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Elasticity mapping of murine abdominal organs in vivo using harmonic motion imaging (HMI).

ABSTRACT: Recently, ultrasonic imaging of soft tissue mechanics has been increasingly studied to image otherwise undetectable pathologies. However, many underlying mechanisms of tissue stiffening remain unknown, requiring small animal studies and adapted elasticity mapping techniques. Harmonic motion imaging (HMI) assesses tissue viscoelasticity by inducing localized oscillation from a periodic acoustic radiation force. The objective of this study was to evaluate the feasibility of HMI for in vivo elasticity mapping of abdominal organs in small animals. Pathological cases, i.e. chronic pancreatitis and pancreatic cancer, were also studied in vivo to assess the capability of HMI for detection of the change in mechanical properties. A 4.5 MHz focused ultrasound transducer (FUS) generated an amplitude-modulated beam resulting in 50 Hz harmonic tissue oscillations at its focus. Axial tissue displacement was estimated using 1D-cross-correlation of RF signals acquired with a 7.8 MHz diagnostic transducer confocally aligned with the FUS. In vitro results in canine liver and kidney showed the correlation between HMI displacement and Young's moduli measured by rheometry compression testing. HMI was capable of providing reproducible elasticity maps of the mouse abdominal region in vivo allowing the identification of, from stiffest to softest, the murine kidney, pancreas, liver, and spleen. Finally, pancreata affected by pancreatitis and pancreatic cancer showed HMI displacements 1.7 and 2.2 times lower than in the control case, respectively, indicating higher stiffness. The HMI displacement amplitude was correlated with the extent of fibrosis as well as detecting the very onset of stiffening even before fibrosis could be detected on H&E. This work shows that HMI can produce reliable elasticity maps of mouse abdominal region in vivo, thus providing a potentially critical tool to assess pathologies affecting organ elasticity.

SUBMITTER: Payen T

PROVIDER: S-EPMC5048218 | biostudies-other | 2016 Aug

REPOSITORIES: biostudies-other

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Project description:BackgroundPlaque vulnerability to rupture has emerged as a critical correlate to risk of adverse coronary events but there is as yet no clinical method to assess plaque stability in vivo. In the search to identify biomarkers of vulnerable plaques an association has been found between macrophages and plaque stability--the density and pattern of macrophage localization in lesions is indicative of probability to rupture. In very unstable plaques, macrophages are found in high densities and concentrated in the plaque shoulders. Therefore, the ability to map macrophages in plaques could allow noninvasive assessment of plaque stability. We use a multimodality imaging approach to noninvasively map the distribution of macrophages in vivo. The use of multiple modalities allows us to combine the complementary strengths of each modality to better visualize features of interest. Our combined use of Positron Emission Tomography and Magnetic Resonance Imaging (PET/MRI) allows high sensitivity PET screening to identify putative lesions in a whole body view, and high resolution MRI for detailed mapping of biomarker expression in the lesions.Methodology/principal findingsMacromolecular and nanoparticle contrast agents targeted to macrophages were developed and tested in three different mouse and rat models of atherosclerosis in which inflamed vascular plaques form spontaneously and/or are induced by injury. For multimodal detection, the probes were designed to contain gadolinium (T1 MRI) or iron oxide (T2 MRI), and Cu-64 (PET). PET imaging was utilized to identify regions of macrophage accumulation; these regions were further probed by MRI to visualize macrophage distribution at high resolution. In both PET and MR images the probes enhanced contrast at sites of vascular inflammation, but not in normal vessel walls. MRI was able to identify discrete sites of inflammation that were blurred together at the low resolution of PET. Macrophage content in the lesions was confirmed by histology.Conclusions/significanceThe multimodal imaging approach allowed high-sensitivity and high-resolution mapping of biomarker distribution and may lead to a clinical method to predict plaque probability to rupture.

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Elasticity mapping of murine abdominal organs in vivo using harmonic motion imaging (HMI).

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