T2* measurements in human brain at 1.5, 3 and 7 T

Measurements have been carried out in six subjects at magnetic fields of 1.5, 3 and 7 T, with the aim of characterizing the variation of T2* with field strength in human brain. Accurate measurement of T2* in the presence of macroscopic magnetic field inhomogeneity is problematic due to signal decay resulting from through-slice dephasing. The approach employed here allowed the signal decay due to through-slice dephasing to be characterized and removed from data, thus facilitating an accurate measurement of T2* even at ultrahigh field. Using double inversion recovery turbo spin-echo images for tissue classification, an analysis of T2* relaxation times in cortical grey matter and white matter was carried out, along with an evaluation of the variation of T2* with field strength in the caudate nucleus and putamen. The results show an approximately linear increase in relaxation rate R2* with field strength for all tissues, leading to a greater range of relaxation times across tissue types at 7 T that can be exploited in high-resolution T2*-weighted imaging.     

Quantitative NumART2* mapping in functional MRI studies at 1.5 T

Quantitative mapping of the effective transverse relaxation time, T₂* and proton density was performed in a motor activation functional MRI (fMRI) study using multi-echo, echo planar imaging (EPI) and NumART₂* (Numerical Algorithm for Real time T₂*). Comparisons between NumART₂* and conventional single echo EPI with an echo time of 64 ms were performed for five healthy participants examined twice. Simulations were also performed to address specific issues associated with the two techniques, such as echo time-dependent signal variation. While the single echo contrast varied with the baseline T₂* value, relative changes in T₂* remained unaffected. Statistical analysis of the T₂* maps yielded fMRI activation patterns with an improved statistical detection relative to conventional EPI but with less activated voxels, suggesting that NumART₂* has superior spatial specificity. Two effects, inflow and dephasing, that may explain this finding were investigated. Particularly, a statistically significant increase in proton density was found in a brain area that was detected as activated by conventional EPI but not by NumART₂* while no such changes were observed in brain areas that showed stimulus correlated signal changes on T₂* maps.     

A statistical fMRI model for differential T2* contrast incorporating T1 and T2* of gray matter

Relaxation parameter estimation and brain activation detection are two main areas of study in magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI). Relaxation parameters can be used to distinguish voxels containing different types of tissue whereas activation determines voxels that are associated with neuronal activity. In fMRI, the standard practice has been to discard the first scans to avoid magnetic saturation effects. However, these first images have important information on the MR relaxivities for the type of tissue contained in voxels, which could provide pathological tissue discrimination. It is also well-known that the voxels located in gray matter (GM) contain neurons that are to be active while the subject is performing a task. As such, GM MR relaxivities can be incorporated into a statistical model in order to better detect brain activation. Moreover, although the MR magnetization physically depends on tissue and imaging parameters in a nonlinear fashion, a linear model is what is conventionally used in fMRI activation studies. In this study, we develop a statistical fMRI model for Differential T₂^? ConTrast Incorporating T₁ and T₂^? of GM, so-called DeTeCT-ING Model, that considers the physical magnetization equation to model MR magnetization; uses complex-valued time courses to estimate T₁ and T₂^? for each voxel; then incorporates gray matter MR relaxivities into the statistical model in order to better detect brain activation, all from a single pulse sequence by utilizing the first scans.     

The zonal architecture of human articular cartilage described by T2 relaxation time in the presence of Gd-DTPA2-

The depth-wise variation of T(2) relaxation time is known to reflect the collagen network architecture in cartilage, while the delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC) technique is sensitive to tissue proteoglycan (PG) concentration. As the cartilage PG content varies along the tissue depth, the depth-dependent accumulation of the contrast agent may affect the inherent T(2) of cartilage in a nonconstant manner. Therefore, T(2) and dGEMRIC are typically measured in separate MRI sessions. In the present in vitro MRI study at 9.4 T, depth-wise T(2) profiles and collagenous zone thicknesses as determined from T(2) maps in the absence and presence of Gd-DTPA(2-) (T(2) and T(2Gd), respectively) were compared in samples of intact human articular cartilage (n=65). These T(2) measures were further correlated with birefringence (BF) of polarized light microscopy (PLM) to quantify the ability of MRI to predict the properties of the collagen fibril network. The reproducibility of the T(2) measurement in the current setup was also studied. Typical tri-laminar collagen network architecture was observed both with and without Gd-DTPA(2-). The inverse of BF (1/BF) correlated significantly with both T(2) and T(2Gd) (r=0.91, slope=0.56 and r=0.90, slope=0.63), respectively. The statistically significant linear correlations between zone thicknesses as determined from T(2) and T(2Gd) were r=0.55 (slope=0.49), r=0.74 (slope=0.71) and r=0.95 (slope=0.94) for superficial, middle and deep tissue zones, respectively. Reproducibility of the T(2) measurement was worst for superficial cartilage. Consistent with PLM, T(2) and T(2Gd) measurements reveal highly similar depth-dependent information on collagen network in intact human cartilage. Thus, dGEMRIC and T(2) measurements in one MRI session are feasible for intact articular cartilage in vitro.     

Improved in vivo human carotid artery wall T2 estimation

T₂^? quantification has been shown to noninvasively and accurately estimate tissue iron content in the liver and heart; applying this to thin-walled carotid arteries introduces a new challenge to the estimation process. With most imaging voxels in a vessel being along its boundaries, errors in parameter estimation may result from partial volume mixing and misregistration due to motion in addition to noise and other common error sources. To minimize these errors, we propose a novel technique to reliably estimate T₂^? in thin regions of vessel wall. The technique weights data points to reduce the influence of expected error sources. It uses neighborhoods of data to increase the number of points for fitting and to assess lack of fit for automated outlier detection and deletion. The performance of this method was observed in simulations, phantom and in vivo patient studies and compared to results obtained using a pixelwise linear least squares estimation of T₂^?. The new proposed method showed a closer match to the expected results, and a 4.2-fold decrease in interobserver variability for in vivo studies. This increased confidence in estimation should improve the ability to reliably quantify iron noninvasively in the arterial wall.     

In vivo multiecho T2 relaxation measurements using variable TR to decrease scan time

Multiecho T2 relaxation measurements to determine geometric mean T2 (GMT2) and myelin water fraction (MWF) are lengthy, resulting in increased motion artefacts from patient discomfort and reduced patient compliance. The goal of this study was to shorten the acquisition time for multiecho T2 measurements without affecting T1 weighting by varying TR across k-space. Six phantoms and 10 healthy volunteers were imaged with both a constant TR and a variable TR multiecho T2 sequence. T1 weighting was determined by TR at the center of k-space; for variable TR measurement, TR was shortened linearly from the center to the edges of k-space. Phantoms showed excellent agreement for proton density and GMT2 between constant and variable TR measurements. No significant differences were found in proton density or MWF for any of the brain structures between the two measurements. The average GMT2 over all structures between the two experiments was not significantly different. In summary, with the variable TR approach, scan time was reduced by >20%, with minimal loss of image resolution and no significant affect on proton density, MWF or GMT2.     

The effect of varying echo spacing within a multiecho acquisition: better characterization of long T2 components

A 48-echo pulse sequence with five different echo-spacing combinations was examined to determine how one can most effectively measure the T2 relaxation characteristics of cerebral tissue containing a long T2 component. For each scan, the first 32 echoes had an echo spacing of 10 ms, while the spacing for Echoes 33-48 (DeltaTE2) was 10, 20, 30, 40 or 50 ms. In an in vivo study using 10 normal volunteers, it was found that the resolution of T2 distribution peaks for both myelin water (approximately 20 ms) and intracellular/extracellular (IE) water (approximately 80 ms) improved as DeltaTE2 increased. The geometric mean T2 values of the main peak agreed within the error for all DeltaTE2 values. A phantom study simulated T2 relaxation distributions that are expected in the brains of patients with demyelinating diseases. For phantoms in which the T2 values of the IE and lesion (200-500 ms) water compartments were separated by at least a factor of 3, each compartment in the distribution was better resolved when DeltaTE2=40 or 50 ms. On the basis of these results, we recommend the use of extended DeltaTE2 values for imaging patients with lesions, without the risk of losing valuable short T2 information.     

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.     

Comparison of T2 and LASER T2dagger image contrast in a rat model of acute cerebral ischemia

Previous studies have shown that T2(dagger)-weighted magnetic resonance images acquired using localization by adiabatic selective refocusing (LASER) can provide early tissue contrast following ischemia, possibly due to alterations in microscopic susceptibility within the tissue. The purpose of this study was to make a direct in vivo comparison of T2-, T2(dagger)- and diffusion-weighted image contrast during acute ischemia. Acute middle cerebral artery (MCA) occlusion was attempted in 14 rats using a modified Tamura approach incorporating electrocoagulation of the left MCA. T2(dagger)-weighted LASER images (Echo Time [TE]=108 ms), T2-weighted Carr-Purcell-Meiboom-Gill (CPMG) images (TE=110 ms) and diffusion-weighted images (b value=105 s/mm(2)) were acquired at 4 T within 1.5 h of ischemia onset. Tissue contrast in the MCA territory was quantified for histologically verified ischemic tissue (n=6) and in sham controls (n=4). T2(dagger)-weighted LASER images demonstrated greater contrast compared to the T2-weighted CPMG images, and more focal contrast compared to the diffusion-weighted images, suggesting different contrast mechanisms were involved.     

Determination of blood longitudinal relaxation time (T1) at high magnetic field strengths

In this study, a circulation system was used to measure T(1) values of bovine blood under physiological conditions at field strengths of 4.7, 7 and 9.4 T. Results show that T(1) increases linearly with magnetic field B(0) and can be described with the equation T(1)=129 ms/T B(0)+1167 ms for magnetic field strengths between 1.5 and 9.4 T.     

Improved T2* assessment in liver iron overload by magnetic resonance imaging

In the clinical MRI practice, it is common to assess liver iron overload by T2* multi-echo gradient-echo images. However, there is no full consensus about the best image analysis approach for the T2* measurements. The currently used methods involve manual drawing of a region of interest (ROI) within MR images of the liver. Evaluation of a representative liver T2* value is done by fitting an appropriate model to the signal decay within the ROIs vs. the echo time. The resulting T2* value may depend on both ROI placement and choice of the signal decay model. The aim of this study was to understand how the choice of the analysis methodology may affect the accuracy of T2* measurements. A software model of the iron overloaded liver was inferred from MR images acquired from 40 thalassemia major patients. Different image analysis methods were compared exploiting the developed software model. Moreover, a method for global semiautomatic T2* measurement involving the whole liver was developed. The global method included automatic segmentation of parenchyma by an adaptive fuzzy-clustering algorithm able to compensate for signal inhomogeneities. Global liver T2* value was evaluated using a pixel-wise technique and an optimized signal decay model. The global approach was compared with the ROI-based approach used in the clinical practice. For the ROI-based approach, the intra-observer and inter-observer coefficients of variation (CoVs) were 3.7% and 5.6%, respectively. For the global analysis, the CoVs for intra-observers and inter-observers reproducibility were 0.85% and 2.87%, respectively. The variability shown by the ROI-based approach was acceptable for use in the clinical practice; however, the developed global method increased the accuracy in T2* assessment and significantly reduced the operator dependence and sampling errors. This global approach could be useful in the clinical arena for patients with borderline liver iron overload and/or requiring follow-up studies.     

Feasibility of similarity coefficient map in improving morphological evaluation of T2* weighted MRI for renal cancer

The purpose of this paper is to investigate the feasibility of similarity coefficient map (SCM) in improving morphological evaluation of T₂^* weighted (T₂^*W) magnatic resonance imaging (MRI) for renal cancer. Simulation studies and in vivo 12-echo T₂^*W experiments for renal cancers were performed for this purpose. The results of the first simulation study suggest that SCM can reveal small structures which are hard to be distinguished from the background tissue in T₂^*W images and the corresponding T₂^* map. The capability of improving morphological evaluation is likely due to the improvement in signal to noise ratio (SNR) and carrier to noise ratio (CNR) by SCM technique. Compared with T₂^*W images, SCM can improve SNR by a factor ranging from 1.87 to 2.47. Compared with T₂^* maps, SCM can improve SNR by a factor ranging from 3.85 to 33.31. Compared with T₂^*W images, SCM can improve CNR by a factor raging from 2.09 to 2.43. Compared with T₂^* maps SCM can improve CNR by a factor raging from 1.94 to 8.14. For a given noise level, the improvements of SNR and CNR depend mainly on the original SNRs and CNRs in T₂^*W images, respectively. In vivo experiments confirmed the results of the first simulation study. The results of the second simulation study suggest that more echoes are used to generate SCM, and higher SNR and CNR can be achieved in SCM. In conclusion, SCM can provide improved morphological evaluation of T₂^*W MR images for renal cancer by unveiling fine structures which are ambiguous or invisible in the corresponding T₂^*W MR images and T₂^* maps. What is more, in practical application, for a fixed total sampling time, one should increase the number of echoes as much as possible to achieve SCMs with better SNR and CNR.     

Quantitative O imaging towards oxygen consumption study in tumor bearing mice at 7 T

¹⁷O magnetic resonance imaging (MRI) using a conventional pulse sequence was explored as a method of quantitative imaging towards regional oxygen consumption rate measurement for tumor evaluation in mice. At 7 T, fast imaging with steady state (FISP) was the best among gradient echo, fast spin echo and FISP for the purpose. The distribution of natural abundance H₂¹⁷O in mice was visualized under spatial resolution of 2.5 × 2.5 mm² by FISP in 10 min. The signal intensity by FISP showed a linear relationship with ¹⁷O quantity both in phantom and mice. Following the injection of 5% ¹⁷O enriched saline, ¹⁷O re-distribution was monitored in temporal resolution down to 5 sec with an image quality sufficient to distinguish each organ. The image of labeled water produced from inhaled ¹⁷O₂ gas was also obtained. The present method provides quantitative ¹⁷O images under sufficient temporal and spatial resolution for the evaluation of oxygen consumption rate in each organ. Experiments using various model compounds of R-OH type clarified that the signal contribution of body constituents other than water in the present in vivo¹⁷O FISP image was negligible.     

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.     

TriTone: a radiofrequency field (B1)-insensitive T1 estimator for MRI at high magnetic fields

Fast, high-resolution, longitudinal relaxation time (T1) mapping is invaluable in clinical and research applications. It has been shown that two spoiled gradient recalled echo (SPGR) images acquired in steady state with variable flip angles is an attractive alternative to the multi-image sets previously acquired with inversion or saturation recovery. The known sensitivity of the two-point method to transmit radiofrequency field (B1) inhomogeneity exacerbated at 3 T and above, however, mandates its combination with an additional, time-consuming and possibly specific-absorption-rate-intensive B1 measurement, preventing direct migration of the method to these fields. To address this, we introduce a method designed to be free of systematic errors caused by B1 inhomogeneity in which the value of T1 is extracted from three SPGR images acquired with echo planar imaging (EPI) readout. The precision of the T1 maps produced is found to be comparable to the two-point method, while the accuracy is greatly improved in the same time and spatial resolution. A welcome byproduct of the method is a map of B1 that can be used to correct other acquisitions in the same session. Tables of the optimal acquisition protocols are provided for several total imaging times.     

Use of fat suppression in R₂ relaxometry with MRI for the quantification of tissue iron overload in beta-thalassemic patients

Purpose

To assess the performance and results of R₂ relaxometry using a fat-suppressed (FS) multiecho sequence and compare these to conventional R₂ relaxometry in estimating tissue iron overload.

Materials and Methods

Relaxation rate values (R₂=1/T2) of the liver, spleen, pancreas and vertebral bone marrow (VBM) were estimated in 21 patients with β-thalassemia major, using a respiratory-triggered 16-echo Carr-Purcell-Meiboom-Gill (CPMG) spin-echo sequence before (R₂) and after (R₂ FS) the application of chemically selective fat suppression.

Results

Hepatic and splenic R₂ FS values correlated with respective R₂ values (r=0.98 and r=0.96, P<.001), whereas correlations between R₂ FS and R₂ values for pancreas and VBM were not statistically significant. Bland–Altman plots show disagreement between R₂ and R₂ FS values, particularly for pancreas and VBM. Hepatic, pancreatic and VBM R₂ FS values correlated with serum ferritin (r=0.88, P<.001; r=0.51, P<.003; and r=0.75, P<.002, respectively). Hepatic R₂ FS values correlated with splenic R₂ FS (r=0.77, P<.03), pancreatic R₂ FS (r=0.61, P<.006) and VBM R₂ FS values (r=0.70, P<.001), whereas pancreatic R₂ FS values correlated also with VMB R₂ FS values. On the contrary, among the R₂ values of the above tissues, obtained without fat suppression, only hepatic R₂ values correlated with serum ferritin, whereas no correlation was documented between hepatic and pancreatic or VBM R₂ values. The application of fat suppression did not improve breathing or flow artifacts.

Conclusion

Application of fat suppression in the standard CPMG sequence improved the capability of MRI in noninvasive quantification of iron, particularly in lipid-rich tissues, such as vertebral bone marrow (VBM) and pancreas.     

Measurement and correction of stimulated echo contamination in T2-based iron quantification

The purpose of this study was to characterize the effects of stimulated echo contamination on MR-based iron measurement derived from quantitative T₂ images and develop a method for retrospective correction. Two multiple spin-echo (MSE) pulse sequences were implemented with different amounts of stimulated echo contamination. Agarose-based phantoms were constructed that simulate the relaxation and susceptibility properties of tissue with different concentrations of dispersed (ferritin-like) and aggregated (hemosiderin-like) iron. Additionally, myocardial iron was assessed in nine human subjects with transfusion iron overload. These data were used to determine the influence of stimulated echoes on iron measurements made by an MR-based iron quantification model that can separately measure dispersed and aggregated iron. The study found that stimulated echo contamination caused an underestimation of dispersed (ferritin-like) iron and an overestimation of aggregated (hemosiderin-like) iron when applying this model. The relationship between the measurements made with and without stimulated echo appears to be linear. The findings suggest that while it is important to use MSE sequences with minimal stimulated echo in T₂-based iron quantification, it appears that data acquired with sub-optimal sequences can be retrospectively corrected using the methodology described here.     

The impact of physiologic noise correction applied to functional MRI of pain at 1.5 and 3.0 T

This study quantified the impact of the well-known physiologic noise correction algorithm RETROICOR applied to a pain functional magnetic resonance imaging (FMRI) experiment at two field strengths: 1.5 and 3.0 T. In the 1.5-T acquisition, there was an 8.2% decrease in time course variance (σ) and a 227% improvement in average model fit (increase in mean R²_a). In the 3.0-T acquisition, significantly greater improvements were seen: a 10.4% decrease in σ and a 240% increase in mean R²_a. End-tidal carbon dioxide data were also collected during scanning and used to account for low-frequency changes in cerebral blood flow; however, the impact of this correction was trivial compared to applying RETROICOR. Comparison between two implementations of RETROICOR demonstrated that oversampled physiologic data can be applied by either downsampling or modification of the timing in the RETROICOR algorithm, with equivalent results. Furthermore, there was no significant effect from manually aligning the physiologic data with corresponding image slices from an interleaved acquisition, indicating that RETROICOR accounts for timing differences between physiologic changes and MR signal changes. These findings suggest that RETROICOR correction, as it is commonly implemented, should be included as part of the data analysis for pain FMRI studies performed at 1.5 and 3.0 T.     

Novel S-Gal analogs as H MRI reporters for in vivo detection of β-galactosidase

The quantitative assessment of gene expression and related enzyme activity in vivo could be important for the characterization of gene altering diseases and therapy. The development of imaging techniques, based on specific reporter molecules may enable routine non-invasive assessment of enzyme activity and gene expression in vivo. We recently reported the use of commercially available S-Gal^® as a β-galactosidase reporter for ¹H MRI, and the synthesis of several S-Gal^® analogs with enhanced response to β-galactosidase activity. We have now compared these analogs in vitro and have identified the optimal analog, C3-GD, based on strong T₁ and T₂ response to enzyme presence (ΔR₁ and ΔR₂ ~ 1.8 times S-Gal^®). Moreover, application is demonstrated in vivo in human breast tumor xenografts. MRI studies in MCF7-lacZ tumors implanted subcutaneously in athymic nude mice (n = 6), showed significant reduction in T₁ and T₂ values (each ~ 13%) 2 h after intra-tumoral injection of C3-GD, whereas the MCF7 (wild type) tumors showed slight increase. Thus, C3-GD successfully detects β-galactosidase activity in vivo and shows promise as a lacZ gene ¹H MR reporter molecule.     

常规T2像和组织学研究APPswe/PS1dE9转基因小鼠模型

用常规的T₂加权像研究阿尔茨海默病双转基因APPswe/PS1dE9小鼠模型,拟合了海马和顶叶皮层的T₂,并用组织学方法研究了APP/PS1小鼠在这2个感兴趣区域随年龄相关的淀粉样斑块病理的发展及铁质的沉积. T₂拟合的结果显示,较高月龄的APP/PS1小鼠相比于低月龄APP/PS1小鼠T₂有升高但不显著,各月龄组APP/PS1小鼠与同窝生非阳性小鼠之间也无明显差异;组织学的结果则显示年龄相关的淀粉样斑块的增多,铁质在16月龄的APP/PS1小鼠脑区中有明显沉积且和斑块具有“共域性”. 两方面的实验结果提示：在该模型淀粉样斑块沉积病理发展的早期,这2个脑区的T₂并不能作为特异性的病理发展的标志.