Influence of MRI Examinations on Animal Welfare and Study Results

Abstract

Objectives Magnetic resonance imaging (MRI) is considered to be well tolerated by laboratory animals. However, no systematic study has been performed yet, proving this assumption. Therefore, the aim of this study was to investigate the possible effects of longitudinal native and contrast-enhanced (CE) 1-T and 7-T MRI examinations on mouse welfare as well as 4T1 breast cancers progression and therapy response. Material and Methods Forty-seven healthy and 72 breast cancer-bearing mice (4T1) were investigated. One-Tesla (ICON) and 7-T (Biospec) MRI measurements were performed thrice per week under isoflurane anesthesia in healthy BALB/c mice for 4 weeks and 3 times within 2 weeks in tumor-bearing animals. Animal welfare was examined by an observational score sheet, rotarod performance, heart rate measurements, and assessment of fecal corticosterone metabolites. Furthermore, we investigated whether CE-MRI influences the study outcome. Therefore, hemograms and organ weights were obtained, and 4T1 tumor growth, perfusion, immune cell infiltration, as well as response to the multikinase inhibitor regorafenib were investigated. Statistical comparisons between groups were performed using analysis of variance and Tukey or Bonferroni post hoc tests. Results Mice showed no alterations in the observational score sheet rating, rotarod performance, heart rate, and fecal corticosterone metabolites (P > 0.05) after repeated MRI at both field strengths. However, spleen weights were reduced in all healthy mouse groups that received isoflurane anesthesia (P < 0.001) including the groups investigated by 1-T and 7-T MRI (P = 0.02). Neither tumor progression nor response to the regorafenib treatment was affected by isoflurane anesthesia or CE-MRI monitoring. Furthermore, immunohistological tumor analysis did not indicate an effect of isoflurane and MRI on macrophage infiltration of tumors, perfusion of tumor vessels, and apoptotic cell rate (P > 0.05). Conclusions Repeated MRI did not influence the welfare of mice and did not affect tumor growth and therapy response of 4T1 tumors. However, systemic immunological effects of isoflurane anesthesia need to be considered to prevent potential bias.

Characterizing Fibrosis and Inflammation in a Partial Bile Duct Ligation Mouse Model by Multiparametric Magnetic Resonance Imaging

“…Magnetic resonance imaging (MRI) is a non‐invasive method with excellent spatial resolution 12 . Laboratory animals have been shown to well tolerate imaging techniques 13 . Several recent studies only found the single association between MRI features and hepatic fibrosis 14,15 .…”

Diagnostic Ability of Methods Depicting Distress of Tumor-Bearing Mice

“…FCMs can assess the distress of various animal models and have also been used to evaluate the distress of tumor-bearing mice [ 35 , 40 , 41 , 42 ]. In our study, FCM concentrations were not significantly increased when mice had relatively small SCL-2 tumors (<300 mm 3 ), but were significantly higher when mice had relatively large A-375 tumors (>1000 mm 3 ).…”

“…Our conclusion is supported by several other studies. For example, FCM concentrations were not significantly increased in an orthotopic breast tumor mouse model, when tumors were smaller than 600 mm 3 [ 40 ]. In a mouse model for pancreatic cancer, it was also observed that FCM concentrations did not significantly change when the tumors were small [ 35 ].…”

Orthotopic Versus Allotopic Implantation: Comparison of Radiological and Pathological Characteristics

“…19 This technique is well-tolerated by humans and laboratory animals and it has been shown that repeated study does not influence animal welfare or tumor growth. 20 Thus, the aim of this study was to investigate the effects of orthotopic and heterotopic (intrahepatic and subcutaneous) implantation in mouse models with highly vascularized and syngeneic 4T1 breast cancer using MRI.…”