Dataset Information

Assessing Amide Proton Transfer (APT) MRI Contrast Origins in 9 L Gliosarcoma in the Rat Brain Using Proteomic Analysis.

ABSTRACT: PURPOSE:To investigate the biochemical origin of the amide photon transfer (APT)-weighted hyperintensity in brain tumors. PROCEDURES:Seven 9 L gliosarcoma-bearing rats were imaged at 4.7 T. Tumor and normal brain tissue samples of equal volumes were prepared with a coronal rat brain matrix and a tissue biopsy punch. The total tissue protein and the cytosolic subproteome were extracted from both samples. Protein samples were analyzed using two-dimensional gel electrophoresis, and the proteins with significant abundance changes were identified by mass spectrometry. RESULTS:There was a significant increase in the cytosolic protein concentration in the tumor, compared to normal brain regions, but the total protein concentrations were comparable. The protein profiles of the tumor and normal brain tissue differed significantly. Six cytosolic proteins, four endoplasmic reticulum proteins, and five secreted proteins were considerably upregulated in the tumor. CONCLUSIONS:Our experiments confirmed an increase in the cytosolic protein concentration in tumors and identified several key proteins that may cause APT-weighted hyperintensity.

SUBMITTER: Yan K

PROVIDER: S-EPMC4496258 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Assessing Amide Proton Transfer (APT) MRI Contrast Origins in 9 L Gliosarcoma in the Rat Brain Using Proteomic Analysis.

Yan Kun K Fu Zongming Z Yang Chen C Zhang Kai K Jiang Shanshan S Lee Dong-Hoon DH Heo Hye-Young HY Zhang Yi Y Cole Robert N RN Van Eyk Jennifer E JE Zhou Jinyuan J

Molecular imaging and biology 20150801 4

<h4>Purpose</h4>To investigate the biochemical origin of the amide photon transfer (APT)-weighted hyperintensity in brain tumors.<h4>Procedures</h4>Seven 9 L gliosarcoma-bearing rats were imaged at 4.7 T. Tumor and normal brain tissue samples of equal volumes were prepared with a coronal rat brain matrix and a tissue biopsy punch. The total tissue protein and the cytosolic subproteome were extracted from both samples. Protein samples were analyzed using two-dimensional gel electrophoresis, and t ...[more]

PMID: 25622812

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Project description:Amide proton transfer (APT) imaging is a variation of chemical exchange saturation transfer MRI that has shown promise in diagnosing tumors, ischemic stroke, multiple sclerosis, traumatic brain injury, etc. Specific quantification of the APT effect is crucial for the interpretation of APT contrast in pathologies. Conventionally, magnetization transfer ratio with asymmetric analysis (MTRasym ) has been used to quantify the APT effect. However, some studies indicate that MTRasym is contaminated by water longitudinal relaxation time (T1w ), and thus it is necessary to normalize T1w in MTRasym to obtain specific quantification of the APT effect. So far, whether to use MTRasym or the T1w -normalized MTRasym is still under debate in the field. In this paper, the influence of T1w on the quantification of APT was evaluated through theoretical analysis, numerical simulations, and phantom studies for different experimental conditions. Results indicate that there are two types of T1w effect (T1w recovery and T1w -related saturation), which have inverse influences on the steady-state MTRasym . In situations with no or weak direct water saturation (DS) effect, there is only the T1w recovery effect, and MTRasym linearly depends on T1w . In contrast, in situations with significant DS effects, the dependence of MTRasym on T1w is complex, and is dictated by the competition of these two T1w effects. Therefore, by choosing appropriate irradiation powers, MTRasym could be roughly insensitive to T1w . Moreover, in non-steady-state acquisitions with very short irradiation time, MTRasym is also roughly insensitive to T1w . Therefore, for steady-state APT imaging at high fields or with very low irradiation powers, where there are no significant DS effects, it is necessary to normalize T1w to improve the specificity of MTRasym . However, in clinical MRI systems (usually low fields or non-steady-state acquisitions), T1w normalization may not be necessary when appropriate sequence parameters are chosen.

Project description:PurposeTo evaluate the role of amide proton transfer-weighted (APT-w) magnetic resonance imaging (MRI) in differentiating neoplastic and infective mass lesions using different contrast normalizations, region of interest (ROI) selection, and histogram analysis.ProceduresRetrospective study included 32 treatment-naive patients having intracranial mass lesions (ICMLs): low-grade glioma (LGG) = 14, high-grade glioma (HGG) = 10, and infective mass lesions = 8. APT-w MRI images were acquired along with conventional MRI images at 3 T. APT-w contrast, corrected for B0-field inhomogeneity, was computed and optimized with respect to different types of normalizations. Different ROIs on lesion region were selected followed by ROI analysis and histogram analysis. Statistical analysis was performed using Shapiro-Wilk's test, t tests, ANOVA with Tukey's post hoc test, and receiver operation characteristic (ROC) analysis.ResultsICMLs showed significantly (p < 0.01) higher APT-w contrast in lesion compared with contralateral side. There was a substantial overlap between mean APT-w contrast of neoplastic and infective mass lesions as well as among different groups of ICMLs irrespective of ROI selection and normalizations. APT-w contrast (using type 4 normalization: normalized with reference signal at negative offset frequency and APT-w contrast in normal-appearing white matter) reduced variability of APT-w contrast across different subjects, and overlap was less compared with other types of normalizations. There was a significant difference (p < 0.05) between neoplastic and infective mass lesions using t test for different histogram parameters of type 4 normalized APT-w contrast. ANOVA with post hoc showed significant difference (p < 0.05) for different histogram parameters of APT-w contrast (Type 4 normalization) between LGG and HGG, LGG, and infective mass lesion. Histogram parameters such as standard deviation, mean of top percentiles, and median provided improved differentiation between neoplastic and infective mass lesions compared with mean APT-w contrast. A greater number of histogram parameters of type 4 normalized APT-w contrast corresponding to active lesion region can significantly differentiate between ICMLs than other types of normalizations and ROIs.ConclusionsAPT-w contrast using type 4 normalization and active lesion region (ROI-2) should be used for studying APT. APT-MRI should be combined with other MRI techniques to further improve the differential diagnosis of ICMLs.

Project description:BackgroundThe three-dimensional chemical exchange saturation transfer (3D CEST) technique is a novel and promising magnetic resonance sequence; however, its application in nasopharyngeal carcinoma (NPC) lacks sufficient evaluation. This study aimed to assess the feasibility of the 3D CEST technique in predicting the short-term treatment outcomes for chemoradiotherapy (CRT) in NPC patients.MethodsForty NPC patients and fourteen healthy volunteers were enrolled and underwent the pre-treatment 3D CEST magnetic resonance imaging and diffusion-weighted imaging (DWI). The reliability of 3D CEST was assessed in healthy volunteers by calculating the intra- and inter-observer correlation coefficient (ICC) for amide proton transfer weighted-signal intensity (APTw-SI) and magnetization transfer ratio (MTR) values. NPC patients were divided into residual and non-residual groups based on short-term treatment outcomes after CRT. Whole-tumor regions of interest (ROIs) were manually drawn to measure APTw-SI, MTR and apparent diffusion coefficient (ADC) values. Multivariate analysis and the receiver operating characteristic curve (ROC) were used to evaluate the prediction performance of clinical characteristics, APTw-SI, MTR, ADC values, and combined models in predicting short-term treatment outcomes in NPC patients.ResultsFor the healthy volunteer group, all APTw-SI and MTR values exhibited good to excellent intra- and inter-observer agreements (0.736-0.910, 0.895-0.981, all P > 0.05). For NPC patients, MTR values showed a significant difference between the non-residual and residual groups (31.24 ± 5.21% vs. 34.74 ± 1.54%, P = 0.003) while no significant differences were observed for APTw-SI and ADC values (P > 0.05). Moreover, the diagnostic power of MTR value was superior to APTw-SI (AUC: 0.818 vs. 0.521, P = 0.017) and comparable to ADC values (AUC: 0.818 vs. 0.649, P > 0.05) in predicting short-term treatment outcomes for NPC patients. The prediction performance did not improve even when combining MTR values with APTw-SI and/or ADC values (P > 0.05).ConclusionsThe pre-treatment MTR value acquired through 3D CEST demonstrated superior predictive performance for short-term treatment outcomes compared to APTw-SI and ADC values in NPC patients after CRT.

Dataset Information

Assessing Amide Proton Transfer (APT) MRI Contrast Origins in 9 L Gliosarcoma in the Rat Brain Using Proteomic Analysis.

Publications

Assessing Amide Proton Transfer (APT) MRI Contrast Origins in 9 L Gliosarcoma in the Rat Brain Using Proteomic Analysis.

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