Purpose The mammalian target of rapamycin is an enzyme that regulates cell metabolism and proliferation. It is up‐regulated in aggressive tumors, such as glioblastoma, leading to increased glucose uptake and consumption. It has been suggested that glucose CEST signals reflect the delivery and tumor uptake of glucose. The inhibitor rapamycin (sirolimus) has been applied as a glucose deprivation treatment; thus, glucose CEST MRI could potentially be useful for monitoring the tumor responses to inhibitor treatment. Methods A human U87‐EGFRvIII xenograft model in mice was studied. The mice were treated with a mammalian target of Rapamycin inhibitor, rapamycin . The effect of the treatment was evaluated in vivo with dynamic glucose CEST MRI. Results Rapamycin treatment led to significant increases ( P < 0.001) in dynamic glucose‐enhanced signal in both the tumor and contralateral brain as compared to the no‐treatment group, namely a maximum enhancement of 3.7% ± 2.3% (tumor, treatment) versus 1.9% ± 0.4% (tumor, no‐treatment), 1.7% ± 1.1% (contralateral, treatment), and 1.0% ± 0.4% (contralateral, no treatment). Dynamic glucose‐enhanced contrast remained consistently higher in treatment versus no‐treatment groups for the duration of the experiment (17 min). This was confirmed with area‐under‐curve analysis. Conclusion Increased glucose CEST signal was found after mammalian target of Rapamycin inhibition treatment, indicating potential for dynamic glucose‐enhanced MRI to study tumor response to glucose deprivation treatment.
Purpose Dynamic glucose‐enhanced (DGE) MRI relates to a group of exchange‐based MRI techniques where the uptake of glucose analogues is studied dynamically. However, motion artifacts can be mistaken for true DGE effects, while motion correction may alter true signal effects. The aim was to design a numerical human brain phantom to simulate a realistic DGE MRI protocol at 3T that can be used to assess the influence of head movement on the signal before and after retrospective motion correction. Methods MPRAGE data from a tumor patient were used to simulate dynamic Z‐spectra under the influence of motion. The DGE responses for different tissue types were simulated, creating a ground truth. Rigid head movement patterns were applied as well as physiological dilatation and pulsation of the lateral ventricles and head‐motion‐induced B 0 ‐changes in presence of first‐order shimming. The effect of retrospective motion correction was evaluated. Results Motion artifacts similar to those previously reported for in vivo DGE data could be reproduced. Head movement of 1 mm translation and 1.5 degrees rotation led to a pseudo‐DGE effect on the order of 1% signal change. B 0 effects due to head motion altered DGE changes due to a shift in the water saturation spectrum. Pseudo DGE effects were partly reduced or enhanced by rigid motion correction depending on tissue location. Conclusion DGE MRI studies can be corrupted by motion artifacts. Designing post‐processing methods using retrospective motion correction including B 0 correction will be crucial for clinical implementation. The proposed phantom should be useful for evaluation and optimization of such techniques.
Purpose To develop prospectively accelerated 3D CEST imaging using compressed sensing (CS), combined with a saturation scheme based on time‐interleaved parallel transmission. Methods A variable density pseudo‐random sampling pattern with a centric elliptical k‐space ordering was used for CS acceleration in 3D. Retrospective CS studies were performed with CEST phantoms to test the reconstruction scheme. Prospectively CS‐accelerated 3D‐CEST images were acquired in 10 healthy volunteers and 6 brain tumor patients with an acceleration factor (R CS ) of 4 and compared with conventional SENSE reconstructed images. Amide proton transfer weighted (APTw) signals under varied RF saturation powers were compared with varied acceleration factors. Results The APTw signals obtained from the CS with acceleration factor of 4 were well‐preserved as compared with the reference image (SENSE R = 2) both in retrospective phantom and prospective healthy volunteer studies. In the patient study, the APTw signals were significantly higher in the tumor region (gadolinium [Gd]‐enhancing tumor core) than in the normal tissue ( p < .001). There was no significant APTw difference between the CS‐accelerated images and the reference image. The scan time of CS‐accelerated 3D APTw imaging was dramatically reduced to 2:10 minutes (in‐plane spatial resolution of 1.8 1.8 mm 2 ; 15 slices with 4‐mm slice thickness) as compared with SENSE (4:07 minutes). Conclusion Compressed sensing acceleration was successfully extended to 3D‐CEST imaging without compromising CEST image quality and quantification. The CS‐based CEST imaging can easily be integrated into clinical protocols and would be beneficial for a wide range of applications.
Motivation: Many long-COVID patients experience fatigue and post exertional malaise which are primary symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Understanding the similarities and differences between long-COVID and classic ME/CFS could provide insights into the disease mechanisms. Goal(s): To measure brain anatomy and oxygen metabolism between the two groups. Approach: Clinical standard and advanced MRI techniques measuring the venous oxygenation were applied. The fatigue level was assessed by questionnaires. Results: No differences in brain anatomy were observed between the groups, but the long-COVID group had significant lower venous oxygenation than the healthy control group and the classic CFS group. Impact: Many long-COVID patients fulfill diagnostic criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Compared to structural changes, metabolism-related parameters, such as venous oxygenation of the brain, may be more sensitive to changes related to long-COVID and CFS disease mechanisms.
To develop a pulsed CEST magnetization-transfer method for rapidly acquiring relayed nuclear Overhauser enhancement (rNOE)-weighted images with magnetic transfer contrast (MTC) suppression at clinical field strength (3 T).Using a pulsed CEST magnetization-transfer method with low saturation powers (B1 ) and long mixing time (tmix ) to suppress contributions due to strong MTC from solid-like macromolecules, a low B1 also minimized direct water saturation. These MTC contributions were further reduced by subtracting the Z-spectral signals at two or three offsets by assuming that the residual MTC is a linear function between -3.5 ppm and -12.5 ppm.Phantom studies of a lactic acid (Lac) solution mixed with cross-linked bovine serum albumin show that strong MTC interference has a significant impact on the optimum B1 for detecting rNOEs, due to lactate binding. The MTC could be effectively suppressed using a pulse train with a B1 of 0.8 μT, a pulse duration (tp ) of 40 ms, a tmix of 60 ms, and a pulse number (N) of 30, while rNOE signal was well maintained. As a proof of concept, we applied the method in mouse brain with injected hydrogel and a cell-hydrogel phantom. Results showed that rNOE-weighted images could provide good contrast between brain/cell and hydrogel.The developed pulsed CEST magnetization-transfer method can achieve MTC suppression while preserving most of the rNOE signal at 3 T, which indicates the potential for translation of this technique to clinical applications related to mobile proteins/lipids change.
Abstract The present study was designed to investigate the role of amylin, H2S, and connexin 43 in vascular dysfunction and enhanced ischemia–reperfusion (I/R)-induced myocardial injury in diabetic rats. A single dose of streptozotocin (65 mg/kg) was employed to induce diabetes mellitus. After 8 weeks, there was a significant decrease in the plasma levels of amylin, an increase in I/R injury to isolated hearts (increase in CK-MB and cardiac troponin release) on the Langendorff apparatus. Moreover, there was a significant impairment in vascular endothelium function as assessed by quantifying acetylcholine-induced relaxation in norepinephrine-precontracted mesenteric arteries. There was also a marked decrease in the expression of H2S and connexin 43 in the hearts following I/R injury in diabetic rats. Treatment with amylin agonist, pramlintide (100 and 200 µg/kg), and H2S donor, NaHS (10 and 20 μmol/kg) for 2 weeks improved the vascular endothelium function, abolished enhanced myocardial injury and restored the levels of H2S along with connexin 43 in diabetic animals. However, pramlintide and NaHS failed to produce these effects the presence of gap junction blocker, carbenoxolone (20 and 40 mg/kg). Carbenoxolone also abolished the myocardial levels of connexin 43 without affecting the plasma levels of amylin and myocardial levels of H2S. The decrease in the amylin levels with a consequent reduction in H2S and connexin 43 may contribute to inducing vascular dysfunction and enhancing I/R-induced myocardial injury in diabetic rats.
Glycogen plays a central role in glucose homeostasis and is abundant in several types of tissue. We report an MRI method for imaging glycogen noninvasively with enhanced detection sensitivity and high specificity, using the magnetic coupling between glycogen and water protons through the nuclear Overhauser enhancement (NOE). We show in vitro that the glycogen NOE (glycoNOE) signal is correlated linearly with glycogen concentration, while pH and temperature have little effect on its intensity. For validation, we imaged glycoNOE signal changes in mouse liver, both before and after fasting and during glucagon infusion. The glycoNOE signal was reduced by 88 ± 16% ( n = 5) after 24 h of fasting and by 76 ± 22% ( n = 5) at 1 h after intraperitoneal (i.p.) injection of glucagon, which is known to rapidly deplete hepatic glycogen. The ability to noninvasively image glycogen should allow assessment of diseases in which glucose metabolism or storage is altered, for instance, diabetes, cardiac disease, muscular disorders, cancer, and glycogen storage diseases.
Site-specific spin polarization labeling of a peptide was conducted by homogeneous hydrogenation with parahydrogen. Surprisingly, polarization transfer to a remote alanine residue was observed. The diastereoselectivity of the hydrogenation reaction was determined, and these results show that parahydrogen can be used to enhance signals and elucidate the hydrogenation processes of dehydropeptide units in complex molecules.
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