Off-resonance proton T1p dispersion imaging of 17O-enriched tissue phantoms

Proton T_1p dispersion imaging is a recently described method for indirect detection of ¹⁷O. However, clinical implementation of this technique is hindered by the requirement for a high-amplitude spin-locking field (γB₁ > 1 kHz) that exceeds current limitations in specific absorption rate (SAR). Here, a strategy is offered for circumventing high SAR in T_1p dispersion imaging of ¹⁷O through the use of low-amplitude off-resonance spin-locking pulses (γB₁ < 300 Hz). Proton spin-lattice relaxation times in the off-resonance rotating frame were measured in H₂¹⁷O-enriched tissue phantoms. On- and off-resonance T_1p dispersion imaging was implemented at 2 T using a spin-locking preparatory pulse cluster appended to a standard spin-echo sequence. On- and off-resonance dispersion images exhibited similar ¹⁷O-based image contrast. Magnetization transfer effects did not depend on ¹⁷O concentration and had no effect on image contrast. In conclusion, off-resonance proton T_1p dispersion imaging shows promise as a safe, sensitive technique for generating ¹⁷O-based T_1p contrast without exceeding SAR limitations.     

Quantification techniques to minimize the effects of native T1 variation and B1 inhomogeneity in dynamic contrast‐enhanced MRI of the breast at 3 T

The variation of the native T₁ (T₁₀) of different tissues and B₁ transmission‐field inhomogeneity at 3 T are major contributors of errors in the quantification of breast dynamic contrast‐enhanced MRI. To address these issues, we have introduced new enhancement indices derived from saturation‐recovery snapshot‐FLASH (SRSF) images. The stability of the new indices, i.e., the SRSF enhancement factor (EF_SRSF) and its simplified version (EF′_SRSF) with respect to differences in T₁₀ and B₁ inhomogeneity was compared against a typical index used in breast dynamic contrast‐enhanced MRI, i.e., the enhancement ratio (ER), by using computer simulations. Imaging experiments with Gd‐DTPA‐doped gel phantoms and a female volunteer were also performed. A lower error was observed in the new indices compared to enhancement ratio in the presence of typical T₁₀ variation and B₁ inhomogeneity. At changes of relaxation rate (ΔR₁) of 8 s^?1, the differences between a T₁₀ of 1266 and 566 ms are <1, 12, and 58%, respectively, for EF_SRSF, EF′_SRSF, and ER, whereas differences of 20, 8, and 51%, respectively, result from a 50% B₁ field reduction at the same ΔR₁. These quantification techniques may be a solution to minimize the effect of T₁₀ variation and B₁ inhomogeneity on dynamic contrast‐enhanced MRI of the breast at 3 T. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.     

Comparison of two ultrashort echo time sequences for the quantification of T(1) within phantom and human Achilles tendon at 3 T

Ultrashort echo time (UTE) techniques enable direct imaging of musculoskeletal tissues with short T₂ allowing measurement of T₁ relaxation times. This article presents comparison of optimized 3D variable flip angle UTE (VFA‐UTE) and 2D saturation recovery UTE (SR‐UTE) sequences to quantify T₁ in agar phantoms and human Achilles tendon. Achilles tendon T₁ values for asymptomatic volunteers were compared to Achilles tendon T₁ values calculated from patients with clinical diagnoses of spondyloarthritis (SpA) and Achilles tendinopathy using an optimized VFA‐UTE sequence. T₁ values from phantom data for VFA‐ and SR‐UTE compare well against calculated T₁ values from an assumed gold standard inversion recovery spin echo sequence. Mean T₁ values in asymptomatic Achilles tendon were found to be 725 ± 42 ms and 698 ± 54 ms for SR‐ and VFA‐UTE, respectively. The patient group mean T₁ value for Achilles tendon was found to be 957 ± 173 ms (P < 0.05) using an optimized VFA‐UTE sequence with pulse repetition time of 6 ms and flip angles 4, 19, and 24°, taking a total 9 min acquisition time. The VFA‐UTE technique appears clinically feasible for quantifying T₁ in Achilles tendon. T₁ measurements offer potential for detecting changes in Achilles tendon due to SpA without need for intravenous contrast agents. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.     

Removal of local field gradient artifacts in T2*-weighted images at high fields by gradient-echo slice excitation profile imaging

Development of high magnetic field MRI techniques is hampered by the significant artifacts produced by B₀ field inhomogeneities in the excited slices. A technique, gradient-echo slice excitation profile imaging (GESEPI), is presented for recovering the signal lost caused by intravoxel phase dispersion in T₂*-weighted images. This technique superimposes an incremental gradient offset on the slice refocusing gradient to sample Jr-space over the full range of spatial frequencies of the excitation profile. A third Fourier transform of the initial two-dimensional image set generates an image set in which the artifacts produced by the low-order B₀ inhomogeneity field gradients in the sample are separated and removed from the high-order microscopic field gradients responsible for T₂* contrast. Application to high field brain imaging, at 3.0 T for human and at 9.4 T for immature rat imaging demonstrates the significant improvement in quality of the T₂*-weighted contrast images.     

A MnCl2-based phantom for IVD hydration status determination using MRI: Pre-clinical reliability analyses

Introduction

Non-biological, yet signal-responsive, MR phantom materials are becoming increasingly commonplace. One such novel agent, semi-solid manganese chloride (MnCl₂), has recently been described as a potential calibration standard for direct assessment of in vivo cartilage fluid content. Given the established correlation between intervertebral disc (IVD) hydration state and physiologic spinal functioning, such a tool, allowing calibration for ‘quantitative’ appraisal of disc fluid content, has many potential applications. The purpose of this study was to demonstrate MR signal-to-noise ratio (SNR) measurement reliability of a novel MnCl₂-based signal calibration phantom for in vivo disc hydration analysis, using a 10 × 10 inter- and intra-observer reliability analysis in the pre-clinical setting.

Materials and methods

A series of novel MnCl₂ calibration phantoms were imaged to assess intra-/inter-observer reliability during measurement of signal intensity. The phantoms were imaged under ten different MR sequences, generating 75 signal regions from which SNR values were measured. Inter-observer reliability was tested by inviting ten individuals to obtain signal measurements from each image, on a single occasion. To test intra-observer reliability, a single participant was asked to record measurements of the same features on ten separate occasions.

Results

1425 Discrete measurement points were available for combined reliability analyses. Single-measure intraclass correlation coefficients showed high measurement agreement, with both intra- and inter-observer values approaching 1.00.

Conclusion

This study demonstrates that signal measurements can be obtained using MnCl₂ disc phantoms, with a high degree of observer reliability, supporting their use as a signal calibration standard during orthopaedic MR-based cartilage imaging.     

Proton T1ρ-dispersion imaging of rodent brain at 1.9 T

Detection of H₂¹⁷O with proton T_1ρ-dispersion imaging holds promise as a means of quantifying metabolism and blood flow with MRI. However, this technique requires a priori knowledge of the intrinsic T_1ρ dispersion of tissue. To investigate these properties, we implemented a T_1ρ imaging sequence on a 1.9-T Signa GE scanner. A series of T_1ρ images for different locking frequencies and locking durations were obtained from rat brain in vivo and compared with 5 % (wt/vol) gelatin phantoms containing different concentrations of ¹⁷O ranging from .037 % (natural abundance) to 2.0 atom%. Results revealed that, although there is considerable T_1ρ-dispersion in phantoms doped with H₂¹⁷O, the T_1ρ of rat brain undergoes minimal dispersion for spin-locking frequencies between .2 and 1.5 kHz. A small degree of T_1ρ dispersion is present below .2 kHz, which we postulate arises from natural-abundance H₂¹⁷O. Moreover, the signal-to-noise ratios of T_1ρ-weighted images are significantly better than comparable T2-weighted images, allowing for improved visualization of tissue contrast. We have also demonstrated the feasibility of proton T_1ρ-dispersion imaging for detecting intravenous H₂¹⁷O on a live mouse brain. The potential application of this technique to study brain perfusion is discussed.     

Quantitative sodium MRI of the mouse prostate

A method was developed for quantitative sodium MRI of the mouse prostate at 9.4 T. A small loop‐gap radiofrequency coil was constructed and dual‐tuned to both the proton and sodium frequencies. The location and boundary of the mouse prostate were localized using high‐resolution T₂‐weighted proton images, and sodium images were acquired with 1mm isotropic resolution using a short echo time (0.6 ms) and a long pulse repetition time (300 ms) for sodium density weighting with minimal T₁ and T₂ contrast. Sodium concentration in the prostate was estimated by comparing pixel intensities within the prostate to the pixel intensities in a pair of reference vials with known sodium concentrations, and a radiofrequency field inhomogeneity correction was performed based on field maps of a homogeneous phantom. In a group of five healthy, 5‐month‐old BALB/c mice, the average sodium concentration within their prostates was measured to be 173 ± 38 mM. Muscle tissue and bladder were also clearly visible in the sodium images, and their sodium concentrations were estimated to be 40 ± 15 mM and 210 ± 72 mM, respectively. Magn Reson Med 63:822–827, 2010. © 2010 Wiley‐Liss, Inc.     

Spectrally selective B1‐insensitive T2 magnetization preparation sequence

A T₂ magnetization‐preparation (T₂ Prep) sequence is proposed that is insensitive to B₁ field variations and simultaneously provides fat suppression without any further increase in specific absorption rate (SAR). Increased B₁ inhomogeneity at higher magnetic field strength (B₀ ≥ 3T) necessitates a preparation sequence that is less sensitive to B₁ variations. For the proposed technique, T₂ weighting in the image is achieved using a segmented B₁‐insensitive rotation (BIR‐4) adiabatic pulse by inserting two equally long delays, one after the initial reverse adiabatic half passage (AHP), and the other before the final AHP segment of a BIR‐4 pulse. This sequence yields T₂ weighting with both B₁ and B₀ insensitivity. To simultaneously suppress fat signal (at the cost of B₀ insensitivity), the second delay is prolonged so that fat accumulates additional phase due to its chemical shift. Numerical simulations as well as phantom and in vivo image acquisitions were performed to show the efficacy of the proposed technique. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

T1ρ of protein solutions at very low fields: Dependence on molecular weight,concentration, and structure

The effect of molecular weight, concentration, and structure on 1/T₁ρ, the rotating frame relaxation rate, was investigated for several proteins using the on-resonance spin-lock technique, for locking fields B₁ < 200 μT. The measured values of 1/T₁ρ, were fitted to a simple theoretical model to obtain the dispersion curves 1/T₁ρ(ω₁) and the relaxation rate at zero B₁ field, 1/T₁ρ,(O). 1/T₁ρ, was highly sensitive to the molecular weight, concentration, and structure of the protein. The amount of intra- and intermolecular hydrogen and disulfide bonds especially contributed to 1/T₁ρ. In all samples, 1/T₁ρ(O) was equal to 1/T₂ρ measured at the main magnetic field B_o = 0.1 T, but at higher locking fields the dispersion curves mono-tonically decreased. The results of this work indicate that a model considering the effective correlation time of molecular motions as the main determinant for 1/T₁ρ relaxation in protein solutions is not valid at very low B₁ fields. The underlying mechanism for the relaxation rate 1/T₁ρ at B₁ fields below 200 μT is discussed.     

In vivo measurement of transverse relaxation time in the mouse brain at 17.6 T

Purpose: To establish regional T₁ and T₂ values of the healthy mouse brain at ultra‐high magnetic field strength of 17.6 T and to follow regional brain T₁ and T₂ changes with age. Methods: In vivo T₁ and T₂ values in the C57BL/6J mouse brain were followed with age using multislice‐multiecho sequence and multiple spin echo saturation recovery with variable repetition time sequence, respectively, at 9.4 and 17.6 T. Gadolinium‐tetra‐azacyclo‐dodecane‐tetra‐acetic acid phantoms were used to validate in vivo T₂ measurements. Student's t‐test was used to compare mean relaxation values. Results: A field‐dependent decrease in T₂ is shown and validated with phantom measurements. T₂ values at 17.6 T typically increased with age in multiple brain regions except in the hypothalamus and the caudate‐putamen, where a slight decrease was observed. Furthermore, T₁ values in various brain regions of young and old mice are presented at 17.6 T. A large gain in signal‐to‐noise ratio was observed at 17.6 T. Conclusions: This study establishes for the first time the normative T₁ and T₂ values at 17.6 T over different mouse brain regions with age. The estimates of in vivo T₁ and T₂ will be useful to optimize pulse sequences for optimal image contrast at 17.6 T and will serve as baseline values against which disease‐related relaxation changes can be assessed in mice. Magn Reson Med, 70:985–993, 2013. © 2012 Wiley Periodicals, Inc.     

Motion and flow insensitive adiabatic T2‐preparation module for cardiac MR imaging at 3 tesla

A versatile method for generating T₂‐weighting is a T₂‐preparation module, which has been used successfully for cardiac imaging at 1.5T. Although it has been applied at 3T, higher fields (B₀ ≥ 3T) can degrade B₀ and B₁ homogeneity and result in nonuniform magnetization preparation. For cardiac imaging, blood flow and cardiac motion may further impair magnetization preparation. In this study, a novel T₂‐preparation module containing multiple adiabatic B₁‐insensitive refocusing pulses is introduced and compared with three previously described modules [(a) composite MLEV4, (b) modified BIR‐4 (mBIR‐4), and (c) Silver‐Hoult–pair]. In the static phantom, the proposed module provided similar or better B₀ and B₁ insensitivity than the other modules. In human subjects (n = 21), quantitative measurement of image signal coefficient of variation, reflecting overall image inhomogeneity, was lower for the proposed module (0.10) than for MLEV4 (0.15, P < 0.0001), mBIR‐4 (0.27, P < 0.0001), and Silver‐Hoult–pair (0.14, P = 0.001) modules. Similarly, qualitative analysis revealed that the proposed module had the best image quality scores and ranking (both, P < 0.0001). In conclusion, we present a new T₂‐preparation module, which is shown to be robust for cardiac imaging at 3T in comparison with existing methods. Magn Reson Med 70:1360–1368, 2013. © 2012 Wiley Periodicals, Inc.     

Method for the quantitative assessment of contrast agent uptake in dynamic contrast-enhanced MRI

In previous papers relative signal intensity increase was used as a quantitative assessment parameter for contrast uptake in contrastenhanced MRI. However, relative signal intensity increase does not only reflect contrast uptake but depends also on tissue parameters (native T₁ relaxation time) and sequence parameters (repetition time and flip angle); thus, the contrast uptake cannot be assessed accurately using relative signal intensity increase. Based on an analysis of the contrast behavior of spoiled gradient echo sequences, a method is described in this paper that overcomes the limitations of relative signal intensity increase measurement. A parameter, called “enhancement factor” (EF) is introduced that approximates differential T₁ relaxation rate. The enhancement factor scales linearly with contrast uptake and is independent of tissue and sequence parameters. The additional measurement time involved in determining the enhancement factor is less than 1 min and computation is straightforward. The practicality of the new method was confirmed by phantom measurements using T₁-weighted and proton density-weighted spoiled gradient echo sequences (FLASH-2D). Enhancing tissues were simulated by water phantoms doped with increasing concentrations of Gd-DTPA.     

T1 corrected B1 mapping using multi‐TR gradient echo sequences

This work presents a new approach toward a fast, simultaneous amplitude of radiofrequency field (B₁) and T₁ mapping technique. The new method is based on the “actual flip angle imaging” (AFI) sequence. However, the single pulse repetition time (TR) pair used in the standard AFI sequence is replaced by multiple pulse repetition time sets. The resulting method was called “multiple TR B₁/T₁ mapping” (MTM). In this study, MTM was investigated and compared to standard AFI in simulations and experiments. Feasibility and reliability of MTM were proven in phantom and in vivo experiments. Error propagation theory was applied to identify optimal sequence parameters and to facilitate a systematic noise comparison to standard AFI. In terms of accuracy and signal‐to‐noise ratio, the presented method outperforms standard AFI B₁ mapping over a wide range of T₁. Finally, the capability of MTM to determine T₁ was analyzed qualitatively and quantitatively, yielding good agreement with reference measurements. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Modified Look‐Locker T1 evaluation using Bloch simulations: Human and phantom validation

Modified Look‐Locker imaging is frequently used for T₁ mapping of the myocardium. However, the specific effect of various MRI parameters (e.g., encoding scheme, modifications of flip angle, heart rate, T₂, and inversion times) on the accuracy of T₁ measurement has not been studied through Bloch simulations. In this work, modified Look‐Locker imaging was characterized through a numerical solution for Bloch equations. MRI sequence parameters that may affect T₁ accuracy were systematically varied in the simulation. For validation, phantoms were constructed with various T₂ and T₁ times and compared with Bloch equation simulations. Human volunteers were also evaluated with various pulse sequences parameters to assess the validity of the numerical simulations. There was close agreement between simulated T₁ times and T₁ times measured in phantoms and volunteers. Lower T₂ times (i.e., <30 ms) resulted in errors greater than 5% for T₁ determination. Increasing maximum inversion time value improved T₁ accuracy particularly for precontrast myocardial T₁. Balanced steady‐state free precession k space centric encoding improved accuracy for short T₁ times (post gadolinium), but linear encoding provided improved accuracy for precontrast T₁ values. Lower flip angles are preferred if the signal‐to‐noise ratio is sufficiently high. Bloch simulations for modified Look‐Locker imaging provide an accurate method to comprehensively quantify the effect of pulse sequence parameters on T₁ accuracy. As an alternative to otherwise lengthy phantom studies or human studies, such simulations may be useful to optimize the modified Look‐Locker imaging sequence and compare differences in T₁‐derived measurements from different scanners or institutions. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Imaging of the active B1 field in vivo

The authors describe a method for accurate In vivo muttislice imaging of the active component of the B₁ field which is based on a previously proposed method, which uses the signal intensity ratio of two images measured with different excitation angles, and a repetition time TR≥ 5 T₁ The new method essentially reduces repetition and scan time by means of an additional compensating pulse. The suppression of T₁ effects by this pulse are verified with simulations and measurements. Further investigations concerned the influence of slice selective excitation and magnetization transfer in multislice imaging to the B₁ field determination. The stability and accuracy of the presented method is shown by several phantom and in vivo measurements. With the described method the active B₁ field can be determined in vivo in 23 cross-sections in less than 6 min.     

Pulsed magnetization transfer contrast for MR imaging with application to breast

The relative populations and transverse relaxation times of the solid-like hydrogen pool (P_B and T_2B) and the magnetization transfer (MT) rates between the solid-like and liquid-like hydrogen pools (K) have been determined for three different agar gel concentrations (2%, 4%, and 8% by weight) as well as excised fibroglandular breast tissue specimens. P_B was determined to be .003(.001), .01(.002), .02(.01), and .06(.01); T_2B was determined to be 13.0(.2), 14.0(.1), 14.5(.1) and 15.2(1.3) μs; and K was determined to be 0.78(.01), 1.15(.02), 2.00(.02), and 3.55(1.5) sec^?1 for the 2%, 4%, and 8% agar gels and the fibroglandular tissue, respectively. The image signal intensities of a pulsed MTC-prepared gradient-echo imaging technique are predicted using these MT parameters and are shown to agree well with experimental data obtained from a clinical MR imaging system. This technique is shown to suppress signal intensity of fibroglandular breast tissue by 40%–50% without exceeding SAR limits (≤ 8W/kg) and is helpful for visualizing lesions and silicone implants.     

Comparison of T1 relaxation times of the neurochemical profile in rat brain at 9.4 tesla and 14.1 tesla

Knowledge of T₁ relaxation times can be important for accurate relative and absolute quantification of brain metabolites, for sensitivity optimizations, for characterizing molecular dynamics, and for studying changes induced by various pathological conditions. ¹H T₁ relaxation times of a series of brain metabolites, including J‐coupled ones, were determined using a progressive saturation (PS) technique that was validated with an adiabatic inversion‐recovery (IR) method. The ¹H T₁ relaxation times of 16 functional groups of the neurochemical profile were measured at 14.1T and 9.4T. Overall, the T₁ relaxation times found at 14.1T were, within the experimental error, identical to those at 9.4T. The T₁s of some coupled spin resonances of the neurochemical profile were measured for the first time (e.g., those of γ‐aminobutyrate [GABA], aspartate [Asp], alanine [Ala], phosphoethanolamine [PE], glutathione [GSH], N‐acetylaspartylglutamate [NAAG], and glutamine [Gln]). Our results suggest that T₁ does not increase substantially beyond 9.4T. Furthermore, the similarity of T₁ among the metabolites (～1.5 s) suggests that T₁ relaxation time corrections for metabolite quantification are likely to be similar when using rapid pulsing conditions. We therefore conclude that the putative T₁ increase of metabolites has a minimal impact on sensitivity when increasing B₀ beyond 9.4T. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

High-resolution in vivo measurements of transverse relaxation times in rats at 7 Tesla

A multi-echo imaging sequence suitable for high-resolution and accurate in vivo transverse relaxation time (T₂) mapping has been implemented. The sequence was tested on phantoms and was used to measure T₂ values in vivo in the rat brain, muscle, and fat at 7 T. Brain T₂ maps are shown and regional variations in brain T₂ are reported (41.8 ms in cortex, 47.9 ms in hippocampus). Results are compared to literature values obtained at lower field in vivo as well as high-field T₂ measurements on excised rat tissues. The reported T₂ values are generally smaller compared to lower-field-strength literature values. A discussion of the possible causes of these field effects on T₂ is included (dipolar interaction, fast chemical exchange, and diffusion in susceptibility gradients).     

Manganese‐guided cellular MRI of human embryonic stem cell and human bone marrow stromal cell viability

This study investigated the ability of MnCl₂ as a cellular MRI contrast agent to determine the in vitro viability of human embryonic stem cells (hESC) and human bone marrow stromal cells (hBMSC). Basic MRI parameters including T₁ and T₂ values of MnCl₂‐labeled hESC and hBMSC were measured and viability signal of manganese (Mn²⁺)‐labeled cells was validated. Furthermore, the biological activity of Ca²⁺‐channels was modulated utilizing both Ca²⁺‐channel agonist and antagonist to evaluate concomitant signal changes. Metabolic effects of MnCl₂‐labeling were also assessed using assays for cell viability, proliferation, and apoptosis. Finally, in vivo Mn²⁺‐guided MRI of the transplanted hESC was successfully achieved and validated by bioluminescence imaging. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Optimized inversion recovery sequences for quantitative T1 and magnetization transfer imaging

Inversion recovery sequences that vary the inversion time (t_i) have been employed to determine T₁ and, more recently, quantitative magnetization transfer parameters. Specifically, in previous work, the inversion recovery pulse sequences varied t_i only while maintaining a constant delay (t_d) between repetitions. T₁ values were determined by fitting to a single exponential function, and quantitative magnetization transfer parameters were then determined by fitting to a biexponential function with an approximate solution. In the current study, new protocols are employed, which vary both t_i and t_d and fit the data with minimal approximations. Cramer‐Rao lower bounds are calculated to search for acquisition schemes that will maximize the precision efficiencies of T₁ and quantitative magnetization transfer parameters. This approach is supported by Monte Carlo simulations. The optimal T₁ schemes are verified by measurements on MnCl₂ samples. The optimal quantitative magnetization transfer schemes are confirmed by measurements on a series of cross‐linked bovine serum albumin phantoms of varying concentrations. The effects of varying the number of sampling data points are also explored, and a rapid acquisition scheme is demonstrated in vivo. These new optimized quantitative imaging methods provide an improved means for determining T₁ and magnetization transfer parameter values compared to previous inversion recovery based methods. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.