Distinction between normal and leukemic bone marrow by water protons nuclear magnetic resonance relaxation times

Pulsed nuclear magnetic resonance studies have been carried out on bone marrow of normal human subjects and patients with leukemia: chronic myeloid leukemia (CML) and acute myeloid leukemia (AML). It was observed that the proton spin-lattice relaxation time (T₁) value was discriminatory in the normal and leukemic cases with a statistical significance of (p < 0.01). Ouabain treatment of cells did not show any perceptible change of T₁ value when compared with the nontreated cells, indicating that the concomitant cation effluxes do not affect spin-lattice relaxation time. The water contents of normal, leukemic, and ouabain treated cells were in the range 60%–80%. Higher Fe levels were encountered in the normal than the leukemic samples, while levels of Zn, Cu, Mn, Co, and Ni were elevated in the leukemic samples compared with the normals. Despite the T₁ differences observed, the multiparameter studies do not uniquely pinpoint factors responsible for the elevation of T₁ in the malignant state.     

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.     

Proton magnetic resonance microimaging of human trabecular bone

Proton magnetic resonance (1H magnetic resonance imaging (MRI)) images of human trabecular bone were acquired and discussed for two samples with different porosity. Three-dimensional 3D Spin Echo (3D SE) and Multi-Slice Multi-Echo (MSME) pulse sequences were examined. A very high slice resolution of (38 microm)2 was achieved (MSME). The intensity histograms were found useful for the characterization of the bone porosity. A spatial distribution of the spin-spin relaxation time T2 was monitored with the MSME pulse program. The work demonstrates the great potential of the proton MRI technique in the study of the trabecular bone morphology.     

Continuous distribution analysis of marrow 1H magnetic resonance relaxation in bone

Longitudinal and transverse NMR relaxation of 1H nuclei were studied in vitro on fresh animal femur samples. A large number of data points were taken, starting at 100 micros for T(1) by inversion-recovery, at 200 micros for T(2) by single-echo sequences, and at 600 micros for T(2) by CPMG echo-trains. Quasi-continuous distributions of relaxation times were computed, giving wide distributions for all samples. Bulk marrow removed from the medullary cavity showed T(2) distributions from about 20 ms to 600 ms and T(1) distributions from about 40 ms to 2 s. The 1H nuclei in trabecular bone samples, where marrow is confined, may show long tails for T(2) at relaxation times down to 250 micros, the origin of which is still not known. These tails are absent in bulk marrow from the medullary cavity. The differences observed in T(1) distributions among trabecular bone samples are in accordance with the different marrow compositions. Discrete exponential fits were computed also, and in most cases four discrete exponential components were required to fit the experimental data adequately. However, the discrete components do not seem to correspond to any physically distinguishable separate compartments.     

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.     

Proton magnetic relaxation in bone marrow related to age and bone mineral density: low-resolution in vitro studies.

Detailed analysis of proton spin-spin and spin-lattice relaxation behaviors of the bone marrow in the presence of trabecular bone network was performed at low-resolution (B(0) = 0.496T) on rat vertebrae specimens deprived of spinal cord. Two groups of samples, from young and old healthy animals, were investigated before cellular necrosis had started. BMD measurements were carried out to quantify the expected age-related modifications of the trabecular bone network. 1H-MR measurements were also performed on the same samples, deprived of marrow and saturated with water, in order to control the validity of a possible interpretation of the marrow 1H-MR characteristics, in terms of marrow components, and to investigate the possible employment of these samples to study the trabecular bone network properties. We pointed out that: 1) a bimodal distribution of T(2i) and T(1i) values (distinguishing "fast" and "slow" relaxations) describes satisfactorily all the 1H-MR experimental decays; 2) age-related modifications of the trabecular bone network are marked by correlate variations of the BMD value and of the proton spin-spin relaxation rates in water saturated samples; 3) age-related modifications of marrow are underlined by variations of the average value of the "fast" T(2i) and of the "slow" T(1i) relaxation time distributions, which could be attributed to the marrow components different from the fat granules of the adipose cells.Our results suggest that studies in vitro on bone tissue, by 1H-MR techniques at low-resolution, may contribute to a better bone function characterization and, therefore, to a better clinical utilization of MRI techniques.     

Effects of recombinant human erythropoietin on the haemopoietic bone marrow monitored by magnetic resonance spectroscopy in patients with end-stage renal disease

Volume selective magnetic resonance (MR) proton spectroscopy was used to investigate changes in the haemopoietic bone marrow in patients with end-stage renal disease undergoing treatment with recombinant human erythropoietin (rHuEPO). Significant changes could be detected in the spectra 14 days after the beginning of treatment, before any response was seen in the haemoglobin concentration of peripheral blood. The spectral changes indicate an alteration in cellular composition of haemopoietic bone marrow with an increase in the amount of haemopoietic active tissue. One patient showed a major change in the spectrum four days after treatment began, indicating that MR spectroscopy may detect early changes in the cellular composition of the bone marrow. This noninvasive method may be useful in evaluating treatment effects of recombinant human haemopoietic growth factors in the bone marrow, as well as investigating bone marrow response from different modes of rHuEPO administration.     

Proton spin-lattice relaxation times in ytterbium hydrides

The measurements of the proton (NMR) spinlattice relaxation times have been made in a series of ytterbium hydrides, YbH _x . Results are reported forx=1.80, 1.95, 2.00 and 2.62 and temperatures 4.2T297K. In the orthorhombic phase (1.80x2.00), the spin-lattice relaxation times are dominated by the hyperfine interaction of protons with conduction electrons and the spin diffusion mechanism. In the cubic phase (x=2.62), the relaxation times are five orders of magnitude shorter than in the orthorhombic one. This is interpreted in terms of the proton coupling with the Yb³⁺ ion spin fluctuations.     

Proton magnetic resonance spectroscopy of the kidney in renal stone disease

Previous studies of renal stone disease (RSD) in Thailand indicated abnormal urinary aggregator and inhibitor composition among farmers with excessive sweat loss. Our aim was to compare the proton MR spectra obtained from the kidneys of 32 proven cases of RSD (aged 38 to 65 yrs) with nine age-matched normal control subjects. We used the STEAM sequence with TE = 15 ms and TR = 2000 ms. The spectra at 3.25, 3.6 and 3.9 ppm were analyzed. The results showed a correlation between the three peaks (p < 0.001), however, there was no significant difference between the RSD group and the normal control subjects. We therefore concluded that there was no overloading of these osmolytes among the renal stone patients.     

Proton spin relaxation in 2-chloroacrylontirile by double resonance

Nuclear magnetic double resonance experiments were performed on the strongly coupled two-proton system (AB) in 2-chloroacrylontirile to study the spin relaxation processes. The single resonance parameters of the AB spectrum are (operating frequency 100 MHz): |vA - vB|=9.85±0.1 Hz and J _AB=2.8±0.1 Hz. Frequency-sweep double resonance spectra were obtained by irradiating each of the four transitions at different strengths of irradiation in the range 0.015 Hz to 2.35 Hz. These spectra were analysed by using the ‘Bloch approximation’ in the rotating frame for the ‘high’ irradiation strengths and the ‘simple line’ approximation for the ‘low’ irradiation strengths. The analysis showed that the proton relaxation in this molecule can be described by interaction with isotropic random fields of nearly equal strengths at the two nuclei with no appreciable correlation between them. Internal dipole-dipole interaction is not a significant mechanism (at room temperature). It is shown that for analysing ‘low’ irradiation spectra the choice of certain functions of intensity changes would lead to a marked distinction between the different relaxation mechanisms.     

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.     

Proton magnetic resonance imaging and phosphorus-31 magnetic resonance spectroscopy studies of bromobenzene-induced liver damage in the rat.

Respiratory-gated proton magnetic resonance imaging was used to study the response of the rat liver in situ to bromobenzene, a classic hepatotoxicant. A localized region of high proton signal intensity in the perihilar region of the liver was seen 24-48 hr after an intraperitoneal injection of bromobenzene. Localized proton magnetic resonance spectra from within this region indicated that the increased proton signal intensity was not due to accumulation of fat in the liver, but primarily due to a longer T2 for the proton resonance of water. This is consistent with acute edema in this localized region. In vivo 31P magnetic resonance spectroscopy studies of the same rat livers in situ were performed. Spectroscopic conditions were determined whereby localized, quantitative 31P spectra could be obtained. Using these methods, 10 mmol/kg bromobenzene was found after 24 hr to cause a number of statistically significant (p less than 0.05) effects: a decrease in adenosine 5'-triphosphate levels from 4.1 +/- 0.5 to 3.0 +/- 0.5 mM, a decrease in phosphodiester levels from 11.3 +/- 0.9 to 9.3 +/- 0.7 mM and an increase in the phosphomonoesters from 3.0 +/- 0.4 to 5.5 +/- 1.2 mM (mean +/- standard deviation). High resolution in vitro 31P spectra of perchloric acid extracts of these rat livers showed that the increased phosphomonoester resonance was due to a selective 4.3-fold increase in phosphocholine. Thus, our in vivo and in vitro 31P magnetic resonance spectra are consistent with the hypothesis that a phosphatidylcholine-specific phospholipase C (generating phosphocholine and diacylglycerol) is activated during tissue damage. Both the imaging and spectroscopy results obtained with bromobenzene closely resemble CCl4-induced liver changes previously reported, and may reflect a generalized response of the liver to any acutely acting toxic chemical.     

Proton relaxation times in 7LiCl and 6LiCl solutions

Measurements of the proton spin-lattice relaxation times have been made as a function of concentration and temperature in aqueous solutions of ⁷LiCl and ⁶LiCl. The difference in the relaxation times for two isotopic solutions of the same concentration and temperature is small, corresponding to a difference n reciprocal relaxation times of 0·004 sec^-1. c at 25°c, where c is the molarity of the solutions. This value decreases with increasing temperature. It is shown that the difference in relaxation times arises solely from the magnetic dipole interaction between the ⁷Li ion nucleus and water protons. The concept of a long-lived, rigid hydrated complex around the Li ion is shown to be inconsistent with the results.     

Proton magnetic resonance spectroscopy of brain lesions in children with neurofibromatosis type 1.

Two of the recognized cranial MRI findings in children with neurofibromatosis type 1 (NF1) are neurofibromatosis bright objects (NBO) and brain glioma. Their differential diagnosis can be problematic. This study aimed to determine the features of these abnormalities on short echo-time in-vivo proton magnetic resonance spectroscopy. Twenty children under the age of 16 with NF1 were studied. A single voxel, short echo-time technique (TE = 20 ms; TR = 5000 ms) was used to obtain proton spectra of typical NBO and any regions suggestive of atypical bright objects or tumor. Nine children without neurofibromatosis with no structural brain abnormality acted as aged-matched comparisons. A semi-quantitative analysis indicated significant increase in choline and myo-inisitol in tumors compared to typical NBO (p < 0.05) and compared to controls (p < 0.05); reduction in the levels of N-acetyl moieties in NBO compared to controls (p < 0.05); reduction in N-acetyl in tumors compared to controls (p < 0.001); and reduction in glutamate/glutamine in tumors compared to controls (p < 0.05). This cross-sectional data suggests that proton spectroscopy can aid differentiating between NBO and brain (non-optic/hypothalamic) glioma. Typical NBO have different short echo-time spectroscopic appearances compared to normal brain.     

Proton magnetic relaxation in NH4IO4

Proton relaxation times T₁ and T_1ϱ have been measured in NH₄IO₄ between 77 and 300 K. Ammonium ion reorientation with an activation energy of 8.64 ± 0.2 kJ/mole dominates the relaxation, but above about 200 K dipolar coupling between protons and ¹²⁷I nuclei, which are rapidly relaxed by quadrupolar coupling to the lattice, makes a large contribution to proton relaxation in the rotating frame.     

Radiotherapy effects on vertebral bone marrow: Easily recognizable changes in T2 relaxation times

The effect of localized radiotherapy on vertebral bone marrow was demonstrated in two patients using quantitative MRI studies with pixel-by-pixel measurement of T₂ relaxation times with generation of T₂ images. Conventional T₁-weighted spin-echo images were obtained as well. Irradiated vertebral bone marrow was found to have longer T₂ relaxation times than the neighboring nonirradiated bone marrow. These changes corresponded to the increased signal intensity on T₁-weighted images and to the field of radiotherapy and were noted 2.5 to 32 mo after radiotherapy. Radiologists should be aware of the increased T₂ relaxation times in irradiated bone marrow to correctly assess spinal disorders in irradiated patients. The reported T₂ changes may reflect the abundance of adipose cells that proliferate in bone marrow after radiotherapy, or may indicate an additional histological change, such as bone marrow necrosis or edema. Conclusive histological proof remains to be obtained.     

Proton magnetic resonance in four-coordinated ferrous porphyrins

The N.M.R. spectra of ferrous four-coordinated octaethylporphyrin, deuteroporphyrin IX dimethylester, meso-tetraphenylporphin and mesotetra(αααα-o-pivalamidophenyl)porphin (the so-called ‘picket fence’ porphyrin) show that these paramagnetic complexes are in the same spin state in non-polar solvents. The isotropic paramagnetic shifts have been analysed using fluorine substituted tetraphenylporphins as probes for the estimation of the pseudocontact contribution to the observed shifts. The anisotropy of the pseudocontact interaction and the distribution pattern of the contact hyperfine interaction suggest that the spin state of these complexes corresponds to S=1. The electronic relaxation time for this configuration is very short, (T ₁=5 × 10^-13s), enabling the observation of high resolution spectra for these axially non-coordinated ferrous prophyrins.     

Investigation of the mobility of paraffin molecules in channel urea clathrates by nuclear magnetic resonance relaxation spectroscopy

The temperature dependence of the proton spin-lattice relaxation time (T ₁) is investigated for channel urea clathrates with paraffin molecules. The results obtained are interpreted within the reorientational model of paraffin molecules and their fragments in clathrate channels. The specific features of the dynamics of normal paraffins in urea clathrates are associated with incommensurate regions in the structure of these compounds.