Abstract
In magnetic resonance metabolic imaging, signal from the water content is frequently used for normalization to derive quantitative or semi-quantitative values of metabolites in vivo or ex vivo tumors and tissues. Ex vivo high-resolution metabolic characterization of tumors with magnetic resonance spectroscopy (MRS) provides valuable information that can be used to drive the development of noninvasive MRS biomarkers and to identify metabolic therapeutic targets. Variability in the water content between tumor and normal tissue can result in over or underestimation of metabolite concentrations when assuming a constant water content. Assuming a constant water content can lead to masking of differences between malignant and normal tissues both in vivo and ex vivo. There is a critical need to develop biomarkers to detect pancreatic cancer and to develop novel treatments. Our purpose here was to determine the differences in water content between pancreatic tumors and normal pancreatic tissue as well as other organs to accurately quantify metabolic differences when using the water signal for normalization. Our data identify the importance of factoring the differences in water content between tumors and organs. High-resolution proton spectra of tumors and pancreatic tissue extracts normalized to the water signal, assuming similar water content, did not reflect the significantly increased total choline observed in tumors in vivo without factoring the differences in water content. We identified significant differences in the collagen 1 content between Panc1 and BxPC3 pancreatic tumors and the pancreas that can contribute to the differences in water content that were observed.
Highlights
Most pancreatic cancers are histologically classified as pancreatic ductal adenocarcinoma (PDAC), and have a 5-year survival rate of less than 5% [1]
The ratio of the tumor water content to the pancreas water content was used as a correction factor for the 1H Magnetic resonance spectroscopic imaging (MRSI) data
In the MRSI data, the total choline (tCho) concentration is calculated based on the water content, assuming a constant water concentration of water
Summary
Most pancreatic cancers are histologically classified as pancreatic ductal adenocarcinoma (PDAC), and have a 5-year survival rate of less than 5% [1]. PDAC is an aggressive and lethal disease that develops relatively symptom-free and is advanced at the time of diagnosis. Water and Collagen Content in Pancreatic Cancer radiotherapy. We previously observed elevated levels of tCho in several pancreatic cancer cell lines and tumor xenografts [5]. Initial single voxel studies performed in humans suggest that the tCho signal normalized to water may be relatively high in normal pancreas compared to PDAC [6, 7]. Our initial high-resolution ex vivo 1H MR spectra of tumors and pancreatic tissue normalized to the water signal, assuming similar water content, did not reflect the significantly increased tCho observed in vivo. We measured the water content in human pancreatic cancer xenografts, in mouse pancreas, and in mouse lungs, liver, heart, kidney and muscle
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