Phase-independent thermometry by Z-spectrum MR imaging.

PURPOSE: Z-spectrum imaging, defined as the consecutive collection of images after saturating over a range of frequency offsets, has been recently proposed as a method to measure the fat-water fraction by the simultaneous detection of fat and water resonances. By incorporating a binomial pulse irradiated at each offset before the readout, the spectral selectivity of the sequence can be further amplified, making it possible to monitor the subtle proton resonance frequency shift that follows a change in temperature. METHODS: We tested the hypothesis in aqueous and cream phantoms and in healthy mice, all under thermal challenge. The binomial module consisted of 2 sinc-shaped pulses of opposite phase separated by a delay. Such a delay served to spread out off-resonance spins, with the resulting excitation profile being a periodic function of the delay and the chemical shift. RESULTS: During heating experiments, the water resonance shifted downfield, and by fitting the curve to a sine function it was possible to quantify the change in temperature. Results from Z-spectrum imaging correlated linearly with data from conventional MRI techniques like T1 mapping and phase differences from spoiled GRE. CONCLUSION: Because the measurement is performed solely on magnitude images, the technique is independent of phase artifacts and is therefore applicable in mixed tissues (e.g., fat). We showed that Z-spectrum imaging can deliver reliable temperature change measurement in both muscular and fatty tissues.

Improving the detection specificity of endogenous MRI for reactive oxygen species (ROS).

BACKGROUND: The detection of tissue reactive oxygen species (ROS) using endogenous MRI methods has great potential applications in research and the clinic. We recently demonstrated that ROS produce a significant T1 -shortening effect. However, T1 or T1 -weighted contrast is not specific, as there are many other factors that alter tissue T1 . PURPOSE: To investigate whether the presence of ROS alters tissue environmental conditions such as the proton exchange rate (K ex ) to improve the detection specificity of endogenous ROS MRI. STUDY TYPE: Prospective. SUBJECTS/PHANTOM: The ROS-producing phantoms consisted of fresh egg white treated with H2 O2 and healthy mice injected with pro-oxidative rotenone. FIELD STRENGTH/SEQUENCE: T1 mapping was performed based on fast spin-echo sequence and K ex was evaluated using chemical exchange saturation transfer (CEST) MRI with varied saturation power (QUESP) on a 9.4 T animal scanner. ASSESSMENT: Phantom experiments were conducted to evaluate the overall K ex of CEST-expressing metabolites in fresh egg white treated with H2 O2 of various concentrations (0, 0.025, 0.05, 0.1, and 0.25 v/v%). The egg white phantom continuously produced ROS for more than 3 hours. Various experiments were performed to rule out potential contributing factors to the observed K ex changes. In addition, in vivo MRI study was conducted with a well-established rotenone-exposed mouse model. STATISTICAL TESTS: Student's t-test. RESULTS: Egg white phantoms treated with H2 O2 of various concentrations showed a 26-85% increase in K ex compared with controls. In addition, the K ex of egg white is negligibly affected by other potential confounding factors, including paramagnetic contrast agents (<11%), oxygen (2.3%), and iron oxidation (<10%). Changes in temperature (<1°C) and pH (ΔpH <0.1) in H2 O2 -treated egg white were also negligible. Results from the in vivo rotenone study were consistent with the phantom studies by showing reduced T1 relaxation time (6%) and increased K ex (9%) in rotenone-treated mice. DATA CONCLUSION: We demonstrate that the specificity of endogenous ROS MRI can be improved with the aid of proton exchange rate mapping. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:583-591.

Imaging short-lived reactive oxygen species (ROS) with endogenous contrast MRI.

PURPOSE: To characterize the relaxation properties of reactive oxygen species (ROS) for the development of endogenous ROS contrast magnetic resonance imaging (MRI). MATERIALS AND METHODS: ROS-producing phantoms and animal models were imaged at 9.4T MRI to obtain T1 and T2 maps. Egg white samples treated with varied concentrations of hydrogen peroxide (H2 O2 ) were used to evaluate the effect of produced ROS in T1 and T2 for up to 4 hours. pH and temperature changes due to H2 O2 treatment in egg white were also monitored. The influences from H2 O2 itself and oxygen were evaluated in bovine serum albumin (BSA) solution producing no ROS. In addition, dynamic temporal changes of T1 in H2 O2 -treated egg white samples were used to estimate ROS concentration over time and hence the detection sensitivity of relaxation-based endogenous ROS MRI. The relaxivity of ROS was compared with that of Gd-DTPA as a reference. Finally, the feasibility of in vivo ROS MRI with T1 mapping acquired using an inversion recovery sequence was demonstrated with a well-established rotenone-treated mouse model (n = 6). RESULTS: pH and temperature changes in treated egg white samples were insignificant (<0.1 unit and <1°C, respectively). T1 relaxation time in the H2 O2 -treated egg white was reduced significantly (P < 0.05), while there was only small reduction in T2 (<10%). In the H2 O2 -treated BSA solution that produce no ROS, there was a small change in T1 due to H2 O2 itself (±1%), although a significant T2 -shortening effect was observed (>10%, P < 0.05). Also, there was a small reduction in T1 (13 ± 1%) and T2 (1 ± 2%) from molecular oxygen. The detection sensitivity of ROS MRI was estimated around 10 pM. The T1 relaxivity of ROS was found to be much higher than that of Gd-DTPA (3.4 × 107 vs. 0.9 s-1 ·mM-1 ). Finally, significantly reduced T1 was observed in rotenone-treated mouse brain (5.1 ± 2.5%, P < 0.05). CONCLUSION: We demonstrated in the study that endogenous ROS MRI based on the paramagnetic effect has sensitivity for in vitro and in vivo applications. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2018;47:222-229.

Influence of Free Radicals on the Intrinsic MRI Relaxation Properties.

Free radicals are critical contributors in various conditions including normal aging, Alzheimer's disease, cancer, and diabetes. Currently there is no non-invasive approach to image tissue free radicals based on endogenous contrast due to their extremely short lifetimes and low in vivo concentrations. In this study we aim at characterizing the influence of free radicals on the MRI relaxation properties. Phantoms containing free radicals were created by treating egg white with various H 2 O 2 concentrations and scanned on a 9.4 T MRI scanner at room temperature. T1 and T2 relaxation maps were generated from data acquired with an inversion recovery sequence with varied inversion times and a multi-echo spin echo sequence with varied echo times (TEs), respectively. Results demonstrated that free radicals express a strong shortening effect on T1, which was proportional to the H 2 O 2 concentration, and a relatively small reduction in T2 (<10%). Furthermore, the sensitivity of this approach in the detection of free radicals was estimated to be in the pM range that is within the physiological range of in vivo free radical expression. In conclusion, the free radicals show a strong paramagnetic effect that may be utilized as an endogenous MRI contrast for its non-invasive in vivo imaging.

Creatine CEST MRI for Differentiating Gliomas with Different Degrees of Aggressiveness.

PURPOSE: Creatine (Cr) is a major metabolite in the bioenergetic system. Measurement of Cr using conventional MR spectroscopy (MRS) suffers from low spatial resolution and relatively long acquisition times. Creatine chemical exchange saturation transfer (CrCEST) magnetic resonance imaging (MRI) is an emerging molecular imaging method for tissue Cr measurements. Our previous study showed that the CrCEST contrast, obtained through multicomponent Z-spectral fitting, was lower in tumors compared to normal brain, which further reduced with tumor progression. The current study was aimed to investigate if CrCEST MRI can also be useful for differentiating gliomas with different degrees of aggressiveness. PROCEDURES: Intracranial 9L gliosarcoma and F98 glioma bearing rats with matched tumor size were scanned with a 9.4 T MRI scanner at two time points. CEST Z-spectra were collected using a customized sequence with a frequency-selective rectangular saturation pulse (B1 = 50 Hz, duration = 3 s) followed by a single-shot readout. Z spectral data were fitted pixel-wise with five Lorentzian functions, and maps of CrCEST peak amplitude, linewidth, and integral were produced. For comparison, single-voxel proton MR spectroscopy (1H-MRS) was performed to quantify and compare the total Cr concentration in the tumor. RESULTS: CrCEST contrasts decreased with tumor progression from weeks 3 to 4 in both 9L and F98 phenotypes. More importantly, F98 tumors had significantly lower CrCEST integral compared to 9L tumors. On the other hand, integrals of other Z-spectral components were unable to differentiate both tumor progression and phenotype with limited sample size. CONCLUSIONS: Given that F98 is a more aggressive tumor than 9L, this study suggests that CrCEST MRI may help differentiate gliomas with different aggressiveness.