Advances in diffuse glioma assessment: preoperative and postoperative applications of chemical exchange saturation transfer.

Chemical Exchange Saturation Transfer (CEST) is a technique that uses specific off-resonance saturation pulses to pre-saturate targeted substances. This process influences the signal intensity of free water, thereby indirectly providing information about the pre-saturated substance. Among the clinical applications of CEST, Amide Proton Transfer (APT) is currently the most well-established. APT can be utilized for the preoperative grading of gliomas. Tumors with higher APTw signals generally indicate a higher likelihood of malignancy. In predicting preoperative molecular typing, APTw values are typically lower in tumors with favorable molecular phenotypes, such as isocitrate dehydrogenase (IDH) mutations, compared to IDH wild-type tumors. For differential diagnosis, the average APTw values of meningiomas are significantly lower than those of high-grade gliomas. Various APTw measurement indices assist in distinguishing central nervous system lesions with similar imaging features, such as progressive multifocal leukoencephalopathy, central nervous system lymphoma, solitary brain metastases, and glioblastoma. Regarding prognosis, APT effectively differentiates between tumor recurrence and treatment effects, and also possesses predictive capabilities for overall survival (OS) and progression-free survival (PFS).

Multimodal imaging evaluation of early neurological deterioration following acute ischemic stroke.

Background: Early neurologic deterioration occurs in up to one-third of patients with acute ischemic stroke (IS), often leading to poor functional outcomes. At present, few studies have applied amide proton transfer (APT) imaging to the evaluation of early neurological deterioration (END). This study analyzed the value of computed tomography perfusion (CTP) combined with multimodal magnetic resonance imaging (MRI) in patients with acute IS with END. Methods: This retrospective study included patients with acute IS who were admitted to the neurology inpatient department in a tertiary hospital from October 2021 to June 2023. Patients with acute IS underwent CTP within 24 hours of stroke onset and MRI [arterial spin labeling (ASL), susceptibility-weighted imaging (SWI), and APT] within 7 days. END was defined as an elevation of ≥2 points on the National Institute of Health Stroke Scale (NIHSS) within 7 days of stroke onset. Univariable and multivariable analyses were used to compare clinical and imaging biomarkers in patients with acute IS with and without END. The performance of potential biomarkers in distinguishing between the two groups was evaluated using receiver operating characteristic (ROC) curve analysis. Results: Among the 70 patients with acute IS, 20 (29%) had END. After conducting univariable analysis, variables were selected for entry into a binary logistic regression analysis based on our univariable analysis results, previous research findings, clinical experience, and methodological standards. The results indicated that relative cerebral blood volume (CBV) on CTP, relative cerebral blood flow (CBF) on ASL, and relative signal intensity on amide proton transfer-weighted (APTw) imaging were independent risk factors for END. The areas under the ROC curves for these risk factors were 0.710 [95% confidence interval (CI): 0.559-0.861, P=0.006], 0.839 (95% CI: 0.744-0.933, P<0.001), and 0.804 (95% CI: 0.676-0.932, P<0.001), respectively. The combined area under the curve (AUC), sensitivity, and specificity of the four indices (0.941, 100%, and 78%, respectively) were higher than those of the four indices alone. Conclusions: CTP combined with multi-modal MRI better evaluated hemodynamics, tissue metabolism, and other relevant patient information, providing an objective basis for the clinical assessment of patients with acute IS with END and facilitating the development of accurate and personalized treatment plans.

Amide Proton Transfer-Weighted Imaging in Assessing the Aggressive and Proliferative Potential of Bladder Cancer.

BACKGROUND: Ki-67 and human epidermal growth factor receptor 2 (HER2) are known oncogenes involved in bladder cancer (BCa) patient risk stratification. Preoperative assessment of their expression level can assist in clinical treatment decision-making. Recently, amide proton transfer-weighted (APTw) MRI has shown promising potential in the diagnosis of several malignancies. However, few studies reported the value of APTw imaging in evaluating Ki-67 and HER2 status of BCa. PURPOSE: To investigate the feasibility of APTw MRI in assessing the aggressive and proliferative potential regarding the expression levels of Ki-67 and HER2 in BCa. STUDY TYPE: Retrospective. SUBJECTS: 114 patients (mean age, 64.78 ± 11.93 [SD] years; 97 men) were studied. FIELD STRENGTH/SEQUENCE: APTw MRI acquired by a three-dimensional fast-spin-echo sequence at 3.0 T MRI system. ASSESSMENT: Patient pathologic findings, included histologic grade and the expression status of Ki-67 and HER2, were reviewed by one uropathologist. The APTw values of BCa were independently measured by two radiologists and were compared between high-/low-tumor grade group, high-/low-Ki-67 expression group, and high-/low-HER2 expression group. STATISTICAL TESTS: The interclass correlation coefficient, independent sample t-test, Mann-Whitney U test, Spearman's rank correlation, and receiver operating characteristic curve (ROC) analysis were used. P < 0.05 was considered statistically significant. RESULTS: Significantly higher APTw values were found in high-grade BCa patients (7.72% vs. 4.29%, P < 0.001), high-Ki-67 expression BCa patients (8.40% vs. 3.25%, P < 0.001) and HER2 positive BCa patients (8.24% vs. 5.40%, P = 0.001). APTw values were positively correlated with Ki-67 (r = 0.769) and HER2 (r = 0. 356) expression status. The area under the ROC curve of the APTw values for detecting Ki-67 and HER2 expression status were 0.883 (95% CI: 0.790-0.945) and 0.713 (95% CI: 0.592-0.816), respectively. DATA CONCLUSIONS: APTw MRI is a potential method to assess the biological and proliferation potential of BCa. TECHNICAL EFFICACY: Stage 2.

Amide proton transfer-weighted imaging with a short acquisition time based on a self B0 correction using the turbo spin echo-Dixon method: A phantom study.

PURPOSE: Conventional amide proton transfer (APT)-weighted imaging requires a chemical exchange saturation transfer (CEST) sequence with multiple saturation frequency offsets and a B0 correction sequence, plus a long acquisition time that can be reduced by applying the conventional method using CEST images with seven radiation pulses (i.e., the seven-points method). For a further reduction of acquisition times, we propose fast two-dimensional (2D) APT-weighted imaging based on a self B0 correction using the turbo spin echo (TSE)-Dixon method. We conducted a phantom study to investigate the accuracy of TSE-Dixon APT-weighted imaging. METHODS: We prepared two types of phantoms with six samples for a concentrationdependent evaluation and a pH-dependent evaluation. APT-weighted images were acquired by the conventional, seven-points, and TSE-Dixon methods. Linear regression analyses assessed the dependence between each method's APT signal intensities (SIs) and the concentration or pH. We performed a one-way analysis of variance with Tukey's honestly significant difference post hoc test to compare the APT SIs among the three methods. The agreement of the APT SIs between the conventional and seven-points or TSE-Dixon methods was assessed by a Bland- Altman plot analysis. RESULTS: The APT SIs of all three acquisition methods showed positive concentration dependence and pH dependence. No significant differences were observed in the APT SIs between the conventional and TSE-Dixon methods at each concentration. The Bland-Altman plot analyses showed that the APT SIs measured with the seven-points method resulted in 0.42% bias and narrow 95% limits of agreement (LOA) (0.93%-0.09%) compared to the conventional method. The APT SIs measured using the TSE-Dixon method showed 0.14% bias and similar 95% LOA (-0.33% to 0.61%) compared with the seven-points method. The APT SIs of all three methods showed positive pH dependence. At each pH, no significant differences in the APT SIs were observed among the methods. Bland-Altman plot analyses showed that the APT SIs measured with the seven-points method resulted in low bias (0.03%) and narrow 95% LOA (-0.30% to 0.36%) compared to the conventional method. The APT SIs measured by the TSE-Dixon method showed slightly larger bias (0.29%) and similar 95% LOA (from -0.15% to 0.72%) compared to those measured by the seven-points method. CONCLUSION: These results demonstrated that our proposed method has the same concentration dependence and pH dependence as the conventional method and the seven-points method. We thus expect that APT-weighted imaging with less influence of motion can be obtained in clinical examinations.

Utilizing the amide proton transfer technique to characterize diffuse gliomas based on the WHO 2021 classification of CNS tumors.

PURPOSE: Diffuse gliomas present a significant challenge for healthcare systems globally. While brain MRI plays a vital role in diagnosis, prognosis, and treatment monitoring, accurately characterizing gliomas using conventional MRI techniques alone is challenging. In this study, we explored the potential of utilizing the amide proton transfer (APT) technique to predict tumor grade and type based on the WHO 2021 Classification of CNS Tumors. METHODS: Forty-two adult patients with histopathologically confirmed brain gliomas were included in the study. They underwent 3T MRI imaging, which involved APT sequence. Multinomial and binary logistic regression models were employed to classify patients into clinically relevant groups based on MRI findings and demographic variables. RESULTS: We found that the best model for tumor grade classification included patient age along with APT values. The highest sensitivity (88%) was observed for Grade 4 tumors, while Grade 3 tumors showed the highest specificity (79%). For tumor type classification, our model incorporated four predictors: APT values, patient's age, necrosis, and the presence of hemorrhage. The glioblastoma group had the highest sensitivity and specificity (87%), whereas balanced accuracy was the lowest for astrocytomas (0.73). CONCLUSION: The APT technique shows great potential for noninvasive evaluation of diffuse gliomas. The changes in the classification of gliomas as per the WHO 2021 version of the CNS Tumor Classification did not affect its usefulness in predicting tumor grade or type.

The Value of Amide Proton Transfer MRI in the Diagnosis of Malignant and Benign Urinary Bladder Lesions: Comparison With Diffusion-Weighted Imaging.

BACKGROUND: Conventional magnetic resonance imaging (MRI) has certain limitations in distinguishing between malignant and benign urinary bladder (UB) lesions. Amide proton transfer (APT) imaging may provide more diagnostic information than diffusion-weighted imaging (DWI) to distinguish between malignant and benign UB. PURPOSE: To investigate the potential of APT imaging in the diagnosis of malignant and benign UB lesions and to compare its diagnostic efficacy with that of conventional DWI. STUDY TYPE: Prospective. SUBJECTS: Eighty patients with UB lesions. FIELD STRENGTH/SEQUENCE: A 3.0 T/turbo spin echo (TSE) T1-weighted and T2-weighted imaging, single-shot echo planar DWI, and three-dimensional TSE APT imaging. ASSESSMENT: Patients underwent radical cystectomy or transurethral resection of the bladder lesions within 2 weeks after CT urography and MRI examination. APT signal intensity in UB lesions was quantified by the asymmetric magnetization transfer ratio (MTRasym). MTRasym and apparent diffusion coefficient (ADC) values were measured and compared between malignant and benign UB lesions. STATISTICAL TESTS: Kolmogorov-Smirnov test, Student's t test or Mann-Whitney U test, Spearman rank correlation coefficient, area under the receiver operating characteristic (ROC) curve (AUC), Delong test, and intraclass correlation coefficient (ICC). The significance threshold was set at P < 0.05. RESULTS: Thirty-two patients had pathologically confirmed benign UB lesions, including 2 bladder leiomyomas, 1 submucosal amyloidosis, 1 inflammatory myofibroblastic tumor, and 28 inflammatory lesions, and 48 patients had pathologically confirmed urothelial carcinoma. Urothelial carcinomas showed significantly higher MTRasym values (1.53% [0.74%] vs. 0.85% [0.23%]) and significantly lower ADC values (1.24 ± 0.34 × 10-3 mm2/s vs. 1.43 ± 0.22 × 10-3 mm2/s) than benign UB lesions. The MTRasym value (AUC = 0.928) was significantly better in differentiating urothelial carcinoma from benign UB lesions than the ADC value (AUC = 0.722). DATA CONCLUSION: APT imaging may have value in discriminating malignant from benign UB lesions and has better diagnostic performance than DWI. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Added-value of 3D amide proton transfer MRI in assessing prognostic factors of cervical cancer: a comparative study with multiple model diffusion-weighted imaging.

Background: Amide proton transfer (APT) imaging has been gradually applied to cervical cancer, yet the relationships between APT and multiple model diffusion-weighted imaging (DWI) have yet to be investigated. This study attempted to evaluate the added value of 3-dimensional (3D) APT imaging to multiple model DWI for assessing prognostic factors of cervical cancer. Methods: This prospective diagnostic study was conducted in The First Affiliated Hospital of Zhengzhou University. A total of 88 consecutive patients with cervical cancer underwent APT imaging and DWI with 11 b-values (0-2,000 s/mm2). The apparent diffusion coefficient (ADC), pure molecular diffusion (D), perfusion fraction (f), pseudo-diffusion (D*), mean kurtosis (MK), and mean diffusivity (MD) were calculated based on mono-exponential, bi-exponential, and kurtosis models. The mean, minimum, and maximum values of APT signal intensity (APT SI) and DWI-derived metrics were compared based on tumor stages, subtypes, grades, and lymphovascular space invasion status by Student's t-test or Mann-Whitney U test. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of the parameters. Results: APT SImax, APT SImin, MKmean, and MKmax showed significant differences between adenocarcinoma (AC) and squamous cell carcinoma (SCC) (all P<0.05). APT SImean, APT SImax, and MKmax were higher and ADCmin, Dmean, Dmin, and MDmin were lower in the high-grade tumor than in low-grade tumor (all P<0.05). For distinguishing lymphovascular space invasion, only MKmean showed significant difference (P=0.010). APT SImax [odds ratio (OR) =2.347, P=0.029], APT SImin (OR =0.352; P=0.024), and MKmean (OR =6.523; P=0.001) were the independent predictors for tumor subtype, and APT SImax (OR =2.885; P=0.044), MDmin (OR =0.155, P=0.012) were the independent predictors for histological grade of cervical cancer. When APT SImin and APT SImax was combined with MKmean and MKmax, the diagnostic performance was significantly improved for differentiating AC and AC [area under the curve (AUC): 0.908, sensitivity: 87.5%; specificity: 83.3%; P<0.001]. The combination of APT SImean, APT SImax, ADCmin, MKmax, and MDmin demonstrated the highest diagnostic performance for predicting tumor grade (AUC: 0.903, sensitivity: 78.6%; specificity: 88.9%; P<0.001). Conclusions: Addition of APT to DWI may improve the ability to noninvasively predict poor prognostic factors of cervical cancer.

Amide proton transfer (APT) and magnetization transfer (MT) in predicting short-term therapeutic outcome in nasopharyngeal carcinoma after chemoradiotherapy: a feasibility study of three-dimensional chemical exchange saturation transfer (CEST) MRI.

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

Semi-solid MT and APTw CEST-MRI predict clinical outcome of patients with glioma early after radiotherapy.

PURPOSE: The purpose of this study was to compare the potential of asymmetry-based (APTwasym ), Lorentzian-fit-based (PeakAreaAPT and MTconst ), and relaxation-compensated (MTRRex APT and MTRRex MT) CEST contrasts of the amide proton transfer (APT) and semi-solid magnetization transfer (ssMT) for early response assessment and prediction of progression-free survival (PFS) in patients with glioma. METHODS: Seventy-two study participants underwent CEST-MRI at 3T from July 2018 to December 2021 in a prospective clinical trial four to 6 wk after the completion of radiotherapy for diffuse glioma. Tumor segmentations were performed on T2w -FLAIR and contrast-enhanced T1w images. Therapy response assessment and determination of PFS were performed according to response assessment in neuro oncology (RANO) criteria using clinical follow-up data with a median observation time of 9.2 mo (range, 1.6-40.8) and compared to CEST MRI metrics. Statistical testing included receiver operating characteristic analyses, Mann-Whitney-U-test, Kaplan-Meier analyses, and logrank-test. RESULTS: MTconst (AUC = 0.79, p < 0.01) showed a stronger association with RANO response assessment compared to PeakAreaAPT (AUC = 0.71, p = 0.02) and MTRRex MT (AUC = 0.71, p = 0.02), and enabled differentiation of participants with pseudoprogression (n = 8) from those with true progression (AUC = 0.79, p = 0.02). Furthermore, MTconst (HR = 3.04, p = 0.01), PeakAreaAPT (HR = 0.39, p = 0.03), and APTwasym (HR = 2.63, p = 0.02) were associated with PFS. MTRRex APT was not associated with any outcome. CONCLUSION: MTconst , PeakAreaAPT, and APTwasym imaging predict clinical outcome by means of progression-free survival. Furthermore, MTconst enables differentiation of radiation-induced pseudoprogression from disease progression. Therefore, the assessed metrics may have synergistic potential for supporting clinical decision making during follow-up of patients with glioma.

CEST 2022-three-dimensional amide proton transfer (APT) imaging can identify the changes of cerebral cortex in Parkinson's disease.

PURPOSE: Amide proton transfer (APT) imaging has shown its diagnostic and predictive superiority in Parkinson's disease (PD) in our previous studies using 2D APT imaging based on deep nuclei. We hypothesized that the pathophysiological abnormality of PD will change the APT-related parameters in the cerebral cortex, and the signal changes can contribute to accurate diagnosis of PD. METHODS: 34 patients with idiopathic Parkinson's disease (IPD) and 29 age- and sex-matched normal controls (NC) were enrolled in this prospective study. 3D-APT imaging and 3D-T1WI was performed in our participants. A volume-based morphometry algorithm was used and get automated cortical segmentations. Quantitative parameter maps of APT-related metrics were calculated by using SPM and MATLAB. The unpaired Student's t-test or Mann-Whitney U test was used for comparison of these values between IPD and NC groups. The associations between APT-related metrics and clinical assessments were investigated by Spearman correlation analysis. The receiver-operating characteristic (ROC) analysis was used to assess the diagnostic performances. The binary logistic regression model was used to combine the imaging parameters. RESULTS: There wasn't any correlations between cortical APT-related signals and clinical assessment, including the H&Y scale, the disease duration, the UPDRS III scores and the MMSE scores. The MTRasym, CESTRnr and MTRRex had significantly higher values (p <0.001, corrected by Bonferroni methods) in the IPD group than NC groups in the region of bilateral and total temporal grey matter. The single parameters achieved the best diagnostic performance among all APT-related metrics was MTRRex on the right temporal grey matter, with an area under the ROC curve (AUC) of 0.865. The combined parameters achieved the highest diagnostic performance (AUC: 0.932). CONCLUSIONS: 3D-APT imaging could identify the changes of the cerebral cortex in Parkinson's disease. The cortical changes of APT-related parameters could potentially serve as imaging biomarkers to aid in the non-invasive diagnosis of PD.

Amide Proton Transfer-Chemical Exchange Saturation Transfer Imaging of Intracranial Brain Tumors and Tumor-like Lesions: Our Experience and a Review.

Chemical exchange saturation transfer (CEST) is a molecular magnetic resonance imaging (MRI) method that can generate image contrast based on the proton exchange between labeled protons in solutes and free, bulk water protons. Amide proton transfer (APT) imaging is the most frequently reported amide-proton-based CEST technique. It generates image contrast by reflecting the associations of mobile proteins and peptides resonating at 3.5 ppm downfield from water. Although the origin of the APT signal intensity in tumors is unclear, previous studies have suggested that the APT signal intensity is increased in brain tumors due to the increased mobile protein concentrations in malignant cells in association with an increased cellularity. High-grade tumors, which demonstrate a higher proliferation than low-grade tumors, have higher densities and numbers of cells (and higher concentrations of intracellular proteins and peptides) than low-grade tumors. APT-CEST imaging studies suggest that the APT-CEST signal intensity can be used to help differentiate between benign and malignant tumors and high-grade gliomas and low-grade gliomas as well as estimate the nature of lesions. In this review, we summarize the current applications and findings of the APT-CEST imaging of various brain tumors and tumor-like lesions. We report that APT-CEST imaging can provide additional information on intracranial brain tumors and tumor-like lesions compared to the information provided by conventional MRI methods, and that it can help indicate the nature of lesions, differentiate between benign and malignant lesions, and determine therapeutic effects. Future research could initiate or improve the lesion-specific clinical applicability of APT-CEST imaging for meningioma embolization, lipoma, leukoencephalopathy, tuberous sclerosis complex, progressive multifocal leukoencephalopathy, and hippocampal sclerosis.

The combined application of amide proton transfer imaging and diffusion kurtosis imaging for differentiating stage Ia endometrial carcinoma and endometrial polyps.

OBJECTIVE: This study aims to explore the diagnostic performance of amide proton transfer (APT) imaging combined with diffusion kurtosis imaging (DKI) in differentiating stage Ia endometrial carcinoma (EC) and endometrial polyps (EP). METHODS: All patients were scanned with APT and DKI sequences with 3.0 T MRI before surgery. The MRI data of 32 patients with histopathologically confirmed stage Ia EC and 17 patients with EP were retrospectively analyzed. Amide proton transfer, mean kurtosis (MK) and mean diffusivity (MD) values were measured. ROC curves were employed to evaluate the efficiency of differentiating and diagnosing stage Ia EC and EP, followed by the Delong test to compare the differences between the areas under the curve (AUCs) of each parameter. Additionally, the Pearson correlation analysis was performed to assess the correlation between APT values and MK and MD. RESULTS: The measured APT, MK, and MD values of the patients with stage Ia EC were 2.609 ± 0.504%,0.641 ± 0.113 and 0.904(0.816, 1.108) µm2/ms, while those of patients with EP were1.909 ± 0.418%, 0.495 ± 0.069, and 1.650 (1.458, 1.815) µm2/ms. The AUCs of APT, MK, MD, MK + MD, and APT + MK + MD in differentiating stage Ia EC and EP were.850, 0.879, 0.893, 0.930 and 0.976, respectively. The AUCs of APT + MK + MD were significantly higher than the AUCs of APT or MK (P < 0.05). The APT value was weakly and positively correlated with the MK value (r = 0.299, P = 0.037), while the APT value was moderately and negatively correlated with the MD value (r = -0.520, P < 0.001). CONCLUSION: Both APT and DKI effectively differentiated stage Ia EC and EP; however, when combined, APT and DKI improved the ability to differentiate these diseases, boosting the value of using a combination of these modalities in clinical applications.

Research Progress on Amide Proton Transfer Imaging in Preoperative and Postoperative Glioma Assessment.

Amide proton transfer (APT) imaging is a technique that reflects the level of amide proton transport of hydrogen ions in water to peptides and proteins within the tumour by using magnetic resonance imaging without contrast administration. This technique can more accurately reflect the protein level, pH value, and other relevant information within the tumour. Currently, APT is widely used in glioma research. In this paper, we briefly describe the research progress on this technique.

Evaluation of amide proton transfer imaging for bladder cancer histopathologic features: A comparative study with diffusion- weighted imaging.

PURPOSE: To assess the ability of amide proton transfer (APT) imaging, in comparison with diffusion-weighted imaging (DWI), to differentiate low-grade from high-grade bladder tumors and predict the aggressiveness of bladder cancer (BCa). METHODS: Forty-eight patients diagnosed with BCa confirmed by histopathological findings who underwent magnetic resonance (MR) imaging, including APT imaging and DWI (b = 0, 1000 sec/mm2), were enrolled in this study. The asymmetric magnetization transfer ratio (MTRasym) was defined as the magnetization transfer asymmetry at 3.5 ppm. MTRasym and apparent diffusion coefficients (ADCs) were compared between the low- and high-grade groups and between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) in terms of the areas under the receiver operating characteristic curves (AUCs). RESULTS: The MTRasym values were significantly higher in patients with high-grade bladder tumors than in those with low-grade tumors (1.61 % [0.76 %], 1.12 ± 0.3 %; P = 0.000) and in MIBC than in NMIBC (2.53 ± 0.67 %, 1.38 % [0.35 %]; P = 0.000). The AUCs of MTRasym were significantly larger than those of ADC for differentiating MIBC from NMIBC (0.973, 0.771; P = 0.016). Adding APT imaging to DWI significantly improved the diagnostic accuracy for differentiating MIBC from NMIBC versus DWI alone (0.985, 0.876; P = 0.013). CONCLUSIONS: APT imaging can predict tumor grade and aggressiveness in BCa. The diagnostic performance of APT imaging in predicting tumor aggressiveness was better than that of DWI, and adding APT imaging to DWI significantly improved the diagnostic accuracy of predicting tumor aggressiveness versus DWI alone.

Effect of Saturation Pulse Duration and Power on pH-weighted Amide Proton Transfer Imaging: A Phantom Study.

PURPOSE: Amide proton transfer (APT) imaging may detect changes in tissues' pH based on the chemical exchange saturation transfer (CEST) phenomenon, and thus it may be useful for identifying the penumbra in ischemic stroke patients. We investigated the effect of saturation pulse duration and power on the APT effect in phantoms with different pH values. METHODS: Five samples were prepared from a 1:10 solution of egg-white albumin in phosphate-buffered saline at pH 6.53-7.65. The APT signal intensity (SI) was defined as asymmetry of the magnetization transfer ratio at 3.5 ppm. We measured the APT SIs in the egg-white albumin samples of different pH values with saturation pulse durations of 0.5, 1.0, 2.0, and 3.0 sec and saturation pulse powers of 0.5, 1.5, and 2.5 µT. The relative change in the APT SI in relation to the saturation duration and power at different pH values was defined as follows: (APT SI each saturation pulse - APT SI shortest or weakest pulse)/APT SIshortest or weakest pulse. The dependence of the APT SI on pH and the relative change in the APT SI were calculated as the slope of the linear regression. RESULTS: The lower the pH, the larger the relative change in the APT SI, due to the change in saturation pulse duration and power. The APT SI was highly correlated with the pH at all saturation pulse durations and powers. CONCLUSION: The influence of saturation duration and power on the APT effect was greater at lower pH than higher pH. The combination of saturation pulse ≥ 1.0 s and power ≥ 1.5 µT was useful for the sensitive detection of changes in APT effects in the egg-white albumin samples with different pH values.

Differentiation of true progression from treatment response in high-grade glioma treated with chemoradiation: a comparison study of 3D-APTW and 3D-PcASL imaging and DWI.

PURPOSE: To assess and compare the diagnostic performance of 3D amide proton-transfer-weighted (3D-APTW) imaging, 3D pseudocontinuous arterial spin-labeling (3D-PcASL) imaging, and diffusion-weighted imaging in distinguishing true progression (TP) from treatment response (TR) in posttreatment malignant glioma patients. MATERIALS AND METHODS: Forty-eight patients with suspected tumor recurrence were prospectively enrolled. Histological or longitudinal routine MRI follow-up over six months was assessed to confirm lesion type. The apparent diffusion coefficient (ADC), relative APTWmax (rAPTW), and relative CBFmax values (rCBF) were measured in lesions with enhancing regions on post-gadolinium T1 -weighted MRI. MRI parameters between the TP and TR groups were compared using Student's t tests. In addition, a receiver operating characteristic (ROC) curve was constructed, and the area under the ROC curve (AUC) was calculated to assess the differentiation diagnostic performance of each parameter. RESULTS: The TP group showed a significantly higher rAPTW and rCBF than the TR group; the AUCs of rAPTW and rCBF to distinguish between TP and TR were 0.911 (with sensitivity of 90.3% and specificity of 82.4%) and 0.852 (with sensitivity of 80.6% and specificity of 82.4%), respectively. By adding the rAPTW values to rCBF values, the diagnostic ability was improved from 0.852 to 0.951. ADC showed no significant differences between the TP and TR groups, with an AUC lower than 0.70. CONCLUSION: Both 3D-PcASL and 3D-APTW imaging could distinguish TP from TR, and 3D-APTW had a better diagnostic performance. Combining the rAPTW values and rCBF values achieved a better diagnostic performance.

Amide proton transfer MRI differentiates between progressive multifocal leukoencephalopathy and malignant brain tumors: a pilot study.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nerve system caused by the John Cunningham virus. On MRI, PML may sometimes appear similar to primary central nervous system lymphoma (PCNSL) and glioblastoma multiforme (GBM). The purpose of this pilot study was to evaluate the potential of amide proton transfer (APT) imaging for differentiating PML from PCNSL and GBM. METHODS: Patients with PML (n = 4; two men; mean age 52.3 ± 6.1 years), PCNSL (n = 7; four women; mean age 74.4 ± 5.8 years), or GBM (n = 11; 6 men; mean age 65.0 ± 15.2 years) who underwent APT-CEST MRI between January 2021 and September 2022 were retrospectively evaluated. Magnetization transfer ratio asymmetry (MTRasym) values were measured on APT imaging using a region of interest within the lesion. Receiver operating characteristics curve analysis was used to determine diagnostic cutoffs for MTRasym. RESULTS: The mean MTRasym values were 0.005 ± 0.005 in the PML group, 0.025 ± 0.005 in the PCNSL group, and 0.025 ± 0.009 in the GBM group. There were significant differences in MTRasym between PML and PCNSL (P = 0.023), and between PML and GBM (P = 0.015). For differentiating PML from PCNSL, an MTRasym threshold of 0.0165 gave diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of 100% (all). For differentiating PML from GBM, an MTRasym threshold of 0.015 gave diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of 100%, 90.9%, 80.0%, and 100%, respectively. CONCLUSION: MTRasym values obtained from APT imaging allowed patients with PML to be clearly discriminated from patients with PCNSL or GBM.

Predicting treatment response to concurrent chemoradiotherapy in squamous cell carcinoma of the cervix using amide proton transfer imaging and intravoxel incoherent motion imaging.

PURPOSE: The purpose of this study was to investigate whether amide proton transfer (APT) imaging and intravoxel incoherent motion (IVIM) imaging can predict tumor response to concurrent chemoradiotherapy (CCRT) in patients with squamous cell carcinoma of the cervix (SCCC). MATERIAL AND METHODS: Fifty-nine women (mean age, 54 years ± 10 [standard deviation] years; age range: 32-81 years) with pathologically confirmed SCCC underwent magnetic resonance imaging examination of the pelvis including APT and IVIM before concurrent chemoradiotherapy. They were divided into complete remission (CR) and non-CR groups according to therapeutic effect. APT values and IVIM-derived parameters were measured. Intra- and interobserver agreement for IVIM and APT parameters was assessed using intraclass correlation coefficient (ICC) The independent samples t-test was performed to compare the evaluated parameters between the two groups. Predictive performance for treatment response was evaluated by receiver operator characteristic (ROC) curve analysis. RESULTS: There were 38 and 21 patients in the non-CR and CR groups, respectively. Excellent interobserver and intraobserver agreement were obtained for all IVIM and APT parameters, with ICCs ranging from 0.844 to 0.962. Perfusion fraction (f) and APT values were lower in the CR group compared with the non-CR group (both P < 0.05). The combination of f and APT values showed good diagnostic performances in predicting response to concurrent chemoradiotherapy, with an area under the ROC curve of 0.852 (95% CI: 0.744-0.961), 79% sensitivity (95% CI: 63-90%), 90% specificity (95% CI: 70-99%) and 83% accuracy (95% CI: 71-92%). CONCLUSION: APT and IVIM imaging may serve as noninvasive tools for predicting response to concurrent chemoradiotherapy in patients with SCCC.

Effect of changes in the menstrual cycle and age on the signal intensity of amide proton transfer imaging in the normal uterus: a preliminary study.

PURPOSE: To analyze the effect of changes in the menstrual cycle and age on the signal intensity of amide proton transfer (APT) imaging in normal uterine structures. METHODS: Thirty-one healthy females (age: 21-50 years old) underwent regular pelvic MRI and APT sequences during their menstrual cycle. The APT values of the endometrium, myometrium, and junctional zone were measured. One-way and multi-way analyses of variance were used to analyze the data. Intraindividual difference and Pearson's correlation analyses were also conducted. RESULTS: The APT values of the uterine structures during the menstrual, proliferative, and secretory phases were 3.413 ± 0.682%, 4.776 ± 0.829%, and 5.218 ± 0.772% for the endometrium; 2.966 ± 0.533%, 3.597 ± 0.380%, and 4.324 ± 0.583% for the myometrium; and 1.703 ± 0.393%, 2.362 ± 0.486%, and 2.779 ± 0.528% for the junctional zone. The individual variation in the APT values of the normal uterus during the three menstrual phases was 1.1-1.7%.There were no significant differences in APT values of uterine structures with age. The APT values of the endometrium were greater than those of other structures (P < 0.05).The Pearson correlation coefficients between APT values of uterine structures and menstrual cycle were 0.686, 0.743, and 0.684, respectively. CONCLUSION: The menstrual cycle had a significant effect on the APT signal intensities of the uterine structures, whereas premenopausal age had no significant effect. Changes in the uterine structures during the menstrual cycle should be considered when using APT to diagnose suspected uterine lesions.