Determination of saturation transfer parameters of human tissues in vivo

In order to study the applicability of magnetization transfer contrast (MTC) to tissue differentiation, the determination of the magnetization transfer (MT) parameters of normal tissues is necessary for the evaluation of pathological conditions. The time-dependent saturation transfer technique was used to investigate the observed magnetization transfer parameters in several human tissues in vivo at 0.1 T. The length of the off-resonance saturation pulse varied from 0 to 750 ms. The magnetization transfer contrast (MTC) was 0.71 in striated muscle, 0.49 in liver, 0.49 in renal cortex, and 0.50 in spleen. The observed magnetization transfer rates (R_wm) were 5.5 s⁻¹ for muscle, 3.1 s⁻¹ for liver, and 1.5 s⁻¹ for both renal cortex and spleen. Our results indicate that measuring R_wm and possibly other relaxation parameters could be useful in tissue differentiation.     

Effects of off-resonance irradiation, cross-relaxation, and chemical exchange on steady-state magnetization and effective spin-lattice relaxation times

In the presence of an off-resonance radiofrequency field, recovery of longitudinal magnetization to a steady state is not purely monoexponential. Under reasonable conditions with zero initial magnetization, recovery is nearly exponential and an effective relaxation rate constant R_1eff = 1/T_1eff can be obtained. Exact and approximate formulas for R_1eff and steady-state magnetization are derived from the Bloch equations for spins undergoing cross-relaxation and chemical exchange between two sites in the presence of an off-resonance radiofrequency field. The relaxation formulas require that the magnetization of one spin is constant, but not necessarily zero, while the other spin relaxes. Extension to three sites with one radiofrequency field is explained. The special cases of off-resonance effects alone and with cross-relaxation or chemical exchange, cross-relaxation alone, and chemical exchange alone are compared. The inaccuracy in saturation transfer measurements of exchange rate constants by published formulas is discussed for the creatine kinase reaction.     

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.     

Proton nuclear magnetic resonance spectroscopy of normal and edematous brain tissue in vitro: Changes in relaxation during tissue storage

Proton nuclear magnetic resonance relaxation times, T₁ and T₂, of water in unfixed gray and white matter from normal and edematous rabbit brain tissues were measured in vitro at 23°C and 100 MHz to evaluate the effects of the temperature (?25°C to 37°C) and duration (0 to 96 h) of tissue storage on relaxation times. T₁ and T₂ tended to decrease during storage, probably from slow dehydration of the tissue. This effect was greatest in tissues stored at 37°C and least in those stored at 4 and ?25°C; decreases in T₁ and T₂ were greater in white matter than in gray matter. Freezing brain tissue to ?25°C caused a sudden decrease in the T₂ of normal white matter. Relaxation times were constant for 5 h in tissues stored at 23°C and for 40 h at 4°C. These results correlated well with corresponding tissue water loss.     

Multi-component T1 relaxation and magnetisation transfer in peripheral nerve

We report here a study of longitudinal relaxation (T₁) and magnetisation transfer (MT) in peripheral nerve. Amphibian sciatic nerve was maintained in vitro and studied at a magnetic field strength of 3 T. A CPMG pulse sequence was modified to include either a saturation pulse to measure T₁ relaxation or an off-resonance RF irradiation pulse to measure MT. The resulting transverse relaxation (T₂) spectra yielded four components corresponding to three nerve compartments, taken to result from myelinic, axonal, and inter-axonal water, and a fourth corresponding to the buffer solution water in which the nerve sample was bathed. Each nerve component was analysed for T₁ relaxation and MT. All three nerve T₂ components exhibited unique T₁ relaxation and MT characteristics, providing further support for the assignment of the components to unique physical compartments of water. Numerical investigation of T_1sat measurements of each of the three nerve T₂ components indicates that while the two shorter-lived exhibit similar steady-state magnetisation transfer ratios (MTRs), their respective MT properties are quite different. Simulations demonstrate that mobile water exchange between these two components is not necessary to explain their similar steady-state MTR. In the context of the assignment of these two components to signal from myelinic and axonal water, this is to say that these two microanatomical regions of nerve may exhibit similar steady-state MTR characteristics despite possessing widely different MT exchange rates. Therefore, interpreting changes in MTR solely to reflect a change in degree of myelination could lead to erroneous conclusions.     

MRI of human tumor xenografts in vivo: Proton relaxation times and extracellular tumor volume

Proton T₁ and T₂ differ substantially between tumors, but the tumor properties causing heterogeneity in T₁ and T₂ have not been fully recognized. The purpose of the study reported here was to investigate whether differences in T₁ and T₂ between tumors are mainly a consequence of differences in the fractional volume of the extracellular compartment. The study was performed using a single human tumor xenograft line showing large naturally occurring intratumor heterogeneity in the size of the extracellular compartment. The size of the extracellular compartment was calculated from the volume and the density of the tumor cells. Cell volume was measured by an electronic particle counter. Cell density was determined by stereological analysis of histological preparations. T₁ and T₂ were measured by MRI in vivo both in the absence and presence of Gd-DTPA. Two spin-echo pulse sequences were used, one with a repetition time (TR) of 600 ms and echo times (TEs) of 20, 40, 60, and 80 ms and the other with a TR of 2,000 ms and TEs of 20, 40, 60, and 80 ms. Measurements of T₁ and T₂ in the presence of Gd-DTPA were performed in a state of semi-equilibrium between uptake and clearance of Gd-DTPA. MR-images and histological preparations of tumor subregions homogeneous in extracellular volume were analysed in pairs. The extracellular volume differed between tumor subregions from 5 to 70%. T₁ and T₂ measured in the absence of Gd-DTPA differed between tumor subregions by a factor of approximately 1.5 and increased with increasing extracellular volume. The relative decrease in T₁ caused by Gd-DTPA, represented by $\text{(T}{}_{\mathrm{<mtext>1\; control</mtext>}}\text{−T}{}_{\mathrm{<mtext>1\; Gd-DTPA</mtext>}}\text{)}\text{T}{}_{\mathrm{<mtext>1\; control</mtext>}}$, also increased with increasing extracellular volume. The relative decrease in T₂ did not change significantly as the extracellular volume increased. These observations strongly suggest that the size of the extra-cellular compartment is a major determinant of proton T₁s and T₂s of tumors, possibly because the ratios of free to structured and free to bound water increase with increasing extracellular tumor volume.     

Quantification of Gd-DTPA concentration in neuroimaging using T₁3D MP-RAGE sequence at 3.0 T

Purpose

To propose a simple and accurate quantitative method based on the linear relationship between magnetic resonance (MR) signal enhancement (ΔSI=SI_postcontrast−SI_precontrast) and gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) concentration (C) by using T₁-weighted three-dimensional magnetization-prepared rapid acquisition gradient-echo (T₁ 3D MP-RAGE) sequence for the in vivo measurement of Gd-DTPA concentration in real-time neuroimaging at 3.0 T.

Methods

Phantom experiment was carried out to study the linear fitting of signal intensity change vs. Gd-DTPA concentration (ΔSI-C) curve. A goodness-of-fit test was performed to compare the accuracy between the proposed method and the conventional method based on longitudinal relaxation rate (R₁=1/T₁) measurement. The influences on the goodness of fit (R²) and the signal-to-noise ratio (SNR) by sequence parameters were explored. Six human subjects with different brain tumors, who underwent a Gd-DTPA-enhanced MRI, were enrolled for in vivo application of the novel method.

Results

A good linear relationship between ΔSI and Gd-DTPA concentration existed over the concentration range of 0-1 mM (R²=0.985). The linearity of the ΔSI-C curve was as good as that of the 1/T₁-C curve (R²=0.988). Concentrations calculated by both methods had a strong correlation (R²=0.920). An improved linearity of the ΔSI-C curve and an increased SNR can be achieved using sequences with a shorter inversion time (TI) and a higher flip angle. The concentration range of Gd-DTPA in human brain tumors was within the quantitative scope of 0-1 mM.

Conclusions

The proposed quantitative method based on ΔSI measurement is accurate and applicable for real-time neuroimaging at 3.0 T.     

Magnetization transfer contrast (MTC) and long repetition time spin-echo MR imaging in multiple sclerosis

Purpose: To study whether application of magnetization transfer contrast (MTC) improves visibility and detection of multiple sclerosis (MS) lesions on long repetition time (TR) conventional spin-echo (CSE) or fast spin-echo (FSE) magnetic resonance (MR) imaging.Material and methods: In 20 patients and 5 controls, MR images were obtained using long repetition time CSE and FSE sequences with and without MTC. Signal-to-noise ratios of normal appearing white matter (NAWM) and selected lesions, and contrast-to-noise ratios between lesions and NAWM, were calculated. Lesions were counted and total lesion volume was measured in a blinded fashion for each sequence.Results: In controls, MT effect in white matter (16.3% vs. 12.2%) was higher for CSE than for FSE (p < 0.01). Application of MTC to either CSE or FSE resulted in a significantly lower decrease in signal intensity of NAWM in patients compared to white matter in controls (p < 0.01). Furthermore, in patients signal intensity of lesions was less decreased than signal intensity of NAWM (p < 0.01). Compared to sequences without MTC, contrast-to-noise ratios were significantly higher on both CSE (10.9%) and FSE (6.3%) when MTC was applied (p < 0.01). Despite better visibility, the number of lesions detected on either sequences did not increase when MTC was applied. For CSE with MTC, we found an almost equal number of lesions and for FSE with MTC, we found even less lesions (p < 0.01). Total lesion volume did not change significantly when MTC was applied.Conclusion: Although contrast between lesions and NAWM improved when magnetization transfer contrast was applied, this did not increase detection of MS lesions on either CSE or FSE MR imaging.     

Spin relaxation studies on conducting poly(tetrathiafulvalene)

Magnetic parameters and the relaxation behavior of paramagnetic centers in an iodine-doped poly(tetrathiafulvalene) semiconductor with a d.c. conductivity of 10^?5 S·cm^?1 have been studied using mainly the 2 mm waveband EPR technique in the temperature range of 110–270 K. The EPR line shape analysis confirms the existence of immobile radicals pinne on short polymer chains and mobile polarons with different relaxation parameters in slightly doped poly(tetrathiafulvalene). The temperature dependences of electron spin-lattice and spin-spin relaxation times of paramagnetic centers of both types have been determined independently using the saturation method at the operation frequency ν _e = 140 GHz. An anisotropic slow libration of immobile polarons with an activation energy of 0.02 eV have been registered for the first time using the saturation transfer EPR method. The temperature dependences of intrachain diffusion and interchain hopping rates in poly(tetrathiafulvalene) are determined from theT ₁ andT ₂ EPR data. The interchain spin dynamics is shown to correlate with libration of polarons trapped on polymer chains and is in good agreement with a hopping charge transport mechanism.     

Critical nuclear relaxation in cobalt metal

Nuclear magnetic resonance of cobalt metal was investigated in the paramagnetic and ferromagnetic states and in the critical region below T_c. The Knight shift and spin lattice relaxation times were measured in the paramagnetic phase in the solid and liquid states from 1578 K to 1825 K. The resonant frequency, spin-lattice and spin-spin relaxation times were measured in the ferromagnetic phase from room temperature to 1385 K. The main part of (T₁T)^-1 results from fluctuating orbital moments in both phases except near T_c where this process forms the background for critical spin relaxation. The critical exponents for T^-1₁ and for the magnetization in the ferromagnetic state were found to be n' = 0.96 ± 0.07 and β = 0.308 ± 0.012, respectively.     

Analysis of longitudinal relaxation rate constants from magnetization transfer MR images of human tissues at 0.1 T.

The human calf muscle was examined by using the magnetization transfer MR imaging technique. The time-dependent saturation transfer (TDST) method was applied at low magnetic field 0.1 T in order to measure the mobile water relaxation time T1w, the magnetization transfer rate Rwm from water to solid macromolecules, and the magnetization transfer contrast (MTC) of the human tissue. The magnetization transfer contrast of 0.67 was attained. The transfer rate Rwm was 4.5 sec-1 (+/- 0.3 sec-1) for the anterior tibial muscle and 5.0 sec-1 (+/- 0.4 sec-1) for the gastrocnemius muscles. The values of Rwm are considerably larger than the values of corresponding relaxation rates measured at high fields. The relaxation rate measurements of human tissues in vivo was shown to be possible at 0.1 T even within the framework of normal routine MR imaging. Magnetization transfer MR imaging is a very promising and practical method in order to assess the relaxation processes in heterogeneous human tissues in vivo, and it can improve the tissue characterization possibilities of MR imaging techniques.     

Effect of fasting and food intake on magnetization transfer of human liver tissue

Magnetization transfer (MT) technique is a promising method in differential diagnosis of diseases in parenchymal tissues. Basic knowledge about circumstances and elementary factors that influence MT and its parameters is still insufficient, however. Having a meal before the magnetic resonance (MR) examination could change liver MT parameters compared to fasting state through alteration in liver perfusion, blood flow, and content of portal blood (proteins and other derivates from a meal). If MT parameters can be altered by a meal, then MR liver studies should always be performed after fasting. Before MRI examinations we examined three healthy volunteers after a high-fat meal with Doppler ultrasound technique to find out duration and magnitude of changes in portal blood flow. Duration of ≥50% increased peak-flow value compared to fasting state in portal vein was >90 min, which is enough for our MR examination. With a low-field 0.1-T MR imager we examined 10 healthy volunteers after a short (range from 3 h 45 min to 17 h 30 min) fast and also immediately after a high-fat meal. Magnetization transfer parameters, magnetization transfer ratio (MTR) and magnetization transfer rate R_wm of liver tissue were determined. MTR changed significantly (Student paired two-tailed t-test, p = .0044) after a meal, but R_wm did not (p = .0952). We recommend a 4 h fast before MR examination that aims to determine the MTR of liver tissue.     

The concentration dependence of relaxation times of hydrogen proton in the aqueous solution of iron ferrite magnetic nanoparticles

By the direct coprecipitation of the aqueous solution of iron salt and tetramethylammonium hydroxide solution the stable iron ferrite nanoparticles were formulated. These nanoparticles were found to have uniform sizes of about 7 nm, and also showed no coalescence in the aqueous solution for a few months. The superparamagnetic behavior of these nanoparticles was checked by a vibrating sample magnetometer. Also, the temperature dependence of saturation magnetization of nanoparticles was observed using a superconducting quantum interface device magnetometer. The relaxation times of T₁ and T₂ of hydrogen proton in the colloidal aqueous solution of magnetic nanoparticles were measured using a nuclear magnetic resonance spectrometer for the wide range of concentration of nanoparticles in the aqueous solution. The inverse of relaxation times was observed to be directly dependent on the concentration of nanoparticles.     

Anomalous magnetism and 209Bi nuclear spin relaxation in Bi4Ge3O12 crystals

The quadrupole ²⁰⁹Bi spin–spin and spin–lattice relaxation were studied within 4.2–300 K for pure and doped Bi₄Ge₃O₁₂ single crystals which exhibit, as was previously found, anomalous magnetic properties. The results revealed an unexpectedly strong influence of minor amounts of paramagnetic dopants (0.015–0.5 mol.%) on the relaxation processes. Various mechanisms (quadrupole, crystal electric field, electron spin fluctuations) govern the spin–lattice relaxation time T ₁ in pure and doped samples. Unlike T ₁, the spin–spin relaxation time T ₂ for pure and Nd-doped samples was weakly dependent on temperature within 4.2–300 K. Doping Bi₄Ge₃O₁₂ with paramagnetic atoms strongly elongated T ₂. The elongation, although not so strong, was also observed for pure and doped crystals under the influence of weak (～30 Oe) external magnetic fields. To confirm the conclusion about strong influence of crystal field effects on the temperature dependence of T ₁ in the temperature range 4.2–77 K, the magnetization vs. temperature and magnetic field was measured for Nd- and Gd-doped Bi₄Ge₃O₁₂ crystals using a SQUID magnetometer. The temperature behavior of magnetic susceptibility for the Nd-doped crystal was consistent with the presence of the crystal electric field effects. For the Gd-doped crystal, the Brillouin formula perfectly fitted the curve of magnetization vs. magnetic field, which pointed to the absence of the crystal electric field contribution into the spin–lattice relaxation process in this sample.     

Assessment of interstitial water content of articular cartilage with T1 relaxation

The interstitial water content typically increases in the early degeneration of articular cartilage. Previously, T₂ relaxation has been related to water content, yet it is known to be strongly affected by the collagen orientation. Articular cartilage plugs from the bovine patella, femur and tibia (N=20) were mapped for T₁ and T₂ at 9.4 T to test the ability of T₁ relaxation to reflect cartilage water content. As a reference, water and proteoglycan (PG) contents were determined. Significant (P<.01) linear associations were demonstrated between the relaxation rates and tissue water content (R₁: r=−.81, R₂: r=−.60) and PG content (R₁: r=.75). After adjustment for the tissue water content, partial correlation analysis did not show significant associations between the relaxation rates and tissue PG content. After the effect of PGs was removed, significant (P<.05) linear correlation between the relaxation rates and tissue water content (R₁: r=−.48, R₂: r=−.50) was observed. Thus, the spin-lattice relaxation rate is proposed to provide a biomarker for water content in articular cartilage.     

A relaxation phenomenon observed in fine gold wire

Two modulation techniques were used to determine the heat capacity of 1 mil gold wire as a function of temperature. A frequency effect was observed at high temperature in the directly measured parameter C_p/(1/R_m) (dR/dT)T_m where C_p is the specific heat at constant pressure and R_m is the resistance of the specimen at temperature T_m. It is believed that the vacancy defect is responsible for this frequency effect. The relaxation phenomenon observed suggests the surface of the wire as the source of the vacancies.     

Can transverse relaxation rates in deep gray matter be approximated from functional and T2-weighted FLAIR scans for relative brain iron quantification?

Alterations in iron concentration in certain deep gray matter regions are known to occur in aging and several clinical conditions. In vivo measurements of R₂¹ transverse relaxation rates and quantitative susceptibility mapping (QSM) have been shown to be strongly correlated with iron concentration in tissue, but their calculation requires the acquisition of a multi-echo gradient recalled echo sequence (MGRE). In the current study, we examined the feasibility of approximating R₂¹ rates using metrics derived from fMRI-EPI and T₂-weighted FLAIR images, which are widely available. In a sample of 40 healthy subjects, we obtained these metrics (v_EPI and v_FLAIR), as well as R₂¹ rates and QSM estimates, and found significant correlations between v_EPI and v_FLAIR and R₂¹ rates in several subcortical gray matter regions known to accumulate iron, but not in a control corticospinal white matter region. These relationships were preserved after referencing v_EPI and v_FLAIR with respect to the values in the control region. Effect sizes (above 0.5 for some of the regions, particularly the largest ones) were calculated and put in relation to those of the correlation between QSM and R₂¹ rates. We propose that the metrics described here may be applied, possibly in a retrospective fashion, to analyze datasets with available EPI or T₂-weighted FLAIR scans (and lacking a MGRE sequence), to devise new hypotheses regarding links between iron concentration in brain tissue and other variables of interest.     

Magnetism,spin relaxation and hyperfine interactions of rare earths in RM6Al6(M = Cr,Mn, Cu)

The systems RM₆Al₆ (R = rare earth or Y, M = Cr, Mn, Cu, Rh) were studied by magnetization measurements and by Mossbauer spectroscopy of ¹⁵⁵Gd, ¹⁶¹Dy, ¹⁶⁶Er and ¹⁷⁰Yb. The magnetization studies show weak R-R antiferromagnetic exchange interactions in RCu₆Al₆(T_n)Gd) = 21 K, less than 4 K for all other R and strong crystalline field effects. Similar phenomena are observed in RMn₆Al₆ and RCr₆Al₆, however, due to the presence of a Mn or Cr local moment the systems order ferrimagnetically. In RCr₆Al₆the order temperatures are low T_c ～ 25 K, yet T_c(GdCr₆Al₆) = 170 K. The Mossbauer studies observations are consistent with the magnetiza results. In the case where Er and Yb are not ordered at 4.1 K, the spectra still show magnetic hyperfine structure however of paramagnetic nature. The spectra yield the hyperfine interaction spin Hamiltonian parameters and the spin relaxation rates. These turn out to be extremely slow (1O⁸–1O⁹ sec^?1, a very uncommon phenomenon for a concentrated Er or Yb metallic system.     

A new method for determining the relaxation times,T 1 andT 2, from progressive saturation of inhomogeneously broadened lines

An analytical method to determine the spin-lattice (T ₁), and spin-spin (T ₂), relaxation times for inhomogeneously broadened lines obtained from electron paramagnetic resonance (EPR) experiments is presented in this work. To apply this method, the knowledge of the lineshape of the saturation curve is not necesssary, only the Lorentzian and Gaussian widths are required and these are obtained from a non-saturated line. The relaxation times are calculated by using continuous saturation under slow passage conditions. An explicit algebraic equation for the direct calculation ofT ₁, and the general form of the saturation curve for a single line in an EPR signal are given. The equation given to calculateT ₁ can also be used for substances in which the full saturation can not be obtained experimentally. A comparison of the results obtained for some substances by using the present method with respect to other existent ones, is carried out to show its reliability.     

Transverse relaxation time constraints on resolution in one-dimensional,phase- and frequency-encoded nuclear magnetic resonance imaging

The theoretical dependence of the resolution on the relationship of sampling time to transverse relaxation time (T₂) for frequency-encoded, one-dimensional NMR imaging using constant field gradients has been investigated. A resolution function that is explicitly dependent on the sampling time is derived, and it is shown that the observed image of an object can be written as a convolution of the sample magnetization with this resolution function. This function is explicitly calculated for two cases of interest: (1) for sampling times much shorter than T₂, and (2) for sampling times much longer than T₂. These cases are illustrated for two examples: (1) a uniform magnetic bar, and (2) uniform periodic magnetic bars. When oscillating gradients are utilized, these results still hold in the limit of slow oscillation. The resolution in phase-encoded NMR imaging is not explicitly dependent on the sampling time.