3D APT and NOE CEST-MRI of healthy volunteers and patients with non-enhancing glioma at 3 T

Objective Clinical application of chemical exchange saturation transfer (CEST) can be performed with investigation of amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) effects. Here, we investigated APT- and NOE-weighted imaging based on advanced CEST metrics to map tumor heterogeneity of non-enhancing glioma at 3 T. Materials and methods APT- and NOE-weighted maps based on Lorentzian difference (LD) and inverse magnetization transfer ratio (MTRREX) were acquired with a 3D snapshot CEST acquisition at 3 T. Saturation power was investigated first by varying B1 (0.5–2 µT) in 5 healthy volunteers then by applying B1 of 0.5 and 1.5 µT in 10 patients with non-enhancing glioma. Tissue contrast (TC) and contrast-to-noise ratios (CNR) were calculated between glioma and normal appearing white matter (NAWM) and grey matter, in APT- and NOE-weighted images. Volume percentages of the tumor showing hypo/hyperintensity (VPhypo/hyper,CEST) in APT/NOE-weighted images were calculated for each patient. Results LD APT resulting from using a B1 of 1.5 µT was found to provide significant positive TCtumor,NAWM and MTRREX NOE (B1 of 1.5 µT) provided significant negative TCtumor,NAWM in tissue differentiation. MTRREX-based NOE imaging under 1.5 µT provided significantly larger VPhypo,CEST than MTRREX APT under 1.5 µT. Conclusion This work showed that with a rapid CEST acquisition using a B1 saturation power of 1.5 µT and covering the whole tumor, analysis of both LD APT and MTRREX NOE allows for observing tumor heterogeneity, which will be beneficial in future studies using CEST-MRI to improve imaging diagnostics for non-enhancing glioma.

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.

Can Chemical Exchange Saturation Transfer (CEST MRI) be used as biomarker of disease progression in Prion Disease?

Human prion diseases are fatal neurodegenerative disorders that may have prolonged asymptomatic incubation periods. However, the underlying mechanism by which prions cause brain damage remains unclear. In turn, characterization of early pathological aspects would be of benefit for the diagnosis and potential treatment of these progressive neurodegenerative disorders. We investigated chemical exchange saturation transfer (CEST) MRI based on its exquisite sensitivity to cytosol protein content as a surrogate for prion disease pathology. Three groups of prion-infected mice at different stages of the disease underwent conventional magnetic resonance imaging and CEST MRI at 9.4T. For each mouse, chemical exchange contrasts were measured by applying five RF powers at various frequency offsets using magnetization transfer asymmetries. Relayed Nuclear Overhauser effects (NOE*) and amide proton transfer (APT*) were also assessed. For comparison, CEST MRI measurements were also made in healthy control mice brains. Here we show that alterations in CEST signal were detected before structural modifications or any clinical signs of prion disease. The detected CEST signal displayed different patterns at different stages of the disease indicating its potential for use as a longitudinal marker of disease progression. Highly significant correlations were found between CEST metrics and histopathological findings. A decline in NOE signal was positively correlated with abnormal prion protein deposition (R2 = 0.91) in the thalami of prion infected mice. Moreover, the NOE signal was negatively correlated with astrogliosis (R2 = 0.71) in the thalamus. No significant correlations were detected between NOE signals and spongiosis. MTR asymmetry at 3.5 ppm was also correlated with astrogliosis (R2 = 0.59), and prion protein deposition (R2 = 0.63) in thalamus. No significant changes were detected in APT* between prion-infected and control mice at all stages of the disease. Finally, MTR asymmetry between 2.8 and 3.2 ppm was correlated with prion protein deposition (R2 = 0.47) in the thalamus of prion -infected mice. To conclude, CEST MRI has potential utility as a biomarker of neurodegenerative processes in prion disease

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.