Comparison of pulsed three-dimensional CEST acquisition schemes at 7 tesla: steady state versus pseudosteady state

Purpose: To compare two pulsed, volumetric chemical exchange saturation transfer (CEST) acquisition schemes: steady state (SS) and pseudosteady state (PS) for the same brain coverage, spatial/spectral resolution and scan time. Methods: Both schemes were optimized for maximum sensitivity to amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) effects through Bloch McConnell simulations, and compared in terms of sensitivity to APT and NOE effects, and to transmit field inhomogeneity. Five consented healthy volunteers were scanned on a 7 Tesla Philips MRsystem using the optimized protocols at three nominal B1 amplitudes: 1 mT, 2 mT, and 3 mT. Results: Region of interest based analysis revealed that PS is more sensitive (P < 0.05) to APT and NOE effects compared with SS at low B1 amplitudes (0.7–1.0 mT). Also, both sequences have similar dependence on the transmit field inhomogeneity. For the optimum CEST presaturation parameters (1 mT and 2 mT for APT and NOE, respectively), NOE is less sensitive to the inhomogeneity effects (15% signal to noise ratio [SNR] change for a B1 dropout of 40%) compared with APT (35% SNR change for a B1 dropout of 40%). Conclusion: For the same brain coverage, spatial/spectral resolution and scan time, at low power levels PS is more sensitive to the slow chemical exchange-mediated processes compared with SS

Relayed nuclear Overhauser enhancement sensitivity to membrane Cho phospholipids

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155956/1/mrm28258_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155956/2/mrm28258.pd

Endogenous chemical exchange saturation transfer (CEST) MR imaging for the diagnosis and therapy response assessment of brain tumors: A systematic review

Purpose: To generate a narrative synthesis of published data on the use of endogenous chemical exchange saturation transfer (CEST) MR imaging in brain tumors. Materials and Methods: A systematic database search (PubMed, Ovid Embase, Cochrane Library) was used to collate eligible studies. Two researchers independently screened publications according to predefined exclusion and inclusion criteria, followed by comprehensive data extraction. All included studies were subjected to a bias risk assessment using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Results: The electronic database search identified 430 studies, of which 36 studies fulfilled the inclusion criteria. The final selection of included studies was categorized into 5 groups as follows: grading gliomas, 19 studies (areas under the curve (AUC) 0.500-1.000); predicting molecular subtypes of gliomas, 5 studies (AUC 0.610-0.920); distinction of different brain tumor types, 7 studies (AUC 0.707-0.905); therapy response assessment, 3 studies (AUC not given) and differentiating recurrence from treatment-related changes, 5 studies (AUC 0.880- 0.980). A high bias risk was observed in a substantial proportion of studies. Conclusion: Endogenous CEST imaging offers valuable, potentially unique information in brain tumors, but its diagnostic accuracy remains incompletely known. Further research is required to assess the method’s role in support of molecular genetic diagnosis, to investigate its use in the post treatment phase, and to compare techniques with a view to standardization

The z-spectrum from human blood at 7T

Chemical Exchange Saturation Transfer (CEST) has been used to assess healthy and pathological tissue in both animals and humans. However, the CEST signal from blood has not been fully assessed. This paper presents the CEST and nuclear Overhauser enhancement (NOE) signals detected in human blood measured via z-spectrum analysis. We assessed the effects of blood oxygenation levels, haematocrit, cell structure and pH upon the z-spectrum in ex vivo human blood for different saturation powers at 7T. The data were analysed using Lorentzian difference (LD) model fitting and AREX (to compensate for changes in T1), which have been successfully used to study CEST effects in vivo. Full Bloch-McConnell fitting was also performed to provide an initial estimate of exchange rates and transverse relaxation rates of the various pools. CEST and NOE signals were observed at 3.5 ppm, -1.7ppm and -3.5 ppm and were found to originate primarily from the red blood cells (RBCs), although the amide proton transfer (APT) CEST effect, and NOEs showed no dependence upon oxygenation levels. Upon lysing, the APT and NOE signals fell significantly. Different pH levels in blood resulted in changes in both the APT and NOE (at -3.5ppm), which suggests that this NOE signal is in part an exchange relayed process. These results will be important for assessing in vivo z-spectra

MR-based protein imaging of the human brain by means of dualCEST

Chemical exchange saturation transfer (CEST) is an emerging magnetic resonance imaging (MRI) technique enabling indirect detection of low-concentration cellular compounds in living tissue by their magnetization transfer with water. In particular, protein-attributed CEST signals have been shown to provide valuable diagnostic information for various diseases. While conventional CEST approaches suffer from confounding signals from metabolites and macromolecules, the novel dual-frequency irradiation CEST (dualCEST) technique enables increased protein specificity by selectively detecting the intramolecular spin-diffusion. However, application of this technique has so far been limited to spectroscopic investigations of model solutions at ultrahigh magnetic field strengths. In this thesis, dualCEST was translated to a clinical whole-body MR scanner, enabling protein imaging of the human brain. To this end, several methodological developments were implemented and optimized: (i) improved dual-frequency pulses for signal preparation, (ii) a fast and robust volumetric image readout, (iii) a weighted acquisition scheme, and (iv) an adaptive denoising technique. The resulting improvements are not limited to dualCEST but are relevant for the research field of CEST-MRI in general. Extensive measurements of biochemical model solutions and volunteers demonstrated the protein specificity and reproducibility of dualCEST-MRI. The clinical applicability was verified in pilot studies with tumor and Alzheimer’s patients

In Vivo Application of Proton-Electron Double-Resonance Imaging

This work was partially supported by NIH grants 1ZIABC010477-14 (MKC), CA194013 (VVK), CA192064 (VVK), U54GM104942 (VVK); by KAKENHI grant 16H05113 (H.U.) from the Japan Society for the Promotion of Science (HU) and start-up grant from the WVCTSI (VVK).Peer reviewedPostprin

Evolution of Cerebral Ischemia Assessed by Amide Proton Transfer-Weighted MRI

In today’s stressful world, psychopathy (especially anxiety) is receiving increased importance. Most of the drugs used to treat this disease have several side effects. Medicinal plants derived from natural products have fewer side effects and can be used in the treatment of this disease. The aim of this study was to evaluate the effect of the hydroalcoholic extract of Rosmarinus officinalis L. on anxiety in mice. In this experimental study, 50 male mice were randomly divided into 5 groups. To evaluate anxiety, the Elevated Plus Maze test was performed. The control group received normal saline, the positive control group received diazepam (1 mg/kg) as intraperitoneal injection, and the experimental groups received doses of 100, 200, and 400 mg/kg body weight of rosemary extract. The data were analyzed using SPSS 15 and ANOVA statistical tests. The results show that rosemary extract dose-dependently increases the mice spending time and the entries number of mice in plus maze open arms (indicating less stress). This effect at a dose of 400 mg/kg was similar to diazepam, which, in comparison to the control group, was statistically significant ( P .05). On the other hand, the rosemary extract, similar to the standard drug diazepam, showed an anti-anxiety effect. This effect is probably due to the presence of flavonoids in this plant and their antioxidant property

The role of APT imaging in gliomas grading: A systematic review and meta-analysis

Purpose: Gliomas are diagnosed and staged by conventional MRI. Although non-conventional sequences such as perfusion-weighted MRI may differentiate low-grade from high-grade gliomas, they are not reliable enough yet. The latter is of paramount importance for patient management. In this regard, we aim to evaluate the role of Amide Proton Transfer (APT) imaging in grading gliomas as a non-invasive tool to provide reliable differentiation across tumour grades. Methods: A systematic search of PubMed, Medline and Embase was conducted to identify relevant publications between 01/01/2008 and 15/09/2020. Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used to assess studies’ quality. A random-effects model standardized mean difference meta-analysis was performed to assess APT's ability to differentiate low-grade gliomas (LGGs) from high-grade gliomas (HGGs), WHO 2–4 grades, wild-type from mutated isocitrate dehydrogenase (IDH) gliomas, methylated from unmethylated O6-methylguanine-DNA methyltransferase (MGMT) gliomas. Area under the curve (AUC) of the Receiver Operating Characteristic (ROC) meta-analysis was employed to assess the diagnostic performance of APT. Results: 23 manuscripts met the inclusion criteria and reported the use of APT to differentiate glioma grades with histopathology as reference standard. APT-weighted signal intensity can differentiate LGGs from HGGs with an estimated size effect of (-1.61 standard deviations (SDs), p < 0.0001), grade 2 from grade 3 (-1.83 SDs, p = 0.005), grade 2 from grade 4 (-2.34 SDs, p < 0.0001) and IDH wild-type from IDH mutated (0.94 SDs, p = 0.003) gliomas. The combined AUC of 0.84 highlights the good diagnostic performance of APT-weighted imaging in differentiating LGGs from HGGs. Conclusions: APT imaging is an exciting prospect in differentiating LGGs from HGGs and with potential to predict the histopathological grade. However, more studies are required to optimize and improve its reliability