Research / Clinical Summary

Yuko Kono MD, PhD Assistant Clinical Professor, Medicine Contact by Email

Contrast enhanced ultrasound, Molecular imaging, Cancer, Angiogenesis 

My main research has been contrast enhanced ultrasound imaging, particularly in tumor diagnosis and assessment of tumor response to treatment. Contrast ultrasound is a new imaging modality that allows us not only to diagnose tumors but also to quantitate tumor blood flow and fractional blood volume, which is potentially useful to monitor therapeutic response at bedside.

The ultrasound machine we currently have for small animal imaging is the Siemens Antares with a 13 MHz transducer, which is located at the UCSD Hillcrest Medical Center. This transducer has a focused beam that produces a 1.8 mm slice thickness at the focal zone that can be moved from the near field to the far field with an imaging window as small as 2 cm wide by 1.5 cm deep. The 2D frame-rate is sufficiently high to freeze respiratory and cardiac motion. Duplex and color Doppler as well as M-mode and 3D are all available on the 13 MHz transducer. The detail and information content of these images suggest that sonography of the mouse at 13 MHz should be capable of detecting tumors in the liver or any deep tissue to monitor their size or any other parameter.

In-vivo imaging of live animals with implanted or naturally occurring tumors is a powerful technique for the development and testing of therapies and interventions. The ability to detect and monitor tumors without the need to kill the animal allows for longitudinal studies to follow tumor size during growth and after interventions. Since biological variations among animals can be large, monitoring the same animals over time decreases variance and therefore the number of animals needed. Combining the ability to image the same animal over the course of tumor growth and therapy with the assessment of tumor characteristics such as blood flow, micro vascular density, and degree of angiogenic response adds the ability to detect tumor response to therapy other than change in tumor size. Relative blood flow and fractional blood volume indices can be assessed with ultrasound contrast intermittent imaging. We showed that fractional blood volume determined by intermittent imaging following long interscan delay using a Vx2 tumor model correlates with micro vascular density, an index of angiogenesis. The use of dynamic CT or MRI that acquires several images during the arrival and washout of contrast media allows the calculation of a capillary surface product that correlates with the angiogenic response. The acquisition of these dynamic series can then be evaluated by the Computing and Kinetics to extract these perfusion indices. Developing imaging capabilities of animal models, particularly mice, will allow the exploration of innovative imaging tools such as targeting specific receptors, altered or up-regulated cellular process, or detection of gene expression in gene-therapy strategies.