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. 2020 Jan;39(1):60-69.
doi: 10.14366/usg.19010. Epub 2019 Jun 10.

Evaluation of Lymph Node Metastasis in a Rabbit Tumor Model: Correlations Between Contrast-Enhanced Ultrasound and Pathologic Findings

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Free PMC article

Evaluation of Lymph Node Metastasis in a Rabbit Tumor Model: Correlations Between Contrast-Enhanced Ultrasound and Pathologic Findings

Shin-Woo Ha et al. Ultrasonography. .
Free PMC article

Abstract

Purpose: The purpose of this study was to evaluate the ability of contrast-enhanced ultrasonography (CEUS) with microbubbles to detect metastatic lymph nodes (LNs) for treatment planning and prognosis.

Methods: For the metastatic LN model, ground VX2 tumor tissues were injected subcutaneously in 12 rabbits, just below the right hind limb. The rabbits were classified into three groups based on the LN area: group A (n=4, >1.9 cm2 ), group B (n=4, 1-1.9 cm2 ), and group C (n=4, <1 cm2 ). The LNs were monitored on CEUS for 10 seconds after injecting 2.5 mL of microbubbles. The percent area of metastatic LNs was calculated on pathologic images and compared with CEUS images.

Results: In group A, the mean percent area of metastasis was 40.7%±19.4%. In all cases of metastasis, round-shaped perfusion defects were clearly observed in CEUS images. The metastatic areas were strongly correlated with pathologic findings. The mean percent area in group B was 21.5%±14.4%. The CEUS findings showed multiple nodular perfusion defects, clearly revealing the metastatic areas. In group B, the CEUS and pathologic findings were concordant for three of the four cases. The mean percent area in group C was 9.1%±6.4%. However, in this group, CEUS only detected a small perfusion defect in one case.

Conclusion: CEUS has the potential to depict characteristic imaging features of metastatic LNs but still has limitations in early detection.

Keywords: Diagnostic imaging; Lymph nodes; Lymphatic metastasis; Microbubbles; Ultrasonography.

Conflict of interest statement

No potential conflict of interest relevant to this article was reported.

Figures

Fig. 1.
Fig. 1.. The morphology and size of microbubbles.
A. A microscopic image shows variably-sized microbubbles. B. Dynamic light scattering analysis revealed that the sizes of microbubbles ranged from few hundred nanometers to 10 µm, with a mean size of 2.2±0.6 µm.
Fig. 2.
Fig. 2.. Gross specimen showing metastatic and normal lymph nodes (LNs) in each group and a graph showing the LN length.
A. Gross specimen shows metastatic and normal LNs in each group. CL, control. B. The size of the metastatic and normal LNs was statistically significantly different in each group. a)P<0.05 relative to tumor of group A. b)P<0.005 relative to tumor of each group by Student's t test.
Fig. 3.
Fig. 3.. Metastatic lymph node seen with lobulated perfusion defects on contrast-enhanced ultrasonography (CEUS) in group A.
A, B. CEUS (A) and gray-scale ultrasonography (B) show lobulated perfusion defects in a metastatic lymph node (arrows). C, D. A gross specimen (C) and a hematoxylin and eosinstained slide (D) show a lobulated metastatic tumor in the lymph node (arrows).
Fig. 4.
Fig. 4.. Metastatic lymph node seen as multiple nodular perfusion defects on contrast-enhanced ultrasonography (CEUS) in group B.
A, B. CEUS (A) and gray-scale ultrasonography (B) show multiple nodular perfusion defects in a metastatic lymph node (arrows). C, D. A gross specimen (C) and a hematoxylin and eosin-stained slide (D) also show multiple tumor deposits in the lymph nodes (arrows).
Fig. 5.
Fig. 5.. Metastatic lymph node not seen on contrast-enhanced ultrasonography (CEUS) in group C.
A, B. CEUS (A) and gray-scale ultrasonography (B) show no definite perfusion defects. C, D. A gross specimen (C) and a hematoxylin and eosin-stained slide (D) show small areas of metastatic tumors (arrowheads) in the lymph node.
Fig. 6.
Fig. 6.. Schematic drawings of the stages of lymph node metastasis.
There are small perfusion defects in the peripheral portion of lymph node in the initial stage. Then, the metastatic areas grow into multiple nodular lesions. In the advanced stage, the multiple nodules are conglomerated and show lobulated contours.

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