Quasi–steady‐state amide proton transfer (QUASS APT) MRI enhances pH‐weighted imaging of acute stroke

Abstract

Purpose: Chemical exchange saturation transfer (CEST) imaging measurement depends not only on the labile proton concentration and pH-dependent exchange rate but also on experimental conditions, including the relaxation delay and radiofrequency (RF) saturation time. Our study aimed to extend a quasi-steady-state (QUASS) solution to a modified multi-slice CEST MRI sequence and test if it provides enhanced pH imaging after acute stroke. Methods: Our study derived the QUASS solution for a modified multislice CEST MRI sequence with an unevenly segmented RF saturation between image readout and signal averaging. Numerical simulation was performed to test if the generalized QUASS solution corrects the impact of insufficiently long relaxation delay, primary and secondary saturation times, and multi-slice readout. In addition, multiparametric MRI scans were obtained after middle cerebral artery occlusion, including relaxation and CEST Z-spectrum, to evaluate the performance of QUASS CEST MRI in a rodent acute stroke model. We also performed Lorentzian fitting to isolate multi-pool CEST contributions. Results:The QUASS analysis enhanced pH-weighted magnetization transfer asymmetry contrast over the routine apparent CEST measurements in both contralateral normal (−3.46% ± 0.62% (apparent) vs. −3.67% ± 0.66% (QUASS), P < 0.05) and ischemic tissue (−5.53% ± 0.68% (apparent) vs. −5.94% ± 0.73% (QUASS), P < 0.05). Lorentzian fitting also showed significant differences between routine and QUASS analysis of ischemia-induced changes in magnetization transfer, amide, amine, guanidyl CEST, and nuclear Overhauser enhancement (−1.6 parts per million) effects. Conclusion:Our study demonstrated that generalized QUASS analysis enhanced pH MRI contrast and improved quantification of the underlying CEST contrast mechanism, promising for further in vivo applications. K E Y W O R D Samide proton transfer (APT), CEST, magnetization transfer MTR asymmetry (MTR asym ), pH imaging, stroke This study was supported by a National Institutes of Health (NIH), grant R01NS083654 (p.z.s.).

Demonstration of pH imaging in acute stroke with endogenous ratiometric chemical exchange saturation transfer magnetic resonance imaging at 2 ppm

“…Recently, a quasi-steady-state algorithm has been proposed that enables equilibrium CEST effect reconstruction despite the use of not sufficiently long saturation time and relaxation delay, which provides a potential solution to reduce the total scan time. [53][54][55]61,62,63 Third, the guanidine exchange rate is much faster than amide protons, which probably makes ratiometric CEST@2 ppm MRI more sensitive to pH changes.…”

“…Second, although RF amplitude‐based ratiometric analysis provides concentration‐independent pH measurement, less susceptible to changes such as edema and proteolysis, it requires the acquisition of two Z‐spectra, hence, doubling the scan time. Recently, a quasi‐steady‐state algorithm has been proposed that enables equilibrium CEST effect reconstruction despite the use of not sufficiently long saturation time and relaxation delay, which provides a potential solution to reduce the total scan time 53–55,61,62,63 . Third, the guanidine exchange rate is much faster than amide protons, which probably makes ratiometric CEST@2 ppm MRI more sensitive to pH changes.…”

Use of multimodality imaging, histology, and treatment feasibility to characterize a transgenic Rag2-null rat model of glioblastoma

“…Because of this, no volumetric comparisons between PET and CEST data could be made. Now that the feasibility of studying MR-CEST in this animal model has been established, we intend to acquire 3D CEST volumetric tumor data in future studies in a manner that can be compared with the 18 F-FET PET volumes (77)(78)(79)(80) In addition, the emerging quasi-steady-state CEST reconstruction potentially aids the standardization of in vivo image analysis, which can be adopted in future studies for quantitative CEST MRI (81)(82)(83). Another limitation that deserves consideration is the scarce availability of hybrid PET/MRI scanners for small animals, which means that the simultaneous acquisition of 18 F-FET and CEST MRI data for animal model development will only be possible for a few investigators.…”

Generalization of quasi‐steady‐state reconstruction to CEST MRI with two‐tiered RF saturation and gradient‐echo readout—Synergistic nuclear Overhauser enhancement contribution to brain tumor amide proton transfer–weighted MRI

“…Our work generalized the QUASS solution to a sequence of two‐tiered RF saturation with GRE‐EPI readout, as shown in Figure S1 39 . Because GRE readout introduces a carryforward signal between signal averaging, an iterative numerical solution is needed, extending a recent QUASS derivation for spin echo readout 42 . Specifically, the control signal without RF saturation from the first average (na = 1) for the i th slice is given by $$$$ {\displaystyle \begin{array}{ll}& {I}_0^{\mathrm{app}}\left(i,\mathrm{ns},\mathrm{na}=1\right)\approx \left(\cos \alpha \cdot {e}^{-{R}_{1w}\cdot \left[\left( Td+ Ts1\right)+ Ts2\ast \left(i-1\right)\right]}\right.\\ {}& \left.\kern8em +1-{e}^{-{R}_{1w}\cdot \left[\left( Td+ Ts1\right)+ Ts2\ast \left(i-1\right)\right]}\right)\cdot \sin \alpha \end{array}} $$$$ where i denotes the i th slice of a total of slices (ns); α is the flip angle (FA); R 1 w is the longitudinal relaxation rate; and Td, Ts1, and Ts2 are the relaxation delay, primary RF saturation, and secondary RF saturation duration, respectively.…”

“…39 Because GRE readout introduces a carryforward signal between signal averaging, an iterative numerical solution is needed, extending a recent QUASS derivation for spin echo readout. 42 Specifically, the control signal without RF saturation from the first average (na = 1) for the ith slice is given by…”