Signal-to-noise improvement in NMR imaging byB 1 homogeneity optimization

Summary The role of the RF magnetic-field homogeneity for the quality of the signal-to-noise ratio is here discussed. Its effects on the e.m.f. generated by the nuclear magnetization is analysed as well. We also report here some results of a modified coil which improves the RF field homogeneity and thus the signal to noise. Work partially supported by Progetto, Finalizzato Tecnologie Biomediche of CNR and by Esacontrol, Genoa.     

Diffusion-weighted spatial information from1H relaxation in restricted geometries

Summary NMR relaxation of water¹H confined in restricted geometries, whatever is the nature of the system (porous media saturated by water as well as biological tissues), exhibits common characteristics. Artificial microporous media saturated by water have been chosen as model systems to study the longitudinal and transverse relaxation of¹H magnetization of water molecules diffusing in restricted geometries. These systems are very stable, easy to prepare, with well-characterized pore size distribution and connections, and with highly homogeneous surface properties. The response was compared with that from more complex natural porous media. Scanning Electron Microscopy techniques demonstrated spatial characteristics and surface properties of the samples. The information content of longitudinal relaxation curves associated with spatial structure and due to restricted diffusion is shown in these samples. The effect on transverse relaxation of self-diffusion in the presence of spatially varying magnetic fields due to susceptibility differences is shown. A simple linear relationship has been found in all samples between the transverse relaxation rate and the interpulse delay in CPMG experiments, in spite of the variety of pore shapes and sizes. In general, one can say that relaxation curves beardiffusion-weighted information on the pore space framework. The role of the investigated relaxation mechanisms is important also in the response of biological tissues, including in the presence of MR Imaging contrast agents inducing microscopic magnetic-field gradients. Work partially supported by CNR and MURST Grants.     

Selective measurements of heteronuclear overhauser effects: Structural applications

Summary A NMR method for determining internuclear distances between dipolarly coupled nuclei is here proposed. As a model system, salicylaldehyde has been investigated. A selective presaturation of C₁H and O ₂ ^′ H protons yields Overhauser effects on C₁, C ₁ ^′ and C ₂ ^′ resonances. From a combined use of these Overhauser effects and¹³C spin-lattice relaxation rates, internuclear distances between irradiated protons and carbon nuclei dipolarly coupled to them can be calculated. Furthermore, the obtained selective Overhauser effects can simultaneously evidentiate donor and acceptor moieties of hydrogen bonds, as in the present study in which the hydrogen bonding between the C₁ carbonyl and the O ₂ ^′ H proton was clearly delineated.

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Riassunto Si propone un metodo NMR per determinare distanze tra nuclei diversi nel caso che questi siano dipolarmente accoppiati. La salicilaldeide è stata studiata come composto modello. Per questa molecola l'eccitazione selettiva dei protoni C₁H e O ₂ ^′ H e O ₂ ^′ H genera effetti Overhauser sui picchi dei C₁, C ₁ ^′ e C ₂ ^′ . Un uso combinato di questi effetti Overhauser e delle velocità di rilassamento spin-lattice dei nuclei¹³C della salicilaldeide permette di calcolare le distanze internucleari tra i protoni irradiati ed i carboni ad essi dipolarmente accoppiati. Inoltre in questo modo è stata messa in evidenza la presenza di un legame a idrogeno tra il gruppo C₁=O e l'idrogeno O ₂ ^′ H.

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Резюме В работе предагается метоя ЯМР для определения расстояний между ядрами в случае, когда ядра связаны дипольным образом. Исследуется модельная система: салициловый альдегид. Селективное возбуждение протонов в C₂H и O ₂ ^′ H приводит к возникновению эффекта Оверхаузера на резонансах C₁, C ₁ ^′ и C ₂ ^′ . Объединяя эффекты Оверхаузера и скорости спих-решеточной релаксации¹³C, можно вычислитю расстояния между облученными протонами и ядрами углерода, связанными дипольным образом. Кроме того, в предложенном подходе подтверждено наличие водородной связи между группой C₁=0 и протоном O ₂ ^′ H.

     

NMR and IR investigations of biologically active peptides in solution

Summary Nuclear-magnetic-resonance and infra-red spectroscopic features in solution have been investigated for the delineation of conformation and dynamics of the chemotactic peptide formyl-L-methionyl-L-leucyl-L-phenylalanine. The main conformation is unfolded and characterized by a certain degree of weak intermolecular hydrogen bounding. The steric hindrance of neighbouring side chains limits the motional averaging of the several possible conformers by excluding some of the rotamers. Dipolar and scalar connectivities, as detected by 2D NMR spectroscopy, point to a cis configuration of the H−N−C−H_α moiety in the case of leucine and trans in the cases of methionine and phenylalanine.

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Riassunto Per il chiarimento della conformazione e della dinamica molecolare del peptide chemotattico formil-L-metionil-L-leucil-L-fenilalanina sono stati studiati i parametri spettroscopici di risonanza magnetica nucleare ed infrarosso in soluzione. La conformazione principale è distesa e caratterizzata da un certo grado di deboli legami a idrogeno intermolecolari. L’impedimento sterico di catene laterali vicine limita la possibilità che i vari conformeri possibili siano mediati dai moti molecolari, escludendo alcuni rotameri. Le connettività dipolari e scalari, messe in evidenza dalla spettroscopia 2D NMR, suggeriscono una configurazione cis del residuo H−N−C−H_α nel caso della leucina e trans nei casi della metionina e della fenila lanina.

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Реэюме Исследуются ядерный магнитный резонанс и инфра-красные спектроскопические характеристики в растворе с целью описания конформации и динамики хемотактичного пептида формия-Л-метионил-Л-лейцил-Л-фенилаланина. Основная конформация явлется раэвернутой и характериэуется определенной степенью слабой межмолекулярной водородной связй. Стерическое припятствие для соседних боковых цепей ограничивает динамическое усреднение для некоторых конформаций, исключая некоторые ротамеры. Дипольнье и скалярные связности, зарегистрированные с помощью 2D ЯМР-спектроскопии, указывают на цис-конфигурацию H−N−C−H_α в случае лейцина и на транс-конфигурацию в случаях метионина и фенилаланина.

     

Probing the analogy of the proton relaxation in biological tissues and porous media

Summary Experimental data are reported that show the analogy of longitudinal and transverse proton relaxation in heterogeneous systems as different as biological tissues and water-saturated rocks. Published data on the τ-dependence of the transverse-relaxation rate for biological tissues with magnetite grains, used as a contrast agent in MRI, are discussed in the light of our recent results on water-saturated porous media, and give for the liver another case of a behaviour parallel to that in rocks. There are enough similarities between NMR relaxation in tissues and in other porous media that, for work in either area, attention to the other is likely to be fruitful. Work supported by Italian CNR and MURST grants     

Aspects of structural order in 209Bi-containing particles for potential MRI contrast agents based on quadrupole enhanced relaxation

ABSTRACT

Quadrupole relaxation enhancement (QRE) has been suggested as the key mechanism for a novel class of field-selective, potentially responsive magnetic resonance imaging contrast agents. In previous publications, QRE has been confirmed for solid compounds containing ²⁰⁹Bi as the quadrupolar nucleus (QN). For QRE to be effective in aqueous dispersions, several conditions must be met, i.e. high transition probability of the QN at the ¹H Larmor frequency, water exchange with the bulk and comparatively slow motion of the Bi-carrying particles. In this paper, the potential influence of structural order within the compounds (‘crystallinity’) on QRE was studied by nuclear quadrupole resonance (NQR) spectroscopy in one crystalline and two amorphous preparations of Triphenylbismuth (BiPh₃). The amorphous preparations comprised (1) a shock-frozen melt and (2) a granulate of polystyrene which contained homogeneously distributed BiPh₃ after common dissolution in THF and subsequent evaporation of the solvent. In contrast to the crystalline powder which exhibits strong, narrow NQR peaks the amorphous preparations did not reveal any NQR signals above the noise floor. From these findings, we conclude that the amorphous state leads to a significant spectral peak broadening and that for efficient QRE in potential contrast agents structures with a high degree of order (near crystalline) are required.     

CaSO4·(1/2) H2O粉末中结晶水与吸附水1H的Goldman-Shen实验

本文利用Goldman-Shen脉冲序列测量了CaSO₄·(1/2) H₂O样品中结晶水与吸附水¹H的交叉弛豫时间为55.1ms。在实验中,发现剩余窄线的磁化矢量随时间的衰减有三个过程。本文对此现象作了一些分析讨论。     

Mechanical detection of nuclear spin relaxation in a micron-size crystal

A room temperature nuclear magnetic resonance force microscope (MRFM), fitted in a 1 tesla electromagnet, has been used to measure the nuclear spin relaxation of ¹H in a micron-size (70 ng) crystal of ammonium sulfate. NMR sequences, combining both pulsed and continuous wave radio-frequency fields, have allowed us to measure mechanically T₂ and T₁, the transverse and longitudinal spin relaxation times. Because two spin species with different T₁ values are measured in our 7 μm thick crystal, magnetic resonance imaging of their spatial distribution inside the sample section have been performed. To understand quantitatively the measured signal, we carefully study the influence of spin-lattice relaxation and non-adiabaticity of the continuous-wave sequence on the intensity and time dependence of the detected signal. Received 23 February 2000     

The dependence of relaxation rates and chemical shift on the size of the imaged molecules and the concentration of MRI contrast agents

An intriguing phenomenon on enhancement of the relaxation rates and chemical shift of two typical magnetic resonance imaging (MRI) contrast agents based on gadolinium complex is observed. The relaxation enhancement or chemical shift change depends on the size of the molecule where the imaged nuclear species is located: the small molecules show a perfect linear relationship between the concentration and the relaxation enhancement or chemical shift change while for macromolecules pronounced nonlinearity is observed. The phenomenon is also confirmed with real images of a macromolecular sample. A quantitative theoretical interpretation of the phenomenon is proposed and the significance of this phenomenon to MRI of materials and biological systems is discussed.     

Electrical detection of nuclear spin echoes

We show, via a straightforward calculation, that it is feasible to detect nuclear spin echoes in a ferromagnetic thin film by electrical means. The detection scheme is based on the deflection of the electronic magnetization when the nuclear magnetization reforms during an echo. This deflection is observed as a time-dependent magnetoresistive signal.     

Nuclear spin-lattice relaxation due to dissipative domain walls

The influence of the dissipative motion of domain walls in the nuclear spin-lattice relaxation rate is studied as a function of the external magnetic field and the temperature. Although only the specific case of the TMMC antiferromagnet below T_N is presented, the results are valid for all magnets described within the semiclassical approach by a double sine-Gordon equation for the spin degree of freedom.     

NMR of water in biological systems

Summary A simple relationship has been thought to exist between the dynamics of water in heterogeneous (liquid-solid) systems and the NMR response. This relationship is usually expressed by the Bloembergen-Purcell-Pound (BPP) equations for relaxation and the phase model. However, a requirement for the use of the BPP theory is that motions take place in an isotropic, infinite and three-dimensional space. It is shown that the mere presence of solid surfaces causes the appearance of solidlike features in the NMR response of the liquid even if its dynamics is directly affected by the surfaces. Some of these ?topological? or ?indirect? surface effects are of the same kind as the low-dimensionality effects. Their order of magnitude is estimated for simple geometries and by treating the liquid motion in a hydrodynamic approximation. Comparison with the experiment is carried on in a companion paper. To speed up publication, the authors of this paper have agreed to not receive the proofs for correction.     

Multicomponent water proton transverse relaxation and T2-discriminated water diffusion in myelinated and nonmyelinated nerve

The influence of compartmental boundaries on water proton transverse relaxation and diffusion measurements was investigated in three distinct excised nerves, namely, the non-myelinated olfactory nerve, the Schwann cell myelinated trigeminal nerve, and the oligodendrocyte myelinated optic nerve of the garfish. The transverse relaxation decay curves were multiexponential and their decomposition yielded three primary components with T₂ values 30–50, 150, and 500 ms, which were subsequently assigned to water protons in the myelin, axoplasm, and interaxonal compartments. The short T₂ component was absent in the non-myelinated olfactory nerve, but present in both myelinated nerves and thus provides supporting evidence for the use of quantitative T₂ measurements to measure the degree of myelination. The signal contribution of each T₂ component to the apparent diffusion coefficient measurements was varied by incrementing the spin-echo time with a preparatory CPMG train of radiofrequency pulses. The apparent diffusion coefficient and its anisotropy were shown to be independent of the spin-echo time over the range of 70 to 450 ms.     

Molecular dynamics and interactions of human ceruloplasmin: A spin labelling study

Summary Ceruloplasmin, a paramagnetic copper-containing protein, has been spin labelled with different nitroxide spin labels in order to study its molecular dynamics and to gain further information about its interaction with other biosystems. Spin labelling with a maleimide derivative resulted in an electron spin resonance spectrum which was a superposition of two different absorptions due to paramagnetic species in different microenvironments. The first one, a three-line isotropic spectrum, is due to a fast-moving spin label (with a rotational correlation time τ_c≃10^-9s); the second one is an anisotropic, asymmetrical signal arising from an immobilized spin in a slow-motion domain (τ_c=10^-7). The assumption of a spherical shape for the molecule provided, through the Stokes-Einstein relation, an estimate of the molecular-radius value consistent with smallangle neutron scattering measurements. The interaction with other biosystems, as deduced from the protein molecule dynamics, is discussed.

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Riassunto La ceruloplasmina, una proteina umana contenente ioni Cu⁺⁺ paramagnetici, è stata marcata con differenti spin labels per studiarne la dinamica molecolare e la sua interazione con altri biosistemi. Il marcaggio mediante spin labels di tipo maleimidico ha portato ad uno spettro di risonanza elettronica di spin composto da due differenti gruppi di righe dovuti a specie paramagnetiche in differenti microambienti. Il primo segnale è costituito da un tripletto isotropico dovuto ad uno spin label in rapida rotazione (τ_c≃10^-9s), mentre il secondo è alquanto asimmetrico (anisotropico) e deriva da uno spin label ruotante in un dominio temporale piuttosto lento (τ_c=10^-7). L'assunzione di una forma sferica per la proteina in soluzione ha portato, attraverso la relazione di Stokes-Einstein, ad una determinazione del raggio molecolare in buon accordo con il risultato di misure di diffrazione a basso angolo di neutroni. Si discute inoltre l'interazione con altri biosistemi come desunta dalla dinamica molecolare della proteina.

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Резюме Церулоплазмин, человеческий белок, содержащий парамагнитные ионы меди Cu⁺⁺, помечается с помощью различных спиновых меток для исследования молекулярной динамики и взаимодействий с другими биосистемами. Спиновая метка в случае производной меламида приводит к спектру электронного спинового резонанса, который представляет суперпозицию двух различных групп линий, обусловленных парамагнитными разновидностями при различных микро-окружениях. Первый спектр, изотропный триплет линий, обусловлен быстро движущейся спиновой меткой (с временем ротационной корреляции (τ_c≃10^-9 c); второй спектр представляет анизотропный асимметричный сигнал, возникающий от медленно движущейся спиновой метки (τ_c=10^-7 c). Предположение сферической формы бекла в растворе, которое следует из соотношения Стокса-Эйнштейна, позволяет оценить радиус молекулы, величина которого хорошо согласуется с измерениями малоуг лового рассеяния нейтронов. Обсуждается взаимодействие с другими биосистемами на основе анализа динамики молекул белка.

     

19F nuclear spin relaxation and spin diffusion effects in the single-ion magnet LiYF4:Ho3+

Temperature and magnetic field dependences of the ¹⁹F nuclear spin-lattice relaxation in a single crystal of LiYF₄ doped with holmium are described by an approach based on a detailed consideration of the magnetic dipole-dipole interactions between nuclei and impurity paramagnetic ions and nuclear spin diffusion processes. The observed non-exponential long time recovery of the nuclear magnetization after saturation at intermediate temperatures is in agreement with predictions of the spin-diffusion theory in a case of the diffusion limited relaxation. At avoided level crossings in the spectrum of electron-nuclear states of Ho^{3 +} ions, rates of nuclear spin-lattice relaxation increase due to quasi-resonant energy exchange between nuclei and paramagnetic ions in contrast to the predominant role played by electronic cross-relaxation processes in the low-frequency ac-susceptibility.     

Magnetic and relaxometric properties of polyethylenimine-coated superparamagnetic MRI contrast agents

Novel systems to be employed as superparamagnetic contrast agents (CA) for magnetic resonance imaging (MRI) have been synthesized. These compounds are composed of an iron oxide magnetic core coated by polyethylenimine (PEI) or carboxylated polyethylenimine (PEI-COOH). The aim of the present work was to prepare and study new nanostructured systems (with better or at least comparable relaxivities, R₁ and R₂, with respect to the commercial ones) with controlled, almost monodisperse average dimensions and shape, as candidates for molecular targeting. By means of atomic force microscopy (AFM) measurements we determined the average diameter, of the order of 200 nm, and the shape of the particles. The superparamagnetic behavior was assessed by SQUID measurements. From X-ray data the estimated average diameters of the magnetic cores were found to be 5.8 nm for PEI-COOH60 and 20 nm for the compound named PEI25. By NMR-dispersion (NMRD), we found that PEI-COOH60 presents R₁ and R₂ relaxivities slightly lower than Endorem^®. The experimental results suggest that these novel compounds can be used as MRI CA.     

Myocardial proton spin-lattice relaxation times in vitro: Effect of elapsed time after excision

An assumption made in using excised tissue for in vitro nuclear magnetic resonance (NMR) studies is that variables of interest, such as spin-lattice (T₁) relaxation times, remain stable for periods of time after excision sufficient to perform NMR spectroscopy. In this study, we evaluated the changes in T₁ of rat myocardium, measured at two NMR field strengths, at serial time intervals up to 72 hours postmortem. Left ventricular myocardium from six male Sprague-Dawley rats was excised and stored at room temperature in sealed NMR sample tubes. Spin-lattice relaxation times were determined with a modified inversion-recovery pulse sequence immediately postmortem and at intervals up to 72 hours post-excision; NMR studies were performed using 90 MHz and 360 MHz spectrometers. A gradual decrease in T₁ was noted with increasing time post-excision; T₁ was not significantly shorter than baseline until 72 hours postmortem at either field strength. The rate of change of T₁ was similar at the two field strengths. At any given time post-excision, T₁ was significantly higher (p < 0.001) at 360 MHz than at 90 MHz. We conclude that, with proper tissue handling and storage techniques, rat myocardial T₁ is stable postmortem sufficiently long to permit meaningful NMR studies of excised tissue.     

CaSO_4·(1/2)H_2O粉末中结晶水与吸附水1~H的Goldman-Shen实验

本文利用Goldman-Shen脉冲序列测量了CaSO_4·(1/2)H_2O样品中结晶水与吸附水~1H的交叉弛豫时间为55.1ms。在实验中,发现剩余窄线的磁化矢量随时间的衰减有三个过程。本文对此现象作了一些分析讨论。     

Anisotropic spin fluctuations in CeCoIn5

CeCoIn₅ is an unconventional heavy fermion superconductor with a relatively large transition temperature . NMR measurements of the spin lattice relaxation rate at the In(1) site reveal a significant anisotropy of the fluctuating hyperfine fields, which reverses below 30 K. These results suggest that two-dimensional fluctuations of the Ce 4f moments are relevant for the superconducting pairing.