The current study aims to assign and estimate the total creatine (tCr) signal contribution to the Z-spectrum in mouse brain at 11.7 Tesla. Creatine (Cr), phosphocreatine (PCr) and protein phantoms were used to confirm presence of a guanidinium resonance at this field strength. Wild type (WT) and knockout mice with Guanidinoacetate N-Methyltransferase deficiency (GAMT−/−) that have low Cr and PCr concentrations in the brain were used to assign the tCr contribution to the Z-spectrum. To estimate the total guanidinium concentrations, two pools for the Z-spectrum around 2 ppm were assumed: (i) a Lorentzian function representing the guanidinium CEST at 1.95 ppm in the 11.7 T Z-spectrum; (ii) a background signal that can be fitted by a polynomial function. Comparison between the WT and GAMT−/− mice provided strong evidence for three types of contributions to the peak in the Z-spectrum at 1.95 ppm, namely proteins, Cr and PCr, the latter fitted as tCr. A ratio of 20±7% (Protein) and 80±7% tCr was found in brain with 2 μT and 2 s saturation. Based on phantom experiments, the tCr peak was estimated to consist of about 83±5% Cr and 17±5% PCr. Maps for tCr of mouse brain were generated based on the peak at 1.95 ppm after concentration calibration with in vivo MRS.

IB consisting of CMV, HSV-1, B. burgdorferi, C. pneumoniae and H. pylori is associated with AD. This study supports the role of infection/inflammation in the etiopathogenesis of AD.

Purpose Recently, natural d-glucose was suggested as a potential biodegradable contrast agent. The feasibility of using d-glucose for dynamic perfusion imaging was explored to detect malignant brain tumors based on blood brain barrier breakdown. Methods Mice were inoculated orthotopically with human U87-EGFRvIII glioma cells. Time-resolved glucose signal changes were detected using chemical exchange saturation transfer (glucoCEST) MRI. Dynamic glucose enhanced (DGE) MRI was used to measure tissue response to an intravenous bolus of d-glucose. Results DGE images of mouse brains bearing human glioma showed two times higher and persistent changes in tumor compared to contralateral brain. Area-under-curve (AUC) analysis of DGE delineated blood vessels and tumor and had contrast comparable to the AUC determined using dynamic contrast enhanced (DCE) MRI with GdDTPA, both showing a significantly higher AUC in tumor than in brain (p<0.005). Both CEST and relaxation effects contribute to the signal change. Conclusion DGE MRI is a feasible technique for studying brain tumor enhancement reflecting differences in tumor blood volume and permeability with respect to normal brain. We expect DGE will provide a low-risk and less expensive alternative to DCE MRI for imaging cancer in vulnerable populations, such as children and patients with renal impairment.

Recent animal studies have shown that D-glucose is a potential biodegradable MRI contrast agent for imaging glucose uptake in tumors. Here, we show the first translation of that use of D-glucose to human studies. Chemical exchange saturation transfer (CEST) MRI at a single frequency offset optimized for detection of hydroxyl protons in D-glucose (glucoCEST) was used to image dynamic signal changes in the human brain at 7T during and after infusion of D-glucose. Dynamic glucose-enhanced (DGE) image data from four normal volunteers and three glioma patients showed strong signal enhancement in blood vessels, while the enhancement varied spatially over the tumor. Areas of enhancement differed spatially between DGE and conventional Gd-enhanced imaging, suggesting complementary image information content for these two types of agents. In addition, different tumor areas enhanced with D-glucose at different times post-infusion, suggesting a sensitivity to perfusion-related properties such as substrate delivery and blood-brain barrier (BBB) permeability. These preliminary results suggest that DGE MRI is feasible to study glucose uptake in humans, providing a time-dependent set of data that contains information regarding arterial input function (AIF), tissue perfusion, glucose transport across the BBB and cell membrane, and glucose metabolism.

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.

Alzheimer’s disease (AD) is one of most devastating diseases affecting elderly people. Amyloid-β (Aβ) accumulation and the downstream pathological events such as oxidative stress play critical roles in pathogenesis of AD. Lessons from failures of current clinical trials suggest that targeting multiple key pathways of the AD pathogenesis is necessary to halt the disease progression. Here we show that Edaravone, a free radical scavenger that is marketed for acute ischemic stroke, has a potent capacity of inhibiting Aβ aggregation and attenuating Aβ-induced oxidation in vitro. When given before or after the onset of Aβ deposition via i.p. injection, Edaravone substantially reduces Aβ deposition, alleviates oxidative stress, attenuates the downstream pathologies including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, synaptic dysfunction, and rescues the behavioral deficits of APPswe/PS1 mice. Oral administration of Edaravone also ameliorates the AD-like pathologies and memory deficits of the mice. These findings suggest that Edaravone holds a promise as a therapeutic agent for AD by targeting multiple key pathways of the disease pathogenesis.

Purpose To use the Variable Delay Multi-Pulse (VDMP) CEST approach to obtain clean Amide Proton Transfer (APT) and relayed Nuclear Overhauser (rNOE) Chemical Exchange Saturation Transfer (CEST) images in human brain by suppressing the conventional magnetization transfer contrast (MTC) and reducing the direct water saturation (DS) contribution. Methods The VDMP CEST scheme consists of a train of RF pulses with a specific mixing time. The CEST signal with respect to the mixing time shows distinguishable characteristics for protons with different exchange rates. Exchange rate filtered CEST images are generated by subtracting images acquired at two mixing times at which the MTC signals are equal, while the APT and rNOE-CEST signals differ. Since the subtraction is done at the same frequency offset for each voxel and the CEST signals are broad, no B0 correction is needed. Results MTC-suppressed APT and rNOE-CEST images of human brain were obtained using the VDMP method. The APT-CEST data shows hyper-intensity in gray matter versus white matter while the rNOE-CEST images show negligible contrast between gray and white matter. Conclusion The VDMP approach provides a simple and rapid way of recording MTC-suppressed APT-CEST and rNOE-CEST images without a need for B0 field correction.

Purpose Dynamic glucose enhanced (DGE) MRI has shown potential for imaging glucose delivery and blood–brain barrier permeability at fields of 7T and higher. Here, we evaluated issues involved with translating d‐glucose weighted chemical exchange saturation transfer (glucoCEST) experiments to the clinical field strength of 3T. Methods Exchange rates of the different hydroxyl proton pools and the field‐dependent T2 relaxivity of water in d‐glucose solution were used to simulate the water saturation spectra (Z‐spectra) and DGE signal differences as a function of static field strength B0, radiofrequency field strength B1, and saturation time tsat. Multislice DGE experiments were performed at 3T on 5 healthy volunteers and 3 glioma patients. Results Simulations showed that DGE signal decreases with B0, because of decreased contributions of glucoCEST and transverse relaxivity, as well as coalescence of the hydroxyl and water proton signals in the Z‐spectrum. At 3T, because of this coalescence and increased interference of direct water saturation and magnetization transfer contrast, the DGE effect can be assessed over a broad range of saturation frequencies. Multislice DGE experiments were performed in vivo using a B1 of 1.6 µT and a tsat of 1 second, leading to a small glucoCEST DGE effect at an offset frequency of 2 ppm from the water resonance. Motion correction was essential to detect DGE effects reliably. Conclusion Multislice glucoCEST‐based DGE experiments can be performed at 3T with sufficient temporal resolution. However, the effects are small and prone to motion influence. Therefore, motion correction should be used when performing DGE experiments at clinical field strengths.