Amide Proton Transfer Magnetic Resonance Research Articles

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.

Comparison Between Amide Proton Transfer Magnetic Resonance Imaging Using 3-Dimensional Acquisition and Diffusion-Weighted Imaging for Characterization of Prostate Cancer: A Preliminary Study.

This study aimed to compare diagnostic performance for tumor detection and for assessment of tumor aggressiveness in prostate cancer (PC) between amide proton transfer magnetic resonance imaging (MRI) with 3-dimensional acquisition (3DAPT) and diffusion-weighted imaging. The subjects were 23 patients with 27 pathologically proven PCs who underwent 3T multiparametric MRI. With reference to the pathology findings, 2 readers in consensus identified the location of PC on multiparametric MRI and measured APT signal intensity (APT SI [%]) and mean apparent diffusion coefficient (ADC) of the benign region and each PC lesion. The mean ADC showed a significant difference between benign regions and PC lesions (0.74 ± 0.15 vs 1.37 ± 0.21, P < 0.001), whereas APT SI did not ( P = 0.091). Lesion APT SI was significantly higher and lesion ADC was significantly lower in PCs with Gleason group (GG) ≥3 than in PCs with GG ≤2 (3.37 ± 1.30 vs 1.78 ± 0.67, P < 0.001, and 0.71 ± 0.18 vs 0.79 ± 0.10, P = 0.038, respectively). The APT SI was significantly higher in GG3 than in GG1, in GG3 than in GG2, and in GG4 than in GG2 ( P = 0.009, P = 0.001, and P = 0.006, respectively). The area under the curve for separating tumor lesions and benign regions was 0.601 for 3DAPT and 0.983 for ADC ( P < 0.001). The area under the curve for separating tumors with GG ≤2 from tumors with GG ≥3 was 0.912 for 3DAPT and 0.734 for ADC ( P = 0.172). In patients with PC, it might be preferable to use ADC to discriminate benign from malignant tissue and use APT SI for assessment of tumor aggressiveness.

Amide proton transfer magnetic resonance imaging to evaluate renal impairment in patients with chronic kidney disease

ObjectiveWe aimed to investigate the value of amide proton transfer magnetic resonance imaging (APT-MRI) in the classification of chronic kidney disease (CKD). Materials and methodsA total of 30 patients with chronic kidney disease (CKD) and 25 healthy volunteers were enrolled in this study. Patients with chronic kidney disease were divided into two groups according to glomerular filtration rates: mild and moderate-to-severe renal impairment. Differences in cortical and medullary APT values were compared, and the correlation between corticomedullary APT values and glomerular filtration rates was analyzed. Data were statistically analyzed using SPSS 23.0. ResultsBased on glomerular filtration rates, 14 patients were assigned to the mild renal impairment group, and 16 were assigned to the moderate-to-severe renal impairment group. Both of the cortical and medullary APT values showed a gradually increasing trend in the control, the mild, and the moderate-to-severe renal impairment groups. Cortical APT values were higher than medullary APT values in all the control and renal impairment groups (P < 0.05). APT values of the right renal cortex (r = −0.80, P < 0.05) and medulla (r = −0.83, P < 0.05) were negatively correlated with the glomerular filtration rate. Results of the receiver operating characteristic (ROC) curve analysis showed that corticomedullary APT values had high diagnostic efficacy in assessing different degrees of renal impairment. ConclusionsThe APT values of the cortex and medulla in patients with CKD gradually increased with disease progression. These findings indicated that APT imaging can be used to evaluate renal function and renal injury in patients with CKD.

Study of common quantification methods of amide proton transfer magnetic resonance imaging for ischemic stroke detection

To assess the correlation and differences between common amide proton transfer (APT) quantification methods in the diagnosis of ischemic stroke. Five APT quantification methods, including asymmetry analysis and its variants as well as two Lorentzian model-based methods, were applied to data acquired from six rats that underwent middle cerebral artery occlusion scanned at 9.4T. Diffusion and perfusion-weighted images, and water relaxation time maps were also acquired to study the relationship of these conventional imaging modalities with the different APT quantification methods. The APT ischemic area estimates had varying sizes (Jaccard index: 0.544 ≤ J ≤ 0.971) and had varying correlations in their distributions (Pearson correlation coefficient: 0.104 ≤ r ≤ 0.995), revealing discrepancies in the quantified ischemic areas. The Lorentzian methods produced the highest contrast-to-noise ratios (CNRs; 1.427 ≤ CNR ≤ 2.002), but generated APT ischemic areas that were comparable in size to the cerebral blood flow (CBF) deficit areas; asymmetry analysis and its variants produced APT ischemic areas that were smaller than the CBF deficit areas but larger than the apparent diffusion coefficient deficit areas, though having lower CNRs (0.561 ≤ CNR ≤ 1.083). There is a need to further investigate the accuracy and correlation of each quantification method with the pathophysiology using a larger scale multi-imaging modality and multi-time-point clinical study. Future studies should include the magnetization transfer ratio asymmetry results alongside the findings of the study to facilitate the comparison of results between different centers and also the published literature.

Early identification of neonatal mild hypoxic-ischemic encephalopathy by amide proton transfer magnetic resonance imaging: A pilot study

PurposeThis study aimed to evaluate the amide proton transfer (APT) values in neonates with mild hypoxic-ischemic encephalopathy (HIE) using APT imaging. MethodA total of 30 full-term neonates with mild HIE (16 males and 14 females; mean postnatal age 4.2 days, age range 2–7 days) and 12 normal neonates (six males and six females; mean postnatal age 3.3 days, age range 2–5 days) underwent conventional magnetic resonance imaging and APT imaging. APT measurements were performed in multiple regions of interest (ROIs) in the brain. APT values were statistically analyzed to assess for significant differences between the mild HIE and normal neonates in different regions of the brain, and correlation with neonatal gestational age. ResultsIn 30 neonates with mild HIE, 10% (3/30) of the HIE patients had normal conventional MRI. There were significant differences in APT values of the HIE group in bilateral caudate, bilateral thalamus, bilateral centrum semiovale and left globus pallidus/putamen (p < 0.05), and no statistical difference was observed in right globus pallidus/putamen (p = 0.051) and brainstem (p = 0.073) between the two groups. Furthermore, APT values in bilateral caudate, bilateral globus pallidus/putamen, bilateral thalamus, and brainstem regions (p < 0.05) exhibited positive linear correlations with gestational age in the control group, except for bilateral centrum semiovale (right: Pearson’s r = 0.554, p = 0.062; left: Pearson’s r = 0.561, p = 0.058). In the mild HIE groups, no significant correlation with gestational age was found in all regions. ConclusionsAPT imaging is a feasible and useful technique with diagnostic capability for neonatal HIE.

Tumor pH and Protein Concentration Contribute to the Signal of Amide Proton Transfer Magnetic Resonance Imaging.

Abnormal pH is a common feature of malignant tumors and has been associated clinically with suboptimal outcomes. Amide proton transfer magnetic resonance imaging (APT MRI) holds promise as a means to noninvasively measure tumor pH, yet multiple factors collectively make quantification of tumor pH from APT MRI data challenging. The purpose of this study was to improve our understanding of the biophysical sources of altered APT MRI signals in tumors. Combining in vivo APT MRI measurements with ex vivo histological measurements of protein concentration in a rat model of brain metastasis, we determined that the proportion of APT MRI signal originating from changes in protein concentration was approximately 66%, with the remaining 34% originating from changes in tumor pH. In a mouse model of hypopharyngeal squamous cell carcinoma (FaDu), APT MRI showed that a reduction in tumor hypoxia was associated with a shift in tumor pH. The results of this study extend our understanding of APT MRI data and may enable the use of APT MRI to infer the pH of individual patients' tumors as either a biomarker for therapy stratification or as a measure of therapeutic response in clinical settings. SIGNIFICANCE: These findings advance our understanding of amide proton transfer magnetic resonance imaging (APT MRI) of tumors and may improve the interpretation of APT MRI in clinical settings.

Amide proton transfer magnetic resonance imaging in detecting intracranial hemorrhage at different stages: a comparative study with susceptibility weighted imaging

Amide proton transfer (APT) imaging is a noninvasive molecular magnetic resonance imaging (MRI) technique based on the chemical exchange-dependent saturation transfer mechanism. The purpose of this study was to investigate the diagnostic performance of APT MRI in detecting intracranial hemorrhage (ICH) at hyperacute, acute and subacute stages by comparing with susceptibility weighted imaging (SWI). APT MRI and SWI were performed on 33 included patients with ICH by using a 3-T MRI unit. A two-sided Mann-Whitney U test was used to detect differences in APT-weighted (APTw) and SWI signal intensities of ICH at hyperacute, acute and subacute stages. Receiver operating characteristic analysis was used to assess the diagnostic utilities of APT MRI and SWI. Our results showed that APT MRI could detect ICH at hyperacute, acute and subacute stages. Therefore, APTw signal intensity may serve as a reliable, noninvasive imaging biomarker for detecting ICH at hyperacute, acute and subacute stages. Moreover, APT MRI could provide additional information for the ICH compared with SWI.

Preliminary application of amide proton transfer imaging signal in acute ischemic stroke

To apply amide proton transfer magnetic resonance imaging (APT-MRI) technique to acute ischemic stroke, and to discuss clinical values of the APT-MRI main parameter - MTRasym(3.5 ppm). A total of 18 emergency admitted patients, with acute ischemic stroke from Beijing Hospital, were recruited from March to November 2015. Eventually, 18 patients (male 14, female 4, average age 72 years old, age ranged from 52 to 92 years, symptom onset ≤24 hours, 2 patients≤ 6 hours) were included in this study. All patients underwent MR scanning on the brain at 3.0 Tesla. Besides the conventional scans for stroke, the APT sequence (saturation time 0.8 s, saturation power 2 μT) was performed. APT weighted (APTW) images were calculated using magnetization transfer ratio asymmetry at 3.5 ppm with respect to water. MRI signals in APTW, diffusion weighted images (DWI) and fluid attenuated iversion recovery (FLAIR) were visually evaluated. Shapiro-Wilk tests were performed to find out the distribution of MTRasym(3.5 ppm) in the whole sample, infarction regions, and normal appearing white matter (NAWMs), respectively. Detrended normal P-P plots were also used to evaluate its normality. Paired-t test and two-sample t test were applied to compare the mean MTRasym(3.5 ppm) of infarction regions with that of contra lateral NAWMs. (1) High signal intensity was observed in DWI and FLAIR in all 18 patients. However, signal intensity was somewhat different in APTW. 13 patients were found decreased APT effect, and 5 patients were with equal APT effect in infarction regions. In NAWMs, 14 patients were found equal APT effect, and 4 patients were with decreased APT effect. (2) MTRasym(3.5 ppm)s were proven, with Shapiro-Wilk test, to distribute normally within the whole sample (W=0.964, P=0.288), infarction regions (W=0.962, P=0.645), and NAWMs(W=0.929, P=0.187). However, its normality was not so satisfactory due to greater deviations (absolute value>0.06) of some cases in detrended normal P-P plots. (3) Paired-t test analysis showed that MTRasym(3.5 ppm) in infarction regions (-0.035%±1.020%) was significantly lower than that in NAWMs (0.386%±0.790%) (t=-2.273, P=0.036). However, there was no statistically significant difference between infarction regions and NAWMs when two sample t-test was performed (t=-1.386, P=0.175). MTRasym(3.5 ppm) can be used to evaluate acute ischemic stroke with a broad future scope in clinical.

Amide proton transfer magnetic resonance imaging of Alzheimer's disease at 3.0 Tesla: a preliminary study.

Background:Amide proton transfer (APT) imaging has recently emerged as an important contrast mechanism for magnetic resonance imaging (MRI) in the field of molecular and cellular imaging. The aim of this study was to evaluate the feasibility of APT imaging to detect cerebral abnormality in patients with Alzheimer's disease (AD) at 3.0 Tesla.Methods:Twenty AD patients (9 men and 11 women; age range, 67–83 years) and 20 age-matched normal controls (11 men and 9 women; age range, 63–82 years) underwent APT and traditional MRI examination on a 3.0 Tesla MRI system. The magnetic resonance ratio asymmetry (MTRasym) values at 3.5 ppm of bilateral hippocampi (Hc), temporal white matter regions, occipital white matter regions, and cerebral peduncles were measured on oblique axial APT images. MTRasym (3.5 ppm) values of the cerebral structures between AD patients and control subjects were compared with independent samples t-test. Controlling for age, partial correlation analysis was used to investigate the associations between mini-mental state examination (MMSE) and the various MRI measures among AD patients.Results:Compared with normal controls, MTRasym (3.5 ppm) values of bilateral Hc were significantly increased in AD patients (right 1.24% ± 0.21% vs. 0.83% ± 0.19%, left 1.18% ± 0.18% vs. 0.80%± 0.17%, t = 3.039, 3.328, P = 0.004, 0.002, respectively). MTRasym (3.5 ppm) values of bilateral Hc were significantly negatively correlated with MMSE (right r = −0.559, P = 0.013; left r = −0.461, P = 0.047).Conclusions:Increased MTRasym (3.5 ppm) values of bilateral Hc in AD patients and its strong correlations with MMSE suggest that APT imaging could potentially provide imaging biomarkers for the noninvasive molecular diagnosis of AD.

Novel gradient echo sequence-based amide proton transfer magnetic resonance imaging in hyperacute cerebral infarction

In the progression of ischemia, pH is important and is essential in elucidating the association between metabolic disruption, lactate formation, acidosis and tissue damage. Chemical exchange-dependent saturation transfer (CEST) imaging can be used to detect tissue pH and, in particular, a specific form of CEST magnetic resonance imaging (MRI), termed amide proton transfer (APT) MRI, which is sensitive to pH and can detect ischemic lesions, even prior to diffusion abnormalities. The critical parameter governing the ability of CEST to detect pH is the sequence. In the present study, a novel strategy was used, based on the gradient echo sequence (GRE), which involved the insertion of a magnetization transfer pulse in each repetition time (TR) and minimizing the TR for in vivo APT imaging. The proposed GRE-APT MRI method was initially verified using a tissue-like pH phantom and optimized MRI parameters for APT imaging. In order to assess the range of acute cerebral infarction, rats (n=4) were subjected to middle cerebral artery occlusion (MCAO) and MRI scanning at 7 telsa (T). Hyperacute ischemic tissue damage was characterized using multiparametric imaging techniques, including diffusion, APT and T2-Weighted MRI. By using a magnetization transfer pulse and minimizing TR, GRE-APT provided high spatial resolution and a homogeneous signal, with clearly distinguished cerebral anatomy. The GRE-APT and diffusion MRI were significantly correlated with lactate content and the area of cerebral infarction in the APT and apparent diffusion coefficient (ADC) maps matched consistently during the hyperacute period. In addition, compared with the infarction area observed on the ADC MRI map, the APT map contained tissue, which had not yet been irreversibly damaged. Therefore, GRE-APT MRI waa able to detect ischemic lactic acidosis with sensitivity and spatiotemporal resolution, suggesting the potential use of pH MRI as a surrogate imaging marker of impaired tissue metabolism for the diagnosis and prognosis of hyperacute stroke.

Identifying the ischaemic penumbra using pH-weighted magnetic resonance imaging.

The original concept of the ischaemic penumbra suggested imaging of regional cerebral blood flow and metabolism would be required to identify tissue that may benefit from intervention. Amide proton transfer magnetic resonance imaging, a chemical exchange saturation transfer technique, has been used to derive cerebral intracellular pH in preclinical stroke models and has been proposed as a metabolic marker of ischaemic penumbra. In this proof of principle clinical study, we explored the potential of this pH-weighted magnetic resonance imaging technique at tissue-level. Detailed voxel-wise analysis was performed on data from a prospective cohort of 12 patients with acute ischaemic stroke. Voxels within ischaemic core had a more severe intracellular acidosis than hypoperfused tissue recruited to the final infarct (P < 0.0001), which in turn was more acidotic than hypoperfused tissue that survived (P < 0.0001). In addition, when confined to the grey matter perfusion deficit, intracellular pH (P < 0.0001), but not cerebral blood flow (P = 0.31), differed between tissue that infarcted and tissue that survived. Within the presenting apparent diffusion coefficient lesion, intracellular pH differed between tissue with early apparent diffusion lesion pseudonormalization and tissue with true radiographic recovery. These findings support the need for further investigation of pH-weighted imaging in patients with acute ischaemic stroke.

Pilot Study Using Amide Proton Transfer Magnetic Resonance Imaging Distinguishing Glioma

Pilot Study Using Amide Proton Transfer Magnetic Resonance Imaging Distinguishing Glioma