Dataset Information

Tumor pH and Protein Concentration Contribute to the Signal of Amide Proton Transfer Magnetic Resonance Imaging.

ABSTRACT: Abnormal pH is a common feature of malignant tumors and has been associated clinically with suboptimal outcomes. Amide proton transfer magnetic resonance imaging (APT MRI) holds promise as a means to noninvasively measure tumor pH, yet multiple factors collectively make quantification of tumor pH from APT MRI data challenging. The purpose of this study was to improve our understanding of the biophysical sources of altered APT MRI signals in tumors. Combining in vivo APT MRI measurements with ex vivo histological measurements of protein concentration in a rat model of brain metastasis, we determined that the proportion of APT MRI signal originating from changes in protein concentration was approximately 66%, with the remaining 34% originating from changes in tumor pH. In a mouse model of hypopharyngeal squamous cell carcinoma (FaDu), APT MRI showed that a reduction in tumor hypoxia was associated with a shift in tumor pH. The results of this study extend our understanding of APT MRI data and may enable the use of APT MRI to infer the pH of individual patients' tumors as either a biomarker for therapy stratification or as a measure of therapeutic response in clinical settings. SIGNIFICANCE: These findings advance our understanding of amide proton transfer magnetic resonance imaging (APT MRI) of tumors and may improve the interpretation of APT MRI in clinical settings.

SUBMITTER: Ray KJ

PROVIDER: S-EPMC6462213 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Tumor pH and Protein Concentration Contribute to the Signal of Amide Proton Transfer Magnetic Resonance Imaging.

Ray Kevin J KJ Simard Manon A MA Larkin James R JR Coates James J Kinchesh Paul P Smart Sean C SC Higgins Geoff S GS Chappell Michael A MA Sibson Nicola R NR

Cancer research 20190124 7

Abnormal pH is a common feature of malignant tumors and has been associated clinically with suboptimal outcomes. Amide proton transfer magnetic resonance imaging (APT MRI) holds promise as a means to noninvasively measure tumor pH, yet multiple factors collectively make quantification of tumor pH from APT MRI data challenging. The purpose of this study was to improve our understanding of the biophysical sources of altered APT MRI signals in tumors. Combining <i>in vivo</i> APT MRI measurements w ...[more]

PMID: 30679178

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Project description:Background:Amide proton transfer-weighted (APTw) imaging has been revealed to hold great potential in the diagnosis of several brain diseases. The purpose of this proof-of-concept study was to evaluate the feasibility and value of APTw magnetic resonance imaging (MRI) in characterizing normal brain aging. Methods:A total of 106 healthy subjects were recruited and scanned at 3.0 Tesla, with APTw and conventional magnetization transfer (MT) sequences. Quantitative image analyses were performed in 12 regions of interest (ROIs) for each subject. The APTw or MT ratio (MTR) signal differences among five age groups (young, mature, middle-aged, young-old, and middle-old) were assessed using the one-way analysis of variance, with the Benjamini-Hochberg correction for multiple comparisons. The relationship between APTw and MTR signals and the age dependencies of APTw and MTR signals were assessed using the Pearson correlation and non-linear regression. Results:There were no significant differences between the APTw or MTR values for males and females in any of the 12 ROIs analyzed. Among the five age groups, there were significant differences in the three white matter regions in the temporal, occipital, and frontal lobes. Overall, the mean APTw values in the older group were higher than those in the younger group. Positive correlations were observed in relation to age in most brain regions, including four with significant positive correlations (r=0.2065-0.4182) and five with increasing trends. As a comparison, the mean MTR values did not appear to be significantly different among the five age groups. In addition, the mean APTw and MTR values revealed significant positive correlations in 10 ROIs (r=0.2214-0.7269) and a significant negative correlation in one ROI (entorhinal cortex, r=-0.2141). Conclusions:Our early results show that the APTw signal can be used as a promising and complementary imaging biomarker with which normal brain aging can be evaluated at the molecular level.

Project description:BackgroundMore effective risk stratification of prostate cancer (PCa) than that possible with current methods can reduce undertreatment and guard against overtreatment. The aim of this study is to validate the differences and combined effects of amide proton transfer (APT) imaging and apparent diffusion coefficient (ADC) in discriminating the PCa grade group (GG) ≤2 from GG ≥3 PCa.MethodsThis is an ongoing prospective study conducted in the radiology department of Nanxishan Hospital of Guangxi Zhuang Autonomous Region. Patients pathologically diagnosed with PCa were enrolled consecutively according to the eligibility criteria. A total of 180 patients (age range, 42-92 years) were included in this study. Using histopathology as the reference standard, we placed 71 cases in GG ≤2 (mean age 67.03±8.696 years) and 109 cases in GG ≥3 (age 69.60±9.638 years). Magnetic resonance imaging (MRI) parameters, including APT and ADC values, were analyzed using an independent samples t-test and binary logistic regression analysis stratified with GG. Receiver operating characteristic curve was used to analyze the diagnostic performance for different parameters distinguishing GG ≤2 and GG ≥3.ResultsAPT [odds ratio (OR) for the transitional zone (TZ) PCa: 3.20, 95% CI: 1.14-8.98, P=0.02; OR for the peripheral zone (PZ) PCa: 86.32, 95% CI: 13.24-562.88, P=0.003] and ADC values (OR for TZ PCa: 89.79; 95% CI: 2.85-2,827.99, P=0.01; OR for PZ PCa: 39.92; 95% CI: 3.22-494.18, P=0.004) were independent predictors that differentiated the GG of patients. The sensitivity and specificity of the APT values were 61.1% and 81.0%, respectively, while the sensitivity and specificity of the ADC values were 83.3% and 61.9%, respectively. The optimal cutoff value of APT was 3.35% and which of ADC was 1.25×10-3 mm2/s in TZ origin PCa. At the optimal cutoff values of 3.31% (APT) and 0.79×10-3 mm2/s (ADC) in PZ PCa, the sensitivity and specificity of the APT values were 74.0% and 83.6%, respectively, while the sensitivity and specificity of the ADC values were 94.0% and 53.4%, respectively. The area under the curve of the combination of APT and ADC was significantly higher than either of APT or ADC alone in Delong test (TZ: P=0.002 and P=0.020; PZ: P=0.033 and P<0.001).ConclusionsAPT and ADC have complementary effects on the sensitivity and specificity for identifying different PCa GGs. A combination model of APT and ADC could improve the diagnostic efficacy of PCa differentiation.

Dataset Information

Tumor pH and Protein Concentration Contribute to the Signal of Amide Proton Transfer Magnetic Resonance Imaging.

Publications

Tumor pH and Protein Concentration Contribute to the Signal of Amide Proton Transfer Magnetic Resonance Imaging.

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