Longitudinal changes in left ventricular blood flow kinetic energy after myocardial infarction: predictive relevance for cardiac remodeling

Background Four-dimensional (4D) flow cardiac magnetic resonance (cardiac MR) imaging provides quantification of intracavity left ventricular (LV) flow kinetic energy (KE) parameters in three dimensions. ST-elevation myocardial infarction (STEMI) patients have been shown to have altered intracardiac blood flow compared to controls; however, how 4D flow parameters change over time has not been explored previously. Purpose Measure longitudinal changes in intraventricular flow post-STEMI and ascertain its predictive relevance of long-term cardiac remodeling. Study Type Prospective. Population Thirty-five STEMI patients (M:F = 26:9, aged 56 +/- 9 years). Field Strength/Sequence A 3 T/3D EPI-based, fast field echo (FFE) free-breathing 4D-flow sequence with retrospective cardiac gating. Assessment Serial imaging at 3-7 days (V1), 3-months (V2), and 12-months (V3) post-STEMI, including the following protocol: functional imaging for measuring volumes and 4D-flow for calculating parameters including systolic and peakE-wave LVKE, normalized to end-diastolic volume (iEDV) and stroke volume (iSV). Data were analyzed by H.B. (3 years experience). Patients were categorized into two groups: preserved ejection fraction (pEF, if EF > 50%) and reduced EF (rEF, if EF < 50%). Statistical Tests Independent sample t-tests were used to detect the statistical significance between any two cohorts. P < 0.05 was considered statistically significant. Results Across the cohort, systolic KEi(sv) was highest at V1 (28.0 +/- 4.4 mu J/mL). Patients with rEF retained significantly higher systolic KEi(sv) than patients with pEF at V2 (18.2 +/- 3.4 mu J/mL vs. 6.9 +/- 0.6 mu J/mL, P < 0.001) and V3 (21.6 +/- 5.1 mu J/mL vs. 7.4 +/- 0.9 mu J/mL, P < 0.001). Patients with pEF had significantly higher peakE-wave KEi(EDV) than rEF patients throughout the study (V1: 25.4 +/- 11.6 mu J/mL vs. 18.1 +/- 9.9 mu J/mL, P < 0.03, V2: 24.0 +/- 10.2 mu J/mL vs. 17.2 +/- 12.2 mu J/mL, P < 0.05, V3: 27.7 +/- 14.8 mu J/mL vs. 15.8 +/- 7.6 mu J/mL, P < 0.04). Data Conclusion Systolic KE increased acutely following MI; in patients with pEF, this decreased over 12 months, while patients with rEF, this remained raised. Compared to patients with pEF, persistently lower peakE-wave KE in rEF patients is suggestive of early and fixed impairment in diastolic function. Evidence Level 1 Technical Efficacy Stage 3Cardiovascular Aspects of Radiolog

Stay on the Beat With Tensor-Valued Encoding: Time-Dependent Diffusion and Cell Size Estimation in ex vivo Heart

Diffusion encoding with free gradient waveforms can provide increased microstructural specificity in heterogeneous tissues compared to conventional encoding approaches. This is achieved by considering specific aspects of encoding, such as b-tensor shape, sensitivity to bulk motion and to time-dependent diffusion (TDD). In tensor-valued encoding, different b-tensor shapes are used, such as in linear tensor encoding (LTE) or spherical tensor encoding (STE). STE can be employed for estimation of mean diffusivity (MD) or in combination with LTE to probe average microscopic anisotropy unconfounded by orientation dispersion. While tensor-valued encoding has been successfully applied in the brain and other organs, its potential and limitations have not yet been fully explored in cardiac applications. To avoid artefacts due to motion, which are particularly challenging in cardiac imaging, arbitrary b-tensors can be designed with motion compensation, i.e. gradient moment nulling, while also nulling the adverse effects of concomitant gradients. Encoding waveforms with varying degrees of motion compensation may however have significantly different sensitivities to TDD. This effect can be prominent in tissues with relatively large cell sizes such as in the heart and can be used advantageously to provide further tissue information. To account for TDD in tensor-valued encoding, the interplay between asynchronous gradients simultaneously applied along different directions needs to be considered. As the first step toward in vivo cardiac applications, our overarching goal was to explore the feasibility of acceleration compensated tensor-valued encoding on preclinical and clinical scanners ex vivo. We have demonstrated strong and predictable variation of MD due to TDD in mouse and pig hearts using a wide range of LTE and STE with progressively increasing degrees of motion compensation. Our preliminary data from acceleration compensated STE and LTE at high b-values, attainable on the preclinical scanner, indicate that TDD needs to be considered in experiments with varying b-tensor shapes. We have presented a novel theoretical framework, which enables cell size estimation, helps to elucidate limitations and provides a basis for further optimizations of experiments probing both mean diffusivity and microscopic anisotropy in the heart

Detection of Intramyocardial Iron in Patients Following ST-Elevation Myocardial Infarction Using Cardiac Diffusion Tensor Imaging

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

Insight Into Myocardial Microstructure of Athletes and Hypertrophic Cardiomyopathy Patients Using Diffusion Tensor Imaging

Background Hypertrophic cardiomyopathy (HCM) remains the commonest cause of sudden cardiac death among young athletes. Differentiating between physiologically adaptive left ventricular (LV) hypertrophy observed in athletes' hearts and pathological HCM remains challenging. By quantifying the diffusion of water molecules, diffusion tensor imaging (DTI) MRI allows voxelwise characterization of myocardial microstructure. Purpose To explore microstructural differences between healthy volunteers, athletes, and HCM patients using DTI. Study Type Prospective cohort. Population Twenty healthy volunteers, 20 athletes, and 20 HCM patients. Field Strength/Sequence 3T/DTI spin echo. Assessment In‐house MatLab software was used to derive mean diffusivity (MD) and fractional anisotropy (FA) as markers of amplitude and anisotropy of the diffusion of water molecules, and secondary eigenvector angles (E2A)—reflecting the orientations of laminar sheetlets. Statistical Tests Independent samples t‐tests were used to detect statistical significance between any two cohorts. Analysis of variance was utilized for detecting the statistical difference between the three cohorts. Statistical tests were two‐tailed. A result was considered statistically significant at P ≤ 0.05. Results DTI markers were significantly different between HCM, athletes, and volunteers. HCM patients had significantly higher global MD and E2A, and significantly lower FA than athletes and volunteers. (MDHCM = 1.52 ± 0.06 × 10−3 mm2/s, MDAthletes = 1.49 ± 0.03 × 10−3 mm2/s, MDvolunteers = 1.47 ± 0.02 × 10−3 mm2/s, P < 0.05; E2AHCM = 58.8 ± 4°, E2Aathletes = 47 ± 5°, E2Avolunteers = 38.5 ± 7°, P < 0.05; FAHCM = 0.30 ± 0.02, FAAthletes = 0.35 ± 0.02, FAvolunteers = 0.36 ± 0.03, P < 0.05). HCM patients had significantly higher E2A in their thickest segments compared to the remote (E2Athickest = 66.8 ± 7, E2Aremote = 51.2 ± 9, P < 0.05). Data Conclusion DTI depicts an increase in amplitude and isotropy of diffusion in the myocardium of HCM compared to athletes and volunteers as reflected by increased MD and decreased FA values. While significantly higher E2A values in HCM and athletes reflect steeper configurations of the myocardial sheetlets than in volunteers, HCM patients demonstrated an eccentric rise in E2A in their thickest segments, while athletes demonstrated a concentric rise. Further studies are required to determine the diagnostic capabilities of DTI. Evidence Level 1 Technical Efficacy Stage

Assessing Myocardial Microstructure with Biophysical Models of Diffusion MRI

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

Measuring cardiomyocyte cellular characteristics in cardiac hypertrophy using diffusion‐weighted MRI

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