Advances in ultrasound based methods for the non-invasive assessment of the
tumor microcirculation are described. Two new ultrasound approaches are hi
ghlighted. The first method relies on commercially available ultrasound con
trast agents in combination with specialized nonlinear imaging sequences. N
onlinear scattering by microbubble contrast agents provides a unique intrav
ascular signature that can be distinguished from the echoes caused by surro
unding tissues. Through destruction-reperfusion experiments it is possible
to use microbubble contrast agents as a tracer revealing the kinetics of tu
mor blood flow. The second ultrasound method for examining the microcircula
tion involves the use of much higher frequencies. At frequencies on the ord
er of 50 MHz, Doppler processing allows the direct assessment of flow dynam
ics in realtime in arterioles as small as 15 mum. Three dimensional Doppler
maps of flow patterning are presented. The strengths and weaknesses of the
se new methods are discussed and the potential for their use in preclinical
animal drug studies, clinical drug trials, and prognostic studies is descr
ibed.