In vivo preclinical photoacoustic imaging of tumor vasculature development and therapy

Abstract

The use of a novel all-optical photoacoustic scanner for imaging the development of tumor vasculature and its response to a therapeutic vascular disrupting agent is described. The scanner employs a Fabry-Perot polymer film ultrasound sensor for mapping the photoacoustic waves and an image reconstruction algorithm based upon attenuation-compensated acoustic time reversal. The system was used to noninvasively image human colorectal tumor xenografts implanted subcutaneously in mice. Label-free three-dimensional in vivo images of whole tumors to depths of almost 10 mm with sub-100-micron spatial resolution were acquired in a longitudinal manner. This enabled the development of tumor-related vascular features, such as vessel tortuosity, feeding vessel recruitment, and necrosis to be visualized over time. The system was also used to study the temporal evolution of the response of the tumor vasculature following the administration of a therapeutic vascular disrupting agent (OXi4503). This revealed the well-known destruction and recovery phases associated with this agent. These studies illustrate the broader potential of this technology as an imaging tool for the preclinical and clinical study of tumors and other pathologies characterized by changes in the vasculature.

Optical coherence tomography today: speed, contrast, and multimodality

“…218) to the centimeter level in whole-body illumination PAT with a resolution of ∼100 μm. 219 A table comparing OCT and photoacoustic imaging is given below in Table 3 for a brief comparison of some important features of these two modalities.…”

Multiplexed imaging for diagnosis and therapy

“…PAI provides activatable molecular contrast, which can then be superimposed on an anatomical background provided by traditional US using macroscopic or microscopic imaging configurations 95 . Some endogenous biological molecules naturally exhibit sufficient photoacoustic conversion efficiency necessary for PAI contrast (in particular haemoglobin, for probing hypoxia 96 or angiogenesis 97 ), and likewise do exogenous fluorescent dyes used in traditional molecularly targeted OI strategies 98 . However, the customisable structure and composition of nanomaterials have motivated their status as perhaps the most 'engineerable' platforms for PAI, particularly for integrating photoacoustic imaging with MRI, OI and therapeutic strategies.…”

Photoacoustic imaging of fluorophores using pump-probe excitation

“…For the PA imaging experiments in tissue phantoms, the output of the OPO was coupled into two separate fibers (1.5 mm core dia.) to direct the pump and probe pulses to an all-optical PA scanner based on a Fabry-Pérot etalon ultrasound sensor, which is described in detail elsewhere [32][33][34]. The PA imaging experiments are described in section 3.4.…”