Nuclear magnetic resonance relaxometry of the normal heart: Relationship between collagen content and relaxation times of the four chambers

The use of nuclear magnetic resonance (NMR) relaxation time measurements for characterization of abnormal cardiac tissue depends upon knowledge of variations of relaxation times of normal myocardium and determinants of these variations. We calculated in vitro NMR T₁ and T₂ relaxation times of canine myocardium from the four cardiac chambers, and determined hydroxyproline concentration (as a measure of collagen) and percent water content of the samples. We found both water content and T₁ relaxation time of the right ventricle to be significantly greater than the left atrium (p < 0.05). T₂ relaxation time of the left ventricle was found to be shorter than each of the other three chambers (p < 0.05). There were significant correlations between the spin-lattice relaxation time and both percent water content (r = 0.58) and hydroxyproline concentration (r = 0.45). A significant correlation was also found between T₂ relaxation time and hydroxyproline concentration (r = 0.49). When T₁ and T₂ were adjusted for water and hydroxyproline content, there was no longer any evidence for significant interchamber differences for either T₁ or T₂. These data suggest that differences in NMR relaxation times exist among the four chambers of the normal canine heart. Furthermore, a major determinant of myocardial spin-lattice relaxation time is tissue water content while both collagen content and percent water content significantly contribute to variability in cardiac chamber T₂ relaxation times.     

Magnetic resonance imaging of the normal and pathologic muscular system

Evaluation of the muscular system with magnetic resonance (MR) was conducted: (1) to assess the capability of MR to depict muscular abnormalities; (2) to evaluate the ability of MR to discriminate between various types of muscular pathologies based on relaxation parameters; and (3) to determine the optimal spin echo (SE) sequence that produced optimal contrast. Retrospective analysis was performed on 59 consecutive patients with a variety of muscular abnormalities. MR muscle analysis included visual inspection of contour and size; muscle intensity changes in relation to various TR/TE combinations; measurement of T1 and T2 relaxation and spin density; and calculation of percent contrast variation with different SE imaging combinations. Contour and size abnormalities were not reliable for detection of muscular pathology. For each individual subject intensity and relaxation times of all muscles involved by pathology differed from normal muscle. Although all pathologies caused increase in signal intensity of muscle, the alterations in relaxation times were variable. Fatty atrophy caused a decrease in T1 and increase in T2; while post-surgical changes, infection, acute intramuscular hemorrhage, and tumor invasion caused an increase in both T1 and T2. Percent contrast indicated that the optimum sequence for evaluation of fatty atrophy was a short (0.5 sec) repetition time (TR) and echo delay time (TE) of 56 msec, while for demonstration of the remaining muscular abnormalities, including post-surgical changes, infection, acute intramuscular hemorrhage, and tumor invasion, a long TR (TR = 2.0 sec) and TE (56 msec) was optimal. Differentiation between various benign and malignant muscular abnormalities (excluding fatty atrophy) was not possible using either quantitative intensity values or relaxation times.     

1H-NMR relaxation times and water compartmentalization in experimental tumor models

The present studies were conducted with RIF-1, M5076 and Panc02 subcutaneous tumor models to assess the relationship between tissue-free water compartmentalization and observed tissue T1 and T2 changes at 10 MHz. Observed T1 was shown to correlate directly with total extracellular water and interstitial water volumes. T1 and T2 were also inversely related to intracellular water volumes. T1 and T2 decreases after dexamethasone treatment were, however, most closely correlated with changes in tumor extracellular water and not changes in cell or total water volumes. Studies to assess Gd-DTPA-dimeg dose dependent T1 and T2 modification in model serum protein solutions indicated that although the Gd concentration that reduced T2 by 50% was about 2.5 fold greater than that required to reduce T1 equally, the of the concentration dependent T1 and T2 modifications were similar. In studies with tumor models, the injected dose of Gd-DTPA-dimeg that reduced T1 by 50% was inversely correlated with tumor extracellular water volumes. The slopes for dose dependent T1 modification in all tumors were similar and similar to that observed for model protein solutions. Gd-DTPA-dimeg had a different effect on observed T2 values for the 3 tumor models. Exponential slopes were about twice that observed for T2 modification of serum protein solutions, and Gd-DTPA-dimeg doses that reduced observed tumor T2 ranged from 9 to 50 times that necessary to similarly reduce T1. The results from these studies indicate that the observed T1, for these tumors, was dominated by relaxation of water protons in interstitial water but that the observed T2 was most strongly influenced by proton relaxation in water compartments that were unavailable to the Gd labeled probe.     

In vivo NMR T2 relaxation of experimental brain tumors in the cat: a multiparameter tissue characterization.

Experimental gliomas (F98) were inoculated in cat brain for the systematic study of their in vivo T₂ relaxation time behavior. With a CPMG multi-echo imaging sequence, a train of 16 echoes was evaluated to obtain the transverse relaxation time and the magnetization M(0) at time T = 0. The magnetization decay curves were analyzed for biexponentiality. All tissues showed monoexponential T₂, only that of the ventricular fluid and part of the vital tumor tissue were biexponential. Based on these NMR relaxation parameters the tissues were characterized, their correct assignment being assured by comparison with histological slices. T₂ of normal grey and white matter was 74 ± 6 and 72 ± 6 msec, respectively. These two tissue types were distinguished through M(0) which for white matter was only 0.88 of the intensity of grey matter in full agreement with water content, determined from tissue specimens. At the time of maximal tumor growth and edema spread a tissue differentiation was possible in NMR relaxation parameter images. Separation of the three tissue groups of normal tissue, tumor and edema was based on T₂ with T_2(normal) < T_2(tumor) < T_2(edema). Using M(0) as a second parameter the differentiation was supported, in particular between white matter and tumor or edema. Animals were studied at 1–4 wk after tumor implantation to study tumor development. The magnetization M(0) of both tumor and peritumoral edema went through a maximum between the second and third week of tumor growth. T₂ of edema was maximal at the same time with 133 ± 4 msec, while the relaxation time of tumor continued to increase during the whole growth period, reaching values of 114 ± 12 msec at the fourth week. Thus, a complete characterization of pathological tissues with NMR relaxometry must include a detailed study of the developmental changes of these tissues to assure correct experimental conditions for the goal of optimal contrast between normal and pathological regions in the NMR images.     

The measurement of extracellular water volumes in tissues by gadolinium modification of 1H-NMR spin lattice (T1) relaxation

The present studies were conducted in RIF-1, M5076 and Panc02 murine tumor models to compare extracellular water measurements made by 51Cr-EDTA dilution techniques and a new method which exploits the concentration dependent modification of 1H-NMR proton relaxation by Gadolinium-DTPA-dimethyl glucamine (Gd-DTPA-dimeg) in plasma and tissues. The time dependent changes in T1 modification in tissue and plasma were determined at various intervals after i.v. injection of 0.1 ml of 100 mM Gd-DTPA-dimeg and Gd concentrations determined from standard curves of Gd concentration dependent T1 modification of mouse plasma. Comparison of tissue and plasma Gd concentrations permitted the calculation of Gd-DTPA-dimeg distribution volumes. In unperturbed RIF-1, M5076 and Panc02 tumors, Gd-DTPA-dimeg distribution volumes determined by the T1 modification technique were similar to extracellular water spaces determined by 51Cr-EDTA dilution assays. In mouse liver, the 51Cr-EDTA assay resulted in artifactually high extracellular water space estimates due to internalization of the probe; Gd-DTPA-dimeg distribution volumes determined in liver with both the 153Gd-DTPA-dimeg and by the T1 modification method were approximately 150 ul/gram. The Gd-DTPA-dimeg T1 modification method also provided good approximations of changes in extracellular water volumes in RIF-1 tumors after dexamethasone and cyclophosphamide treatments. These results indicate that Gd-DTPA-dimeg modification of proton relaxation may be extremely useful for monitoring changes in tumor water dynamics during cancer therapy.     

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.     

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.     

Spin-lattice relaxation times of bound water—Its determination and implications for tissue discrimination

Measurements were made of T1 of bound water (T1b) and bound water fraction () for gelatin solutions and human tissues (sera, brain tumor, cerebral white matter). Bound water fraction in each sample was measured by means of thermal analysis (differential scanning calorimetry: DSC). T1 values were measured by FONAR QED 80-. T1b values were calculated by an equation derived from the fast-exchange two-state model. In the study of gelatin solutions, the relationship between T1 and water content differed depending on the sort of solutions. This was considered to be due to differences in T1b values. In each biological tissue the values of T1b and had different distributions. These results indicate that values of T1b and for biological tissues may be altered in correspondence to the changes in pathophysiological states in those tissues.     

Validity of NMR pore-size analysis of cultural heritage ancient building materials containing magnetic impurities

NMR relaxation time distributions, obtained with laboratory and portable devices, are utilized to characterize the pore-size distributions of building materials coming from the Roman remains of the Greek-Roman Theatre of Taormina. To validate the interpretation of relaxation data in terms of pore-size distribution, comparison of results from standard and in situ NMR experiments with results of the mercury intrusion porosimetry (MIP) has been made. Although the pore-size distributions can be obtained by NMR in terms of either longitudinal (T₁) or transverse (T₂) relaxation times distributions, the shorter duration of the T₂ measurement makes it, in principle, preferable, although the determination of T₂ distributions is not necessarily an easy alternative to finding T₁ distributions. Among other things, the T₁ distribution is almost independent of the inhomogeneity of the magnetic field, while the T₂ distribution is strongly influenced by it. This paper was aimed at answering two questions: what are the validity limits to interpret NMR data in terms of pore-size distributions and whether the portable device can successfully be applied as a non-destructive and non-invasive tool for in situ NMR analysis of building materials, particularly those of Cultural Heritage interest.     

NMR relaxation of protons in tissues and other macromolecular water solutions

Nuclear magnetic resonance (NMR) longitudinal (T₁) and transverse (T₂) relaxation parameters have been evaluated for protein solutions, cellular suspensions and tissues using both data from our laboratory and the extensive literature. It is found that this data can be generalized and explained in terms of three water phases: free water, hydration water, and crystalline water. The proposed model which we refer to as the FPD model differs from similar models in that it assumes that free and hydration water are two phases with distinct relaxation times but that T₁ = T₂ in each phase. In addition there is a single correlation time for each rather than a distribution as assumed in most other models. Longitudinal decay is predicted to be single exponent in character resulting from a fast exchange between the free and hydration compartments. Transverse decay is predicted to be multiphasic with crystalline (T₂ 10 μsec), hydration (T₂ 10 sec) and free (T₂ 100 sec) water normally visible. The observed or effective transverse relaxation times for both the hydration and free water phases are greatly affected by the crystalline phase and are much shorter than the inherent relaxation times.     

Microscopic measurements in La-NQR of the ternary carbide superconductor LaNiC2

¹³⁹La-NQR measurements have been carried out in the ternary carbide superconductor LaNiC₂. The nuclear quadrupole frequency and the asymmetry parameter of ¹³⁹La in LaNiC₂ were estimated to be about 1.9 MHz and 0, respectively. In the normal state, the nuclear spin relaxation rate (1/T₁) in the ¹³⁹La NQR signal was proportional to temperature (T) in zero external field above the superconducting transition temperature (T_c) or in an external field larger than the superconducting critical field, which means the system is in the Fermi-liquid state. In the superconducting state, on the other hand, 1/T₁ decreases no more linearly with T, but decreases rapidly exponentially as exp (−Δ/k_BT) at low T with an appreciable enhancement just below T_c. The value of the superconducting energy gap, 2Δ, was estimated to be 3.34k_BT_c, compared with 3.52k_BT_c of the BCS-value. This result strongly suggests that the superconductivity in LaNiC₂ is of a conventional BCS type.     

Proton spectroscopy of human stroke: Assessment of transverse relaxation times and partial volume effects in single volume STEAM MRS

Proton T₂ relaxation times were measured in 13 stroke patients and 13 aged-matched normal subjects at 2.1 T. Spectra were acquired from an 8-cc volume using the STEAM sequence with echo times (TE) of 30.4 ms and 270.0 ms and repetition time of 2.8 s. Transverse relaxation times were estimated using two-point calculations. Percentage volume of infarct in the STEAM voxel was measured on spin-echo MRI encompassing the infarct and correlated with the peak amplitude of N-acetylated compounds (NA). T₂ values of NA, creatine, and choline resonances showed no significant difference between patients and controls. T₂ for lactate in patients was 780 ± 257 ms, respectively (mean ± SE, n = 7). In stroke patients, high inverse correlation was found between the absolute NA signal and partial volume of normal brain contributing to each spectrum (p < .001, r = 0.97). Together with unchanged T₂, this suggests that NAA largely disappears from infarcted tissue within 24 hr postinfarct.     

Fiber-to-field angle dependence of proton nuclear magnetic relaxation in collagen

Longitudinal and transverse proton relaxation times were measured on pig tendon. For T₁, dispersion curves and more accurate measurements at 20 MHz are presented. Values of T₂ were obtained from CPMG pulse sequences, at 20 MHz. The dependence of relaxation times against the fiber-to-field angle was particularly investigated. Longitudinal relaxation rate was found to be almost orientation independent, and presented quadrupolar peaks between 1 and 4 MHz. On the contrary, transverse relaxation, that was well fitted by the sum of four exponentials, was highly orientation dependent. Deconvolution showed that the exponentials decaying most quickly are most orientation dependent. For those two fractions, a cross-relaxation model allowed explaining the fiber-to-field angle dependence, and the specially low rate corresponding to the magic angle of 55°. Finally, each decaying mode was assigned to a fraction of protons localized in the macromolecular structure and characterized by particular dynamics.     

固体核磁共振研究半晶聚-3-羟基丁酸酯和聚羟基丁酸戊酸酯的分子动力学

本文在150~370 K温度范围内,采用固体核磁共振（NMR）测定了半晶聚-3-羟基丁酸酯（PHB）,以及3-羟基戊酸酯单体质量分数分别为5%（PHBV5）和12%（PHBV12）的聚羟基丁酸戊酸酯共聚物在实验室坐标系和旋转坐标系条件下质子的自旋-晶格弛豫时间T₁和T_1ρ.通过弛豫时间随温度变化的理论拟合,分别获得上述半晶聚合物晶区和结晶区的分子动力学参数（包括E_a和τ₀）.这些结果从分子水平上阐述了PHB结构修饰和增强的原因.     

MRI of hepatic lymphoma

Thirteen patients with biopsy proven hepatic lymphoma (2 Hodgkin, 11 Non-Hodgkin) and a control group of 15 patients with hepatic metastases were analyzed quantitatively and qualitatively by MRI. Focal hepatic lymphoma was most reliably detected (eight of eight patients) and appeared hypointense relative to liver on T₁ weighted (CNR − 7.4 ± 2.3) and hyperintense on T₂ weighted (CNR + 8.4 ± 2.9) images. The mean T₁ and T₂ relaxation times of focal hepatic lymphoma (T₁ = 832 ± 234 msec, T₂ = 84 ± 16 ms) differed significantly from adjacent non-tumorous liver (T₁ = 420 ± 121 ms, T₂ = 51 ± 9 ms; p < 0.05), however CNR values and relaxation times were similar to those of hepatic metastases. Diffuse hepatic lymphoma (microscopic periportal infiltration) was undetectable by MRI in three patients by either morphologic features or quantitative criteria. A mixed pattern of hepatic lymphoma (focal lesions and diffuse infiltration) showed focal areas of slightly decreased signal intensity on T₁ weighted images (CNR = −1.7 ± 0.4) while T₂ weighted images revealed multiple regions of focal hyperintensity (CNR = +13.3 ± 8.4) superimposed on a diffusely hyperintense liver. Our experience demonstrates that either T₁ or T₂ weighted techniques are useful in detecting focal and that T₂ weighted techniques are useful in detecting mixed hepatic lymphoma. Conventional image derived relaxation time measurements and quantitative parameters were of no additional diagnostic value.     

In vivo relaxation of N-acetyl-aspartate, creatine plus phosphocreatine, and choline containing compounds during the course of brain infarction: a proton MRS study.

Localized water suppressed proton spectroscopy has opened up a new field of pathophysiological studies of severe brain ischemia. The signals obtained with the pulse sequences used so far are both T₁ and T₂ weighted. In order to evaluate the extent to which changes in metabolite signals during the course of infarction can be explained by changes in T₁ and T₂ relaxation times, eight patients with acute stroke were studied. STEAM sequences with varying echo delay times and repetition times were used to measure T₁ and T₂ of N-acetyl-aspartate (NAA), creatine plus phosphocreatine (Cr+PCr) and choline containing compounds (CHO) in a 27-ml voxel located in the affected area of the brain. Ten healthy volunteers served as controls. We found no difference in T₁ or T₂ of the metabolites between the patients and the normal controls. The T₂ of CHO was longer than that of NAA and Cr+PCr. Our results indicate that spectra obtained in brain infarcts and normal tissue with the same acquisition parameters are directly comparable with respect to relative signal intensities as well as signals scaled with internal and external standards.     

Thermal transport properties in a He---He mixture near and below the superfluid transition

Measurements of the thermal conductivity and of X/T are reported for a ³He---⁴He mixture with a ³He mole fraction X = 0.622. At T_λ, X/T passes through a sharp peak. A comparison with the theory of Khalatnikov is presented. The relaxation times τ(T) to reach steady state conditions show qualitatively the same behaviors as X/T.     

Radiation-induced changes in phosphorus T1values in human melanoma xenografts studied by P-MRS

³¹P-magnetic resonance spectroscopy (MRS) has been shown to be a promising method for monitoring tumor response to radiation therapy. The purpose of the work reported here was to investigate whether the usefulness of ³¹P-MRS might be enhanced by measurement of spin-lattice relaxation times (T₁s) in addition to resonance ratios. The work was based on the hypothesis that tumors having a high probability of being controlled locally would show shortened T₁s during the treatment course due to reoxygenation and development of necrosis. BEX-t human melanoma xenografts, which show efficient reoxygenation and development of necrosis following single dose irradiation, were used as tumor models. Tumors were treated with single doses of 5.0 or 15.0 Gy and the T₁s of the inorganic phosphate and nucleoside triphosphate β resonances were measured as a function of time after irradiation by using the superfast inversion recovery method. Fractional tumor water content was determined by drying excised tumors at 50°C until a constant weight was reached. The T₁s in irradiated tumors were either longer than or not significantly different from those in unirradiated control tumors. The increase in the T₁s following irradiation coincided in time with a radiation-induced increase in tumor water content, suggesting a causal relationship. The effects of reoxygenation and development of necrosis on T₁s were probably overshadowed by the effects of tumor water content. Consequently, the usefulness of ³¹P-MRS in monitoring tumor response to radiation therapy might not be significantly enhanced by measurement of T₁s.     

Molecular dynamics in solid riboflavin as studied by 1H NMR

Spin–lattice relaxation times T₁ and T_1d as well as NMR second moment were employed to study the molecular dynamics of riboflavin (vitamin B₂) in the temperature range 55–350 K. The broad and flat T₁ minimum observed at low temperatures is attributed to the motion of two nonequivalent methyl groups. The motion of the methyl groups is interpreted in terms of Haupt's theory, which takes into account the tunneling assisted relaxation. An additional mechanism of relaxation in the high temperature region is provided by the motion of a proton in one of the hydroxyl groups. The Davidson–Cole distribution of correlation times for this motion is assumed.     

Quantitative cerebral magnetic resonance imaging during ACTH treatment of multiple sclerosis

Serial MR scans were performed with the 2DFT imaging method and the filtered backprojection imaging method on 12 patients with multiple sclerosis in acute phase, 4 in a relapsing/remitting form, and 8 in a progressive form, before, during and after ACTH treatment. Both T₁ and T_2mono relaxation times, obtained by fitting transverse magnetization decay curves with a monoexponential function within the apparently normal white matter and the areas of increased signal, were measured. With the backprojection method it was possible to fit the transverse magnetization decay curve with a biexponential function and obtain T_2long and T_2short relaxation times. The T_2mono and T₁ relaxation times of the apparently normal white matter were significantly different from those obtained for volunteers, but no significant differences were found before, during, or after treatment. The transverse magnetization decay curves of the areas of increased signal were better fitted by a biexponential function. No significant changes in these relaxation times were observed after ACTH treatment. These results argue against an anti-oedematous action of ACTH and may suggest that it has an immunosuppressant effect.