Those interested in understanding of tumor Amide Proton Transfer (APT) contrast.The purpose of this study was to provide insight into the effect of water-T1-relaxation (T1w) on APT contrast in tumors. Three different metrics of APT contrast: three-point-method-based [1] magnetization transfer ratio (MTRRex, APT signal free from the effects of direct water saturation and conventional magnetization transfer) [2] and relaxation-compensated MTRRex (AREX) [2], and traditional asymmetry (MTRasym) [3] were compared in normal and tumor tissues in a variety of intracranial tumors at 7T.Six consented patients with intracranial brain tumors were scanned on a 7T Philips MR system. A pulsed 3D steady-state CEST sequence [4] was used with the following parameters: saturation prepulse (a rectangular-shaped 1.8 μT 50 ms pulse followed by a 50 mT/m spoiler of 25ms) interleaved with a readout (segmented EPI, EPI factor of 15 with a binomial RF pulse for water only excitation, TR/TE/FA=106/6.4ms/18.5°, FOV 224x224x100 mm3, 2 mm isotropic); time per volume 20.3 s, inter-volume delay 2 s, total scan time 6min40s. A quantitative T1 map was obtained using the method in [5,6]. The 3T protocol included a T1-weighted post gadolinium (postGd-T1w) scan. A 7T fluid attenuated inversion recovery (FLAIR) [7] was used to visualize edema and cystic regions.All images were co-registered to the FLAIR images. Masks of normal and diseased tissues were drawn on postGd-T1w and FLAIR images (Fig. 1) by an experienced neuroradiologist. B0 was corrected by using WASSR [8]. All metrics were quantified in the range of 3 to 4 ppm to increase SNR.The dependence of APT signal build-up on T1w of the mediating bulk water proton pool can be seen in Fig. 2 (left inset). The APT signal (area under the linear baseline) tends to increase as T1w of tissue increases. The same T1w dependence is obvious for traditional asymmetry analysis (MTRasym), shown in the right inset. An overview of the data of the six patients is shown in Fig. 3. While MTRasym is enhanced in tumor region in all cases, its contrast resembles that of the T1 map. The “randomness” of MTRrex and AREX is most likely an issue of pixel-wise implementation of the three-point method.Region-averaged APT assessments are often sufficient for diagnosis and assessment of therapy response. ROI analysis was performed on both normal and diseased tissues. As expected, a positive correlation was found between MTRRex of tissue types and their T1w values (Fig. 4 A, R=0.88, p<0.05), suggesting that the contribution of T1w effect to APT can be significant. Surprisingly, after T1w correction, there was no difference between normal and pathological tissues for AREX as demonstrated by the overlapping data points (Fig. 4 B, R=-0.21, p=0.69). Interestingly, the difference between low (Fig. 4 A, red open circles) and high grade (Fig. 4 B, red solid circles) glioma disappears for AREX, where the relaxation effects are accounted for. A strong positive correlation with T1w is also evident for MTRasym (Fig. 4 C, R=0.92, p<<0.05).Much of APT contrast in tumors for the low-power 3D acquisition scheme at 7T, typically explained by an increase in the content endogenous amides, originates from the inherent-tissue-water-T1-relaxation properties.