ORIGINAL ARTICLES: Translational researchIn-vivo longitudinal MRI study an assessment of melanoma brain metastases in a clinically relevant mouse modelHenry, Mariama N.a,b; Chen, Yuhuaa; McFadden, Catherine D.a; Simedrea, Felicia C.c; Foster, Paula J.a,bAuthor Information aRobarts Research Institute bDepartment of Medical Biophysics, Western University cLondon Regional Cancer Program, London, Ontario, Canada Correspondence to Mariama N. Henry, MSc, 3004 Brimley Dr., Windsor, Ontario, Canada N8R 1M2 Tel: +1 519 735 2207; fax: +1 519 663 3404; e-mail: [email protected] Received March 14, 2014 Accepted November 10, 2014 Melanoma Research: April 2015 - Volume 25 - Issue 2 - p 127-137 doi: 10.1097/CMR.0000000000000136 Buy Metrics Abstract Brain metastases are an important clinical problem. Few animal models exist for melanoma brain metastases; many of which are not clinically relevant. Longitudinal MRI was implemented to examine the development of tumors in a clinically relevant mouse model of melanoma brain metastases. Fifty thousand human metastatic melanoma (A2058) cells were injected intracardially into nude mice. Three Tesla MRI was performed using a custom-built gradient insert coil and a mouse solenoid head coil. Imaging was performed on consecutive days at four time points. Tumor burden and volumes of metastases were measured from balanced steady-state free precession image data. Metastases with a disrupted blood–tumor barrier were identified from T1-weighted spin echo images acquired after administration of gadopentetic acid (Gd-DTPA). Metastases permeable to Gd-DTPA showed signal enhancement. The number of enhancing metastases was determined by comparing balanced steady-state free precession images with T1-weighted spin echo images. After the final imaging session, ex-vivo permeability and histological analyses were carried out. Imaging showed that both enhancing and nonenhancing brain metastases coexist in the brain, and that most metastases switched from the nonenhancing to the enhancing phenotype. Small numbers of brain metastases were enhancing when first detected by MRI and remained enhancing, whereas other metastases remained nonenhancing to Gd-DTPA throughout the experiment. No clear relationship existed between the permeability of brain metastases and size, brain location and age. Longitudinal in-vivo MRI is key to studying the complex and dynamic processes of metastasis and changes in the blood–tumor barrier permeability, which may lead to a better understanding of the variable responses of brain metastases to treatments. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.