| 1. |
- Knutsson, Linda, et al.
(författare)
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Dynamic Susceptibility Contrast MRI at 7 T:Tail-Scaling Analysis and Inferences About Field Strength Dependence
- 2017
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Ingår i: Tomography : a journal for imaging research. - : MDPI AG. - 2379-1381. ; 3:2, s. 8-74
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Tidskriftsartikel (refereegranskat)abstract
- Dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) following bolus injection of gadolinium contrast agent (CA) is widely used for the estimation of brain perfusion parameters such as cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) for both clinical and research purposes. Although it is predicted that DSC-MRI will have superior performance at high magnetic field strengths, to the best of our knowledge, there are no reports of 7 T DSC-MRI in the literature. It is plausible that the transfer of DSC-MRI to 7 T may be accompanied by increased R2* relaxivity in tissue and a larger difference in ΔR2*-versus-concentration relationships between tissue and large vessels. If not accounted for, this will subsequently result in apparent CBV and CBF estimates that are higher than those reported previously at lower field strengths. The aims of this study were therefore to assess the feasibility of 7 T DSC-MRI and to investigate the apparent field-strength dependence of CBV and CBF estimates. In total, 8 healthy volunteers were examined using DSC-MRI at 7 T. A reduced CA dose of 0.05 mmol/kg was administered to decrease susceptibility artifacts. CBV, CBF, and MTT maps were calculated using standard DSC-MRI tracer-kinetic theory. Subject-specific arterial partial volume correction factors were obtained using a tail-scaling approach. Compared with literature values obtained using the tail-scaling approach at 1.5 T and 3 T, the CBV and CBF values of the present study were found to be further overestimated. This observation is potentially related to an inferred field-strength dependence of transverse relaxivities, although issues related to the CA dose must also be considered.
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| 2. |
- van Zijl, Peter C. M., et al.
(författare)
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Hyperpolarized MRI, functional MRI, MR spectroscopy and CEST to provide metabolic information in vivo
- 2021
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Ingår i: Current Opinion in Chemical Biology. - : Elsevier BV. - 1367-5931. ; 63, s. 209-218
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Tidskriftsartikel (refereegranskat)abstract
- Access to metabolic information in vivo using magnetic resonance (MR) technologies has generally been the niche of MR spectroscopy (MRS) and spectroscopic imaging (MRSI). Metabolic fluxes can be studied using the infusion of substrates labeled with magnetic isotopes, with the use of hyperpolarization especially powerful. Unfortunately, these promising methods are not yet accepted clinically, where fast, simple, and reliable measurement and diagnosis are key. Recent advances in functional MRI and chemical exchange saturation transfer (CEST) MRI allow the use of water imaging to study oxygen metabolism and tissue metabolite levels. These, together with the use of novel data analysis approaches such as machine learning for all of these metabolic MR approaches, are increasing the likelihood of their clinical translation.
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| 3. |
- Xu, Xiang, et al.
(författare)
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Dynamic Glucose-Enhanced (DGE) MRI: Translation to Human Scanning and First Results in Glioma Patients.
- 2015
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Ingår i: Tomography : a journal for imaging research. - : MDPI AG. - 2379-1381. ; 1:2, s. 105-114
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 4. |
- Zhou, Jinyuan, et al.
(författare)
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Review and consensus recommendations on clinical APT-weighted imaging approaches at 3T : Application to brain tumors
- 2022
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 1522-2594 .- 0740-3194. ; 88:2, s. 546-574
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Tidskriftsartikel (refereegranskat)abstract
- Amide proton transfer-weighted (APTw) MR imaging shows promise as a biomarker of brain tumor status. Currently used APTw MRI pulse sequences and protocols vary substantially among different institutes, and there are no agreed-on standards in the imaging community. Therefore, the results acquired from different research centers are difficult to compare, which hampers uniform clinical application and interpretation. This paper reviews current clinical APTw imaging approaches and provides a rationale for optimized APTw brain tumor imaging at 3 T, including specific recommendations for pulse sequences, acquisition protocols, and data processing methods. We expect that these consensus recommendations will become the first broadly accepted guidelines for APTw imaging of brain tumors on 3 T MRI systems from different vendors. This will allow more medical centers to use the same or comparable APTw MRI techniques for the detection, characterization, and monitoring of brain tumors, enabling multi-center trials in larger patient cohorts and, ultimately, routine clinical use.
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| 5. |
- Cao, Di, et al.
(författare)
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Concurrent measurement of perfusion parameters related to small blood vessels and cerebrospinal fluid circulation in the human brain using dynamic dual-spin-echo perfusion MRI
- 2023
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Ingår i: NMR in Biomedicine. - 0952-3480. ; 36:10
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Tidskriftsartikel (refereegranskat)abstract
- Accumulating evidence from recent studies has indicated the importance of studying the interaction between the microvascular and lymphatic systems in the brain. To date, most imaging methods can only measure blood or lymphatic vessels separately, such as dynamic susceptibility contrast (DSC) MRI for blood vessels and DSC MRI-in-the-cerebrospinal fluid (CSF) (cDSC MRI) for lymphatic vessels. An approach that can measure both blood and lymphatic vessels in a single scan offers advantages such as a halved scan time and contrast dosage. This study attempts to develop one such approach by optimizing a dual-echo turbo-spin-echo sequence, termed "dynamic dual-spin-echo perfusion (DDSEP) MRI". Bloch simulations were performed to optimize the dual-echo sequence for the measurement of gadolinium (Gd)-induced blood and CSF signal changes using a short and a long echo time, respectively. The proposed method furnishes a T1-dominant contrast in CSF and a T2-dominant contrast in blood. MRI experiments were performed in healthy subjects to evaluate the dual-echo approach by comparing it with existing separate methods. Based on simulations, the short and long echo time were chosen around the time when blood signals show maximum difference between post- and pre-Gd scans, and the time when blood signals are completely suppressed, respectively. The proposed method showed consistent results in human brains as previous studies using separate methods. Signal changes from small blood vessels occurred faster than from lymphatic vessels after intravenous Gd injection. In conclusion, Gd-induced signal changes in blood and CSF can be detected simultaneously in healthy subjects with the proposed sequence. The temporal difference in Gd-induced signal changes from small blood and lymphatic vessels after intravenous Gd injection was confirmed using the proposed approach in the same human subjects. Results from this proof-of-concept study will be used to further optimize DDSEP MRI in subsequent studies.
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| 6. |
- 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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| 7. |
- 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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| 8. |
- Knutsson, Linda, et al.
(författare)
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Arterial Input Functions and Tissue Response Curves in Dynamic Glucose-Enhanced (DGE) Imaging: Comparison Between glucoCEST and Blood Glucose Sampling in Humans
- 2018
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Ingår i: Tomography : a journal for imaging research. - : MDPI AG. - 2379-1381. ; 4:4, s. 164-171
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Tidskriftsartikel (refereegranskat)abstract
- Dynamic glucose-enhanced (DGE) imaging uses chemical exchange saturation transfer magnetic resonance imaging to retrieve information about the microcirculation using infusion of a natural sugar (D-glucose). However, this new approach is not yet well understood with respect to the dynamic tissue response. DGE time curves for arteries, normal brain tissue, and cerebrospinal fluid (CSF) were analyzed in healthy volunteers and compared with the time dependence of sampled venous plasma blood glucose levels. The arterial response curves (arterial input function [AIF]) compared reasonably well in shape with the time curves of the sampled glucose levels but could also differ substantially. The brain tissue response curves showed mainly negative responses with a peak intensity that was of the order of 10 times smaller than the AIF peak and a shape that was susceptible to both noise and partial volume effects with CSF, attributed to the low contrast-to-noise ratio. The CSF response curves showed a rather large and steady increase of the glucose uptake during the scan, due to the rapid uptake of D-glucose in CSF. Importantly, and contrary to gadolinium studies, the curves differed substantially among volunteers, which was interpreted to be caused by variations in insulin response. In conclusion, while AIFs and tissue response curves can be measured in DGE experiments,partial volume effects, low concentration of D-glucose in tissue, and osmolality effects between tissue and blood may prohibit quantification of normal tissue perfusion parameters. However, separation of tumor responses from normal tissue responses would most likely be feasible.
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| 9. |
- Knutsson, Linda, et al.
(författare)
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CEST, ASL, and magnetization transfer contrast : How similar pulse sequences detect different phenomena
- 2018
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194. ; 80:4, s. 1320-1340
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Forskningsöversikt (refereegranskat)abstract
- Chemical exchange saturation transfer (CEST), arterial spin labeling (ASL), and magnetization transfer contrast (MTC) methods generate different contrasts for MRI. However, they share many similarities in terms of pulse sequences and mechanistic principles. They all use RF pulse preparation schemes to label the longitudinal magnetization of certain proton pools and follow the delivery and transfer of this magnetic label to a water proton pool in a tissue region of interest, where it accumulates and can be detected using any imaging sequence. Due to the versatility of MRI, differences in spectral, spatial or motional selectivity of these schemes can be exploited to achieve pool specificity, such as for arterial water protons in ASL, protons on solute molecules in CEST, and protons on semi-solid cell structures in MTC. Timing of these sequences can be used to optimize for the rate of a particular delivery and/or exchange transfer process, for instance, between different tissue compartments (ASL) or between tissue molecules (CEST/MTC). In this review, magnetic labeling strategies for ASL and the corresponding CEST and MTC pulse sequences are compared, including continuous labeling, single-pulse labeling, and multi-pulse labeling. Insight into the similarities and differences among these techniques is important not only to comprehend the mechanisms and confounds of the contrasts they generate, but also to stimulate the development of new MRI techniques to improve these contrasts or to reduce their interference. This, in turn, should benefit many possible applications in the fields of physiological and molecular imaging and spectroscopy.
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| 10. |
- 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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