Technology of Ultrasound-Guided Therapy
The first published medical use of ultrasound was in 1942 when Dr. Karl Dussik measured transmission attenuation through the head to diagnose brain tumors. Twenty years later, Berlyne was the first to use ultrasound to guide a needle, in this case for renal biopsies. Since then, ultrasound has grown into the multidimensional, multimodality technology of today, used daily for image-guided therapies.
KeywordsAttenuation Paclitaxel Doxorubicin Curcumin Rapamycin
The first published medical use of ultrasound was in 1942 when Dr. Karl Dussik measured transmission attenuation through the head to diagnose brain tumors . Twenty years later, Berlyne was the first to use ultrasound to guide a needle, in this case for renal biopsies . Since then, ultrasound has grown into the multidimensional, multimodality technology of today, used daily for image-guided therapies.
Ultrasound has several valuable qualities for image-guided therapy, primarily its high frame rate, portability, and safety. It can be incorporated easily into almost all medical and surgical environments and can be used repeatedly without risk of ionizing radiation. It can be used to assess the dynamic aspects of procedures, such as tissue and instrument motion. The ultrasound signal also carries a great deal of information for visualizing structure, blood flow, stiffness, and other tissue properties from a single device. A wide range of transducers are available, allowing imaging both from inside and outside the body. Depending on the transducer, a user can image across an entire organ or focus on detailed substructure over a small area.
This chapter reviews ultrasound technology for use in image-guided therapy. While it is assumed that most readers are familiar with the subject, some basic principles and uses of ultrasound are included for completeness. Following this, the subset of ultrasound technologies and applications relevant to image-guided therapy via tissue characterization and guidance are presented.
Ultrasound Imaging Modes
B-Mode and Doppler
Recent investigations of 3-dimensional contrast quantification have shown that the reproducibility and quality of quantification is much greater than in two dimensions [22, 23]. Such techniques may enable more precise determination of a patient’s response to therapy to more rapidly optimize treatment. Another active research area is targeted contrast. In this case, contrast microbubbles are coated with ligands designed to preferentially bind to proteins expressed within the body by specific diseases or disease states . For instance, a VEGF receptor may preferentially bind to angiogenic factors, highlighting areas of possible tumor growth . Such techniques would enable both early and more precise therapy by detecting areas where therapy may be most effective.
Finally, while microbubble contrast agents remain intact under low sonic intensity, they collapse and break apart under only slightly higher intensity. This contrast destruction offers a potential vector for targeted drug delivery . Microbubbles can be filled with drugs, which are nonreactive while contained, and then released preferentially in target tissues under ultrasound visualization and control. Examples of drugs being investigated include rapamycin, curcumin, doxorubicin, and paclitaxel [27, 28].
Elastography based on manual compression has been investigated for identifying and characterizing suspicious lesions in many organs, including the breast, prostate, and thyroid . Barr et al. report, for instance, that a ratio of the longest dimension of a lesion in elastography versus B-mode greater than one is characteristic of malignancy . Other studies characterize lesions based on the ratio of stiffness inside and outside a lesion, known as the strain ratio . Manual elastography has also been used to visualize lesions both before and after radiofrequency ablation [32, 33].
Acoustic Radiation Force Impulse (ARFI) is a novel method of achieving tissue compression at greater depths and with greater consistency than that achievable through surface compression. This technique uses the sonic pulse, known as a “push pulse” to compress tissue along a scan line. Like manual elastography, ARFI has been investigated for lesion characterization [34, 35] and evaluating lesions before and after radiofrequency ablation .
Beyond relative stiffness, quantitative measurement of tissue modulus holds promise for more precise localization and characterization of lesions. Compression elastography, however, cannot quantify modulus because physical boundary conditions cannot be controlled . Recently a novel technique has been developed to achieve this quantification, which measures the speed of shear waves generated by an ARFI push pulse . Shear waves travel perpendicular to the push pulse, and their velocity is proportional to tissue modulus and independent of push pulse intensity. A related technique called supersonic shear imaging uses multiple push pulses at progressively increasing depth to create shear waves, which constructively interfere to form plane shear waves . Using imaging at up to 5,000 frames/s, the velocity of these plane shear waves are measured to produce a map of tissue elasticity.
Various tools have been investigated for aligning the volume data with the tracking system for fusion display [47, 48, 49, 50]. Clinical implementation of fusion imaging has suffered, however, due to the time required to achieve adequate alignment using traditional methods. Recent advancements in automatic image analysis may potentially reduce this time greatly.
Given the variety of technologies available both for imaging and navigation, it is clear that ultrasound offers tremendous value and potential. Whether for detecting, localizing, characterizing, or treating lesions, the variety of imaging modalities, including B-mode, Doppler, contrast, and elastography, and the variety of transducer types provide a powerful toolkit all in a single machine. As research progresses and yet more modalities and transducers become available, ultrasound will no doubt continue to be a mainstay of image-guided therapy well into the future.
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