Unipolar MR elastography: Theory, numerical analysis and implementation

In MR elastography (MRE), zeroth moment balanced motion-encoding gradients (MEGs) are incorporated into MRI sequences to induce a phase shift proportional to the local displacement caused by external actuation. To maximize the signal-to-noise ratio (SNR), fractional encoding is employed, i.e., the MEG duration is reduced below the wave period. Here, gradients encode primarily the velocity of the motion-reducing encoding efficiency. Thus, in GRE-MRE, T2 * decay and motion sensitivity have to be balanced, imposing a lower limit on repetition times (TRs). We propose to use a single trapezoidal gradient, a "unipolar gradient", to directly encode spin displacement. Such gradients cannot be used in conventional sequences as they exhibit a large zeroth moment and dephase magnetization. By time-reversing a spoiled SSFP sequence, the spoiling gradient becomes an efficient unipolar MEG. The proposed "unipolar MRE" technique benefits from this approach in three ways: first, displacement encoding is split over multiple TRs increasing motion sensitivity; second, spoiler and MEG coincide, allowing a reduction in TR; third, motion sensitivity of a typical unipolar lobe is of an order of magnitude higher than a bipolar MEG of equal duration. In this work, motion encoding using unipolar MRE is analyzed using the extended phase graph (EPG) formalism with a periodic motion propagator. As an approximation, the two-transverse TR approximation for diffusion-weighted SSFP is extended to incorporate cyclic motion. A complex encoding efficiency metric is introduced to compare the displacement fields of unipolar and conventional GRE-MRE sequences in both magnitude and phase. The derived theoretical encoding equations are used to characterize the proposed sequence using an extensive parameter study. Unipolar MRE is validated against conventional GRE-MRE in a phantom study showing excellent agreement between measured displacement fields. In addition, unipolar MRE yields significantly increased octahedral shear strain-SNR relative to conventional GRE-MRE and allows for the recovery of high stiffness inclusions, where conventional GRE-MRE fails

Characterization and Correction of Diffusion Gradient-Induced Eddy Currents in Second-Order Motion-Compensated Echo-Planar and Spiral Cardiac DTI

Purpose Very high gradient amplitudes played out over extended time intervals as required for second-order motion-compensated cardiac DTI may violate the assumption of a linear time-invariant gradient system model. The aim of this work was to characterize diffusion gradient-related system nonlinearity and propose a correction approach for echo-planar and spiral spin-echo motion-compensated cardiac DTI. Methods Diffusion gradient-induced eddy currents of 9 diffusion directions were characterized at b values of 150 s/mm2 and 450 s/mm2 for a 1.5 Tesla system and used to correct phantom, ex vivo, and in vivo motion-compensated cardiac DTI data acquired with echo-planar and spiral trajectories. Predicted trajectories were calculated using gradient impulse response function and diffusion gradient strength- and direction-dependent zeroth- and first-order eddy current responses. A reconstruction method was implemented using the predicted -space trajectories to additionally include off-resonances and concomitant fields. Resulting images were compared to a reference reconstruction omitting diffusion gradient-induced eddy current correction. Results Diffusion gradient-induced eddy currents exhibited nonlinear effects when scaling up the gradient amplitude and could not be described by a 3D basis alone. This indicates that a gradient impulse response function does not suffice to describe diffusion gradient-induced eddy currents. Zeroth- and first-order diffusion gradient-induced eddy current effects of up to −1.7 rad and −16 to +12 rad/m, respectively, were identified. Zeroth- and first-order diffusion gradient-induced eddy current correction yielded improved image quality upon image reconstruction. Conclusion The proposed approach offers correction of diffusion gradient-induced zeroth- and first-order eddy currents, reducing image distortions to promote improvements of second-order motion-compensated spin-echo cardiac DTI.ISSN:0740-3194ISSN:1522-259

Motion and eddy current–induced signal dephasing in in vivo cardiac DTI

Purpose To address motion in cardiac DWI, stimulated‐echo acquisition mode (STEAM) and second‐order motion‐compensated spin‐echo (SE) sequences have been proposed. Despite applying motion‐compensation strategies, residual motion can cause misleading signal attenuation. The purpose of this study is to estimate the motion‐induced error in both sequences by analysis of image phase. Methods Diffusion‐weighted motion‐compensated SE sequences and STEAM imaging was applied in vivo with diffusion encoding along 3 orthogonal directions. A b‐value range of 100 to 600 s/mm2 and trigger delays of 25%, 50%, and 75% of end systole and middiastole were used. Eddy‐current contributions were obtained from phantom measurements. After computation of motion‐induced phase maps, the amount of signal dephasing was computed from phase gradients, and the resulting errors in diffusion tensor parameters were calculated. Results Motion‐induced dephasing from the STEAM sequence showed less dependency on the b‐value and no dependency on the heart phase, whereas SE imaging performed best at 75% end systole followed by 50% end systole and middiastole. For a typical experimental setting, errors of 3.3%/3.0% mean diffusivity, 4.9%/4.8% fractional anisotropy, 2.9º/3.2º helix angulation, 0.8º/0.7º transverse angulation, and 9.9º/10.0º sheet angulation (SE/STEAM) were calculated. Conclusion Image phase contains valuable information regarding uncompensated motion and eddy currents in cardiac DTI. Although the trigger delay window for SE is narrower compared with the STEAM‐based approach, imaging in both systole and diastole is feasible and both sequences perform similarly if the trigger delays are selected carefully with SE

Analysis and correction of off-resonance artifacts in echo-planar cardiac diffusion tensor imaging

Purpose Cardiac diffusion tensor imaging using EPI readout is prone to image distortions in the presence of field inhomogeneities. In this work, a framework to analyze and correct image distortions in cardiac diffusion tensor imaging is presented. Methods A multi‐coil reconstruction framework was implemented to enable field map‐based off‐resonance correction. Numerical simulations were used to examine reconstruction performance for EPI phase‐encode directions blip up‐down and down‐up for different degrees of off‐resonance gradients and varying field map resolution. The impact of coil encoding was analyzed using the g‐factor and normalized RMSE. Finally, the proposed method was tested on free‐breathing in vivo cardiac diffusion tensor imaging data acquired in healthy subjects at 3 Tesla. Results Depending on the local field map gradient strength and polarity and the selected phase‐encode direction, field inhomogeneities lead to either local spatial compression or stretching with standard image reconstruction. Although spatial compression results in loss of image resolution upon field map‐based reconstruction, spatial stretching can be recovered once multiple receive coils are utilized. Multi‐coil reconstruction was found to reduce the normalized RMSE from 34.3% to 8.1% for image compression, and 33.6% to 1.8% for image stretching, with resulting average g‐factors 14.7 ± 2.9 and 1.2 ± 0.1, respectively. In vivo, multi‐coil field map‐based reconstruction yielded improved alignment of angle maps with anatomical cine data. Conclusion Multi‐coil, field map‐based image reconstruction for echo‐planar cardiac diffusion tensor imaging allows accurate image reconstruction provided that the phase‐encode direction and polarity is chosen to principally align with the direction and polarity of the prominent gradients of field inhomogeneities.ISSN:0740-3194ISSN:1522-259

Analysis and correction of off‐resonance artifacts in echo‐planar cardiac diffusion tensor imaging

Purpose Cardiac diffusion tensor imaging using EPI readout is prone to image distortions in the presence of field inhomogeneities. In this work, a framework to analyze and correct image distortions in cardiac diffusion tensor imaging is presented. Methods A multi‐coil reconstruction framework was implemented to enable field map‐based off‐resonance correction. Numerical simulations were used to examine reconstruction performance for EPI phase‐encode directions blip up‐down and down‐up for different degrees of off‐resonance gradients and varying field map resolution. The impact of coil encoding was analyzed using the g‐factor and normalized RMSE. Finally, the proposed method was tested on free‐breathing in vivo cardiac diffusion tensor imaging data acquired in healthy subjects at 3 Tesla. Results Depending on the local field map gradient strength and polarity and the selected phase‐encode direction, field inhomogeneities lead to either local spatial compression or stretching with standard image reconstruction. Although spatial compression results in loss of image resolution upon field map‐based reconstruction, spatial stretching can be recovered once multiple receive coils are utilized. Multi‐coil reconstruction was found to reduce the normalized RMSE from 34.3% to 8.1% for image compression, and 33.6% to 1.8% for image stretching, with resulting average g‐factors 14.7 ± 2.9 and 1.2 ± 0.1, respectively. In vivo, multi‐coil field map‐based reconstruction yielded improved alignment of angle maps with anatomical cine data. Conclusion Multi‐coil, field map‐based image reconstruction for echo‐planar cardiac diffusion tensor imaging allows accurate image reconstruction provided that the phase‐encode direction and polarity is chosen to principally align with the direction and polarity of the prominent gradients of field inhomogeneities

Understanding Heterogeneity and Permeability of Brain Metastases in Murine Models of HER2-Positive Breast Cancer Through Magnetic Resonance Imaging: Implications for Detection and Therapy

OBJECTIVES: Brain metastases due to breast cancer are increasing, and the prognosis is poor. Lack of effective therapy is attributed to heterogeneity of breast cancers and their resulting metastases, as well as impermeability of the blood–brain barrier (BBB), which hinders delivery of therapeutics to the brain. This work investigates three experimental models of HER2+ breast cancer brain metastasis to better understand the inherent heterogeneity of the disease. We use magnetic resonance imaging (MRI) to quantify brain metastatic growth and explore its relationship with BBB permeability. DESIGN: Brain metastases due to breast cancer cells (SUM190-BR3, JIMT-1-BR3, or MDA-MB-231-BR-HER2) were imaged at 3 T using balanced steady-state free precession and contrast-enhanced T1-weighted spin echo sequences. The histology and immunohistochemistry corresponding to MRI were also analyzed. RESULTS: There were differences in metastatic tumor appearance by MRI, histology, and immunohistochemistry (Ki67, CD31, CD105) across the three models. The mean volume of an MDA-MB-231-BR-HER2 tumor was significantly larger compared to other models (F2,12 = 5.845, P < .05); interestingly, this model also had a significantly higher proportion of Gd-impermeable tumors (F2,12 = 22.18, P < .0001). Ki67 staining indicated that Gd-impermeable tumors had significantly more proliferative nuclei compared to Gd-permeable tumors (t[24] = 2.389, P < .05) in the MDA-MB-231-BR-HER2 model. CD31 and CD105 staining suggested no difference in new vasculature patterns between permeable and impermeable tumors in any model. CONCLUSION: Significant heterogeneity is present in these models of brain metastases from HER2+ breast cancer. Understanding this heterogeneity, especially as it relates to BBB permeability, is important for improvement in brain metastasis detection and treatment delivery

Characterizing cardiac involvement in amyloidosis using cardiovascular magnetic resonance diffusion tensor imaging

BACKGROUND In-vivo cardiovascular magnetic resonance (CMR) diffusion tensor imaging (DTI) allows imaging of alterations of cardiac fiber architecture in diseased hearts. Cardiac amyloidosis (CA) causes myocardial infiltration of misfolded proteins with unknown consequences for myocardial microstructure. This study applied CMR DTI in CA to assess microstructural alterations and their consequences for myocardial function compared to healthy controls. METHODS Ten patients with CA (8 AL, 2 ATTR) and ten healthy controls were studied using a diffusion-weighed second-order motion-compensated spin-echo sequence at 1.5 T. Additionally, left ventricular morphology, ejection fraction, strain and native T1 values were obtained in all subjects. In CA patients, T1 mapping was repeated after the administration of gadolinium for extracellular volume fraction (ECV) calculation. CMR DTI analysis was performed to yield the scalar diffusion metrics mean diffusivity (MD) and fractional anisotropy (FA) as well as the characteristics of myofiber orientation including helix, transverse and E2A sheet angle (HA, TA, E2A). RESULTS MD and FA were found to be significantly different between CA patients and healthy controls (MD 1.77 ± 0.17 10 vs 1.41 ± 0.07 10 mm/s, p <  0.001; FA 0.25 ± 0.04 vs 0.35 ± 0.03, p <  0.001). MD demonstrated an excellent correlation with native T1 (r = 0.908, p <  0.001) while FA showed a significant correlation with ECV in the CA population (r = - 0.851, p <  0.002). HA exhibited a more circumferential orientation of myofibers in CA patients, in conjunction with a higher TA standard deviation and a higher absolute E2A sheet angle. The transmural HA slope was found to be strongly correlated with the global longitudinal strain (r = 0.921, p < 0.001). CONCLUSION CMR DTI reveals significant alterations of scalar diffusion metrics in CA patients versus healthy controls. Elevated MD and lower FA values indicate myocardial disarray with higher diffusion in CA that correlates well with native T1 and ECV measures. In CA patients, CMR DTI showed pronounced circumferential orientation of the myofibers, which may provide the rationale for the reduction of global longitudinal strain that occurs in amyloidosis patients. Accordingly, CMR DTI captures specific features of amyloid infiltration, which provides a deeper understanding of the microstructural consequences of CA