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

Abstract

Rationale and Objectives Liver is a common site for distal metastases in colon and rectal cancer. Numerous clinical studies have analyzed the relative merits of different imaging modalities for detection of liver metastases. A number of exciting new therapies are being investigated in preclinical models. But, technical challenges in preclinical imaging make it difficult to translate conclusions from clinical studies to the preclinical environment. This study addresses the technical challenges of preclinical MR and micro-CT to enable comparison of state-of-the-art methods for following metastatic liver disease. Materials and Methods We optimized two promising preclinical protocols to enable a parallel longitudinal study tracking metastatic human colon carcinoma growth in a mouse model: T2-weighted MRI using 2-shot PROPELLER (Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction), and contrast-enhanced micro-CT using a liposomal contrast agent. Both methods were tailored for high throughput with attention to animal support and anesthesia to limit biological stress. Results and Conclusions Each modality has its strengths. Micro-CT permitted more rapid acquisition (<10 minutes) with the highest spatial resolution (88-micron isotropic resolution). But detection of metastatic lesions requires the use of a blood pool contrast agent, which could introduce a confound in the evaluation of new therapies. MR imaging was slower (30 minutes) and had lower anisotropic spatial resolution. But MR eliminates the need for a contrast agent and the contrast-to-noise between tumor and normal parenchyma was higher, making earlier detection of small lesions possible. Both methods supported a relatively high-throughput, longitudinal study of the development of metastatic lesions.

Small Animal X-ray Computed Tomography

“…Because these blood pool contrast agents are taken up by normal-functioning liver and spleen, they can be used to identify necrotic regions (Chouker et al 2008), liver tumors (Almajdub et al 2007, Montet et al 2007, Desnoyers et al 2008, Graham et al 2008, Kim et al 2008, Boll et al 2011b, and spleen tumors (Almajdub et al 2007), as well as to measure organ volume, quantify hepatic necrosis (Varenika et al 2013), and determine liver anatomy (Fiebig et al 2012). shows slices in a coronal orientation of a liver in mice with HT-29 colon adenocarcinoma tumors (Pandit et al 2013). The mouse was injected with a liposomal iodinated contrast agent and imaged one day and five days post-injection.…”

“…A liposomal iodinated contrast agent has been used. (Reproduced fromPandit, P. et al 2013. Acad Radiol 20(4Micro-computed tomography (micro-CT) images of murine kidneys with low molecular weight contrast enhancement.…”

In vivo X-Ray Computed Tomographic Imaging of Soft Tissue with Native, Intravenous, or Oral Contrast

“…MRI, however, did not require P.O. contrast enhancement, and the increased signal to noise ratio enabled the earlier detection of smaller lesions [9]. …”

“…One of the primary clinical differences between CT and MRI is that the former is generally used for imaging dense structures like bones, while the latter is typically better at resolving soft tissues [8]. For pre-clinical research in particular, the use of MRI is hindered by significantly longer acquisition times to achieve similar levels of resolution, thus reducing throughput [9]. Further, the availability of small animal MRI systems is generally restricted to larger medical research institutions.…”

Dextrin-coated zinc substituted cobalt-ferrite nanoparticles as an MRI contrast agent: In vitro and in vivo imaging studies

“…Finding ultrasensitive contrast agents (CAs) for earlier detection of pathology has attracted a lot of attention in recent years [6,7]. CAs reduce the relaxation times and improve the MRI sensitivity [8,9].…”