Purpose To quantify APT and NOE contributions to in vivo chemical exchange saturation transfer MRI signals in tumors. Theory and Methods Two-pool (free water and semi-solid protons) and four-pool (free water, semi-solid, amide, and upfield NOE-related protons) tissue models combined with the super-Lorentzian lineshape for semi-solid protons were used to fit wide and narrow frequency-offset magnetization-transfer (MT) data, respectively. Extrapolated semi-solid MT signals at 3.5 and −3.5 ppm from water were used as reference signals to quantify APT and NOE, respectively. Six glioma-bearing rats were scanned at 4.7 T. Quantitative APT and NOE signals were compared at three saturation power levels. Results The observed APT signals were significantly higher in the tumor (center and rim) than in the contralateral normal brain tissue at all saturation powers, and were the major contributor to the APT-weighted image contrast (based on MT asymmetry analysis) between the tumor and the normal brain tissue. The NOE (a positive confounding factor) enhanced this APT-weighted image contrast. The fitted amide pool sizes were significantly larger, while the NOE-related pool sizes were significantly smaller in the tumor than in the normal brain tissue. Conclusion The EMR provides a relatively accurate approach for quantitatively measuring pure APT and NOE signals.

Purpose To evaluate the use of three EMR methods to quantify APT and NOE signals in human glioma. Methods Eleven patients with high-grade glioma were scanned at 3 T. aEMR2 (asymmetric magnetization-transfer or MT model to fit two-sided, wide-offset data), sEMR2 (symmetric MT model to fit two-sided, wide-offset data), and sEMR1 (symmetric MT model to fit one-sided, wide-offset data) were assessed. ZEMR and experimental data at 3.5 ppm and −3.5 ppm were subtracted to calculate the APT and NOE signals (APT# and NOE#), respectively. Results The aEMR2 and sEMR1 models provided quite similar APT# signals, while the sEMR2 provided somewhat lower APT# signals. The aEMR2 had an erroneous NOE# quantification. Calculated APT# signal intensities of glioma (~4%), much larger than the values reported previously, were significantly higher than those of edema and normal tissue. Compared to normal tissue, gadolinium-enhancing tumor cores were consistently hyperintense on the APT# maps and slightly hypointense on the NOE# maps. Conclusion The sEMR1 model is the best choice for accurately quantifying APT and NOE signals. The APT-weighted hyperintensity in the tumor was dominated by the APT effect, and the MT asymmetry at 3.5 ppm is a reliable and valid metric for APT imaging of gliomas at 3 T.

Amide proton transfer-weighted (APTw) MR imaging shows promise as a biomarker of brain tumor status. Currently used APTw MRI pulse sequences and protocols vary substantially among different institutes, and there are no agreed-on standards in the imaging community. Therefore, the results acquired from different research centers are difficult to compare, which hampers uniform clinical application and interpretation. This paper reviews current clinical APTw imaging approaches and provides a rationale for optimized APTw brain tumor imaging at 3 T, including specific recommendations for pulse sequences, acquisition protocols, and data processing methods. We expect that these consensus recommendations will become the first broadly accepted guidelines for APTw imaging of brain tumors on 3 T MRI systems from different vendors. This will allow more medical centers to use the same or comparable APTw MRI techniques for the detection, characterization, and monitoring of brain tumors, enabling multi-center trials in larger patient cohorts and, ultimately, routine clinical use. K E Y W O R D APTw standardization, APT-weighted imaging, brain tumor, CEST imaging How to cite this article: Zhou J, Zaiss M, Knutsson L, et al. Review and consensus recommendations on clinical APT-weighted imaging approaches at 3T: Application to brain tumors.

Purpose To quantify APT effects in acidic ischemic lesions and assess the spatial-temporal relationship between diffusion, perfusion, and pH deficits in acute stroke patients. Methods Thirty acute stroke patients were scanned at 3 T. Quantitative APT (APT#) effects in acidic ischemic lesions were measured using an extrapolated semisolid magnetization transfer reference signal (EMR) technique and compared with commonly used MTRasym(3.5ppm) or APT-weighted parameters. Results APT# images showed clear pH deficits in the ischemic lesion, whereas MTRasym(3.5ppm) signals were slightly hypointense. The APT# contrast between acidic ischemic lesions and normal tissue in acute stroke patients was more than 3 times larger than MTRasym(3.5ppm) contrast (−1.45 ± 0.40 % for APT# vs. −0.39 ± 0.52 % for MTRasym(3.5ppm), p < 4.6 × 10-4). Hypoperfused and acidic areas without an apparent diffusion coefficient abnormality were observed and assigned to an ischemic acidosis penumbra. Hypoperfused areas at normal pH were also observed and assigned to benign oligemia. Hyperintense APT signals were observed in a hemorrhage area in one case. Conclusion The quantitative APT study using the EMR approach enhances APT MRI sensitivity to pH compared to conventional APT-weighted MRI, allowing more reliable delineation of an ischemic acidosis in the penumbra.