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 focus of neuro-oncology research has changed from histopathologic grading to molecular characteristics, and medical imaging routinely follows this change.PurposeTo compare the diagnostic performance of amide proton transfer (APT) and four diffusion models in gliomas grading and isocitrate dehydrogenase (IDH) genotype.Study typeProspective.PopulationA total of 62 participants (37 males, 25 females; mean age, 52 ± 13 years) whose IDH genotypes were mutant in 6 of 14 grade II gliomas, 8 of 20 of grade III gliomas, and 4 of 28 grade IV gliomas.Field strength/sequenceAPT imaging using sampling perfection with application optimized contrasts by using different flip angle evolutions (SPACE) and DWI with q-space Cartesian grid sampling were acquired at 3 T.AssessmentThe ability of diffusion kurtosis imaging, diffusion kurtosis imaging, neurite orientation dispersion and density imaging (NODDI), mean apparent propagator (MAP), and APT imaging for glioma grade and IDH status were assessed, with histopathological grade and genetic testing used as a reference standard. Regions of interest (ROIs) were drawn by two neuroradiologists after consensus.Statistical testsT-test and Mann-Whitney U test; one-way analysis of variance (ANOVA); receiver operating curve (ROC) and area under the curve (AUC); DeLong test. P value < 0.05 was considered statistically significant.ResultsCompared with IDH-mutant gliomas, IDH-wildtype gliomas showed a significantly higher mean, 5th-percentile (APT5 ), and 95th-percentile from APTw, the 95th-percentile value of axial, mean, and radial diffusivity from DKI, and 95th-percentile value of isotropic volume fraction from NODDI, and no significantly different parameters from DTI and MAP (P = 0.075-0.998). The combined APT model showed a significantly wider area under the curve (AUC 0.870) for IDH status, when compared with DKI and NODDI. APT5 was significantly different between two of the three groups (glioma II vs. glioma III vs. glioma IV: 1.35 ± 0.75 vs. 2.09 ± 0.93 vs. 2.71 ± 0.81).Data conclusionAPT has higher diagnostic accuracy than DTI, DKI, MAP, and NODDI in glioma IDH genotype. APT5 can effectively identify both tumor grading and IDH genotyping, making it a promising biomarker for glioma classification.Evidence level1 TECHNICAL EFFICACY: Stage 2.

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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