T₁-weighted ultrashort echo time method for positive contrast imaging of magnetic nanoparticles and cancer cells bound with the targeted nanoparticles

Purpose

To obtain positive contrast based on T₁ weighting from magnetic iron oxide nanoparticle (IONP) using ultrashort echo time (UTE) imaging and investigate quantitative relationship between positive contrast and the core size and concentration of IONPs.

Materials and Methods

Solutions of IONPs with different core sizes and concentrations were prepared. T₁ and T₂ relaxation times of IONPs were measured using the inversion recovery turbo spin echo (TSE) and multi‐echo spin echo sequences at 3 Tesla. T₁‐weighted UTE gradient echo and T₂‐weighted TSE sequences were used to image IONP samples. U87MG glioblastoma cells bound with arginine‐glycine‐aspartic acid (RGD) peptide and IONP conjugates were scanned using UTE, T₁ and T₂‐weighted sequences.

Results

Positive contrast was obtained by UTE imaging from IONPs with different core sizes and concentrations. The relative‐contrast‐to‐water ratio of UTE images was three to four times higher than those of T₂‐weighted TSE images. The signal intensity increases as the function of the core size and concentration. Positive contrast was also evident in cell samples bound with RGD‐IONPs.

Conclusion

UTE imaging allows for imaging of IONPs and IONP bound tumor cells with positive contrast and provides contrast enhancement and potential quantification of IONPs in molecular imaging applications. J. Magn. Reson. Imaging 2011;33:194–202. © 2010 Wiley‐Liss, 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.     

Improved fat suppression using multipeak reconstruction for IDEAL chemical shift fat‐water separation: Application with fast spin echo imaging

Purpose

To evaluate and quantify improvements in the quality of fat suppression for fast spin‐echo imaging of the knee using multipeak fat spectral modeling and IDEAL fat‐water separation.

Materials and Methods

T₁‐weighted and T₂‐weighted fast spin‐echo sequences with IDEAL fat‐water separation and two frequency‐selective fat‐saturation methods (fat‐selective saturation and fat‐selective partial inversion) were performed on 10 knees of five asymptomatic volunteers. The IDEAL images were reconstructed using a conventional single‐peak method and precalibrated and self‐calibrated multipeak methods that more accurately model the NMR spectrum of fat. The signal‐to‐noise ratio (SNR) was measured in various tissues for all sequences. Student t‐tests were used to compare SNR values.

Results

Precalibrated and self‐calibrated multipeak IDEAL had significantly greater suppression of signal (P < 0.05) within subcutaneous fat and bone marrow than fat‐selective saturation, fat‐selective partial inversion, and single‐peak IDEAL for both T₁‐weighted and T₂‐weighted fast spin‐echo sequences. For T₁‐weighted fast spin‐echo sequences, the improvement in the suppression of signal within subcutaneous fat and bone marrow for multipeak IDEAL ranged between 65% when compared to fat‐selective partial inversion to 86% when compared to fat‐selectivesaturation. For T2‐weighted fast spin‐echo sequences, the improvement for multipeak IDEAL ranged between 21% when compared to fat‐selective partial inversion to 81% when compared to fat‐selective saturation.

Conclusion

Multipeak IDEAL fat‐water separation provides improved fat suppression for T₁‐weighted and T₂‐weighted fast spin‐echo imaging of the knee when compared to single‐peak IDEAL and two widely used frequency‐selected fat‐saturation methods. J. Magn. Reson. Imaging 2009;29:436–442. © 2009 Wiley‐Liss, Inc.     

Clinically compatible MRI strategies for discriminating bound and pore water in cortical bone

Advances in modern magnetic resonance imaging (MRI) pulse sequences have enabled clinically practical cortical bone imaging. Human cortical bone is known to contain a distribution of T₁ and T₂ components attributed to bound and pore water, although clinical imaging approaches have yet to discriminate bound from pore water based on their relaxation properties. Herein, two clinically compatible MRI strategies are proposed for selectively imaging either bound or pore water by utilizing differences in their T₁s and T₂s. The strategies are validated in a population of ex vivo human cortical bones, and estimates obtained for bound and pore water are compared to bone mechanical properties. Results show that the two MRI strategies provide good estimates of bound and pore water that correlate to bone mechanical properties. As such, the strategies for bound and pore water discrimination shown herein should provide diagnostically useful tools for assessing bone fracture risk, once applied to clinical MRI. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.     

Ultrashort TE imaging with off‐resonance saturation contrast (UTE‐OSC)

Short T₂ species such as the Achilles tendon and cortical bone cannot be imaged with conventional MR sequences. They have a much broader absorption lineshape than long T₂ species, therefore they are more sensitive to an appropriately placed off‐resonance irradiation. In this work, a technique termed ultrashort TE (UTE) with off‐resonance saturation contrast (UTE‐OSC) is proposed to image short T₂ species. A high power saturation pulse was placed +1 to +2 kHz off the water peak to preferentially saturate signals from short T₂ species, leaving long T₂ water and fat signals largely unaffected. The subtraction of UTE images with and without an off‐resonance saturation pulse effectively suppresses long T₂ water and fat signals, creating high contrast for short T₂ species. The UTE‐OSC technique was validated on a phantom, and applied to bone samples and healthy volunteers on a clinical 3T scanner. High‐contrast images of the Achilles tendon and cortical bone were generated with a high contrast‐to‐noise ratio (CNR) of the order of 12 to 20 between short T₂ and long T₂ species within a total scan time of 4 to 10 min. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Magnetic resonance imaging: Comparison of four pulse sequences in assessing primary bone tumours

A prospective magnetic resonance imaging (MRI) study was carried out in 13 patients (19 examinations) with primary bone tumours to assess the relative value of each of four pulse sequences in showing the extent and nature of the lesion. The four pulse sequences used were a T₁-weighted spin-echo (SE544/44), a T₂-weighted spin echo (SE1500/80), a short TI inversion recovery (STIR) (IR500/100/44), and a partial saturation (PS) (PS500/22) with field echo data collection. For soft tissue disease the combination of PS and STIR gave better definition of the boundary of the tumour than the more conventional T₁ and T₂-weighted spin echo sequences. For the demonstration of bone cortex, periosteal change and calcification, T₁ and T₂-weighted spin echo sequences were better. However, for calcified tissues, plain radiographs were better than either MRI combination. On the assumption that plain films will be available in all cases, PS and STIR sequences could therefore be substituted for T1 and T2-weighted spin echo sequences allowing an increase in soft tissue detectability for lesions in both red and yellow marrow.     

Direct imaging and quantification of carotid plaque calcification

Carotid plaque calcification normally appears as a signal void with clinical MR sequences. Here, we describe the use of an adiabatic inversion recovery prepared two‐dimensional ultrashort echo time sequence to image and characterize carotid plaque calcification using a clinical 3‐T scanner. T₁, T, and free water content were measured for seven carotid samples, and the results were compared with micro‐CT imaging. Conventional gradient echo and fast spin echo images were also acquired for comparison. Correlations between T₁, T, free water concentration, and mineral density were performed. There was a close correspondence between inversion recovery prepared two‐dimensional ultrashort echo time morphologic and micro‐CT appearances. Carotid plaque calcification varied significantly from sample to sample, with T₁s ranging from 94 ± 19 to 328 ± 21 msec, Ts ranging from 0.31 ± 0.12 to 2.15 ± 0.25 msec, and free water concentration ranging from 5.7 ± 2.3% to 16.8 ± 3.4%. There was a significant positive correlation between T₁ (R = 0.709; P < 0.074), T (R = 0.816; P < 0.025), and free water concentration, a negative correlation between T₁ (R = 0.773; P < 0.042), T (R = 0.948; P < 0.001) and CT measured mineral density, and a negative correlation between free water concentration (R = 0.936; P < 0.002) and mineral density. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

MR imaging near metal with undersampled 3D radial UTE‐MAVRIC sequences

Recently developed techniques such as the multiple acquisition with variable resonance image combination and slice encoding for metal artifact correction techniques have improved the ability of clinical magnetic resonance scanners to image near metal implants. These sequences are based on fast spin echo sequences which preclude detection of short T₂ tissues such as tendons, ligaments, and cortical bone. Ultrashort echo time sequences have the potential to detect signals from these tissues. In this study, we investigate the potential of combining ultrashort echo time with multiple acquisition with variable resonance image combination to image short T₂ musculoskeletal tissues adjacent to metallic implants. Different radio frequency excitation pulse types and spectral binning strategies were studied. We found that ultrashort echo time‐multiple acquisition with variable resonance image combination sequences were able to significantly reduce typical artifacts near metal, as well as detect very short T₂ signals that are usually not visualized using clinical pulse sequences. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Single‐shot T1 mapping using simultaneous acquisitions of spin‐ and stimulated‐echo‐planar imaging (2D ss‐SESTEPI)

The conventional stimulated‐echo NMR sequence only measures the longitudinal component while discarding the transverse component, after tipping up the prepared magnetization. This transverse magnetization can be used to measure a spin echo, in addition to the stimulated echo. Two‐dimensional single‐shot spin‐ and stimulated‐echo‐planar imaging (ss‐SESTEPI) is an echo‐planar‐imaging‐based single‐shot imaging technique that simultaneously acquires a spin‐echo‐planar image and a stimulated‐echo‐planar image after a single radiofrequency excitation. The magnitudes of the spin‐echo‐planar image and stimulated‐echo‐planar image differ by T₁ decay and diffusion weighting for perfect 90° radiofrequency and thus can be used to rapidly measure T₁. However, the spatial variation of amplitude of radiofrequency field induces uneven splitting of the transverse magnetization for the spin‐echo‐planar image and stimulated‐echo‐planar image within the imaging field of view. Correction for amplitude of radiofrequency field inhomogeneity is therefore critical for two‐dimensional ss‐SESTEPI to be used for T₁ measurement. We developed a method for amplitude of radiofrequency field inhomogeneity correction by acquiring an additional stimulated‐echo‐planar image with minimal mixing time, calculating the difference between the spin echo and the stimulated echo and multiplying the stimulated‐echo‐planar image by the inverse functional map. Diffusion‐induced decay is corrected by measuring the average diffusivity during the prescanning. Rapid single‐shot T₁ mapping may be useful for various applications, such as dynamic T₁ mapping for real‐time estimation of the concentration of contrast agent in dynamic contrast enhancement MRI. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Optimizing MR signal contrast of the temporomandibular joint disk

Purpose:

To use a tissue specific algorithm to numerically optimize UTE sequence parameters to maximize contrast within temporomandibular joint (TMJ) donor tissue.

Materials and Methods:

A TMJ specimen tissue block was sectioned in a true sagittal plane and imaged at 3 Tesla (T) using UTE pulse sequences with dual echo subtraction. The MR tissue properties (PD, T₂, T₂*, and T₁) were measured and subsequently used to calculate the optimum sequences parameters (repetition time [TR], echo time [TE], and θ).

Results:

It was found that the main contrast available in the TMJ could be obtained from T₂ (or T₂*) contrast. With the first echo time fixed at 8 μs and using TR = 200 ms, the optimum parameters were found to be: θ ≈ 60°, and TE2 ≈ 15 ms, when the second echo is acquired using a gradient echo and θ ≈ 120°, and TE2 ≈ 15 ms, when the second echo is acquired using a spin echo.

Conclusion:

Our results show that MR signal contrast can be optimized between tissues in a systematic manner. The MR contrast within the TMJ was successfully optimized with facile delineation between disc and soft tissues. J. Magn. Reson. Imaging 2011;. © 2011 Wiley Periodicals, Inc.     

UTE imaging in the musculoskeletal system

Tissues, such as bone, tendon, and ligaments, contain a high fraction of components with "short" and "ultrashort" transverse relaxation times and therefore have short mean transverse relaxation times. With conventional magnetic resonance imaging (MRI) sequences that employ relatively long echo times (TEs), there is no opportunity to encode the decaying signal of short and ultrashort T₂/T₂* tissues before it has reached zero or near zero. The clinically compatible ultrashort TE (UTE) sequence has been increasingly used to study the musculoskeletal system. This article reviews the UTE sequence as well as various modifications that have been implemented since its introduction. These modifications have been used to improve efficiency or contrast as well as provide quantitative analysis. This article reviews several clinical musculoskeletal applications of UTE. J. Magn. Reson. Imaging 2015;41:870–883 . © 2014 Wiley Periodicals, Inc .     

Effect of blood flow on double inversion recovery vessel wall MRI of the peripheral arteries: Quantitation with T2 mapping and comparison with flow‐insensitive T2‐prepared inversion recovery imaging

Blood suppression in the lower extremities using flow‐reliant methods such as double inversion recovery may be problematic due to slow blood flow. T₂ mapping using fast spin echo (FSE) acquisition was utilized to quantitate the effectiveness of double inversion recovery blood suppression in 13 subjects and showed that 25 ± 12% of perceived vessel wall pixels in the popliteal arteries contained artifactual blood signal. To overcome this problem, a flow‐insensitive T₂‐prepared inversion recovery sequence was implemented and optimal timing parameters were calculated for FSE acquisition. Black blood vessel wall imaging of the popliteal and femoral arteries was performed using two‐dimensional T₂‐prepared inversion recovery‐FSE in the same 13 subjects. Comparison with two‐dimensional double inversion recovery‐FSE showed that T₂‐prepared inversion recovery‐FSE reduced wall‐mimicking blood artifacts that inflated double inversion recovery‐FSE vessel wall area measurements in the popliteal artery. Magn Reson Med 63:736–744, 2010. © 2010 Wiley‐Liss, Inc.     

Radiofrequency pulses for simultaneous short T2 excitation and long T2 suppression

Magnetic resonance imaging of short T₂ musculoskeletal tissues such as ligaments, tendon, and cortical bone often requires specialized pulse sequences to detect sufficiently high levels of signal, as well as additional techniques to suppress unwanted long T₂ signals. We describe a specialized radiofrequency technique for imaging short T₂ tissues based on applying hard 180° radiofrequency excitation pulses to achieve simultaneous short T₂ tissue excitation and long T₂ tissue signal suppression for three‐dimensional ultrashort echo time applications. A criterion for the pulse duration of the 180° radiofrequency pulses is derived that allows simultaneous water and fat suppression. This opens up possibilities for direct imaging of short T₂ tissues, without the need for additional suppression techniques. Bloch simulations and experimental studies on short T₂ phantoms and specimen were used to test the sequence performance. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.     

Ultrashort TE MR imaging of bovine cortical bone: The effect of water loss on the T1 and T2* relaxation times

The effects of water loss on the T₁ and T₂* of bovine cortical bone were investigated using ultrashort echo time sequences with signals excited either by a short hard pulse or by two longer half pulses. Nine bovine femur samples were prepared and sequentially air‐ and oven‐dried. On average 3.42% of bone by weight was lost after air‐drying for 3 days, with another 5.98% of bone weight loss after oven‐drying at 100°C for 24 h. T₁ and T₂* were measured after every 1% decrease in weight, with 9–10% bone weight loss at the termination of the drying process. After both forms of drying, the overall T₁ decreased 33% from 153 ± 18 ms to 102 ± 17 ms when measured using the hard pulse and from 186 ± 25 ms to 122 ± 23 ms when using the half pulses. T₂* decreased by 45–50% from 368 ± 29 μs to 201 ± 19 μs using the hard pulse and from 379 ± 35 μs to 191 ± 17 μs using the half pulses. A steady decrease of 26–31% was observed in both T₁ and T₂* with the first 3–4% bone water loss after air‐drying. Oven‐drying at 100°C for 24 h resulted on an additional 4% T₁ reduction but 25% T₂* reduction. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Simultaneous estimation of T(2) and apparent diffusion coefficient in human articular cartilage in vivo with a modified three-dimensional double echo steady state (DESS) sequence at 3 T

T₂ mapping and diffusion‐weighted imaging complement morphological imaging for assessing cartilage disease and injury. The double echo steady state sequence has been used for morphological imaging and generates two echoes with markedly different T₂ and diffusion weighting. Modifying the spoiler gradient area and flip angle of the double echo steady state sequence allows greater control of the diffusion weighting of both echoes. Data from two acquisitions with different spoiler gradient areas and flip angles are used to simultaneously estimate the T₂ and apparent diffusion coefficient of each voxel. This method is verified in phantoms and validated in vivo in the knee; estimates from different regions of interest in the phantoms and cartilage are compared to those obtained using standard spin‐echo methods. The Pearson correlations were 0.984 for T₂ (～2% relative difference between spin‐echo and double echo steady state estimates) and 0.997 for apparent diffusion coefficient (?1% relative difference between spin‐echo and double echo steady state estimates) for the phantom study and 0.989 for T₂ and 0.987 for apparent diffusion coefficient in regions of interest in the human knee in vivo. High accuracy for simultaneous three‐dimensional T₂ and apparent diffusion coefficient measurements are demonstrated, while also providing morphologic three‐dimensional images without blurring or distortion in reasonable scan times. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

NMR Microscopy of Single Neurons Using Spin Echo and Line Narrowed 2DFT Imaging

NMR microimages of single neural cells were acquired at 500 MHz using a conventional spin echo pulse sequence and a line-narrowing sequence that eliminates susceptibility effects. The data show that any contribution to the measured T₂ relaxation rate arising from diffusion in local field inhomogeneities using spin echo sequences at high fields and high spatial resolution is relatively small. We conclude that the measured T₂ difference between the nucleus and cytoplasm in these cells represents primarily a true T₂ relaxation effect arising from the interactions of water with macromolecules in the two compartments and does not result from microsusceptibility differences. These observations have implications regarding water compartmentation in single cells and the interpretation of the MR characteristics of tissues in vivo.     

Improved T2 mapping accuracy with dual‐echo turbo spin echo: Effect of phase encoding profile orders

Turbo spin echo (TSE) pulse sequences have been applied to estimate T₂ relaxation times in clinically feasible scan times. However, T₂ estimations using TSE pulse sequences has been shown to differ considerable from reference standard sequences due to several sources of error. The purpose of this work was to apply voxel‐sensitivity formalism to correct for one such source of error introduced by differing phase encoding profile orders with dual‐echo TSE pulse sequences. The American College of Radiology phantom and the brains of two healthy volunteers were imaged using dual‐echo TSE as well as 32‐echo spin‐echo acquisitions and T₂ estimations from uncorrected and voxel‐sensitivity formalism‐corrected dual‐echo TSE and 32‐echo acquisitions were compared. In all regions of the brain and the majority of the analyses of the American College of Radiology phantom, voxel‐sensitivity formalism correction resulted in considerable improvements in dual‐echo TSE T₂ estimation compared with the 32‐echo acquisition, with improvements in T₂ value accuracy ranging from 5.2% to 18.6%. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Assessment of anterior cruciate ligament reconstruction using 3D ultrashort echo‐time MR imaging

This work demonstrates the potential of ultrashort TE (UTE) imaging for visualizing graft material and fixation elements after surgical repair of soft tissue trauma such as ligament or meniscal injury. Three asymptomatic patients with anterior cruciate ligament (ACL) reconstruction using different graft fixation methods were imaged at 1.5T using a 3D UTE sequence. Conventional multislice turbo spin‐echo (TSE) measurements were performed for comparison. 3D UTE imaging yields high signal from tendon graft material at isotropic spatial resolution, thus facilitating direct positive contrast graft visualization. Furthermore, metal and biopolymer graft fixation elements are clearly depicted due to the high contrast between the signal‐void implants and the graft material. Thus, the ability of UTE MRI to visualize short‐T₂ tissues such as tendons, ligaments, or tendon grafts can provide additional information about the status of the graft and its fixation in the situation after cruciate ligament repair. UTE MRI can therefore potentially support diagnosis when problems occur or persist after surgical procedures involving short‐T₂ tissues and implants. J. Magn. Reson. Imaging 2009;29:443–448. © 2009 Wiley‐Liss, Inc.     

Contrast‐enhanced,three‐dimensional,whole‐brain,black‐blood imaging: Application to small brain metastases

Contrast‐enhanced three‐dimensional T₁‐weighted imaging based on magnetization‐prepared rapid‐gradient recalled echo is widely used for detecting small brain metastases. However, since contrast materials remain in both blood and the tumor parenchyma and thus increase the signal intensity of both regions, it is often challenging to distinguish brain tumors from blood. In this work, we develop a T₁‐weighted, black‐blood version of single‐slab three‐dimensional turbo/fast spin echo whole‐brain imaging, in which the signal intensity of the brain tumor is selectively enhanced while that of blood is suppressed. For blood suppression, variable refocusing flip angles with flow‐sensitizing gradients are employed. To avoid a signal loss resulting from the flow‐sensitizing scheme, the first refocusing flip angle is forced to 180°. Composite restore pulses at the end of refocusing pulse train are applied to achieve partial inversion recovery for the T₁‐weighted contrast. Simulations and in vivo volunteer and patient experiments are performed, demonstrating that this approach is highly efficient in detecting small brain metastases. Magn Reson Med 63:553–561, 2010. © 2010 Wiley‐Liss, Inc.     

SWIFT‐CEST: A new MRI method to overcome T2 shortening caused by PARACEST contrast agents

The exchange of water molecules between the inner sphere of a paramagnetic chemical exchange saturation transfer (PARACEST) contrast agent and bulk water can shorten the bulk water T₂ through the T₂‐exchange (T_2ex) mechanism. The line‐broadening T_2ex effect is proportional to the agent concentration, the chemical shift of the exchanging water molecule, and is highly dependent on the water molecule exchange rate. A significant T_2ex contribution to the bulk water linewidth can make the regions of agent uptake appear dark when imaging with conventional sequences like gradient‐echo and fast spin‐echo. The minimum echo times for these sequences (1–10 ms) are not fast enough to capture signal from the regions of shortened T₂. This makes “Off” (saturation at ?Δω) minus “On” (saturation at +Δω) imaging of PARACEST agents difficult, because the regions of uptake are dark in both images. It is shown here that the loss of bulk water signal due to T_2ex can be reclaimed using the ultrashort echo times (<10 μs) achieved with the sweep imaging with Fourier transform pulse sequence. Modification of the sweep imaging with Fourier transform sequence for PARACEST imaging is first discussed, followed by parameter optimization using in vitro experiments. In vivo PARACEST studies comparing fast spin‐echo to sweep imaging with Fourier transform were performed using EuDOTA‐(gly) uptake in healthy mouse kidneys. The results show that the negative contrast caused by T_2ex can be overcome using the ultrashort echo time achieved with sweep imaging with Fourier transform, thereby enabling fast and sensitive in vivo PARACEST imaging. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.