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.

Figure 1

Illustration of the experimental setup and the processing performed to obtain HMI displacement maps in vivo.

Figure 2

Comparison of Young’s moduli obtained with rheometry against HMI displacement in in vitro canine liver, renal cortex and renal pelvis (Two-tail T-test: * p < 0.05, ** p < 0.01).

Figure 3

Bmode images and HMI elasticity maps obtained in vivo in two planes from the same mouse. Imaging plane #1 (first row) shows the kidney and the liver separated by intestines. The second plane displays the pancreas, the spleen and the kidney.

Figure 4

HMI displacement maps overlaid on Bmode images obtained ex vivo in the kidney and the liver of the mouse shown in Figure 3.

Figure 5

H&E stained slides of pancreas with different degrees of fibrosis (10× magnification). The corresponding HMI displacement maps overlaid on Bmode images are also shown below.

Figure 6

HMI displacements measured in vivo in normal pancreas, in inflamed pancreas with different stages of fibrosis, and in pancreatic tumors (Two-tail T-test: ** p <0.01, *** p < 0.001).