Amide Proton Transfer-weighted Values Research Articles

Feasibility of Amide Proton Transfer-Weighted Imaging at 3T for Renal Masses: A Preliminary Study.

To investigate the optimal B1,rms value of renal amide proton transfer-weighted (APTw) images and the reproducibility of this value, and to explore the utility of APT imaging of renal masses and kidney tissues. APTw images with different B1,rms values were repeatedly recorded in 15 healthy volunteers to determine the optimal value. Two 4-point Likert scales (poor [1] to excellent [4]) were used to evaluate contour clarity and artifacts in masses and normal tissues. The APTw values of masses and normal tissues were then compared in evaluable images (contour clarity score > 1, artifacts score > 1). The APTw of malignant masses, normal tissues, and benign masses were calculated and compared with the Mann-Whitney U test. The optimal scanning parameter of B1,rms was 2 μT, and the APTw images had good agreement in the volunteers. Our study of APTw imaging examined 70 renal masses (13 benign, 57 malignant) and 49 normal kidneys (including those from 15 healthy volunteers). The mean APTw value for renal malignant masses (2.28(1.55)) was different from that for benign masses (0.91(1.30)) (P<0.001), renal cortex (1.30 (1.25)) (P<0.001), renal medulla (1.64 (1.33)) (P<0.05), and renal pelvis (5.49 (2.65)) (P<0.001). These preliminary data demonstrate that APTw imaging of the kidneys has potential use as an imaging biomarker for the differentiation of normal tissues, malignant masses, and benign masses.

Amide proton transfer weighted imaging in pediatric neuro-oncology: initial experience.

Amide proton transfer weighted (APTw) imaging enables in vivo assessment of tissue-bound mobile proteins and peptides through the detection of chemical exchange saturation transfer. Promising applications of APTw imaging have been shown in adult brain tumors. As pediatric brain tumors differ from their adult counterparts, we investigate the radiological appearance of pediatric brain tumors on APTw imaging. APTw imaging was conducted at 3 T. APTw maps were calculated using magnetization transfer ratio asymmetry at 3.5 ppm. First, the repeatability of APTw imaging was assessed in a phantom and in five healthy volunteers by calculating the within-subject coefficient of variation (wCV). APTw images of pediatric brain tumor patients were analyzed retrospectively. APTw levels were compared between solid tumor tissue and normal-appearing white matter (NAWM) and between pediatric high-grade glioma (pHGG) and pediatric low-grade glioma (pLGG) using t-tests. APTw maps were repeatable in supratentorial and infratentorial brain regions (wCV ranged from 11% to 39%), except those from the pontine region (wCV between 39% and 50%). APTw images of 23 children with brain tumor were analyzed (mean age 12 years ± 5, 12 male). Significantly higher APTw values are present in tumor compared with NAWM for both pHGG and pLGG (p< 0.05). APTw values were higher in pLGG subtype pilocytic astrocytoma compared with other pLGG subtypes (p< 0.05). Non-invasive characterization of pediatric brain tumor biology with APTw imaging could aid the radiologist in clinical decision-making.

Amide proton transfer-weighted MRI for renal tumors: Comparison with diffusion-weighted imaging

ObjectiveTo investigate the potential of amide proton transfer-weighted (APTw) MRI in identifying benign and malignant renal tumors and to evaluate whether APTw MRI can add diagnostic value to diffusion-weighted imaging (DWI). Materials and methodsParticipants with renal tumor underwent preoperative multiparametric MRI, including APTw MRI and DWI. The APTw and apparent diffusion coefficient (ADC) of malignant tumors and benign tumors were calculated independently by two radiologists and compared. The value of the mean APTw and the mean ADC for differentiating malignant and benign tumors was evaluated by receiver operating characteristic analysis. ResultsIn total, 65 participants (mean age, 59 years ±14; 41 men) were evaluated: 54 with malignant and 11 with benign renal tumors. Malignant renal tumors showed higher mean APTw values [2.03% (1.63) vs 1.00% (1.60); P < 0.01] and lower mean ADC values (1.22 × 10-3 mm2/s ± 0.37 vs 1.51 × 10-3 mm2/s ± 0.37; P < 0.05) than benign renal tumors. The area under the receiver operating characteristic curve (AUC) of APTw, ADC and the combination of them for the identification of benign and malignant renal tumors was 0.78(95% CI: 0.66, 0.87; P < 0.001),0.70(95% CI: 0.54, 0.86; P < 0.05) and 0.79 (95% CI: 0.67, 0.88; P < 0.001). The optimal cutoff value for mean APTw was 2.14% (sensitivity, 74%; specificity, 73%). There was no difference between these three parameters for differentiating malignant from benign renal tumors (P > 0.05). ConclusionThe APTw MRI has the potential use as an imaging biomarker for renal malignant and benign tumors.

Amide Proton Transfer-Weighted MRI and Diffusion-Weighted Imaging in Bladder Cancer: A Complementary Tool to the VI-RADS

To investigate the feasibility of amide proton transfer-weighted (APTw) and diffusion-weighted Magnetic Resonance Imaging (MRI) as a means by which to add value to the Vesical Imaging Reporting and Data System (VI-RADS) for discriminating muscle invasive bladder cancer (MIBC) from nonmuscle invasive bladder cancer (NMIBC). This prospective study enrolled participants with pathologically confirmed bladder cancer (BCa) who underwent preoperative multiparametric MRI, including APTw and diffusion-weighted MRI, from July 2020 to January 2023. The exclusion criteria were lesions smaller than 10mm, missing smooth muscle layer in the operation specimen, neoadjuvant therapy before MRI, inadequate image quality, and malignancy other than urothelial neoplasm. Two radiologists independently assigned the VI-RADS score for each participant. Quantitative parameters derived from APTw and diffusion-weighted MRI were obtained by another two radiologists. Receiver operating characteristic (ROC) curve analysis with the area under the ROC curve (AUC) was performed to evaluate the diagnostic performances of quantitative parameters for discriminating BCa detrusor muscle invasion status. A total of 106 participants were enrolled (mean age, 64 ± 12 years [SD]; 90 men): 32 with MIBC and 74 with NMIBC. Lower apparent diffusion coefficient (ADC)values (0.88×10-3 mm2/s±0.12 vs. 1.08×10-3 mm2/s±0.25; P<0.001) and higher APTw values (6.89% [interquartile range {IQR}, 5.05%-12.17%] vs. 3.61% [IQR, 2.23%-6.83%]; P<0.001) were observed in the MIBC group. Compared to VI-RADS alone, both APTw (P=0.003) and ADC (P=0.020) values could improve the diagnostic performance of VI-RADS in differentiating MIBC from NMIBC. The combination of the three yielded the highest diagnostic performance (AUC, 0.93; 95% CI:0.87,0.97) for evaluating muscle invasion status. The addition of the APTw values to the combination of VI-RADS and ADC values notably improved the diagnostic performance for differentiating NMIBC from MIBC (VI-RADS+ADC vs. VI-RADS+APTw+ADC, P=0.046). MRI parameters derived from APTw and diffusion-weighted MRI can be used to accurately assess muscle invasion status in BCa and provide additional value to VI-RADS.

CEST 2022 - Differences in APT-weighted signal in T1 weighted isointense lesions, black holes and normal-appearing white matter in people with relapsing-remitting multiple sclerosis

PurposeTo evaluate amide proton transfer weighted (APTw) signal differences between multiple sclerosis (MS) lesions and contralateral normal-appearing white matter (cNAWM). Cellular changes during the demyelination process were also assessed by comparing APTw signal intensity in T1weighted isointense (ISO) and hypointense (black hole -BH) MS lesions in relation to cNAWM. MethodsTwenty-four people with relapsing-remitting MS (pw-RRMS) on stable therapy were recruited. MRI/APTw acquisitions were undertaken on a 3 T MRI scanner. The pre and post-processing, analysis, co-registration with structural MRI maps, and identification of regions of interest (ROIs) were all performed with Olea Sphere 3.0 software. Generalized linear model (GLM) univariate ANOVA was undertaken to test the hypotheses that differences in mean APTw were entered as dependent variables. ROIs were entered as random effect variables, which allowed all data to be included. Regions (lesions and cNAWM) and/or structure (ISO and BH) were the main factor variables. The models also included age, sex, disease duration, EDSS, and ROI volumes as covariates. Receiver operating characteristic (ROC) curve analyses were performed to evaluate the diagnostic performance of these comparisons. ResultsA total of 502 MS lesions manually identified on T2-FLAIR from twenty-four pw-RRMS were subcategorized as 359 ISO and 143 BH with reference to the T1-MPRAGE cerebral cortex signal. Also, 490 ROIs of cNAWM were manually delineated to match the MS lesion positions. A two-tailed t-test showed that mean APTw values were higher in females than in males (t = 3.52, p < 0.001). Additionally, the mean APTw values of MS lesions were higher than those of cNAWM after accounting for covariates (mean lesion = 0.44, mean cNAWM = 0.13, F = 44.12, p < 0.001).The mean APTw values of ISO lesions were higher than those of cNAWM after accounting for covariates (mean ISO lesions = 0.42, mean cNAWM = 0.21, F = 12.12, p < 0.001). The mean APTw values of BH were also higher than those of cNAWM (mean BH lesions = 0.47, mean cNAWM = 0.033, F = 40.3, p < 0.001). The effect size (i.e., difference between lesion and cNAWM) for BH was found to be higher than for ISO (14 vs. 2).Diagnostic performance showed that APT was able to discriminate between all lesions and cNAWM with an accuracy of >75% (AUC = 0.79, SE = 0.014). Discrimination between ISO lesions and cNAWM was accomplished with an accuracy of >69% (AUC = 0.74, SE = 0.018), while discrimination between BH lesions and cNAWM was achieved at an accuracy of >80% (AUC = 0.87, SE = 0.021). ConclusionsOur results highlight the potential of APTw imaging for use as a non-invasive technique that is able to provide essential molecular information to clinicians and researchers so that the stages of inflammation and degeneration in MS lesions can be better characterized.

Amide proton transfer-weighted MRI features of acute ischemic stroke subtypes.

Stroke is a highly heterogeneous disorder with distinct subtypes, and the stroke subtype influences the outcome. Amide proton transfer-weighted (APTW) MRI has been demonstrated to be promising in stroke patients, but the image characteristics of stroke subtypes have not been sufficiently investigated. The purpose of this study was to investigate the APTW MRI features of different subtypes of acute ischemic stroke (AIS). Ninety-two AIS patients presenting within 96 h of symptom onset were enrolled and examined with a 3.0-T MRI system. Patients were grouped into four subtypes: lacunar circulation infarcts (LACI, n = 33); total anterior circulation infarcts (TACI, n = 9); partial anterior circulation infarcts (PACI, n = 28); and posterior circulation infarcts (POCI, n = 22). APTW values in the lesion (APTWlesion ) and the contralateral normal-appearing region (APTWcontral ) were measured. The change in APTW values between the acute ischemic lesion and the contralateral normal-appearing region (APTWles-con ) was calculated. A two-sample t-test, one-way ANOVA, and the Chi-square method were used. There were significant differences between APTWlesion and APTWcontral in the three categories of nonlacunar strokes (TACI, PACI, and POCI, all p < 0.01), but not for lacunar strokes (LACI, p = 0.080). TACI patients had the lowest APTWlesion and APTWles-con in all groups (p < 0.05). In the POCI group, patients with supratentorial infarcts showed significant differences between APTWlesion and APTWcontral (p = 0.001), while the differences were not significant for infratentorial infarcts (p = 0.135). Our results suggest that the APT effect was heterogeneous in different stroke subtypes, and that APTW MRI gave an excellent performence in depicting nonlacunar AIS in supratentorial locations.

Altered glutamate-glutamine and amide proton transfer-weighted values in the hippocampus of patients with amnestic mild cognitive impairment: A novel combined imaging diagnostic marker.

Early diagnosis of amnestic mild cognitive impairment (aMCI) and timely management to delay the onset of Alzheimer's disease (AD) would benefit patients. Pathological metabolic changes of excitatory/inhibitory neurotransmitters and abnormal protein deposition in the hippocampus of aMCI may provide a new clue to imaging diagnosis. However, the diagnostic performance using these hippocampal metabolite measurements is still unclear. We aimed to quantify right hippocampal glutamate-glutamine (Glx) and gamma-aminobutyric acid (GABA) levels as well as protein-based amide proton transfer-weighted (APTw) signals of patients with aMCI and investigate the diagnostic performance of these metabolites. In this cross-sectional study, 20 patients with aMCI and 20 age- and gender-matched healthy controls (HCs) underwent MEGA Point Resolved Spectroscopy (MEGA-PRESS) and APTw MR imaging at 3 T. GABA+, Glx, and APTw signals were measured in the right hippocampus. The GABA+ levels, Glx levels, Glx/GABA+ ratios, and APTw values were compared between the HCs and aMCI groups using the Mann-Whitney U test. Binary logistic regression and receiver operating characteristic (ROC) curve analyses were used to evaluate MEGA-PRESS and APTw parameters' diagnostic performance. Compared with HCs, patients with aMCI had significantly lower Glx levels in the right hippocampus (7.02 ± 1.41 i.u. vs. 5.81 ± 1.33 i.u., P = 0.018). No significant changes in the GABA+ levels were observed in patients with aMCI (HCs vs. aMCI: 2.54 ± 0.28 i.u. vs. 2.47 ± 0.36 i.u., P = 0.620). In addition, Glx/GABA+ ratios between the two groups (HCs vs. aMCI: 2.79 ± 0.60 vs. 2.37 ± 0.55, P = 0.035) were significantly different. Compared with HCs, patients with aMCI showed higher APTw values in the right hippocampus (0.99 ± 0.26% vs. 1.26% ± 0.28, P = 0.006). The ROC curve analysis showed that Glx, GABA+, Glx/GABA+, and APTw values had an area under the curve (AUC) of 0.72, 0.55, 0.70, and 0.75, respectively, for diagnosing aMCI. In the ROC curve analysis, the AUC of the combination of the parameters increased to 0.88, which is much higher than that observed in the univariate analysis (P < 0.05). The combination of right hippocampal Glx levels and APTw values improved the diagnostic performance for aMCI, indicating it as a promising combined imaging diagnostic marker. Our study provided a potential imaging diagnostic strategy of aMCI, which may promote early detection of aMCI and facilitate timely intervention to delay the pathological progress toward AD.

APTw combined with mDixon-Quant imaging to distinguish the differentiation degree of cervical squamous carcinoma.

To investigate the value of amide proton transfer weighted (APTw) imaging combined with modified Dixon fat quantification (mDixon-Quant) imaging in determining the degree of differentiation of cervical squamous carcinoma (CSC) against histopathologic. Magnetic resonance imaging (MRI) data were collected from 52 CSC patients. According to histopathologic results, patients were divided into the poorly differentiated group (37 cases) and the well/moderately differentiated group (15 cases). The APTw value by APTw imaging and the fat fraction (FF) and transverse relaxation rate values by mDixon-Quant were independently measured by two radiologists. Intra-class correlation coefficients (ICCs) were used to test the consistency of APTw, FF, and values measured by the two observers. The Mann-Whitney U test was used to analyze the difference in each parameter between the two groups. Logistic regression analysis was used to assess the association between the degree of differentiation on histopathology and imaging parameters by APTw and mDixon Quant. The ROC curve was used to evaluate the diagnostic efficacy of various parameters and their combination in distinguishing the degree of CSC differentiation on histopathology. The DeLong test was used to access the differences among the area under the ROC curves (AUCs). The Pearson correlation coefficient was used to evaluate the correlation between APTw and mDixon-Quant imaging parameters. The APTw means were 2.95 ± 0.78% and 2.05 (1.85, 2.65)% in the poorly and well/moderately differentiated groups, respectively. The values were 26.62 (21.99, 33.31)/s and 22.93 ± 6.09/s in the poorly and well/moderately differentiated groups, respectively (P < 0.05). The AUCs of APTw, , and their combination were 0.762, 0.686, and 0.843, respectively. The Delong test suggested statistical significance between and the combination of APTw and . values showed a significant correlation with APTw values in the poorly differentiated group. APTw combined with mDixon-Quant can be used to efficiently distinguish the differention degrees of CSC diagnosed on histopathology.

Amide Proton Transfer-weighted MRI in Predicting Histologic Grade of Bladder Cancer.

Background Bladder cancer is classified into high and low grades with different clinical treatments and prognoses. Thus, accurate preoperative evaluation of the histologic grade through imaging techniques is essential. Purpose To investigate the potential of amide proton transfer-weighted (APTw) MRI in evaluating the grade of bladder cancer and to evaluate whether APTw MRI can add value to diffusion-weighted imaging (DWI) at MRI. Materials and Methods In this single-center prospective study, participants with pathologic analysis-confirmed bladder cancer with no previous treatment, lesions larger than 10 mm, and adequate MRI quality were enrolled from July 2020 to September 2021 in a university teaching hospital. All participants underwent preoperative multiparametric MRI, including APTw MRI and DWI. The mean APTw and apparent diffusion coefficient (ADC) values of the primary tumor were measured independently by two radiologists. Receiver operating characteristic curves were generated to evaluate the diagnostic performance of these quantitative parameters. Results In total, 83 participants (mean age, 64 years ± 13 [SD]; 72 men) were evaluated: 51 with high-grade and 32 with low-grade bladder cancer. High-grade bladder cancer showed higher APTw values (6% [IQR, 4%-12%] vs 2% [IQR, 1%-3%]; P < .001) and lower ADC values (0.92 × 10-3 mm2/sec ± 0.17 vs 1.21 × 10-3 mm2/sec ± 0.25; P < .001) than low-grade bladder cancer. The area under the receiver operating characteristic curve (AUC) of APTw and ADC for differentiating low- and high-grade bladder cancer was similar (0.84 for both; P = .94). Moreover, the combination of the two techniques improved the diagnostic performance (AUC, 0.93; all P = .01). Conclusion The combination of amide proton transfer-weighted and diffusion-weighted MRI has the potential to improve the histologic characterization of bladder cancer by differentiating low- from high-grade cancers. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Milot in this issue. An earlier incorrect version appeared online. This article was corrected on July 7, 2022.

Using amide proton transfer-weighted MRI to non-invasively differentiate mismatch repair deficient and proficient tumors in endometrioid endometrial adenocarcinoma

ObjectivesTo investigate the utility of three-dimensional (3D) amide proton transfer-weighted (APTw) imaging to differentiate mismatch repair deficient (dMMR) and mismatch repair proficient (pMMR) tumors in endometrioid endometrial adenocarcinoma (EEA).MethodsForty-nine patients with EEA underwent T1-weighted imaging, T2-weighted imaging, 3D APTw imaging, and diffusion-weighted imaging at 3 T MRI. Image quality and measurement confidence of APTw images were evaluated on a 5-point Likert scale. APTw and apparent diffusion coefficient (ADC) values were calculated and compared between the dMMR and pMMR groups and among the three EEA histologic grades based on the Federation of Gynecology and Obstetrics (FIGO) grading system criteria. Student’s t-test, analysis of variance with Scheffe post hoc test, and receiver operating characteristic analysis were performed. Statistical significance was set at p < 0.05.ResultsThirty-five EEA patients (9 with dMMR tumors and 26 with pMMR tumors) with good image quality were enrolled in quantitative analysis. APTw values were significantly higher in the dMMR group than in the pMMR group (3.2 ± 0.3% and 2.8 ± 0.5%, respectively; p = 0.019). ADC values of the dMMR and pMMR groups were 0.874 ± 0.104 × 10−3 mm2/s and 0.903 ± 0.100 × 10−3 mm2/s, respectively. No significant between-group difference was noted (p = 0.476). No statistically significant differences were observed in APTw values or ADC values among the three histologic grades (p = 0.766 and p = 0.295, respectively).ConclusionsAPTw values may be used as potential imaging markers to differentiate dMMR from pMMR tumors in EEA.

Amide Proton Transfer-Weighted MRI Might Help Distinguish Amnestic Mild Cognitive Impairment From a Normal Elderly Population.

Objectives: To evaluate whether 3D amide proton transfer weighted (APTw) imaging based on magnetization transfer analysis can be used as a novel imaging marker to distinguish amnestic mild cognitive impairment (aMCI) patients from the normal elderly population by measuring changes in APTw signal intensity in the hippocampus and amygdala.Materials and Methods: Seventy patients with aMCI and 74 age- and sex-matched healthy volunteers were recruited for routine MRI and APT imaging examinations. Magnetic transfer ratio asymmetry (MTRasym) of the amide protons (at 3.5 ppm), or APTw values, were measured in the bilateral hippocampus and amygdala on three consecutive cross-sectional APT images and were compared between the aMCI and control groups. The independent sample t-test was used to evaluate the difference in APTw values of the bilateral hippocampus and amygdala between the aMCI and control groups. Receiver operator characteristic analysis was used to assess the diagnostic performance of the APTw. The paired t-test was used to assess the difference in APTw values between the left and right hippocampus and amygdala, in both the aMCI and control groups.Results: The APTw values of the bilateral hippocampus and amygdala in the aMCI group were significantly higher than those in the control group (left hippocampus 1.01 vs. 0.77% p < 0.001; right hippocampus 1.02 vs. 0.74%, p < 0.001; left amygdala 0.98 vs. 0.70% p < 0.001; right amygdala 0.94 vs. 0.71%, p < 0.001). The APTw values of the left amygdala had the largest AUC (0.875) at diagnosis of aMCI. There was no significant difference in APTw values between the left and right hippocampus and amygdala, in either group. (aMCI group left hippocampus 1.01 vs. right hippocampus 1.02%, p = 0.652; healthy control group left hippocampus 0.77 vs. right hippocampus 0.74%, p = 0.314; aMCI group left amygdala 0.98 vs. right amygdala 0.94%, p = 0.171; healthy control group left amygdala 0.70 vs. right amygdala 0.71%, p = 0.726).Conclusion: APTw can be used as a new imaging marker to distinguish aMCI patients from the normal elderly population by indirectly reflecting the changes in protein content in the hippocampus and amygdala.

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.

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.

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.

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.

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.