Amide Proton Transfer Signal Intensity Research Articles

Amide proton transfer MR imaging in the characterization of brain tumors: A review paper

Amide proton transfer (APT) magnetic resonance imaging (MR) is a new imaging technology that has shown promise in the non-invasive characterization of brain malignancies, particularly meningiomas and glioblastomas. Th works aims to evaluate the existing literature in Amide proton transfer (APT) magnetic resonance imaging (MR) to explore the efficacy of APT MR imaging in the characterization of meningiomas and glioblastomas tumors. The review gives an overview of APT MR imaging principles, examines its potential benefits and limits, and highlights the important findings from the selected research. To discover relevant research published up to the current day, a literature search was undertaken in electronic databases such as PubMed and Google Scholar. The search is based on keywords and medical terms related to APT MR imaging, meningiomas, and glioblastomas. The review gives an overview of APT MR imaging principles, examines its potential benefits and limits, and highlights the important findings from the selected research. It showed that the majority of studies found encouraging results in distinguishing meningiomas and glioblastomas from surrounding normal brain tissue using APT MR imaging. For tumor characterization, APT signal intensity assessments such as APT asymmetry analysis and APT ratio analysis were used. The work concluded that the Amide proton transfer MR imaging has the potential to be a non-invasive imaging method for the diagnosis of meningiomas and glioblastomas. It provides useful information about tumor metabolism and cellular composition, which can help with diagnosis, therapy planning, and prognosis.

Characterization of carotid plaques using chemical exchange saturation transfer imaging.

The preoperative assessment of carotid plaques is necessary to render revascularization safe and effective. The aim of this study is to evaluate the usefulness of chemical exchange saturation transfer (CEST)-MRI, particularly amide proton transfer (APT) imaging as a preoperative carotid plaque diagnostic tool. We recorded the APT signal intensity on concentration maps of 34 patients scheduled for carotid endarterectomy. Plaques were categorized into group A (APT signal intensity ≥ 1.90 E-04; n = 12) and group B (APT signal intensity < 1.90 E-04; n = 22). Excised plaques were subjected to histopathological assessment and, using the classification promulgated by the American Heart Association, they were classified as intraplaque hemorrhage-positive [type VI-positive (tVI+)] and -negative [no intraplaque hemorrhage (tVI-)]. Of the 34 patients, 22 (64.7%) harbored tVI+- and 12 (35.3%) had tVI- plaques. The median APT signals were significantly higher in tVI+- than tIVI- patients (2.43 E-04 (IQR = 0.98-4.00 E-04) vs 0.54 E-04 (IQR = 0.14-1.09 E-04), p < .001). Histopathologically, the number of patients with tVI+ plaques was significantly greater in group A (100%, n = 12) than group B (45%, n = 22) (p < .01). The number of symptomatic patients or asymptomatic patients with worsening stenosis was also significantly greater in group A than group B (75% vs 36%, p < .01). In unstable plaques with intraplaque hemorrhage and in patients with symptoms or progressive stenosis, the ATP signals were significantly elevated. CEST-MRI studies has the potential for the preoperative assessment of the plaques' characteristics.

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

PurposeConventional 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. MethodsWe 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. ResultsThe 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. ConclusionThese 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.

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

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. 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. Prospective. Eighty patients with UB lesions. 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. 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. 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. 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). APT imaging may have value in discriminating malignant from benign UB lesions and has better diagnostic performance than DWI. 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.

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. 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. 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). Addition of APT to DWI may improve the ability to noninvasively predict poor prognostic factors of cervical cancer.

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.

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.

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.

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.

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.

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. Thirty-one healthy females (age: 21-50years 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. 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. 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.

The feasibility of amide proton transfer imaging at 3 T for bladder cancer: a preliminary study

To investigate the optimal amide proton transfer (APT) imaging parameters for bladder cancer (BCa), the influence of different protein concentrations and pH values on APT imaging, and to establish the reliability of APT imaging in healthy volunteers and patients with BCa. The optimal APT imaging parameters for BCa were experimentally optimised using cross-linked bovine serum albumin (BSA) phantoms. BSA phantoms were scanned with different values for the saturation power, saturation duration and number of excitations. Meanwhile, BSA phantoms containing different protein concentrations and solutions of different pH levels were scanned. The interobserver agreement of the asymmetric magnetisation transfer ratio (MTRasym) was assessed in 11 healthy volunteers and 18 patients with BCa. The optimal scanning scheme consisted of 1 excitation, a saturation power of 2 μT, and a saturation time of 2 s. The APT signal intensity increased as the protein concentration increased and as the pH decreased. The MTRasym showed good concordance for all subjects. The MTRasym of BCa tissue was significantly higher (1.81±0.71) than that of bladder wall in healthy volunteers (0.34±0.12) and normal bladder wall in patients with BCa (0.31±0.11; p<0.001). There was no significant difference between the bladder wall of healthy volunteers and the normal bladder wall of patients with BCa. APT imaging showed potential value for application in BCa.

Differentiation of hemangioblastoma from brain metastasis using MR amide proton transfer imaging.

Differentiation between hemangioblastoma and brain metastasis remains a challenge in neuroradiology using conventional MRI. Amide proton transfer (APT) imaging can provide unique molecular information. This study aimed to evaluate the usefulness of APT imaging in differentiating hemangioblastomas from brain metastases and compare APT imaging with diffusion-weighted imaging and dynamic susceptibility contrast perfusion-weighted imaging. This retrospective study included 11 patients with hemangioblastoma and 20 patients with brain metastases. Region-of-interest analyses were employed to obtain the mean, minimum, and maximum values of APT signal intensity, apparent diffusion coefficient (ADC), and relative cerebral blood volume (rCBV), and these indices were compared between hemangioblastomas and brain metastases using the unpaired t-test and Mann-Whitney U test. Their diagnostic performances were evaluated using receiver operating characteristic (ROC) analysis and area under the ROC curve (AUC). AUCs were compared using DeLong's method. All MRI-derived indices were significantly higher in hemangioblastoma than in brain metastasis. ROC analysis revealed the best performance with APT-related indices (AUC=1.000), although pairwise comparisons showed no significant difference between the mean ADC and mean rCBV. APT imaging is a useful and robust imaging tool for differentiating hemangioblastoma from metastasis.

Investigation of breast cancer microstructure and microvasculature from time-dependent DWI and CEST in correlation with histological biomarkers

We investigated the associations of time-dependent DWI, non-Gaussian DWI, and CEST parameters with histological biomarkers in a breast cancer xenograft model. 22 xenograft mice (7 MCF-7 and 15 MDA-MB-231) were scanned at 4 diffusion times [Td = 2.5/5 ms with 11 b-values (0–600 s/mm2) and Td = 9/27.6 ms with 17 b-values (0–3000 s/mm2), respectively]. The apparent diffusion coefficient (ADC) was estimated using 2 b-values in different combinations (ADC0–600 using b = 0 and 600 s/mm2 and shifted ADC [sADC200–1500] using b = 200 and 1500 s/mm2) at each of those diffusion times. Then the change (Δ) in ADC/sADC between diffusion times was evaluated. Non-Gaussian diffusion and intravoxel incoherent motion (IVIM) parameters (ADC0, the virtual ADC at b = 0; K, Kurtosis from non-Gaussian diffusion; f, the IVIM perfusion fraction) were estimated. CEST images were acquired and the amide proton transfer signal intensity (APT SI) were measured. The ΔsADC9–27.6 (between {text{sADC}}_{{9,{text{ms}}}}^{200{-}1500} and {text{sADC}}_{{27.6,{text{ms}}}}^{200{-}1500} and ΔADC2.5_sADC27.6 (between {text{ADC}}_{{2.5, {text{ms}}}}^{0{-}600} and {text{sADC}}_{{27.6,{text{ms}}}}^{200{-}1500}) was significantly larger for MCF-7 groups, and ΔADC2.5_sADC27.6 was positively correlated with Ki67max and APT SI. ADC0 decreased significantly in MDA-MB-231 group and K increased significantly with Td in MCF-7 group. APT SI and cellular area had a moderately strong positive correlation in MDA-MB-231 and MCF-7 tumors combined, and there was a positive correlation in MDA-MB-231 tumors. There was a significant negative correlation between APT SI and the Ki-67-positive ratio in MDA-MB-231 tumors and when combined with MCF-7 tumors. The associations of ΔADC2.5_sADC27.6 and API SI with Ki-67 parameters indicate that the Td-dependent DW and CEST parameters are useful to predict the histological markers of breast cancers.

Amide Proton Transfer Weighted and Intravoxel Incoherent Motion Imaging in Evaluation of Prognostic Factors for Rectal Adenocarcinoma.

ObjectivesTo analyze the value of amide proton transfer (APT) weighted and intravoxel incoherent motion (IVIM) imaging in evaluation of prognostic factors for rectal adenocarcinoma, compared with diffusion weighted imaging (DWI).Materials and MethodsPreoperative pelvic MRI data of 110 patients with surgical pathologically confirmed diagnosis of rectal adenocarcinoma were retrospectively evaluated. All patients underwent high-resolution T2-weighted imaging (T2WI), APT, IVIM, and DWI. Parameters including APT signal intensity (APT SI), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), and apparent diffusion coefficient (ADC) were measured in different histopathologic types, grades, stages, and structure invasion statuses. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy, and the corresponding area under the curves (AUCs) were calculated.ResultsAPT SI, D and ADC values of rectal mucinous adenocarcinoma (MC) were significantly higher than those of rectal common adenocarcinoma (AC) ([3.192 ± 0.661%] vs. [2.333 ± 0.471%], [1.153 ± 0.238×10-3 mm2/s] vs. [0.792 ± 0.173×10-3 mm2/s], and [1.535 ± 0.203×10-3 mm2/s] vs. [0.986 ± 0.124×10-3 mm2/s], respectively; all P<0.001). In AC group, the APT SI and D values showed significant differences between low- and high-grade tumors ([2.226 ± 0.347%] vs. [2.668 ± 0.638%], and [0.842 ± 0.148×10-3 mm2/s] vs. [0.777 ± 0.178×10-3 mm2/s], respectively, both P<0.05). The D value had significant difference between positive and negative extramural vascular invasion (EMVI) tumors ([0.771 ± 0.175×10-3 mm2/s] vs. [0.858 ± 0.151×10-3 mm2/s], P<0.05). No significant difference of APT SI, D, D*, f or ADC was observed in different T stages, N stages, perineural and lymphovascular invasions (all P>0.05). The ROC curves showed that the AUCs of APT SI, D and ADC values for distinguishing MC from AC were 0.921, 0.893 and 0.995, respectively. The AUCs of APT SI and D values in distinguishing low- from high-grade AC were 0.737 and 0.663, respectively. The AUC of the D value for evaluating EMVI involvement was 0.646.ConclusionAPT and IVIM were helpful to assess the prognostic factors related to rectal adenocarcinoma, including histopathological type, tumor grade and the EMVI status.

NI-15 Comparison of amide proton transfer imaging with perfusion imaging of using arterial spin-labeling for evidence of tumor cells in glioma

BACKGROUND: Infiltrative gliomas show cerebral edema and tumor infiltration as areas of hyperintensity in FLAIR image. Amide proton transfer (APT) and cerebral blood flow (CBF) are useful for evaluating the tumor invasion. In this study, arterial spin-labeling (ASL)-CBF and APT were compared to determine which method was superior for predicting tumor infiltration in gliomas, pathologically. METHODS: Fifteen specimens from 5 glioma patients with confirmed selective sampling were obtained. Based on APT signal intensity (SI), regions of interests (ROIs) were selected for biopsy. Same regions of these ROIs were marked on the same slice of ASL imaging. Samples were pathologically assessed for cell density and vessel density. APT SI and ASL-CBF were analyzed for each specimen. RESULTS: APT signal intensity (SI) showed a strong correlation with cell density (R = 0.887, P < 0.0001). ASL-CBF showed no correlation with cell density (R = 0.240; P = 0.3836) but a correlation with vessel density (R = 0.697; P = 0.0038). In linear regression analysis, APT SI showed a positive relationship with cell density (R2 = 0.787, P < 0.0001, linear regression; y = 30.70 + 6.24E-3*x). CONCLUSIONS: APT imaging was superior in predicting cellular proliferation than ASL-CBF and a powerful predictor of cell density. APT imaging allowed revelation of novel clues reflecting tumor proliferation in brain tumor; to date, this is the first known report to assess cell density among various brain tumors and conditions after treatment.

Dynamic Change of Amide Proton Transfer Imaging in Irradiated Nasopharyngeal Carcinoma and Related Histopathological Mechanism.

To investigate the dynamic change of amide proton transfer (APT) imaging before and after irradiation in nasopharyngeal carcinoma (NPC) and the underlying histopathological mechanism. Tumor-bearing BALB/C nude mouse models were established and randomly divided into three groups: high-dose group (20 Gy/2 fractions), low-dose group (10 Gy/2 fractions), and control group (0 Gy). MRI scanning was performed before irradiation and 3rd, 6th, and 9th day post-irradiation. Scanning sequence included T1 weighted, T2 weighted, and APT. HE staining and TUNEL immunofluorescence detection were performed to detect necrosis and apoptosis. After high-dose irradiation, the mean tumor APT values decreased significantly on the 3rd day and 6th day (from 3.83 before radiotherapy to 2.41%, P < 0.001, 3rd day; from 2.41 to 1.80%, P = 0.001, 6th day). For low-dose irradiation, the mean tumor APT values decreased slightly on the 3rd day and 6th day (from 3.52 to 3.13%, P = 0.109, 3rd day; from 3.13 to 3.05%, P = 0.64, 6th day). The mean APT values of nonirradiated tumor changed slightly. In contrast, the average volume of high-dose irradiated tumors did not decrease obviously until the 9th day post-irradiation (from 290 before radiotherapy to 208 mm3 on the 9th day). The low-dose irradiated tumors showed slow growth, and the nonirradiated tumors showed rapid growth. Subsequent HE staining and TUNEL staining showed obvious necrosis characteristics and higher proportion of positive apoptotic cell nucleus in high-dose irradiated tumors, but not nonirradiated tumors. The APT signal intensity decreased after irradiation, which is earlier than the change of tumor volume. What is more, the decrease of APT signal intensity is more significant in high-dose group. Histological analysis showed obvious apoptosis and necrosis histological characteristic in irradiated tumor, which may explain the decrease of APT signal intensity. These results indicate that APT imaging has the potential to serve as a reliable biomarker for response assessment in NPC.

Comparative Study of Amide Proton Transfer Imaging and Intravoxel Incoherent Motion Imaging for Predicting Histologic Grade of Hepatocellular Carcinoma.

Background: Preoperative grading of hepatocellular carcinoma (HCC) is an important factor associated with prognosis after liver resection. The promising prediction of the differentiation of HCC remains a challenge. The purpose of our study was to investigate the value of amide proton transfer (APT) imaging in predicting the histological grade of HCC, compared with the intravoxel incoherent motion (IVIM) imaging.Methods: From September 2018 to February 2020, 88 patients with HCC were enrolled and divided into four groups (G1, G2, G3, and G4) based on the histologic grades. Preoperative APT signal intensity (SI), apparent diffusion coefficient (ADC), true molecular diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f ) of HCC were independently measured by two radiologists. The averaged values of those parameters were compared using an analysis of variance. The Spearman rank analysis was used to compare the correlation between those imaging parameters and the histological grades. Receiver operating characteristic (ROC) curve analysis was used to explore the predictive performance.Results: There were significant differences in APT SI, ADC, D, and f among the four grades of HCC (all P < 0.001). A moderate to good relationship was found between APT SI and the histologic grade of HCC (r = 0.679, P < 0.001). APT SI had an area under the ROC curve (AUC) of 0.890 (95% CI: 0.805–0.947) for differentiating low- from high-grade HCC, and the corresponding sensitivity and specificity were 85.71% and 82.05%, respectively. Comparison of ROC curves demonstrated that the AUC of APT SI was significantly higher than those of IVIM-derived parameter (Z = 2.603, P = 0.0092; Z = 2.099, P = 0.0358; Z = 4.023, P = 0.0001; Z = 2.435, P = 0.0149, compared with ADC, D, D*, and f , respectively). Moreover, the combination of both techniques further improved the diagnostic performance, with an AUC of 0.929 (95% CI: 0.854–0.973).Conclusion: APT imaging may be a potential noninvasive biomarker for the prediction of histologic grading of HCC and complements IVIM imaging for the more accurate and comprehensive characterization of HCC.

Amide Proton Transfer Imaging vs Diffusion Kurtosis Imaging for Predicting Histological Grade of Hepatocellular Carcinoma.

BackgroundTo investigate the value of amide proton transfer (APT) imaging in predicting the histological grade of hepatocellular carcinoma (HCC), compared with diffusion kurtosis imaging (DKI).MethodsA total of 88 patients with HCC were enrolled and divided into four groups (G1, G2, G3, and G4) based on histologic grades. Preoperative APT signal intensity (SI), mean diffusivity (MD), mean kurtosis (MK) of HCC were measured and compared. Those quantitative magnetic resonance imaging (qMRI) parameters were compared using an analysis of variance. The correlations between the qMRI parameters and the histological grades were determined using Spearman's rank analysis. In addition, the predictive performance for differentiating low- (G1 and G2) from high-grade (G3 and G4) HCC was evaluated using receiver operating characteristic (ROC) curve analysis.ResultsSignificant differences were found in APT SIs, MD, and MK among the four groups (P<0.05). Moderate to good relationships were found between the histologic grade of HCC and APT SI and MK (r=0.679, P<0.001 and r=0.539, P<0.001, respectively). The area under the ROC curves (AUCs) of APT SI, MK, and MD for differentiating low- from high-grade HCC were 0.890 (95%CI: 0.805–0.947), 0.765 (95%CI: 0.662–0.849) and 0.717 (95%CI: 0.611–0.808), respectively. Comparison of ROC curves showed a significantly higher AUC of APT SI compared with those of the DKI-derived parameters (P <0.05).ConclusionThe APT imaging may be more accurate than DKI for predicting the histological grade of HCC.

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

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