Constrained modeling for spectroscopic measurement of bi-exponential spin-lattice relaxation of water in vivo

The (1)H NMR water signal from spectroscopic voxels localized in gray matter contains contributions from tissue and cerebral spinal fluid (CSF). A typically weak CSF signal at short echo times makes separating the tissue and CSF spin-lattice relaxation times (T(1)) difficult, often yielding poor precision in a bi-exponential relaxation model. Simulations show that reducing the variables in the T(1) model by using known signal intensity values significantly improves the precision of the T(1) measurement. The method was validated on studies on eight healthy subjects (four males and four females, mean age 21 +/- 2 years) through a total of twenty-four spectroscopic relaxation studies. Each study included both T(1) and spin-spin relaxation (T(2)) experiments. All volumes were localized along the Sylvian fissure using a stimulated echo localization technique with a mixing time of 10 ms. The T(2) experiment consisted of 16 stimulated echo acquisitions ranging from a minimum echo time (TE) of 20 ms to a maximum of 1000 ms, with a repetition time of 12 s. All T(1) experiments consisted of 16 stimulated echo acquisition, using a homospoil saturation recovery technique with a minimum recovery time of 50 ms and a maximum 12 s. The results of the T(2) measurements provided the signal intensity values used in the bi-exponential T(1) model. The mean T(1) values when the signal intensities were constrained by the T(2) results were 1055.4 ms +/- 7.4% for tissue and 5393.5 ms +/- 59% for CSF. When the signal intensities remained free variables in the model, the mean T(1) values were 1085 ms +/- 19.4% and 5038.8 ms +/- 113.0% for tissue and CSF, respectively. The resulting improvement in precision allows the water tissue T(1) value to be included in the spectroscopic characterization of brain tissue.     

The systemic effect of cancers on human sera proton NMR relaxation times

In animal models of cancer, an elevation of T1 and T2 in uninvolved tissues and in the blood of tumor bearing animals has been termed "the systemic effect." This study reports T1 values in sera of human patients from Genoa, Italy, with several types of cancer and non-cancerous diseases. T1 values were significantly elevated over normal controls (1628 +/- 113 ms) in colorectal cancers (1725 +/- 149 ms) and stomach cancers (1817 +/- 219 ms). However a systemic effect was not demonstrated in acute myeloid leukemia, chronic lymphatic leukemia, chronic myeloid leukemia, or plasma cell myeloma, or in pancreatic and lung cancers. Noncancerous states of cirrhosis, chronic hepatitis, and monoclonal gammapathies did not show a T1 elevation. In general, T1 values of sera correlated with protein content of the sera; however, a disproportionate contribution of gamma-globulin protein on water proton relaxation times was observed in several cases.     

Ex vivo magnetic resonance imaging of rat spinal cord at 9.4 T

The magnetic resonance (MR) properties of the rat spinal cord were characterized at the T9 level with ex vivo experiments performed at 9.4 T. The inherent endogenous contrast parameters, proton density (PD), longitudinal and transverse relaxation times T1 and T2, and magnetization transfer ratio (MTR) were measured separately for the grey matter (GM) and white matter (WM). Analysis of the measurements indicated that these tissues have statistically different proton densities with means PD(GM)=54.8+/-2.5% versus PD(WM)=45.2+/-2.4%, and different T1 values with means T1GM=2.28+/-0.23 s versus T1WM=1.97+/-0.21 s. The corresponding values for T2 were T2GM=31.8+/-4.9 ms versus T2WM=29.5+/-4.9 ms, and the difference was insignificant. The difference between MTR(GM)=31.2+/-6.1% and MTR(WM)=33.1+/-5.9% was also insignificant. These results collectively suggest that PD and T1 are the two most important parameters that determine the observed contrast on spinal cord images acquired at 9.4 T. Therefore, in MR imaging studies of spinal cord at this field strength, these parameters need to be considered not only in optimizing the protocols but also in signal enhancement strategies involving exogenous contrast agents.     

Discrimination of components in atherosclerotic plaques from human carotid endarterectomy specimens by magnetic resonance imaging ex vivo

Specific MRI techniques have been used to determine the dimensional and compositional properties of atherosclerotic lesions in carotid endarterectomy tissues. A quantitative comparison of areas of specific features in typical tissue segments was performed using MR images and histologic images. The mean difference for the measurements by the two methods was 4.5% for the total vessel, 5.3% for the internal carotid artery lumen, and 5.0% for the external carotid lumen. For other less abundant components, the mean difference was 14.2%. For direct characterization, individual tissue components were isolated by microdissection and their T1 and T2 relaxation times measured. Highly calcified areas typically had rather short T1 (452-837 ms) and short T2 (10.4-18.4 ms). In contrast, regions enriched in lipid had much longer T1 (1,380-1,480 ms) and longer T2 (35.3-49.0 ms). Other components such as thrombus had intermediate T1 (1,180 ms) and short T2 (15.4 ms). T2 parametric imaging was used as a complementary approach for segmentation and quantitation of tissue components. In fresh tissue, several different components exhibited different T2 ranges: calcified/solid lipid (13-18 ms). cellular/ECM (9-30 ms), fluid lipid (35-40 ms): fibrous (50-60 ms). These results demonstrate the utility of MRI for identifying and quantifying specific components of atherosclerotic plaque ex vivo, and suggest its value for these measurements in vivo as well.     

Quantitative magnetic resonance imaging of 'Fuyu' persimmon fruit during development and ripening

Qualitative and quantitative proton magnetic resonance imaging techniques were applied to persimmon (Diospyros kaki cv 'Fuyu') fruit during development and post-harvest ripening. Spin-lattice (T(1)) relaxation times in mesocarp parenchyma and vascular tissue exhibited a sigmoidal pattern of increase leading to commercial harvest, but declined abruptly during ripening, 2.5 weeks after picking. T(1) times in parenchyma tissue were 1000 and 2100 ms in fruitlets, and at commercial harvest, respectively. T(1) times in vascular tissue were consistently shorter than those in parenchyma tissue by 300 to 600 ms. In contrast, spin-spin (T(2)) relaxation varied over a narrow range during development, i.e., 82 to 106 ms, and 59 to 73 ms, for parenchyma and vascular tissue, respectively. During ripening, T(2) measurements increased smoothly, commencing one week after harvest. Dry matter, water content, skin color, water-soluble tannins, soluble solids, and mineral and carbohydrate composition was also determined in companion fruit. No obvious associations linking physico-chemical and MR parameters were established, implying that the changes in relaxation measurements observed in 'simple' fruit systems can not be rationalised without recourse to more complex investigations involving SEM and different NMR spectroscopic and imaging techniques.     

Magnetization transfer of water T(2) relaxation components in human brain: implications for T(2)-based segmentation of spectroscopic volumes

Biexponential T(2) relaxation of the localized water signal can be used for segmentation of spectroscopic volumes. To assess the specificity of the components an iterative relaxation measurement of the localized water signal (STEAM, 12 echo times, geometric spacing from 30 ms to 2000 ms) was combined with magnetization transfer (MT) saturation (40 single lobe pulses, 12 ms duration, 1440 degrees nominal flip angle, 1 kHz offset, repeated every 30 ms). Voxels including CSF were examined in parietal cortex and periventricular parietal white matter (10 each), as well as 13 voxels in central white matter and 16 T(1)-hypointense non-enhancing multiple sclerosis lesions without CSF inclusion. Biexponential models (excluding myelin water) were fitted to the relaxation data. In periventricular VOIs the component of long T(2) (1736 +/- 168 ms) that is attributed to CSF was not affected by MT. In cortical VOIs this component had markedly shorter T(2)'s (961 +/- 239 ms) and showed both attenuation and prolongation with MT, indicating contributions from tissue. MS lesions and central WM showed a second tissue component of intermediate T(2) (160-410 ms). In white matter similar MT attenuation indicated strong exchange between the two tissue components, prohibiting segmentation. In MS lesions, however, markedly less MT of the intermediate component was found, which is consistent with decreased cellularity and exchange in a region that is large compared to diffusion motion.     

Quantification of cerebral metabolites in glioma patients with proton MR spectroscopy using T2 relaxation time correction

This study was aimed to investigate the significance of absolute concentration of metabolites in glioma patients using proton MR spectroscopy (MRS) with T2 relaxation time correction using three different echo times. The absolute concentrations of metabolites in 7 normal subjects and in 23 gliomas (10 low-grade, 13 high-grade) were obtained by proton MRS using a tissue water signal as an internal standard. The signal intensities of metabolites and tissue water were corrected by T2 relaxation time. In low-grade glioma, the T2 relaxation time of NAA was shorter, and T2 relaxation time of water was prolonged as compared to normal subjects (p < 0.001). In high-grade glioma, the T2 relaxation time of NAA (p < 0.001) and T2 relaxation time of Cr (p < 0.01) were shorter, and T2 relaxation time of water (p < 0.001) was prolonged as compared to normal subjects. Moreover, high-grade gliomas revealed a shorter T2 relaxation time of Cr than low-grade gliomas (p < 0.05). In glioma, NAA and Cr concentration were decreased, and Cho were increased as compared to normal subjects. Moreover, high-grade glioma revealed a significant lower Cr (p < 0.001) and Cho (p < 0.01) concentration compared to low-grade gliomas. Low Cr concentration is the most reliable indicator of malignancy in glioma. Cho concentration did not correlate with malignancy in gliomas.     

Two-exponential analysis of spin-spin proton relaxation times in MR imaging using surface coils

Proton relaxation time measurements were performed on a standard whole body MR imager operating at 1.5 T using a conventional surface coil of the manufacturer. A combined CP/CPMG multiecho, multislice sequence was used for the T1 and T2 relaxation time measurements. Two repetition times of 2000 ms (30 echoes) and 600 ms (2 echoes) with 180 degrees-pulse intervals of 2 tau = 22 ms were interleaved in this sequence. A two-exponential T2 analysis of each pixel of the spin-echo images was computed in a case of an acoustic neurinoma. The two-exponential images show a "short" component (T2S) due to white and gray matter and a "long" component (T2S) due to the cerebrospinal fluid. In the fatty tissue two components with T2S = 35 +/- 3 ms and T2L = 164 +/- 7 ms were measured. Comparing with Gd-DTPA imaging the relaxation time images show a clear differentiation of vital tumor tissue and cerebrospinal fluid.     

Analysis of 1H-NMR relaxation time distributions in L1 to L6 rat lumbar vertebrae

A better knowledge of the NMR relaxation behavior of bone tissue can improve the definition of imaging protocols to detect bone diseases like osteoporosis. The six rat lumbar vertebrae, from L1 to L6, were analyzed by means of both transverse (T(2)) and longitudinal (T(1)) relaxation of (1)H nuclei at 20 MHz and 30 degrees C. Distributions of relaxation times, computed using the multiexponential inversion software uniform penalty inversion, extend over decades for both T(2) and T(1) relaxation. In all samples, the free induction decay (FID) from an inversion-recovery (IR) T(1) measurement shows an approximately Gaussian (solid-like) component, exp[-1/2(t/T(GC))2], with T(GC) approximately 12 micros (GC for Gaussian component) and a liquid-like component (LLC) with initially simple-exponential decay. Averaging and smoothing procedures are adopted to obtain the ratio alpha between GC and LLC signals and to get separate T(1) distributions for GC and LLC. Distributions of T(1) for LLC show peaks centered at 300-500 ms and shoulders going down to 10 ms, whereas distributions of T(1) for GC are single broad peaks centered at roughly 100 ms. The T(2) distributions by Carr-Purcell-Meiboom-Gill at 600 micros echo spacing are very broad and extend from 1 ms to hundreds of ms. This long echo spacing does not allow one to see a peak in the region of hundreds of micros, which is better seen by single spin-echo T(2) measurements. Results of the relaxation analysis were then compared with densitometric data. From the study, a clear picture of the intratrabecular and intertrabecular (1)H signals emerges. In particular, the GC is presumed to be due to (1)H in collagen, LLC due to all the fluids in the bone including water and fat, and the very short T(2) peak due to the intratrabecular water. Overall, indications of some trends in composition and in pore-space distributions going from L1 to L6 appeared. Published results on rat vertebrae obtained by fitting the curves by discrete two-component models for both T(2) and T(1) are consistent with our results and can be better interpreted in light of the shown distributions of relaxation times.     

Significance of proton relaxation time measurement in brain edema, cerebral infarction and brain tumors

We examined the proton relaxation times in vitro in various neurological diseases using experimental and clinical materials, and consequently obtained significant results for making a fundamental analysis of magnetic resonance imaging (MRI) as followings. 1) In the brain edema and cerebral infarction, T1 prolonged and T2 separated into two components, one fast and one slow. Prolongation of T1 referred to the volume of increased water in tissue. The slow component of T2 reflects both the volume and the content of increased edema fluid in tissue. 2) In the edematous brain tissue with the damaged Blood-Brain-Barrier (BBB), the slow component of T2 became shorter after the injection of Mn-EDTA. Paramagnetic ion could be used as an indicator to demonstrate the destruction of BBB in the brain. 3) After the i.v. injection of glycerol, the slow component of T2 became shorter in the edematous brain with the concomitant decrease of water content. The effects of therapeutic drug could be evaluated by the measurement of proton relaxation times. 4) Almost all tumor tissue showed a longer T1 and T2 values than the normal rat brain, and many of them showed two components in T2. It was difficult to determine the histology of tumor tissue by the relaxation time alone because of an overlap of T1 and T2 values occurred among various types of brain tumors. 5) In vivo T1 values of various brain tumor were calculated from the data of MRIs by zero-crossing method, and they were compared with the in vitro T1 values which were measured immediately after the surgical operation. Though the absolute value did not coincide with each other due to differences in magnetic field strength, the tendency of the changes was the same among all kinds of tumors. It is concluded that the fundamental analysis of proton relaxation times is essentially important not only for the study of pathophysiology in many diseases but also for the interpretation of clinical MRI.     

Fast and precise T1 imaging using a TOMROP sequence

Proton spin-lattice (T1) relaxation time images were computed from a data set of 32 gradient-echo images acquired with a fast TOMROP (T One by Multiple Read Out Pulses) sequence using a standard whole-body MR imager operating at 64 MHz. The data acquisition and analysis method which permits accurate pixel-by-pixel estimation of T1 relaxation times is described. As an example, the T1 parameter image of a human brain is shown demonstrating an excellent image quality. For white and gray brain matter, the measured longitudinal relaxation processes are adequately described by a single-component least-squares fit, while more than one proton component has to be considered for fatty tissue. A quantitative analysis yielded T1 values of 547 +/- 36 msec and 944 +/- 73 msec for white and gray matter, respectively.     

Tissue characterization of benign brain tumors: use of NMR-tissue parameters

To evaluate the potentials of NMR tissue parameters for tissue characterization we investigated 68 patients with benign brain tumors. Tissue parameters were accurately measured by a recently developed interlaced triple sequence. Each individual tumor was characterized by a set of three numbers (relaxation times T1 and T2 and proton density Rho). Different tumors exhibited significant overlaps of the three tissue parameters. Therefore a reliable prediction of the histological diagnosis based on the quantitative analysis of tissue parameters alone was not possible. T2-prolongation correlated well with water content and "regressive changes" in meningiomas and neuromas.     

Temperature-dependent chemical shift and relaxation times of (23)Na in Na(4)HTm[DOTP

We describe the characterization of a (23)Na temperature-dependent chemical shift and relaxation rates in the complex, Na(4)HTm[DOTP]. This is the first characterization of a (23)Na temperature-dependent chemical shift in a nonmetallic sample. The (23)Na temperature-dependent chemical shift coefficient is approximately -0. 5 PPM/ degrees C for both an aqueous solution and a 6% agarose gel of this compound. This is 50 times the magnitude of the temperature-dependent chemical shift coefficient of water protons. The relaxation times, T(1), T(2f), and T(2s) increased by 0.1, 0.01, and 0.05 ms/ degrees C, respectively. Applications of these unique properties for designing an MRI technique for monitoring heat deposition in tissue and tissue phantoms are discussed.     

Effect of hyperosmotic mannitol on magnetic resonance relaxation parameters in reperfused canine myocardial infarction

To determine how administration of a hyperosmotic agent alters regional nuclear magnetic resonance (NMR) relaxation parameters and imaging characteristics in ischemic-reperfused myocardium, 7 dogs were infused with mannitol for 15 minutes before and after the release of a 3 hour left anterior descending coronary artery (LAD) occlusion. Nine control animals received normal saline during the 3 hour occlusion and 1 hour reperfusion periods. Normal posterior left ventricular (LV) wall and the ischemic anterior LV wall (risk area) myocardium was sampled for calculation of segmental microsphere myocardial blood flow, % tissue water content, NMR relaxation times (T1, T2) and myocyte ultrastructure using electron microscopy. Mean infarct T1 values were 14% greater than normal segments in saline-treated controls, but only 5% greater after mannitol. The difference in tissue water content between infarcted and normal segments was 4% in saline-treated (83 vs. 79%) compared to 2% in mannitol-treated dogs (79 vs. 77%). T1, T2 and % water content of control infarct segments were greater than treated infarcts (p less than 0.01). T1 and T2 rose as occlusion flow fell below 0.5 ml/min/g in control hearts but did not rise until flows were reduced to 0.1 ml/min/g in mannitol-treated hearts. Areas of increased signal in T1 and T2 NMR images correlated well with histochemical infarct volume (r = 0.98, SEE = 1.1 cc) in mannitol-treated dogs, but infarct borders were qualitatively less well-defined than in controls. We concluded that mannitol (1) diminishes tissue edema and reduces NMR relaxation parameters (T1, T2) in infarcted myocardium; and (2) attenuates the rise in T1 and T2 and ultrastructural myocyte injury in ischemic-reperfused myocardium.     

Proton spin relaxation studies of fatty tissue and cerebral white matter

Proton spin longitudinal (T1) and transverse (T2) relaxation and proton density studies were carried out on human fatty tissue and bovine white matter, both in the native state and after immersion in D2O. It is concluded that nuclear magnetic resonance signals from fatty tissue result mainly from methyl and methylene protons of hydrocarbons. No contribution from lipid protons could be detected for white matter, although it contains a high percentage of lipids. Imaging experiments, resulting in T1, T2, and proton density maps, support the results obtained with spectroscopic relaxation studies.     

Bone tissue and porous media: common features and differences studied by NMR relaxation

Despite significant differences between bone tissues and other porous media such as oilfield rocks, there are common features as well as differences in the response of NMR relaxation measurements to the internal structures of the materials. Internal surfaces contribute to both transverse (T2) and longitudinal (T1) relaxation of pore fluids, and in both cases the effects depend on, among other things, local surface-to-volume ratio (S/V). In both cases variations in local S/V can lead to distributions of relaxation times, sometimes over decades. As in rocks, it is useful to take bone data under different conditions of cleaning, saturation, and desaturation. T1 and T2 distributions are computed using UPEN. In trabecular bone it is easy to see differences in dimensions of intertrabecular spaces in samples that have been de-fatted and saturated with water, with longer T1 and T2 for larger pores. Both T1 and T2 distributions for these water-saturated samples are bimodal, separating or partly separating inter- and intratrabecular water. The T1 peak times have a ratio of from 10 to 30, depending on pore size, but for the smaller separations the distributions may not have deep minima. The T2 peak times have ratios of over 1000, with intratrabecular water represented by large peaks at a fraction of a ms, which we can observe only by single spin echoes. CPMG data show peaks at about a second, tapering down to small amplitudes by a ms. In all samples the free induction decay (FID) from an inversion-recovery (IR) T1 measurement shows an approximately Gaussian (solid-like) component, exp[-1/2 (T/TGC), with TGC approximately 11.7+/-0.7 micros (GC for "Gaussian Component"), and a liquid-like component (LLC) with initially simple-exponential decay at the rate-average time T(2-FID) for the first 100 micros. Averaging and smoothing procedures are adopted to derive T(2-FID) as a function of IR time and to get T1 distributions for both the GC and the LLC. It appears that contact with the GC, which is presumed to be 1H on collagen, leads to the T2 reduction of at least part of the LLC, which is presumed to be water. Progressive drying of the cleaned and water-saturated samples confirms that the long T1 and T2 components were in the large intertrabecular spaces, since the corresponding peaks are lost. Further drying leads to further shortening of T2 for the remaining water but eventually leads to lengthening of T1 for both the collagen and the water. After the intertrabecular water is lost by drying, T1 is the same for GC and LLC. T(2-FID) is found to be roughly 320/alpha micros, where alpha is the ratio of the extrapolated GC to LLC, appearing to indicate a time tau of about 320 micros for 1H transverse magnetization in GC to exchange with that of LLC. This holds for all samples and under all conditions investigated. The role of the collagen in relaxation is confirmed by treatment to remove the mineral component, observing that the GC remains and has the same TGC and has the same effect on the relaxation times of the associated water. Measurements on cortical bone show the same collagen-related effects but do not have the long T1 and T2 components.     

Proton NMR relaxation as a probe for setting cement pastes

We report a 20-MHz proton nuclear magnetic resonance T1 relaxation study of cement paste hydration in the early stages of setting, using different centimeter-sized samples of cements of various origins and different water-to-cement ratios. In every sample, during the first few minutes of hydration, it is found that inverse Laplace processing of inversion-recovery measurements systematically exhibits at least two T1 values: a long one, around 100 ms, whose value correlates well with water content and which may be attributed to bulk water surrounding cement grains; and a short one, around 2 ms, which is quite insensitive to water-to-cement ratio and which may be attributed to water embedded in floculated cement grains before setting occurs. The time evolution of the longest T1 value for several hours is also shown to exhibit a characteristic five-stage behavior that is well correlated with known stages of the hydration process: initial reaction, induction period, acceleration period, deceleration period and slow hydration reaction. These results are compared with calorimetric measurements and electrical conductivity literature.     

Temperature dependence of proton relaxation times in vitro

Accurate measurement of tissue relaxation characteristics is dependent on many factors, including field strength and temperature. The purpose of this study was to evaluate the relationship between sample temperature, viscosity and proton spin-lattice relaxation time (T1) and spin-spin relaxation time (T2). A review of two basic models of relaxation the simple molecular motion model and the fast exchange two state model is given with reference to their thermal dependencies. The temperature dependence for both T1 and T2 was studied on a 0.15 Tesla whole body magnetic resonance imager. Thirteen samples comprising both simple and complex materials were investigated by using a standard spin-echo (SE) technique and a modified Carr-Purcell-Meiboom-Gill (CPMG) multi-echo sequence. A simple linear relationship between T1 and temperature was observed for all samples over the range of 20 degrees C to 50 degrees C. There is an inverse relationship between viscosity and T1 and T2. A quantity called the temperature dependence coefficient (TDC) is introduced and defined as the percent rate of change of the proton relaxation time referenced to a specific temperature. The large TDC found for T1 values, e.g. 2.37%/degrees C for CuSO4 solutions and 3.59%/degrees C for light vegetable oils at 22 degrees C, indicates that a temperature correction should be made when comparing in-vivo and in-vitro T1 times. The T2 temperature dependence is relatively small.     

Magic sandwich echo relaxation mapping of anisotropic systems

The main objective of this article was (i) to refocus the residual dipolar and quadrupolar interactions in anisotropic tissues employing magic sandwich echo (MSE) imaging and to compare the results with that of conventional spin-echo (SE) imaging, and (ii) to quantify MSE relaxation and dispersion characteristics in bovine Achilles tendon and compare with spin-lattice relaxation time constant in the rotating frame (T(1rho)). Magic sandwich echo weighted images are approximately 75-100% higher in signal-to-noise ratio than the corresponding T(2)-weighted images. Magic sandwich echo relaxation times varied from 13+/-2 to 19+/-3 ms (mean+/-S.D.), depending upon the structural location of tendon. T(2) relaxation times only varied from 4+/-1 to 10+/-3 ms (mean+/-S.D.) on the same corresponding locations. Magic sandwich echo provides approximately 100% enhancement in relaxation times compared to T(2). Preliminary results based on bovine Achilles tendon and cartilage specimens suggest that the MSE technique has potential for refocusing residual dipolar as well as quadrupolar interactions in anisotropic systems and yields higher intensities than conventional SE imaging as well as T(1rho)-encoded imaging, especially at low-burst pulse amplitudes (250 and 500 Hz).