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Article ; Online: Prevalence and nature of extracardiac findings in PET/CT myocardial perfusion imaging.

David, Sthuthi / Packard, René R Sevag

Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology

2023 Volume 30, Issue 4, Page(s) 1469–1473

MeSH term(s)	Humans ; Positron Emission Tomography Computed Tomography ; Myocardial Perfusion Imaging/methods ; Prevalence ; Tomography, Emission-Computed, Single-Photon/methods ; Positron-Emission Tomography/methods ; Coronary Artery Disease/diagnostic imaging
Language	English
Publishing date	2023-04-03
Publishing country	United States
Document type	Editorial ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	1212505-2
ISSN	1532-6551 ; 1071-3581
ISSN (online)	1532-6551
ISSN	1071-3581
DOI	10.1007/s12350-023-03239-x
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Article ; Online: genomeSidekick: A user-friendly epigenomics data analysis tool.

Chen, Junjie / Zhu, Ashley J / Packard, René R S / Vondriska, Thomas M / Chapski, Douglas J

Frontiers in bioinformatics

2022 Volume 2, Page(s) 831025

Abstract: ... user interface written in R that allows researchers to perform bespoke analyses on their transcriptomic and ...

Abstract	Recent advances in epigenomics measurements have resulted in a preponderance of genomic sequencing datasets that require focused analyses to discover mechanisms governing biological processes. In addition, multiple epigenomics experiments are typically performed within the same study, thereby increasing the complexity and difficulty of making meaningful inferences from large datasets. One gap in the sequencing data analysis pipeline is the availability of tools to efficiently browse genomic data for scientists that do not have bioinformatics training. To bridge this gap, we developed genomeSidekick, a graphical user interface written in R that allows researchers to perform bespoke analyses on their transcriptomic and chromatin accessibility or chromatin immunoprecipitation data without the need for command line tools. Importantly, genomeSidekick outputs lists of up- and downregulated genes or chromatin features with differential accessibility or occupancy; visualizes omics data using interactive volcano plots; performs Gene Ontology analyses locally; and queries PubMed for selected gene candidates for further evaluation. Outputs can be saved using the user interface and the code underlying genomeSidekick can be edited for custom analyses. In summary, genomeSidekick brings wet lab scientists and bioinformaticians into a shared fluency with the end goal of driving mechanistic discovery.
Language	English
Publishing date	2022-07-18
Publishing country	Switzerland
Document type	Journal Article
ISSN	2673-7647
ISSN (online)	2673-7647
DOI	10.3389/fbinf.2022.831025
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Article ; Online: Extended reality for biomedicine.

Yuan, Jie / Hassan, Sohail S / Wu, Jiaojiao / Koger, Casey R / Packard, René R Sevag / Shi, Feng / Fei, Baowei / Ding, Yichen

Nature reviews. Methods primers

2023 Volume 3

Abstract: Extended reality (XR) refers to an umbrella of methods that allows users to be immersed in a three-dimensional (3D) or a 4D (spatial + temporal) virtual environment to different extents, including virtual reality (VR), augmented reality (AR), and mixed ... ...

Abstract	Extended reality (XR) refers to an umbrella of methods that allows users to be immersed in a three-dimensional (3D) or a 4D (spatial + temporal) virtual environment to different extents, including virtual reality (VR), augmented reality (AR), and mixed reality (MR). While VR allows a user to be fully immersed in a virtual environment, AR and MR overlay virtual objects over the real physical world. The immersion and interaction of XR provide unparalleled opportunities to extend our world beyond conventional lifestyles. While XR has extensive applications in fields such as entertainment and education, its numerous applications in biomedicine create transformative opportunities in both fundamental research and healthcare. This Primer outlines XR technology from instrumentation to software computation methods, delineating the biomedical applications that have been advanced by state-of-the-art techniques. We further describe the technical advances overcoming current limitations in XR and its applications, providing an entry point for professionals and trainees to thrive in this emerging field.
Language	English
Publishing date	2023-03-02
Publishing country	England
Document type	Journal Article
ISSN	2662-8449
ISSN (online)	2662-8449
DOI	10.1038/s43586-023-00208-z
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Article ; Online: Total-Body PET/CT Applications in Cardiovascular Diseases: A Perspective Document of the SNMMI Cardiovascular Council.

Slart, Riemer H J A / Bengel, Frank M / Akincioglu, Cigdem / Bourque, Jamieson M / Chen, Wengen / Dweck, Marc R / Hacker, Marcus / Malhotra, Saurabh / Miller, Edward J / Pelletier-Galarneau, Matthieu / Packard, René R S / Schindler, Thomas H / Weinberg, Richard L / Saraste, Antti / Slomka, Piotr J

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

2024

Abstract: Digital PET/CT systems with a long axial field of view have become available and are emerging as the current state of the art. These new camera systems provide wider anatomic coverage, leading to major increases in system sensitivity. Preliminary results ...

Abstract	Digital PET/CT systems with a long axial field of view have become available and are emerging as the current state of the art. These new camera systems provide wider anatomic coverage, leading to major increases in system sensitivity. Preliminary results have demonstrated improvements in image quality and quantification, as well as substantial advantages in tracer kinetic modeling from dynamic imaging. These systems also potentially allow for low-dose examinations and major reductions in acquisition time. Thereby, they hold great promise to improve PET-based interrogation of cardiac physiology and biology. Additionally, the whole-body coverage enables simultaneous assessment of multiple organs and the large vascular structures of the body, opening new opportunities for imaging systemic mechanisms, disorders, or treatments and their interactions with the cardiovascular system as a whole. The aim of this perspective document is to debate the potential applications, challenges, opportunities, and remaining challenges of applying PET/CT with a long axial field of view to the field of cardiovascular disease.
Language	English
Publishing date	2024-02-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	80272-4
ISSN	1535-5667 ; 0097-9058 ; 0161-5505 ; 0022-3123
ISSN (online)	1535-5667
ISSN	0097-9058 ; 0161-5505 ; 0022-3123
DOI	10.2967/jnumed.123.266858
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Zs.A 114: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Flexible 3-D Electrochemical Impedance Spectroscopy Sensors Incorporating Phase Delay for Comprehensive Characterization of Atherosclerosis.

Chen, Michael / Neverova, Natalia / Xu, Shili / Suwannaphoom, Krit / Lluri, Gentian / Tamboline, Mikayla / Duarte, Sandra / Fishbein, Michael C / Luo, Yuan / Packard, René R Sevag

bioRxiv : the preprint server for biology

2023

Language	English
Publishing date	2023-09-22
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.09.20.558681
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Article ; Online: Cardiac PET perfusion tracers: current status and future directions.

Maddahi, Jamshid / Packard, René R S

Seminars in nuclear medicine

2014 Volume 44, Issue 5, Page(s) 333–343

Abstract: PET myocardial perfusion imaging (MPI) is increasingly being used for noninvasive detection and evaluation of coronary artery disease. However, the widespread use of PET MPI has been limited by the shortcomings of the current PET perfusion tracers. The ... ...

Abstract	PET myocardial perfusion imaging (MPI) is increasingly being used for noninvasive detection and evaluation of coronary artery disease. However, the widespread use of PET MPI has been limited by the shortcomings of the current PET perfusion tracers. The availability of these tracers is limited by the need for an onsite ((15)O water and (13)N ammonia) or nearby ((13)N ammonia) cyclotron or commitment to costly generators ((82)Rb). Owing to the short half-lives, such as 76 seconds for (82)Rb, 2.06 minutes for (15)O water, and 9.96 minutes for (13)N ammonia, their use in conjunction with treadmill exercise stress testing is either not possible ((82)Rb and (15)O water) or not practical ((13)N ammonia). Furthermore, the long positron range of (82)Rb makes image resolution suboptimal and its low myocardial extraction limits its defect resolution. In recent years, development of an (18)F-labeled PET perfusion tracer has gathered considerable interest. The longer half-life of (18)F (109 minutes) would make the tracer available as a unit dose from regional cyclotrons and allow use in conjunction with treadmill exercise testing. Furthermore, the short positron range of (18)F would result in better image resolution. Flurpiridaz F 18 is by far the most thoroughly studied in animal models and is the only (18)F-based PET MPI radiotracer currently undergoing clinical evaluation. Preclinical and clinical experience with Flurpiridaz F 18 demonstrated a high myocardial extraction fraction, high image and defect resolution, high myocardial uptake, slow myocardial clearance, and high myocardial-to-background contrast that was stable over time-important properties of an ideal PET MPI radiotracer. Preclinical data from other (18)F-labeled myocardial perfusion tracers are encouraging.
MeSH term(s)	Animals ; Humans ; Myocardial Perfusion Imaging/methods ; Positron-Emission Tomography/methods ; Radioactive Tracers ; Radiopharmaceuticals
Chemical Substances	Radioactive Tracers ; Radiopharmaceuticals
Language	English
Publishing date	2014-09-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	120248-0
ISSN	1558-4623 ; 0001-2998
ISSN (online)	1558-4623
ISSN	0001-2998
DOI	10.1053/j.semnuclmed.2014.06.011
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Zs.A 763: Show issues

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Article ; Online: Low Wall Shear Stress Is Associated with Saphenous Vein Graft Stenosis in Patients with Coronary Artery Bypass Grafting.

Khan, Muhammad Owais / Tran, Justin S / Zhu, Han / Boyd, Jack / Packard, René R Sevag / Karlsberg, Ronald P / Kahn, Andrew M / Marsden, Alison L

Journal of cardiovascular translational research

2020 Volume 14, Issue 4, Page(s) 770–781

Abstract: Biomechanical forces may play a key role in saphenous vein graft (SVG) disease after coronary artery bypass graft (CABG) surgery. Computed tomography angiography (CTA) of 430 post-CABG patients were evaluated and 15 patients were identified with both ... ...

Abstract	Biomechanical forces may play a key role in saphenous vein graft (SVG) disease after coronary artery bypass graft (CABG) surgery. Computed tomography angiography (CTA) of 430 post-CABG patients were evaluated and 15 patients were identified with both stenosed and healthy SVGs for paired analysis. The stenosis was virtually removed, and detailed 3D models were reconstructed to perform patient-specific computational fluid dynamic (CFD) simulations. Models were processed to compute anatomic parameters, and hemodynamic parameters such as local and vessel-averaged wall shear stress (WSS), normalized WSS (WSS
MeSH term(s)	Aged ; Aged, 80 and over ; Computed Tomography Angiography ; Coronary Angiography ; Coronary Artery Bypass/adverse effects ; Coronary Artery Disease/diagnostic imaging ; Coronary Artery Disease/physiopathology ; Coronary Artery Disease/surgery ; Coronary Circulation ; Coronary Vessels/diagnostic imaging ; Coronary Vessels/physiopathology ; Coronary Vessels/surgery ; Female ; Graft Occlusion, Vascular/diagnostic imaging ; Graft Occlusion, Vascular/etiology ; Graft Occlusion, Vascular/physiopathology ; Hemodynamics ; Humans ; Hydrodynamics ; Male ; Middle Aged ; Patient-Specific Modeling ; Predictive Value of Tests ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Saphenous Vein/diagnostic imaging ; Saphenous Vein/physiopathology ; Saphenous Vein/transplantation ; Stress, Mechanical ; Treatment Outcome
Language	English
Publishing date	2020-04-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2422411-X
ISSN	1937-5395 ; 1937-5387
ISSN (online)	1937-5395
ISSN	1937-5387
DOI	10.1007/s12265-020-09982-7
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Article: Inflammation in atherosclerosis: from vascular biology to biomarker discovery and risk prediction.

Packard, René R S / Libby, Peter

Clinical chemistry

2007 Volume 54, Issue 1, Page(s) 24–38

Abstract: Recent investigations of atherosclerosis have focused on inflammation, providing new insight into mechanisms of disease. Inflammatory cytokines involved in vascular inflammation stimulate the generation of endothelial adhesion molecules, proteases, and ... ...

Abstract	Recent investigations of atherosclerosis have focused on inflammation, providing new insight into mechanisms of disease. Inflammatory cytokines involved in vascular inflammation stimulate the generation of endothelial adhesion molecules, proteases, and other mediators, which may enter the circulation in soluble form. These primary cytokines also induce production of the messenger cytokine interleukin-6, which stimulates the liver to increase production of acute-phase reactants such as C-reactive protein. In addition, platelets and adipose tissue can generate inflammatory mediators relevant to atherothrombosis. Despite the irreplaceable utility of plasma lipid profiles in assessment of atherosclerotic risk, these profiles provide an incomplete picture. Indeed, many cardiovascular events occur in individuals with plasma cholesterol concentrations below the National Cholesterol Education Program thresholds of 200 mg/dL for total cholesterol and 130 mg/dL for low-density lipoprotein (LDL) cholesterol. The concept of the involvement of inflammation in atherosclerosis has spurred the discovery and adoption of inflammatory biomarkers for cardiovascular risk prediction. C-reactive protein is currently the best validated inflammatory biomarker; in addition, soluble CD40 ligand, adiponectin, interleukin 18, and matrix metalloproteinase 9 may provide additional information for cardiovascular risk stratification and prediction. This review retraces the biology of atherothrombosis and the evidence supporting the role of inflammatory biomarkers in predicting primary cardiovascular events in this biologic context.
MeSH term(s)	Atherosclerosis/complications ; Atherosclerosis/immunology ; Atherosclerosis/pathology ; Biomarkers/blood ; Cardiovascular Diseases/etiology ; Cardiovascular Diseases/pathology ; Humans ; Inflammation/immunology ; Inflammation/metabolism ; Inflammation Mediators/blood ; Risk
Chemical Substances	Biomarkers ; Inflammation Mediators
Language	English
Publishing date	2007-12-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80102-1
ISSN	1530-8561 ; 0009-9147
ISSN (online)	1530-8561
ISSN	0009-9147
DOI	10.1373/clinchem.2007.097360
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Article ; Online: Saak Transform-Based Machine Learning for Light-Sheet Imaging of Cardiac Trabeculation.

Ding, Yichen / Gudapati, Varun / Lin, Ruiyuan / Fei, Yanan / Packard, Rene R Sevag / Song, Sibo / Chang, Chih-Chiang / Baek, Kyung In / Wang, Zhaoqiang / Roustaei, Mehrdad / Kuang, Dengfeng / Kuo, C-C Jay / Hsiai, Tzung K

IEEE transactions on bio-medical engineering

2020 Volume 68, Issue 1, Page(s) 225–235

Abstract: Objective: Recent advances in light-sheet fluorescence microscopy (LSFM) enable 3-dimensional (3-D) imaging of cardiac architecture and mechanics in toto. However, segmentation of the cardiac trabecular network to quantify cardiac injury remains a ... ...

Abstract	Objective: Recent advances in light-sheet fluorescence microscopy (LSFM) enable 3-dimensional (3-D) imaging of cardiac architecture and mechanics in toto. However, segmentation of the cardiac trabecular network to quantify cardiac injury remains a challenge. Methods: We hereby employed "subspace approximation with augmented kernels (Saak) transform" for accurate and efficient quantification of the light-sheet image stacks following chemotherapy-treatment. We established a machine learning framework with augmented kernels based on the Karhunen-Loeve Transform (KLT) to preserve linearity and reversibility of rectification. Results: The Saak transform-based machine learning enhances computational efficiency and obviates iterative optimization of cost function needed for neural networks, minimizing the number of training datasets for segmentation in our scenario. The integration of forward and inverse Saak transforms can also serve as a light-weight module to filter adversarial perturbations and reconstruct estimated images, salvaging robustness of existing classification methods. The accuracy and robustness of the Saak transform are evident following the tests of dice similarity coefficients and various adversary perturbation algorithms, respectively. The addition of edge detection further allows for quantifying the surface area to volume ratio (SVR) of the myocardium in response to chemotherapy-induced cardiac remodeling. Conclusion: The combination of Saak transform, random forest, and edge detection augments segmentation efficiency by 20-fold as compared to manual processing. Significance: This new methodology establishes a robust framework for post light-sheet imaging processing, and creating a data-driven machine learning for automated quantification of cardiac ultra-structure.
MeSH term(s)	Algorithms ; Heart/diagnostic imaging ; Image Processing, Computer-Assisted ; Machine Learning ; Microscopy, Fluorescence ; Neural Networks, Computer
Language	English
Publishing date	2020-12-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	160429-6
ISSN	1558-2531 ; 0018-9294
ISSN (online)	1558-2531
ISSN	0018-9294
DOI	10.1109/TBME.2020.2991754
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Zs.A 425: Show issues

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Article ; Online: Displacement analysis of myocardial mechanical deformation (DIAMOND) reveals segmental susceptibility to doxorubicin-induced injury and regeneration.

Chen, Junjie / Ding, Yichen / Chen, Michael / Gau, Jonathan / Jen, Nelson / Nahal, Chadi / Tu, Sally / Chen, Cynthia / Zhou, Steve / Chang, Chih-Chiang / Lyu, Jintian / Xu, Xiaolei / Hsiai, Tzung K / Packard, René R Sevag

JCI insight

2019 Volume 4, Issue 8

Abstract: Zebrafish are increasingly utilized to model cardiomyopathies and regeneration. Current methods evaluating cardiac function have known limitations, fail to reliably detect focal mechanics, and are not readily feasible in zebrafish. We developed a ... ...

Abstract	Zebrafish are increasingly utilized to model cardiomyopathies and regeneration. Current methods evaluating cardiac function have known limitations, fail to reliably detect focal mechanics, and are not readily feasible in zebrafish. We developed a semiautomated, open-source method - displacement analysis of myocardial mechanical deformation (DIAMOND) - for quantitative assessment of 4D segmental cardiac function. We imaged transgenic embryonic zebrafish in vivo using a light-sheet fluorescence microscopy system with 4D cardiac motion synchronization. Our method permits the derivation of a transformation matrix to quantify the time-dependent 3D displacement of segmental myocardial mass centroids. Through treatment with doxorubicin, and by chemically and genetically manipulating the myocardial injury-activated Notch signaling pathway, we used DIAMOND to demonstrate that basal ventricular segments adjacent to the atrioventricular canal display the highest 3D displacement and are also the most susceptible to doxorubicin-induced injury. Thus, DIAMOND provides biomechanical insights into in vivo segmental cardiac function scalable to high-throughput research applications.
MeSH term(s)	Animals ; Animals, Genetically Modified ; Antibiotics, Antineoplastic/adverse effects ; Cardiomyopathies/chemically induced ; Cardiomyopathies/diagnostic imaging ; Cardiomyopathies/physiopathology ; Disease Models, Animal ; Doxorubicin/adverse effects ; Echocardiography ; Embryo, Nonmammalian ; Feasibility Studies ; Heart Ventricles/diagnostic imaging ; Heart Ventricles/drug effects ; Heart Ventricles/physiopathology ; High-Throughput Screening Assays/methods ; Humans ; Imaging, Three-Dimensional/methods ; Myocardial Contraction/drug effects ; Myocardium/pathology ; Neoplasms/drug therapy ; Receptors, Notch/metabolism ; Regeneration/drug effects ; Signal Transduction/drug effects ; Zebrafish
Chemical Substances	Antibiotics, Antineoplastic ; Receptors, Notch ; Doxorubicin (80168379AG)
Language	English
Publishing date	2019-04-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.125362
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