Amide Proton Transfer Imaging Research Articles

CEST and nuclear Overhauser enhancement imaging withdeep learning-extrapolated semisolid magnetization transfer reference: Scan-rescan reproducibility andreliability studies.

To develop a novel MR physics-driven, deep-learning, extrapolated semisolid magnetization transfer reference (DeepEMR) framework to provide fast, reliable magnetization transfer contrast (MTC) and CEST signal estimations, and to determine the reproducibility and reliability of the estimates from the DeepEMR. A neural network was designed to predict a direct water saturation and MTC-dominated signal at a certain CEST frequency offset using a few high-frequency offset features in the Z-spectrum. The accuracy, scan-rescan reproducibility, and reliability of MTC, CEST, and relayed nuclear Overhauser enhancement (rNOE) signals estimated from the DeepEMR were evaluated on numerical phantoms and in heathy volunteers at 3 T. In addition, we applied the DeepEMR method to brain tumor patients and compared tissue contrast with other CEST calculation metrics. The DeepEMR method demonstrated a high degree of accuracy in the estimation of reference MTC signals at ±3.5 ppm for APT and rNOE imaging, and computational efficiency (˜190-fold) compared with a conventional fitting approach. In addition, the DeepEMR method achieved high reproducibility and reliability (intraclass correlation coefficient = 0.97, intersubject coefficient of variation = 3.5%, and intrasubject coefficient of variation = 1.3%) of the estimation of MTC signals at ±3.5 ppm. In tumor patients, DeepEMR-based amide proton transfer images provided higher tumor contrast than a conventional MT ratio asymmetry image, particularly at higher B1 strengths (>1.5 μT), with a distinct delineation of the tumor core from normal tissue or peritumoral edema. The DeepEMR approach is feasible for measuring clean APT and rNOE effects in longitudinal and cross-sectional studies with low scan-rescan variability.

Amide proton transfer imaging in rats after heatstroke.

Metabolic acidosis is the most common acid-base change following heatstroke. This study aimed to evaluate the internal environment changes caused by heatstroke using amide proton transfer (APT) imaging. Nineteen male Sprague-Dawley rats were randomly divided into the control group (CTRL, n = 7) and the heatstroke group (HS, n = 12). All the rats underwent a 7.0-T MRI, which included T2-weighted imaging (T2WI) and APT imaging. Subsequently, the surviving HS group rats repeated the same magnetic resonance scanning after 25 days and were designated as the follow-up group (FU, n = 7). APT values were measured in the hippocampus, thalamus, and corpus callosum. The APT values of the three groups were statistically analyzed and found in the hippocampus (CTRL vs. HS, P = 0.011; CTRL vs. FU, P = 0.078; HS vs. FU, P = 0.484; η ² = 0.276), left thalamus (CTRL vs. HS, P = 0.004; CTRL vs. FU, P = 0.014; HS vs. FU, P = 0.822; η ² = 0.331), right thalamus (CTRL vs. HS, P = 0.003; CTRL vs. FU, P = 0.015; HS vs. FU P = 0.769; η ² = 0.336), and corpus callosum (CTRL vs. HS, P < 0.001; CTRL vs. FU, P = 0.005; HS vs. FU, P = 0.523; η ² = 0.437). APT imaging can be a viable and practical tool for diagnosing heatstroke and monitoring its progression.

Role of amide proton transfer imaging in maximizing tumor resection in malignant glioma: a possibility to take the place of 11C-methionine positron emission tomography.

Amide proton transfer (APT) imaging has been proposed as a technique to assess tumor metabolism. However, the relationship between APT imaging and other quantitative modalities including positron emission tomography (PET) has not been investigated in detail. This study aimed to evaluate the clinical usefulness of APT imaging in determining the metabolic status of malignant glioma and to compare findings with those from 11C-methionine (Met)-PET. This research analyzed APT imaging data from 20 consecutive patients with malignant glioma treated between January 2022 and July 2023. Patients underwent tumor resection and correlations between tumor activity and intensity of APT signal were investigated. We also compared 11C-Met-PET and APT imaging for the same regions of the perifocal tumor invasion area. Clear, diagnostic APT images were obtained from all 20 cases. Mean APT intensity (APTmean) was significantly higher in the glioblastoma (GBM), IDH wild type group (27.2 ± 12.8%) than in other gliomas (6.0 ± 4.7%; p < 0.001). The cut-off APTmean to optimally distinguish between GBM and other malignant gliomas was 12.8%, offering 100% sensitivity and 83.3% specificity. These values for APTmean broadly matched the tumor-to-contralateral normal brain tissue ratio from 11C-Met-PET analysis (r = 0.66). The APT signal was also observed in the gadolinium non-contrast region on T1-weighted imaging, appearing to reflect the surrounding tumor-infiltrated area. APT imaging can be used to evaluate the area of tumor invasion, similar to 11C-Met-PET. APT imaging revealed low invasiveness in patients and was useful in preoperative planning for tumor resection, facilitating maximum tumor resection including the tumor invasive area.

Post-Surgical Depositions of Blood Products Are No Major Confounder for the Diagnostic and Prognostic Performance of CEST MRI in Patients with Glioma.

Amide proton transfer (APT) and semi-solid magnetization transfer (ssMT) imaging can predict clinical outcomes in patients with glioma. However, the treatment of brain tumors is accompanied by the deposition of blood products within the tumor area in most cases. For this reason, the objective was to assess whether the diagnostic interpretation of the APT and ssMT is affected by methemoglobin (mHb) and hemosiderin (Hs) depositions at the first follow-up MRI 4 to 6 weeks after the completion of radiotherapy. A total of 34 participants underwent APT and ssMT imaging by applying reconstruction methods described by Zhou et al. (APTwasym), Goerke et al. (MTRRexAPT and MTRRexMT) and Mehrabian et al. (MTconst). Contrast-enhancing tumor (CE), whole tumor (WT), mHb and Hs were segmented on contrast-enhanced T1wCE, T2w-FLAIR, T1w and T2*w images. ROC-analysis, Kaplan-Meier analysis and the log rank test were used to test for the association of mean contrast values with therapy response and overall survival (OS) before (WT and CE) and after correcting tumor volumes for mHb and Hs (CEC and WTC). CEC showed higher associations of the MTRRexMT with therapy response (CE: AUC = 0.677, p = 0.081; CEC: AUC = 0.705, p = 0.044) and of the APTwasym with OS (CE: HR = 2.634, p = 0.040; CEC: HR = 2.240, p = 0.095). In contrast, WTC showed a lower association of the APTwasym with survival (WT: HR = 2.304, p = 0.0849; WTC: HR = 2.990, p = 0.020). Overall, a sophisticated correction for blood products did not substantially influence the clinical performance of APT and ssMT imaging in patients with glioma early after radiotherapy.

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.

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

PurposeAmide 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. Methods34 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. ResultsThere 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). Conclusions3D-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.

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.

Evaluation of contributors to amide proton transfer-weighted imaging and nuclear Overhauser enhancement-weighted imaging contrast in tumors at a high magnetic field.

The purpose is to evaluate the relative contribution from confounding factors (T1 weighting and magnetization transfer) to the CEST ratio (CESTR)-quantified amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) (-3.5) in tumors as well as whether the CESTR can reflect the distribution of the solute concentration (fs ). We first provided a signal model that shows the separate dependence of CESTR on these confounding factors and the clean CEST/NOE effects quantified by an apparent exchange-dependent relaxation (AREX) method. We then measured the change in these effects in the 9-L tumor model in rats, through which we calculated the relative contribution of each confounding factor. fs was also fitted, and its correlations with the CESTR and AREX were assessed to evaluate their capabilities to reflect fs . The CESTR-quantified APT shows "positive" contrast in tumors, which arises primarily from R1w at low powers and both R1w and magnetization transfer at high powers. CESTR-quantified NOE (-3.5) shows no or weak contrast in tumors, which is due to the cancelation of R1w and NOE (-3.5), which have opposite contributions. CESTR-quantified APT has a stronger correlation with APT fs than AREX-quantified APT. CESTR-quantified NOE (-3.5) has a weaker correlation with NOE (-3.5) fs than AREX-quantified NOE (-3.5). CESTR reflects a combined effect of T1 weighting and CEST/NOE. Both factors depend on fs , which contributes positively to the dependence of CESTR on fs in APT imaging and enhances its correlation with fs . In contrast, these factors have opposite contributions to its dependence on fs in NOE (-3.5) imaging, thereby weakening the correlation.

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.

Amide proton transfer (APT) imaging of breast cancers and its correlation with biological status

PurposeTo assess the usefulness of amide proton transfer (APT) imaging to predict the biological status of breast cancers. MethodSixty-six patients (age range 31–85 years, mean 58.9 years) with histopathologically proven invasive ductal carcinomas of 2 cm or larger in diameter were included in this study. 3D APT weighted imaging was conducted on a 3 T scanner. Mean APT signal intensity (SI) was analyzed in relation to biological subtypes, Ki-67 labeling index, and nuclear grades (NGs). ResultsThe triple-negative (TN) cancers (n = 10; 2.75 ± 0.42%) showed significantly higher APT SI than the luminal type cancers (n = 48; 1.74 ± 0.83) and HER2 cancers (n = 8; 1.83 ± 0.21) (P = 0.0007, 0.03). APT SI had weakly positive correlation with the Ki-67 labeling index (r = 0.38, P = 0.002). The mean APT SIs were significantly higher for high-Ki-67 (>30%) (n = 31; 2.25 ± 0.70) than low-Ki-67 (≤30%) cancers (n = 35; 1.60 ± 0.79) (P = 0.0007). There was no significant difference in the APT SIs between NG 1–2 (n = 31; 1.71 ± 0.84) and NG 3 (n = 35; 2.08 ± 0.76%) cancers (P = 0.06). ConclusionsTN and high-Ki-67 breast cancers showed high APT SIs. APT imaging can help to predict the biological status of breast cancers.

Comparison and combination of amide proton transfer magnetic resonance imaging and the apparent diffusion coefficient in differentiating the grades of prostate cancer.

More effective risk stratification of prostate cancer (PCa) than that possible with current methods can reduce undertreatment and guard against overtreatment. The aim of this study is to validate the differences and combined effects of amide proton transfer (APT) imaging and apparent diffusion coefficient (ADC) in discriminating the PCa grade group (GG) ≤2 from GG ≥3 PCa. This is an ongoing prospective study conducted in the radiology department of Nanxishan Hospital of Guangxi Zhuang Autonomous Region. Patients pathologically diagnosed with PCa were enrolled consecutively according to the eligibility criteria. A total of 180 patients (age range, 42-92 years) were included in this study. Using histopathology as the reference standard, we placed 71 cases in GG ≤2 (mean age 67.03±8.696 years) and 109 cases in GG ≥3 (age 69.60±9.638 years). Magnetic resonance imaging (MRI) parameters, including APT and ADC values, were analyzed using an independent samples t-test and binary logistic regression analysis stratified with GG. Receiver operating characteristic curve was used to analyze the diagnostic performance for different parameters distinguishing GG ≤2 and GG ≥3. APT [odds ratio (OR) for the transitional zone (TZ) PCa: 3.20, 95% CI: 1.14-8.98, P=0.02; OR for the peripheral zone (PZ) PCa: 86.32, 95% CI: 13.24-562.88, P=0.003] and ADC values (OR for TZ PCa: 89.79; 95% CI: 2.85-2,827.99, P=0.01; OR for PZ PCa: 39.92; 95% CI: 3.22-494.18, P=0.004) were independent predictors that differentiated the GG of patients. The sensitivity and specificity of the APT values were 61.1% and 81.0%, respectively, while the sensitivity and specificity of the ADC values were 83.3% and 61.9%, respectively. The optimal cutoff value of APT was 3.35% and which of ADC was 1.25×10-3 mm2/s in TZ origin PCa. At the optimal cutoff values of 3.31% (APT) and 0.79×10-3 mm2/s (ADC) in PZ PCa, the sensitivity and specificity of the APT values were 74.0% and 83.6%, respectively, while the sensitivity and specificity of the ADC values were 94.0% and 53.4%, respectively. The area under the curve of the combination of APT and ADC was significantly higher than either of APT or ADC alone in Delong test (TZ: P=0.002 and P=0.020; PZ: P=0.033 and P<0.001). APT and ADC have complementary effects on the sensitivity and specificity for identifying different PCa GGs. A combination model of APT and ADC could improve the diagnostic efficacy of PCa differentiation.

Predicting a Favorable (mRS 0–2) or Unfavorable (mRS 3–6) Stroke Outcome by Arterial Spin Labeling and Amide Proton Transfer Imaging in Post-Thrombolysis Stroke Patients

(1) Background: The objective of this study was to determine whether arterial spin labeling (ASL), amide proton transfer (APT), or their combination could distinguish between patients with a low and high modified Rankin Scale (mRS) and forecast the effectiveness of the therapy; (2) Methods: Fifty-eight patients with subacute phase ischemic stroke were included in this study. Based on cerebral blood flow (CBF) and asymmetry magnetic transfer ratio (MTRasym) images, histogram analysis was performed on the ischemic area to acquire imaging biomarkers, and the contralateral area was used as a control. Imaging biomarkers were compared between the low (mRS 0-2) and high (mRS 3-6) mRS score groups using the Mann-Whitney U test. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the potential biomarkers in differentiating between the two groups; (3) Results: The rAPT 50th had an area under the ROC curve (AUC) of 0.728, with a sensitivity of 91.67% and a specificity of 61.76% for differentiating between patients with low and high mRS scores. Moreover, the AUC, sensitivity, and specificity of the rASL max were 0.926, 100%, and 82.4%, respectively. Combining the parameters with logistic regression could further improve the performance in predicting prognosis, leading to an AUC of 0.968, a sensitivity of 100%, and a specificity of 91.2%; (4) Conclusions: The combination of APT and ASL may be a potential imaging biomarker to reflect the effectiveness of thrombolytic therapy for stroke patients, assisting in guiding treatment approaches and identifying high-risk patients such as those with severe disability, paralysis, and cognitive impairment.

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

ObjectiveThis 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). MethodsAll 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. ResultsThe 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). ConclusionBoth 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.

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

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. 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. 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. 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.

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

BackgroundProgressive 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.MethodsPatients 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.ResultsThe 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.ConclusionMTRasym values obtained from APT imaging allowed patients with PML to be clearly discriminated from patients with PCNSL or GBM.

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

PurposeTo 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). MethodsForty-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). ResultsThe 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). ConclusionsAPT 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.

Amide Proton Transfer Imaging for Differentiation of Glioblastoma from Brain Metastasis

Objective: To evaluate the difference in amide proton transfer (APT)-weighted imaging between glioblastoma and brain metastasis. Materials and Methods: Fourteen patients including eight males and six females, with age ranging between 46 and 75 years old, were included in the present study. Ten patients with glioblastomas and four patients with brain metastases underwent preoperative brain 3T-MRI with APT-weighted sequence. The magnetization transfer ratio asymmetry (MTRasym) and normalized magnetization transfer ratio asymmetry (nMTRasym) values in enhancing solid portion, peritumoral non-enhancing hyperintense FLAIR area, and contralateral normal appearing white matter (CNAWM) in glioblastomas and brain metastases were obtained and compared for statistical analyses. Final diagnosis was validated by pathological results. Results: The MTRasym and nMTRasym in enhancing solid portion and peritumoral non-enhancing hyperintense FLAIR area of glioblastomas were significantly greater than that of the brain metastases. By visual assessment, the APTw color map also showed higher signal at the perilesional edema in glioblastomas than the metastasis. Conclusion: As a non-invasive imaging method, APT-weighted MR imaging might be helpful to distinguish glioblastomas from brain metastasis. Keywords: Amide proton transfer weighted imaging; Glioblastomas; Brain metastasis

NI-17 NEW ASSESSMENT FOR FLAIR ABNORMALITY AREA OF GLIOMA USING APT IMAGING

Abstract Background In glioma, decision of infiltrating margin in extensive FLAIR hyperintensity area around enhanced area and only FLAIR hyperintensity without enhanced is difficult. For deciding this margin, there are some useful reports using perfusion imaging, diffusion-weighted imaging and PET. Recently, there are some reports that amide proton transfer (APT) imaging is useful for assessment for tumor invasion. In this study, we assessed FLAIR hyperintensity area in gliomas using APT imaging and discussed about pattern of APT signal intensity (SI). Methods For patients with glioblastoma (GBM) and oligodendroglioma (OL: IDH-mutant and 1p/19q-codeleted), APT imaging was performed. Gadolinium T1WI, FLAIR and apparent diffusion coefficient (ADC) were performed for tumor invasion and edema. Areas of these sequences were compared with APT hyperintensity and APT and ADC were determined the quantity by SI. Results 37 sections from 10 GBM and 5 OL patients were assessed. Areas of differences between FLAIR and APT hyperintensity was significantly different between GBM and OL (p = 0.0142). SIs of the hyperintensity area between GBM and OL were different on ADC and APT SIs (ADC: p = 0.0267 / APT: p = 0.055). On GBM, hyperintensity area of APT imaging showed a correlation with hyperintensity area of FLAIR (R2 = 0.600, p &amp;lt; 0.0001). On OL, hyperintensity area of APT imaging showed a strong correlation with hyperintensity area of FLAIR (R2 = 0.806, p &amp;lt; 0.0001), and ADC SI showed correlation with APT SI (R2 = 0.675, p = 0.0019). Conclusions FLAIR hyperintensity area of GBM and OL, APT imaging showed different distribution. In FLAIR hyperintensity area of GBM with various phenomenon, APT imaging may indicate increasing area of tumor cell and reactive cells. Furthermore, mismatch between FLAIR and APT hyperintensity area may be useful for differentiation for glioma subtypes.

Emerging metabolic imaging and spectroscopic methods to study neurodegenerative diseases

Proton magnetic resonance spectroscopy (1H-MRS) allows non-invasive assessment of the metabolic landscape of biological tissue. Despite demonstrating promising findings in clinical practice, single-voxel or single-slice two-dimensional 1H-MRS methods present a few challenges mainly related to limited spatial coverage and low spatial and spectral resolutions. In the recent past, the advent of more sophisticated metabolic imaging and spectroscopic sequences, such as three-dimensional echoplanar spectroscopic imaging (3D-EPSI), two-dimensional correlation spectroscopy (2D-COSY), and chemical exchange saturation technique (CEST) has revolutionized the field of metabolomics. For the metabolic characterization of diffused neurodegenerative diseases, whole brain coverage is essential for a comprehensive overview of the topography and understanding of the underlying pathophysiological processes. The 3D-EPSI sequence allows the acquisition of whole brain (volumetric) metabolite maps with high spatial resolution.1 These metabolite maps can be co-registered to anatomical images for facilitating the mapping of metabolite alterations from different brain regions in a single session, thus providing the true spatial extent of a global disease. The potential of 3D‐EPSI in characterizing several neurological and neurodegenerative disorders has been reported. On conventional one-dimensional 1H-MRS, spectral peaks due to methyl, methylene, and methine protons from N-acetyl aspartate, glutamate, glutamine, gamma-aminobutyric acid, and taurine extensively overlap in the spectral region of 2-4 ppm, often confounding the reliable detection and quantification of these metabolites. In contrast, 2D-COSY offers unambiguous identification of potentially overlapping resonances by dispersing the multiplet structure of scalar (J)-coupled spin systems into a second spectral dimension,2 especially at higher field strength3,4 and by exploiting the unlikely possibility that two metabolites would share identical chemical shifts in two-dimensions. Due to technical limitations and long acquisition time, 2D-COSY sequence has not been widely used to study neurodegenerative diseases. However, future modifications would benefit from implementing faster acquisition schemes and improved spectral fitting methods for data analysis. We believe that these new approaches could make the clinical applications of the 2D-COSY sequence faster, easier, and more versatile. CEST is a relatively novel metabolic imaging modality that allows the detection of specific exogenous and endogenous metabolites/molecules present at millimolar concentrations. Exchangeable solute protons present in chemical functional groups such as amide (-CONH), amine (-NH2) or hydroxyl (-OH) resonate at a frequency different from bulk water protons. These labile protons are selectively saturated using radiofrequency irradiation, which is subsequently transferred to the bulk water pool, leading to a decrease in the water signal intensity proportional to the concentration of solute molecules, number of labile protons and proton exchange rate.5 CEST offers more than two orders of magnitude higher sensitivity compared to 1H-MRS in detecting metabolites such as glutamate, creatine, myoinositol and mobile peptides.5 While amide proton transfer (APT) imaging has been investigated in various neurological disorders, other CEST imaging techniques such as glutamate-CEST, creatine-CEST have been performed only in pre-clinical or pilot clinical studies related to neurodegenerative diseases. We believe that these newer developments in metabolic imaging techniques will have a significant impact in reshaping our understanding of biochemical profiles of various neurodegenerative diseases. However, standardization and harmonization of acquisition parameters are required for fast-tracking the implementation of these metabolic techniques into routine clinical workflow.

Application of amide proton transfer imaging for the diagnosis of neonatal hypoxic-ischemic encephalopathy.

This study aimed to evaluate cerebral amide proton transfer signal intensity (SI) among controls, hypoxic-ischemic encephalopathy (HIE) neonates with normal conventional magnetic resonance imaging (HIE/MRI-) findings, and HIE neonates with abnormal conventional MRI (HIE/MRI+) findings. Forty neonates diagnosed with neonatal HIE and sixteen normal neonates were evaluated. All neonates underwent conventional MRI scans and APT imaging. Cerebral APT SIs were compared to identify cerebral regions with significant APT changes among sixteen controls, thirteen HIE/MRI- patients, and twenty-seven HIE/MRI+ patients. Significantly increased APT SIs were observed in the HIE/MRI- group compared with controls, in the left insula, right occipital lobe, left cingulate gyrus (posterior part), and corpus callosum. Significantly increased APT SIs were found in the HIE/MRI+ group compared with controls, in the right anterior temporal lobe (medial part), anterior parts of the right parahippocampal and ambient gyri, left superior temporal gyrus (middle part), left insula, left cingulate gyrus (posterior part), and right lentiform nucleus. No significant APT SI differences were observed in the cerebellum and brainstem among the three groups. Amide proton transfer imaging plays an important role in detecting hypoxic-ischemic encephalopathy regardless of conventional MRI findings. Changes in APT signal intensity may provide important insights into the characterization of the cerebral internal environment. This study suggests that APT imaging could be used as a complement to conventional MRI in the detection of hypoxic-ischemic encephalopathy in clinical practice.