Mitigation of T1 impact for unbiased tumor magnetic resonance amide proton transfer imaging at 3T

Abstract

Background: Amide proton transfer (APT), a specific type of chemical exchange saturation transfer (CEST) MRI, has proved valuable in tumor diagnosis and characterization by detecting mobile protein/peptides in cancerous tissues. However, T₁ confounds CEST measurements, leading to reduced specificity to amides and potential misinterpretation of APT imaging.

Purpose: The study aimed to investigate the feasibility of the quasi-steady-state (QUASS)-based apparent exchange-dependent relaxation (AREX) analysis in correcting T₁ for unbiased tumor APT MRI at 3T.

Materials and methods: CEST MRI experiments were conducted on an egg white phantom and on prospectively enrolled brain tumor patients with T₁ values modulated by gadolinium (Gd). QUASS algorithm was employed to reconstruct steady-state Z spectra. Conventional T₁-uncorrected CEST effect was quantified with a multipool Lorentzian function from QUASS Z spectra. The non-QUASS AREX and QUASS-based AREX with T₁ correction were calculated from the inverse of non-QUASS and QUASS Z spectra, respectively. The student's t-test and Bland-Altman plots were performed to assess the statistical difference and consistency between pre- and post-Gd measurements.

Results: In the phantom study, vials with different T₁ values showed conspicuous discrepancy on the conventional uncorrected APT and non-QUASS AREX maps, but comparable contrast on the QUASS-based AREX map. In the human study, 13 patients were enrolled. The contralateral normal-appearing white matter exhibited no substantial change in T₁ and similar CEST effect between uncorrected APT, non-QUASS AREX, and QUASS-based AREX pre- and post-Gd (all P > .05). However, the tumor regions showed significantly reduced T₁ post-Gd that altered the CEST measurements obtained from uncorrected APT and non-QUASS AREX (both P < .001). In comparison, QUASS-based AREX measurements were in excellent agreement between pre- and post-Gd (P = .19).

Conclusion: QUASS-based AREX analysis can effectively correct T₁ contamination in CEST measurements, facilitating unbiased tumor APT MRI at 3T.

Keywords: MRI; T1; amide proton transfer; chemical exchange saturation transfer; tumor imaging.

Figure 1.

Multiparametric MR images of a 4-vial fresh egg white phantom with serially varied Gd concentrations of 0.05, 0.10, 0.15, and 0.20 mM, including (A) T₁ map, (B) conventional uncorrected APT, (C) non-QUASS AREX, and (D) QUASS-based AREX images. Abbreviations: APT, amide proton transfer; AREX, apparent exchange-dependent relaxation; Gd, gadolinium; QUASS, quasi-steady-state.

Figure 2.

Multiparametric MR images of a 66-year-old female patient with meningioma (patient No. 2 in Table 1), including (A) Gd-enhanced T₁w image with CNAWM and tumor regions overlaid, and maps of pre- and post-Gd T₁, (B) conventional uncorrected APT, (C) non-QUASS AREX, and (D) QUASS-based AREX and corresponding histograms and Bland-Altman plots between pre- and post-Gd measurements, respectively. The 3 horizontal lines in the Bland-Altman plots depict the mean and the upper and lower limits of agreement (ie, +1.96 and −1.96 times of SD, respectively) with the values shown for each region. Abbreviations: APT, amide proton transfer; AREX, apparent exchange-dependent relaxation; CNAWM, contralateral normal-appearing white matter; Gd, gadolinium; QUASS, quasi-steady-state.

Figure 3.

Multiparametric MR images of a 53-year-old male patient with histologically confirmed postoperative recurrence of metastases (patient No. 9 in Table 1), including (A) Gd-enhanced T₁w image with CNAWM and tumor regions overlaid, and maps of pre- and post-Gd T₁, (B) conventional uncorrected APT, (C) non-QUASS AREX, and (D) QUASS-based AREX and corresponding histograms and Bland-Altman plots between pre- and post-Gd measurements, respectively. The 3 horizontal lines in the Bland-Altman plots depict the mean and the upper and lower limits of agreement (ie, +1.96 and −1.96 times of SD, respectively) with the values shown for each region. Abbreviations: APT, amide proton transfer; AREX, apparent exchange-dependent relaxation; CNAWM, contralateral normal-appearing white matter; Gd, gadolinium; QUASS, quasi-steady-state.

Figure 4.

Bland-Altman plots of (A) conventional uncorrected APT, (B) non-QUASS AREX, and (C) QUASS-based AREX measurements between pre- and post-Gd administration in the CNAWM and tumor regions from the enrolled 13 patients. The 3 horizontal lines depict the mean and the upper and lower limits of agreement (ie, +1.96 and −1.96 times of SD, respectively) with the values shown for each region. Abbreviations: APT, amide proton transfer; AREX, apparent exchange-dependent relaxation; CNAWM, contralateral normal-appearing white matter; Gd, gadolinium; QUASS, quasi-steady-state.