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Chemical exchange saturation transfer MRI to assess cell death in breast cancer xenografts at 7T.

ABSTRACT: Detecting cell death and predicting tumor response early in a course of chemotherapy could help optimize treatment regimens and improve clinical outcomes. Chemical exchange saturation transfer (CEST) MRI was investigated in vivo to study properties that may be able to detect cancer death.Using a magnetization transfer ratio (MTR) cutoff of 0.12 at 1.8 ppm was able to differentiate between viable tumor and cell death regions. Comparison of MTR values at this frequency showed significant differences (p < 0.0001) between viable tumor and cell death regions, matching patterns seen on histology. Using this cutoff, the mean increase in cell death index (± standard error of the mean) after chemotherapy was 4 ± 4%, 10% ± 7%, 10 ± 8%, and 4 ± 9% at 4, 8, 12, and 24 h, respectively.CEST MRI can detect cell death in MDA-231 xenografts but further work is needed to characterize the clinical applications of this finding. Maximum response to chemotherapy occurred at 8-12 h after chemotherapy injection in this in vivo tumor model.Breast cancer xenografts (MDA-MB-231) were scanned using 7 T MRI before and after chemotherapy. As a measure of CEST effect at 0.5 µT saturation amplitude, MTR values at frequency offsets of 1.8 and -3.3 ppm were evaluated. CEST signals after chemotherapy treatment were compared to cell-death histopathology of tumors.

SUBMITTER: Klein J

PROVIDER: S-EPMC6101146 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Chemical exchange saturation transfer MRI to assess cell death in breast cancer xenografts at 7T.

Klein Jonathan J Lam Wilfred W WW Czarnota Gregory J GJ Stanisz Greg J GJ

Oncotarget 20180731 59

<h4>Purpose</h4>Detecting cell death and predicting tumor response early in a course of chemotherapy could help optimize treatment regimens and improve clinical outcomes. Chemical exchange saturation transfer (CEST) MRI was investigated <i>in vivo</i> to study properties that may be able to detect cancer death.<h4>Results</h4>Using a magnetization transfer ratio (MTR) cutoff of 0.12 at 1.8 ppm was able to differentiate between viable tumor and cell death regions. Comparison of MTR values at this ...[more]

PMID: 30140385

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Project description:Chemical exchange saturation transfer (CEST) has emerged as a novel MRI contrast mechanism that is well suited for molecular imaging studies. This new mechanism can be used to detect small amounts of contrast agent through the saturation of rapidly exchanging protons on these agents, allowing a wide range of applications. CEST technology has a number of indispensable features, such as the possibility of simultaneous detection of multiple 'colors' of agents and of changes in their environment (e.g. pH, metabolites, etc.) through MR contrast. Currently, a large number of new imaging schemes and techniques are being developed to improve the temporal resolution and specificity and to correct for the influence of B0 and B1 inhomogeneities. In this review, the techniques developed over the last decade are summarized with the different imaging strategies and post-processing methods discussed from a practical point of view, including the description of their relative merits for the detection of CEST agents. The goal of the present work is to provide the reader with a fundamental understanding of the techniques developed, and to provide guidance to help refine future applications of this technology. This review is organized into three main sections ('Basics of CEST contrast', 'Implementation' and 'Post-processing'), and also includes a brief Introduction and Summary. The 'Basics of CEST contrast' section contains a description of the relevant background theory for saturation transfer and frequency-labeled transfer, and a brief discussion of methods to determine exchange rates. The 'Implementation' section contains a description of the practical considerations in conducting CEST MRI studies, including the choice of magnetic field, pulse sequence, saturation pulse, imaging scheme, and strategies to separate magnetization transfer and CEST. The 'Post-processing' section contains a description of the typical image processing employed for B0 /B1 correction, Z-spectral interpolation, frequency-selective detection and improvement of CEST contrast maps.

Project description:ObjectiveChemical exchange-dependent saturation transfer (CEST) MRI is sensitive for detecting solid-like proteins and may detect changes in the levels of mobile proteins and peptides in tissues. The objective of this study was to evaluate the characteristics of chemical exchange proton pools using the CEST MRI technique in patients with dementia.Materials and methodsOur institutional review board approved this cross-sectional prospective study and informed consent was obtained from all participants. This study included 41 subjects (19 with dementia and 22 without dementia). Complete CEST data of the brain were obtained using a three-dimensional gradient and spin-echo sequence to map CEST indices, such as amide, amine, hydroxyl, and magnetization transfer ratio asymmetry (MTRasym) values, using six-pool Lorentzian fitting. Statistical analyses of CEST indices were performed to evaluate group comparisons, their correlations with gray matter volume (GMV) and Mini-Mental State Examination (MMSE) scores, and receiver operating characteristic (ROC) curves.ResultsAmine signals (0.029 for non-dementia, 0.046 for dementia, p = 0.011 at hippocampus) and MTRasym values at 3 ppm (0.748 for non-dementia, 1.138 for dementia, p = 0.022 at hippocampus), and 3.5 ppm (0.463 for non-dementia, 0.875 for dementia, p = 0.029 at hippocampus) were significantly higher in the dementia group than in the non-dementia group. Most CEST indices were not significantly correlated with GMV; however, except amide, most indices were significantly correlated with the MMSE scores. The classification power of most CEST indices was lower than that of GMV but adding one of the CEST indices in GMV improved the classification between the subject groups. The largest improvement was seen in the MTRasym values at 2 ppm in the anterior cingulate (area under the ROC curve = 0.981), with a sensitivity of 100 and a specificity of 90.91.ConclusionCEST MRI potentially allows noninvasive image alterations in the Alzheimer's disease brain without injecting isotopes for monitoring different disease states and may provide a new imaging biomarker in the future.

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Chemical exchange saturation transfer MRI to assess cell death in breast cancer xenografts at 7T.

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Chemical exchange saturation transfer MRI to assess cell death in breast cancer xenografts at 7T.

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