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.     

Assessment of interstitial water content of articular cartilage with T1 relaxation

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

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.     

Evaluation of muscle degeneration in inherited muscular dystrophy by nuclear magnetic resonance techniques

Nuclear magnetic resonance (NMR) techniques were applied to study the muscular dystrophy in chicks. The water proton spin-lattice relaxation times (T₁) of fast, slow, and mixed muscles and plasma were measured. The T₁ values of dystrophic pectoralis major and posterior latissimus dorsi (PLD) were significantly higher than those of the normal pectoralis and PLD muscles. The present results establish a direct relationship between the differences in T₁ values and the severity of muscle degeneration. Consistent with this conclusion, it was also found that the T₁ values of muscles unaffected in muscular dystrophy, namely, the gastrocnemius, and anterior latissimus dorsi (ALD), were not different between the normal and dystrophic chicks. Although the affected muscles of dystrophic chicks contained higher percent water and fat than those of normal chicks, the results show that the higher T₁ values is dystrophic muscles were not solely due to variations in their water content. The increase in the T₁ values is principally a result of altered interaction between cellular water and macromolecules in the diseased muscles. These data also point out the potential use of NMR imaging in evaluating muscle degeneration.     

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.     

Simultaneous measurement of total water content and myelin water fraction in brain at 3 T using a T2 relaxation based method

PurposeThis work demonstrates the in vivo application of a T₂ relaxation based total water content (TWC) measurement technique at 3 T in healthy human brain, and evaluates accuracy using simulations that model brain tissue. The benefit of using T₂ relaxation is that it provides simultaneous measurements of myelin water fraction, which correlates to myelin content.MethodsT₂ relaxation data was collected from 10 healthy human subjects with a gradient and spin echo (GRASE) sequence, along with inversion recovery for T₁ mapping. Voxel-wise T₂ distributions were calculated by fitting the T₂ relaxation data with a non-negative least squares algorithm incorporating B₁⁺ inhomogeneity corrections. TWC was the sum of the signals in the T₂ distribution, corrected for T₁ relaxation and receiver coil inhomogeneity, relative to either an external water standard or cerebrospinal fluid (CSF). Simulations were performed to determine theoretical errors in TWC.ResultsTWC values measured in healthy human brain relative to both external and CSF standards agreed with literature values. Simulations demonstrated that TWC could be measured to within 3–4% accuracy.ConclusionIn vivo TWC measurement using T₂ relaxation at 3 T works well and provides a valuable tool for studying neurological diseases with both myelin and water changes.     

In vivo NMR imaging and T1 measurements of water protons in the human brain

Nuclear magnetic resonance (NMR) proton density images of the human brain have been made by the FONAR method. Spin-lattice relaxation times, T₁, of water hydrogen protons have been determined at random positions within frontal and temporal regions of the human brain. The primary purpose of this ongoing research is to accumulate a large data base of normal T₁ values for water protons in normal human brain tissue. Our experience to data includes 31 measurements on 18 volunteer subjects, and the mean value ± standard deviation is 215 ± 42 msec. In addition, two metastatic lesions of the brain were studied and found to have T₁ values longer than those for normal brain tissue.     

Optimized gradient spoiling of UTE VFA-AFI sequences for robust T1 estimation with B1-field correction

Quantifying T₁ relaxation times is a challenge because inhomogeneities of the B₁ field have to be corrected to obtain proper values. It is a particular challenge in tissues with short T₂^⁎ values, for which conventional MRI techniques do not provide sufficient signal. Recently, a B₁-field correction technique called AFI (Actual Flip angle Imaging) has been introduced that can be combined with UTE (ultra-short echo-time) sequences, which have much shorter echo times compared to conventional MRI techniques, allowing quantification of signal in short T₂^⁎ tissues. A disadvantage of AFI is that it requires very long relaxation delays between repetitions to minimize the influence of imperfect spoiling of transverse magnetization on signal behavior. In this work, we propose a novel spoiling scheme for the AFI sequence that efficiently provides accurate B₁ correction maps with strongly reduced acquisition time. We validated the method with both phantom and preliminary in vivo results.     

High field NMR microscopic imaging of cultivated strawberry fruit

The experimental conditions required for discrimination of various types of tissue in fruits of cultivated strawberry (Fragaria × Ananassa) at high fields (ca. 7 T) have been investigated. In marked contrast to soft fruits of other species, from which informative images have been derived at high fields using a variety of pulse sequences and acquisition parameters, appreciable image intensities from parenchymal and vascular tissues in healthy strawberry fruits were obtained only with a spin-echo imaging sequence using large sweep widths (ca. 100,000 Hz), and consequently small values for TE (<5 ms), indicating predominantly short T₂ values for these tissues. Damage caused by infection by the fungal pathogen Botrytis cinerea is readily seen as a result of a large increase in T₂ in the infected tissue, whereas ripening processes appear to be characterized primarily by small variations in the T₂-weighted contrast and in the relative magnitudes of T₁ between vascular and parenchymal tissue. In addition, it was possible selectively to enhance the contributions to images from the achenes (“seeds”) by using very short relaxation delays, thereby enhancing T₁-dominated contrast mechanisms.     

Estimation of water content and water mobility in the nucleus and cytoplasm of Xenopus laevis oocytes by NMR microscopy

NMR microscopy is a noninvasive approach for studying cell structure and properties. Spatially resolved measurement of the relaxation times T₁ and T₂ provided information on the water proton spin density and water mobility in different parts of Xenopus laevis oocytes. The spin-lattice relaxation time T₁ was determined using a saturation-recovery sequence and the common spin-echo sequence with increasing repetition times, while the transverse relaxation time T₂ was measured by means of the spin-echo sequence with varying echo times. From the relaxation times, the mole fractions of possible reorientational correlation times τ_c for different types of intracellular water were calculated according to a simple two-phase model. The values for T₁, T₂, and proton spin density (i.e., water content) are: nucleus ⪢ animal cytoplasm > vegetal cytoplasm. Based on the estimation of τ_c, nearly 90% of the nuclear water and 74.4% of the water of the animal pole was considered as free mobile water, whereas 55.5% of the water of the vegetal pole appeared as bound water.     

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.     

Proton relaxation times in human red bone marrow by volume selective magnetic resonance spectroscopy

In hematological diseases the composition of red bone marrow shows alterations. The relaxation timesT ₁ andT ₂ of water and lipids in human hemopoietic bone marrow of 14 normal volunteers and 10 patients with acute leukemia and bone marrow carcinosis are determined using a double spin echo spectroscopy sequencein vivo. The volumes of interest (VOI) of (13 mm)³ in the center of vertebral bodies are examined using different measurement parameters. ForT ₁ measurements an inversion-recovery method is used.T ₂ is evaluated from spectra with differentTE. T ₁ (water) is found in a range between 1000 and 1700 ms,T ₁ (lipids) in a range between 260 and 320 ms in healthy volunteers.T ₂ (water) is determined between 32 and 65 ms. In some cases phase distortions of the water signals occur in the spectra. Water flow within the VOI may be a possible reason.T ₂ (lipids) is evaluated between 73 and 91 ms. The patients with acute leukemia exhibit clearly reduced lipid signals in their spectra. Lipid relaxation times could not be determined in these cases.T ₂ (water) is prolonged in acute leukemia to 51–98 ms.T ₁ (water) was not significantly different from values of healthy volunteers in our measurements. Results are discussed in comparison to relaxometric data from imaging and STEAM spectroscopic methods of other authors.     

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.     

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.     

Multivariate Image Analysis of Magnetic Resonance Images with the Direct Exponential Curve Resolution Algorithm (DECRA): Part 2: Application to Human Brain Images

Owing to the heterogeneity of living tissues, it is challenging to quantify tissue properties using magnetic resonance imaging. Within a single voxel, contributions to the signal may result from several types of¹H nuclei with varied chemical (e.g., −CH₂−, −OH) and physical environments (e.g., tissue density, compartmentalization). Therefore, mixtures of¹H environments are prevalent. Furthermore, each unique type of¹H environment may possess a unique and characteristic spin–lattice relaxation time (T₁) and spin–spin relaxation time (T₂). A method for resolving these unique exponentials is introduced in a separate paper (Part 1. Algorithm and Model System) and uses the direct exponential curve resolution algorithm (DECRA). We present results from an analysis of images of the human head comprising brain tissues.     

Variations in T(2)* and fat content of murine brown and white adipose tissues by chemical-shift MRI

Purpose

The purpose was to compare T₂* relaxation times and proton density fat-fraction (PDFF) values between brown (BAT) and white (WAT) adipose tissue in lean and ob/ob mice.

Materials and Methods

A group of lean male mice (n=6) and two groups of ob/ob male mice placed on similar 4-week (n=6) and 8-week (n=8) ad libitum diets were utilized. The animals were imaged at 3 T using a T₂*-corrected chemical-shift-based water–fat magnetic resonance imaging (MRI) method that provides simultaneous estimation of T₂* and PDFF on a voxel-wise basis. Regions of interest were drawn within the interscapular BAT and gonadal WAT depots on co-registered T₂* and PDFF maps. Measurements were assessed using analysis of variance, Bonferroni-adjusted t test for multigroup comparisons and the Tukey post hoc test.

Results

Significant differences (P<.01) in BAT T₂* and PDFF were observed between the lean and ob/ob groups. The ob/ob animals exhibited longer BAT T₂* and greater PDFF than lean animals. However, only BAT PDFF was significantly different (P<.01) between the two ob/ob groups. When comparing BAT to WAT within each group, T₂* and PDFF values were consistently lower in BAT than WAT (P<.01). The difference was most prominent in the lean animals. In both ob/ob groups, BAT exhibited very WAT-like appearances and properties on the MRI images.

Conclusion

T₂* and PDFF are lower in BAT than WAT. This is likely due to variations in tissue composition. The values were consistently lower in lean mice than in ob/ob mice, suggestive of the former's greater demand for BAT thermogenesis and reflective of leptin hormone deficiencies and diminished BAT metabolic activity in the latter.     

Use of a modified polysaccharide gel in developing a realistic breast phantom for MRI

A polysaccharide material, TX-151, has been used together with water, NaCl, and Al powder to create a tissue equivalent gel to make a realistic, inexpensive, conveniently moldable, temporally stable tissue equivalent MRI phantom. Various phantom compositions were studied for variations in gelling time and relaxation times. Gd-DTPA added as a T₁ (and T₂) modifier and aluminum powder added to decrease T₂ permitted phantoms to be made with a range of relaxation times comparable to human tissues. We have used this polysaccharide gel to create breast phantoms for testing breast coils and evaluating different MRI imaging sequences available for diagnosis. The breast phantoms consisted of a layer of Crisco, a good model for adipose tissue, surrounding the TX-151 gel. Some of these phantoms were created with a silicone implant encapsulated in the gel to simulate an augmented breast. More sophisticated phantoms can easily be developed by additions of other materials to this polysaccharide gel.     

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.     

Electron spinT 2 of a nitroxyl radical at 250 MHz measured by rapid-scan EPR

Rapid-scan electron paramagnetic resonance (EPR) was used to measure the room temperature spin-spin relaxation timeT ₂ for the per-deuterated nitroxyl radical, 4-oxo-2,2,6,6-tetramethylpiperidin-1-oxyl-d₁₆ in water at 250 MHz. Signals were recorded on a locally constructed system using either sinusoidal or triangular magnetic field scans. Values ofT ₂ were obtained by simulation of the rapid-scan response and were systematically shorter for the high-field line (m ₁=?1) than for them ₁=0 or +1 lines. Form ₁=+1, the value ofT ₂ increased from 0.41±0.03 μs at 0.5 mM to 0.53±0.03 μs at 0.1 or 0.2 mM. Form ₁=?1,T ₂ increased from 0.35±0.03 μs at 0.5 mM to 0.42±0.03 μs at 0.1 or 0.2 mM. These values put lower bounds on the values ofT ₁ for this nitroxyl at 250 MHz.     

Relaxation-Time and Diffusion NMR Microscopy of Single Neurons

Relaxation-time and diffusion-weighted NMR micrographs have been obtained for single neurons isolated from Aplysia californica. These images allow the nucleus and cytoplasm to be clearly differentiated, in contrast to proton spin-density images, which appear relatively homogenous. Images of the spatial distribution of T₁ and T₂ relaxivities and the diffusion coefficient (D), as well as average values for T₁, T₂, and D in the cytoplasm and nucleus, were calculated from sets of appropriately weighted images. In all cases, water in the nucleus had relaxation and diffusion properties markedly differing from those of cytoplasmic water, which in turn had properties which were distinct from those of free water. Additionally, the cytoplasmic T₂ was observed to triple following cell death, which is attributed to cytoplasmic dilution as water enters the cell. The work presented represents the first effort at a consistent exploration of the spatial distribution of NMR characteristics of water within intact single cells. These studies have implications both for modeling the NMR characteristics of water in neuronal tissues based on an understanding of the characteristics of water in different cell compartments and for understanding water/macromolecule interactions within cells. NMR microscopy studies such as these may help form a foundation for understanding and interpreting NMR characteristics measured from large assemblies of cells, i.e., spectroscopy and imaging of living tissues.