Altaf Hussain

Correcting photoacoustic signals for fluence variations using acousto-optic modulation.

We present a theoretical concept which may lead to quantitative photoacoustic mapping of chromophore concentrations. The approach supposes a technique capable of tagging light in a well-defined tagging volume at a specific location deep in the medium. We derive a formula that expresses the local absorption coefficient inside a medium in terms of noninvasively measured quantities and experimental parameters and we validate the theory using Monte Carlo simulations. Furthermore, we performed an experiment to basically validate the concept as a strategy to correct for fluence variations in photoacoustics. In the experiment we exploit the possibility of acousto-optic modulation, using focused ultrasound, to tag photons. Results show that the variation in photoacoustic signals of absorbing insertions embedded at different depths in a phantom, caused by fluence variations of more than one order of magnitude, can be corrected for to an accuracy of 5%.We propose a strategy for quantitative photoacoustic mapping of chromophore concentrations that can be performed purely experimentally. We exploit the possibility of acousto-optic modulation using focused ultrasound, and the principle that photons follow trajectories through a turbid medium in two directions with equal probability. A theory is presented that expresses the local absorption coefficient inside a medium in terms of noninvasively measured quantities and experimental parameters. Proof of the validity of the theory is given with Monte Carlo simulations.

Quantitative blood oxygen saturation imaging using combined photoacoustics and acousto-optics

In photoacoustic spectroscopy (PAS), wavelength dependent optical attenuation of biological tissue presents a challenge to measure the absolute oxygen saturation of hemoglobin (sO2). Here, we employ the combination of photoacoustics and acousto-optics (AO) at two optical wavelengths to achieve quantification, where AO serves as a sensor for the relative local fluence. We demonstrate that our method enables compensation of spatial as well as wavelength dependent fluence variations in PAS without a priori knowledge about the optical properties of the medium. The fluence compensated photoacoustic images at two excitation wavelengths are used to estimate the absolute oxygen saturation of blood in a spatially and spectroscopically heterogeneous phantom.

Mapping optical fluence variations in highly scattering media by measuring ultrasonically modulated backscattered light

Abstract. Knowledge of the local optical fluence in biological tissue is of fundamental importance for biomedical optical techniques to achieve quantification. We report a method to noninvasively measure the local optical fluence in optically inhomogeneous scattering media. The concept is based on two aspects: the local tagging of light using ultrasonic modulation and the photon path reversibility principle. Our method has advantages over known computational-based fluence mapping techniques, for its purely experimental nature and without the requirement of prior knowledge of the optical properties of the medium. We provide a theoretical formalism and validation of the method with experiments in tissue-like phantoms. Further, we combine our method with photoacoustic imaging and compensate the photoacoustic signals for fluence variations in optically inhomogeneous media.

Quantitative Photoacoustic Imaging by Acousto-Optically Measured Light Fluence

We propose a methodology to measure the absolute local absorption coefficient in biological tissue using photoacoustics in combination with reflection mode acousto-optics. We provide proof of the concept with numerical simulations and experiments.

Imaging blood flow inside highly scattering media using ultrasound modulated optical tomography

We report the use of ultrasound modulated optical tomography (UOT) with heterodyne parallel detection to locally sense and image blood flow deep inside a highly scattering medium. We demonstrate that the UOT signal is sensitive to the speed of the blood flow in the ultrasound focus and present an analytical model that relates UOT signals to the optical properties (i. e. scattering coefficient, anisotropy, absorption, and flow speed) of the blood and the background medium. We found an excellent agreement between the experimental data and the analytical model. By varying the integration time of the camera in our setup, we were able to spatially resolve blood flow in a scattering medium with a lateral resolution of 1.5 mm.

Fluence compensated photoacoustic tomography in small animals (Conference Presentation)

Light fluence inside turbid media can be experimentally mapped by measuring ultrasonically modulated light (Acousto-optics). To demonstrate the feasibility of fluence corrected Photoacoustic (PA) imaging, we have realized a tri-modality (i.e. photoacoustic, acousto-optic and ultrasound) tomographic small animal imaging system. Wherein PA imaging provides high resolution map of absorbed optical energy density, Acousto-optics yields the fluence distribution map in the corresponding PA imaging plane and Ultrasound provides morphological information. Further, normalization of the PA image with the acousto-optically measured fluence map results in an image that directly represents the optical absorption. Human epidermal growth factor receptor 2 (HER2) is commonly found overexpressed in human cancers, among which breast cancers, resulting in a more aggressive tumor phenotype. Identification of HER2-expression is clinically relevant, because cancers overexpressing this marker are amenable to HER2-directed therapies, among which antibodies trastuzumab and pertuzumab. Here, we investigate the feasibility and advantage of acousto-optically assisted fluence compensated PA imaging over PA imaging alone in visualizing and quantifying HER2 expression. For this experiment, nude mice were xenografted with human breast cancer cell lines SKBR3 and BT474 (both HER2 overexpressing), as well as HER2-negative MDA-MB-231. To visualize HER2 expression in these mice, HER2 monoclonal antibody pertuzumab (Perjeta®, Roche), was conjugated to near-infrared dye IRDye 800CW (800CW, LICOR Biosciences) at a ratio of 1∶2 antibody to 800CW. When xenograft tumors measured ≥ 100 mm3, mice received 100 µg 800CW-pertuzumab intravenously. Three days post injection, mice were scanned for fluorescence signal with an IVIS scanner. After fluorescence scans, mice were euthanized and imaged in our PA tomographic imaging system.

Erratum: Mapping optical fluence variations in highly scattering media by measuring ultrasonically modulated backscattered light( Journal of Biomedical Optics (2014) 19:6 (066002))

This article [J. Biomed. Opt.. 19, (6 ), 066002 (2014)] was originally published online on 2 June 2014 with a typo in the author list. The authors are correct as listed above. This article was corrected online on 6 June 2014. It appears correctly in print. This article [J. Biomed. Opt. 19(6), 066002 (2014)] was originally published online on 2 June 2014 with a typo in the author list. The authors are correct as listed above. This article was corrected online on 6 June 2014. It appears correctly in print.

Fluence mapping inside the highly scattering medium using reflection mode acousto-optics

Optical excitation based imaging modalities, with aim to image structures deep inside the scattering medium, suffer from quantification problem. We propose a methodology to solve the problem of non-invasively mapping the fluence in optically heterogeneous medium without the need of prior knowledge of its optical properties. We present a theoretical model of our concept and provide proof of principle with Monte Carlo simulations. Simulation results show that it is possible to measure the local light fluence in highly scattering medium in absolute terms. Furthermore, we performed an experiment to validate the concept as a strategy to measure local fluence in relative manners. We used reflection mode acousto optics (AO) in our experiment, and showed that with this method we can measure local light fluence (in relative term) in highly scattering medium.