Contrast Agents ch. 17

Chapter 17: Abdominal Applications of Ultrasound

Contrast Agents

Overview

  • Contrast-enhanced sonography (CES) has clinical uses that help in reducing or eliminating some limitations associated with ultrasound imaging (US) and Doppler blood flow detection.

Limitations of Conventional Ultrasound

  1. Spatial and contrast resolution on grayscale images.

  2. Difficulties in detecting low-velocity blood flow and flow in very small vessels when using Doppler flow detection modes.

Vascular Ultrasound Contrast Agents (UCAs)

Functions and Benefits

  • Vascular ultrasound contrast agents (UCAs) serve several purposes:

    • Enhancement of Doppler (color and spectral) flow signals: They add acoustic scatterers to the bloodstream, improving Doppler flow detection.

    • Improvement of blood flow visualization: They enhance grayscale ultrasound imaging of flowing blood, revealing changes to grayscale echogenicity in tissues when utilizing contrast-specific imaging software like harmonic imaging (HI).

Example of UCAs in Action

  • An example demonstrates color Doppler imaging of the right renal artery:

    • Before (A): No vascular abnormality; minimal color-flow information.

    • After (B): Improvement in the visualization of renal artery flow following IV contrast administration.

Historical Context

  • In 1968, researchers injected agitated saline into the ascending aorta during echocardiographic examinations, which created microbubbles that provided strong echoes in echo-free regions. However, due to their size and instability, these saline microbubbles are not suitable for comprehensive sonographic evaluations of the left heart and systemic circulation as they do not persist through the pulmonary and cardiac circulations.

Requirements for Clinically Useful UCAs

  • To qualify as effective UCAs, agents must:

    1. Be nontoxic.

    2. Contain microbubbles or microparticles that are small enough to pass through pulmonary capillary beds (less than 8 microns).

    3. Be stable enough to facilitate multiple recirculations throughout the body.

FDA-Approved UCAs

  • For echocardiographic applications:

    • Definity

    • Optison

    • Imagent

  • Other Agents (used in Europe only):

    • Levovist

    • SonoVue

Types of Ultrasound Contrast Agents

Tissue-Specific UCAs

  • UCAs can be microbubbles that are either removed from the bloodstream or have an affinity for specific tissues, enhancing the visibility of certain structures like the reticuloendothelial system (RES) in the liver and spleen or thrombus formation.

Mechanism of Tissue-Specific UCAs

  1. Sonazoid:

    • An approved tissue-specific UCA in Japan.

    • It initially behaves as a vascular agent by enhancing the detection of flowing blood when injected intravenously.

    • Over time, microbubbles are phagocytosed by macrophages (specifically Kupffer cells) in the liver and spleen, becoming stationary in tissue for several hours.

  2. Insonation Process:

    • When insonated after uptake, stationary contrast microbubbles increase the reflectivity of the tissue containing contrast.

    • If the acoustic energy applied to the tissue is of the appropriate level, microbubbles oscillate (produce harmonic signals detectable via grayscale HI) and can rupture.

    • The rupturing of microbubbles produces random Doppler shifts, appearing as transient colors on a color Doppler display.

Illustrative Example of Sonazoid in Action

  • The rupture of contrast microbubbles within RES cells causes a random color display on imaging, indicative of enhanced tissue reflectivity due to microbubble presence.

Oral Ultrasound Contrast Agents

  • SonoRx™: Contains simethicone-coated cellulose. Upon ingestion, this enhances homogeneous transmission of sound through the contrast-filled stomach.

Ultrasound Equipment Modifications

Contrast-Specific Ultrasound Imaging Modes

  • The implementation of “contrast-specific” ultrasound imaging modes has considerably enhanced the clinical utility of CES. These modifications can be swiftly adapted to current digital and software-driven ultrasound systems.

Harmonic Imaging (HI)

  • Utilizes broadband transducers similar to conventional ultrasound:

    • Configured to exclusively receive echoes at the harmonic frequency (twice the transmission frequency).

    • Microbubbles behave in a way (oscillation) that enables better visualization and detection of blood flow when subjected to the acoustic energy from the ultrasound field.

Signal Characteristics

  • As microbubbles oscillate, the reflected echoes include energy from the fundamental frequency and multiple harmonics. The focus of the technological advances in HI has been mainly on grayscale HI (GSHI), allowing better detection of contrast-enhancement in blood flow and organs during grayscale ultrasound.

Overcoming Limitations of Doppler Ultrasound Techniques

  • GSHI for CES effectively avoids many limitations of conventional Doppler methods, such as angle dependence and “color blooming.”

  • Echoes from microbubbles yield a higher signal-to-noise ratio, making these regions easier to visualize. While body tissues do produce harmonic signals, their contribution to imaging is negligible compared to microbubbles.

Image Processing Algorithms

  • HI technology incorporates image processing algorithms to subtract artifacts from body tissues, ensuring that echoes from microbubbles are prioritized in imaging. The wide-band GSHI technology further enhances differentiation between regions with and without contrast, facilitating better real-time grayscale blood pool imaging (perfusion imaging).

Advantages of GSHI

  1. Higher frame rates.

  2. Improved contrast resolution.

  3. A reduction in artifacts.

  • Typically, these benefits suggest that traditional color-flow imaging may be rendered unnecessary or inadvisable when using GSHI for CES.

Drawbacks and Solutions Regarding Microbubbles

  • Use of microbubble UCAs can lead to their destruction by acoustic energy. A significant number can be destroyed, even under low-pressure conditions in the ultrasound field.

  • To combat this:

    • Maintain a low mechanical index (MI) during operation, although this may limit tissue penetration.

    • Implement intermittent imaging, where the ultrasound system is programmed to transmit and receive data at discrete intervals to minimize microbubble destruction while allowing new bubbles to enter the field.

Future Developments

  • Ongoing enhancements include:

    • On-board video densitometry.

    • Integrated backscatter calculations from contrast agents.

    • Advanced three-dimensional (3D) imaging methods.

Examples of Advanced Imaging

  • Contrast-enhanced 3D power Doppler images allow clinicians to visualize fine details of renal vasculature in animal models.

  • A 3D grayscale harmonic image combined with vascular UCA results in a detailed “ultrasound angiogram.”

Clinical Applications of CES

Liver Sonography

  • CES is particularly sensitive in detecting medium-to-large hepatic lesions, but is limited in finding small (<10 mm), isoechoic lesions, especially in patients affected by obesity or diffuse liver disease.

  • Benefits of UCAs:

    • Enhanced detection and characterization of hepatic masses.

    • Improved visual confirmation of blood flow intra- and extrahepatically.

Vascular UCAs Enhancements

  • The application of vascular UCAs boosts the detection of hepatic blood flow more effectively in normal individuals and those with liver disease, including cases of portal hypertension. Assessments of blood flow through transjugular intrahepatic portosystemic shunts (TIPS) have been made more effective.

Phases of Blood Flow to the Liver

  1. Hepatic Arterial Phase:

    • Enhanced detection occurs first after IV UCA administration, providing the earliest visualization.

  2. Portal Venous Phase:

    • Identifiable portal venous flow follows, typically around 37 seconds after injection, observed in the portal vein.

  3. Late Vascular Phase:

    • Occurs approximately 71 seconds post-injection, where liver parenchyma begins to echogenically enhance, with improved visualization of major hepatic vessels.

Examples in Imaging

  • HCC (Hepatocellular Carcinoma):

    • Practiced before and after contrast administration using GSHI, allowing for better delineation and confirmation of lesions.

  • Focal Nodular Hyperplasia (FNH):

    • Improved detection and delineation before and after contrast administration illustrate the success of UCA applications.

  • Renal Imaging: Attributes of UCAs extend to significant enhancements in the visualization of renal blood flow, including showing lesions, distortions, and even intratumoral flow in renal tumors, drastically improving diagnosis processes.

Spleen and Pancreas Applications

  • Ongoing clinical investigations indicate potential for CES in evaluating:

    • Spleen: Malignant nodules, splenic trauma, and other tumors linked to Hodgkin lymphoma.

    • Pancreas: Tumors, pancreatitis, and lesions neighboring the pancreas.

Organ Transplants

  • CES significantly enhances the evaluation of blood flow in arteries and veins supplying transplanted organs. Improved assessments of blood flow anomalies and differentiating ischemic regions within renal and pancreatic grafts have also been observed.

Other Applications of CES

  • CES is relevant in evaluating:

    • Aortic stent-grafts.

    • Mesenteric arteries for ischemia.

    • Diagnosing and monitoring aortic aneurysms, stenoses, endovascular leaks or dissections, and identifying thromboses or filters in the inferior vena cava (IVC).

IV Insertion for Contrast-Enhanced Imaging

Guidelines for IV Insertion

  • Emphasize patient preparation, appropriate catheter choice, and adherence to safety protocols. Peripheral vein cannulation is the most common access method, typically performed by various health care professionals.

Equipment Preparation:

  • Thorough hand-washing is necessary before the procedure.

  • Essential materials include:

    • IV catheter (18-22 gauge).

    • Tourniquet.

    • Chlorhexidine or alcohol for sterilization.

    • Sterile gloves, gauze, tape, and IV extension tubing.

Venipuncture Techniques

  • Peripheral Vein Cannulation: A common method for vascular access. Utilizes real-time ultrasound to aid in venipuncture using a catheter-over-needle technique, primarily in difficult-access veins of the upper arm.

  • Preferred Veins:

    • Dorsal hand veins.

    • Cephalic vein.

    • Basilic vein.

    • Median cubital vein.

  • Avoid areas with infections, phlebitis, compromised circulation, or near frequently flexing joints.

Administering Contrast Agents

  • Patient Monitoring: Key to watch for any adverse reactions during contrast administration.

  • Adopt aseptic techniques and secure fixation for IV access. Properly tape down to ensure safe access for the injection of contrast agents into the IV line.

Common IV Insertion Vein Locations

  • Cephalic vein, antecubital vein, anchilor vein, and dorsal venous network are common sites where IVs are inserted for contrast-enhanced imaging.