Amide Proton Transfer-weighted Research Articles

Differentiation of fibroadenomas versus malignant breast tumors utilizing three-dimensional amide proton transfer weighted magnetic resonance imaging

ObjectiveTo explore the value of amide proton transfer-weighted (APTw) magnetic resonance imaging (MRI) for differential diagnosis of fibroadenomas and malignant breast tumors. Materials and methodsThis prospective study enrolled 56 patients with suspected breast tumors and performed APTw imaging. Based on the histopathology results, patients were divided into group 1 with malignant breast tumors (n = 41) and group 2 with fibroadenomas (n = 15). The measured image parameters (APTw value, ADC value, type of Time of Intensity Curve, maximum tumor diameter in image) and the maximal diameter of the tumors measured from surgical resection were compared between the two groups, and the diagnostic performance based on these parameters was quantified with ROC curve. Spearman's correlation coefficient was used to analyze the association between APTw or ADC values and ER, PR, HER2, and Ki-67 expressions. ResultsThe intraclass correlation coefficients (ICC = 0.87 and 0.91) indicated a good inter-observer agreement of the measured APTw values. APTw values of malignant lesions were significantly higher than those of fibroadenomas (3.21 ± 1.04% vs 1.50 ± 0.54%, p < 0.001). Area under the curve (AUC) obtained from APTw imaging, DWI, DCE, APTw imaging+DWI, APTw imaging+DWI, and APTw imaging+DWI + DCE was 0.959, 0.897, 0.976, 0.997, and 1 respectively. The APTw value showed a negative correlation with ER expression (r = −0.357). ConclusionAPTw imaging yielded similar diagnosis performance in discriminating fibroadenomas and malignant breast tumors when compared to the DCE and better than DWI imaging, and provided supplement information on tumor cell activity to DWI images. The APTw value showed correlations with some prognostic factors for breast cancer.

Fully automated analysis combining [18F]-FET-PET and multiparametric MRI including DSC perfusion and APTw imaging: a promising tool for objective evaluation of glioma progression

PurposeTo evaluate diagnostic accuracy of fully automated analysis of multimodal imaging data using [18F]-FET-PET and MRI (including amide proton transfer-weighted (APTw) imaging and dynamic-susceptibility-contrast (DSC) perfusion) in differentiation of tumor progression from treatment-related changes in patients with glioma.Material and methodsAt suspected tumor progression, MRI and [18F]-FET-PET data as part of a retrospective analysis of an observational cohort of 66 patients/74 scans (51 glioblastoma and 23 lower-grade-glioma, 8 patients included at two different time points) were automatically segmented into necrosis, FLAIR-hyperintense, and contrast-enhancing areas using an ensemble of deep learning algorithms. In parallel, previous MR exam was processed in a similar way to subtract preexisting tumor areas and focus on progressive tumor only. Within these progressive areas, intensity statistics were automatically extracted from [18F]-FET-PET, APTw, and DSC-derived cerebral-blood-volume (CBV) maps and used to train a Random Forest classifier with threefold cross-validation. To evaluate contribution of the imaging modalities to the classifier’s performance, impurity-based importance measures were collected. Classifier performance was compared with radiology reports and interdisciplinary tumor board assessments.ResultsIn 57/74 cases (77%), tumor progression was confirmed histopathologically (39 cases) or via follow-up imaging (18 cases), while remaining 17 cases were diagnosed as treatment-related changes. The classification accuracy of the Random Forest classifier was 0.86, 95% CI 0.77–0.93 (sensitivity 0.91, 95% CI 0.81–0.97; specificity 0.71, 95% CI 0.44–0.9), significantly above the no-information rate of 0.77 (p = 0.03), and higher compared to an accuracy of 0.82 for MRI (95% CI 0.72–0.9), 0.81 for [18F]-FET-PET (95% CI 0.7–0.89), and 0.81 for expert consensus (95% CI 0.7–0.89), although these differences were not statistically significant (p > 0.1 for all comparisons, McNemar test). [18F]-FET-PET hot-spot volume was single-most important variable, with relevant contribution from all imaging modalities.ConclusionAutomated, joint image analysis of [18F]-FET-PET and advanced MR imaging techniques APTw and DSC perfusion is a promising tool for objective response assessment in gliomas.

Prediction of H3K27M-mutant brainstem glioma by amide proton transfer-weighted imaging and its derived radiomics.

H3K27M-mutant associated brainstem glioma (BSG) carries a very poor prognosis. We aimed to predict H3K27M mutation status by amide proton transfer-weighted (APTw) imaging and radiomic features. Eighty-one BSG patients with APTw imaging at 3T MR and known H3K27M status were retrospectively studied. APTw values (mean, median, and max) and radiomic features within manually delineated 3D tumor masks were extracted. Comparison of APTw measures between H3K27M-mutant and wildtype groups was conducted by two-sample Student's T/Mann-Whitney U test and receiver operating characteristic curve (ROC) analysis. H3K27M-mutant prediction using APTw-derived radiomics was conducted using a machine learning algorithm (support vector machine) in randomly selected train (n = 64) and test (n = 17) sets. Sensitivity analysis with additional random splits of train and test sets, 2D tumor masks, and other classifiers were conducted. Finally, a prospective cohort including 29 BSG patients was acquired for validation of the radiomics algorithm. BSG patients with H3K27M-mutant were younger and had higher max APTw values than those with wildtype. APTw-derived radiomic measures reflecting tumor heterogeneity could predict H3K27M mutation status with an accuracy of 0.88, sensitivity of 0.92, and specificity of 0.80 in the test set. Sensitivity analysis confirmed the predictive ability (accuracy range: 0.71-0.94). In the independent prospective validation cohort, the algorithm reached an accuracy of 0.86, sensitivity of 0.88, and specificity of 0.85 for predicting H3K27M-mutation status. BSG patients with H3K27M-mutant had higher max APTw values than those with wildtype. APTw-derived radiomics could accurately predict a H3K27M-mutant status in BSG patients.

Feasibility evaluation of amide proton transfer-weighted imaging in the parotid glands: a strategy to recognize artifacts and measure APT value.

The feasibility and image quality of three-dimensional (3D) amide proton transfer (APT)-weighted (APTw) in parotid tumor lesions have not been well established in previous studies. This study aimed to evaluate the utility of APT imaging in parotid lesions and glands. Patients with parotid lesions received 3D turbo spin echo (TSE) APTw on a 3.0T scanner. Two radiologists, who were blinded to the clinical data, independently evaluated the APTw image quality using 4-point Likert scales (1= poor, 4= excellent) in terms of integrity and hyperintensity artifacts. An image quality selection protocol was built based on the two scores. Evaluable images (integrity score >1) and trustable images (integrity score >3 and hyperintensity artifacts score >2) were then enrolled for APTw value comparison between parotid lesions and glands. Forty consecutive patients were included in this study. Four patients were excluded due to severe motion (n=3) or dental (n=1) artifacts, and 36 patients received the APT sequence. Among these, more parotid tumor lesions (34/36, 94.4%) than normal parotid glands (23/31, 74.2%) revealed excellent integrity scores (score =4) (P=0.034). Most parotid tumor lesions (24/34, 70.6%) and glands (16/28, 57.1%) revealed no or little hyperintensity artifacts for diagnosis (scores 3 and 4). APT values of parotid lesions and glands in the evaluable groups were 2.11%±1.15% and 1.60%±1.56%, respectively, and the difference was not significant (P=0.197). APT values of parotid lesions and glands in the trustable groups were 1.99%±1.18% and 1.03%±1.09%, respectively, and the difference was statistically significant (P=0.018). 3D APTw could be used to differentiate parotid tumors and normal parotid glands; however, the technology still needs to be improved to remove artifacts. In our study, most APTw images of tumor lesions in parotid glands had acceptable image quality, and these APTw images are feasible for diagnostic use.

Amide Proton Transfer-weighted 7-T MRI Contrast of Myelination after Cuprizone Administration

Background Investigations of amide proton signal changes in the white matter of demyelinating diseases may provide important biophysical information for diagnostic and prognostic assessments. Purpose To evaluate amide proton signals in cuprizone-induced rats using amide proton transfer-weighted (APTw) MRI, which provides in vivo image contrast by changing amide proton concentrations during demyelination (DEM) and subsequent remyelination (REM). Materials and Methods In this animal study, APTw 7-T MRI was performed in 21 male Wistar rats divided into cuprizone-induced (n = 14) and control (n = 7) groups from February to August 2020. The cuprizone-induced group was further subdivided into DEM (n = 7) and REM (n = 7) groups. Seven weeks after cuprizone feeding, rats in the DEM group were killed prior to transmission electron microscopy and myelin staining, while rats in the REM group were changed to a normal chow diet and fed for 5 weeks. In each group, the APTw signals were calculated using a conventional magnetization transfer ratio at 3.5 ppm based on regions of interest in the corpus callosum. Statistical differences in APTw signals among the groups were analyzed with one-way analysis of variance followed by Tukey post hoc tests. Results The mean APTw signals in the control and DEM groups were -4.42% ± 0.60 (standard deviation) (95% CI: -4.98, -3.86) and -2.57% ± 0.48 (95% CI: -3.01, -2.12), respectively, indicating higher in vivo APTw signals in the DEM lesion (P < .001). After REM, mean APTw signal in the REM group was -3.83% ± 0.67 (95% CI: -4.45, -3.22), similar to that in the control group (P = .18) and lower than that in the DEM group (P < .001). Conclusion Significant amide proton transfer-weighted (APTw) metric changes coupled with the histologic characteristics of the demyelination and remyelination processes indicate the potential usefulness of APTw 7-T MRI to monitor earlier myelination processes. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by van Zijl in this issue.

Amide proton transfer weighted (APTw) imaging based radiomics allows for the differentiation of gliomas from metastases

We sought to evaluate the utility of radiomics for Amide Proton Transfer weighted (APTw) imaging by assessing its value in differentiating brain metastases from high- and low grade glial brain tumors. We retrospectively identified 48 treatment-naïve patients (10 WHO grade 2, 1 WHO grade 3, 10 WHO grade 4 primary glial brain tumors and 27 metastases) with either primary glial brain tumors or metastases who had undergone APTw MR imaging. After image analysis with radiomics feature extraction and post-processing, machine learning algorithms (multilayer perceptron machine learning algorithm; random forest classifier) with stratified tenfold cross validation were trained on features and were used to differentiate the brain neoplasms. The multilayer perceptron achieved an AUC of 0.836 (receiver operating characteristic curve) in differentiating primary glial brain tumors from metastases. The random forest classifier achieved an AUC of 0.868 in differentiating WHO grade 4 from WHO grade 2/3 primary glial brain tumors. For the differentiation of WHO grade 4 tumors from grade 2/3 tumors and metastases an average AUC of 0.797 was achieved. Our results indicate that the use of radiomics for APTw imaging is feasible and the differentiation of primary glial brain tumors from metastases is achievable with a high degree of accuracy.

Three-dimensional turbo-spin-echo amide proton transfer-weighted and intravoxel incoherent motion MR imaging for type I endometrial carcinoma: Correlation with Ki-67 proliferation status

BackgroundTo evaluate 3-dimensional amide proton transfer weighted (APTw) imaging for type I endometrial carcinoma (EC), and investigate correlations of Ki-67 labelling index with APTw and intravoxel incoherent motion (IVIM) imaging. Methods54 consecutive patients suspected of endometrial lesions underwent pelvic APTw and IVIM imaging on a 3 T MR scanner. APTw values and IVIM-derived parameters (Dt, D*, f) were independently measured by two radiologists on 22 postoperative pathological confirmed of type I EC lesions. Results were compared between histological grades and Ki-67 proliferation groups. ROC analysis was performed. Pearson's correlation analysis was performed for APTw values and IVIM-derived parameters with Ki-67 labeling index. ResultsAPTw values and Dt, D*, f of all type I EC were 2.9 ± 0.1%, 0.677 ± 0.027 × 10−3 mm2/s, 31.801 ± 11.492 × 10−3 mm2/s, 0.179 ± 0.050 with inter-observer ICC 0.996, 0.850, 0.956, 0.995, respectively. APTw values of Ki-67 low-proliferation group (<30%, n = 8) were 2.5 ± 0.2%, significantly lower than the high-proliferation group (>30%, n = 14) with APTw values of 3.1 ± 0.1% (p = 0.016). Area under the curve was 0.768. APTw values of type I EC were moderately positively correlated with Ki-67 labelling index (r = 0.583, p = 0.004). There was no significant difference of Dt (p = 0.843), D* (p = 0.262), f (p = 0.553) between the two groups. No correlation was found between IVIM-derived parameters and Ki-67 labelling index (Dt, p = 0.717; D* p = 0.151; f, p = 0.153). Conclusion3D TSE APTw imaging is a feasible approach for detecting type I EC. Ki-67 labeling index positively moderately correlates with APTw not with IVIM.

Effect of offset-frequency step size and interpolation methods on chemical exchange saturation transfer MRI computation in human brain.

Chemical exchange saturation transfer (CEST) MRI is a non-invasive molecular imaging technique with potential applications in pre-clinical and clinical studies. Applications of amide proton transfer-weighted (APT-w), glutamate-weighted (Glu-w) and creatine-weighted (Cr-w) CEST, among others, have been reported. In general, CEST data are acquired at multiple offset-frequencies. In reported studies, different offset-frequency step sizes and interpolation methods have been used during B0 inhomogeneity correction of data. The objective of the current study was to evaluate the effects of different step sizes and interpolation methods on CEST value computation. In the current study, simulation (Glu-w, Cr-w and APT-w) and experimental data from the brain were used. Experimental CEST data (Glu-w) were acquired from human volunteers at 7 T and brain tumor patients (APT-w) at 3 T. During B0 inhomogeneity correction, different interpolation methods (polynomial [degree-1, 2 and 3], cubic-Hermite, cubic-spline and smoothing-spline) were compared. CEST values were computed using asymmetry analysis. The effects of different step sizes and interpolation methods were evaluated using coefficient of variation (CV), normalized mean square error (nMSE) and coefficient of correlation parameters. Additionally, an optimum interpolation method for APT-w values was selected based upon fitting accuracy, T-test, receiver operating characteristic analysis, and its diagnostic performance in differentiating low-grade and high-grade tumors. CV and nMSE increase with an increase in step size irrespective of the interpolation method (except for cubic-Hermite and cubic-spline). The nMSE of Cr-w and Glu-w CEST values were least for polynomial (degree-2 and 3). The quality of Glu-w CEST maps became coarse with the increase in step size. There was a significant difference (P < .05) between low-grade and high-grade tumors using polynomial interpolation (degree-1, 2 and 3); however, linear interpolation outperforms other methods for APT-w data, providing the highest sensitivity and specificity. In conclusion, depending upon the saturation parameters and field strength, optimization of step size and interpolation should be carried out for different CEST metabolites/molecules. Glu-w, Cr-w and APT-w CEST data should be acquired with a step size of between 0.2 and 0.3 ppm. For B0 inhomogeneity correction, polynomial (degree-2) should be used for Glu-w and Cr-w CEST data at 7 T and linear interpolation should be used for APT-w data at 3 T for a limited frequency range.

Brain development in children with developmental delay using amide proton transfer-weighted imaging and magnetization transfer imaging.

ABSTRACTImportanceThe process of brain development in children with developmental delay is not well known. Amide proton transfer‐weighted (APTw) imaging is a novel molecular magnetic resonance imaging (MRI) technique that can noninvasively detect cytosolic endogenous mobile proteins and peptides involved in the myelination process, and may be useful for providing insights into brain development.ObjectiveTo assess the contribution of amide proton transfer‐weighted (APTw) imaging and magnetization transfer (MT) imaging to the evaluation of children with developmental delay (DD).MethodsFifty‐one patients with DD were recruited to this study. The patients were divided into two groups according to the state of myelination assessed on conventional magnetic resonance imaging (MRI). Thirty patients (10 girls, 20 boys; age range: 1–8 months; median age: 4 months) in group A showed delayed myelination on MRI, while 21 patients (3 girls, 18 boys; age range: 12–36months; median age: 25months) in group B showed normal myelination on MRI. Fifty‐one age‐ and sex‐matched children with normal developmental quotient (DQ) and normal MRI appearance were recruited as normal controls. Three‐slice APTw/MT axial imaging was performed at the level of the centrum semiovale, the basal ganglia and the pons. Quantitative data of the MT ratio (MTR) and APTw were analyzed for multiple brain regions. Independent‐sample t‐tests were used to compare differences in APTw and MTR signals between the two DD groups and normal controls. Analysis of Covariance was conducted to correct the statistical results. The level of statistical significance was set to P < 0.05.ResultsFor group A, the MTR values were lower in all regions (P = 0.004–0.033) compared with the normal controls, while the APTw values were higher in the pons, middle cerebellar peduncle, corpus callosum, frontal white matter, occipital white matter and centrum semiovale (P = 0.004–0.040 ). For Group B, the MTR values were slightly reduced, and the APTw values were slightly increased compared with the normal controls, but the differences were not statistically significant (P > 0.05).InterpretationFor DD patients showing signs of delayed myelination on MRI, MTR and APTw imaging can help to diagnose myelination delay by quantifying semi‐solid macromolecules and cytosolic endogenous mobile proteins and peptides at a molecular level, providing a new method for comprehensive evaluation of DD. For DD patients with normal myelination on MRI, the clinical values of MTR and APTw imaging remain to be explored.

Non-invasive Differentiation of Endometrial Adenocarcinoma from Benign Lesions in the Uterus by Utilization of Amide Proton Transfer-Weighted MRI.

To evaluate the utility of three-dimensional (3D) amide proton transfer-weighted (APTw) imaging for differentiation of endometrial adenocarcinoma and uterine benign lesions. This prospective study enrolled 22 normal volunteers and 113 patients with suspicious uterine lesions, including endometrial adenocarcinoma, leiomyoma, and adenomyosis. Pelvic APTw MRI was performed on a 3-T MRI scanner with default APTw parameters. Two radiologists blindly evaluated uterine lesion APTw image quality by a 3-point Likert scale and independently measured APTw values on images with excellent to good image quality. Inter-reader agreement was evaluated. The Mann-Whitney U test with Bonferroni correction was used to compare the differences among different types of uterine lesions. A receiver operating characteristic analysis was performed. A total of 111 lesions (33 endometrial adenocarcinoma, 26 leiomyoma, and 52 adenomyosis lesions) from 99 patients revealing a majority of good quality with excellent inter-reader agreement were included for the image quality evaluation. APTw values of endometrial adenocarcinoma were 2.9 ± 0.1 %, significantly higher than those of leiomyoma (1.9 ± 0.1 %), adenomyosis (2.2 ± 0.1 %), and normal uterine myometrium (1.9 ± 0.1 %) (all p < 0.0001). The area under the receiver operating characteristic curve for differentiating endometrial adenocarcinoma from leiomyoma, adenomyosis, and myometrium was 0.87, 0.85, and 0.91, respectively. Feasible threshold APTw values of each group were determined as 2.4 %, 2.7 %, and 2.4 % with a sensitivity of 83.3 %, 76.7 %, and 83.3 % and a specificity of 83.3 %, 81.6 %, and 86.4 %, respectively. Malignant endometrial adenocarcinoma had significantly higher APTw values than leiomyoma, adenomyosis, and normal uterine myometrium. Our study adds to the growing body of validation on 3D APTw imaging and uterine lesions.

Frequency-stabilized chemical exchange saturation transfer imaging with real-time free-induction-decay readout.

To correct the temporal B0 drift in chemical exchange saturation transfer (CEST) imaging in real-time with extra free-induction-decay (FID) readout. The frequency stabilization module of the recently proposed frequency-stabilized CEST (FS-CEST) sequence was further simplified by replacing the original three k-space lines of gradient-echo (GRE) readout with a single k-space line of FID readout. The B0 drift was quantified using the phase difference between the odd and even parts of the FID signal in the frequency stabilization module and then used to update the B0 frequency in the succeeding modules. The proposed FS-CEST sequence with FID readout (FID FS-CEST) was validated in phantoms and 16 human subjects on cross-vendor scanners. In the Siemens experiments, the FID FS-CEST sequence successfully corrected the user-induced B0 drift, generating consistent amide proton transfer-weighted (APTw) images and magnetization transfer ratio asymmetry (MTRasym ) spectra with those from the non-frequency-stabilized CEST (NFS-CEST) sequence without B0 drift. In the Philips experiments, the FID FS-CEST sequence produced more stable APTw images and MTRasym spectra than the NFS-CEST sequence in the presence of practical B0 drift. Quantitatively, the SD of the APTw signal values in the deep gray matter from 15 subjects was 0.26% for the FID FS-CEST sequence compared to 1.03% for the NFS-CEST sequences, with the fluctuations reduced by nearly three-quarters. The proposed FS-CEST sequence with FID readout can effectively correct the temporal B0 drift on cross-vendor scanners.

Correlations of amide proton transfer-weighted MRI of cerebral infarction with clinico-radiological findings.

To clarify the relationship between amide proton transfer-weighted (APTW) signal, which reflects intracellular pH, and clinico-radiological findings in patients with hyperacute to subacute cerebral infarction. Twenty-nine patients (median age, 70 years [IQR, 54 to 74]; 15 men) were retrospectively examined. The 10th, 25th, 50th, 75th, and 90th percentiles of APTW signal (APT10, APT25, APT50, APT75 and APT90, respectively) were measured within the infarction region-of-interest (ROI), and compared between poor prognosis and good prognosis groups (modified Rankin Scale [mRS] score ≥2 and mRS score <2, respectively). Correlations between APTW signal and time after onset, lesion size, National Institutes of Health Stroke Scale (NIHSS) score, mRS score, and mean apparent diffusion coefficient (ADC) were evaluated. The poor prognosis group had lower APT50, APT75, and APT90 than the good prognosis group (-0.66 [-1.19 to -0.27] vs. -0.09 [-0.62 to -0.21]; -0.27 [-0.63 to -0.01] vs. 0.31 [-0.15 to 1.06]; 0.06 [-0.21 to 0.34] vs. 0.93 [0.36 to 1.50] %; p <0.05, respectively). APT50 was positively correlated with time after onset (r = 0.37, p = 0.0471) and negatively with lesion size (r = -0.39, p = 0.0388). APT75 and APT90 were negatively correlated with NIHSS (r = -0.41 and -0.43; p <0.05, respectively). APT50, APT75 and APT90 were negatively correlated with mRS (r = -0.37, -0.52 and -0.57; p <0.05, respectively). APT10 and APT25 were positively correlated with mean ADC (r = 0.37 and 0.38; p <0.05, respectively). We demonstrated correlations between APTW signals of infarctions and clinico-radiological findings in patients with hyperacute to subacute infarctions. The poor prognosis group had a lower APTW signal than the good prognosis group. APTW signal was reduced in large infarctions, infarctions with low ADC, and in patients with high NIHSS and mRS scores.

Pre-treatment amide proton transfer imaging predicts treatment outcome in nasopharyngeal carcinoma.

To investigate the value of pre-treatment amide proton transfer-weighted (APTw) imaging for predicting survival of patients with nasopharyngeal carcinoma (NPC). Pre-treatment APTw imaging was performed in 77 NPC patients and the mean, 90th percentile, skewness, and kurtosis of APT asymmetry (APTmean, APT90, APTskewness, and APTkurtosis, respectively) were obtained from the primary tumor. Associations of APTw parameters with locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) after 2 years were assessed by univariable Cox regression analysis and significant APTw parameters, together with age, sex, treatment, and stage as confounding variables, were added to the multivariable model. Kaplan-Meier analysis was used to determine the prognostic significance of patients with high or low APT values based on a threshold value from receiver operating characteristic curve analysis. Locoregional relapse, distant metastases, and disease relapse occurred in 14/77 (18%), 10/77 (13%), and 20/77 (26%) patients, respectively, at a median follow-up of 48.3 (10.6-67.4) months. Univariable analysis showed significant associations of LRRFS with APTskewness (HR = 1.98; p = 0.034), DMFS with APTmean (HR = 2.44; p = 0.033), and APT90 (HR = 1.93; p = 0.009), and DFS with APTmean (HR = 2.01; p = 0.016), APT90 (HR = 1.68; p = 0.009), and APTskewness (HR = 1.85; p = 0.029). In multivariable analysis, the significant predictors for DMFS were APT90 (HR = 3.51; p = 0.004) and nodal stage (HR = 5.95; p = 0.034) and for DFS were APT90 (HR = 1.97; p = 0.010) and age (HR = 0.92; p = 0.014). An APT90 ≥ 4.38% was associated with a significantly poorer DFS at 2 years than APT90 < 4.38% (66% vs. 91%; HR = 4.01; p = 0.005). APTw imaging may potentially predict survival in patients with NPC. • APTw imaging may provide new markers to predict survival in nasopharyngeal carcinoma. • APT90 is an independent predictor of distant metastases-free survival and disease-free survival. • The APThigh group is at higher risk of disease relapse than the APTlow group.

Applying Amide Proton Transfer-Weighted Imaging (APTWI) to Distinguish Papillary Thyroid Carcinomas and Predominantly Solid Adenomatous Nodules: Comparison With Diffusion-Weighted Imaging.

Background: Amide proton transfer-weighted (ATPw) imaging is a novel MRI technique that has been used to identify benign and malignant tumors. The present study evaluated the role of APTw imaging in differentiating papillary thyroid carcinoma from predominantly solid adenomatous nodule.Methods: This study included 24 cases of solitary papillary thyroid carcinoma, and 20 cases of solid adenomatous nodules. Normal thyroid tissues were examined in 12 healthy subjects. The healthy subjects, eight cases of adenomatous nodule with cystic degeneration, and 12 cases of thyroid goiter, were only considered in the descriptive analysis, not included in our statistical analysis. The mean APTw value and the apparent diffusion coefficients (ADCs) of papillary thyroid carcinoma and solid adenomatous nodule were compared via a Mann-Whitney U test and receiver operating characteristic (ROC)-curve analyses.Results: The adenomatous nodule (3.3 ± 1.3%) exhibited significantly higher APTw value (p < 0.05) than that of the papillary thyroid carcinoma (1.8 ± 0.7%). The optimal cut-off value of the mean APTw value in differentiating papillary thyroid carcinoma from adenomatous nodule was 3.15%, with a sensitivity of 60% and a specificity of 100%. The mean ADC of papillary thyroid carcinoma (1.2 ± 0.2 × 10−3 mm2/s) was significantly lower than that of adenomatous nodule (2.0 ± 0.4 × 10−3 mm2/s). The optimal cut-off value of the mean ADC was 1.35 × 10−3 mm2/s, with a sensitivity of 100% and a specificity of 75%. Based on the ROC-curve analysis of APT and ADC, the ADC showed a higher area under the curve (AUC) than that of APT (AUCAPT = 0.84, AUCADC = 0.95).Conclusion: APTw imaging may be as useful as DWI for the differentiation of papillary thyroid carcinoma from predominantly solid adenomatous nodule. Although the sensitivity of ADC was greater than that of APT, APT had greater specificity.

Amide proton transfer-weighted magnetic resonance imaging of human brain aging at 3 Tesla.

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. 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. 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). 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.

Comparison of the reproducibility of 2D and 3D amide proton transfer weighted imaging in intracranial rat gliomas at 3 T

Magnetic resonance-based amide proton transfer weighted (APTw) imaging is one subset of the chemical exchange saturation transfer (CEST) imaging techniques and could provide a potential novel tool of tumor detection and characterization. The purpose of this study was to compare the reproducibility of APTw imaging with two-dimensional (2D) and three-dimensional (3D) techniques in rat intracranial gliomas. Thirty-two Sprague–Dawley (SD) male rats bearing intracranial C6 glioma underwent 2D and 3D APTw imaging twice with a 3 T scanner, respectively. Paired t test was used to compare the difference of magnetization transfer ratio asymmetry (MTRasym) values obtained from 2D and 3D APTw images with respect to tumor and the contralateral normal-appearing brain tissue. The reproducibility of MTRasym measurement values was evaluated using Bland–Altman plot. Our results showed that the reproducibility of MTRasym measurement values from 3D APTw imaging is superior to 2D APTw technique. Therefore, 3D APTw imaging for the brain tumor would be recommended to use in clinical practice with a clinically relevant time frame and research works considering the good reproducibility compared to 2D APTw imaging.

Amide Proton Transfer Imaging in Predicting Isocitrate Dehydrogenase 1 Mutation Status of Grade II/III Gliomas Based on Support Vector Machine.

BackgroundTo compare the efficacies of univariate and radiomics analyses of amide proton transfer weighted (APTW) imaging in predicting isocitrate dehydrogenase 1 (IDH1) mutation of grade II/III gliomas.MethodsFifty-nine grade II/III glioma patients with known IDH1 mutation status were prospectively included (IDH1 wild type, 16; IDH1 mutation, 43). A total of 1044 quantitative radiomics features were extracted from APTW images. The efficacies of univariate and radiomics analyses in predicting IDH1 mutation were compared. Feature values were compared between two groups with independent t-test and receiver operating characteristic (ROC) analysis was applied to evaluate the predicting efficacy of each feature. Cases were randomly assigned to either the training (n = 49) or test cohort (n = 10) for the radiomics analysis. Support vector machine with recursive feature elimination (SVM-RFE) was adopted to select the optimal feature subset. The adverse impact of the imbalance dataset in the training cohort was solved by synthetic minority oversampling technique (SMOTE). Subsequently, the performance of SVM model was assessed on both training and test cohort.ResultsAs for univariate analysis, 18 features were significantly different between IDH1 wild-type and mutant groups (P < 0.05). Among these parameters, High Gray Level Run Emphasis All Direction offset 8 SD achieved the biggest area under the curve (AUC) (0.769) with the accuracy of 0.799. As for radiomics analysis, SVM model was established using 19 features selected with SVM-RFE. The AUC and accuracy for IDH1 mutation on training set were 0.892 and 0.952, while on the testing set were 0.7 and 0.84, respectively.ConclusionRadiomics strategy based on APT image features is potentially useful for preoperative estimating IDH1 mutation status.

Whole-brain chemical exchange saturation transferimaging with optimized turbo spinecho readout.

To achieve fast whole-brain chemical exchange saturation transfer (CEST) imaging with negligible susceptibility artifact. An optimized turbo spin echo readout module, also known as sampling perfection with application optimized contrasts by using different flipangle evolutions (SPACE), was deployed in the CEST sequence. The SPACE-CEST sequence was tested in a phantom, 6 healthy volunteers, and 3 brain tumor patients on a 3T human scanner. A dual-echo gradientecho sequence was used for B0 inhomogeneity mapping. In addition, the proposed SPACE-CEST sequence was compared with the widely used turbo spin echo-CEST sequence for amide proton transfer-weighted (APTw) images. The SPACE-CEST sequence generated highly consistent APTw maps to those of the turbo spin echo-CEST sequence in the phantom. In healthy volunteers, the SPACE-CEST sequence yielded whole-brain 2.8-mm isotropic APTw source images within 5 minutes, with no discernible susceptibility artifact. As for the B0 maps in the whole brain, its mean, median, and standard deviation B0 offset values were 5.0 Hz, 5.6 Hz, and 16 Hz, respectively. Regarding the APTw map throughout the whole brain, its mean, median, and standard deviation values were 0.78%, 0.56%, and 1.74%, respectively. The SPACE-CEST sequence was also successfully applied to a postsurgery brain tumor patient, suggesting no disease progression. In addition, on the newly diagnosed brain tumor patients, the SPACE-CEST and turbo spin echo-CEST sequences yielded essentially identical APTw values. The proposed SPACE-CEST technique can rapidly generate whole-brain CEST source images with negligible susceptibility artifact.

Imaging glioma biology: spatial comparison of amino acid PET, amide proton transfer, and perfusion-weighted MRI in newly diagnosed gliomas

PurposeImaging glioma biology holds great promise to unravel the complex nature of these tumors. Besides well-established imaging techniques such O-(2-[18F]fluoroethyl)-l-tyrosine (FET)-PET and dynamic susceptibility contrast (DSC) perfusion imaging, amide proton transfer–weighted (APTw) imaging has emerged as a promising novel MR technique. In this study, we aimed to better understand the relation between these imaging biomarkers and how well they capture cellularity and vascularity in newly diagnosed gliomas.MethodsPreoperative MRI and FET-PET data of 46 patients (31 glioblastoma and 15 lower-grade glioma) were segmented into contrast-enhancing and FLAIR-hyperintense areas. Using established cutoffs, we calculated hot-spot volumes (HSV) and their spatial overlap. We further investigated APTw and CBV values in FET-HSV. In a subset of 10 glioblastoma patients, we compared cellularity and vascularization in 34 stereotactically targeted biopsies with imaging.ResultsIn glioblastomas, the largest HSV was found for APTw, followed by PET and CBV (p < 0.05). In lower-grade gliomas, APTw–HSV was clearly lower than in glioblastomas. The spatial overlap of HSV was highest between APTw and FET in both tumor entities and regions. APTw correlated significantly with cellularity, similar to FET, while the association with vascularity was more pronounced in CBV and FET.ConclusionsWe found a relevant spatial overlap in glioblastomas between hotspots of APTw and FET both in contrast-enhancing and FLAIR-hyperintense tumor. As suggested by earlier studies, APTw was lower in lower-grade gliomas compared with glioblastomas. APTw meaningfully contributes to biological imaging of gliomas.

Improving Amide Proton Transfer-Weighted MRI Reconstruction Using T2-Weighted Images.

Current protocol of Amide Proton Transfer-weighted (APTw) imaging commonly starts with the acquisition of high-resolution T2-weighted (T2w) images followed by APTw imaging at particular geometry and locations (i.e. slice) determined by the acquired T2w images. Although many advanced MRI reconstruction methods have been proposed to accelerate MRI, existing methods for APTw MRI lacks the capability of taking advantage of structural information in the acquired T2w images for reconstruction. In this paper, we present a novel APTw image reconstruction framework that can accelerate APTw imaging by reconstructing APTw images directly from highly undersampled k-space data and corresponding T2w image at the same location. The proposed framework starts with a novel sparse representation-based slice matching algorithm that aims to find the matched T2w slice given only the undersampled APTw image. A Recurrent Feature Sharing Reconstruction network (RFS-Rec) is designed to utilize intermediate features extracted from the matched T2w image by a Convolutional Recurrent Neural Network (CRNN), so that the missing structural information can be incorporated into the undersampled APT raw image thus effectively improving the image quality of the reconstructed APTw image. We evaluate the proposed method on two real datasets consisting of brain data from rats and humans. Extensive experiments demonstrate that the proposed RFS-Rec approach can outperform the state-of-the-art methods.