Paramagnetic metal complexes as water proton relaxation agents for NMR imaging:  theory and design

Lauffer, Randall B.

doi:10.1021/cr00081a003

Cited by 1,919 publications

(1,763 citation statements)

References 57 publications

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“…The mean T1 and T2 relaxation times for the deionized water phantom with no contrast agent (deionized water alone) were 4250 ms (T1 0 ) and 2760 ms (T2 0 ), respectively. NMR relaxivity measurements are in reasonable agreement with previously reported results for both the Gd 28 and Mn 29,30 contrast agents used here.…”

supporting

confidence: 91%

Dual Contrast - Magnetic Resonance Fingerprinting (DC-MRF): A Platform for Simultaneous Quantification of Multiple MRI Contrast Agents

Anderson

Donnola

Jiang

et al. 2017

Sci Rep

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Injectable Magnetic Resonance Imaging (MRI) contrast agents have been widely used to provide critical assessments of disease for both clinical and basic science imaging research studies. The scope of available MRI contrast agents has expanded over the years with the emergence of molecular imaging contrast agents specifically targeted to biological markers. Unfortunately, synergistic application of more than a single molecular contrast agent has been limited by MRI's ability to only dynamically measure a single agent at a time. In this study, a new Dual Contrast -Magnetic Resonance Fingerprinting (DC -MRF) methodology is described that can detect and independently quantify the local concentration of multiple MRI contrast agents following simultaneous administration. This "multi-color" MRI methodology provides the opportunity to monitor multiple molecular species simultaneously and provides a practical, quantitative imaging framework for the eventual clinical translation of molecular imaging contrast agents.Over the past 3 decades, Magnetic Resonance Imaging (MRI) has become an essential medical imaging modality due to its exceptional soft tissue contrast and lack of ionizing radiation. Along with a wide variety of endogenous tissue contrast mechanisms, many MRI applications utilize an intravenous injection of an MRI contrast agent (e.g., gadolinium chelates or iron oxides) to enable sensitive identification of numerous pathologies such as tumors 1 , vascular abnormalities 2 , and cardiac infarcts 3 through local alterations in the tissue's magnetic properties (T1 and T2 relaxation times). Clinical use of these contrast-enhanced MRI scans has further expanded as multiple contrast agents have been approved for specific clinical imaging applications (e.g., blood pool contrast agents 4 , hepatobiliary contrast agents 5 ).With the emergence of the field of molecular imaging, there has been a dramatic increase in the number of MRI contrast agents targeted to proteins 6-8 , cell receptors 9, 10 , and other molecular species 11,12 . In addition, a number of activatable agents have been described that have different relaxivities based on the local tissue environment in vivo 13,14 . In a typical preclinical molecular MRI study, the T1 or T2 relaxation time (or MRI signal intensity) is

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supporting

confidence: 91%

Dual Contrast - Magnetic Resonance Fingerprinting (DC-MRF): A Platform for Simultaneous Quantification of Multiple MRI Contrast Agents

Anderson

Donnola

Jiang

et al. 2017

Sci Rep

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“…The formation of the complex was monitored by measuring the shift of the 17 1 H NMR spectra, the water signal was used as internal reference, set at δ 4.75 ppm (at 298 K) and was suppressed by a presaturation pulse. 13 C NMR spectra were measured with broad-band proton decoupling, using the methyl resonance of TSP (sodium-3-trimethylsilylpropionate-2,2-3,3-d 4 ) as internal reference, set at δ ) 0 ppm.…”

Section: Methodsmentioning

confidence: 99%

Synthesis, Characterization, and Relaxivity of Two Linear Gd(DTPA)−Polymer Conjugates

et al. 2001

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Two linear polyamide conjugates of Gd(DTPA) 2-were synthesized and characterized by high-resolution nuclear magnetic resonance (NMR) spectroscopy and size exclusion chromatography (SEC). DTPA was copolymerized with two different diamines, 1,6-hexanediamine and trans-1,4-cyclohexanediamine, yielding the polymers DTPA-HMD and DTPA-CHD, with low polydispersity. Their molecular flexibility in solution was studied using 13 C spin-lattice relaxation time measurements, indicating that the cyclohexanediamine linking moiety of the DTPA-HMD polymer is more rigid than that of DTPA-CHD. The influence of the flexibility of the linking functionalities on the relaxivity of the Gd 3+ -DTPApolymer conjugates was studied by water nuclear magnetic relaxation dispersion (NMRD). The relaxivity of the Gd(DTPA-CHD) polymer was only slightly higher than that of the Gd(DTPA-HMD) polymer, and only two times higher than the usual values for small Gd-DTPA-like chelates. The low relaxivities obtained for both polymers, much lower than expected from the polymer apparent molecular weights, result from their substantial residual flexibility, and also from a too long, nonoptimal, value of the inner-sphere water exchange rate. These polymeric compounds are also cleared very quickly from the blood of rats, indicating that they are of limited value as blood pool contrast agents for MRA.

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“…For contrast enhancement in magnetic resonance imaging (MRI), Gd ions must be administered in a water-soluble state so that they can interact with protons of water molecules (34). For this reason, Gd is bound by ligands.…”

Section: Potential Role Of Gbcas In Nsfmentioning

confidence: 99%

“…GBCAs used for MRI contain a single paramagnetic Gd 3þ ion that is tightly bound by a complexing agent (34). On the basis of the chemical structure of the complexing agent, GBCAs can be divided into two distinct classes: the linear open-chain agents and the macrocyclic agents (44).…”

Section: Role Of Complex Stability: Evaluation Of Marketed Productsmentioning

confidence: 99%

Gadolinium‐based contrast agents and NSF: Evidence from animal experience

Sieber

Steger‐Hartmann

Lengsfeld

et al. 2009

Magnetic Resonance Imaging

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Nephrogenic systemic fibrosis (NSF) is a potentially severe systemic disease typically characterized by fibrosis of the skin and connective tissues. The etiology of NSF is still unknown but is likely to be multifactorial. Specific triggers under scientific evaluation have included surgery and/or the occurrence of thrombosis or other vascular injury, proinflammatory state, the administration of high doses of erythropoietin, and more recently the use of gadolinium-based contrast agents (GBCAs). The aim of this review is to summarize knowledge regarding the pathogenesis of NSF and the potential role of GBCAs in its pathology, with a focus on animal experiments. The potential role of complex stability of GCBAs will be highlighted by results from several in vitro and in vivo experiments in rodent models of NSF.

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Paramagnetic metal complexes as water proton relaxation agents for NMR imaging: theory and design

Cited by 1,919 publications

References 57 publications

Dual Contrast - Magnetic Resonance Fingerprinting (DC-MRF): A Platform for Simultaneous Quantification of Multiple MRI Contrast Agents

Dual Contrast - Magnetic Resonance Fingerprinting (DC-MRF): A Platform for Simultaneous Quantification of Multiple MRI Contrast Agents

Synthesis, Characterization, and Relaxivity of Two Linear Gd(DTPA)−Polymer Conjugates

Gadolinium‐based contrast agents and NSF: Evidence from animal experience

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