Objective
Hepatocellular carcinoma (HCC) is a highly prevalent form of liver cancer diagnosed
annually in 600,000 people worldwide. A common treatment is transarterial chemoembolization
(TACE), which interrupts the blood supply of oxygen and nutrients to the tumor mass.
The need for repeat TACE treatments may be assessed in the weeks after therapy with
contrast-enhanced ultrasound (CEUS) imaging. Although the spatial resolution of traditional
CEUS has been restricted by the diffraction limit of ultrasound (US), this physical
barrier has been overcome by a recent innovation known as super-resolution US (SRUS)
imaging. In short, SRUS enhances the visible details of smaller microvascular structures
on the 10 to 100 µm scale, which unlocks a host of new clinical opportunities for
US.
Methods
In this study, a rat model of orthotopic HCC is introduced and TACE treatment response
(to a doxorubicin-lipiodol emulsion) is assessed using longitudinal SRUS and magnetic
resonance imaging (MRI) performed at 0, 7 and 14 d. Animals were euthanized at 14
d for histological analysis of excised tumor tissue and determination of TACE response,
that is, control, partial response or complete response. CEUS imaging was performed
using a pre-clinical US system (Vevo 3100, FUJIFILM VisualSonics Inc.) equipped with
an MX201 linear array transducer. After administration of a microbubble contrast agent
(Definity, Lantheus Medical Imaging), a series of CEUS images were collected at each
tissue cross-section as the transducer was mechanically stepped at 100 μm increments.
SRUS images were formed at each spatial position, and a microvascular density metric
was calculated. Microscale computed tomography (microCT, OI/CT, MILabs) was used to
confirm TACE procedure success, and tumor size was monitored using a small animal
MRI system (BioSpec 3T, Bruker Corp.).
Results
Although there were no differences at baseline (p > 0.15), both microvascular density levels and tumor size measures from the complete
responder cases at 14 d were considerably lower and smaller, respectively, than those
in the partial responder or control group animals. Histological analysis revealed
tumor-to-necrosis levels of 8.4%, 51.1% and 100%, for the control, partial responder
and complete responder groups, respectively (p < 0.005).
Conclusion
SRUS imaging is a promising modality for assessing early changes in microvascular
networks in response to tissue perfusion-altering interventions such as TACE treatment
of HCC.
Keywords
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Article info
Publication history
Published online: March 01, 2023
Accepted:
January 25,
2023
Received in revised form:
January 23,
2023
Received:
October 13,
2022
Identification
Copyright
© 2023 World Federation for Ultrasound in Medicine & Biology. All rights reserved.
