Quantitative Assessment of Microvascular Dynamics with Spectroscopic Large-Scale Optoacoustic Microscopy
Embargoed until 2026-04-15
Author
Date
2024Type
- Doctoral Thesis
ETH Bibliography
yes
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Abstract
Microcirculation is comprised of arteries, capillaries, and veins with sizes that are mostly invisible to the human eye. It plays a central role in supplying oxygen and nutrients to living tissues, and underlies a myriad of pathological processes. Imaging microcirculation in an unperturbed biological environment over time provides invaluable insights into tissue physiology, organ development and the underlying mechanisms of pathological alterations.
Optoacoustic imaging offers unique capabilities to measure microcirculation by capitalizing on the intrinsic optical absorption of hemoglobin in the visible and near infrared spectrum. By employing focused excitation light, optoacoustic microscopy offers rich morphological and functional information within microvascular structures in a non-invasive and label-free manner. Owing to the hybrid nature of optoacoustic imaging, the seamless integration with pulse-echo ultrasound offers complementary anatomical information and facilitates the interpretation and quantification of microvascular signals.
This thesis is dedicated to the technical development of a hybrid optoacoustic and ultrasound microscopy system and its application in various preclinical studies. A spectroscopic optoacoustic and ultrasound microscopy system was developed to image microvascular morphology and oxygenation in three dimensions at capillary resolution over centimeter field-of-view. Thanks to the excellent endogenous contrast from hemoglobin, the system is well suited to perform longitudinal in vivo studies without repeated injection of contrast agents and invasive procedures. On the application side, the first contribution aimed to track angiogenesis and vascular remodeling processes during murine skull development. Vasculature in the skull was accurately segmented from the cerebral vasculature, and its longitudinal changes were quantified and linked to the skull bone growth. The second contribution targeted the wound healing process in the dorsal murine skin. Skin layer-specific microvascular morphology and oxygenation dynamics were monitored comprehensively at large scale up to 10 days post injury.
A further contribution of the presented work is to enhance optoacoustic imaging performance in the mesoscopic depth regime. Instead of using focused excitation light, broad illumination is used in combination with focused ultrasonic detection, in order to achieve deeper penetration by taking advantage of low ultrasound scattering in biological tissues. In this regime, spatial resolution is determined by the acoustic properties of ultrasound transducer. By numerically modeling the shape and impulse response of the transducer and iteratively correcting for the acoustic detection deficiencies in a model-based reconstruction approach, the mesoscopic imaging performance was significantly enhanced as demonstrated in numerical simulations, phantoms and in vivo images in mice and human volunteers. Show more
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https://doi.org/10.3929/ethz-b-000668682Publication status
publishedExternal links
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Publisher
ETH ZurichSubject
Optoacoustic imaging; intravital microscopy; AngiographyOrganisational unit
09648 - Razansky, Daniel / Razansky, Daniel
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ETH Bibliography
yes
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