In vivo high-frequency, contrast-enhanced ultrasonography of uveal melanoma in mice: imaging features and histopathologic correlations.
OBJECTIVE
To evaluate the usefulness of in vivo imaging of uveal melanoma in mice using high-frequency contrast-enhanced ultrasound (HF-CE-US) with 2D or 3D modes and to correlate the sonographic findings with histopathologic characteristics.


METHODS
Fourteen 12-week-old C57BL6 mice were inoculated into their right eyes with aliquots of 5 × 10(5)/2.5 μL B16LS9 melanoma cells and were randomly assigned to either of two groups. At 7 days after inoculation, tumor-bearing eyes in group 1 (n = 8) were imaged using HF-CE-US to determine the 2D tumor size and relative blood volume; eyes in group 2 (n = 6) were imaged by 3D microbubble contrast-enhanced ultrasound, and the tumor volume was determined. Histologic tumor burden was quantified in enucleated eyes by image processing software, and microvascular density was determined by counting von Willebrand factor-positive vascular channels. Ultrasound images were evaluated and compared with histopathologic findings.


RESULTS
Using HF-CE-US, melanomas were visualized as relatively hyperechoic regions. The intraobserver variability of sonographic measurements was 9.65% ± 7.89%, and the coefficient of variation for multiple measurements was 7.33% ± 5.71%. The correlation coefficient of sonographic volume or size and histologic area was 0.71 (P = 0.11) and 0.79 (P = 0.32). The relative blood volume within the tumor demonstrated sonographically correlated significantly with histologic tumor vascularity (r = 0.83; P < 0.001).


CONCLUSIONS
There was a positive linear correlation between sonographic tumor measurements and histologic tumor burden in the mouse ocular melanoma model. Contrast-enhanced intensity corresponded with microvascular density and blood volume. HF-CE-US is a real-time, noninvasive, reliable method for in vivo evaluation of experimental intraocular melanoma tumor area and relative blood volume.
Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Qing
Q
Zhang
Hua
H
Yang
Shin J
SJ
Kang
Yanggan
Y
Wang
Geoffrey D
GD
Wang
Tonya
T
Coulthard
Hans E
HE
Grossniklaus
D000818:Animals; D001810:Blood Volume; D003287:Contrast Media; D004195:Disease Models, Animal; D005260:Female; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D008545:Melanoma / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D045423:Microbubbles; D009389:Neovascularization, Pathologic / Q000473:pathology; D015588:Observer Variation; D011897:Random Allocation; D014463:Ultrasonography; D014604:Uveal Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000473:pathology; D000098943:Uveal Melanoma
D003287:Contrast Media
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