Multimodal imaging of histotripsy liquefaction

Left Column: Gross observation of liquefaction zone in red blood cell phantom.

Right Column: T2-weighted image of phantom.

Image guidance for histotripsy requires both quantification of the bubble cloud activity and accurate delineation of the treatment zone. Passive cavitation imaging (PCI) is an ultrasound imaging modality that spatially maps the power of ultrasound emissions generated by bubbles. Our recent study shows that PCI is significantly more accurate and sensitive than B-mode ultrasound imaging for predicting histotripsy ablation. Nevertheless, PCI is an inherently two-dimensional image, and suffers from poor range resolution. Magnetic resonance (MR) imaging provides excellent soft-tissue contrast and three-dimensional anatomical details, but has a limited temporal resolution compared to the histotripsy pulse. We have shown that combining magnetic resonance (MR) and diagnostic ultrasound imaging can improve classifying histotripsy ablation. Interestingly, the greatest changes observed on conventional B-mode or MR imaging relative to baseline in the samples do not necessarily indicate the regions of strongest bubble activity. Areas under the ROC curve for predicting phantom or liver liquefaction were significantly greater than 0.5 for passive cavitation imaging power, plane wave and conventional B-mode grayscale, T1, T2, and ADC. The acoustic power mapped via PCI provided a better prediction of liquefaction than assessment of the liquefaction zone via conventional B-mode or MR imaging for all samples. The DSC values for T2-weighted images were greater than those derived from conventional B-mode images. These results indicate diagnostic ultrasound and MR imaging provide complimentary sets of information, demonstrating that multimodal imaging is useful for assessment of histotripsy liquefaction. More information can be found here.

Hematoxylin and eosin clot stains for clots exposed to histotripsy. Clots were formed in (top) Flint glass (elastic modulus 2.9 kPa) or (Bottom) Borosilicate glass (elastic modulus 4.3 kPa) to vary the stiffness. The passive cavitation image (blue colormap overlay) indicate strong bubble cloud activity in locations of clot ablation.

Pre-clinical studies have demonstrated histotripsy efficacious for acute clot ablation. Chronic deep vein thrombi are stiffer than acute thrombi, which will modulate the bubble cloud activity. The Specific Objective of this study was to determine the relationship between medium stiffness and bubble cloud activity necessary for liquefaction. Tissue-mimicking agarose phantoms with elastic moduli ranging from 10 to 150 kPa were exposed to histotripsy pulses of 5-ms duration and peak negative pressures of 12-24 MPa. Bubble cloud emissions mapped with passive cavitation imaging were correlated with the phantom liquefaction zone using receiver operator characteristic analysis. The strength of bubble emissions necessary for liquefaction was extracted for each phantom stiffness. Strong bubble cloud emissions were observed on passive cavitation imaging for all phantoms. No change was observed with phantom stiffness in the emission power necessary for liquefaction. Further, there was no indication of changes in the strength or location of bubble cloud emissions with phantom stiffness. The Key Outcome from this study is a fixed threshold acoustic power mapped with passive cavitation imaging can be utilized for predicting liquefaction of acute and chronic thrombus.

Key References:

Samuel A. Hendley, Viktor Bollen, Jonathan Paul, and Kenneth B. Bader, “In vitro assessment of histotripsy liquefaction with passive cavitation imaging in elastic media,” Physics in Medicine and Biology 64(14):145019, 2019. doi: 10.1088/1361-6560/ab25a6

Kenneth B. Bader, Samuel A. Hendley, Gregory J. Anthony, Viktor Bollen, “Observation and modulation of the dissolution of histotripsy-induced bubble clouds with high frame rate plane wave imaging,” Physics in Medicine and Biology 64(11): 115012. doi: 10.1088/1361-6560/ab1a64

Gregory J. Anthony, Viktor Bollen, Tatjana Antic, Steffen Sammet, and Kenneth B. Bader, “Assessment of histotripsy-induced liquefaction with diagnostic ultrasound and magnetic resonance imaging in vitro and ex vivo,” Physics in Medicine and Biology 64: 095023, 2019. doi: 10.1088/1361-6560/ab143f

Kenneth B. Bader, Kevin J. Haworth, Christy K. Holland, “Post hoc analysis of passive cavitation imaging for classification of histotripsy-induced liquefaction in vitro,” IEEE Transactions on Medical Imaging, 37 (1): 106-115, 2018. doi: 10.1109/TMI.2017.2735238

Kevin J. Haworth, Kenneth B. Bader, Kyle T. Rich, Christy K. Holland, T. Douglas Mast, “Quantitative frequency-domain passive cavitation imaging,” IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control, 64(1): 177-191, 2017. doi: 10.1109/TUFF.2016.2620492