Super-harmonic contrast imaging

Ultrasound contrast imaging detects signals from microbubble contrast agents injected intravenously to visualise blood flow to tissues.  These gas-filled microbubbles contrast agents are safe to inject, stay within the vasculature, and strongly scatter ultrasound waves that are picked up by ultrasound transducers. Ultrasound contrast imaging is used to identify where blood is not properly perfusing different parts of organs, such as the liver or heart, to guide biopsies and diagnose medical conditions. However, ultrasound contrast images from current clinical imaging systems technology have lots of tissue “clutter” signal, so it can be difficult to determine if a received signal is from the contrast agent or the tissue.  

Microbubbles in motion

We are therefore developing and using super harmonic contrast imaging that allows unprecedented visualisation of the microcirculation. This method makes use of the very broad frequency range of acoustic signals scattered by microbubbles to generate images with tissue clutter effectively suppressed.  This method works by using a 2nd transducer, operating about 1/10th of the main imaging frequency, to transmit an ultrasound wave into the tissue. The primary imaging transducer then detects the scattered broad band signal from the microbubbles, from the 3rd to >15th harmonic of the transmitted wave. The tissue signals are limited to the fundamental and 2nd harmonic of the transmitted signal, so are suppressed by the image acquisition method. The superharmonic contrast image, which traces the vasculature where microbubbles have travelled, can be overlaid on a standard ultrasound image of the anatomy acquired with the primary imaging transducer.

We are creating the new dual-frequency ultrasound transducers and systems needed for the superharmonic ultrasound imaging method. The new devices have a standard ultrasound array transducer as the primary imaging transducer (typically 15-30 MHz), with secondary transducers (~1-4 MHz) either flanking or placed behind the primary array. These dual-frequency transducers are connected to programmable imaging control systems so we can investigate the image acquisition sequences to produce high quality superharmonic contrast images.  We are designing, fabricating and testing dual-frequency transducers operating at a range of frequencies and tailored for different imaging settings.  

Dual frequency probe, emitting low frequencies of 2 MHz and receiving high frequencies of 20 MHz


Applications we are investigating with our collaborators include cancer imaging, by measuring the changes in vessel structures as tumours grow or are treated, or for early detection of the dis-ordered vasculature typical of tumours. Superharmonic imaging can be used for molecular imaging because we can detect stopped microbubbles that have attached to biomarkers on vessel walls, where other ultrasound contrast imaging techniques have difficulty. With advanced signal processing, we can measure blood flow velocity in the micro vessels. We are also investigating these methods for imaging the neuro vasculature structure and function and impacts of diseases such as stroke.  

Image shows in vivo tissue imaging using the superharmonic contrast imaging technique.
Author: Jing Yang