Precession Research Articles

Macrovascular contributions to resting-state fMRI signals: A comparison between EPI and bSSFP at 9.4 Tesla

Abstract The draining-vein bias of T2*-weighted sequences, like gradient echo echo-planar imaging (GRE-EPI), can limit the spatial specificity of functional MRI (fMRI). The underlying extravascular signal changes increase with field strength (B0) and the perpendicularity of draining veins to the main axis of B0, and are therefore particularly problematic at ultra-high field (UHF). In contrast, simulations showed that T2-weighted sequences are less affected by the draining-vein bias, depending on the amount of rephasing of extravascular signal. As large pial veins on the cortical surface follow the cortical folding tightly, their orientation can be approximated by the cortical orientation to B→0. In our work, we compare the influence of the cortical orientation to B→0 on the resting-state fMRI signal of three sequences aiming to understand their macrovascular contribution. While 2D GRE-EPI and 3D GRE-EPI (both T2*-weighted) showed a high dependence on the cortical orientation to B→0, especially on the cortical surface, this was not the case for 3D balanced steady-state free precession (bSSFP) (T2/T1-weighted). Here, a slight increase of orientation dependence was shown in depths closest to WM. And while orientation dependence decreased with increased distance to the veins for both EPI sequences, no change in orientationdependence was observed in bSSFP. This indicates the low macrovascular contribution to the bSSFP signal, making it a promising sequence for layer fMRI at UHF.

Wide-spread brain alterations early after the onset of Crohn's disease in children in remission-a pilot study.

The research on possible cerebral involvement in Crohn's disease (CD) has been largely marginalized and failed to capitalize on recent developments in magnetic resonance imaging (MRI). This cross-sectional pilot study searches for eventual macrostructural and microstructural brain affection in CD in remission and early after the disease onset. 14 paediatric CD patients and 14 healthy controls underwent structural, diffusion weighted imaging and quantitative relaxation metrics acquisition, both conventional free precession and adiabatic rotating frame transverse and longitudinal relaxation time constants as markers of myelination, iron content and cellular loss. While no inter-group differences in cortical thickness and relaxation metrics were found, lower mean diffusivity and higher intracellular volume fraction were detected in CD patients over vast cortical regions essential for the regulation of the autonomous nervous system, sensorimotor processing, cognition and behavior, pointing to wide-spread cytotoxic oedema in the absence of demyelination, iron deposition or atrophy. Although still requiring further validation in longitudinal projects enrolling larger numbers of subjects, this study provides an indication of wide-spread cortical oedema in CD patients very early after the disease onset and sets possible directions for further research.

Cardiac compressed sensing real-time cine for the assessment of left ventricular function: a large sample size analysis.

Segmented cine imaging using a balanced steady-state free precession sequence is the gold standard for accurately quantifying cardiac function and myocardial mass. However, this method suffers from inefficient K-space sampling, resulting in long scan times, and requires multiple breath holds that can be difficult for some patients. Real-time compressed sensing (CS) cine reduces image acquisition time through K-space undersampling and iterative reconstruction, enabling rapid magnetic resonance (MR) imaging. Further large-scale studies need to be conducted to validate its effectiveness. In this study, we assessed image quality and left ventricular (LV) function during the routine clinical use of CS imaging in cardiovascular MR (CMR) to determine the feasibility of using CS cine. From April 2022 to March 2023, 242 patients with various heart diseases, including arrhythmia, at outpatient, inpatient, and health examination centers, were consecutively enrolled in this prospective, cross-sectional study and underwent CMR. Two methods [real-time CS cine with free breathing (RTCSCineFB) and conventional breath-hold segmented cine (SegBH)] were used to acquire long- and short-axis cine images of the heart. The total scan time, image quality (Likert score; range, 1-5), LV function parameters, and image fidelity were evaluated for each method. The study cohort comprised 149 men and 75 women with a mean age of 56.2±15.1 years. The mean ± standard deviation (SD) total scan time was significantly shorter for RTCSCineFB than for SegBH (86.44±31.74 vs. 289.81±88.41 s, P<0.001). The overall image quality was slightly lower for RTCSCineFB than for SegBH (P<0.001). The correlations between cardiac function parameters were excellent (0.913-0.984), demonstrating good consistency between the two methods. Both methods were considered equivalent in evaluating LV function and image quality, and showed strong agreement in their diagnostic gradings of ejection fraction (EF) (κ=0.759) and high accuracy. CS cine assessed LV function with high diagnostic accuracy and enhanced image stability for individuals with arrhythmia while maintaining strong consistency in two methods for EF grading condition.

Ferumoxytol-Enhanced Cardiac Cine MRI Reconstruction Using a Variable-Splitting Spatiotemporal Network.

Balanced steady-state free precession (bSSFP) imaging is commonly used in cardiac cine MRI but prone to image artifacts. Ferumoxytol-enhanced (FE) gradient echo (GRE) has been proposed as an alternative. Utilizing the abundance of bSSFP images to develop a computationally efficient network that is applicable to FE GRE cine would benefit future network development. To develop a variable-splitting spatiotemporal network (VSNet) for image reconstruction, trained on bSSFP cine images and applicable to FE GRE cine images. Retrospective and prospective. 41 patients (26 female, 53 ± 19 y/o) for network training, 31 patients (19 female, 49 ± 17 y/o) and 5 healthy subjects (5 female, 30 ± 7 y/o) for testing. 1.5T and 3T, bSSFP and GRE. VSNet was compared to VSNet with total variation loss, compressed sensing and low rank methods for 14× accelerated data. The GRAPPA×2/×3 images served as the reference. Peak signal-to-noise-ratio (PSNR), structural similarity index (SSIM), left ventricular (LV) and right ventricular (RV) end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF) were measured. Qualitative image ranking and scoring were independently performed by three readers. Latent scores were calculated based on scores of each method relative to the reference. Linear mixed-effects regression, Tukey method, Fleiss' Kappa, Bland-Altman analysis, and Bayesian categorical cumulative probit model. A P-value <0.05 was considered statistically significant. VSNet achieved significantly higher PSNR (32.7 ± 0.2), SSIM (0.880 ± 0.004), rank (2.14 ± 0.06), and latent scores (-1.72 ± 0.22) compared to other methods (rank >2.90, latent score < -2.63). Fleiss' Kappa was 0.52 for scoring and 0.61 for ranking. VSNet showed no significantly different LV and RV ESV (P = 0.938) and EF (P = 0.143) measurements, but statistically significant different (2.62 mL) EDV measurements compared to the reference. VSNet produced the highest image quality and the most accurate functional measurements for FE GRE cine images among the tested 14× accelerated reconstruction methods. 3 TECHNICAL EFFICACY: Stage 1.

Feasibility of fetal cardiac function and anatomy assessment by real-time spiral bSSFP MRI at 0.55T

BackgroundContemporary 0.55T MRI is promising for fetal MRI, due to the larger bore, reduced safety concerns, lower acoustic noise, and improved fast imaging capability. In this work, we explore improved fetal cardiac MRI (CMR) without relying on any synchronizing devices, prospective, or retrospective gating. PurposeTo determine the feasibility of real-time MRI evaluation of fetal cardiac function as well as cardiac and great vessel anatomies by using spiral balanced steady-state free precession (bSSFP) at 0.55T. MethodsA real-time spiral bSSFP pulse sequence for fetal CMR was implemented and optimized on a 0.55T whole-body MRI. Fetal CMR was prospectively performed between May 2022 and August 2023. The protocol included: 1) real-time images at standard cardiac views, for 10-20seconds/view and 40 to 43.6 ms/frame and 2) 4-9 stacks of slices at standard cardiac views that each cover the whole heart, with 15-30 slices/stack, and 2-5seconds/slice, at 320 to 349 ms/frame. Images were evaluated by a fetal cardiologist. Quantitative measurements of cardiothoracic area ratio and cardiac axis were compared with previous reports. Diagnostic accuracy was compared against postnatal echocardiographic findings. ResultsTwenty-nine participants were enrolled for 32 CMR exams, with mean maternal age 33.6±5.8 year (range 22-44 year) and mean gestational age 32.8±3.9 weeks (range 23-38 weeks). The proposed sequence enabled evaluation of the fetal heart in <30minutes in all cases (average 22minutes). Real-time MRI allowed easy adjustment of scan plan, automatic whole-heart volumetric sweeping, and flexible choice of reconstruction temporal resolution. For key cardiac anatomic features 60% were delineated well. Mean cardiothoracic area ratio and cardiac axis were 0.27±0.04 and 45.8±7.8. Diagnostic agreement with postnatal echocardiographic findings was 84%. ConclusionA spiral real-time bSSFP pulse sequence at 0.55T can provide both low framerate and high framerate fetal heart images without relying on maternal breath-hold, specialized gating devices, or cardiac gating. The low framerate images offer high diagnostic quality structural evaluations of the fetal heart, while the high framerate images capture fetal heart motion and may enable functional assessments.

Prognostic Value of Left Ventricular Myocardial Strain Parameters Derived from Cardiac Magnetic Resonance Feature Tracking Technique in Light-Chain Cardiac Amyloidosis Patients: A Pilot Study.

Previous research on the prognostic implications of left ventricular myocardial strain using cardiac magnetic resonance feature tracking (CMR-FT) in light-chain cardiac amyloidosis (AL-CA) has shown promising potential. This study aimed to evaluate the prognostic significance of global and segmental left ventricular myocardial strain in AL-CA patients, specifically analyzing the American Heart Association's 16 segments. A total of 75 consecutive patients (50 men, mean age: 55.6 ± 10.0 years) who underwent CMR examination with histologically confirmed systemic AL-CA were retrospectively enrolled between January 2014 and November 2022. Both global and segmental myocardial strain and the American Heart Association's 16 segments were quantified using CMR-FT on the steady-state free precession (SSFP) cine sequence. A comparative analysis was conducted between survivors and non-survivors based on the defined endpoint. Student t-test or Mann-Whitney U, receiver operating characteristic curve, Kaplan-Meier event-free survival curve, and Cox proportional hazards regression were used. Significance was set at p < 0.05. Following a median follow-up of 34 months, 16 out of 75 patients experienced mortality events. B-type natriuretic peptides (BNP) (p < 0.001), global radial strain (RSglobal) (p = 0.033), and RS in the basal inferior segment (RSbas-inferior) (p = 0.025) remained significant as independent predictors of all-cause mortality. The cut-off values were identified as 24.97% for RSglobal, and 20.97% for RSbas-inferior. Kaplan-Meier survival curves revealed significantly reduced event-free survival for individuals in the lower cut-off groups for RSglobal and RSbas-inferior (p = 0.013, p < 0.001, respectively). Radial strain for the global and the basal inferior segment may prove valuable for risk stratification in patients with AL-CA.

An improved method to accelerate the acquisition efficiency of the T1-T2 spectrum based on the IR-BSSFP-CPMG pulse sequence

The correlation map of the longitudinal relaxation time (T1) and the transverse relaxation time (T2) offers valuable information of different proton contributions and is served as a significant data for identifying, quantifying and characterizing complex relaxation components in unconventional reservoirs. However, the acquisition speed and spectral resolution for existing pulse sequences cannot be guaranteed simultaneously. We designed an improved pulse sequence which integrates the inversion recovery-balanced steady-state free precession (IR-BSSFP) sequence and the Carr-Purcell-Meiboom-Gill (CPMG) sequence, allowing for the measurement of two-dimensional T1-T2 spectrums. The IR-BSSFP sequence adopts a low refocusing angle and reduced flip angle pulse transmission power, eliminating the need for complete polarization. Moreover, the parameters of the improved pulse sequence such as the value and the number of the flip angle, the repetition time are discussed by numerical simulations. The result showed that the new pulse sequence achieves high-precision measurement performance, and the T1-T2 spectrum can be achieved within a few seconds.

The comparison of the efficacy of 3D fast spoiled gradient echo sequence and steady state free precession sequence in imaging vascular compression in patients with trigeminal neuralgia

Aims: Trigeminal neuralgia is a condition characterized by sudden and intense pain in the face, affecting the fifth cranial nerve. While it can occur for various reasons, vascular compression is a well-known cause. Additionally, conditions such as tumors, arachnoid cysts, idiopathic inflammation, damage, or demyelination can result in trigeminal neuralgia, extending to the distal branches of the trigeminal nerve from the pons. We aimed to investigate the diagnostic efectiveness of post-contrast three-dimensional fast spoiled gradient echo images (3D-FSPGR) in addition to steady-state free precession (SSFP) images in the imaging of trigeminal neuralgia. Methods: A total of 33 patients with a preliminary diagnosis of trigeminal neuralgia between May 2022 and October 2023 were investigated and five individuals were excluded. Among the remaining 28 patients, vascular compression was observed in only 14 patients. Trigeminal nerve thickness on both side, the distance between trigeminal nerve and superior cerebellar artery on both side, presence of vascular compression, level of the compression, presence or absence of displacement and atrophy were reported for each sequences. The findings and results were compared using independent sample T-test and paired T-test. Results: The mean age of the patient group was calculated to be 56.29 ± 4.5, while for the control group, it was 52.07 ± 3.09. Trigeminal nerve thickness wasn’t different between patient with or without vascular compression (p=0.874 for right side on SSFP, p=0.804 for left side on SSFP, p=0.667 for right side on 3D-FSPGR and 0.769 for left side on 3D-FSPGR). In 10 patients, unilateral compression of the trigeminal nerve was observed, while in 4 patients, it was bilateral. In the right trigeminal nerve, vascular compression was observed in SSFP images in 5 cases in the transitional zone, 2 cases in the nerve root entry zone, and 1 case distally. In 3D-FSPGR images, it was interpreted as being in the transitional zone in 4 cases, in the NR entry zone in 3 cases, and distally in 1 case. On the other hand, for the left trigeminal nerve, vascular compression was observed in both SSFP and 3D FSGPR images in 5 cases in the nerve root entry zone, 3 cases in the distal zone, and 2 cases in the transitional zone. Conclusion: Both SSFP and 3D-FSPGR images can provide comparable information regarding the spatial relationship between the trigeminal nerve and vascular structures. Contrast enhanced imaging allows us diferentiate the tumoral and infammatory demyelinating processes from vascular compression, we recommended to continue with SSFP images in cases where contrast enhanced 3D FSGPR images are inconclusive.

Subclinical myocardial fibrosis is almost ubiquitous in the hearts of older British persons: 'MyoFit46' cardiovascular sub-study of the NSHD

Abstract Background Unprecedented numbers are now surviving to older age, but little is known about the burden or pattern of myocardial fibrosis in the asymptomatic elderly population. Previous 1.5 Tesla (T) cardiovascular magnetic resonance (CMR) studies found a prevalence of unexpected infarct-pattern late gadolinium enhancement (LGE) of 17-20% above 75 years but less is known about non-infarct pattern scar in this group. We investigated the prevalence, patterns, and clinical predictors of left ventricular (LV) scar in a large asymptomatic older age cohort. Methods CMR with a single 3T magnet was performed on participants all born in the same week in March 1946, as part of the longest running continued surveillance birth cohort: the National Survey of Health and Development. LV short-axis stack LGE imaging was performed using a free-breathing motion-corrected balanced steady-state free precession sequence with phase-sensitive inversion-recovery. Two blinded observers independently recorded the prevalence, extent, and pattern of LGE per participant. Logistic regression was used to study the association between clinicodemographic parameters and LGE. Results 460 participants were prospectively recruited of which 406 completed CMR with LGE imaging (77.8 ± 0.1 years, 44% male). 341 (84%) demonstrated LGE affecting a mean of 2.1±1.2 myocardial segments per participant (Figure 1). The commonest pattern of LGE was inferior right ventricular insertion point (RVIP), observed in 66.9%. Other patterns included (Figure 2): Linear mid-wall (19.6%) of which 38% were located in the inferior/lateral walls; subepicardial (12.1%); subendocardial infarct-pattern (8.8%); patchy/diffuse (1.6%); embolic LGE (0.6%). Sub-analysis was performed comparing those without significant unexpected fibrosis (LGE–) vs those with focal fibrosis (LGE+, excluding RVIP and those participants with a known history of prior myocardial infarction). LGE+ participants were more likely to be female (71.7% vs 49.1%, p&amp;lt;0.001) or diabetic (11.3% vs 5.1%, p=0.05), had a higher body surface area (BSA, 1.9 vs 1.8 m2, p&amp;lt;0.001), weight (80.1 vs 72.8 kg, p&amp;lt;0.001), LV indexed end systolic volume (24.2 vs 20.4 ml/m2, p=0.001) and LV indexed mass (59.2 vs 55.4 g/m2, p&amp;lt;0.001), and a lower LV ejection fraction (67.9 vs 71.8%, p&amp;lt;0.001) In multivariable logistic regression: BSA, LV indexed mass, LV ejection fraction and diabetic status were independently associated with LGE+ status (odds ratios [95% confidence intervals]: 9.4 [0.7–3.8]; 1.0 [0.01–0.05]; 0.9 [-0.08--0.02]; and 2.5 [0.03–1.7] respectively, p&amp;lt;0.05). Conclusion Advanced PSIR MOCO LGE imaging at 3T reveals that the majority (84%) of asymptomatic British persons above the age of 75 harbour unexpected ‘subclinical’ focal fibrosis, with a substantial proportion of these scars consistent with probable historical myocarditis events. Further work will now explore the life-course determinants of this scar burden in the older age human heart.

Study design of the CARDIO-TTRansform cardiac magnetic resonance imaging substudy

Abstract Background Cardiac magnetic resonance (CMR) with extracellular volume (ECV) mapping can track treatment response in patients with cardiac amyloidosis by assessing changes in cardiac amyloid burden along with associated changes in structure and function. The CARDIO-TTRansform trial is a phase 3, multicentre, double-blind, randomised, placebo-controlled trial designed to assess the efficacy and safety of eplontersen in transthyretin amyloid cardiomyopathy (ATTR-CM). Eplontersen is a ligand-conjugated antisense oligonucleotide designed to reduce hepatic production of transthyretin protein, the amyloid fibril precursor protein in ATTR-CM. Patients with hereditary or wild-type ATTR-CM on available standard of care were randomized 1:1 to receive 45 mg of eplontersen or placebo via subcutaneous injection every 4 weeks. Patients in the main study with no contraindication to CMR were invited to participate in this sub-study. Purpose The primary objective is to measure the change in amyloid burden (defined as % change in ECV from baseline) over time in patients receiving eplontersen versus placebo. Methods Participants will undergo CMR with ECV mapping at baseline, 25, 49, 97 and 140 weeks (Figure 1). Images will be acquired under a standardized protocol comprising cine imaging with steady state free precession sequence, late gadolinium enhancement imaging (LGE) and T1 mapping. T1 mapping will be performed before the administration of contrast and will be repeated 15 minutes post-contrast using the same slice locations, to produce ECV maps. Results In the main study, 1432 patients were randomized from 120 sites across 20 countries. Of these patients, 157 patients were enrolled in the CMR sub-study, from 6 centers across 4 countries. Images will be read centrally at the end of the study. All participants in the study will also receive serial transthoracic echocardiography with strain analysis to correlate findings with conventional imaging techniques, and a subset of patients from the CMR substudy will be co-enrolled in a scintigraphy substudy for further characterization of amyloid deposition in their heart. Conclusion The CARDIO-TTRansform CMR substudy represents the largest CMR study of ATTR-CM. The CMR sub-study has enrolled a broad global population of patients with hereditary and wild-type ATTR-CM and will provide key information on the impact of eplontersen on the cardiac amyloid load and the associated change in structure and function.

Repeatability, Reproducibility, and Observer Variability of Cortical T1 Mapping for Renal Tissue Characterization.

The global rise in kidney diseases underscores the need for reliable, noninvasive imaging biomarkers. Among these, renal cortical T1 has shown promise but further technical validation is still required. To evaluate the repeatability, reproducibility, and observer variability of kidney cortical T1 mapping in human volunteers without known renal disease. Prospective. Three cohorts without renal disease: 1) 25 volunteers (median age 38 [interquartile range, IQR: 28-42] years, female N = 11) for scan-rescan assessments on GE 1.5 T and Siemens 1.5 T; 2) 29 volunteers (median age 29 [IQR: 24-40] years, female N = 15) for scan-rescan assessments on Siemens 3 T; and 3) 16 volunteers (median age 34 [IQR: 31-42] years, female N = 8) for cross-scanner reproducibility. 1.5 T and 3 T, a modified Look-Locker imaging (MOLLI) sequence with a balanced steady-state free precession (bSSFP) readout. Kidney cortical T1 data was acquired on GE 1.5 T scanner, Siemens 1.5 T and 3 T scanners. Within-scanner repeatability and inter/intra-observer variability: GE 1.5 T and Siemens 1.5 T, and cross-scanner manufacturer reproducibility: Siemens 1.5 T-GE 1.5 T. Bland Altman analysis, coefficient of variation (CoV), intra-class coefficient (ICC), and repeatability coefficient (RC). Renal cortical T1 mapping showed high repeatability and reliability across scanner field strengths and manufacturers (repeatability: CoV 1.9%-2.8%, ICC 0.79-0.88, pooled RC 73 msec; reproducibility: CoV 3.0%, ICC 0.75, RC 90 msec). The method also showed robust observer variability (CoV 0.6%-1.4%, ICC 0.93-0.98, RC 22-48 msec). Kidney cortical T1 mapping is a highly repeatable and reproducible method across MRI manufacturers, field strengths, and observer conditions. 2 TECHNICAL EFFICACY: Stage 2.

3D Vortex-Energetics in the Left Pulmonary Artery for Differentiating Pulmonary Arterial Hypertension and Pulmonary Venous Hypertension Groups Using 4D Flow MRI.

Pulmonary hypertension (PH) is a life-threatening. Differentiation pulmonary arterial hypertension (PAH) from pulmonary venous hypertension (PVH) is important due to distinct treatment protocols. Invasive right heart catheterization (RHC) remains the reference standard but noninvasive alternatives are needed. To evaluate 4D Flow MRI-derived 3D vortex energetics in the left pulmonary artery (LPA) for distinguishing PAH from PVH. Prospective case-control. Fourteen PAH patients (11 female) and 18 PVH patients (9 female) diagnosed from RHC, 23 healthy controls (9 female). 1.5 T; gradient recalled echo 4D flow and balanced steady-state free precession (bSSFP) cardiac cine sequences. LPA 3D vortex cores were identified using the lambda2 method. Peak vortex-contained kinetic energy (vortex-KE) and viscous energy loss (vortex-EL) were computed from 4D flow MRI. Left and right ventricular (LV, RV) stroke volume (LVSV, RVSV) and ejection fraction (LVEF, RVEF) were computed from bSSFP. In PH patients, mean pulmonary artery pressure (mPAP), pulmonary capillary wedge pressure (PCWR) and pulmonary vascular resistance (PVR) were determined from RHC. Mann-Whitney U test for group comparisons, Spearman's rho for correlations, logistic regression for identifying predictors of PAH vs. PVH and develop models, area under the receiver operating characteristic curve (AUC) for model performance. Significance was set at P < 0.05. PAH patients showed significantly lower vortex-KE (37.14 [14.68-78.52] vs. 76.48 [51.07-120.51]) and vortex-EL (9.93 [5.69-25.70] vs. 24.22 [12.20-32.01]) than PVH patients. The combined vortex-KE and LVEF model achieved an AUC of 0.89 for differentiating PAH from PVH. Vortex-EL showed significant negative correlations with mPAP (rho = -0.43), PCWP (rho = 0.37), PVR (rho = -0.64). In the PAH group, PVR was significantly negatively correlated with LPA vortex-KE (rho = -0.73) and vortex-EL (rho = -0.71), and vortex-KE significantly correlated with RVEF (rho = 0.69), RVSV, (rho = 0.70). In the PVH group, vortex-KE (rho = 0.52), vortex-EL significantly correlated with RVSV (rho = 0.58). These preliminary findings suggest that 4D flow MRI-derived LPA vortex energetics have potential to noninvasively differentiate PAH from PVH and correlate with invasive hemodynamic parameters. 1 TECHNICAL EFFICACY: Stage 3.

A pipeline for developing digital cardiac twins integrating cardiovascular magnetic resonance and electrocardiographic imaging: results from the MyoFit46 study

Abstract Background Personalised cardiovascular medicine uses multimodal screening and diagnostic tools, spanning from organ to tissue to molecular levels, to generate a complex and detailed patient phenotype. Cardiac digital twins are powerful tools capable of merging and explore these multimodal data by developing virtual, mechanistic and predictive versions of the patient's heart. State-of-the-art pipelines are mainly based on artificial intelligence and optimization process to replicate clinical data and not used it as an input. We present a proof-of-principle pipeline for building digital heart twins based on cardiovascular magnetic resonance (CMR) imaging and integrated electrocardiographic imaging (ECGI) for diverse clinical scenarios by integrating them into the model (Fig. 1). Methods CMR at 3T was performed on participants all born in the same week in March 1946, as part of the longest-running continued surveillance birth cohort: the National Survey of Health and Development. Cine steady-state free precession end-diastolic frames provided anatomical information per participant while CMR multiparametric mapping and late gadolinium enhancement (LGE) provided tissue characteristics to the electrical myocardial model used in the finite element solver Alya. Lastly, the ECGI activation map was used as a source to define the intrinsic endocardial activation sequence by applying a case-specific correction based on wall thickness and myofibers orientation. Activation-repolarization intervals map was used to introduce the personalised repolarization heterogeneities. Results In total, 406 prospectively recruited participants (77.8 ± 0.1 years, 44% male) had multiparametric CMR with ECGI for digital twin reconstruction. The pipeline’s performance was evaluated by measuring the root mean square error (RMSE) between the ECGI activation and repolarization maps with the in-silico ones obtained without applying the proposed pipeline (Baseline) and after its application (ecgi2model). Results obtained using ecgi2model pipeline presented a significantly reduced activation and repolarization RMSE (Fig. 2b), even providing accurate results in patients with different LGE patterns (Fig. 2c). Conclusion Personalised virtual heart models can be constructed at scale using real-world myocardial structural, functional, and electrical properties, from advanced CMR and ECGI data. Proposed digital twins provide a framework for personalised arrhythmic risk assessment based on real clinical data and also its applicability for in-silico clinical trials. Fig.1 Digital twins pipeline. Fig.2 a) Flattened epicardial map. b) RMSE of activation (ACT), repolarization (RPL) and activation-repolarization intervals (ARI) for the different methods methods. c) ACT and RPL maps obtained from ECGI, baseline simulation and ecgi2model simulation in a healthy participant with normal myocardial tissue, another with subendocardial LGE, and another with subepicardial LGE.Figure 1Figure 2

Impaired myocardial energetics and lower cardiac reserve in response to exercise stress in adults born preterm

Abstract Background/Introduction Preterm birth (&amp;lt;37 weeks’ gestation) affects 10% of live births globally and associates with an increased risk of heart failure, early cardiovascular-related mortality, and altered cardiac morphology. At rest, left ventricular (LV) ejection fraction (EF) is similar between adults born preterm and term, but right ventricular (RV) EF is lower in preterm-born adults. Exercise stress uncovers LVEF impairment in preterm-born adults but RVEF response to exercise stress has not been studied. The underlying cause of the impaired LVEF reserve and lower RVEF at rest in preterm-born adults remains uncertain and whether altered myocardial energetics contribute to this cardiac dysfunction is currently unknown. Purpose To measure resting myocardial energetics and ventricular function at rest and during exercise stress to determine whether reduced cardiac reserve in preterm-born adults may be explained by impaired myocardial energetics. Methods We conducted a cross-sectional, observational, case-control study of preterm (n=64; mean gestational age =31 weeks) and term-born (n=36) adults aged 34±5 years to compare myocardial energetics and ventricular function. Following maximal cardiopulmonary exercise testing (CPET), participants underwent 31-phosphorus magnetic resonance (MR) spectroscopy (31-P MRS) and cardiovascular MR imaging (CMR) on a 3-Tesla Siemens MR scanner. 31-P MRS was used to measure myocardial phosphocreatine to adenosine triphosphate ratio (PCr/ATP) as a measure of myocardial energetics. We obtained CMR-derived LVEF and RVEF at rest and during 40% peak wattage exercise (determined from CPET) using a MR compatible cardio-step module and steady-state free precession real-time cine imaging. Outcomes were analysed using unpaired Student’s t-tests and presented as mean±standard deviation. Results Age, body mass index, and sex did not differ between groups (p&amp;gt;0.05). PCr/ATP was 1.8±0.4 in preterm-born adults and 2.0±0.4 in term-born adults (p=0.01, Figure 1). Preterm-born adults had a similar LVEF versus term-born adults at rest (60.3±7.6 versus 62.1±4.5; p=0.19) though resting RVEF was lower in preterm-born adults (53.4±6.7 versus 55.9±4.5; p=0.05). LVEF increased by 6.5±5.5% in preterm-born adults and 10.9±6.0% in term-born adults from rest to 40% peak exercise (p&amp;lt;0.001), while RVEF increased by 9.2±6.3% in preterm-born adults versus 12.0±6.3% in term-born adults (p=0.06) (Figure 2). PCr/ATP associated with resting RVEF in preterm-born adults (R²=0.27, p=0.002), but was not associated with resting LVEF or the delta change in LVEF and RVEF with exercise stress. Conclusions Resting myocardial energetics is impaired in adults born preterm relative to term-born adults, with both the LV and RV demonstrating reduced functional reserve when challenged with low to moderate exercise stress. Metabolic modulators may help prevent progression to heart failure in preterm-born adults.Figure 1Figure 2

An artificial intelligence-based landmark model for early detection of aortic stenosis in Cardiac MRI

Abstract Background The utilisation of ratiometric intensity measures from cardiac magnetic resonance imaging (CMR) offers a promising biomarker for the diagnosis of aortic stenosis (AS)[1]. The Ao:LV ratio, an approximation of AS severity, is determined by comparing the relative blood signal intensity in the aorta and left ventricle (LV) within three-chamber (3Ch) cine sequences[1]. In patients with AS, the blood signal intensity of aortic blood above the valve is diminished compared to that within the LV in steady-state free precession (SSFP) 3Ch CMR cine. Although the Ao:LV ratio serves as a reliable indicator of AS severity, manual computation of this ratio may encounter difficulties due to visual obstructions caused by small LV cavities or prominent papillary muscles. Purpose This study aims to leverage artificial intelligence (AI) to automate the Ao:LV ratio analysis from 3Ch SSFP cine images and introduce the Ao:LA (aorta to left atrium) ratio, thus enhancing the diagnostic accuracy for AS severity. Methods Our methodology extends the ratiometric analysis to include both Ao:LV and Ao:LA ratios in three main steps: first, developing an AI-based algorithm for automated detection and tracking of cardiac landmarks; second, using these landmarks to automatically compute regions of interest (ROIs) in the cardiac chambers; and third, training and validating classification models with 5-fold cross-validation to select the most effective for AS severity classification. The final model's performance is assessed on a holdout test set. Data for model training and evaluation were sourced from CMR scans across three hospitals and two scanner types. Results We analysed 220 patients of which 78 patients had no AS and 122 had AS (mild AS, n = 29; moderate AS; n = 35, severe AS; n = 78). Our model yielded high efficacy in classifying AS, particularly in differentiating any grade of AS from a normal classification, which is clinically relevant. The Ao:LA ratio demonstrated a stronger correlation with AS severity class than Ao:LV, suggesting a more reliable biomarker. The proposed model demonstrated robust performance in AS classification, achieving an Area Under the Curve (AUC) of 0.845 in the automated binary classification of AS at any grade. The model exhibited a precision of 0.889, recall of 0.865, and an F1 score of 0.877 on a holdout set. Conclusion By the integration of AI in automating the analysis of CMR images through a novel ratiometric approach that includes Ao:LV and Ao:LA ratios, our model significantly improves the accuracy of early AS detection. This advancement enhances imaging strategies for AS evaluation, promoting more efficient and effective use of cardiac MRI sequences as a diagnostic tool for aortic stenosis. It has the potential to be implemented in real-time scanning protocols as a clinical decision support system.AI-inferred cardiac landmarks.ROC curve delineating AS prediction.

Deep learning super-resolution reconstruction for fast and high-quality cine cardiovascular magnetic resonance.

To compare standard-resolution balanced steady-state free precession (bSSFP) cine images with cine images acquired at low resolution but reconstructed with a deep learning (DL) super-resolution algorithm. Cine cardiovascular magnetic resonance (CMR) datasets (short-axis and 4-chamber views) were prospectively acquired in healthy volunteers and patients at normal (cineNR: 1.89 × 1.96 mm2, reconstructed at 1.04 × 1.04 mm2) and at a low-resolution (2.98 × 3.00 mm2, reconstructed at 1.04 × 1.04 mm2). Low-resolution images were reconstructed using compressed sensing DL denoising and resolution upscaling (cineDL). Left ventricular ejection fraction (LVEF), end-diastolic volume index (LVEDVi), and strain were assessed. Apparent signal-to-noise (aSNR) and contrast-to-noise ratios (aCNR) were calculated. Subjective image quality was assessed on a 5-point Likert scale. Student's paired t-test, Wilcoxon matched-pairs signed-rank-test, and intraclass correlation coefficient (ICC) were used for statistical analysis. Thirty participants were analyzed (37 ± 16 years; 20 healthy volunteers and 10 patients). Short-axis views whole-stack acquisition duration of cineDL was shorter than cineNR (57.5 ± 8.7 vs 98.7 ± 12.4 s; p < 0.0001). No differences were noted for: LVEF (59 ± 7 vs 59 ± 7%; ICC: 0.95 [95% confidence interval: 0.94, 0.99]; p = 0.17), LVEDVi (85.0 ± 13.5 vs 84.4 ± 13.7 mL/m2; ICC: 0.99 [0.98, 0.99]; p = 0.12), longitudinal strain (-19.5 ± 4.3 vs -19.8 ± 3.9%; ICC: 0.94 [0.88, 0.97]; p = 0.52), short-axis aSNR (81 ± 49 vs 69 ± 38; p = 0.32), aCNR (53 ± 31 vs 45 ± 27; p = 0.33), or subjective image quality (5.0 [IQR 4.9, 5.0] vs 5.0 [IQR 4.7, 5.0]; p = 0.99). Deep-learning reconstruction of cine images acquired at a lower spatial resolution led to a decrease in acquisition times of 42% with shorter breath-holds without affecting volumetric results or image quality. Question Cine CMR acquisitions are time-intensive and vulnerable to artifacts. Findings Low-resolution upscaled reconstructions using DL super-resolution decreased acquisition times by 35-42% without a significant difference in volumetric results or subjective image quality. Clinical relevance DL super-resolution reconstructions of bSSFP cine images acquired at a lower spatial resolution reduce acquisition times while preserving diagnostic accuracy, improving the clinical feasibility of cine imaging by decreasing breath hold duration.

Lung volumes are increased in fetuses with transposition of the great arteries on intrauterine MRI.

Fetal brain size is decreased in some children with complex CHDs, and the distribution of blood and accompanying oxygen and nutrients is regionally skewed from early fetal life dependent on the CHD. In transposition of the great arteries, deoxygenated blood preferentially runs to the brain, whereas the more oxygenated blood is directed towards the lungs and the abdomen. Knowledge of whether this impactsintrauterine organ development is limited. We investigated lung, liver, and total intracranial volume in fetuses with transposition of the great arteries using MRI.Eight fetuses with dextro-transposition and without concomitant disease or chromosomal abnormalities and 42 fetuses without CHD or other known diseases were scanned once or twice at gestational age 30 through 39 weeks. The MRI scans were conducted on a 1.5T system, using a 2D balanced steady-state free precession sequence. Slices acquired covered the entire fetus, slice thickness was 10 mm, pixel size 1.5 × 1.5 mm, and scan duration was 30 sec.The mean lung z score was significantly larger in fetuses with transposition compared with those without a CHD; mean difference is 1.24, 95% CI:(0.59;1.89), p < 0.001. The lung size, corrected for estimated fetal weight, was larger than in the fetuses without transposition; mean difference is 8.1 cm3/kg, 95% CI:(2.5;13.7 cm3/kg), p = 0.004.In summary, fetuses with dextro-transposition of the great arteries had both absolute and relatively larger lung volumes than those without CHD. No differences were seen in liver and total intracranial volume. Despite the small number of cases, the results are interesting and warrant further investigation.

Heteronuclear Polarization Transfer under Steady-State Conditions: The INEPT-SSFP Experiment.

NMR finds a wide range of applications, ranging from fundamental chemistry to medical imaging. The technique, however, has an inherently low signal-to-noise ratio (SNR)─particularly when dealing with nuclei having low natural abundances and/or low γs. In these cases, sensitivity is often enhanced by methods that, similar to INEPT, transfer polarization from neighboring 1Hs via J-couplings. In 1958, Carr proposed an alternative approach to increase NMR sensitivity, which involves generating and continuously detecting a steady-state transverse magnetization, by applying a train of pulses on an ensemble of noninteracting spins. This study broadens Carr's steady-state free precession (SSFP) framework to encompass the possibility of adding onto it coherent polarization transfers, allowing one to combine the SNR-enhancing benefits of both INEPT and SSFP into a single experiment. Herein, the derivation of the ensuing INEPT-SSFP (ISSFP) sequences is reported. Their use in 13C NMR and MRI experiments leads to ca. 300% improvements in SNR/ over conventional J-driven polarization transfer experiments, and sensitivity gains of over 50% over 13C SSFP performed in combination with 1H decoupling and NOE. These enhancements match well with numerical simulations and analytical evaluations. The conditions needed to optimize these new methods in both spectroscopic and imaging studies are discussed; we also examine their limitations, and the valuable vistas that, in both analytical and molecular imaging NMR, could be opened by this development.

Steady-State Free Precession (SSFP) NMR Spectroscopy for Sensitivity Enhancement in Complex Environmental and Biological Samples Using Both High-Field and Low-Field NMR.

Nuclear magnetic resonance (NMR) spectroscopy is a valuable and complementary tool in environmental research, but it is underutilized due to the cost, size, and maintenance requirements of standard "high-field" NMR spectrometers. "Low-field" NMR spectrometers are a financially and physically accessible alternative, but their lower sensitivity and increased spectral overlap limit the analysis of heterogeneous environmental/biological media, especially with fast-relaxing samples that produce broad, low-intensity spectra. This study therefore investigates the potential of the steady-state free precession (SSFP) experiment to enhance signal-to-noise ratios (SNRs) of fast-relaxing, complex samples at both high- and low-field. SSFP works by obtaining steady-state transverse signal using a train of equally spaced radiofrequency pulses with the same flip angle and a time between pulses less than the transverse relaxation time, allowing for thousands of scans to be summed in a short time period. Here, 13C-SSFP is applied to samples of varying complexity (egg white, dissolved organic matter, and crude oil) at low-field and at high-field for testing and comparison. The potential of in vivo SSFP NMR is additionally investigated by applying 31P-SSFP to live Eisenia fetida at high-field. In some samples, SSFP increased 13C SNR by over 2000% at both high-field and low-field compared to standard 13C NMR and enabled detection of peaks that were not observable by standard 13C NMR. Ultimately, SSFP holds great potential for improving analysis of fast-relaxing, complex samples, which could in turn make low-field NMR spectroscopy a more effective tool not only in environmental/biological research but also in numerous other disciplines.

Enhancement of the lymphatic system following intravenous administration of ferumoxytol.

Lymphatic imaging is becoming increasingly important in the management of patients with congenital heart disease. However, the influence of the intravenous contrast agent ferumoxytol on lymphatic imaging is not well understood. To evaluate the impact of intravenous ferumoxytol on T1-weighted and T2-weighted lymphatic imaging in patients with congenital heart disease. We included consecutive patients receiving ferumoxytol-enhanced 3D angiography for congenital heart disease evaluation. The visibility of the thoracic duct was reviewed on the T1-weighted 3D inversion recovery balanced-steady-state free precession (SSFP) with respiratory navigator gating sequence which is routinely used for angiography and the heavily T2-weighted turbo spin echo sequence which is employed for lymphatic imaging. Data on demographics and time interval between contrast administration and imaging were collected. Statistical analyses were performed using t-tests for continuous variables and chi-squared tests for categorical variables. One hundred nineteen consecutive patients with a mean age of 12.46 years±7.7 years were included. Of these, 45 cases underwent both T1-weighted and T2-weighted imaging; the other 74 underwent only T1-weighted imaging. Of the 45 patients, 20 had thoracic duct enhancement on T1-weighted imaging; among the 26 sedated, only 2 showed enhancement, while 18 of 19 non-sedated patients showed enhancement (P<0.001), indicating a strong association between sedation and reduced thoracic duct visibility. If T2-weighted imaging was performed after contrast administration, the thoracic duct was not visible on those images. For all 45 cases of visible thoracic duct in the entire cohort, the time from contrast administration to imaging ranged from 8 min up to 75 min. The enhancement of the thoracic lymphatic duct on T1-weighted imaging, coupled with degradation observed on T2-weighted imaging, suggests that intravenously administered ferumoxytol rapidly enters the lymphatic fluid. To prevent T2 shortening from degrading the imaging results, T2-weighted imaging for lymphatic evaluation should be performed prior to the administration of ferumoxytol. Sedation and, by inference, fasting may influence this property and warrant further investigation in future studies.