Characterization of proton NMR relaxation times in normal and pathological tissues by correlation with other tissue parameters

To help understand which tissue parameters best account for the water proton NMR relaxation times, the longitudinal relaxation time (T₂), the transverse relaxation time (T₂), and the water content of 16 tissues from normal adult rats were measured at 10.7 MHz and 29°C. Regression analyses between the above and other tissue parameters were performed. These other tissue parameters included: the amounts of various organic and inorganic components, protein synthetic rate, oxygen consumption rate, and morphological composition. In addition, the differences in T₁, T₂, and water content values between normal liver and malignant tumor (Morris #7777 a transplantable hepatoma) were studied to help understand how a disease state can be detected and characterized by NMR spectroscopy. The results of this study and information from the literature allow the following generalizations to be made about tissue T₁ and T₂ values: (1) Each normal tissue has rather consistent and characteristic T₁ and T₂ relaxation times which are always shorter than the T₁ and T₂ of bulk water; (2) tissues with higher water content tend to have longer T₁ relaxation times; (3) tissue T₂ values are not, however, as well correlated with water content as T₁ values; (4) tissues with shorter T₁ values have higher calculated hydration fractions, greater amounts of rough endoplasmic reticulum, and a greater rate of protein synthetic activity; (5) tissues with higher lipid content, associated with intracellular non-membrane bounded lipid droplets, tend to have longer T₂ values; (6) tissues with greater overall surface area, whether in the form of cellular membranes or intracellular or extracellular fibrillar macromolecules, tend to have shorter T₂ values; (7) the differences between T₁ and T₂ values between tumor and normal tissues correlated with differences in the volume fraction (amounts) of extracellular fluid volumes and in the amounts of membrane and fibrillar surface area in the cells. The above generalizations should be useful in predicting T₁ and T₂ changes associated with specific tissue pathologies.     

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.     

MRI phantom for tissue simulation with respect to diffusion coefficient and kurtosis - Validation with injection of liposomal theranostics

This study presents gelatine-based and agar-based phantoms with an addition of glycerol, safflower oil, silicone oil and cellulose microcrystalline with a potential to cover the entire range of tissue diffusion coefficients and kurtosis values. Forty types of phantoms were prepared and examined for NMR relaxation times T₁ and T₂ and diffusional metrics D, K and ADC. Wide ranges of values of D (0.0003–0.0031 mm²s⁻¹), K (0.00–7.24) and ADC (0.0002–0.0031 mm²s⁻¹) were observed. Two of the phantoms closely mimic muscle and cortical gray matter with respect to water diffusion parameters. Although many of the presented phantoms display both D and K values within the range of human tissues, they match different tissues with respect to D and K. The imaging results for the gray matter simulating phantom injected with the liposomal solution, bear a resemblance to the particle size effect described in the literature. The phantoms presented in this work are simple in preparation and affordable tissue-simulating materials to be used primarily in development of diffusion kurtosis-based MRI methods and possibly in a preliminary assessment of MRI contrast agents. Further adjustments of the chemical compositions could potentially lead to development of new types of phantoms mimicking diffusional properties of more kinds of soft tissues.     

NMR study of tomato pericarp tissue by spin-spin relaxation and water self-diffusion

Pericarp tissues of tomato varieties Quest and Cameron were studied by low-field nuclear magnetic resonance (NMR) at a controlled temperature of 20°C. The spin-spin relaxation times and the water diffusion coefficients were measured with Carr-Parcell-Meiboom-Gill and pulsed field gradient multi-spin-echo (PFGMSE) NMR sequences. Four relaxing components were extracted from the spin-spin relaxation. The components withT ₂=11 ms,T ₂=65 ms,T ₂=430 ms andT ₂=1500 ms were related to the nonexchangeable protons and water proton in each cell compartment (i.e., cell wall-extracellular space, cytoplasm and vacuole, respectively). In contrast to the relative intensities, theT ₂ values appeared insensitive to variety and harvest period. The difference in relative intensity was related to the size of the pericarp cell. The water self-diffusion coefficients for each cell compartment were determined simultaneously with the PFGMSE sequence. The water self-diffusion coefficients for the vacuole and cytoplasm were not affected by the harvest date or variety. However, the water self-diffusion in the cell wall-extracellular space was significantly different between the two varieties.     

What are normal relaxation times of tissues at 3 T?

The T₁ and T₂ relaxation times are the basic parameters behind magnetic resonance imaging. The accurate knowledge of the T₁ and T₂ values of tissues allows to perform quantitative imaging and to develop and optimize magnetic resonance sequences. A vast extent of methods and sequences has been developed to calculate the T₁ and T₂ relaxation times of different tissues in diverse centers. Surprisingly, a wide range of values has been reported for similar tissues (e.g. T₁ of white matter from 699 to 1735 ms and T₂ of fat from 41 to 371 ms), and the true values that represent each specific tissue are still unclear, which have deterred their common use in clinical diagnostic imaging. This article presents a comprehensive review of the reported relaxation times in the literature in vivo at 3 T for a large span of tissues. It gives a detailed analysis of the different methods and sequences used to calculate the relaxation times, and it explains the reasons of the spread of reported relaxation times values in the literature.     

Ex vivo study of carotid endarterectomy specimens: quantitative relaxation times within atherosclerotic plaque tissues

Purpose

Previous studies reporting relaxation times within atherosclerotic plaque have typically used dedicated small-bore high-field systems and small sample sizes. This study reports quantitative T₁, T₂ and T₂^? relaxation times within plaque tissue at 1.5 T using spatially co-matched histology to determine tissue constituents.

Methods

Ten carotid endarterectomy specimens were removed from patients with advanced atherosclerosis. Imaging was performed on a 1.5-T whole-body scanner using a custom built 10-mm diameter receive-only solenoid coil. A protocol was defined to allow subsequent computation of T₁, T₂ and T₂^? relaxation times using multi-flip angle spoiled gradient echo, multi-echo fast spin echo and multi-echo gradient echo sequences, respectively. The specimens were subsequently processed for histology and individually sectioned into 2-mm blocks to allow subsequent co-registration. Each imaging sequence was imported into in-house software and displayed alongside the digitized histology sections. Regions of interest were defined to demarcate fibrous cap, connective tissue and lipid/necrotic core at matched slice-locations. Relaxation times were calculated using Levenberg-Marquardt's least squares curve fitting algorithm. A linear-mixed effect model was applied to account for multiple measurements from the same patient and establish if there was a statistically significant difference between the plaque tissue constituents.

Results

T₂ and T₂^? relaxation times were statistically different between all plaque tissues (P=.026 and P=.002 respectively) [T₂: lipid/necrotic core was lower 47±13.7 ms than connective tissue (67±22.5 ms) and fibrous cap (60±13.2 ms); T₂^?: fibrous cap was higher (48±15.5ms) than connective tissue (19±10.6 ms) and lipid/necrotic core (24±8.2 ms)]. T₁ relaxation times were not significantly different (P=.287) [T₁: Fibrous cap: 933±271.9 ms; connective tissue (1002±272.9 ms) and lipid/necrotic core (1044±304.0 ms)]. We were unable to demarcate hemorrhage and calcium following histology processing.

Conclusions

This study demonstrates that there is a significant difference between qT₂ and qT₂^? in plaque tissues types. Derivation of quantitative relaxation times shows promise for determining plaque tissue constituents.     

Prominent signal intensity of T1/T2 prolongation in subcortical white matter of the anterior temporal region on conventional screening MRI of late preterm infants with normal development

Purpose

This study discusses prominent signal intensity of T₁/T₂ prolongation of subcortical white matter within the anterior temporal region in premature infant brains that radiologists may encounter when interpreting conventional screening MRIs.

Materials and Methods

T₁- and T₂-weighted images of 69 preterm and term infants with no neurological abnormalities or developmental delays were evaluated retrospectively for areas of prominent signal intensity of T₁/T₂ prolongation in white matter. We measured signal intensities of anterior temporal white matter, deep temporal white matter, frontopolar white matter and subcortical white matter of the precentral gyrus. We accessed chronological changes in signal intensity in the anterior and deep temporal white matter. We also analyzed variance tests among the signal intensity ratios to the ipsilateral thalamus of white matter areas by gestational age.

Results

There was high frequency of prominent signal intensity of T₁/T₂ prolongation in the temporal tip, particularly at a gestational age of 36–38 weeks. Signal intensity ratio of the anterior temporal white matter was lower on T₁-weighted images and higher on T₂-weighted images, and the finding became less prominent with increasing gestational age. The signal intensity ratios of anterior temporal white matter at a gestational age of 36–37 weeks and 38–39 weeks were significantly different from other regions.

Conclusion

Prominent signal intensity of T₁/T₂ prolongation of subcortical white matter of the anterior temporal region is seen in normal premature infants, especially those at 36–39 gestational weeks. Although it is a prominent finding, radiologists should understand that these findings do not represent a pathological condition.     

Age dependency of the regional cerebral blood volume (rCBV) measured with dynamic susceptibility contrast MR imaging (DSC)

The changes of the regional cerebral blood volume (rCBV) with age were studied using dynamic susceptibility contrast MRI (DSC). We examined an unselected, random sample of 71 consecutive patients referred for work-up of suspected intracranial tumors (35 normal examinations, 36 tumors) with a standard 1.5 T clinical MR system. Determination of the rCBV was performed with a T₂¹-weighted simultaneous dual (SD) FLASH sequence (TR/TE1/TE2/α = 32/25/16/10°, 55 images) after bolus injection of Gd-DTPA. Absolute quantification of the rCBV was achieved by normalizing the measured tissue concentration-time curves with the integrated arterial input function (AIF), which was simultaneously measured in the brain feeding arteries. The rCBV (mean ± SD) was 8.4 ± 2.9 ml/100 g and 4.2 ± 1.7 ml/100 g in gray and white matter, respectively, with a decline of about 3% and 6% per decade for white and gray matter, respectively. We conclude that DSC using a SD FLASH sequence allows the simultaneous measurement of the AIF and the tissue concentration-time curve and thus an absolute quantification of the rCBV, which is the basis for interperson comparisons and follow-up studies.     

Spin-lattice relaxation and magnetization transfer in intracranial tumors in vivo: Effects of Gd-DTPA on relaxation parameters

Spin-lattice relaxation time T₁ and relaxation parameters in magnetization transfer (MT) imaging were measured in 11 intracranial tumors before and after injection of Gd-DTPA at 0.1 T by using the inversion recovery method and the saturation transfer technique, respectively. Preinjection T₁ relaxation times of the tumors were longer than those of white matter, but after Gd-enhancement the relaxation times of most tumors were in the same range as those of white matter. Gd-DTPA shortened the apparent relaxation time in the presence of off-resonance saturation pulse (T_1α) due to marked shortening of the relaxation time of mobile water (T_1w). Gd-DTPA decreased the magnetization transfer contrast (MTC) but did not influence on the magnetization transfer rate (R_wm). The parameters MTC and R_wm differed clearly between Gd-enhanced tumors and normal brain, whereas the relaxation time T_1α was in many Gd-enhanced tumors in the same range as in normal brain.     

Relaxation effects and evidence for one dimensional ordering in KFeCl3 studied by Mössbauer spectroscopy

Mössbauer measurements of KFeCl₃ over the temperature range 4.2–293°K show a transition to a magnetically ordered phase at T_N ? 18.5°K and evidence for one-dimensional order above T_N. In the region 10–25°K striking relaxation effects appear. An approximate analysis of the quadrupole splitting data was used for the determination of the fine structure of the ⁵D levels below T_N which in turn was used for a theoretical reproduction of the relaxation spectra between 10–25°K.     

A comparative study at 3 T of sequence dependence of T2 quantitation in the knee

Objective

T₂ mapping has been used widely in detecting cartilage degeneration in osteoarthritis. Several scanning sequences have been developed in the determination of T₂ relaxation times of tissues. However, the derivation of these times may vary from sequence to sequence. This study seeks to evaluate the sequence-dependent differences in T₂ quantitation of cartilage, muscle, fat and bone marrow in the knee joint at 3 T.

Methods

Three commercial phantoms and 10 healthy volunteers were studied using 3 T MR. T₂ relaxation times of the phantoms, cartilage, muscle, subcutaneous fat and marrow were derived using spin echo (SE), multiecho SE (MESE), fast SE (FSE) with varying echo train length (ETL), spiral and spoiler gradient (SPGR) sequences. The differences between these times were then evaluated using Student's t test. In addition, the signal-to-noise ratio (SNR) efficiency and coefficient of variation of T₂ from each sequence were calculated.

Results

The average T₂ relaxation time was 36.38±5.76 ms in cartilage and 34.08±6.55 ms in muscle, ranging from 27 to 45 ms in both tissues. The times for subcutaneous fat and marrow were longer and more varying, ranging from 41 to 143 ms and from 42 to 160 ms, respectively. In FSE acquisition, relaxation time significantly increases as ETL increases (P<.05). In cartilage, the SE acquisition yields the lowest T₂ values (27.52±3.10 ms), which is significantly lower than those obtained from other sequences (P<.002). T₂ values obtained from spiral acquisition (38.27±6.45 ms) were higher than those obtained from MESE (34.35±5.62 ms) and SPGR acquisition (31.64±4.53 ms). These differences, however, were not significant (P>.05).

Conclusion

T₂ quantification can be a valuable tool for the diagnosis of degenerative disease. Several different sequences exist to quantify the relaxation times of tissues. Sequences range in scan time, SNR efficiency, reproducibility and two- or three-dimensional mapping. However, when choosing a sequence for quantitation, it is important to realize that several factors affect the measured T₂ relaxation time.     

A Comparative Study of Water T1 and T2 Nmr Relaxation Times in Healthy and Pathological Blood Fluid

Water protons T₁ and T₂ relaxation times in samples of whole blood, obtained from healthy people and from patients affected by Macrocytic Anemia on one side and Lymphatic and Myeloid Leukemia on the other, have been measured with the FT NMR technique at 80 Mhz and at 25 °C. No significant difference with respect to the value of the spin lattice relaxation time parameter measured for the healthy control group is experimentally evident in the case of the Macrocytic Anaemia while the spin spin relaxation time increases in magnitude. On the reverse both the leukemic cases present a significant (p < 0.001) increase in the relaxation times with respect to the control group. The experimental relaxation data belonging to the anaemic case show a linear correlation with the red cells volume while that obtained for the two leukaemic cases appear linearly correlated with the total white cell numbers. From the relaxation data an estimate of the amount of water tightly bound to the white cells membrane can be determined which results roughly thirty times lower than that bound to the red cells membrane. In this work is also presented a step by step outline of the water relaxation behavior which starts with the pure water and ends with the water in the whole blood supported by relaxation experiments done on the isolated blood main components.     

Determination of T1ρ values for head and neck tissues at 0.1 T: a comparison to T1 and T2 relaxation times

In order to optimize head and neck magnetic resonance (MR) imaging with the spin-lock (SL) technique, the T₁ρ relaxation times for normal tissues were determined. Furthermore, T₁ρ was compared to T₁ and T₂ relaxation times. Ten healthy volunteers were studied with a 0.1 T clinical MR imager. T₁ρ values were determined by first measuring the tissue signal intensities with different locking pulse durations (TL), and then by fitting the signal intensity values to the equation with the least-squares method. The T₁ρ relaxation times were shortest for the muscle and tongue, intermediate for lymphatic and parotid gland tissue and longest for fat. T₁ρ demonstrated statistically significant differences (p < 0.05) between all tissues, except between muscle and tongue. T₁ρ values measured at locking field strength (B1L) of 35 μT were close to T₂ values, the only exception being fat tissue, which showed T₁ρ values much longer than T₂ values. Determination of tissue relaxation times may be utilized to optimize image contrast, and also to achieve better tissue discrimination potential, by choosing appropriate imaging parameters for the head and neck spin-lock sequences.     

II. A protocol for in vitro proton relaxation studies

A protocol, referred to as the EEC In Vitro NMR Protocol, is offered for use in the measurement of NMR proton relaxation times of excised tissues and associated materials. The protocol, which has been evaluated in an international trial, designates: (a) The type of information which should be provided in all reports; (b) Tissue handling and storage, including initial manipulation, temperature treatment, and short and long storage of tissue; (c) Instrumental parameters, including pulse sequences for T₁ and T₂ measurement, appropriate number of data points, and their distribution along the relaxation curve; and (d) Methods of data analysis. The discussion amplifies some of the points with reasons for the choices of conditions made in the protocol.     

What causes the hyperintense T2-weighting and increased short T2 signal in the corticospinal tract?

The corticospinal tract (CST) appears hyperintense on both T₂-weighted images and myelin water maps. Here, an extended multiecho T₂ relaxation sequence with echoes out to 1120 ms was used to characterize the longer T₂ times present in the CST. The T₂ distribution from the CST was compared to other white matter structures in 14 healthy subjects. The intra-/extracellular T₂ peak of the CST was broadened relative to other white matter structures and often split into two distinct peaks. In the CST, it appeared that the intracellular and extracellular water environments had unique T₂ times, causing the intracellular water peak to be pushed down into the myelin water T₂ regime and the extracellular peak to be pushed up to longer T₂ times. The conventional myelin water T₂ limits of 5-40 ms resulted in an artificial increase in myelin water fraction (MWF), causing the CST to be bright on myelin water images. When the upper limit for MWF was decreased to 25 ms, the CST regions exhibited MWF values similar to those found for adjacent anterior and posterior regions. The CST has unique magnetic resonance characteristics, which should be taken into consideration when being examined, especially when compared to pathological tissue.     

Non-invasive temperature mapping using MRI: comparison of two methods based on chemical shift and T1-relaxation

Purpose: To implement and evaluate the accuracy of non-invasive temperature mapping using MRI methods based on the chemical shift (CS) and T₁ relaxation in media of various heterogeneity during focal (laser) and external thermal energy deposition.Materials and Methods: All measurements were performed on a 1.5 T superconducting clinical scanner using the temperature dependence of the water proton chemical shift and the T₁ relaxation time. Homogeneous gel and heterogeneous muscle phantoms were heated focally with a fiberoptic laser probe and externally of varying degree ex vivo by water circulating in a temperature range of 20–50°C. Magnetic resonance imaging data were compared to simultaneously recorded fiberoptic temperature readings.Results: Both methods provided accurate results in homogeneous media (turkey) with better accuracy for the chemical shift method (CS: ±1.5°C, T₁: ±2.0°C). In gel, the accuracy with the CS method was ±0.6°C. The accuracy decreased in heterogeneous media containing fat (T₁: ±3.5°C, CS: +5°C). In focal heating of turkey muscle, the accuracy was within 1.5°C with the T₁ method.Conclusion: Temperature monitoring with the chemical shift provides better results in homogeneous media containing no fat. In fat tissue, the temperature calculation proved to be difficult.     

Bi-Exponential T2 Decay in Dairy Cream Phantoms

MRI phantoms are an important part of any experiment because they provide a reference of known parameters. There are many choices of mono-exponential T₂ phantoms, but few choices for bi-exponential T₂ phantoms. We have found that dairy cream provides an excellent bi-exponential T₂ model with similar relaxation times to those found in white matter. Five cream phantoms of different milk fat percentages (2, 6, 10, 18 and 35%) were imaged with an optimized Carr–Purcell–Meiboom–Gill sequence. The decay curves for each of the phantoms were fit using Non-Negative Least Squares. We found that the short T₂ component fraction relative to the total energy in the distribution correlated linearly (r = 0.9973) with the milk fat percentage. The short T₂ time was 38 ± 4 ms and the long T₂ time was 135 ± 4 ms.     

Effect of heptamethyldisilazane on the electrochemical performance of LiMn2O4/Li

The effect of heptamethyldisilazane as an electrolyte stabilizer on the cycling performance of a LiMn₂O₄/Li cell at different rates at 30 °C and the storage performance at 60 °C is investigated systematically based on conductivity test, linear sweep voltage, electrochemical impedance spectroscopy, scanning electron microscopy, X-ray diffraction, and charge–discharge measurements. The results show that heptamethyldisilazane added into the LiPF₆-based electrolyte can increase the stability of the original electrolyte; coulomb efficiency, the initial discharge capacity, and cycling performance at different rates in a sense, meanwhile, improve the storage performance at elevated temperature, although the C-rate performance of the cell is a little worse than that without heptamethyldisilazane in the electrolyte. When the LiMn₂O₄/Li cell with heptamethyldisilazane in the LiPF₆-based electrolyte stored at 60 °C for a week cycles 300 times, the capacity retention is up to 91.18 %, which is much higher than that (87.18 %) without the additive in the electrolyte. This is mainly due to the lower solid electrolyte interface resistance (R _f) in the cell, followed by the better morphology and structure of the cathode after storage at 60 °C for a week compared with the LiMn₂O₄/Li cell without heptamethyldisilazane.     

Nuclear magnetic relaxation,correlation time spectrum,and molecular dynamics in a linear polymer

The pulsed nuclear magnetic resonance (NMR) method at a proton frequency of 25 MHz at temperatures of 22–160°C is used to detect the transverse magnetization decay in polyisoprene rubbers with various molecular masses, to determine the NMR damping time T ₂, and to measure spin-lattice relaxation time T ₁ and time T _2eff of damping of solid-echo signals under the action of a sequence of MW-4 pulses modified by introducing 180° pulses. The dispersion dependences of T _2eff obtained for each temperature are combined into one using the temperature-frequency equivalence principle. On the basis of the combined dispersion dependence of T _2eff and the data on T ₂ and T ₁, the correlation time spectrum of molecular movements is constructed. Analysis of the shape of this spectrum shows that the dynamics of polymer molecules can be described in the first approximation by the Doi-Edwards tube-reptation model.     

TSC study of electric dipole relaxations in chlorapatite

Electric dipole relaxations in chlorapatite, Ca₅(PO₄)₃Cl, have been studied with the fractional polarization mode of the thermally stimulated currents (TSC) method. Fifty-one of the fifty-seven sets of data obtained in the range 10–443°K fell naturally into four groups yielding compensation temperatures T_C of T_C1, = 202°C, T_C2: = 202°C, T_C3 = 420°C and T_C4= 644°C, with estimated error < 10°C, and characteristic relaxation times τ_C of τ_C1 = 1.3 × 10^?7s, τ_C2 = 3.2 × 10^?6s, τ_C3 = 8.8 × 10^?5s and τ_C4 = 2.3 × 10^?4s. Atomic-scale physical models involving Cl^? ion motion are offered for the 202°C compensation at the temperature of the reported monoclinic-to-hexagonal phase transition and for the 420°C compensation, at which temperature the Cl^? ions individually are thought to have enough thermal energy to maintain the hexagonal form dynamically.