Application of amide proton transfer imaging to pretreatment risk stratification of childhood neuroblastoma: comparison with neuron-specific enolase.

The diagnosis and treatment of childhood neuroblastoma (NB) varies with different risk groups, thus requiring accurate preoperative risk assessment. This study aimed to verify the feasibility of amide proton transfer (APT) imaging in risk stratification of abdominal NB in children, and compare it with the serum neuron-specific enolase (NSE). This prospective study enrolled 86 consecutive pediatric volunteers with suspected NB, and all subjects underwent abdominal APT imaging on a 3T magnetic resonance imaging scanner. A 4-pool Lorentzian fitting model was used to mitigate motion artifacts and separate the APT signal from the contaminating ones. The APT values were measured from tumor regions delineated by two experienced radiologists. The one-way analysis of variance, independent-sample t-test, Mann-Whitney U-test, and receiver operating characteristic analysis were performed to evaluate and compare the risk stratification performance of the APT value and serum NSE index-a routine biomarker of NB in clinics. Thirty-four cases (mean age, 38.6±32.4 months; 5 very-low-risk, 5 low-risk, 8 intermediate-risk and 16 high-risk ones) were included in the final analysis. The APT values were significantly higher in high-risk NB (5.80%±1.27%) than in the non-high-risk group (3.88%±1.01%) composed of the other three risk groups (P<0.001). However, there was no significant difference (P=0.18) in NSE levels between the high-risk (93.05±97.14 ng/mL) and non-high-risk groups (41.45±30.99 ng/mL). The associated area under the curve (AUC) of the APT parameter (AUC =0.89) in differentiating high-risk NB from non-high-risk NB was significantly higher (P=0.03) than that of NSE (AUC =0.64). As an emerging non-invasive magnetic resonance imaging technique, APT imaging has a promising prospect for distinguishing high-risk NB from non-high-risk NB in routine clinical applications.

Jia X ，Wang W ，Liang J ，Ma X ，Chen W ，Wu D ，Zhang H ，Ni S ，Wu J ，Lai C ，Zhang Y ... -  《-》

Risk stratification of abdominal tumors in children with amide proton transfer imaging.

To evaluate the potential of molecular amide proton transfer (APT) MRI for predicting the risk group of abdominal tumors in children, and compare it with quantitative T1 and T2 mapping. This prospective study enrolled 133 untreated pediatric patients with suspected abdominal tumors from February 2019 to September 2020. APT-weighted (APTw) imaging and quantitative relaxation time mapping sequences were executed for each subject. The region of interest (ROI) was generated with automatic artifact detection and ROI-shrinking algorithms, within which the APTw, T1, and T2 indices were calculated and compared between different risk groups. The prediction performance of different imaging parameters was assessed with the receiver operating characteristics (ROC) analysis and Student's t-test. Fifty-seven patients were included in the final analysis, including 24 neuroblastomas (NB), 18 Wilms' tumors (WT), and 15 hepatoblastomas (HB). The APTw signal was significantly (p < .001) higher in patients with high-risk NB than those with low-risk NB, while the difference between patients with low-risk and high-risk WT (p = .69) or HB (p = .35) was not statistically significant. The associated areas under the curve (AUC) for APT to differentiate low-risk and high-risk NB, WT, and HB were 0.93, 0.58, and 0.71, respectively. The quantitative T1 and T2 values generated AUCs of 0.61-0.70 for the risk stratification of abdominal tumors. APT MRI is a potential imaging biomarker for stratifying the risk group of pediatric neuroblastoma in the abdomen preoperatively and provides added value to structural MRI. • Amide proton transfer (APT) imaging showed significantly (p < .001) higher values in pediatric patients with high-risk neuroblastoma than those with low-risk neuroblastoma, but did not demonstrate a significant difference in patients with Wilms' tumor (p = .69) or hepatoblastoma (p = .35). • The associated areas under the curve (AUC) for APT to differentiate low-risk and high-risk neuroblastoma, Wilms' tumor, and hepatoblastoma were 0.93, 0.58, and 0.71, respectively. • The quantitative T1 and T2 indices generated AUCs of 0.61-0.70 for dichotomizing the risk group of abdominal tumors.

Jia X ，Wang W ，Liang J ，Ma X ，Chen W ，Wu D ，Lai C ，Zhang Y ... -  《-》

Differentiation of low- and high-grade pediatric gliomas with amide proton transfer imaging: added value beyond quantitative relaxation times.

To evaluate whether amide proton transfer (APT) MRI can be used to characterize gliomas in pediatric patients and whether it provides added value beyond relaxation times. In this prospective study, APT imaging and relaxation time mapping were performed in 203 pediatric patients suspected of gliomas from February 2018 to December 2019. The region of interest (ROI) in the tumor was automatically generated with artifact detection and ROI-shrinking algorithms. Several APT-related metrics (CESTR, CESTRnr, MTRRex, AREX, and APT#) and quantitative T1 and T2 were compared between low-grade and high-grade gliomas using the student's t-test or Mann-Whitney U-test. The performance of these parameters was assessed using the receiver operating characteristic (ROC) analysis. A stepwise multivariate logistic regression model was used to combine the imaging parameters. Forty-eight patients (mean age: 6 ± 4 years; 23 males and 25 females) were included in the final analysis. All the APT-related metrics except APT# had significantly (p < 0.05) higher values in the high-grade group than the low-grade group. Under different ROI-shrinking cutoffs, the quantitative T1 (p = 0.045-0.200) and T2 (p = 0.037-0.171) values of high-grade gliomas were typically lower than those of low-grade ones. The stepwise multivariate logistic regression revealed that CESTRnr and APT# were combined significant predictors of glioma grades (p < 0.05), with an area under the ROC curve (AUC) of 0.86 substantially larger than those of T1 (AUC = 0.69) and T2 (AUC = 0.68). APT imaging can be used to differentiate high-grade and low-grade gliomas in pediatric patients and provide added value beyond quantitative relaxation times. • Amide proton transfer (APT) MRI showed significantly (p < 0.05) higher values in pediatric patients with high-grade gliomas than those with low-grade ones. • The area under the curve was 0.86 for APT MRI to differentiate low-grade and high-grade gliomas in pediatric patients, which was substantially higher than that for quantitative T1 (0.69) and T2 (0.68). • APT MRI demonstrated added value beyond quantitative T1 and T2 mapping in characterizing pediatric gliomas.

Zhang H ，Yong X ，Ma X ，Zhao J ，Shen Z ，Chen X ，Tian F ，Chen W ，Wu D ，Zhang Y ... -  《-》

Comparative Analysis of Amide Proton Transfer MRI and Diffusion-Weighted Imaging in Assessing p53 and Ki-67 Expression of Rectal Adenocarcinoma.

The evaluation of prognostic factors in rectal carcinoma patients has important clinical significance. P53 status and the Ki-67 index have served as prognostic factors in rectal carcinoma. Amide proton transfer (APT) imaging has shown great potential in tumor diagnosis. However, few studies reported the value of APT imaging in evaluating p53 and Ki-67 status of rectal carcinoma. To investigate the feasibility of amide proton transfer MRI in assessing p53 and Ki-67 expression of rectal adenocarcinoma, and compare it with conventional diffusion-weighted imaging (DWI). Retrospective. Forty-three patients with rectal adenocarcinoma (age: 34-85 years). 3T/APT imaging using a 3D turbo spin echo (TSE)-Dixon pulse sequence with chemical shift-selective fat suppression, 2D DWI, and 2D T2 -weighted TSE. Mean tumor APT signal intensity (SImean ) and apparent diffusion coefficient (ADCmean ) were measured. Traditional tumor pathological analysis included WHO grades, pT (pathologic tumor) stages, and pN (pathologic node) stages. Expression levels of p53 and Ki-67 were determined by immunohistochemical assay. One-way analysis of variance (ANOVA); Student's t-test; Spearman's correlation coefficient; receiver operating characteristic (ROC) curve analysis. High-grade tumors, more advanced stage tumors, and tumors with lymph node involvement had higher APT SImean values: high grade (n = 15) vs. low-grade (n = 28), P < 0.001; pT2 (n = 10) vs. pT3 (n = 20) vs. pT4 (N = 13), P = 0.021; pN0 (n = 24) vs. pN1-2 (n = 19), P = 0.019. ADCmean differences were found in tumors with different pT stage: pT2 (n = 10) vs. pT3 (n = 20) vs. pT4 (N = 13), P = 0.013, but not in tumors with different histologic grade: high grade (n = 15) vs. low-grade (n = 28), P = 0.3536; or pN stage: pN0 (n = 24) vs. pN1-2 (n = 19), P = 0.624. Tumor with p53 positive status had higher APT SImean than tumor with negative p53 status (2.363 ± 0.457 vs. 2.0150 ± 0.3552, P = 0.014). There was no difference in ADCmean with p53 status (1.058 ± 0.1163 10-3  mm2 /s vs. 1.055 ± 0.128 10-3  mm2 /s, P = 0.935). APT SImean and ADCmean were significantly different in tumors with low and high Ki-67 status (1.7882 ± 0.11386 vs. 2.3975 ± 0.41586, P < 0.001; 1.1741 ± 0.093 10-3  mm2 /s vs. 1.0157 ± 0.10459 10-3  mm2 /s, P < 0.001, respectively). APT SImean exhibited a positive correlation with p53 labeling index and Ki-67 labeling index (r = 0.3741, P = 0.0135; r = 0.7048; P < 0.001, respectively). ADCmean showed no correlation with p53 labeling index, but a negative correlation with Ki-67 labeling index (r = -0.5543, P < 0.0001). ROC curves demonstrated that APT SImean had significantly higher diagnostic ability for differentiation of high Ki-67 expression of rectal adenocarcinoma than ADCmean (81.2% vs. 78.12%, 90.91% vs. 63.64; P < 0.001 vs. P = 0.017), while no difference was found in predicting p53 status (92.86% vs. 71.4%, 53.33% vs. 66.7%; P < 0.001 vs. P = 0.0471). APT SImean was related to p53 and Ki-67 expression levels in rectal adenocarcinoma. APT imaging may serve as a noninvasive biomarker for assessing genetic prognostic factors of rectal adenocarcinoma. 3 TECHNICAL EFFICACY STAGE: 2.

Li L ，Chen W ，Yan Z ，Feng J ，Hu S ，Liu B ，Liu X ... -  《-》

Diagnostic performance of gliomas grading and IDH status decoding A comparison between 3D amide proton transfer APT and four diffusion-weighted MRI models.

The focus of neuro-oncology research has changed from histopathologic grading to molecular characteristics, and medical imaging routinely follows this change. To compare the diagnostic performance of amide proton transfer (APT) and four diffusion models in gliomas grading and isocitrate dehydrogenase (IDH) genotype. Prospective. A 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. APT 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. The 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. T-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. Compared 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). APT 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. 1 TECHNICAL EFFICACY: Stage 2.

Guo H ，Liu J ，Hu J ，Zhang H ，Zhao W ，Gao M ，Zhang Y ，Yang G ，Cui Y ... -  《-》