Comparison of lung T2* during free‐breathing at 1.5 T and 3.0 T with ultrashort echo time imaging

Assessment of lung effective transverse relaxation time (T₂*) may play an important role in the detection of structural and functional changes caused by lung diseases such as emphysema and chronic bronchitis. While T₂* measurements have been conducted in both animals and humans at 1.5 T, studies on human lung at 3.0 T have not yet been reported. In this work, ultrashort echo time imaging technique was applied for the measurement and comparison of T₂* values in normal human lungs at 1.5 T and 3.0 T. A 2D ultrashort echo time pulse sequence was implemented and evaluated in phantom experiments, in which an eraser served as a homogeneous short T₂* sample. For the in vivo study, five normal human subjects were imaged at both field strengths and the results compared. The average T₂* values measured during free‐breathing were 2.11(±0.27) ms at 1.5 T and 0.74(±0.1) ms at 3.0 T, respectively, resulting in a 3.0 T/1.5 T ratio of 2.9. Furthermore, comparison of the relaxation values at end‐expiration and end‐inspiration, accomplished through self‐gating, showed that during normal breathing, differences in T₂* between the two phases may be negligible. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Contrast at high field: Relaxation times,magnetization transfer and phase in the rat brain at 16.4 T

As field strength increases, the magnetic resonance imaging contrast parameters like relaxation times, magnetization transfer or image phase change, causing variations in contrast and signal‐to‐noise ratio. To obtain reliable data for these parameters at 16.4 T, high‐resolution measurements of the relaxation times T₁, T₂ and T₂*, as well as of the magnetization transfer ratio and the local frequency in the rat brain were performed. Tissue‐specific values were obtained for up to 17 brain structures to assess image contrast. The measured parameters were compared to those found at different field strengths to estimate contrast and signal behavior at increasing field. T₁ values were relatively long with (2272 ± 113) ms in cortex and (2073 ± 97) ms in white matter, but did not show a tendency to converge, leading to an almost linear increase in signal‐to‐noise ratio and still growing contrast‐to‐noise ratio. T₂ was short with (25 ± 2) ms in cortex and (20 ± 1) ms in white matter. Magnetization transfer effects increase by around 25% compared to published 4.7 T data, which leads to improved contrast. The image phase, as novel and high‐field specific contrast mechanism, is shown to obtain good contrast in deep brain regions with increasing signal‐to‐noise ratio up to high field strengths. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.     

Characterization of T2* heterogeneity in human brain white matter

Recent in vivo MRI studies at 7.0 T have demonstrated extensive heterogeneity of T₂* relaxation in white matter of the human brain. In order to study the origin of this heterogeneity, we performed T₂* measurements at 1.5, 3.0, and 7.0 T in normal volunteers. Formalin‐fixed brain tissue specimens were also studied using T₂*‐weighted MRI, histologic staining, chemical analysis, and electron microscopy. We found that T₂* relaxation rate (R₂* = 1/T₂*) in white matter in living human brain is linearly dependent on the main magnetic field strength, and the T₂* heterogeneity in white matter observed at 7.0 T can also be detected, albeit more weakly, at 1.5 and 3.0 T. The T₂* heterogeneity exists also in white matter of the formalin‐fixed brain tissue specimens, with prominent differences between the major fiber bundles such as the cingulum (CG) and the superior corona radiata. The white matter specimen with substantial difference in T₂* has no significant difference in the total iron content, as determined by chemical analysis. On the other hand, evidence from histologic staining and electron microscopy demonstrates these tissue specimens have apparent difference in myelin content and microstructure. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

In vivo measurement of T*2 and field inhomogeneity maps in the human heart at 1.5 T

Cardiac echo-planar imaging suffers invariably from regions of severe distortion and T*₂ decay in the myocardium. The purpose of this work was to perform local measurements of T*₂ and field inhomogeneities in the myocardium and to identify the sources of focal signal loss and distortion. Field inhomogeneity maps and T*₂ were measured in five normal volunteers in short-axis slices spanning from base to apex. It was found that T*₂ ranged from 26 ms (SD = 7 ms, n = 5) to 41 ms (SD = 11 ms, n = 5) over most of the heart, and peak-to-peak field inhomogeneity differences were 71 Hz (SD = 14 Hz, n = 5). In all hearts, regions of severe signal loss were consistently adjacent to the posterior vein of the left ventricle; T*₂ in these regions was 12 ms (SD = 2 ms, n = 5), and the difference in resonance frequency with the surrounding myocardium was 70-100 Hz. These effects may be caused by increased magnetic susceptibility from deoxygenated blood in these veins.     

Human imaging at 9.4 T using T2*‐, phase‐, and susceptibility‐weighted contrast

The effect of susceptibility differences on an MR image is known to increase with field strength. Magnetic field inhomogeneities within the voxels influence the apparent transverse relaxation time T₂*, while effects due to different precession frequencies between voxels caused by local field variations are evident in the image phase, and susceptibility‐weighted imaging highlights the veins and deep brain structures. Here, these three contrast mechanisms are examined at a field strength of 9.4 T. The T₂* maps generated allow the identification of white matter structures not visible in conventional images. Phase images with in‐plane resolutions down to 130 μm were obtained, showing high gray/white matter contrast and allowing the identification of internal cortical structures. The susceptibility‐weighted images yield excellent visibility of small venous structures and attain an in‐plane resolution of 175 μm. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.     

Optimization of iron oxide nanoparticle detection using ultrashort echo time pulse sequences: Comparison of T1, T2*, and synergistic T1 − T2* contrast mechanisms

Iron oxide nanoparticles (IONPs) are used in various MRI applications as negative contrast agents. A major challenge is to distinguish regions of signal void due to IONPs from those due to low signal tissues or susceptibility artifacts. To overcome this limitation, several positive contrast strategies have been proposed. Relying on IONP T₁ shortening effects to generate positive contrast is a particularly appealing strategy because it should provide additional specificity when associated with the usual negative contrast from effective transverse relaxation time (T₂*) effects. In this article, ultrashort echo time imaging is shown to be a powerful technique which can take full advantage of both contrast mechanisms. Methods of comparing T₁ and T₂* contrast efficiency are described and general rules that allow optimizing IONP detection sensitivity are derived. Contrary to conventional wisdom, optimizing T₁ contrast is often a good strategy for imaging IONPs. Under certain conditions, subtraction of a later echo signal from the ultrashort echo time signal not only improves IONP specificity by providing long T₂* background suppression but also increases detection sensitivity, as it enables a synergistic combination of usually antagonist T₁ and T₂* contrasts. In vitro experiments support our theory, and a molecular imaging application is demonstrated using tumor‐targeted IONPs in vivo. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Repeatability of ultrashort echo time‐based two‐component T2* measurements on cartilages in human knee at 3 T

Repeatability of in vivo measurement of multicomponent T₂* relaxation in articular cartialges in human knee is important to clinical use. This study evaluated the repeatability of two‐component T₂* relaxation on seven healthy human subjects. The left knee was scanned once a day in three consecutive days, on a clinical 3T MRI scanner with eight‐channel knee coil and ultrashort echo time pulse sequence at 11 echo times = 0.6–40 ms. The intrasubject and intersubject repeatability was evaluated via coefficient of variation (CV = standard deviation/mean) in four typical cartilage regions: patellar, anterior articular, femoral, and tibial regions. It was found that the intrasubject repeatability was good, with CV < 10% for the short‐ and long‐T₂* relaxation time in the layered regions in the four cartilages (with one exception) and CV < 13% for the component intensity fraction (with two exceptions). The intersubject repeatability was also good, with CV ～8% (range 1–15%) for the short‐ and long‐T₂* relaxation time and CV ～10% (range 2–20%) for the component intensity fraction. The long‐T₂* component showed significantly better repeatability (CV ～8%) than the short‐T₂* component (CV～12%) (P < 0.005). These CV values suggest that in vivo measurement of two‐component T₂* relaxation in the knee cartilages is repeatable on clinical scanner at 3 T, with a signal‐to‐noise ratio of 90. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

On using T2 to assess extrinsic magnetic field inhomogeneity effects on T2* measurements in myocardial siderosis in thalassemia

Magnetic resonance T₂* has been validated as a noninvasive means of assessing myocardial iron overload. However, the effect on myocardial T₂* of factors such as shimming, variations in capillary geometry, and susceptibility in relation to the effects of iron has not been fully clarified. Since T₂ is not affected by extrinsic magnetic field inhomogeneity and has different sensitivity to capillary geometry, investigation into the in vivo relationship between myocardial T₂* and T₂ measurements can shed light on this important issue. This study was performed in 136 thalassemia patients. The myocardial T₂ and T₂* thresholds for normality created identical no‐iron‐overload and iron‐overloaded patient groups. In the no‐iron group, there was no correlation between myocardial T₂ and T₂*. In the iron‐overloaded patients, there was a linear correlation (R² = 0.89) between myocardial T₂* and T₂ measurements, which indicates that the iron deposition is the dominant factor in determining these two relaxation values in this scenario. Magn Reson Med, 2009. © 2008 Wiley‐Liss, Inc.     

Independent estimation of T*2 for water and fat for improved accuracy of fat quantification

Noninvasive biomarkers of intracellular accumulation of fat within the liver (hepatic steatosis) are urgently needed for detection and quantitative grading of nonalcoholic fatty liver disease, the most common cause of chronic liver disease in the United States. Accurate quantification of fat with MRI is challenging due the presence of several confounding factors, including T*₂ decay. The specific purpose of this work is to quantify the impact of T*₂ decay and develop a multiexponential T*₂ correction method for improved accuracy of fat quantification, relaxing assumptions made by previous T*₂ correction methods. A modified Gauss‐Newton algorithm is used to estimate the T*₂ for water and fat independently. Improved quantification of fat is demonstrated, with independent estimation of T*₂ for water and fat using phantom experiments. The tradeoffs in algorithm stability and accuracy between multiexponential and single exponential techniques are discussed. Magn Reson Med 63:849–857, 2010. © 2010 Wiley‐Liss, Inc.     

Multicomponent T2* mapping of knee cartilage: Technical feasibility ex vivo

Disorganization of collagen fibers is a sign of early‐stage cartilage degeneration in osteoarthritic knees. Water molecules trapped within well‐organized collagen fibrils would be sensitive to collagen alterations. Multicomponent effective transverse relaxation (T₂*) mapping with ultrashort echo time acquisitions is here proposed to probe short T₂ relaxations in those trapped water molecules. Six human tibial plateau explants were scanned on a 3T MRI scanner using a home‐developed ultrashort echo time sequence with echo times optimized via Monte Carlo simulations. Time constants and component intensities of T₂* decays were calculated at individual pixels, using the nonnegative least squares algorithm. Four T₂*‐decay types were found: 99% of cartilage pixels having mono‐, bi‐, or nonexponential decay, and 1% showing triexponential decay. Short T₂* was mainly in 1‐6 ms, while long T₂* was ～22 ms. A map of decay types presented spatial distribution of these T₂* decays. These results showed the technical feasibility of multicomponent T₂* mapping on human knee cartilage explants. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Regional and global pancreatic T*2 MRI for iron overload assessment in a large cohort of healthy subjects: Normal values and correlation with age and gender

Multiecho gradient‐echo T*₂ magnetic resonance imaging is a well‐established technique for iron overload assessment but there are few reports concerning the pancreas. The aim of this work was to assess the feasibility and reproducibility of the magnetic resonance imaging for measuring pancreatic regional and global T*₂ values, to establish the lower limit of normal in a large cohort of healthy subjects and to correlate the measured values with age and gender. One hundred and twenty healthy subjects (61 males, 51 ± 17 years) underwent magnetic resonance imaging (1.5T) using a multiecho gradient‐echo T*₂ sequence. T*₂ measurements were performed in pancreatic head, body, and tail. The global value was calculated as the mean. Measurement of pancreatic T*₂ values was feasible in all subjects. For the T*₂ global value the coefficient of variation for intraoperator and interoperator reproducibility were 7.7% and 13%, respectively. The global T*₂ values ranged from 24 to 52 ms with the lower limit of normal of 26 ms. There were no significant differences among the regional pancreatic T*₂ values. No significant correlation was found between T*₂ and patient age or gender. In conclusion, pancreatic T*₂ measurements appear to be feasible, reproducible, nontime‐consuming and reliable. Gender‐ and age‐related differences concerning pancreatic T*₂ were not found. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.     

Alternate k-space sampling in EPI: Compensation for T2* and adjustable T2 weighting

In this work, preliminary results are described for a modification of the MBEST sampling scheme such that image resolution can be increased while preserving image contrast. In this new approach, a single spin-echo is used in sampling k-space. The basic idea relies on acquiring a conventional EPI image from the center of k-space and applying a ψ pulse to permit the acquisition of the two outer edges of k-space. Using this new approach, it is possible to obtain an enhancement in EPI image resolution, while reducing the extent of T₂* weighting. As a result, the resulting images possess reduced T₂* contrast and suffer less signal loss from T₂* effects such as spatial variations in susceptibility and field inhomogeneity.     

Chemical shift sodium imaging in a mouse model of thromboembolic stroke at 9.4 T

Purpose:

To estimate changes in the ²³Na density and in the ²³Na relaxation time T₂* in the anatomically small murine brain after stroke.

Materials and Methods:

Three‐dimensional acquisition weighted chemical shift imaging at a resolution of 0.6 × 0.6 × 1.2 mm³ was used for sodium imaging and relaxation parameter mapping. In vivo measurements of the mouse brain (n = 4) were performed 24 hours after stroke, induced by microinjection of purified murine thrombin into the right middle cerebral artery. The measurement time was 14 minutes in one mouse and 65 minutes in the other three. An exponential fit estimation of the free induction decay was calculated for each voxel enabling the reconstruction of locally resolved relaxation parameter maps.

Results:

The infarcted areas showed an increase in sodium density between 160% and 250%, while the T₂* relaxation time increased by 5%–72% compared to unaffected contralateral brain tissue.

Conclusion:

²³Na chemical shift imaging at a resolution of 0.6 × 0.6 × 1.2 mm³ enabled sodium imaging of the anatomical small mouse brain and the acquired data allowed calculating relaxation parameter maps and hence a more exact evaluation of sodium signal changes after stroke. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.     

Glioma cell density in a rat gene therapy model gauged by water relaxation rate along a fictitious magnetic field

Longitudinal and transverse rotating‐frame relaxation time constants, T_1ρ and T_2ρ, have previously been successfully applied to detect gene therapy responses and acute stroke in animal models. Those experiments were performed with continuous‐wave irradiation or with frequency‐modulated pulses operating in an adiabatic regime. The technique called Relaxation Along a Fictitious Field (RAFF) is a recent extension of frequency‐modulated rotating‐frame relaxation methods. In RAFF, spin locking takes place along a fictitious magnetic field, and the decay rate is a function of both T_1ρ and T_2ρ processes. In this work, the time constant characterizing water relaxation with RAFF (T_RAFF) was evaluated for its utility as a marker of response to gene therapy in a rat glioma model. To investigate the sensitivity to early treatment response, we measured several rotating‐frame and free‐precession relaxation time constants and the water apparent diffusion coefficients, and these were compared with histological cell counts in 8 days of treated and control groups of animals. T_RAFF was the only parameter exhibiting significant association with cell density in three different tumor regions (border, intermediate, and core tissues). These results indicate that T_RAFF may provide a marker to identify tumors responding to treatment. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

On the dual contrast enhancement mechanism in frequency‐selective inversion‐recovery magnetic resonance angiography (IRON‐MRA)

The susceptibility of blood changes after administration of a paramagnetic contrast agent that shortens T₁. Concomitantly, the resonance frequency of the blood vessels shifts in a geometry‐dependent way. This frequency change may be exploited for incremental contrast generation by applying a frequency‐selective saturation prepulse prior to the imaging sequence. The dual origin of vascular enhancement depending first on off‐resonance and second on T₁ lowering was investigated in vitro, together with the geometry dependence of the signal at 3T. First results obtained in an in vivo rabbit model are presented. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Estimation of liver T*2 in transfusion‐related iron overload in patients with weighted least squares T*2 IDEAL

MRI imaging of hepatic iron overload can be achieved by estimating T₂* values using multiple‐echo sequences. The purpose of this work is to develop and clinically evaluate a weighted least squares algorithm based on T₂* Iterative Decomposition of water and fat with Echo Asymmetry and Least‐squares estimation (IDEAL) technique for volumetric estimation of hepatic T₂* in the setting of iron overload. The weighted least squares T₂* IDEAL technique improves T₂* estimation by automatically decreasing the impact of later, noise‐dominated echoes. The technique was evaluated in 37 patients with iron overload. Each patient underwent (i) a standard 2D multiple‐echo gradient echo sequence for T₂* assessment with nonlinear exponential fitting, and (ii) a 3D T₂* IDEAL technique, with and without a weighted least squares fit. Regression and Bland–Altman analysis demonstrated strong correlation between conventional 2D and T₂* IDEAL estimation. In cases of severe iron overload, T₂* IDEAL without weighted least squares reconstruction resulted in a relative overestimation of T₂* compared with weighted least squares. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Release activation of iron oxide nanoparticles: (REACTION) A novel environmentally sensitive MRI paradigm

Smart contrast agents for MRI‐based cell tracking would enable the use of MRI methodologies to not only detect the location of cells but also gene expression. Here, we report on a new enzyme/contrast agent paradigm which involves the enzymatic degradation of the polymer coating of magnetic nanoparticles to release encapsulated magnetic cores. Cells were labeled with particles coated with a polymer, which is cleavable by a specific enzyme. This coat restricts the approach of water to the particle, preventing the magnetic core from efficiently relaxing protons. The reactive enzyme was delivered to cells and changes in cellular T₂ and T₂* relaxation times of ～ 35% and ～ 50% were achieved in vitro. Large enhancements of dark contrast volume (240%) and contrast‐to‐noise ratio (48%) within the contrast regions were measured, in vivo, for cells co‐labeled with enzyme and particles. These results warrant exploration of genetic avenues toward achieving release activation of iron oxide nanoparticles. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Spectroscopic imaging of the water resonance with short repetition time to study tumor response to hyperoxia

A variety of treatments that modulate tumor oxygen tension are used clinically to improve the outcome of radiotherapy. High resolution, noninvasive measurements of the effects of these treatments would greatly facilitate the development of improved therapies and could guide treatment of cancer patients. Previous work demonstrated that magnetic resonance (MR) gradient echo imaging of the water proton resonance detects changes in T₂* and T₁ in tumors during hyperoxia that may reflect increased tumor oxygenation. This report describes the use of high resolution MR spectroscopic imaging with short repetition time (TR = 0.2 s) to improve the accuracy with which changes in T₂* and T₁ are measured. Mammary adenocarcinomas grown in the hind limbs of rats were studied. Carbogen inhalation was used to induce hyperoxia. A single 2-mm slice through the center of tumors and underlying muscle was imaged at 4.7 Tesla with in-plane resolution of approximately 1.2 mm and frequency resolution of 5.8 Hz. The peak integral increased by an average of 6% in tumors during carbogen inhalation suggesting a decrease in T₁ (n = 8, P <0.001). Peak height increased by an average of 15% in tumors during carbogen inhalation (n = 8, P <0.001). The large difference between increases in peak height and peak integral demonstrates that the width of the water resonance decreased. Assuming a Lorentzian lineshape, an average increase of 12% in T₂* was observed in tumors. In muscle, peak integral and peak height increased slightly (about 1.2% and 3%. respectively; P <0.02) during carbogen inhalation but no significant change in T₂*was observed. Spectroscopic imaging detects changes in the water proton resonance in tumors during hyperoxia accurately and reproducibly with high signal-to-noise ratio and allows clear separation of T₁ and T₂* effects. Increases in T₂* may be due to decreased deoxyhemoglobin in tumor blood vessels (i.e., the BOLD effect) and may provide a clinically useful index of increases in tumor oxygenation.     

Is the magnetization transfer ratio a marker for myelin in multiple sclerosis?

Purpose

To investigate the correlation between water content (WC) and magnetization transfer ratio (MTR) in normal and multiple sclerosis (MS) brain. The MTR has been proposed as a marker for myelin in central nervous system tissue. However, changes in WC due to inflammation and edema may also affect the MTR.

Materials and Methods

Seven MS subjects with active disease and seven age‐ and gender‐matched controls were scanned using quantitative magnetic resonance techniques. WC, myelin water content, T₁ relaxation time, and MTR were calculated from areas of lesion (divided into new lesions less than 2 months old, isointense T₁ lesions, and hypointense T₁ lesions), contralateral normal‐appearing white matter (NAWM), and location‐matched normal white matter (NWM) in controls. Linear regression was used to determine the correlation between WC and MTR.

Results

A significant correlation was found between WC and MTR across all tissue (R = ?0.65, P < 0.0005).

Conclusion

MTR was correlated with WC in MS tissue, indicating that inflammation and edema influence MTR. Therefore, caution should be used when associating MTR exclusively with myelin content. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.     

One component? Two components? Three? The effect of including a nonexchanging “free” water component in multicomponent driven equilibrium single pulse observation of T1 and T2

Quantitative myelin content imaging provides novel and pertinent information related to underlying pathogenetic mechanisms of myelin‐related disease or disorders arising from aberrant connectivity. Multicomponent driven equilibrium single pulse observation of T₁ and T₂ is a time‐efficient multicomponent relaxation analysis technique that provides estimates of the myelin water fraction, a surrogate measure of myelin volume. Unfortunately, multicomponent driven equilibrium single pulse observation of T₁ and T₂ relies on a two water‐pool model (myelin‐associated water and intra/extracellular water), which is inadequate within partial volume voxels, i.e., containing brain tissue and ventricle or meninges, resulting in myelin water fraction underestimation. To address this, a third, nonexchanging “free‐water” component was introduced to the multicomponent driven equilibrium single pulse observation of T₁ and T₂ model. Numerical simulations and experimental in vivo data show that the model to perform advantageously within partial volume regions while providing robust and reproducible results. It is concluded that this model is preferable for future studies and analysis. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.