Multispectral optoacoustic tomography (MSOT) offers exciting new possibilities in imaging tumor dynamics in preclinical models of cancer. Near infrared laser light is used to excite tissue, and due to the photoacoustic effect, absorbed light energy can be converted into acoustic waves. The detection of ultrasound as opposed to photons enables high resolution optical imaging deep in tissue. Image contrast is based on engdogenous chromophores such as deoxy- and oxy-hemoglobin as well as melanin. In addition, exogenously administered contrast agents with characteristic absorbance in the near infrared can also be used to target cancer cells.
Here, we utilize the fast imaging rate of MSOT to perform dynamic contrast enhanced (DCE-MSOT) studies in vivo, as a method to track the kinetics of dynamic processes such as the clearance of hydrophilic dyes through the metabolic organs and the heterogeneous accumulation of ICG in orthotopic tumors, at high spatial and temporal resolution.
Multispectral optoacoustic tomography (MSOT) offers fast imaging of optical contrast at high spatial resolution. Spectral characteristics of multiple injected optical markers enable separation from endogenous contrast (predominantly hemoglobin) using multispectral excitation, and with a fast imaging rate of up to 5 multispectral images per second
The injected agents are resolved at the sub-organ or tumor level using multispectral unmixing and the temporal evolution of the signal is fitted to pharmacokinetic models on a per-pixel basis, allowing for the analysis of important kinetic parameters such as time-to-peak and half-life. The determined parameters are plotted as parametric maps overlaid on an anatomical image.
When studying the perfusion of orthotopic mammary fat pad tumors with ICG, well-perfused areas in the tumor periphery can be distinguished from hypo-perfused areas in the core of the tumor. This methodology enables assessment of treatment response or vascularization and perfusion. On a different page, this was also shown to enable organ clearance studies in the kidneys.
The presented work introduces DCE-MSOT as a powerful imaging modality that, in addition to whole body imaging with high spatial resolution enabled by MSOT, allows for PK modeling of injected substances non-invasively and at high temporal resolution. It is shown that DCE-MSOT allows for the determination and visualization of important pharmacokinetic parameters in multiple organs and tumor and can supplement DCE-MRI by extending high-rate imaging to the regime of optical contrast.