Longitudinal in vivo susceptibility contrast MRI measurements of LS174T colorectal liver metastasis in nude mice

Abstract

Purpose: To characterize longitudinal tumor progression in a murine orthotopic model of liver metastasis using susceptibility contrast magnetic resonance imaging (MRI). Materials and Methods:Nude mice were inoculated intrasplenically with LS174T colorectal carcinoma cells 24 hours postadministration of 2.5 mgFe/kg of the ultrasmall superparamagnetic iron oxide particle preparation feruglose. Contiguous T 2 and T 2 *-weighted multislice MR images were acquired 10, 15, 20, 25, 30, and 35 days postinoculation to longitudinally evaluate metastatic progression. Functional tumor vasculature and hypoxia were histologically evaluated at the final timepoint using Hoechst 33342 uptake, pimonidazole and hematoxylin and eosin staining. A parallel cohort of subcutaneous tumors was included for comparison.Results: All intrasplenically inoculated mice developed liver metastases, evident in both T 2 *-and T 2 -weighted images as high-signal deposits, compared to feruglose-nulled normal liver. Small lesions were detected as early as day 10 and all mice exhibited progressing lesions over 35 days. Liver metastases took longer to establish, but exhibited a similar volume doubling time to the subcutaneously propagated tumors of Ϸ2-3 days. Different functional tumor vascular architectures between the two growth sites were apparent.Conclusion: Susceptibility-contrast MRI using a single dose of feruglose can be used to easily detect and longitudinally monitor orthotopically propagated liver metastases in vivo.

The Utility of Micro-CT and MRI in the Assessment of Longitudinal Growth of Liver Metastases in a Preclinical Model of Colon Carcinoma

“…What are the most appropriate preclinical modalities and how does one optimize them for our given task—non-invasive study of liver metastases? Preclinical studies of mouse models of liver cancer have used several imaging modalities: positron emission tomography (PET) (2), bioluminescence imaging (3) (4), computed tomography (CT) (5), and magnetic resonance imaging (MRI) (6) (7) (8), albeit independently. PET provides excellent functional information regarding tumor metabolism.…”

Non‐invasive in vivo imaging of vessel calibre in orthotopic prostate tumour xenografts

“…Orthotopically propagated human prostate tumours have been found to metastasise more easily, and are associated with greater vascular volume and permeability, a higher proliferative index and lower extracellular pH than equivalent subcutaneous xenografts 26. The exploitation of orthotopic murine tumour models, coupled with non‐invasive MRI, represents a powerful symbiotic preclinical research tool for the longitudinal investigation of disease progression and response in small animal cohorts 27…”

“…26 The exploitation of orthotopic murine tumour models, coupled with non-invasive MRI, represents a powerful symbiotic preclinical research tool for the longitudinal investigation of disease progression and response in small animal cohorts. 27 In this study, the vascular architecture of orthotopically propagated prostate tumour xenografts was assessed in vivo prior to, and following, treatment with the vascular disrupting agent ZD6126 using susceptibility contrast MRI. A novel Bayesian hierarchical model was used to maximise the inferential power of the MRI data and improve the accuracy and precision of individual parameter estimates.…”

Characterization and longitudinal monitoring of melanoma growth in ret‐transgenic mice using a single‐sequence MRI protocol

“…Magnetic resonance imaging enables the longitudinal observation of tumor progression, dose‐ and time‐dependent therapeutic effects. Furthermore, our sequential experimental design, facilitated by MRI, allows the achievement of the same statistical power when analysing tumor volume or number as conventional designs while utilizing fewer animals .…”