Cardiac chemical exchange saturation transfer-magnetic resonance imaging (CEST-MRI) has been used to probe levels of various metabolites that provide insight into myocardial structure and function. However, imaging of the heart using CEST-MRI is prolonged by the need to repeatedly acquire multiple images for a full Z-spectrum and to perform saturation and acquisition around cardiac and respiratory cycles. Compressed sensing (CS) reconstruction of sparse data enables accelerated acquisition, but reconstruction artifacts may bias subsequently derived measures of CEST contrast. In this study, we examine the impact of CS reconstruction of increasingly under-sampled cardiac CEST-MRI data on subsequent CEST contrasts of amine-containing metabolites and amide-containing proteins. Cardiac CEST-MRI data sets were acquired in six mice using low and high RF saturation for single and dual contrast generation, respectively. CEST-weighted images were reconstructed using CS methods at 2–5× levels of under-sampling. CEST contrasts were derived from corresponding Z-spectra and the impact of accelerated imaging on accuracy was assessed via analysis of variance. CS reconstruction preserved myocardial signal to noise ratio as compared to conventional reconstruction. However, greater absolute error and distribution of derived contrasts was observed with increasing acceleration factors. The results from this study indicate that acquisition of radial cardiac CEST-MRI data can be modestly, but meaningfully, accelerated via CS reconstructions with little error in CEST contrast quantification.
During four solar eclipse events (two annular, one total and one partial) a correlation was observed between a change in water surface tension and the magnitude of the optical coverage. During one eclipse, evaporation experiments were carried out which showed a reduction in water evaporation at the same time as a rise in the surface tension. The changes did not occur on a day without a solar eclipse and are not correlated to changes in temperature, pressure, humidity of the environment. The effects are delayed by 20, 85, 30 and 37 min, respectively, compared to the maximum eclipse. Possible mechanisms responsible for this effect are presented, the most likely hypothesis being reduced water/muon interaction due to solar wind and cosmic radiation blocking during an eclipse. As an alternative hypotheses, we propose a novel neutrino/water interaction and overview of other, less likely mechanisms.
Purpose: Gene therapy employing AAV vector-mediated gene delivery has undergone substantial growth in recent years with promising results in both preclinical and clinical studies, as well as emerging regulatory approval. However, the lack of methods for quantifying the efficacy of gene therapy from cellular delivery of gene editing technology to specific functional outcomes remains an obstacle for the efficient development of gene therapy treatments. Building upon prior works that utilized a genetically encoded Lysine Rich Protein as a chemical exchange saturation transfer (CEST) reporter, we hypothesized that AAV viral capsids may generate endogenous CEST contrast from the large number of surface lysine residues. Methods: Water-suppressed NMR and NMR-CEST experiments were performed on isolated solutions of AAV serotypes 1-9 on a Bruker 800MHz vertical scanner. A series of in vitro experiments were performed for thorough testing of NMR-CEST contrast of AAV2 capsids under varying pH, density, biological transduction stage, and later across multiple serotypes and mixed biological media. Reverse transcriptase (RT)-polymerase chain reaction (PCR) was used to quantify virus concentration. Subsequent experiments determined the pH-dependent exchange rate and optimized CEST saturation schemes for AAV contrast detection at 7 T. Results: NMR-CEST experiments revealed CEST contrast up to 52% for AAV2 viral capsids between 0.6-0.8 ppm. Evaluation of CEST contrast generated by AAV2 demonstrates high levels of CEST contrast across a variety of chemical environments, concentrations, and saturation schemes. AAV2 CEST contrast displayed significant positive correlations with capsid density (R2>0.99, P<0.001), pH (R2=0.97, P=0.01), and viral titer per cell count (R2=0.92, P<0.001). Transition to a preclinical field strength yielded up to 11.8% CEST contrast following optimization of saturation parameters. Conclusion: AAV2 viral capsids exhibit strong capacity as an endogenous CEST contrast agent and can potentially be used for monitoring and evaluation of AAV vector-mediated gene therapy protocols.
PurposeCEST MRI has been used to probe changes in cardiac metabolism via assessment of CEST contrast from Cr. However, B1 variation across the myocardium leads to spatially variable Cr CEST contrast in healthy myocardium.MethodsWe developed a spatial–spectral (SPSP) saturation pulsed CEST protocol to compensate for B1 variation. Flip angle maps were used to individually tailor SPSP pulses comprised of a train of one‐dimensional spatially selective subpulses selective along the principal B1 gradient dimension. Complete Z‐spectra in the hearts of (n = 10) healthy individuals were acquired using conventional Gaussian saturation and SPSP schemes and supported by phantom studies.ResultsIn simulations, the use of SPSP pulses reduced the average SD of the effective saturation B1 values within the myocardium (n = 10) from 0.12 ± 0.02 μT to 0.05 ± 0.01 μT (p < 0.01) and reduced the average SD of Cr CEST contrast in vivo from 10.0 ± 4.3% to 6.1 ± 3.5% (p < 0.05). Results from the hearts of human subjects showed a significant reduction of CEST contrast distribution at 2 ppm, as well as amplitude, when using SPSP saturation. Corresponding phantom experiments revealed PCr‐specific contrast generation at body temperature when SPSP saturation was used but combined PCr and Cr contrast generation when Gaussian saturation was used.ConclusionThe use of SPSP saturation pulsed CEST resulted in PCr‐specific contrast generation and enabled ratiometric mapping of PCr to total Cr CEST contrast in the human heart at 3T.
Chemical Exchange Saturation Transfer (CEST) MRI is highly susceptible to B1 inhomogeneities, resulting in inconsistent contrast for tissues with equal metabolite concentrations. To enhance B1-uniformity of saturation across the myocardium, a spectral-spatially selective pulse for CEST preparation was tailored for each subject. Simulations showed the tailored pulse reduced B1 variation from 6.85⁰ to 2.9⁰. These results were investigated on a Siemens 3T Trio scanner by performing full cardiac CEST exams using a conventional Gaussian or a tailored pulse for saturation. The tailored pulse resulted in reduced water and MT contrast variation across the myocardium when compared to the conventional pulse.
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