Ultrasound in Radiology: From Anatomic, Functional, Molecular Imaging to Drug Delivery and Image-Guided Therapy

Abstract

During the past decade, ultrasound has expanded medical imaging well beyond the "traditional" radiology setting: a combination of portability, low cost, and ease of use makes ultrasound imaging an indispensable tool for radiologists as well as for other medical professionals who need to obtain imaging diagnosis or guide a therapeutic intervention quickly and efficiently. Ultrasound combines excellent ability for deep penetration into soft tissues with very good spatial resolution, with only a few exceptions (ie, those involving overlying bone or gas). Real-time imaging (up to hundreds and thousands of frames per second) enables guidance of therapeutic procedures and biopsies; characterization of the mechanical properties of the tissues greatly aids with the accuracy of the procedures. The ability of ultrasound to deposit energy locally brings about the potential for localized intervention encompassing the following: tissue ablation, enhancing penetration through the natural barriers to drug delivery in the body and triggering drug release from carrier microparticles and nanoparticles. The use of microbubble contrast agents brings the ability to monitor and quantify tissue perfusion, and microbubble targeting with ligand-decorated microbubbles brings the ability to obtain molecular biomarker information, that is, ultrasound molecular imaging. Overall, ultrasound has become the most widely used imaging modality in modern medicine; it will continue to grow and expand.

Figure 1

Portable ultrasound equipment. (Left) “SonicWindow” Handheld C-scan device (Reprinted with permission, image courtesy of Analogic, Copyright, 2014) (Right) “V-Scan” Handheld B-scan device (Reprinted with permission, image courtesy of GE Healthcare, Copyright 2013)

Figure 2

Selected frames from a cardiac cycle obtained with using ultrafast compound Doppler. (a) Average flow in the artery indicating the selected frames. (b) Before the opening of the aortic valve, there is a minimal laminar flow. (c) and (d) Acceleration of the flow. (e) Inversion of the parabolic profile in the deceleration. (f) Local turbulence is present and propagates in the artery. (g) and (h) Laminar flows in diastole. Reprinted with permission from [61], Copyright, 2011, IEEE.

Figure 3

Components of Photoacoustic Tomography, with representative in vivo images across multiple resolution scales (A) Optical Resolution Photoacoustic Microscopy of sO2 in a mouse ear. (B) Acoustic Resolution Photoacoustic Microscopy of normalized total hemoglobin concentration, [hemoglobin], in a human palm. (C) Linear-array Photoacoustic Computed Tomography of normalized Methylene Blue concentration, [dye], in a rat sentinel lymph node (SLN). (D) Circular-array Photoacoustic Computed Tomography of cerebral hemodynamic changes, Δ [hemoglobin], in response to one-sided whisker stimulation in a rat. (E) Photoacoustic endoscopy of a rabbit esophagus and adjacent internal organs, including the trachea and lung. UST, ultrasonic transducer. Reprinted with permission from [100]; Copyright, 1012, American Association for the Advancement of Science.

Figure 4

Ultrasound imaging of subcutaneneous tumor in a murine model. Top Left: B-mode grayscale imaging (anatomy). Top Right: contrast mode (Cadence CPS), prior to microbubble administration. Bottom Left: contrast mode (Cadence CPS), following microbubble administration (at peak, ∼5 sec following iv bolus). Bottom Right: contrast mode (Cadence CPS), following microbubble administration (at peak, ∼30 sec following iv bolus). Imaging performed with Sequoia 512 scanner equipped with 15L8 probe.

Figure 5

Contrast ultrasound imaging of tumor vasculature perfusion in destruction-replenishment mode in a subcutaneous murine tumor model. Top Left: microbubbles within the tumor vasculature after intravenous administration, prior to the destructive pulse. Top Center: immediately after 2 s destructive pulse. Top Right: 2 s after cessation of the destructive pulse. Bottom Right: 6 s after destructive pulse. Bottom Center: 10 s after destructive pulse. Bottom Right: 20 s after destructive pulse. Imaging performed with Sequoia 512 scanner equipped with 15L8 probe (7 MHz, MI 0.2 for imaging, MI 1.9 for destruction).

Figure 6

Ultrasound Molecular Imaging of VEGFR2 with scVEGF-decorated microbubbles. Ultrasound imaging of subcutaneous colon adenocarcinoma. A, B-mode US image of tumor tissue marked by dotted line. B, Contrast US image of nontargeted MB after 6-minute dwell time. C, Contrast US image illustrates higher pixel intensity because of adherent scVEGF-MB. Copyright, 2010, Lippincott, Williams and Wilkins, reprinted with permission from reference [140].

Figure 7

Ultrasound-induced opening of blood brain barrier in a rat model. Decafluorobutane microbubbles (stabilized with DSPC and PEG Stearate) were injected intravenously, immediately followed by focused ultrasound treatment (IGT, 1 Hz, 20ms pulses, 1–2 min treatment duration) and intravenous administration of Gd-DTPA. MRI contrast extravasation and accumulation (white focal spots in the center of the image) observed minutes after ultrasound treatment and Gd-DTPA administration. Imaging performed at UVA Molecular Imaging Center (7T MRI Clinscan, Bruker/Siemens). Copyright, Max Wintermark, 2014, reprinted with permission.