| 1. |
- Huang, Jianpan, et al.
(författare)
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Altered d-glucose in brain parenchyma and cerebrospinal fluid of early Alzheimer's disease detected by dynamic glucose-enhanced MRI
- 2020
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 6:20
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Tidskriftsartikel (refereegranskat)abstract
- Altered cerebral glucose uptake is one of the hallmarks of Alzheimer's disease (AD). A dynamic glucose-enhanced (DGE) magnetic resonance imaging (MRI) approach was developed to simultaneously monitor d-glucose uptake and clearance in both brain parenchyma and cerebrospinal fluid (CSF). We observed substantially higher uptake in parenchyma of young (6 months) transgenic AD mice compared to age-matched wild-type (WT) mice. Notably lower uptakes were observed in parenchyma and CSF of old (16 months) AD mice. Both young and old AD mice had an obviously slower CSF clearance than age-matched WT mice. This resembles recent reports of the hampered CSF clearance that leads to protein accumulation in the brain. These findings suggest that DGE MRI can identify altered glucose uptake and clearance in young AD mice upon the emergence of amyloid plaques. DGE MRI of brain parenchyma and CSF has potential for early AD stratification, especially at 3T clinical field strength MRI.
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| 2. |
- Han, Zheng, et al.
(författare)
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Dynamic contrast-enhanced CEST MRI using a low molecular weight dextran
- 2022
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Ingår i: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 35:3
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Tidskriftsartikel (refereegranskat)abstract
- Natural and synthetic sugars have great potential for developing highly biocompatible and translatable chemical exchange saturation transfer (CEST) MRI contrast agents. In this study, we aimed to develop the smallest clinically available form of dextran, Dex1 (molecular weight, MW ~ 1 kDa), as a new CEST agent. We first characterized the CEST properties of Dex1 in vitro at 11.7 T and showed that the Dex1 had a detectable CEST signal at ~1.2 ppm, attributed to hydroxyl protons. In vivo CEST MRI studies were then carried out on C57BL6 mice bearing orthotopic GL261 brain tumors (n = 5) using a Bruker BioSpec 11.7 T MRI scanner. Both steady-state full Z-spectral images and single offset (1.2 ppm) dynamic dextran-enhanced (DDE) images were acquired before and after the intravenous injection of Dex1 (2 g/kg). The steady-state Z-spectral analysis showed a significantly higher CEST contrast enhancement in the tumor than in contralateral brain (∆MTRasym 1.2 ppm = 0.010 ± 0.006 versus 0.002 ± 0.008, P = 0.0069) at 20 min after the injection of Dex1. Pharmacokinetic analyses of DDE were performed using the area under the curve (AUC) in the first 10 min after Dex1 injection, revealing a significantly higher uptake of Dex1 in the tumor than in brain tissue for tumor-bearing mice (AUC[0-10 min] = 21.9 ± 4.2 versus 5.3 ± 6.4%·min, P = 0.0294). In contrast, no Dex1 uptake was foundling in the brains of non-tumor-bearing mice (AUC[0-10 min] = -1.59 ± 2.43%·min). Importantly, the CEST MRI findings were consistent with the measurements obtained using DCE MRI and fluorescence microscopy, demonstrating the potential of Dex1 as a highly translatable CEST MRI contrast agent for assessing tumor hemodynamics.
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| 3. |
- Knutsson, Linda, et al.
(författare)
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Imaging of sugar-based contrast agents using their hydroxyl proton exchange properties
- 2023
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Ingår i: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 36:6
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Tidskriftsartikel (refereegranskat)abstract
- The ability of CEST MRI to detect the presence of millimolar concentrations of non-metallic contrast agents has made it possible to study, noninvasively, important biological molecules such as proteins and sugars, as well as drugs already approved for clinical use. Here, we review efforts to use sugar and sugar polymers as exogenous contrast agents, which is possible based on the exchange of their hydroxyl protons with water protons. While this capability has raised early enthusiasm, for instance about the possibility to image D-glucose metabolism with MRI in a way analogous to PET, experience over the past decade has shown that this is not trivial. On the other hand, many studies have confirmed the possibility to image a large variety of sugar analogues, each with potentially interesting applications to assess tissue physiology. Some promising applications are the study of (i) sugar delivery and transport to assess blood brain barrier integrity, (ii) sugar uptake by cells for their characterization (e.g. cancer vs healthy), as well as (iii) clearance of sugars to assess tissue drainage for instance through the glymphatic system. To judge these opportunities and their challenges, especially in the clinic, it is needed to understand the technical aspects of detecting the presence of rapidly exchanging protons through the water signal in MRI, especially as a function of magnetic field strength. We expect that novel approaches in terms of MRI detection (both saturation transfer and relaxation based), MRI data analysis, and sugar design will push this young field forward in the next decade.
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| 4. |
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| 5. |
- Xu, Xiang, et al.
(författare)
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The effect of the mTOR inhibitor rapamycin on glucoCEST signal in a preclinical model of glioblastoma
- 2019
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194. ; 81:6, s. 3798-3807
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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