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Multi-Spectral Optoacoustic Tomography: Methods and Applications
Andreas B. Bühler
(Black Polyethylene: 50um)
Macroscopic optical small animal imaging plays an increasingly important role in
biomedical research, as it can noninvasively examine structural, physiological, and
molecular tissue features in vivo. A novel modality that emerged in the last
decade is optoacoustic (photoacoustic) imaging, which combines versatile optical
absorption contrast with high ultrasonic resolution and real-time imaging
capabilities by capitalizing on the optoacoustic (photoacoustic) effect. Using
illumination with multiple wavelengths and spectral unmixing methods,
multispectral optoacoustic tomography (MSOT) has the potential to specifically
resolve tissue chromophores or administered extrinsic molecular agents noninvasively
in deep tissue with unprecedented resolution performance and in realtime.
The presented work explores MSOT in the context of small animal imaging.
Different instrumentation and detection geometry related effects are analyzed
regarding their influence on the imaging performance. Based on the findings, two
dedicated MSOT imaging platforms for 2D and 3D real-time imaging of small
animals and tissue samples are conceived, implemented and imaging performance
is characterized by simulation, on phantoms and ex vivo in mice.
Beside instrumentation, the utilized signal processing, image reconstruction and
spectral unmixing strategy is of great importance for achieving best imaging
results. The research presented shows how reconstruction artifacts can be
reduced by compensating for the electrical impulse response of the system and
that the calculation of intermediate projections can alleviate artifacts due to
sparse angular sampling. Moreover, two regularization approaches for 2D limited
view reconstructions are presented and a 3D model-based inversion scheme for
improving 3D reconstructions in the developed systems by modeling the shape of
the detection elements. Finally, the challenges of multispectral unmixing in deep
tissue are discussed; two unmixing schemes for detection of molecular agents are
presented and a method to partially compensate for the effect of light
attenuation is proposed.
Using the unique imaging performance of the developed methods, it is further
established that MSOT can actually resolve anatomical, dynamic and molecular
information in mice and that it can be used for assessing biodistribution and
pharmacokinetic parameters of molecular probes and contrast agents in tissue. A
complete whole-body mouse scan is shown, resolving anatomical hemoglobinbased
contrast. Functional imaging is presented by tracking contrast enhancement
in the kidneys due to perfusion of systemically administered Indocyanine green
(ICG). Also the clearance rate of ICG and liposomal ICG from the blood pool is
determined by means of MSOT. Molecular imaging performance is shown by
detecting optical reporter agents (here a phosphatidylserine targeting fluorescent
dye) within mouse xenograft tumors.