Photoacoustic imaging in regenerative medicine using endogenous and exogenous contrast agents

With the advent of stem cell therapy for degenerative diseases and disorders, the need to track the homing, survival, migration, differentiation and pathophysiology of stem cells administered in a clinical study is crucial. Photoacoustic imaging (PAI) or Optoacoustic imaging combines optical absorption contrast with ultrasonic resolution and utilises both endogenous and exogenous contrast agents for gathering molecular information in real-time. This enables longitudinal detection at clinically relevant penetration depths in vivo. The motivation of the thesis is to explore the imaging capability of multispectral optoacoustic tomography (MSOT) using both exogenous and endogenous contrast agents. First, gold nanostars were designed and developed to have absorption in the second near-infrared window, particularly at 1064 nm. Moreover, the surface functionalisation with Chitosan improved the cellular labelling efficiency with gold nanostars. This translated to the in vitro visualisation of 50 mesenchymal stem cells (MSCs) in 1 µL volume. Next, the therapeutic response of the MSCs was monitored after labelling with gold nanostars in an osteoarthritis murine model. This study revealed that the labelled stem cells were tracked for 80 days in the knee while the gold nanostars administered on their own were cleared from the knee between 5 - 10 days. Most importantly, it was observed that the gold nanostars did not interfere with the regenerative properties of the MSCs and demonstrated a therapeutic response similar to the animals administered with unlabelled MSCs. Finally, the capability of MSOT to acquire functional information using endogenous contrast in comparison to laser Doppler imaging (LDI) was demonstrated in a hind limb ischaemia murine model. In comparison to LDI, MSOT facilitated a three-dimensional volumetric quantification of total haemoglobin and oxygen saturation while keeping extraneous variability to a minimum. Moreover, the need for using an exogenous contrast agent like gold nanostars in conjunction with PAI is demonstrated.

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University of Galway

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Attribution-NonCommercial-NoDerivatives 4.0 International

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University of Galway Theses (PhD Theses)