Characterisation of magnetic resonance imaging (MRI) contrast agents using NMR relaxometry

ABSTRACT

This contribution describes the use of Fast Field-cycling relaxometry (FFC-NMR) for the characterisation of Gd(III)- and Mn(II)-based contrast agents for MRI. Through a series of selected examples, we analyse the role of different structural and dynamic parameters on ¹H relaxivity and on the shape of the ¹H Nuclear Magnetic Relaxation Dispersion (NMRD) profiles. The amplitude and shape of the profiles is affected by the number of water molecules coordinated to the metal ion, the water exchange rate, the rotational correlation time of the complex and the relaxation of the electron spin. As a result, ¹H NMRD profiles represent a powerful tool for the understanding of the properties of MRI contrast agent candidates at the molecular level.     

Nuclear magnetic resonance pulse sequence and discrimination of high- and low-fat tissues

Signal size compared to independently measured T1 is described for various pulse sequences on the Aberdeen Mk II nuclear magnetic resonance imager. The ability of these sequences to discriminate between certain tissue types, and in particular between adipose tissue and muscle, is discussed. Inversion recovery, with a t interval of 200 ms, gives the best discrimination for this purpose, with a contrast ratio of 6 between fat and muscle. Other image types, and especially T1, give better contrast for low-lipid soft tissue such as liver and spleen.     

Influence of radiofrequency amplifier nonlinearities on nuclear magnetic resonance image quality

The quality of nuclear magnetic resonance (NMR) image is degraded by a number of disturbing influences. In this article the influence of a nonlinear radiofrequency receiving amplifier is investigated. The effect of a cubic nonlinearity on the NMR signal is analyzed. Finally, the influence on the NMR image is studied for Fourier reconstruction techniques. As a result, the images are degraded by an additional term which is proportional to a parameter characterizing the nonlinearity. The additional term causes homogeneous objects to appear inhomogeneous and gives rise to image intensity outside the object. Under normal conditions the image degradation is negligible.     

Proton nuclear magnetic resonance spectra of brain tumors

Proton nuclear magnetic resonance (NMR) spectra were successfully measured in human brain tumor tissues and experimental rat brain tumors. The investigation was performed on clinical materials which consisted of tissue from one normal brain and 36 brain tumors. Normal rat brain tissue and rat glioma implanted in the brain were also analysed. NMR measurements were carried out at the resonance frequency of 99.54 MHz. The proton NMR spectrum of the normal brain consisted of one broad component and eight superimposed sharp peaks. The sharp peaks obtained from the brain tumors varied from those of the normal brain. A decrease in the signal intensity from N-acetyl aspartate was the most common finding in all tumors. Spectral patterns were similar within the same histological types, but varied among the different types. Therefore, ¹H-NMR spectra might indicate the metabolism characteristic of each tumor type which would be invaluable for clinical differential dagnosis of brain tumors.     

A computer algorithm for the simulation of any nuclear magnetic resonance (NMR) imaging method

More than a dozen Nuclear Magnetic Resonance (NMR) imaging methods have been described using different radio-frequency pulse sequences, magnetic field gradient variations, and data processing. In order to have a theoretical understanding in the most general case, we have conceived a computer program for the simulation of NMR imaging techniques. The algorithm uses the solution of the Bloch equations at each point of a simulated object. The direction of every elementary magnetic moment is computed at each instant, and stored in an array giving the global signal to be processed, whatever the pulse and gradient sequence. To test the validity of this program, we have simulated some well-known experimental results. Some applications are presented which contribute to the understanding of image distortions and to techniques such as selective radio-frequency pulse or oscillating gradients. This program can be used to unravel physical and technological causes of image distortions, to have a "microscopic" look at any parameter of an experiment, and to study the contrast given by various NMR imaging techniques as a function of the three NMR parameters, i.e., the hydrogen nuclei density rho and the relaxation times T1 and T2.     

High-pressure NMR study of water exchange on magnetic resonance imaging contrast agents

Abstract

The knowledge of water exchange reaction mechanism in aqueous solutions of Gd³⁺ polyaminocarboxylates is important for the understanding of the relatively slow water exchange rates measured for these complexes. Variable ressure measurements show a change of mechanism from associatively activated on [Gd(H₂O)₈]³⁺ and [Gd(PDTA)(H₂O₂)₂]^? to probably limiting dissociative on the MRI contrast agents [Gd(DOTA)(H₂O)]^?, [Gd(DTPA)(H₂O)]^2? and [Gd(DTPA-BMA)(H₂O)].     

Nuclear magnetic resonance (NMR) imaging in the diagnosis of spinal osteomyelitis

Nuclear Magnetic Resonance Imaging (NMR) was performed on two patients whose clinical radiograph and bone scanning suggested spinal osteomyelitis before and after successful antimicrobial therapy. The images obtained suggest that NMR may be more useful in the diagnosis of this condition than other conventional imaging techniques. Hitherto NMR has not been considered particularly useful for the diagnosis of bone disease. This may be true for cortical bone, from which no signal is obtained using the NMR technique, but for medullary bone it appears to be a potentially useful, non-invasive and safe method of diagnosis.     

Selection of pulse sequences producing maximum tissue contrast in magnetic resonance imaging

The importance of spin density [N(H)] and spin-lattice (T₁) and spin-spin (T₂) relaxation in the characterization of tissue by nuclear magnetic resonance (NMR) is clearly recognized. This work considers which optimized pulse sequences provide the best tissue discrimination between a given pair of tissues. The effects of tissue spin density and machine-imposed minimum rephasing echo times (TE_MIN) for achieving maximum signal tissue contrast are discussed. A long TE_MIN sacrifices T₁-dependent contrast in saturation recovery (SR) and inversion recovery (IR) pulse sequences so that spin-echo (SE) becomes the optimum sequence to provide tissue contrast, due to T₂ relaxation. Pulse sequences providing superior performance may be selected based on spin density and T₁ and T₂ ratios for a given pair of tissues. Selection of the preferred pulse sequence and interpulse delay times to produce maximum tissue contrast is strongly dependent on knowledge of tissue spin densities as well as T₁ and T₂ characteristics. As the spin density ratio increases, IR replaces SR as the preferred sequence and SE replaces IR and SR as the pulse sequence providing superior contrast. To select the optimal pulse sequence and interpulse delay times, an accurate knowledge of tissue spin density, T₁ and T₂ must be known for each tissue.     

Concentration dependence of F nuclear magnetic resonance decay shapes and second moments in bone mineral

¹⁹F nuclear magnetic resonance (NMR) spin-echoes and free induction decays (FIDs) have been observed from samples of fluoridated trabecular canine bone powder, with fluoride concentrations ([F]) ranging from approximately 10 to 33 mg F/g Ca. Curve fitting of echo envelopes and FIDs was performed using a two-component model function, where one of the components incorporates the effects of one-dimensional dipolar coupling. This function provides a good match for both echo envelopes and FIDs. Estimates of the total second moment and its homonuclear (F–F coupling) component were obtained from the fitting procedure. Based on the second moment measurements, it is argued that ¹⁹F spins in bone mineral typically experience weaker heteronuclear dipolar coupling than those in the mineral hydroxyapatite (HAP), which is often considered to be a prototype for bone mineral.     

Supercycled SW(f)-TPPM sequence for heteronuclear dipolar decoupling in solid-state nuclear magnetic resonance

The performance of a supercycled SW(f)-TPPM sequence for heteronuclear dipolar decoupling in solid-state NMR is analyzed here. The decoupling performance of this sequence with respect to experimental parameters, such as, the phase angle, proton offset and MAS frequency is studied. A comparison is made with two other commonly used decoupling schemes in solid-state NMR namely, SPINAL-64 and SW(f)-TPPM, on a sample of U-13C-labeled tyrosine. Our results show that supercycled SW(f)-TPPM performs better than the former sequences. Also, numerical spin dynamics studies are presented which support the experimentally observed efficiency in the decoupling.     

The oral administration of MnCl2: A potential alternative to IV injection for tissue contrast enhancement in magnetic resonance imaging

Mn⁺² (as MnCl₂) was administered to rabbits intravenously and orally (a route of administration which based upon our previous experiments in rats⁷ promises to give selective hepatobiliary enhancement with less systemic toxicity). Nuclear magnetic relaxation dispersion or T₁ (NMRD) was performed on selected tissues (heart, liver, kidney, serum, and bile) in both animal groups to examine possible qualitative and semiquantitative differences in T₁ relaxation at equivalent sacrifice times. One animal was given an oral dose of MnCl₂ (620 micromoles/kg) and imaged sequentially (T₁ weighted sequence, .12T) for 30 minutes. The NMRD curves for organ tissues show an increase in relaxation efficacy in the 10–20MHz range characteristic of Mn-macromolecular complexes and are similar irrespective of the route of administration. The lack of increased relaxation enhancement for bile in this frequency range reflects cleavage of this complex upon excretion. Decreased overall relaxation in the liver is observed when oral Mn⁺² is compared to IV Mn⁺² due to the small fraction of administered dose that is absorbed. However, the images document a significant increase in the intensity of liver signal after the oral dose. We suspect this dose may ultimately be adjusted downward to give selective hepatobiliary effects.     

Noninvasive (1)H and (23)Na nuclear magnetic resonance imaging of ancient Egyptian human mummified tissue

Historic mummies are a unique example of the human desire for immortality. Therefore, it is not surprising that modern diagnostic imaging has been widely applied to study them. Yet, magnetic resonance imaging (MRI) of such old remains has never been successfully achieved in a noninvasive way without rehydration. Furthermore, the impact of artificial mummification as done in ancient Egypt by natron (a blend of NaCl, Na(2)CO(3), NaHCO(3) and NaP(2)SO(4)) on human tissue with a particular focus on the sodium spatial distribution has never been addressed. Here, we show for the very first time completely noninvasive (1)H and (23)Na imaging of an ancient Egyptian mummified finger by nuclear magnetic resonance (NMR). Protons could be visualized by NMR only in the tissue close to surface and sodium primarily in the bone, while computer tomography images both, soft tissue and bone but does not distinguish between different chemical elements. The selective enrichment of sodium in the bone may by due to postmortem incorporation of (23)Na into the tissue by natron-based mummification because our reference measurement of a historical finger not subjected to artificial mummification showed no sodium signal at all. Our results demonstrate not only the general feasibility of nonclinical MRI to visualize historic dry human tissues but also shows the specific (1)H and (23)Na spatial distributions in such mummy tissue, which is particularly interesting for archeology and may open up a new application for MRI.     

Effects of the operating magnetic field on potential NMR contrast agents

Paramagnetic metal ions have shown promise as contrast agents for nuclear magnetic resonance (NMR) imaging. Their ability depends upon modification of the relaxation times (T1 and T2) through dipolar interactions. These interactions cause the effectiveness of the agents to be sensitive to the operating magnetic field. Studies are presented of the operating field dependence (frequency dispersion) of two metal-chelate complexes, Gd+3-ethylenediaminetetraacetate (EDTA) and Mn+2-EDTA, in a physiologically balanced electrolyte solution. Inversion recovery experiments were performed on two concentrations of each metal-chelate complex at five resonant frequencies. The frequency dispersion curves were similar in appearance for those of the corresponding aqueous solutions. The Mn+2 complex showed no unusual concentration effects. The Gd+3 complex showed an unexpected concentration dependence in the dispersion behavior. This is attributed to a difference in the dipolar correlation time between the two solutions. With its unique correlation time in electrolyte solutions, predictions of relaxation rate changes in studies in vivo may be easier for the Mn+2-EDTA complex.     

Review of nuclear magnetic resonance studies on iron-based superconductors

The newly discovered iron-based superconductors have triggered renewed enormous research interest in the condensed matter physics community. Nuclear magnetic resonance （NMR） is a low-energy local probe for studying strongly correlated electrons, and particularly important for high-Tc superconductors. In this paper, we review NMR studies on the structural transition, antiferromagnetic order, spin fluctuations, and superconducting properties of several iron-based high-Tc superconductors, including LaFeAsOl_xFx, LaFeAsOl_x, BaFe2As2, Bal_xKxFe2As2, Cao.23Nao.67Fe2As2, BaFe2（Asl_xPx）2, Ba（Fel_xRux）2As2, Ba（Fel_xCox）2As2, Lil＋xFeAs, LiFel_xCoxAs, NaFeAs, NaFel_xCoxAs, KyFe2_xSe2, and （T1,Rb）yFe2_xSe2.     

Characterization of polyalkylvinyl ether phases by solid-state and suspended-state nuclear magnetic resonance investigations

Pure organic polyalkylvinyl ether phases were synthesized by suspension polymerization using different ratios and compositions of n-butylvinyl ether (C₄VE) and n-octadecylvinyl ether (C₁₈VE) with triethylene glycol divinyl ether or divinylbenzene as crosslinkers, respectively. These phases were investigated by means of solid-state ¹³C cross-polarization magic angle spinning nuclear magnetic resonance (NMR) spectroscopy and ¹H high-resolution magic angle spinning (HR MAS) NMR spectroscopy in suspended-state. A comparison of these two methods showed the substantial advantages of ¹H HR MAS NMR measurements. Structure elucidation was achieved using a 2D H,H-COSY NMR experiment performed under MAS conditions enabling full peak assignment of the ¹H NMR spectra of these phases. The dynamic behavior of the polyalkylvinyl ether phases was determined by employing temperature-dependent measurements of spin–lattice relaxation times (T₁) as well as accumulation of a 2D wide line separation NMR spectrum.     

The effects of restricted diffusion in nuclear magnetic resonance microscopy

A stochastic computer simulation is used to investigate the effects of restricted diffusion in NMR microscopy. It is shown that diffusion contributes to a loss of interfacial resolution through two main mechanisms. The first applies to spatial regions bound by impermeable interfaces and involves diffusive averaging of the frequency differences set up by the applied field gradients. This effect can be made arbitrarily small by increasing the magnitude of the field gradient. The second mechanism involves diffusion through permeable membranes or interfaces defining the sample morphology. This effect can, in principle, be reduced by multiple echo imaging with short pulse spacings. The possibility of imaging diffusive flow through a permeable interface is discussed.     

量子算法核磁共振实现脉冲序列设计程序问题研究

从两量子位核磁共振量子处理器物理模型出发,利用Raedt小组提出的自旋-1/2代数理论,根据量子控制非门的定义及Grover量子算法原理,介绍了量子控制非门的4种不同脉冲序列及两量子位Grover量子算法的两种不同脉冲序列的设计过程,通过数值求解含时薛定谔方程模拟量子控制非门和两量子位Grover量子算法,等价于执行量...