Photothermal optical coherence tomography (PT-OCT) has the potential to increase the molecular specificity of OCT for
in vivo pre-clinical studies of cancer, in order to better understand drug uptake and treatment response. However, the use
of PT-OCT to image contrast agents in vivo has yet to be demonstrated. Here, we characterize PT-OCT imaging of gold
nanorod (GNR) contrast agents, and we further apply these techniques for in vivo imaging. The PT-OCT signal was
characterized and compared to a numerical model of the bio-heat equation with respect to varying photothermal chop
frequency, photothermal laser power, OCT image reflectivity, and concentration of GNRs. PT-OCT images were taken
of GNR+ and GNR- solid agarose phantoms in capillary tubes, and 400 pM GNR matrigel injections into a mouse ear.
Experimental PT-OCT data varied as predicted with closed form models of the bio-heat equation. Increasing the
concentration of GNRs caused a linear increase in the PT-OCT signal, with GNR sensitivity as low as 7.5 pM compared
to a scattering control (p<0.01). PT-OCT images in capillary tubes and the live mouse ear demonstrated an appreciable
increase in signal in the presence of GNRs compared to controls. The demonstrated in vivo PT-OCT capabilities using
GNR contrast agents is sufficient to image molecular expression, based on published molecular imaging studies
employing GNR contrast agents in vivo. Therefore, this work demonstrates an important transition of PT-OCT to in vivo
imaging, and marks the next step towards its use for in vivo molecular imaging.
Peripheral arterial disease (PAD) leads to an increased risk of myocardial infarction and stroke, increased mortality, and
reduced quality of life. The mouse hind limb ischemia (HLI) model is the most commonly used system for studying the
mechanisms of collateral vessel formation and for testing new PAD therapies, but there is a lack of techniques for
acquiring physiologically-relevant, quantitative data intravitally in this model. In this work, non-invasive, quantitative
optical imaging techniques were applied to the mouse HLI model over a time course. Optical coherence tomography
(OCT) imaged changes in blood flow (Doppler OCT) and microvessel morphology (speckle variance OCT) through the
skin of haired mice with high resolution. Hyperspectral imaging was also used to quantify blood oxygenation. In
ischemic limbs, blood oxygenation in the footpad was substantially reduced after induction of ischemia followed by
complete recovery by three weeks, consistent with standard measures. Three dimensional images of the vasculature
distal to vessel occlusion acquired with speckle variance OCT revealed changes in OCT flow signal and vessel
morphology. Taken together, OCT and hyperspectral imaging enable intravital acquisition of both functional and
morphological data which fill critical gaps in understanding structure-function relationships that contribute to recovery
in the mouse HLI model. Therefore, these optical imaging methods hold promise as tools for studying the mechanisms
of vascular recovery and evaluating novel therapeutic treatments in preclinical studies.
Preclinical molecular imaging of cancer has the potential to increase the understanding of fundamental cancer biology,
elucidate mechanisms of cancer treatment resistance, and increase effectiveness of drug candidates. Optical and
magnetic resonance imaging contain complementary strengths, suitable for gaining a wealth of knowledge when
combined. Here, we demonstrate the inherent contrast sensitivity of single walled carbon nanotubes to absorption based
photothermal optical coherence tomography (PT-OCT), and magnetic resonance imaging spin dephasing contrast (T2).
A spectral-domain OCT system was interfaced with an amplitude-modulated (100 Hz) titanium sapphire pump beam for
PT-OCT imaging. MRI was performed with a commercial 4.7 T animal scanner. With both imaging tools, contrast
agent signal linearity (r2 > 0.95) and nM sensitivity over background (p < 0.05) was experimentally determined with
serially dilute solutions of carbon nanotubes coated in amine-terminated polyethylene glycol. The surface functionalization chemistry for carbon nanotubes is well understood, and molecular targeting has been demonstrated in vitro and in vivo, making carbon nanotubes an attractive agent for molecular imaging in preclinical models. We have demonstrated the initial characterization steps for using carbon nanotubes for multi-modality imaging with PT-OCT and MRI.
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