The significance of intracellular sodium in cellular metabolism in tumors as a measure of cytotoxicity is potentially important as a clinical indicator of response to cancer therapy. Malignant tumors have been generally shown to have elevated intracellular sodium and the chemotherapeutic treatment itself kills tumor cells, which elevates intracellular sodium even further. Accessing the signal from intracellular sodium using magnetic resonance imaging (MRI) and/or spectroscopy has been hindered by the large intracellular sodium using magnetic resonance imaging (MRI) and/or spectroscopy has been hindered by the large extracellular sodium signal detected with conventional single quantum techniques. Approaches such as use of chemical shift reagents or multiple quantum filtering to detect intracellular sodium also suffer serious shortcoming when applied in vivo. The objective of this study is to evaluate and refine a new inversion recovery nulling (IR Na-MRI) approach which suppresses the large extracellular sodium in tumor thus is more sensitive to the early sodium signal changes resulting from chemotherapy. Proposed study will conducted in an animal tumor model using nude mice propagated with human prostate cancer cell lines and treated with known anti-neoplastics.
The specific aims are: 1. Technical development: (a) Employ high temperature superconducting (HTS) RF coil to increase the intrinsically low signal-to-noise ratio (SNR) in sodium MRI; (b) Optimize sodium MRI data acquisition to improve SNR for a given scan time; (c) o-register sodium tumor images acquired during different imaging sessions based on the high resolution proton images so to precisely measure the regional change of sodium signal in tumor. 2. Evaluation of IR Na-MRI in tumor: Correlate morphological proton MRI, single quantum Na-MRI, IR Na-MRI, and hematoxylin and eosin (H&E) pathology staining of tumor. 3. Evaluation of IR Na-MRI for chemotherapy monitoring: (a) Correlate tumor changes in IR Na-MRI during chemotherapy to the postmortem tumor pathology examination including H&E staining, mitosis measurement, and apoptosis staining; (b) Determine the sensitivity and specificity of IR Na-MRI for detecting and assessing early tumor response to chemotherapy in vivo. 4. Experimental optimization of IR Na-MRI for sensitivity and specificity in chemotherapy monitoring.
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