Christopher Nguyen's research while affiliated with Heart & Vascular Outcomes Research Institute and other places

Publications (63)

Article
Background: Myocardial infarction (MI) is a major risk factor for the development of heart failure with reduce ejection fraction (HFrEF). While previous studies have focused on HFrEF, the cardiovascular effects of ketone bodies in acute MI are unclear. We examined the effects of oral ketone supplementation as a potential treatment strategy in a sw...
Article
Background: Obesity is associated with derangement of cardiac metabolism and the development of subclinical cardiovascular disease. This prospective study examined the impact of bariatric surgery on cardiac function and metabolism. Methods: Subjects with obesity underwent cardiac magnetic resonance imaging (CMR) at Massachusetts General Hospital...
Article
Aortic stenosis (AS) affects about 1.5 million people in the United States and is associated with a 5-year survival rate of 20% if untreated. In these patients, aortic valve replacement is performed to restore adequate hemodynamics and alleviate symptoms. The development of next-generation prosthetic aortic valves seeks to provide enhanced hemodyna...
Article
Full-text available
In the following case series, we describe the clinical presentation of 2 patients with myocardial infarction with nonobstructive coronary arteries with different underlying pathophysiologic mechanisms. In both scenarios, cardiac magnetic resonance (CMR) imaging provided comprehensive tissue characterization with both conventional parametric mapping...
Article
The breaking of bilateral symmetry in most vertebrates is critically dependent upon the motile cilia of the embryonic left-right organizer (LRO), which generate a directional fluid flow; however, it remains unclear how this flow is sensed. Here, we demonstrated that immotile LRO cilia are mechanosensors for shear force using a methodological pipeli...
Article
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Purpose: To substantially shorten the acquisition time required for quantitative three-dimensional (3D) chemical exchange saturation transfer (CEST) and semisolid magnetization transfer (MT) imaging and allow for rapid chemical exchange parameter map reconstruction. Methods: Three-dimensional CEST and MT magnetic resonance fingerprinting (MRF) d...
Article
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In young adults, overweight and hypertension possibly already trigger cardiac remodeling as seen in mature adults, potentially overlapping non-ischemic cardiomyopathy findings. To this end, in young overweight and hypertensive adults, we aimed to investigate changes in left ventricular mass (LVM) and cardiac volumes, and the impact of different bod...
Article
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Molecular phenotyping by imaging of intact tissues has been used to reveal 3D molecular and structural coherence in tissue samples using tissue clearing techniques. However, clearing and imaging of cardiac tissue remains challenging for large-scale (>100 mm ³ ) specimens due to sample distortion. Thus, directly assessing tissue microstructural geom...
Article
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Hypoplastic left heart syndrome (HLHS) is characterized by underdevelopment of left sided structures including the ventricle, valves, and aorta. Prevailing paradigm suggests that HLHS is a multigenic disease of co-occurring phenotypes. Here, we report that zebrafish lacking two orthologs of the RNA binding protein RBFOX2 , a gene linked to HLHS in...
Article
Purpose: The noninvasive measurement of biological tissue elasticity is an evolving technology that enables the robust characterization of soft tissue mechanics for a wide array of biomedical engineering and clinical applications. We propose, design, and implement here a new MRI technique termed asynchronous magnetic resonance elastography (aMRE)...
Article
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Preclinical models of aortic stenosis can induce left ventricular pressure overload and coarsely control the severity of aortic constriction. However, they do not recapitulate the haemodynamics and flow patterns associated with the disease. Here we report the development of a customizable soft robotic aortic sleeve that can mimic the haemodynamics...
Preprint
Aortic stenosis (AS) affects approximately 1.5 million people in the US and is associated with a 5-year survival rate of 20% if untreated. In these patients, aortic valve replacement is performed to restore adequate hemodynamics and alleviate symptoms. The development of next-generation prosthetic aortic valves seeks to provide enhanced hemodynamic...
Article
Full-text available
Purpose of Review We review the clinical benefits of altering myocardial substrate metabolism in heart failure. Recent Findings Modulation of cardiac substrates (fatty acid, glucose, or ketone metabolism) offers a wide range of therapeutic possibilities which may be applicable to heart failure. Augmenting ketone oxidation seems to offer great prom...
Preprint
Full-text available
Purpose: To substantially shorten the acquisition time required for quantitative 3D chemical exchange saturation transfer (CEST) and semisolid magnetization transfer (MT) imaging and allow for rapid chemical exchange parameter map reconstruction. Methods: Three-dimensional CEST and MT magnetic resonance fingerprinting (MRF) datasets of L-arginine p...
Article
Objective: Soft-tissue sarcoma spreads preferentially along muscle fibers. We explore the utility of deriving muscle fiber orientations from diffusion tensor MRI (DT-MRI) for defining the boundary of the clinical target volume (CTV) in muscle tissue. Approach: We recruited eight healthy volunteers to acquire MR images of the left and right thigh...
Article
As one of the highest energy consumer organs in the body, the heart requires tremendous amount of adenosine triphosphate (ATP) to maintain its continuous mechanical work. Fatty acids, glucose, and ketone bodies are the primary fuel source of the heart to generate ATP with perturbations in ATP generation possibly leading to contractile dysfunction....
Article
Full-text available
Both exercise-induced molecular mechanisms and physiological cardiac remodeling have been previously studied on a whole heart level. However, the regional microstructural tissue effects of these molecular mechanisms in the heart have yet to be spatially linked and further elucidated. We show in exercised mice that the expression of CITED4, a transc...
Article
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Purpose: Powerful MRI gradient systems can surpass the International Electrotechnical Commission (IEC) 60601-2-33 limit for cardiac stimulation (CS), which was determined by simple electromagnetic simulations and electrode stimulation experiments. Only a few canine studies measured magnetically induced CS thresholds in vivo and extrapolating them...
Article
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Background RBPs (RNA-binding proteins) perform indispensable functions in the post-transcriptional regulation of gene expression. Numerous RBPs have been implicated in cardiac development or physiology based on gene knockout studies and the identification of pathogenic RBP gene mutations in monogenic heart disorders. The discovery and characterizat...
Preprint
Full-text available
Objective: Soft-tissue sarcoma spreads preferentially along muscle fibers. We explore the utility of deriving muscle fiber orientations from diffusion tensor MRI (DT-MRI) for defining the boundary of the clinical target volume in muscle tissue. Approach: We recruited eight healthy volunteers to acquire MR images of the left and right thigh. The ima...
Preprint
Full-text available
Training deep learning models on cardiac magnetic resonance imaging (CMR) can be a challenge due to the small amount of expert generated labels and inherent complexity of data source. Self-supervised contrastive learning (SSCL) has recently been shown to boost performance in several medical imaging tasks. However, it is unclear how much the pre-tra...
Article
Background: Functional dyspepsia (FD) is a disorder of gut-brain interaction, and its putative pathophysiology involves dysregulation of gastric motility and central processing of gastric afference. The vagus nerve modulates gastric peristalsis and carries afferent sensory information to brainstem nuclei, specifically the nucleus tractus solitarii...
Article
Full-text available
Background Young adult populations with the sedentary lifestyle-related risk factors overweight, hypertension, and type 2 diabetes (T2D) are growing, and associated cardiac alterations could overlap early findings in non-ischemic cardiomyopathy on cardiovascular MRI. We aimed to investigate cardiac morphology, function, and tissue characteristics f...
Article
Introduction: Cardiac diffusion tensor imaging (DTI) is an emerging technique for the in vivo characterisation of myocardial microstructure, and there is a growing need for its validation and standardisation. We sought to establish accuracy, precision, repeatability and reproducibility of state-of-the-art pulse sequences for cardiac DTI between te...
Article
During newborn lung injury, excessive activity of lysyl oxidases (LOXs) disrupts extracellular matrix (ECM) formation. Previous studies indicate that TGFβ activation in the O 2 -injured mouse pup lung increases lysyl oxidase (LOX) expression. But how TGFβ regulates this, and whether the LOXs generate excess pulmonary aldehydes are unknown. First, w...
Article
Objective Arterial stiffness is a risk factor for cardiovascular disease, including heart failure with preserved ejection fraction. MGP (matrix Gla protein) is implicated in vascular calcification in animal models, and circulating levels of the uncarboxylated, inactive form of MGP (ucMGP) are associated with cardiovascular disease-related and all-c...
Article
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Aims: Microvascular dysfunction in hypertrophic cardiomyopathy (HCM) is predictive of clinical decline, however underlying mechanisms remain unclear. Cardiac diffusion tensor imaging (cDTI) allows in vivo characterization of myocardial microstructure by quantifying mean diffusivity (MD), fractional anisotropy (FA) of diffusion, and secondary eigen...
Article
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Automating cardiac function assessment on cardiac magnetic resonance short-axis cines is faster and more reproducible than manual contour-tracing; however, accurately tracing basal contours remains challenging. Three automated post-processing software packages (Level 1) were compared to manual assessment. Subsequently, automated basal tracings were...
Article
Full-text available
Myocardial strain analysis from cinematic magnetic resonance imaging (cine-MRI) data provides a more thorough characterization of cardiac mechanics than volumetric parameters such as left-ventricular ejection fraction, but sources of variation including segmentation and motion estimation have limited its wider clinical use. We designed and validate...
Article
Accumulating evidence suggests that the failing heart reverts energy metabolism toward increased utilization of ketone bodies. Despite many discrepancies in the literature, evidence from both bench and clinical research demonstrates beneficial effects of ketone bodies in heart failure. Ketone bodies are readily oxidized by cardiomyocytes and can pr...
Article
Full-text available
Cardiomyocyte growth can occur in both physiological (exercised-induced) and pathological (e.g., volume overload and pressure overload) conditions leading to left ventricular (LV) hypertrophy. Studies using animal models and histology have demonstrated the growth and remodeling process at the organ level and tissue–cellular level, respectively. How...
Article
The cover image is based on the Original Article Non‐uniform gastric wall kinematics revealed by 4D Cine magnetic resonance imaging in humans by Roberta Sclocco et al., https://doi.org/10.1111/nmo.14146.
Article
Purpose For in vivo cardiac DTI, breathing motion and B0 field inhomogeneities produce misalignment and geometric distortion in diffusion-weighted (DW) images acquired with conventional single-shot EPI. We propose using a dimensionality reduction method to retrospectively estimate the respiratory phase of DW images and facilitate both distortion co...
Preprint
Full-text available
Existing models of aortic stenosis (AS) are limited to inducing left ventricular pressure overload. As they have reduced control over the severity of aortic constriction, the clinical relevance of these models is largely hindered by their inability to mimic AS hemodynamics and recapitulate flow patterns associated with congenital valve defects, res...
Article
Purpose: To develop and assess a residual deep learning algorithm to accelerate in vivo cardiac diffusion-tensor MRI (DT-MRI) by reducing the number of averages while preserving image quality and DT-MRI parameters. Materials and methods: In this prospective study, a denoising convolutional neural network (DnCNN) for DT-MRI was developed; a total...
Article
Functional dyspepsia (FD) is a common gastrointestinal (GI) disorder of the upper GI tract associated with a variety of symptoms, such as abdominal pain and bloating, but lacking identifiable organic abnormalities. Altered motility patterns in FD occur in the stomach, pylorus and small intestine during digestive or interdigestive periods, and up to...
Article
Background Assessment of gastric function in humans has relied on modalities with varying degrees of invasiveness, which are usually limited to the evaluation of single aspects of gastric function, thus requiring patients to undergo a number of often invasive tests for a full clinical understanding. Therefore, the development of a non‐invasive tool...
Preprint
Rationale The identification of novel cardiomyocyte-intrinsic factors that support heart function will expand the number of candidate genes and therapeutic options for heart failure, a leading cause of death worldwide. Objective To identify and characterize conserved regulators of cardiomyocyte function. Methods and Results We report that the RNA...
Preprint
Full-text available
Myocardial strain analysis from cinematic magnetic resonance imaging (cine-MRI) data could provide a more thorough characterization of cardiac mechanics than volumetric parameters such as left-ventricular ejection fraction, but sources of variation including segmentation and motion estimation have limited its wide clinical use. We designed and vali...
Article
Purpose We aimed to develop a novel free‐breathing cardiac diffusion tensor MRI (DT‐MRI) approach, M2‐MT‐MOCO, capable of whole left ventricular coverage that leverages second‐order motion compensation (M2) diffusion encoding and multitasking (MT) framework to efficiently correct for respiratory motion (MOCO). Methods Imaging was performed in 16 h...
Poster
Cardiac diffusion tensor imaging (DTI) is increasingly used for non-invasive in vivo characterisation of cardiac microstructure. To help reconcile the variation in DTI metrics in the literature, we investigated the inter- and intra-site variation of DTI across twelve clinical scanners. Data were acquired at two time points, with a standardised isot...
Conference Paper
Cardiac diffusion tensor imaging (DTI) is increasingly used for non-invasive in vivo characterisation of cardiac microstructure. To help reconcile the variation in DTI metrics in the literature, we investigated the inter-and intra-site variation of DTI across twelve clinical scanners. Data were acquired at two time points, with a standardised isotr...
Article
Full-text available
Background: Despite considerable research on exercise-induced neuroplasticity in the brain, a major ongoing challenge in translating findings from animal studies to humans is that clinical and preclinical settings employ very different techniques. Objective: Here we aim to bridge this divide by using diffusion tensor imaging MRI (DTI), an advanc...
Conference Paper
Cardiac diffusion tensor imaging (DTI) continues to develop as a non-invasive contrast-free method for in vivo characterization of cardiac microstructure. Currently, data from healthy subjects 1,2,3,4 report a wide range for both mean diffusivity (MD, 0.75 × 10-3 to 1.72 × 10-3 mm 2 /s) and fractional anisotropy (FA, 0.29 to 0.61). Consequently, th...
Article
Full-text available
The complex motion of the beating heart is accomplished by the spatial arrangement of contracting cardiomyocytes with varying orientation across the transmural layers, which is difficult to imitate in organic or synthetic models. High-fidelity testing of intracardiac devices requires anthropomorphic, dynamic cardiac models that represent this compl...
Article
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Background Myocardial oxygenation imaging could help determine the presence of microvascular dysfunction associated with increased cardiovascular risk. However, it is challenging to depict the potentially small oxygenation alterations with current noninvasive cardiac MRI blood oxygen level-dependent (BOLD) techniques. Purpose To demonstrate the car...
Article
Purpose: To develop a simultaneous T1 , T2 , and ADC mapping method that provides co-registered, distortion-free images and enables multiparametric quantification of 3D brain coverage in a clinically feasible scan time with the MR Multitasking framework. Methods: The T1 /T2 /diffusion weighting was generated by a series of T2 preparations and di...
Article
Full-text available
Although the zebrafish embryo is a powerful animal model of human heart failure, the methods routinely employed to monitor cardiac function produce rough approximations that are susceptible to bias and inaccuracies. We developed and validated a deep learning-based image-analysis platform for automated extraction of volumetric parameters of cardiac...

Citations

... However, exceptions to this rule exist, as both non-"9+2" motile cilia and "9+2" immotile cilia have been described, thus the "9+2" structure appears neither necessary nor sufficient for ciliary motility. Nodal cilia in the developing embryo, for example, have a "9+0" axonemal structure and are famous for their rotational movement that drives morphogen flow, which serves in L-R axis determination [61][62][63][64][65]. Meanwhile, the "9+2" kinocilia in auditory hair cells are non-motile and represent one of the heterogeneous cilia forms in the organ of Corti [66]. ...
... However, recently proposed frameworks for AI-based acquisition and quantification have rendered the rapid extraction of these parameters a viable option. A few such examples include the mapping of T 1 and T 2 relaxation times [54][55][56][57][58], semisolid magnetization transfer (MT) and chemical exchange saturation transfer (CEST) proton volume fraction and exchange rate [59][60][61][62][63], and susceptibility [64]. ...
... Another family of critical AS regulators comprises the RBFOX genes. Primarily described with roles in neuronal and striated muscle developmental programmes including cardiac muscle [23-31], members of this family, especially RBFOX2, are heavily associated with heart failure conditions [18,[32][33][34][35][36][37]. In the vasculature, a splicing regulatory role for RBFOX2 has been described in the endothelium [38] and in VSMCs, which express high levels of this protein, for only a few events including calcium channel genes (CACNA1C) [39]. ...
... Leveraging our previous work, in which we demonstrated the ability of a non-patient-specific aortic sleeve to recreate the hemodynamics of AS in a porcine model (30), we propose a soft roboticsenabled 3D-printed anatomical hydrodynamic system that is capable of recreating the hemodynamics of AS and congenital defects in a patient-specific fashion. In addition, using an analogous design workflow, we developed a patient-specific soft robotic LV sleeve that allows us to mimic changes in cardiac function observed in these patients, simulating longitudinal disease progression. ...
... In fact, it produces and consumes approximatively 6 kg of ATP every day and has high oxygen demand to maintain its work. It possesses an efficient and complex machinery capable of producing ATP starting from various substrates, such as fatty acid (FA), carbohydrate, ketone bodies (KB), and, less frequenly, pyruvate, lactate, and aminoacids (17). FA is the most important fuel source for the heart (18), producing energy by FA β-oxidation (FAO) (19). ...
... Limited data suggest that functional lumen imaging of the pylorus may help identify those gastroparesis patients who will benefit from pylorus-directed interventions such as gastric peroral endoscopic myotomy (G-POEM) or intra-pyloric botulinum toxic injection [109]. Brain functional MRI (fMRI) imaging has also been recently used to link altered brain activity and connectivity with examinations of gastric physiologic functions [110]. Each of these methods may allow enhanced understanding of gastric motility and its contribution to the pathogenesis and treatment of disorders such as functional dyspepsia and gastroparesis. ...
... Unfavorable cardiovascular risk is found in the young because of lifestyle changes like less physical activity, sedentary lifestyle, stress and intake of commercial food. As a result, there is low cardiovascular fitness and a high percentage of body fat in them [5]. With the advancement in technology, the prevalence of obesity has increased drastically among children and teenagers worldwide. ...
... By combining immunofluorescent analysis, nuclear isolation followed by LOX activity assays, Kagan and colleagues demonstrated the presence of active LOX within the nuclei of vascular smooth muscle cells (VSMCs), and the presence of mature LOX at the intranuclear and peri-nuclear compartment of fibroblasts [41]. In another study, transforming growth factor-β (TGFβ) was shown to directly increase nuclear LOX protein expression in interstitial fibroblasts isolated from O 2 -injured (85% O 2 ) mouse pup lung [42]. Additional studies demonstrating nuclear activity of LOX focused on its' tumor-suppressor properties in the ras-transformed cells, RS485 (NIH 3T3 transformed by c-H-ras), cells which normally express low LOX levels [43][44][45][46]. ...
... These particles transport calcium and phosphate to bones and prevent vascular calcification by inhibiting growth and aggregation of hydroxyapatite (Jahnen-Dechent et al., 2011). MGP deficiency upregulates the expression of runt-related transcription factor 2 (Runx2), which promotes transdifferentiation of vascular smooth muscle cells (VSMCs) into osteochondrogenic cells (Malhotra et al., 2022). These transdifferentiated VSMCs secrete calcium ions and phosphate ions, accelerating vascular calcification (Speer et al., 2009;Neven et al., 2011). ...
... Despite a normal LVEF, this patient has a low cardiac output, and his prognosis is related to several consequences, such as renal impairment and respiratory infections. In fact, the term preserved ejection fraction seems reassuring, but it hides energetic, structural and functional heart abnormalities [23,24]. Of note, LVEF-based classification it is not closely related to HF prognosis, and often, HFpEF patients show worse outcomes than HFrEF's group, with increased mortality and hospitalisation [10]. ...