Rapid acquisition of multifrequency,multislice and multidirectional MR elastography data with a fractionally encoded gradient echo sequence

In MR elastography (MRE), periodic tissue motion is phase encoded using motion‐encoding gradients synchronized to an externally applied periodic mechanical excitation. Conventional methods result in extended scan time for quality phase images, thus limiting the broad application of MRE in the clinic. For practical scan times, researchers have been relying on one‐dimensional or two‐dimensional motion‐encoding, low‐phase sampling and a limited number of slices, and artifact‐prone, single‐shot, echo planar imaging (EPI) readout. Here, we introduce a rapid multislice pulse sequence capable of three‐dimensional motion encoding that is also suitable for simultaneously encoding motion with multiple frequency components. This sequence is based on a gradient‐recalled echo (GRE) sequence and exploits the principles of fractional encoding. This GRE MRE pulse sequence was validated as capable of acquiring full three‐dimensional motion encoding of isotropic voxels in a large volume within less than a minute. This sequence is suitable for monofrequency and multifrequency MRE experiments. In homogeneous paraffin phantoms, the eXpresso sequence yielded similar storage modulus values as those obtained with conventional methods, although with markedly reduced variances (7.11 ± 0.26 kPa for GRE MRE versus 7.16 ± 1.33 kPa for the conventional spin‐echo EPI sequence). The GRE MRE sequence obtained better phase‐to‐noise ratios than the equivalent spin‐echo EPI sequence (matched for identical acquisition time) in both paraffin phantoms and in vivo data in the liver (59.62 ± 11.89 versus 27.86 ± 3.81, 61.49 ± 14.16 versus 24.78 ± 2.48 and 58.23 ± 10.39 versus 23.48 ± 2.91 in the X, Y and Z components, respectively, in the case of liver experiments). Phase‐to‐noise ratios were similar between GRE MRE used in monofrequency or multifrequency experiments (75.39 ± 14.93 versus 86.13 ± 18.25 at 28 Hz, 71.52 ± 24.74 versus 86.96 ± 30.53 at 56 Hz and 95.60 ± 36.96 versus 61.35 ± 26.25 at 84Hz, respectively). Copyright © 2013 John Wiley & Sons, Ltd.     

MR elastography and diffusion‐weighted imaging of ex vivo prostate cancer: quantitative comparison to histopathology

The purpose of this work was (1) to develop a magnetic resonance elastography (MRE) system for imaging of the ex vivo human prostate and (2) to assess the diagnostic power of mono‐frequency and multi‐frequency MRE and diffusion weighted imaging (DWI) alone and combined as correlated with histopathology in a patient study. An electromagnetic driver was designed specifically for MRE studies in small‐bore MR scanners. Ex vivo prostate specimens (post‐fixation) of 14 patients who underwent radical prostatectomy were imaged with MRE at 7 T (nine cases had DWI). In six patients, the MRE examination was performed at three frequencies (600, 800, 1000 Hz) to extract the power‐law exponent Gamma. The images were registered to wholemount pathology slides marked with the Gleason score. The areas under the receiver‐operator‐characteristic curves (AUC) were calculated. The methods were validated in a phantom study and it was demonstrated that (i) the driver does not interfere with the acquisition process and (ii) the driver can generate amplitudes greater than 100 µm for frequencies less than 1 kHz. In the quantitative study, cancerous tissue with Gleason score at least 3 + 3 was distinguished from normal tissue in the peripheral zone (PZ) with an average AUC of 0.75 (G_d), 0.75 (G_l), 0.70 (Gamma‐G_d), 0.68 (apparent diffusion coefficient, ADC), and 0.82 (G_d + G_l + ADC). The differentiation between PZ and central gland was modest for G_d (p < 0.07), G_l (p < 0.06) but not significant for Gamma (p < 0.2). A correlation of 0.4 kPa/h was found between the fixation time of the prostate specimen and the stiffness of the tissue, which could affect the diagnostic power results. DWI and MRE may provide complementary information; in fact MRE performed better than ADC in distinguishing normal from cancerous tissue in some cases. Multi‐frequency (Gamma) analysis did not appear to improve the results. However, in light of the effect of tissue fixation, the clinical implication of our results may be inconclusive and more experiments are needed. Copyright © 2014 John Wiley & Sons, Ltd.     

MR elastography of prostate cancer: quantitative comparison with histopathology and repeatability of methods

The purpose of this work was to assess trans‐perineal prostate magnetic resonance elastography (MRE) for (1) repeatability in phantoms/volunteers and (2) diagnostic power as correlated with histopathology in prostate cancer patients. The three‐dimensional (3D) displacement field was obtained using a fractionally encoded gradient echo sequence using a custom‐made transducer. The repeatability of the method was assessed based on three repeat studies and by changing the driving frequency by 3% in studies on a phantom and six healthy volunteers. Subsequently, 11 patients were examined with MRE prior to radical prostatectomy. The areas under the receiver operating characteristic curves were calculated using a windowed voxel‐to‐voxel approach by comparing the 2D registered slides, masked with the Gleason score. For the repeatability study, the average intraclass correlation coefficient for elasticity images was 99% for repeat phantom studies, 98% for ±6 Hz phantom studies, 95% for volunteer repeat studies with 2 min acquisition time, 82% for ±2 Hz volunteer studies with 2 min acquisition time and 73% for repeat volunteer studies with 8 min acquisition time. For the patient study, the average elasticity was 8.2 ± 1.7 kPa in the prostate capsule, 7.5 ± 1.9 kPa in the peripheral zone (PZ), 9.7 ± 3.0 kPa in the central gland (CG) and 9.0 ± 3.4 kPa in the transition zone. In the patient study, cancerous tissue with Gleason score at least 3 + 3 was significantly (p < 0.05) different from normal tissue in 10 out of 11 cases with tumors in the PZ, and 6 out of 9 cases with tumors in the CG. However, the overall case‐averaged area under the curve was 0.72 in the PZ and 0.67 in the CG. Cancerous tissue was not always stiffer than normal tissue. The inversion algorithm was sensitive to (i) vibration amplitude and displacement nodes and (ii) misalignment of the 3D wave field due to subject movement. Copyright © 2014 John Wiley & Sons, Ltd.     

Microvasculature alters the dispersion properties of shear waves – a multi‐frequency MR elastography study

Magnetic Resonance Elastography (MRE) uses macroscopic shear wave propagation to quantify mechanical properties of soft tissues. Micro‐obstacles are capable of affecting the macroscopic dispersion properties of shear waves. Since disease or therapy can change the mechanical integrity and organization of vascular structures, MRE should be able to sense these changes if blood vessels represent a source for wave scattering. To verify this, MRE was performed to quantify alteration of the shear wave speed c_s due to the presence of vascular outgrowths using an aortic ring model. Eighteen fragments of rat aorta included in a Matrigel matrix (n=6 without outgrowths, n=6 with a radial outgrowth extent of ~600µm and n=6 with ~850µm) were imaged using a 7 Tesla MR scanner (Bruker, PharmaScan). High resolution anatomical images were acquired in addition to multi‐frequency MRE (ν = 100, 115, 125, 135 and 150 Hz). Average c_s was measured within a ring of ~900µm thickness encompassing the aorta and were normalized to c_s0 of the corresponding Matrigel. The frequency dependence was fit to the power law model c_s ~ν^y. After scanning, optical microscopy was performed to visualize outgrowths. Results demonstrated that in presence of vascular outgrowths (1) normalized c_s significantly increased for the three highest frequencies (Kruskal‐Wallis test, P = 0.0002 at 125 Hz and P = 0.002 at 135 Hz and P = 0.003 at 150 Hz) but not for the two lowest (Kruskal‐Wallis test, P = 0.63 at 100 Hz and P = 0.87 at 115 Hz), and (2) normalized c_s followed a power law behavior not seen in absence of vascular outgrowths (ANOVA test, P < 0.0001). These results showed that vascular outgrowths acted as micro‐obstacles altering the dispersion relationships of propagating shear waves and that MRE could provide valuable information about microvascular changes. Copyright © 2015 John Wiley & Sons, Ltd.     

Comparison of spoiled gradient echo and steady‐state free‐precession imaging for native myocardial T1 mapping using the slice‐interleaved T1 mapping (STONE) sequence

Cardiac T₁ mapping allows non‐invasive imaging of interstitial diffuse fibrosis. Myocardial T₁ is commonly calculated by voxel‐wise fitting of the images acquired using balanced steady‐state free precession (SSFP) after an inversion pulse. However, SSFP imaging is sensitive to B₁ and B₀ imperfection, which may result in additional artifacts. A gradient echo (GRE) imaging sequence has been used for myocardial T₁ mapping; however, its use has been limited to higher magnetic field to compensate for the lower signal‐to‐noise ratio (SNR) of GRE versus SSFP imaging. A slice‐interleaved T₁ mapping (STONE) sequence with SSFP readout (STONE–SSFP) has been recently proposed for native myocardial T₁ mapping, which allows longer recovery of magnetization (>8 R–R) after each inversion pulse. In this study, we hypothesize that a longer recovery allows higher SNR and enables native myocardial T₁ mapping using STONE with GRE imaging readout (STONE–GRE) at 1.5T. Numerical simulations and phantom and in vivo imaging were performed to compare the performance of STONE–GRE and STONE–SSFP for native myocardial T₁ mapping at 1.5T. In numerical simulations, STONE–SSFP shows sensitivity to both T₂ and off resonance. Despite the insensitivity of GRE imaging to T₂, STONE–GRE remains sensitive to T₂ due to the dependence of the inversion pulse performance on T₂. In the phantom study, STONE–GRE had inferior accuracy and precision and similar repeatability as compared with STONE–SSFP. In in vivo studies, STONE–GRE and STONE–SSFP had similar myocardial native T₁ times, precisions, repeatabilities and subjective T₁ map qualities. Despite the lower SNR of the GRE imaging readout compared with SSFP, STONE–GRE provides similar native myocardial T₁ measurements, precision, repeatability, and subjective image quality when compared with STONE–SSFP at 1.5T.     

Arterial spin labeling‐fast imaging with steady‐state free precession (ASL‐FISP): a rapid and quantitative perfusion technique for high‐field MRI

Arterial spin labeling (ASL) is a valuable non‐contrast perfusion MRI technique with numerous clinical applications. Many previous ASL MRI studies have utilized either echo‐planar imaging (EPI) or true fast imaging with steady‐state free precession (true FISP) readouts, which are prone to off‐resonance artifacts on high‐field MRI scanners. We have developed a rapid ASL‐FISP MRI acquisition for high‐field preclinical MRI scanners providing perfusion‐weighted images with little or no artifacts in less than 2 s. In this initial implementation, a flow‐sensitive alternating inversion recovery (FAIR) ASL preparation was combined with a rapid, centrically encoded FISP readout. Validation studies on healthy C57/BL6 mice provided consistent estimation of in vivo mouse brain perfusion at 7 and 9.4 T (249 ± 38 and 241 ± 17 mL/min/100 g, respectively). The utility of this method was further demonstrated in the detection of significant perfusion deficits in a C57/BL6 mouse model of ischemic stroke. Reasonable kidney perfusion estimates were also obtained for a healthy C57/BL6 mouse exhibiting differential perfusion in the renal cortex and medulla. Overall, the ASL‐FISP technique provides a rapid and quantitative in vivo assessment of tissue perfusion for high‐field MRI scanners with minimal image artifacts. Copyright © 2014 John Wiley & Sons, Ltd.     

Dynamic 2D and 3D mapping of hyperpolarized pyruvate to lactate conversion in vivo with efficient multi‐echo balanced steady‐state free precession at 3 T

The aim of this study was to acquire the transient MRI signal of hyperpolarized tracers and their metabolites efficiently, for which specialized imaging sequences are required. In this work, a multi‐echo balanced steady‐state free precession (me‐bSSFP) sequence with Iterative Decomposition with Echo Asymmetry and Least squares estimation (IDEAL) reconstruction was implemented on a clinical 3 T positron‐emission tomography/MRI system for fast 2D and 3D metabolic imaging. Simulations were conducted to obtain signal‐efficient sequence protocols for the metabolic imaging of hyperpolarized biomolecules. The sequence was applied in vitro and in vivo for probing the enzymatic exchange of hyperpolarized [1–¹³C]pyruvate and [1–¹³C]lactate. Chemical shift resolution was achieved using a least‐square, iterative chemical species separation algorithm in the reconstruction. In vitro, metabolic conversion rate measurements from me‐bSSFP were compared with NMR spectroscopy and free induction decay‐chemical shift imaging (FID‐CSI). In vivo, a rat MAT‐B‐III tumor model was imaged with me‐bSSFP and FID‐CSI. 2D metabolite maps of [1–¹³C]pyruvate and [1–¹³C]lactate acquired with me‐bSSFP showed the same spatial distributions as FID‐CSI. The pyruvate‐lactate conversion kinetics measured with me‐bSSFP and NMR corresponded well. Dynamic 2D metabolite mapping with me‐bSSFP enabled the acquisition of up to 420 time frames (scan time: 180‐350 ms/frame) before the hyperpolarized [1–¹³C]pyruvate was relaxed below noise level. 3D metabolite mapping with a large field of view (180 × 180 × 48 mm³) and high spatial resolution (5.6 × 5.6 × 2 mm³) was conducted with me‐bSSFP in a scan time of 8.2 seconds. It was concluded that Me‐bSSFP improves the spatial and temporal resolution for metabolic imaging of hyperpolarized [1–¹³C]pyruvate and [1–¹³C]lactate compared with either of the FID‐CSI or EPSI methods reported at 3 T, providing new possibilities for clinical and preclinical applications.     

Characterization of gradient echo signal decays in healthy and cancerous prostate at 3T improves with a Gaussian augmentation of the mono‐exponential (GAME) model

A biomarker of cancer aggressiveness, such as hypoxia, could substantially impact treatment decisions in the prostate, especially radiation therapy, by balancing treatment morbidity (urinary incontinence, erectile dysfunction, etc.) against mortality. R₂^* mapping with Mono‐Exponential (ME) decay modeling has shown potential for identifying areas of prostate cancer hypoxia at 1.5T. However, Gaussian deviations from ME decay have been observed in other tissues at 3T. The purpose of this study is to assess whether gradient‐echo signal decays are better characterized by a standard ME decay model, or a Gaussian Augmentation of the Mono‐Exponential (GAME) decay model, in the prostate at 3T. Multi‐gradient‐echo signals were acquired on 20 consecutive patients with a clinical suspicion of prostate cancer undergoing MR‐guided prostate biopsies. Data were fitted with both ME and GAME models. The information contents of these models were compared using Akaike's information criterion (second order, AIC_C), in skeletal muscle, the prostate central gland (CG), and peripheral zone (PZ) regions of interest (ROIs). The GAME model had higher information content in 30% of the prostate on average (across all patients and ROIs), covering up to 67% of cancerous PZ ROIs, and up to 100% of cancerous CG ROIs (in individual patients). The higher information content of GAME became more prominent in regions that would be assumed hypoxic using ME alone, reaching 50% of the PZ and 70% of the CG as ME R₂^* approached 40 s^?1. R₂^* mapping may have important applications in MRI; however, information lost due to modeling could mask differences in parameters due to underlying tissue anatomy or physiology. The GAME model improves characterization of signal behavior in the prostate at 3T, and may increase the potential for determining correlates of fit parameters with biomarkers, for example of oxygenation status.