Imaging the microcirculation with high frequency ultrasound

Imaging with high frequency (HF) ultrasound at center frequencies of 20 MHz and higher allows visualization and mapping of vessels smaller than 100 microns in peripheral tissues. The primary limitations of moving to high frequencies addressed in this work include the lack of transducer arrays, thus requiring much slower mechanical scanning of single element transducers; increased sensitivity to tissue motion; and difficulties in detecting flow in the smallest vessels due to limited dynamic range. The goals of this research are to overcome these limitations and to demonstrate that HF ultrasound can be a useful tool for mapping blood flow in the microcirculation.; In this work, the HF color flow acquisition time is improved from on the order of 1 minute to 1 second by the first such application of a continuously scanned acquisition mode at high frequencies, called swept-scanning. The development of the first near real-time, HF ultrasound system based on swept-scanning for color flow imaging above 20 MHz is detailed. An eigendecomposition-based adaptive clutter filter is introduced for swept-scan data to optimally reject tissue echoes that overlap low velocity blood echoes. The color flow system is characterized though simulation, in vitro, and in vivo experiments. The use of the proposed HF color flow system is investigated for in vivo applications including mapping blood flow in the anterior chamber of the rabbit eye and in the skin. Color flow measurements are made to investigate changes in blood flow in the major arterial circle of the iris following administration of a vasoactive drug and following changes in temperature. The use of an ultrasound contrast agent (UCA) to improve the detection of flow in the smallest vessels of the microcirculation is investigated theoretically and experimentally as a means to overcome dynamic range requirements of detecting blood flow in arterioles and capillaries. To reduce angle dependency and improve flow quantification, a 25 MHz destruction/replenishment imaging mode is presented. A theoretical acoustic scattering analysis performed in the linear scattering regime for an UCA shows the possible existence of dipole resonances near 30 MHz for a 100 nm thick shell.