Purpose
Structure‐guided total variation is a recently introduced prior that allows reconstruction of images using knowledge of the location and orientation of edges in a reference image. In this ...work, we demonstrate the advantages of a variant of structure‐guided total variation known as directional total variation (DTV), over traditional total variation (TV), in the context of compressed‐sensing reconstruction and super‐resolution.
Methods
We compared TV and DTV in retrospectively undersampled ex vivo diffusion tensor imaging and diffusion spectrum imaging data from healthy, sham, and hypertrophic rat hearts.
Results
In compressed sensing at an undersampling factor of 8, the RMS error of mean diffusivity and fractional anisotropy relative to the fully sampled ground truth were 44% and 20% lower in DTV compared with TV. In super‐resolution, these values were 29% and 14%, respectively. Similarly, we observed improvements in helix angle, transverse angle, sheetlet elevation, and sheetlet azimuth. The RMS error of the diffusion kurtosis in the undersampled data relative to the ground truth was uniformly lower (22% on average) with DTV compared to TV.
Conclusion
Acquiring one fully sampled non‐diffusion‐weighted image and 10 diffusion‐weighted images at 8× undersampling would result in an 80% net reduction in data needed. We demonstrate efficacy of the DTV algorithm over TV in reducing data sampling requirements, which can be translated into higher apparent resolution and potentially shorter scan times. This method would be equally applicable in diffusion MRI applications outside the heart.
Purpose
Diffusion‐weighted MRI is sensitive to incoherent tissue motion, which may confound the measured signal and subsequent analysis. We propose a “motion‐compensated” gradient waveform design for ...tensor‐valued diffusion encoding that negates the effects bulk motion and incoherent motion in the ballistic regime.
Methods
Motion compensation was achieved by constraining the magnitude of gradient waveform moment vectors. The constraint was incorporated into a numerical optimization framework, along with existing constraints that account for b‐tensor shape, hardware restrictions, and concomitant field gradients. We evaluated the efficacy of encoding and motion compensation in simulations, and we demonstrated the approach by linear and planar b‐tensor encoding in a healthy heart in vivo.
Results
The optimization framework produced asymmetric motion‐compensated waveforms that yielded b‐tensors of arbitrary shape with improved efficiency compared with previous designs for tensor‐valued encoding, and equivalent efficiency to previous designs for linear (conventional) encoding. Technical feasibility was demonstrated in the heart in vivo, showing vastly improved data quality when using motion compensation. The optimization framework is available online in open source.
Conclusion
Our gradient waveform design is both more flexible and efficient than previous methods, facilitating tensor‐valued diffusion encoding in tissues in which motion would otherwise confound the signal. The proposed design exploits asymmetric encoding times, a single refocusing pulse or multiple refocusing pulses, and integrates compensation for concomitant gradient effects throughout the imaging volume.
Motion is a major confound in diffusion‐weighted imaging (DWI) in the body, and it is a common cause of image artefacts. The effects are particularly severe in cardiac applications, due to the ...nonrigid cyclical deformation of the myocardium. Spin echo‐based DWI commonly employs gradient moment‐nulling techniques to desensitise the acquisition to velocity and acceleration, ie, nulling gradient moments up to the 2nd order (M2‐nulled). However, current M2‐nulled DWI scans are limited to encode diffusion along a single direction at a time.
We propose a method for designing b‐tensors of arbitrary shapes, including planar, spherical, prolate and oblate tensors, while nulling gradient moments up to the 2nd order and beyond. The design strategy comprises initialising the diffusion encoding gradients in two encoding blocks about the refocusing pulse, followed by appropriate scaling and rotation, which further enables nulling undesired effects of concomitant gradients. Proof‐of‐concept assessment of in vivo mean diffusivity (MD) was performed using linear and spherical tensor encoding (LTE and STE, respectively) in the hearts of five healthy volunteers. The results of the M2‐nulled STE showed that (a) the sequence was robust to cardiac motion, and (b) MD was higher than that acquired using standard M2‐nulled LTE, where diffusion‐weighting was applied in three orthogonal directions, which may be attributed to the presence of restricted diffusion and microscopic diffusion anisotropy.
Provided adequate signal‐to‐noise ratio, STE could significantly shorten estimation of MD compared with the conventional LTE approach. Importantly, our theoretical analysis and the proposed gradient waveform design may be useful in microstructure imaging beyond diffusion tensor imaging where the effects of motion must be suppressed.
Diffusion MRI in the heart is confounded by motion and long acquisition times. A novel design strategy for diffusion encoding is proposed to generate q‐trajectories corresponding to b‐tensors of arbitrary shapes, with gradient moment nulling up to arbitrary order and compensation for concomitant gradient effects. We demonstrate proof‐of‐concept application of acceleration‐compensated isotropic diffusion encoding (q‐trajectory shown in figure) for rapid in vivo mean diffusivity measurement in the human heart.
Cardiac electrical excitation-propagation is influenced by myocyte orientations (cellular organization). Quantitatively understanding this relationship presents a significant research challenge, ...especially during arrhythmias in which excitation patterns become complex. Tissue-scale simulations of cardiac electrophysiology, incorporating both dynamic action potential behavior and image-based myocardial architecture, provide an approach to investigate three-dimensional (3D) propagation of excitation waves in the heart. In this study, we aimed to assess the importance of natural variation in myocyte orientations on cardiac arrhythmogenesis using 3D tissue electrophysiology simulations. Three anatomical models (i.e., describing myocyte orientations) of healthy rat ventricles—obtained using diffusion tensor imaging at 100 μm resolution—were registered to a single biventricular geometry (i.e., a single cardiac shape), in which the myocyte orientations could be represented by each of the diffusion tensor imaging data sets or by an idealized rule-based description. The Fenton-Karma cellular excitation model was modified to reproduce rat ventricular action potential duration restitution to create reaction-diffusion cardiac electrophysiology models. Over 250 3D simulations were performed to investigate the effects of myocyte orientations on the following: 1) ventricular activation, 2) location-dependent arrhythmia induction via rapid pacing, and 3) dynamics of re-entry averaged over multiple episodes. It was shown that 1) myocyte orientation differences manifested themselves in local activation times, but the influence on total activation time was small; 2) differences in myocyte orientations could critically affect the inducibility and persistence of arrhythmias for specific stimulus-location/cycle-length combinations; and 3) myocyte orientations alone could be an important determinant of scroll wave break, although no significant differences were observed in averaged arrhythmia dynamics between the four myocyte orientation scenarios considered. Our results show that myocyte orientations are an important determinant of arrhythmia inducibility, persistence, and scroll wave break. These findings suggest that where specificity is desired (for example, when predicting location-dependent, patient-specific arrhythmia inducibility), subject-specific myocyte orientations may be important.
Mitochondrial creatine kinase (Mt-CK) is a major determinant of cardiac energetic status and is down-regulated in chronic heart failure, which may contribute to disease progression. We hypothesised ...that cardiomyocyte-specific overexpression of Mt-CK would mitigate against these changes and thereby preserve cardiac function. Male Mt-CK overexpressing mice (OE) and WT littermates were subjected to transverse aortic constriction (TAC) or sham surgery and assessed by echocardiography at 0, 3 and 6 weeks alongside a final LV haemodynamic assessment. Regardless of genotype, TAC mice developed progressive LV hypertrophy, dilatation and contractile dysfunction commensurate with pressure overload-induced chronic heart failure. There was a trend for improved survival in OE-TAC mice (90% vs 73%,
P
= 0.08), however, OE-TAC mice exhibited greater LV dilatation compared to WT and no functional parameters were significantly different under baseline conditions or during dobutamine stress test. CK activity was 37% higher in OE-sham versus WT-sham hearts and reduced in both TAC groups, but was maintained above normal values in the OE-TAC hearts. A separate cohort of mice received in vivo cardiac
31
P-MRS to measure high-energy phosphates. There was no difference in the ratio of phosphocreatine-to-ATP in the sham mice, however, PCr/ATP was reduced in WT-TAC but preserved in OE-TAC (1.04 ± 0.10 vs 2.04 ± 0.22;
P
= 0.007). In conclusion, overexpression of Mt-CK activity prevented the changes in cardiac energetics that are considered hallmarks of a failing heart. This had a positive effect on early survival but was not associated with improved LV remodelling or function during the development of chronic heart failure.
This work reports for the first time on the implementation and application of cardiac diffusion-weighted MRI on a Connectom MR scanner with a maximum gradient strength of 300 mT/m. It evaluates the ...benefits of the increased gradient performance for the investigation of the myocardial microstructure.
Cardiac diffusion-weighted imaging (DWI) experiments were performed on 10 healthy volunteers using a spin-echo sequence with up to second- and third-order motion compensation (
and
) and
, and 1000
(twice the
commonly used on clinical scanners). Mean diffusivity (MD), fractional anisotropy (FA), helix angle (HA), and secondary eigenvector angle (E2A) were calculated for b = 100, 450
and b = 100, 1000
for both
and
.
The MD values with
are slightly higher than with
with
for
and
for
. A reduction in MD is observed by increasing the
from 450 to 1000
(
for
and
for
). The difference between FA, E2A, and HA was not significant in different schemes (
).
This work demonstrates cardiac DWI in vivo with higher b-value and higher order of motion compensated diffusion gradient waveforms than is commonly used. Increasing the motion compensation order from
to
and the maximum b-value from 450 to 1000
affected the MD values but FA and the angular metrics (HA and E2A) remained unchanged. Our work paves the way for cardiac DWI on the next-generation MR scanners with high-performance gradient systems.
Background
Intramyocardial hemorrhage (IMH) following ST‐elevation myocardial infarction (STEMI) is associated with poor prognosis. In cardiac magnetic resonance (MR), T2* mapping is the reference ...standard for detecting IMH while cardiac diffusion tensor imaging (cDTI) can characterize myocardial architecture via fractional anisotropy (FA) and mean diffusivity (MD) of water molecules. The value of cDTI in the detection of IMH is not currently known.
Hypothesis
cDTI can detect IMH post‐STEMI.
Study Type
Prospective.
Subjects
A total of 50 patients (20% female) scanned at 1‐week (V1) and 3‐month (V2) post‐STEMI.
Field Strength/Sequence
A 3.0 T; inversion‐recovery T1‐weighted‐imaging, multigradient‐echo T2* mapping, spin‐echo cDTI.
Assessment
T2* maps were analyzed to detect IMH (defined as areas with T2* < 20 msec within areas of infarction). cDTI images were co‐registered to produce averaged diffusion‐weighted‐images (DWIs), MD, and FA maps; hypointense areas were manually planimetered for IMH quantification.
Statistics
On averaged DWI, the presence of hypointense signal in areas matching IMH on T2* maps constituted to true‐positive detection of iron. Independent samples t‐tests were used to compare regional cDTI values. Results were considered statistically significant at P ≤ 0.05.
Results
At V1, 24 patients had IMH on T2*. On averaged DWI, all 24 patients had hypointense signal in matching areas. IMH size derived using averaged‐DWI was nonsignificantly greater than from T2* (2.0 ± 1.0 cm2 vs 1.89 ± 0.96 cm2, P = 0.69). Compared to surrounding infarcted myocardium, MD was significantly reduced (1.29 ± 0.20 × 10−3 mm2/sec vs 1.75 ± 0.16 × 10−3 mm2/sec) and FA was significantly increased (0.40 ± 0.07 vs 0.23 ± 0.03) within areas of IMH. By V2, all 24 patients with acute IMH continued to have hypointense signals on averaged‐DWI in the affected area. T2* detected IMH in 96% of these patients. Overall, averaged‐DWI had 100% sensitivity and 96% specificity for the detection of IMH.
Data Conclusion
This study demonstrates that the parameters MD and FA are susceptible to the paramagnetic properties of iron, enabling cDTI to detect IMH.
Evidence Level
1
Technical Efficacy
Stage 2
Purpose
This paper presents a hierarchical modeling approach for estimating cardiomyocyte major and minor diameters and intracellular volume fraction (ICV) using diffusion‐weighted MRI (DWI) data in ...ex vivo mouse hearts.
Methods
DWI data were acquired on two healthy controls and two hearts 3 weeks post transverse aortic constriction (TAC) using a bespoke diffusion scheme with multiple diffusion times (Δ$$ \Delta $$), q‐shells and diffusion encoding directions. Firstly, a bi‐exponential tensor model was fitted separately at each diffusion time to disentangle the dependence on diffusion times from diffusion weightings, that is, b‐values. The slow‐diffusing component was attributed to the restricted diffusion inside cardiomyocytes. ICV was then extrapolated at Δ=0$$ \Delta =0 $$ using linear regression. Secondly, given the secondary and the tertiary diffusion eigenvalue measurements for the slow‐diffusing component obtained at different diffusion times, major and minor diameters were estimated assuming a cylinder model with an elliptical cross‐section (ECS). High‐resolution three‐dimensional synchrotron X‐ray imaging (SRI) data from the same specimen was utilized to evaluate the biophysical parameters.
Results
Estimated parameters using DWI data were (control 1/control 2 vs. TAC 1/TAC 2): major diameter—17.4 μ$$ \mu $$m/18.0 μ$$ \mu $$m versus 19.2 μ$$ \mu $$m/19.0 μ$$ \mu $$m; minor diameter—10.2 μ$$ \mu $$m/9.4 μ$$ \mu $$m versus 12.8 μ$$ \mu $$m/13.4 μ$$ \mu $$m; and ICV—62%/62% versus 68%/47%. These findings were consistent with SRI measurements.
Conclusion
The proposed method allowed for accurate estimation of biophysical parameters suggesting cardiomyocyte diameters as sensitive biomarkers of hypertrophy in the heart.
Purpose
Tensor‐valued diffusion encoding can probe more specific features of tissue microstructure than what is available by conventional diffusion weighting. In this work, we investigate the ...technical feasibility of tensor‐valued diffusion encoding at high b‐values with q‐space trajectory imaging (QTI) analysis, in the human heart in vivo.
Methods
Ten healthy volunteers were scanned on a 3T scanner. We designed time‐optimal gradient waveforms for tensor‐valued diffusion encoding (linear and planar) with second‐order motion compensation. Data were analyzed with QTI. Normal values and repeatability were investigated for the mean diffusivity (MD), fractional anisotropy (FA), microscopic FA (μFA), isotropic, anisotropic and total mean kurtosis (MKi, MKa, and MKt), and orientation coherence (Cc). A phantom, consisting of two fiber blocks at adjustable angles, was used to evaluate sensitivity of parameters to orientation dispersion and diffusion time.
Results
QTI data in the left ventricular myocardium were MD = 1.62 ± 0.07 μm2/ms, FA = 0.31 ± 0.03, μFA = 0.43 ± 0.07, MKa = 0.20 ± 0.07, MKi = 0.13 ± 0.03, MKt = 0.33 ± 0.09, and Cc = 0.56 ± 0.22 (mean ± SD across subjects). Phantom experiments showed that FA depends on orientation dispersion, whereas μFA was insensitive to this effect.
Conclusion
We demonstrated the first tensor‐valued diffusion encoding and QTI analysis in the heart in vivo, along with first measurements of myocardial μFA, MKi, MKa, and Cc. The methodology is technically feasible and provides promising novel biomarkers for myocardial tissue characterization.