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Abstract Background High-resolution magic angle proton magnetic resonance spectroscopy (HR 1H MAS MRS) provides a broad metabolic mapping of intact tumor samples and allows for microscopy investigations of the samples after spectra acquisition. Experimental studies have suggested that the method can be used for detection of apoptosis, but this has not been investigated in a clinical setting so far. We have explored this hypothesis in cervical cancers by searching for metabolites associated with apoptosis that were not influenced by other histopathological parameters like tumor load and tumor cell density. Methods Biopsies (n = 44) taken before and during radiotherapy in 23 patients were subjected to HR MAS MRS. A standard pulse-acquire spectrum provided information about lipids, and a spin-echo spectrum enabled detection of non-lipid metabolites in the lipid region of the spectra. Apoptotic cell density, tumor cell fraction, and tumor cell density were determined by histopathological analysis after spectra acquisition. Results The apoptotic cell density correlated with the standard pulse-acquire spectra (p < 0.001), but not with the spin-echo spectra, showing that the lipid metabolites were most important. The combined information of all lipids contributed to the correlation, with a major contribution from the ratio of fatty acid -CH2 to CH3 (p = 0.02). In contrast, the spin-echo spectra contained the main information on tumor cell fraction and tumor cell density (p < 0.001), for which cholines, creatine, taurine, glucose, and lactate were most important. Significant correlations were found between tumor cell fraction and glucose concentration (p = 0.001) and between tumor cell density and glycerophosphocholine (GPC) concentration (p = 0.024) and ratio of GPC to choline (p < 0.001). Conclusion Our findings indicate that the apoptotic activity of cervical cancers can be assessed from the lipid metabolites in HR MAS MR spectra and that the HR MAS data may reveal novel information on the metabolic changes characteristic of apoptosis. These changes differed from those associated with tumor load and tumor cell density, suggesting an application of the method to explore the role of apoptosis in the course of the disease.

The purpose of this study was to evaluate the use of dynamic contrast-enhanced (DCE) MRI, in vivo 1H MRS and ex vivo high resolution magic angle spinning (HR MAS) MRS of tissue samples as methods to detect early treatment effects of docetaxel in a breast cancer xenograft model (MCF-7) in mice. MCF-7 cells were implanted subcutaneously in athymic mice and treated with docetaxel (20, 30, and 40 mg/kg) or saline six weeks later. DCE-MRI and in vivo 1H MRS were performed on a 7 T MR system three days after treatment. The dynamic images were used as input for a two-compartment model, yielding the vascular parameters Ktrans and ve. HR MAS MRS, histology, and immunohistochemical staining for proliferation (Ki-67), apoptosis (M30 cytodeath), and vascular/endothelial cells (CD31) were performed on excised tumor tissue. Both in vivo spectra and HR MAS spectra were used as input for multivariate analysis (principal component analysis (PCA) and partial least squares regression analysis (PLS)) to compare controls to treated tumors. Tumor growth was suppressed in docetaxel-treated mice compared to the controls. The anti-tumor effect led to an increase in Ktrans and ve values in all the treated groups. Furthermore, in vivo MRS and HR MAS MRS revealed a significant decrease in choline metabolite levels for the treated groups, in accordance with reduced proliferative index as seen on Ki-67 stained sections. In this study DCE-MRI, in vivo MRS and ex vivo HR MAS MRS have been used to demonstrate that docetaxel treatment of a human breast cancer xenograft model results in changes in the vascular dynamics and metabolic profile of the tumors. This indicates that these MR methods could be used to monitor intra-tumoral treatment effects. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: High-resolution magic angle proton magnetic resonance spectroscopy (HR 1H MAS MRS) provides a broad metabolic mapping of intact tumor samples and allows for microscopy investigations of the samples after spectra acquisition. Experimental studies have suggested that the method can be used for detection of apoptosis, but this has not been investigated in a clinical setting so far. We have explored this hypothesis in cervical cancers by searching for metabolites associated with apoptosis that were not influenced by other histopathological parameters like tumor load and tumor cell density. Methods: Biopsies (n = 44) taken before and during radiotherapy in 23 patients were subjected to HR MAS MRS. A standard pulse-acquire spectrum provided information about lipids, and a spin-echo spectrum enabled detection of non-lipid metabolites in the lipid region of the spectra. Apoptotic cell density, tumor cell fraction, and tumor cell density were determined by histopathological analysis after spectra acquisition. Results: The apoptotic cell density correlated with the standard pulse-acquire spectra (p <0.001), but not with the spin-echo spectra, showing that the lipid metabolites were most important. The combined information of all lipids contributed to the correlation, with a major contribution from the ratio of fatty acid -CH2 to CH3 (p =0.02). In contrast, the spin-echo spectra contained the main information on tumor cell fraction and tumor cell density (p < 0.001), for which cholines, creatine, taurine, glucose, and lactate were most important. Significant correlations were found between tumor cell fraction and glucose concentration (p = 0.001) and between tumor cell density and glycerophosphocholine (GPC) concentration (p = 0.024) and ratio of GPC to choline (p < 0.001). Conclusion: Our findings indicate that the apoptotic activity of cervical cancers can be assessed from the lipid metabolites in HR MAS MR spectra and that the HR MAS data may reveal novel information on the metabolic changes characteristic of apoptosis. These changes differed from those associated with tumor load and tumor cell density, suggesting an application of the method to explore the role of apoptosis in the course of the disease. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the use of dynamic contrast-enhanced (DCE) MRI, in vivo (1)H MRS and ex vivo high resolution magic angle spinning (HR MAS) MRS of tissue samples as methods to detect early treatment effects of docetaxel in a breast cancer xenograft model (MCF-7) in mice. MCF-7 cells were implanted subcutaneously in athymic mice and treated with docetaxel (20, 30, and 40 mg/kg) or saline six weeks later. DCE-MRI and in vivo (1)H MRS were performed on a 7 T MR system three days after treatment. The dynamic images were used as input for a two-compartment model, yielding the vascular parameters K(trans) and v(e). HR MAS MRS, histology, and immunohistochemical staining for proliferation (Ki-67), apoptosis (M30 cytodeath), and vascular/endothelial cells (CD31) were performed on excised tumor tissue. Both in vivo spectra and HR MAS spectra were used as input for multivariate analysis (principal component analysis (PCA) and partial least squares regression analysis (PLS)) to compare controls to treated tumors. Tumor growth was suppressed in docetaxel-treated mice compared to the controls. The anti-tumor effect led to an increase in K(trans) and v(e) values in all the treated groups. Furthermore, in vivo MRS and HR MAS MRS revealed a significant decrease in choline metabolite levels for the treated groups, in accordance with reduced proliferative index as seen on Ki-67 stained sections. In this study DCE-MRI, in vivo MRS and ex vivo HR MAS MRS have been used to demonstrate that docetaxel treatment of a human breast cancer xenograft model results in changes in the vascular dynamics and metabolic profile of the tumors. This indicates that these MR methods could be used to monitor intra-tumoral treatment effects.