With the development of numerous mouse models of cancer, there is a tremendous need for an appropriate imaging technique to study the disease evolution. High-field T2-weighted imaging using PROPELLER MRI meets this need. The 2-shot PROPELLER technique presented here, provides (a) high spatial resolution, (b) high contrast resolution, and (c) rapid and non-invasive imaging, which enables high-throughput, longitudinal studies in free-breathing mice. Unique data collection and reconstruction makes this method robust against motion artifacts. The 2-shot modification introduced here, retains more high-frequency information and provides higher SNR than conventional single-shot PROPELLER, making this sequence feasible at high-fields, where signal loss is rapid. Results are shown in a liver metastases model to demonstrate the utility of this technique in one of the more challenging regions of the mouse, which is the abdomen.
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.
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