Diffusion in biological tissues is known to be hindered by the structural complexity of the underlying medium. In the heart, improved characterisation on how this complexity influences acquired ...diffusion weighted signals is key to advancing our interpretation of diffusion magnetic resonance imaging, as well as to propose novel biomarkers to further characterise myocardial microstructure. In this work, we propose stretched Mittag-Leffler signal decay models for the quantification of the anomalous decay observed in acquired diffusion weighted signals. Our results, analysed in ex vivo healthy, fixed rat ventricles, indicate that such a representation suffices to capture the anomalous signal decay observed in the myocardial syncytium. The subdiffusive order of signal decay is shown to encode independent information to that encapsulated by standard diffusion tensor metrics, and thus may provide additional information on tissue microstructure. Moreover, subdiffusion gradients are shown to be indicative of the total structural heterogeneity spanning the left ventricular wall, which includes progressive myolaminae branching and spatially varying densities of perimysial collagen, microvasculature and adipose tissue. The proposed approach may therefore have important implications for the characterisation of tissue microstructure, both in cardiac and other tissue types.
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.
DTI characterizes tissue microstructure and provides proxy measures of nerve health. Echo-planar imaging is a popular method of acquiring DTI but is susceptible to various artifacts (e.g., ...susceptibility, motion, and eddy currents), which may be ameliorated via preprocessing. There are many pipelines available but limited data comparing their performance, which provides the rationale for this study.
DTI was acquired from the upper limb of heathy volunteers at 3T in blip-up and blip-down directions. Data were independently corrected using (i) FSL's TOPUP & eddy, (ii) FSL's TOPUP, (iii) DSI Studio, and (iv) TORTOISE. DTI metrics were extracted from the median, radial, and ulnar nerves and compared (between pipelines) using mixed-effects linear regression. The geometric similarity of corrected b = 0 images and the slice matched T1-weighted (T1w) images were computed using the Sörenson-Dice coefficient.
Without preprocessing, the similarity coefficient of the blip-up and blip-down datasets to the T1w was 0·80 and 0·79, respectively. Preprocessing improved the geometric similarity by 1% with no difference between pipelines. Compared to TOPUP & eddy, DSI Studio and TORTOISE generated 2% and 6% lower estimates of fractional anisotropy, and 6% and 13% higher estimates of radial diffusivity, respectively. Estimates of anisotropy from TOPUP & eddy versus TOPUP were not different but TOPUP reduced radial diffusivity by 3%. The agreement of DTI metrics between pipelines was poor.
Preprocessing DTI from the upper limb improves geometric similarity but the choice of the pipeline introduces clinically important variability in diffusion parameter estimates from peripheral nerves.
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.
Adverse LV remodeling post–ST-segment elevation myocardial infarction (STEMI) is associated with a poor prognosis, but the underlying mechanisms are not fully understood. Diffusion tensor ...(DT)-cardiac magnetic resonance (CMR) allows in vivo characterization of myocardial architecture and provides unique mechanistic insight into pathophysiologic changes following myocardial infarction.
This study evaluated the potential associations between DT-CMR performed soon after STEMI and long-term adverse left ventricular (LV) remodeling following STEMI.
A total of 100 patients with STEMI underwent CMR at 5 days and 12 months post-reperfusion. The protocol included DT-CMR for assessing fractional anisotropy (FA), secondary eigenvector angle (E2A) and helix angle (HA), cine imaging for assessing LV volumes, and late gadolinium enhancement for calculating infarct and microvascular obstruction size. Adverse remodeling was defined as a 20% increase in LV end-diastolic volume at 12 months.
A total of 32 patients experienced adverse remodeling at 12 months. Compared with patients without adverse remodeling, they had lower FA (0.23 ± 0.03 vs 0.27 ± 0.04; P < 0.001), lower E2A (37 ± 6° vs 51 ± 7°; P < 0.001), and, on HA maps, a lower proportion of myocytes with right-handed orientation (RHM) (8% ± 5% vs 17% ± 9%; P < 0.001) in their acutely infarcted myocardium. On multivariable logistic regression analysis, infarct FA (odds ratio OR: <0.01; P = 0.014) and E2A (OR: 0.77; P = 0.001) were independent predictors of adverse LV remodeling after adjusting for left ventricular ejection fraction (LVEF) and infarct size. There were no significant changes in infarct FA, E2A, or RHM between the 2 scans.
Extensive cardiomyocyte disorganization (evidenced by low FA), acute loss of sheetlet angularity (evidenced by low E2A), and a greater loss of organization among cardiomyocytes with RHM, corresponding to the subendocardium, can be detected within 5 days post-STEMI. These changes persist post-injury, and low FA and E2A are independently associated with long-term adverse remodeling.
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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
A model of cardiac microstructure and diffusion MRI is presented, and compared with experimental data from ex vivo rat hearts. The model includes a simplified representation of individual cells, with ...physiologically correct cell size and orientation, as well as intra- to extracellular volume ratio. Diffusion MRI is simulated using a Monte Carlo model and realistic MRI sequences. The results show good correspondence between the simulated and experimental MRI signals. Similar patterns are observed in the eigenvalues of the diffusion tensor, the mean diffusivity (MD), and the fractional anisotropy (FA). A sensitivity analysis shows that the diffusivity is the dominant influence on all three eigenvalues of the diffusion tensor, the MD, and the FA. The area and aspect ratio of the cell cross-section affect the secondary and tertiary eigenvalues, and hence the FA. Within biological norms, the cell length, volume fraction of cells, and rate of change of helix angle play a relatively small role in influencing tissue diffusion. Results suggest that the model could be used to improve understanding of the relationship between cardiac microstructure and diffusion MRI measurements, as well as in testing and refinement of cardiac diffusion MRI protocols.
In hypertrophic cardiomyopathy (HCM), myocyte disarray and microvascular disease (MVD) have been implicated in adverse events, and recent evidence suggests that these may occur early. As novel ...therapy provides promise for disease modification, detection of phenotype development is an emerging priority. To evaluate their utility as early and disease-specific biomarkers, we measured myocardial microstructure and MVD in 3 HCM groups-overt, either genotype-positive (G+LVH+) or genotype-negative (G-LVH+), and subclinical (G+LVH-) HCM-exploring relationships with electrical changes and genetic substrate.
This was a multicenter collaboration to study 206 subjects: 101 patients with overt HCM (51 G+LVH+ and 50 G-LVH+), 77 patients with G+LVH-, and 28 matched healthy volunteers. All underwent 12-lead ECG, quantitative perfusion cardiac magnetic resonance imaging (measuring myocardial blood flow, myocardial perfusion reserve, and perfusion defects), and cardiac diffusion tensor imaging measuring fractional anisotropy (lower values expected with more disarray), mean diffusivity (reflecting myocyte packing/interstitial expansion), and second eigenvector angle (measuring sheetlet orientation).
Compared with healthy volunteers, patients with overt HCM had evidence of altered microstructure (lower fractional anisotropy, higher mean diffusivity, and higher second eigenvector angle; all
<0.001) and MVD (lower stress myocardial blood flow and myocardial perfusion reserve; both
<0.001). Patients with G-LVH+ were similar to those with G+LVH+ but had elevated second eigenvector angle (
<0.001 after adjustment for left ventricular hypertrophy and fibrosis). In overt disease, perfusion defects were found in all G+ but not all G- patients (100% 51/51 versus 82% 41/50;
=0.001). Patients with G+LVH- compared with healthy volunteers similarly had altered microstructure, although to a lesser extent (all diffusion tensor imaging parameters;
<0.001), and MVD (reduced stress myocardial blood flow
=0.015 with perfusion defects in 28% versus 0 healthy volunteers
=0.002). Disarray and MVD were independently associated with pathological electrocardiographic abnormalities in both overt and subclinical disease after adjustment for fibrosis and left ventricular hypertrophy (overt: fractional anisotropy: odds ratio for an abnormal ECG, 3.3,
=0.01; stress myocardial blood flow: odds ratio, 2.8,
=0.015; subclinical: fractional anisotropy odds ratio, 4.0,
=0.001; myocardial perfusion reserve odds ratio, 2.2,
=0.049).
Microstructural alteration and MVD occur in overt HCM and are different in G+ and G- patients. Both also occur in the absence of hypertrophy in sarcomeric mutation carriers, in whom changes are associated with electrocardiographic abnormalities. Measurable changes in myocardial microstructure and microvascular function are early-phenotype biomarkers in the emerging era of disease-modifying therapy.
Biophysical models are a promising means for interpreting diffusion weighted magnetic resonance imaging (DW-MRI) data, as they can provide estimates of physiologically relevant parameters of ...microstructure including cell size, volume fraction, or dispersion. However, their application in cardiac microstructure mapping (CMM) has been limited. This study proposes seven new two-compartment models with combination of restricted cylinder models and a diffusion tensor to represent intra- and extracellular spaces, respectively. Three extended versions of the cylinder model are studied here: cylinder with elliptical cross section (ECS), cylinder with Gamma distributed radii (GDR), and cylinder with Bingham distributed axes (BDA). The proposed models were applied to data in two fixed mouse hearts, acquired with multiple diffusion times, q-shells and diffusion encoding directions. The cylinderGDR-pancake model provided the best performance in terms of root mean squared error (RMSE) reducing it by 25% compared to diffusion tensor imaging (DTI). The cylinderBDA-pancake model represented anatomical findings closest as it also allows for modelling dispersion. High-resolution 3D synchrotron X-ray imaging (SRI) data from the same specimen was utilized to evaluate the biophysical models. A novel tensor-based registration method is proposed to align SRI structure tensors to the MR diffusion tensors. The consistency between SRI and DW-MRI parameters demonstrates the potential of compartment models in assessing physiologically relevant parameters.
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.
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