NMR in experimental cerebral edema: value of T1 and T2 calculations

In an experimental investigation, the efficacy of nuclear magnetic resonance (NMR) relaxation times in measuring brain water was studied. Cerebral edema was induced in four dogs with a freeze lesion, which was produced by contact with a steel cylinder cooled in liquid nitrogen and placed on the exposed dural surface of the brain. NMR proton imaging was performed 2, 3, 6, or 24 hr after production of the lesion, at a field strength of 0.35 T, using multiparametric spin-echo (SE) technique. The animals were sacrificed immediately after imaging, and brain samples were analyzed for water content (wet-to-dry, microgravimetry). Correlation between water content, NMR imaging, and resulting T1, T2 relaxation times and mobile proton density values calculated with SE technique was performed. Brain sample analysis showed elevation of water content in the white matter subjacent to the lesion in all four dogs, rising at least 15% in each of the animals. NMR imaging detected the freeze lesion and subjacent vasogenic edema of the white matter in all animals. The 2 sec pulse interval SE technique was most sensitive in the detection of the abnormality, and provided optimal differentiation of gray and white matter. The second echo sampling (56 msec) was most sensitive to the detection of edema. The T1 and T2 relaxation values, as well as the mobile proton density values, were elevated in the normal gray matter and in the abnormal white matter when compared with normal white matter in any given animal.(ABSTRACT TRUNCATED AT 250 WORDS)     

Characterization of the NMR behavior of white matter in bovine brain.

In vitro experiments on 15 white matter samples from five bovine brains were performed on a 1H-NMR spectrometer at 24 degrees C and 37 degrees C. The average myelin water fractions (MWFs) were 10.9% and 11.8% for samples at 24 degrees C and 37 degrees C, respectively. The T1 relaxation time at 37 degrees C was found to be 830 ms, exhibiting monoexponential behavior. A four-pool model including intra/extracellular (IE) water, myelin water, nonmyelin tissue, and myelin tissue was proposed to simulate the NMR behavior of bovine white matter. A cross-relaxation correction was introduced to compensate for shifting of the measured data points and T2 times over the duration of the Carr-Purcell-Meiboom-Gill (CPMG) measurement due to cross relaxation. This correction was found to be slight, providing evidence that MWFs measured using a multiecho technique are near physical values. At 24 degrees C the cross-relaxation times between myelin tissue and myelin water, myelin water and IE water, and IE water and nonmyelin tissue were found to be approximately 227, 2064, and 402 ms, respectively. At 37 degrees C these same cross-relaxation times were 158, 1021, and 170 ms, respectively. The exchange rate between myelin water and myelin was found to be 11.8 s-1 at 37 degrees C, while the exchange rate between IE water and nonmyelin tissue was found to be 6.8 s-1. These exchange rates are of similar magnitude, which indicates that the interaction between IE water and nonmyelin tissue cannot be ignored.     

The effect of pulmonary edema on proton nuclear magnetic resonance relaxation times

This study was done to determine the effect of permeability pulmonary edema on proton nuclear magnetic resonance (NMR) relaxation times. Permeability edema was induced in rats by the intravenous injection of alloxan in saline. Control animals received only saline. The rats were ventilated through a tracheostomy; and after a time sufficient for the edema to become uniform, they were sacrificed. T1, and T2 and extravascular lung water were measured on lung samples. A linear relationship was found between the relaxation times and the extravascular lung water. Any diffuse alveolar process including pulmonary edema can increase proton density as well. The T1 and T2 relaxation times may be used to distinguish among different causes of increased proton density in the lung.     

Frequency dependence of magnetic resonance spin-lattice relaxation of protons in biological materials

The frequency dependence of spin-lattice (T1) relaxation times of protons in tissues and other macromolecular solutions was investigated. This dependence can be principally assigned to reduced mobility of water molecules "hydrated" on the surface of macromolecular structures. The T1 relaxation time of "hydration water" was found to increase linearly with frequency in the range from 5 to 100 MHz (T1 = 1.83 f + 25.0). It is assumed that the remainder of water in the tissue has a relaxation rate that is independent of frequency, as is characteristic of bulk tap water. Variations occur in the fraction of water hydrated or bound from one organ to the next. As the observed relaxation rate is a weighted average of the two rates as described by the fast exchange model, the above empirical relationship can be used to take a tissue T1 relaxation time measured at one frequency and then calculate the tissue T1 relaxation time that would be expected at another frequency. Good agreements were obtained between such calculated tissue T1 values and the T1 values actually measured at the second frequency. Variations between the calculated and measured T1 values in some classes of tissues indicate that there are also less important secondary factors such as lipid content.     

Tumours of the central nervous system. Proton magnetic resonance relaxation times T1 and T2 and histopathologic correlates

Proton MR relaxation times T1 and T2 were determined in vitro in 136 small specimens of astrocytomas grades I-IV, of oligodendrogliomas, metastases of adenocarcinomas, meningiomas and acoustic neuromas. In addition, 7 samples of peritumoural white matter were analysed. The analysed specimens were studied microscopically in their entirety regarding tumour type and occurrence of necrosis and non-tumour tissue admixture, such as fibrosis and haemorrhage. Most of the gliomas had longer relaxation times than normal white matter and T2 was significantly longer than in the other three tumour groups. The metastases had longer T1 than normal white matter, while T2 varied. The astrocytomas tended to show shorter relaxation times with increasing degree of malignancy, and shortening of T1 and T2 correlating with the proportion of tissue necrosis. Similarly, the metastases with tissue necrosis had shorter T1 and T2 than non-necrotic samples. The meningiomas had T1 values comparable with normal cortex, while the T2 values varied. Tumours containing a large proportion of fibrous tissue had shorter relaxation times than the others. Acoustic neuromas had only slightly longer T1 than normal white matter, while T2 was not prolonged. Both T1 and T2 were significantly shorter than in all other tumours studied. Peritumoural white matter had prolonged relaxation times compared with normal white matter, correlating to increased water content. These in vitro differences regarding relaxation times in various types of tumours of the central nervous system, dependent on various types of tissue alterations, should be of interest for the interpretation of in vivo images.     

Multiexponential proton spin-spin relaxation in MR imaging of human brain tumors

In vivo measurements of proton relaxation processes in human brain tumors have been performed by magnetic resonance (MR) imaging using a whole-body superconductive MR scanner, operating at 1.5 T. The T1 and T2 relaxation time measurements were based on a combined Carr-Purcell/Carr-Purcell-Meiboom-Gill sequence with two interleaved repetition times and 32 echoes. First, comparative measurements in the imager and with the spectrometer of relaxation times were performed on phantoms containing fluids of different T1 and T2 to evaluate accuracy. A maximum deviation of approximately 10% was found. Multislicing with a gap width of one slice thickness influenced the accuracy of T1 relaxation measurement. A gap width of at least two times the slice thickness was necessary for reliable determination of T1. No influence on T2 values was observed by multislicing. Second, in human head imaging the multiexponential behavior of the T2 decay curves has been analyzed in each pixel, where the mean square deviation has been used as a criterion to discriminate between mono- and biexponential behavior. Mean values of monoexponential T1 and multiexponential T2 relaxation data for white matter, gray matter, CSF, edema, and tumor were sampled in 12 patients with brain tumors. T2 showed monoexponential behavior in white and gray matter, whereas CSF, edema, and tumor showed distinct biexponentiality. The biexponential analysis generally yields "fast" and "slow" components with T2f = 80 +/- 17 ms and T2s = 2,030 +/- 210 ms for CSF (partial volume effect), T2f = 104 +/- 25 ms and T2s = 677 +/- 152 ms for edematous tissues, T2f = 97 +/- 19 ms and T2s = 756 +/- 99 ms for tumor tissues, respectively. Using a stepwise discriminant analysis by forward selection, the two best discriminating parameters of the multiexponential relaxation analysis for each pair of classification groups have been selected. For the discrimination of edematous and tumor tissues a retrospective overall accuracy of 94% has been found.     

Tissue characterization with T1, T2, and proton density values: results in 160 patients with brain tumors

A method by which the tissue parameters - T1, T2, and proton density - can be measured simultaneously was used in 160 patients with brain tumors to test the complete potential of magnetic resonance (MR) imaging for quantitative tissue characterization. MR tissue parameters of a wide variety of tumors, edema, white matter, and gray matter were determined. While normal brain tissues showed only small interindividual variations of tissue parameters, pathologic entities (tumor, edema) were characterized by wide ranges of T1, T2, and proton density values. The considerable overlapping of tissue parameters in different tumor entities, which were analyzed in a three-dimensional T1/T2/proton density space, indicates that a reliable diagnosis cannot be made on the basis of a quantitative evaluation of T1, T2, and proton density alone.     

Multi-component apparent diffusion coefficients in human brain: relationship to spin-lattice relaxation.

In vivo measurements of the human brain tissue water signal decay with b-factor over an extended b-factor range up to 6,000 s/mm(2) reveal a nonmonoexponential decay behavior for both gray and white matter. Biexponential parametrization of the decay curves from cortical gray (CG) and white matter voxels from the internal capsule (IC) of healthy adult volunteers describes the decay process and serves to differentiate between these two tissues. Inversion recovery experiments performed in conjunction with the extended b-factor signal decay measurements are used to make separate measurements of the spin-lattice relaxation times of the fast and slow apparent diffusion coefficient (ADC) components. Differences between the spin-lattice relaxation times of the fast and slow ADC components were not statistically significant in either the CG or IC voxels. It is possible that the two ADC components observed from the extended b-factor measurements arise from two distinct water compartments with different intrinsic diffusion coefficients. If so, then the relaxation results are consistent with two possibilities. Either the spin-lattice relaxation times within the compartments are similar or the rate of water exchange between compartments is "fast" enough to ensure volume averaged T(1) relaxation yet "slow" enough to allow for the observation of biexponential ADC decay curves over an extended b-factor range. Magn Reson Med 44:292-300, 2000.     

The contribution of chemical exchange to MRI frequency shifts in brain tissue

Recent high‐field MRI studies based on resonance frequency contrast have revealed brain structure with unprecedented detail. Although subtle magnetic susceptibility variations caused by iron and myelin seem to be important to this contrast, recent research on protein solutions suggests that chemical exchange between water and macromolecular protons may contribute substantially to the observed gray‐white matter frequency contrast. To investigate this, we performed spectroscopic MRI experiments at 14 T on samples of fixed human visual cortex and fresh pig brain. To allow direct observation of any exchange‐induced frequency shifts, these samples were soaked in reference chemicals (TSP and dioxane) that are assumed not to be involved in exchange. For both fresh and fixed tissues and with both reference chemicals, substantial negative exchange‐induced gray‐white matter frequency contrast (–6.3 to –13.5 ppb) was found, whereas intracortical contrast was negligible. The sign of the gray‐white matter exchange‐induced frequency difference was opposite to the overall gray‐white matter frequency difference observed in vivo. This suggests that exchange contributes to, but is not sufficient to explain, the frequency contrast in vivo and tissue susceptibility differences may have a greater contribution than previously thought. The exchange‐dependent contribution may report on tissue chemical composition and pH. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Correlation of human NMR T1 values measured in vivo and brain water content

A relationship has been demonstrated between nuclear magnetic resonance (NMR) longitudinal relaxation times (T1 values) obtained in vivo in both normal and oedematous (peritumoral) brain tissue, and measurements of brain water obtained by gravimetric analysis of operative samples. Significant correlations were found in seven patients in both cortex (r = 0.97, P less than 0.001) and white matter (r = 0.92, P less than 0.001). These findings suggest that NMR may prove a useful technique for monitoring brain oedema.     

The magnetic field dependence of water T1 in tissues

The magnetic field dependence of the composite (1)H(2)O nuclear magnetic resonance signal T(1) was measured for excised samples of rat liver, muscle, and kidney over the field range from 0.7 to 7 T (35-300 MHz) with a nuclear magnetic resonance spectrometer using sample-shuttle methods. Based on extensive measurements on simpler component systems, the magnetic field dependence of T(1) of all tissues studied are readily fitted at Larmor frequencies above 1 MHz with a simple relaxation equation consisting of three contributions: a power law, A*ω(-0.60) related to the interaction of water with long-lived-protein binding sites, a logarithmic term B*τ(d) *log(1+1/(ωτ(d))(2)) related to water diffusion at macromolecular interfacial regions, and a constant term associated with the high frequency limit of water-spin-lattice relaxation. The parameters A and B include the concentration and surface area dependences respectively. The logarithmic diffusion term becomes significant at high magnetic fields and is consistent with rapid translational dynamics at macromolecular surfaces. The data are fitted well with translational correlation times of approximately 15 ps for human brain white matter, but with a B value three times larger than gray matter tissues. This analysis suggests that the water-surface translational correlation time is approximately three times longer than in gray matter.     

Pulsed magnetization transfer spin-echo MR imaging

Cross relaxation between macromolecular protons and water protons is known to be important in biologic tissue. In magnetic resonance (MR) imaging sequences, selective saturation of the characteristically short T2 macromolecular proton pool can produce contrast called magnetization transfer contrast, based on the cross-relaxation process. Selective saturation can be achieved with continuous wave irradiation several kilohertz off resonance or short, intense 0° pulses on resonance. The authors analyze 0° binomial pulses for T2 selective saturation, present design guidelines, and demonstrate the use of these pulses in spin-echo imaging sequences in healthy volunteers and patients. Using the phenomenologic Bloch equations modified for two-site exchange, the authors derive the analytic expressions for water proton relaxation under periodic pulsed saturation of the macromolecular protons. This relaxation is shown to be monoexpo-nential, with a rate constant dependent on the saturation pulse repetition rate and the individual and cross-relaxation rates.     

Relaxation induced by ferritin and ferritin-like magnetic particles: the role of proton exchange.

Proton T1 and T2 in solutions of ferritin and fercayl (a ferritin-like iron-dextran particle) solutions were measured, over a wide range of various parameters (Bo, temperature, interecho-time and pH). The window of the previously referred linear dependence of 1/T2 on the static field was increased, up to 500 MHz, and the independence of T2 on the echo time was confirmed. Correlation times were extracted from T1 nuclear magnetic relaxation dispersion profiles. In the pH range studied, no strong variation of the relaxivities of ferritin solutions was noticed. Fercayl, which, unlike ferritin, remains stable under large pH variations, is characterized by strongly pH-dependent relaxation rates. This feature is interpreted as due to the effect of proton exchange in the water relaxation process. Outer sphere theory, which ignores proton binding, is shown to be unable to describe the relaxation of ferritin and ferritin-like particles solutions, first because it predicts a quadratic rate dependence on Bo, but also because it severely underestimates the relaxation rate. Explaining relaxation induced by ferritin and ferritin-like particle solutions will likely require a model that accounts for proton binding.     

High-resolution NMR spectroscopy of cerebral white matter in multiple sclerosis

Multiple sclerosis (MS) lesions have been shown by conventional methods to have major alterations in water and myelin lipid contents. To characterize these abnormalities more efficiently, NMR spectroscopy was used to evaluate water content by measuring relaxation times at 0.5 and 2.0 T. Subsequently, cholesterol content was obtained by using 1H NMR spectroscopy, while 31P NMR spectroscopy allowed measurement of the four main phospholipids and the inorganic phosphate concentrations in normal and pathological cerebral white matter samples. The relaxation times were significantly prolonged in MS lesions relative to normal white matter. Measured in different sample types, T1 and T2 times increased with water content. Moreover, the T2 of normal-appearing white matter was considerably lengthened. Analysis of white matter lipid composition using this method gave accurate values, which showed a significant decrease in phospholipids and cholesterol content in MS samples.     

Development of a composite material phantom mimicking the magnetic resonance parameters of the neonatal brain at 3.0 Tesla

OBJECTIVE: Development of a composite material phantom, comprised of polyvinyl alcohol cryogel (PVA-C) and an agarose additive, to effectively mimic the magnetic resonance relaxation times (T1 and T2) of neonatal white matter (WM) and gray matter (GM) at 3.0 T. MATERIALS AND METHODS: Samples of PVA-C with and without agarose were prepared with 1 cycle of freezing/thawing. Measurements of T1 and T2, at 3.0 T, were performed on the samples at temperatures ranging from 20 degrees C to 40 degrees C. RESULTS: A sample temperature of 40 degrees C was required to achieve a T1 value sufficiently long to represent neonatal WM. At this temperature, neonatal WM relaxation times required 3% PVA-C with 0.3% agarose, whereas gray matter relaxation times required 8% PVA-C with 1.4% agarose. CONCLUSIONS: By adjusting the sample temperature, polyvinyl alcohol concentration, and agarose concentration, the relaxation times of neonatal brain tissues can be obtained using this composite material.     

Relative contributions of chemical exchange and other relaxation mechanisms in protein solutions and tissues

Transverse relaxation times T2 of water protons were measured in 5% protein solutions and soaked rat liver in different static magnetic fields (0.15 to 11 T). Protein molecular weight varied between 1.4 and 480 kDa in solutions of varying degrees of deuteration. The data obtained are analyzed in terms of a model system consisting of three phases of different relaxation characteristics: protein protons, hydration layer water protons, and bulk water protons. The contributions to relaxation due to hydrodynamic effects on water protons, cross relaxation between the hydration layer water protons and the protein protons, and chemical exchange between the hydration layer water protons and the bulk water protons are separately estimated. The experimental results indicate that the "hydrodynamic interactions" are about the same magnitude in rat liver and all the proteins studied, but the contribution of the cross relaxation differs by several orders in different protein systems. Fast chemical exchange between the hydration layer water and the bulk water causes considerable shortening of T2 at high magnetic fields for all the protein solutions and rat tissue studied. Selected samples were studied at different temperatures (213-318 K) and with different intervals in the CPMG sequence. The rates of chemical exchange and fractional populations of different phases are determined, and the results obtained provide support for the model in which fast exchange among the different water phases is an important feature of the overall relaxation behavior.     

Regional differences in the proton magnetic resonance relaxation times T1 and T2 within the normal human brain

The proton magnetic resonance (MR) relaxation times T1 and T2 were determined in autopsy specimens from 13 different regions of normal human brains. One hundred and seventy-four tissue samples from 25 brains were examined in a pulsed MR analyzer of 0.25 T and were then also studied histologically. There were regional differences in T1 and T2 within the cerebral gray matter but not within the white matter. These regional differences might reflect the different composition and cytoarchitectonic structure of the cortical regions and should be taken into consideration in the interpretation of cortical lesions on MR images.     

Quantitative T(1rho) and adiabatic Carr-Purcell T2 magnetic resonance imaging of human occipital lobe at 4 T.

The feasibility of performing quantitative T(1rho) MRI in human brain at 4 T is shown. T(1rho) values obtained from five volunteers were compared with T2 and adiabatic Carr-Purcell (CP) T2 values. Measured relaxation time constants increased in order from T2, CP-T2, T(1rho) both in white and gray matter, demonstrating differential sensitivities of these methods to dipolar interactions and/or proton exchange and diffusion in local microscopic field gradients, which are so-called dynamic averaging (DA) processes. In occipital lobe, all relaxation time constants were found to be higher in white matter than in gray matter, demonstrating contrast denoted as an "inverse transverse relaxation contrast." This contrast persisted despite changing the delay between refocusing pulses or changing the magnitude of the spin-lock field strength, which suggests that it does not originate from DA, as might be induced by the presence of Fe, but rather is related to dipolar interactions in the brain tissue.     

Nuclear relaxation of human brain gray and white matter: analysis of field dependence and implications for MRI

The dependence of 1/T1 on the magnetic field strength (the relaxation dispersion) has been measured at 37 degrees C on autopsy samples of human brain gray and white matter at field strengths corresponding to proton Larmor frequencies between 10 kHz and 50 MHz (0.0002-1.2 T). Additional measurements of 1/T1 and 1/T2 have been performed at 200 MHz (4.7 T) and 20 MHz (0.47 T), respectively. Absolute signal amplitudes are found to be proportional to the sample water content, not to the "proton density," and it is concluded that the myelin lipids do not contribute to the signal. Transverse magnetization decay data can be fitted with a triple exponential function, giving characteristic results for each tissue type, and are insensitive to variations of the pulse spacing interval. The longitudinal relaxation dispersion curves show characteristic shapes for each tissue type. The most striking difference is a large dispersion for white matter at very high fields. As a consequence, the relative difference in 1/T1 between gray and white matter shows a marked maximum around 10 MHz. Possible implications for MRI are discussed. A weighted least-squares fit of the dispersions has been performed using a four-parameter function of the form 1/T1 = 1/T1,w + D + A/(1 + (f/fc)beta'). The quality of the fit is superior to that of other functions proposed previously. The results of these fits are used to predict image contrast between gray and white matter at different field strengths.     

Chronically obstructed sinonasal secretions: observations on T1 and T2 shortening

Clinically assessed chronic proteinacious sinonasal secretions usually have long T1 and T2 relaxation times reflecting their high water content. However, in some cases variable combinations of short and long T1 and T2 relaxation times are found. To study the causes of these findings, the magnetic resonance (MR) images of 41 patients with surgically proved, chronically obstructed sinonasal secretions were studied. The relative signal intensities on both T1- and T2-weighted sequences of the sinus specimens were correlated with the gross viscosity of the specimens at surgery. Ten specimens were collected that were not contaminated with either blood or saline. UV spectrophotometric analysis of four of these samples excluded the presence of methemoglobin. Total protein content was determined in five samples, and in vitro T1 and T2 values were measured in one sample. These T1 and T2 relaxation times were accurately predicted with use of a standard pure lysozyme protein solution with the same concentration as the specimen. In addition, the observed T1- and T2-weighted signal intensities on the 41 MR images were predicted from an analysis of pure protein solutions. This study concludes that the primary causes of the variable T1 and T2 relaxation times of chronic sinonasal secretions are the macromolecular protein concentration, the amount of free water, and the specimen viscosity. Furthermore, an orderly and predictable transition of these signal intensities occurs over time.