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Deuterium metabolic imaging - Back to the future.
De Feyter, HM, de Graaf, RA
Journal of magnetic resonance (San Diego, Calif. : 1997). 2021;:106932
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Abstract
Deuterium metabolic spectroscopy (DMS) and imaging (DMI) have recently been described as simple and robust MR-based methods to map metabolism with high temporal and/or spatial resolution. The metabolic fate of a wide range of suitable deuterated substrates, including glucose and acetate, can be monitored with deuterium MR methods in which the favorable MR characteristics of deuterium prevent many of the complications that hamper other techniques. The short T1 relaxation times lead to good MR sensitivity, while the low natural abundance prevents the need for water or lipid suppression. The sparsity of the deuterium spectra in combination with the low resonance frequency provides relative immunity to magnetic field inhomogeneity. Taken together, these features combine into a highly robust metabolic imaging method that has strong potential to become a dominant MR research tool and a viable clinical imaging modality. This perspective reviews the history of deuterium as a metabolic tracer, the use of NMR as a detection method for deuterium in vitro and in vivo and the recent development of DMS and DMI. Following a review of the NMR characteristics and the biological effects of deuterium, the promising future of DMI is outlined.
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Myocardial inflammation and energetics by cardiac MRI: a review of emerging techniques.
Tsampasian, V, Swift, AJ, Assadi, H, Chowdhary, A, Swoboda, P, Sammut, E, Dastidar, A, Cabrero, JB, Del Val, JR, Nair, S, et al
BMC medical imaging. 2021;(1):164
Abstract
The role of inflammation in cardiovascular pathophysiology has gained a lot of research interest in recent years. Cardiovascular Magnetic Resonance has been a powerful tool in the non-invasive assessment of inflammation in several conditions. More recently, Ultrasmall superparamagnetic particles of iron oxide have been successfully used to evaluate macrophage activity and subsequently inflammation on a cellular level. Current evidence from research studies provides encouraging data and confirms that this evolving method can potentially have a huge impact on clinical practice as it can be used in the diagnosis and management of very common conditions such as coronary artery disease, ischaemic and non-ischaemic cardiomyopathy, myocarditis and atherosclerosis. Another important emerging concept is that of myocardial energetics. With the use of phosphorus magnetic resonance spectroscopy, myocardial energetic compromise has been proved to be an important feature in the pathophysiological process of several conditions including diabetic cardiomyopathy, inherited cardiomyopathies, valvular heart disease and cardiac transplant rejection. This unique tool is therefore being utilized to assess metabolic alterations in a wide range of cardiovascular diseases. This review systematically examines these state-of-the-art methods in detail and provides an insight into the mechanisms of action and the clinical implications of their use.
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MR imaging and spectroscopy in degenerative ataxias: toward multimodal, multisite, multistage monitoring of neurodegeneration.
Öz, G, Harding, IH, Krahe, J, Reetz, K
Current opinion in neurology. 2020;(4):451-461
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PURPOSE OF REVIEW Degenerative ataxias are rare and currently untreatable movement disorders, primarily characterized by neurodegeneration in the cerebellum and brainstem. We highlight MRI studies with the most potential for utility in pending ataxia trials and underscore advances in disease characterization and diagnostics in the field. RECENT FINDINGS With availability of advanced MRI acquisition methods and specialized software dedicated to the analysis of MRI of the cerebellum, patterns of cerebellar atrophy in different degenerative ataxias are increasingly well defined. The field further embraced rigorous multimodal investigations to study network-level microstructural and functional brain changes and their neurochemical correlates. MRI and magnetic resonance spectroscopy were shown to be more sensitive to disease progression than clinical scales and to detect abnormalities in premanifest mutation carriers. SUMMARY Magnetic resonance techniques are increasingly well placed for characterizing the expression and progression of degenerative ataxias. The most impactful work has arguably come through multi-institutional studies that monitor relatively large cohorts, multimodal investigations that assess the sensitivity of different measures and their interrelationships, and novel imaging approaches that are targeted to known pathophysiology (e.g., iron and spinal imaging in Friedreich ataxia). These multimodal, multi-institutional studies are paving the way to clinical trial readiness and enhanced understanding of disease in degenerative ataxias.
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Characterization of Carbonic Anhydrase In Vivo Using Magnetic Resonance Spectroscopy.
Tomar, JS, Shen, J
International journal of molecular sciences. 2020;(7)
Abstract
Carbonic anhydrase is a ubiquitous metalloenzyme that catalyzes the reversible interconversion of CO2/HCO3-. Equilibrium of these species is maintained by the action of carbonic anhydrase. Recent advances in magnetic resonance spectroscopy have allowed, for the first time, in vivo characterization of carbonic anhydrase in the human brain. In this article, we review the theories and techniques of in vivo 13C magnetization (saturation) transfer magnetic resonance spectroscopy as they are applied to measuring the rate of exchange between CO2 and HCO3- catalyzed by carbonic anhydrase. Inhibitors of carbonic anhydrase have a wide range of therapeutic applications. Role of carbonic anhydrases and their inhibitors in many diseases are also reviewed to illustrate future applications of in vivo carbonic anhydrase assessment by magnetic resonance spectroscopy.
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NMR Metabolomics Applied on the Discrimination of Variables Influencing Tomato (Solanum lycopersicum).
Abreu, AC, Fernández, I
Molecules (Basel, Switzerland). 2020;(16)
Abstract
Tomato composition and nutritional value are attracting increasing attention and interest from both consumers and producers. The interest in enhancing fruits' quality with respect to beneficious nutrients and flavor/aroma components is based not only in their economic added value but also in their implications involving organoleptic and healthy properties and has generated considerable research interest among nutraceutical and horticultural industries. The present article reviews up to March 2020 some of the most relevant studies based on the application of NMR coupled to multivariate statistical analysis that have addressed the investigation on tomato (Solanum lycopersicum). Specifically, the NMR untargeted technique in the agri-food sector can generate comprehensive data on metabolic networks and is paving the way towards the understanding of variables affecting tomato crops and composition such as origin, variety, salt-water irrigation, cultivation techniques, stage of development, among many others. Such knowledge is helpful to improve fruit quality through cultural practices that divert the metabolism towards the desired pathways and, probably more importantly, drives further efforts towards the differentiation of those crops developed under controlled and desired agronomical conditions.
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Elucidating ligand-bound structures of membrane proteins using solid-state NMR spectroscopy.
Elkins, MR, Hong, M
Current opinion in structural biology. 2019;:103-109
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Abstract
Magic-angle-spinning (MAS) solid-state NMR spectroscopy is a versatile technique to elucidate functionally important protein-ligand interactions in lipid membranes. Here, we review recent solid-state NMR studies of membrane protein interactions with cholesterol, lipids, transported substrates, and peptide ligands. These studies are conducted in synthetic or native lipid bilayers to provide an accurate environment for ligand binding. The solid-state NMR approaches include multinuclear detection to gain comprehensive structural information, distance measurements to locate ligand-binding sites, and dynamic nuclear polarization and 1H detection to enhance spectral sensitivity. These studies provide novel insights into the mechanisms of virus budding, virus entry into cells, transmembrane signaling, substrate transport, antibacterial action, and many other biological processes.
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Magnetization Transfer Contrast and Chemical Exchange Saturation Transfer MRI. Features and analysis of the field-dependent saturation spectrum.
van Zijl, PCM, Lam, WW, Xu, J, Knutsson, L, Stanisz, GJ
NeuroImage. 2018;:222-241
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Abstract
Magnetization Transfer Contrast (MTC) and Chemical Exchange Saturation Transfer (CEST) experiments measure the transfer of magnetization from molecular protons to the solvent water protons, an effect that becomes apparent as an MRI signal loss ("saturation"). This allows molecular information to be accessed with the enhanced sensitivity of MRI. In analogy to Magnetic Resonance Spectroscopy (MRS), these saturation data are presented as a function of the chemical shift of participating proton groups, e.g. OH, NH, NH2, which is called a Z-spectrum. In tissue, these Z-spectra contain the convolution of multiple saturation transfer effects, including nuclear Overhauser enhancements (NOEs) and chemical exchange contributions from protons in semi-solid and mobile macromolecules or tissue metabolites. As a consequence, their appearance depends on the magnetic field strength (B0) and pulse sequence parameters such as B1 strength, pulse shape and length, and interpulse delay, which presents a major problem for quantification and reproducibility of MTC and CEST effects. The use of higher B0 can bring several advantages. In addition to higher detection sensitivity (signal-to-noise ratio, SNR), both MTC and CEST studies benefit from longer water T1 allowing the saturation transferred to water to be retained longer. While MTC studies are non-specific at any field strength, CEST specificity is expected to increase at higher field because of a larger chemical shift dispersion of the resonances of interest (similar to MRS). In addition, shifting to a slower exchange regime at higher B0 facilitates improved detection of the guanidinium protons of creatine and the inherently broad resonances of the amine protons in glutamate and the hydroxyl protons in myoinositol, glycogen, and glucosaminoglycans. Finally, due to the higher mobility of the contributing protons in CEST versus MTC, many new pulse sequences can be designed to more specifically edit for CEST signals and to remove MTC contributions.
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The NMR contribution to protein-protein networking in Fe-S protein maturation.
Banci, L, Camponeschi, F, Ciofi-Baffoni, S, Piccioli, M
Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry. 2018;(4):665-685
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Abstract
Iron-sulfur proteins were among the first class of metalloproteins that were actively studied using NMR spectroscopy tailored to paramagnetic systems. The hyperfine shifts, their temperature dependencies and the relaxation rates of nuclei of cluster-bound residues are an efficient fingerprint of the nature and the oxidation state of the Fe-S cluster. NMR significantly contributed to the analysis of the magnetic coupling patterns and to the understanding of the electronic structure occurring in [2Fe-2S], [3Fe-4S] and [4Fe-4S] clusters bound to proteins. After the first NMR structure of a paramagnetic protein was obtained for the reduced E. halophila HiPIP I, many NMR structures were determined for several Fe-S proteins in different oxidation states. It was found that differences in chemical shifts, in patterns of unobserved residues, in internal mobility and in thermodynamic stability are suitable data to map subtle changes between the two different oxidation states of the protein. Recently, the interaction networks responsible for maturing human mitochondrial and cytosolic Fe-S proteins have been largely characterized by combining solution NMR standard experiments with those tailored to paramagnetic systems. We show here the contribution of solution NMR in providing a detailed molecular view of "Fe-S interactomics". This contribution was particularly effective when protein-protein interactions are weak and transient, and thus difficult to be characterized at high resolution with other methodologies.
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The potential of multiparametric MRI of the breast.
Pinker, K, Helbich, TH, Morris, EA
The British journal of radiology. 2017;(1069):20160715
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Abstract
MRI is an essential tool in breast imaging, with multiple established indications. Dynamic contrast-enhanced MRI (DCE-MRI) is the backbone of any breast MRI protocol and has an excellent sensitivity and good specificity for breast cancer diagnosis. DCE-MRI provides high-resolution morphological information, as well as some functional information about neoangiogenesis as a tumour-specific feature. To overcome limitations in specificity, several other functional MRI parameters have been investigated and the application of these combined parameters is defined as multiparametric MRI (mpMRI) of the breast. MpMRI of the breast can be performed at different field strengths (1.5-7 T) and includes both established (diffusion-weighted imaging, MR spectroscopic imaging) and novel MRI parameters (sodium imaging, chemical exchange saturation transfer imaging, blood oxygen level-dependent MRI), as well as hybrid imaging with positron emission tomography (PET)/MRI and different radiotracers. Available data suggest that multiparametric imaging using different functional MRI and PET parameters can provide detailed information about the underlying oncogenic processes of cancer development and progression and can provide additional specificity. This article will review the current and emerging functional parameters for mpMRI of the breast for improved diagnostic accuracy in breast cancer.
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Applications of high-resolution magic angle spinning MRS in biomedical studies II-Human diseases.
Dietz, C, Ehret, F, Palmas, F, Vandergrift, LA, Jiang, Y, Schmitt, V, Dufner, V, Habbel, P, Nowak, J, Cheng, LL
NMR in biomedicine. 2017;(11)
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Abstract
High-resolution magic angle spinning (HRMAS) MRS is a powerful method for gaining insight into the physiological and pathological processes of cellular metabolism. Given its ability to obtain high-resolution spectra of non-liquid biological samples, while preserving tissue architecture for subsequent histopathological analysis, the technique has become invaluable for biochemical and biomedical studies. Using HRMAS MRS, alterations in measured metabolites, metabolic ratios, and metabolomic profiles present the possibility to improve identification and prognostication of various diseases and decipher the metabolomic impact of drug therapies. In this review, we evaluate HRMAS MRS results on human tissue specimens from malignancies and non-localized diseases reported in the literature since the inception of the technique in 1996. We present the diverse applications of the technique in understanding pathological processes of different anatomical origins, correlations with in vivo imaging, effectiveness of therapies, and progress in the HRMAS methodology.