. Kooyman, J. Biomed. Optic. 14, 034031 (2009).
“Acousto-optic spectroscopy as a tool for quantitative determination of chemical compounds in tissue: a model study” by A. Bratchenia, R. Molenaar, R. P. H. Kooyman, Proceedings Vol. 6437 of Photons Plus Ultrasound: Imaging and Sensing 2007: The Eighth Conference on Biomedical Thermoacoustics, Optoacoustics, and Acousto-optics, Alexander A. Oraevsky; Lihong V. Wang, Editors, 64371P
“Application of intense ultrasound bursts for quantitative acousto-optic sensing”, by A. Bratchenia, R. Molenaar, R. P. H. Kooyman, [6856-36], Proceedings Vol. 6856 of Photons Plus Ultrasound: Imaging and Sensing 2008: The Ningth Conference on Biomedical Thermoacoustics, Optoacoustics, and Acousto-optics, Alexander A. Oraevsky; Lihong V. Wang, Editors, 685611
“Three-dimensional acousto-optic mapping using planar scanning with ultrasound bursts”, by A. Bratchenia, R. Molenaar, R. P. H. Kooyman, Proceedings Vol. 7177 of Photons Plus Ultrasound: Imaging and Sensing 2009: The 10th Conference on Biomedical Thermoacoustics, Optoacoustics, and Acousto-optics, Alexander A. Oraevsky; Lihong V. Wang, Editors, 71771H
“Quantitative acousto-optic imaging in tissue-mimicking phantoms”, by R. Molenaar, A. Bratchenia, R. P. H. Kooyman, Proceedings Vol. 7265: Medical Imaging 2009: Ultrasonic Imaging and Signal Processing, Stephen A. McAleavey; Jan D'hooge, Editors, 72650M