Diagnostic ultrasound ( PDFDrive )

CHAPTER 3 Contrast Agents for Ultrasound 67
FIG. 3.17 Disruption-Replenishment Imaging Used to Quantify Flow in a Renal Cell Carcinoma in a Patient Undergoing Antiangiogenic
Treatment. A side-by-side contrast image (conventional on right, simultaneous contrast-enhanced ultrasound [CEUS] on left) of a large renal cell
carcinoma is made during a steady intravenous infusion of the agent Deinity. Analysis software (QLAB, Philips Ultrasound, Bothell WA) measures
wash-in of a region of interest from the cineloop record. The steeper the initial slope, the greater the low rate; the higher the asymptote, the
greater the vascular volume. Disruption-replenishment imaging thus allows quantitation of changes in tumor low and relative vascular volume.
Considerable experience accumulated to date suggests that
dynamic contrast-enhanced ultrasound, with its advantage of
high sensitivity, portability, and a pure intravascular tracer, is a
strong candidate for this role 70-75 ; it has been incorporated into
the current European guidelines for the clinical use of contrast
agents. 76
SAFETY CONSIDERATIONS AND
REGULATORY STATUS
Contrast ultrasound examinations expose patients to ultrasound
in a way that is identical to that of a normal ultrasound examination.
Yet the use of ultrasound pulses to disrupt bubbles that sit
in microscopic vessels, and the knowledge that ultrasound and
bubbles can be used deliberately to penetrate cell membranes
for the purpose of drug delivery and other therapies, 77 raise
questions about the potential for hazard. When a bubble produces
the brief echo that is associated with its disruption, it releases
energy it has stored during its exposure to the ultrasound ield.
Can this energy damage the surrounding tissue? At higher
exposure levels, ultrasound is known to produce bioefects in
tissue, the thresholds for which have been studied extensively. 78
Do these thresholds change when bubbles are present in the
vasculature? Whereas the safety of ultrasound contrast agents
as drugs has been established to the satisfaction of the most
stringent requirements of the regulating authorities in a number
of countries, it is probably fair to say that there is much to be
learned about the interaction between ultrasound and tissue
when bubbles are present.
he most extreme of these interactions is known as inertial
cavitation, which refers to the rapid formation, growth, and
collapse of a gas cavity in luid as a result of ultrasound exposure.
It was studied extensively before the development of microbubble
contrast agents. 79 In fact, most of the mathematical models used
to describe contrast microbubbles were originally developed to
describe cavitation. 80 When sound waves of suicient intensity
travel through a luid, the rarefactional half-cycle of the sound
wave can actually tear the luid apart, creating spherical cavities
within the luid. he subsequent rapid collapse of these cavities
during the compressional half-cycle of the sound wave can focus
large amounts of energy into a very small volume, raising the
temperature at the center of the collapse to thousands of degrees
Kelvin, forming free radicals and even emitting electromagnetic
radiation. 81 he concern over potential cavitation-induced bioeffects
in diagnostic ultrasound has led to many experimental
studies, many of them assessing whether the presence of contrast
microbubbles can act as cavitation seeds, potentiating bioefects. 82-87
his work has been reviewed by ter Haar 88 and by the World
Federation for Ultrasound in Medicine and Biology. 89,90 Although
it has been shown that adding contrast agents to blood decreases
the threshold for cavitation and related bioefects (e.g., hemolysis,