In vivo high-frequency contrast-enhanced ultrasonography of choroidal melanoma in rabbits: imaging features and histopathologic correlations

Abstract

Purpose To evaluate the utility of in vivo imaging of rabbit model of choroidal melanoma utilizing high-frequency contrast-enhanced ultrasound (HF-CE-US) with 2-or 3-dimensional modes, and to correlate the sonographic findings with histopathologic characteristics. Methods Five New Zealand white rabbits which were immunosuppressed with daily cyclosporin A were inoculated into their right eyes with aliquots of 1.5×106 / 50 µL of 92.1 human uveal melanoma cells cultured in RPMI. At week 4, the tumor-bearing eyes were imaged using high-frequency ultrasound with microbubble contrast agent to determine the 2-dimensional tumor size and relative blood volume and by 3-dimensional mode to determine tumor volume. Histologic tumor burden was quantified in enucleated eyes by ImageJ software, and microvascular density (MVD) was determined by counting vascular channels in PAS without hematoxylin sections. Results Utilizing HF-CE-US, melanomas were visualized as relatively hyperechoic regions in the images. The correlation coefficients of sonographic size or volume compared with histologic area were 0.72 and 0.70, respectively. The sonographic tumor relative blood volume correlated with the histologic tumor vascularity (R2=0.92, P=0.04) Conclusions There is a positive correlation between in vivo sonographic tumor volume/size and histologic tumor size in our rabbit choroidal melanoma model. HF-CE-US corresponds to microvascular density and blood volume.

The use of sulfur hexafluoride microbubbles for contrast‐enhanced ocular ultrasonography of the pecten oculi in birds

“…20,21 Previous studies showing success of SF6 microbubble enhancement of the microvasculature in the eyes of small animals such as rabbits and mice, combined with the results shown here of successful enhancement of the pecten oculi in several avian species, are encouraging when considering the small eyes and delicate microvasculature of many avian species. 37,42 Enhanced visualization of the pecten oculi and its vasculature using a readily available diagnostic imaging method such as CE-US would facilitate future studies evaluating the role of the pecten oculi in posterior segment diseases, including retinal degenerations, such as rdd, rge, and beg. [43][44][45][46] In the future, CE-US could be employed in the diagnosis of pecten oculi abnormalities as well as in the monitoring of progression vs. healing in pathological processes.…”

“…For example, one study showed a correlation between CE‐US and histologic results of assessing microvascular density and blood volume in murine uveal melanomas, which suggests that CE‐US is a reliable examination modality for evaluation of intraocular tumors even in small species . Similar results were shown more recently in a study evaluating CE‐US and histologic characteristics of choroidal melanomas in rabbits . Monitoring the vascular status of the pecten oculi is also important for primary or other secondary retinal diseases.…”

“…37 Similar results were shown more recently in a study evaluating CE-US and histologic characteristics of choroidal melanomas in rabbits. 42 Monitoring the vascular status of the pecten oculi is also important for primary or other secondary retinal diseases. For example, atrophy of the pecten oculi and its microvasculature were observed in spontaneously occurring inherited retinopathies in chicken, such as rdd, rge, and beg.…”

Clinical utility, dose determination, and safety of ocular contrast‐enhanced ultrasonography in horses: A pilot study

“…The tolerability of CEUS was unknown until Seiler et al 7 examined equine soft tissue structures of the distal limb by intravenous and regional intra-arterial perfluorobutane. In experimental ophthalmology, CEUS visualized normal vs impaired choroidal perfusion, 15 and correlated with histologic size and vascularity of uveal melanomas in rabbits 16 and mice. 17 The characterization of perfusional features of intraocular masses such as melanoma, hemangiosarcoma, 18 medulloepithelioma/retinoblastoma, 19 or lymphoma might be a future CEUS indication in horses.…”

Animal Eye Models for Uveal Melanoma

“…In a study on circulating malignant cells, all of the 17 rabbits that were available for testing had metastases in the lungs [49], and 18% developed liver micrometastases. Subsequently, several experiments were undertaken based on the same rabbit model [50,51,52,53]. …”