Anthony G. Christodoulou

Purpose: To improve free‐breathing low‐dose quantitative dynamic contrast‐enhanced (DCE) MRI for imaging pancreatic ductal adenocarcinoma. Methods: We introduced non‐rigid (NR) motion compensation (MoCo) into MR Multitasking using a novel “in‐subspace” formulation that directly applies motion fields to spatial feature maps (eigenimages), reducing computational cost relative to warping in the spatiotemporal domain. We evaluated NR‐MoCo DCE Multitasking in n = 11 healthy volunteers scanned using 20% (0.02 mmol/kg) of the standard Gd dose; 10 of these volunteers underwent a repeat 20%‐dose scan after exiting and re‐entering the scanner. Data were reconstructed without MoCo (No‐MoCo), translation MoCo (Tr‐MoCo), and NR‐MoCo Multitasking. We assessed motion by measuring respiratory motion energy ratio and liver dome position across time within the end‐expiration respiratory bin. We estimated pharmacokinetic parameters from all reconstruction frameworks, evaluating the test–retest repeatability of parameters in the head, body, and tail of the pancreas. Results: Non‐rigid MoCo of eigenimages was compatible with MR Multitasking, using > 3000× fewer Fourier transforms and motion deformations. Compared with Tr‐MoCo and No‐MoCo, NR‐MoCo showed the best performance in reducing artifactual intra‐bin motion along DCE dimension, indicated by the smallest liver‐dome position variation ( p = 0.026). NR‐MoCo lowered the effective tensor rank and improved repeatability of quantitative kinetic vascular properties across healthy volunteers as compared to No‐MoCo. The Bland–Altman analysis indicated that NR‐MoCo narrowed K ^trans limits of agreement by 2.1× relative to No‐MoCo and Tr‐MoCo. Conclusion: Non‐rigid motion compensation reduces respiratory motion and improves K ^trans repeatability in low‐dose free‐breathing, whole‐abdomen quantitative dynamic contrast enhanced (DCE) MR Multitasking.

Fetal Alcohol Spectrum Disorder, caused by prenatal alcohol exposure, remains a major public health concern, affecting up to 1 in 20 U.S. schoolchildren. Pregnancy is typically not recognized until six weeks of gestation, alcohol exposure often occurs unknowingly during the peri-conceptional period, a highly vulnerable developmental window of oocyte maturation. The placenta is increasingly recognized as a mediator of alcohol-induced neurodevelopmental risk through the placenta–brain axis. We characterize peri-conceptional alcohol exposure on placental development in a mouse PCA model mimicking human drinking patterns. Single-cell transcriptomic analyses on late gestation placentas revealed disruption of extracellular matrix and collagen-remodeling pathways within the labyrinth; processes essential for placental vascular development. Mitochondria isolated from E17.5 placentas showed compromised respiration. We assess placental vascular functions with non-invasive dynamic contrast-enhanced MRI, enabling analysis across placental compartments for longitudinal evaluation of perfusion, substrate delivery, and contractile function. We demonstrate that PCA exposure arrests placental vascularization, perfusion, and morphological maturation. PCA exposure before implantation altered long-term placental programming, resulting in impaired placental perfusion and mitochondrial functions across gestation. These findings implicate placental dysfunction as a critical mechanism in Fetal Alcohol Spectrum Disorder pathogenesis and identify extracellular matrix remodeling and mitochondria as potential therapeutic targets following PCA exposure.

Purpose: To develop a unified image reconstruction framework that bridges real‐time and gated cardiac MRI, including quantitative MRI. Methods: We introduce generative multitasking, which learns subject‐ and dataset‐specific implicit neural temporal bases from sequence timings and an interpretable latent space for cardiac and respiratory motion. Cardiac motion is modeled as a complex harmonic, with phase encoding timing and a latent amplitude capturing beat‐to‐beat functional variability, linking cardiac phase‐resolved (“gated‐like”) and time‐resolved (“real‐time‐like”) views. We implemented the framework using a conditional variational autoencoder (CVAE) and evaluated it for free‐breathing, non‐ECG‐gated radial GRE in three settings: steady‐state cine imaging, multicontrast T2prep/inversion‐recovery imaging, and dual‐flip‐angle T1/T2 mapping, compared with conventional multitasking. Results: Generative multitasking provided flexible cardiac motion representation, enabling reconstruction of archetypal cardiac phase‐resolved cines (like gating) as well as time‐resolved series that reveal beat‐to‐beat variability (like real‐time imaging). Conditioning on the previous k‐space angle and modifying this term at inference removed eddy‐current artifacts without globally smoothing high temporal frequencies. For quantitative mapping, generative multitasking reduced intraseptal T1 and T2 coefficients of variation (CoV) compared with conventional multitasking (T1: 0.13 vs. 0.31; T2: 0.12 vs. 0.32; p < 0.001), indicating higher SNR. Conclusion: Generative multitasking uses a CVAE with complex harmonic cardiac coordinates to unify gated and real‐time CMR within a single free‐breathing, non‐ECG‐gated acquisition. The framework allows flexible cardiac motion representation, suppresses trajectory‐dependent artifacts, and improves T1 and T2 mapping, suggesting a path toward cine, multicontrast, and quantitative imaging without separate gated and real‐time scans.

Background: Existing strategies for free‐breathing cine cardiac MR, including real‐time imaging, struggle with complex arrhythmias such as atrial fibrillation (AF). Dynamic regularized adaptive clustering optimization (DRACO) has been proposed to generate high‐quality and quantifiable breath‐held cine images for patients in AF. Purpose: To tailor DRACO for free‐breathing and evaluate its potential to simultaneously handle cardiac and respiratory motion. Study Type: Prospective. Subjects: 10 sinus rhythm (10 males), 20 AF (18 males). Field Strength/Sequence: 3.0 T, balanced steady‐state free precession (bSSFP) with sorted golden‐step, ECG‐gated segmented cine, and real‐time. Assessment: Patients were imaged using the golden‐step sequence under breath‐held and free‐breathing conditions, and the reference bSSFP cine sequence. Signal‐to‐noise ratio (SNR), contrast‐to‐noise ratio (CNR), edge sharpness, and image quality (4‐point Likert scale) were assessed. Statistical Tests: Paired t ‐test, Friedman test, regression analysis, Fleiss' Kappa. Significance level p < 0.05. Results: The SNR and CNR values of DRACO images showed no significant differences between breath‐held and free‐breathing conditions in both sinus rhythm (SNR p = 0.53; CNR p = 0.87) and in AF (SNR p = 0.56; CNR p = 0.55). Image sharpness was not significantly different between breath‐held and free‐breathing in both sinus rhythm ( p = 0.24) and AF ( p = 0.79). In AF patients, breath‐held DRACO and free‐breathing DRACO had significantly higher image quality scores than real‐time cine. In sinus rhythm patients, there was no significant difference ( p = 0.13) between breath‐held or free‐breathing DRACO and segmented cine. Despite significant within‐patient ejection fraction (EF) differences between breath‐held versus free‐breathing in 80% of sinus rhythm and 70% of AF patients, the average EF between breath‐held versus free‐breathing DRACO showed high correlation (sinus rhythm R ² = 0.71; AF R ² = 0.71), demonstrating DRACO's robustness to motion variation. Data Conclusion: DRACO is robust to respiratory motion and AF‐related irregular cardiac motion. It enables high‐quality cine image generation in both regular and irregular cardiac motion, with or without breath holding. Level of Evidence: 1. Technical Efficacy: Stage 2.

Relentless mechanical work of the heart is powered by continuous oxygen consumption. How the heart uses oxygen is a defining feature of its health. Invasive studies have established that impaired oxygen consumption by the myocardium predicts contractile dysfunction and adverse outcomes. Despite its importance, noninvasive quantification of myocardial oxygen use remains limited. Magnetic resonance imaging (MRI) signal is known to be sensitive to blood oxygenation and has the potential to quantify myocardial oxygen consumption noninvasively, without exogenous contrast agents and free of ionizing radiation. However, its clinical translation has been impeded by the need for complex biophysical calibration, vulnerability to imaging artifacts and consistent vital motions, and the requirement of lengthy acquisition times. Here, we introduce a rapid, self-calibrated cardiac MRI framework that overcomes these barriers through high-resolution, motion-resolved coronary sinus oximetry, which can quantify myocardial oxygen extraction of the whole heart within 3 minutes. We optimized the imaging parameters via numerical simulations and validated them against invasive coronary sinus catheterization in a porcine model. We combined the method with clinical MRI sequences and demonstrated the feasibility of quantifying myocardial oxygen consumption and myocardial oxygen efficiency in patients with and without heart failure secondary to myocardial infarction in a single institution. This needle-free approach establishes a practical framework for noninvasive characterization of myocardial oxygen metabolism. It holds the potential to facilitate early disease detection, inform personalized therapeutic strategies, and guide the development of cardiometabolic therapies aimed at addressing the ongoing heart failure epidemic.

Background: Staging irreversible tissue injury in myocardial infarction (MI) enables risk assessment for post-MI major cardiovascular events. While cardiac MRI is the preferred modality for staging the severity of tissue injury, conventional scan protocols require long acquisition times with multiple breath-held and ECG-gated acquisitions, limiting its utilization. Purpose: To develop a free-breathing, whole-heart, non-ECG gated cardiac MRI for staging irreversible tissue injury in MI that can be completed in 50%. The cardiac MRI evidence of tissue injury was confirmed on histopathology in all cases. The agreements between the proposed and conventional methods for LVEF, MI volume, persistent MVO volume and IMH volume were excellent; limits of agreement (LoA) were −2.1%-1.8%, −2.9%-3.3%, −2.4%-4.1%, and −1.5%-1.5%, respectively. MI transmurality and early MVO showed good agreement; LoA were −6.8%-9.7% and −6.6%-8.2%, respectively. Conclusion: The proposed free-breathing, whole-heart, non-ECG gated cardiac MRI approach permits accurate determination of tissue injury in a canine model with >2-fold reduction in scan time. While the method remains to be tested in patients, it has the potential to facilitate efficient use of cardiac MRI for staging the severity of tissue injury in patients with reperfused MI.

Purpose: To improve cardiac motion representation and reduce artifacts for cardiac‐ and respiratory‐resolved imaging through a synergistic combination of retrospective cardiac phased array RF focusing and rigid respiratory motion compensation (MoCo). Methods: We incorporated cardiac receive focusing using region‐optimized virtual coils (ROVir) and MoCo into cardiac‐ and respiratory‐resolved low‐rank tensor (LRT) reconstruction, hypothesizing that the combination of MoCo + ROVir would prioritize the LRT representation of cardiac motion over respiratory motion. We compared LRT, MoCo‐LRT, ROVir‐LRT, and the proposed MoCo + ROVir‐LRT reconstructions of retrospective data from N = 24 pediatric patients with congenital heart disease (CHD) scanned at 3.0 T using ROCK‐MUSIC. Technical evaluation metrics included the proportion of cardiac‐to‐respiratory motion energy in self‐gating lines, cardiac motion priority in the temporal basis, flickering energy, and edge sharpness in end‐expiratory cardiac cine. Reconstructed cardiac cines were scored by two expert image readers. Results: MoCo + ROVir significantly increased the proportion of cardiac‐to‐respiratory motion energy in self‐gating lines ( p < 0.001) and prioritized cardiac motion in the temporal basis ( p < 0.001). MoCo + ROVir reduced flickering energy in cardiac cine images ( p < 0.001), sharpened the liver–lung interface ( p < 0.001), and improved flickering‐specific scores ( p = 0.001). Myocardium–blood pool interface sharpness ( p = 0.831), cardiac‐specific image scores ( p = 0.188), and vascular‐specific scores ( p = 0.901) were not significantly different. Together, these two techniques allowed 3.7–5.2× faster reconstruction times versus LRT‐only. Conclusion: The synergy of MoCo + ROVir successfully prioritized cardiac motion, suppressed respiratory motion, and reduced flickering artifacts, with an added benefit of accelerating reconstruction times. The improved respiratory motion handling may provide an avenue for free‐breathing cardiac scans in pediatric patients with CHD.

Background: Interstitial myocardial fibrosis is a crucial pathological feature of many cardiovascular disorders. Myocardial fibrosis resulting in extracellular volume (ECV) expansion can be quantified via cardiac MRI (CMR) with T₁ mapping before and after minimally invasive gadolinium (Gd) contrast agent administration. However, longitudinal repetitive ECV measurements are challenging in rodents due to the prolonged scan time with cardiac and respiratory gating that is required for conventional T₁ mapping and the invasive nature of the rodent intravenous lines. Methods: To address these challenges, the objective of this study is to establish a fast, free-breathing, and gating-free ECV procedure using a minimally invasive subcutaneous catheter for in-scanner Gd administration that can allow longitudinal repetitive ECV evaluations in rodent models. This is achieved by the (1) IntraGate sequence for free-breathing, gating-free cardiac imaging; (2) minimally invasive subcutaneous in-scanner Gd administration; and (3) fast T₁ mapping with a varied flip angle (VFA) in conjunction with (4) triple jugular vein blood T₁ normalization. Additionally, full cine CMR (multi-slice short-axis, long-axis 2-chamber, and long-axis 4-chamber) was acquired during the waiting period to assess comprehensive cardiac function and strain. Results: We successfully established a minimally invasive fast ECV quantification protocol to enable longitudinal repetitive ECV quantifications in rodents. Minimally invasive subcutaneous Gd bolus administration induced a reasonable dynamic contrast enhancement (DCE) time course, reaching a steady state in ~20 min for stable T₁ quantification. The free-breathing gating-free VFA T₁ quantification scheme allows for rapid cardiac (~2.5 min) and jugular vein (49 s) T₁ quantification with no motion artifacts. The triple jugular vein T₁ acquisitions (1 pre-contrast and 2 post-contrast) immediately flanking the heart T₁ acquisitions enable accurate myocardial ECV quantification. Our data demonstrated that left-ventricular myocardial ECV quantification was highly reproducible with repeated scans, and the ECV values (0.25) are comparable to reported ranges among humans and rodents. This protocol was successfully applied to the ischemia–reperfusion injury model to detect myocardial fibrosis, which was validated by histopathology. Conclusions: We established a simple, fast, minimally invasive, and robust CMR protocol in rodents that can enable longitudinal repetitive ECV quantification for cardiovascular disease progression. It can be used to monitor disease regression with interventions.

A novel continuous-acquisition cardiac MRI technique combines non–contrast-enhanced and contrast-enhanced imaging into a single 20-minute, free-breathing, non–electrocardiographically gated examination, yielding cardiac cine, precontrast T1 and T2, extracellular volume, and late gadolinium enhancement measurements.