Intrinsic Gating for Small-Animal Computed Tomography: A Robust ECG-Less Paradigm for Deriving Cardiac Phase Information and Functional Imaging

Background—A projection-based method of intrinsic cardiac gating in small-animal computed tomography imaging is presented. Methods and Results—In this method, which operates without external ECG monitoring, the gating reference signal is derived from the raw data of the computed tomography projections. After filtering, the derived gating reference signal is used to rearrange the projection images retrospectively into data sets representing different time points in the cardiac cycle during expiration. These time-stamped projection images are then used for tomographic reconstruction of different phases of the cardiac cycle. Intrinsic gating was evaluated in mice and rats and compared with extrinsic retrospective gating. An excellent agreement was achieved between ECG-derived gating signal and self-gating signal (coverage probability for a difference between the 2 measurements to be less than 5 ms was 89.2% in mice and 85.9% in rats). Functional parameters (ventricular volumes and ejection fraction) obtained from the intrinsic and the extrinsic data sets were not significantly different. The ease of use and reliability of intrinsic gating were demonstrated via a chemical stress test on 2 mice, in which the system performed flawlessly despite an increased heart rate. Because of intrinsic gating, the image quality was improved to the extent that even the coronary arteries of mice could be visualized in vivo despite a heart rate approaching 430 bpm. Feasibility of intrinsic gating for functional imaging and assessment of cardiac wall motion abnormalities was successfully tested in a mouse model of myocardial infarction. Conclusions—Our results demonstrate that self-gating using advanced software postprocessing of projection data promises to be a valuable tool for rodent computed tomography imaging and renders ECG gating with external electrodes superfluous.

[1]  Willi A Kalender,et al.  Kymogram detection and kymogram-correlated image reconstruction from subsecond spiral computed tomography scans of the heart. , 2002, Medical physics.

[2]  Fumito Ichinose,et al.  Quantitative Assessment of Regional Myocardial Function in Mice by Tissue Doppler Imaging: Comparison With Hemodynamics and Sonomicrometry , 2005, Circulation.

[3]  B. Lüderitz,et al.  Echocardiographic Assessment of Left Ventricular Mass in Neonatal and Adult Mice: Accuracy of Different Echocardiographic Methods , 2006, Echocardiography.

[4]  Wolfhard Semmler,et al.  Retrospective Motion Gating in Small Animal CT of Mice and Rats , 2007, Investigative radiology.

[5]  G. Mitchell,et al.  Measurement of heart rate and Q-T interval in the conscious mouse. , 1998, American journal of physiology. Heart and circulatory physiology.

[6]  E. Gilpin,et al.  Impact of anesthesia on cardiac function during echocardiography in mice. , 2002, American journal of physiology. Heart and circulatory physiology.

[7]  N. Pallikarakis,et al.  Estimation of the heart respiratory motion with applications for cone beam computed tomography imaging: a simulation study , 2003, IEEE Transactions on Information Technology in Biomedicine.

[8]  G Allan Johnson,et al.  4-D Micro-CT of the Mouse Heart , 2005, Molecular imaging.

[9]  Wolfhard Semmler,et al.  Intrinsic respiratory gating in small-animal CT , 2008, European Radiology.

[10]  Mark E. Anderson,et al.  Temporal changes in ventricular function assessed echocardiographically in conscious and anesthetized mice. , 2003, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[11]  Maria Drangova,et al.  Fast Retrospectively Gated Quantitative Four-Dimensional (4D) Cardiac Micro Computed Tomography Imaging of Free-Breathing Mice , 2007, Investigative radiology.

[12]  Andrew C Larson,et al.  Self‐gated cardiac cine MRI , 2004, Magnetic resonance in medicine.

[13]  S. Tanada,et al.  Cardiac imaging using 256-detector row four-dimensional CT: preliminary clinical report , 2007, Radiation Medicine.

[14]  J. J. Smith,et al.  Ventricular remodeling in a mouse model of myocardial infarction. , 1998, The American journal of physiology.

[15]  L. Leatherbury,et al.  Noninvasive phenotypic analysis of cardiovascular structure and function in fetal mice using ultrasound. , 2003, Birth defects research. Part C, Embryo today : reviews.

[16]  Wolfhard Semmler,et al.  Potential applications of flat-panel volumetric CT in morphologic and functional small animal imaging. , 2005, Neoplasia.

[17]  Jeffrey Robbins,et al.  Principles of genetic murine models for cardiac disease. , 2007, Circulation.

[18]  Maria Drangova,et al.  Prospective respiratory-gated micro-CT of free breathing rodents. , 2005, Medical physics.

[19]  W. Weninger,et al.  Phenotyping transgenic embryos: a rapid 3-D screening method based on episcopic fluorescence image capturing , 2002, Nature Genetics.

[20]  Stefan Neubauer,et al.  How to perform an accurate assessment of cardiac function in mice using high-resolution magnetic resonance imaging. , 2006, Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance.

[21]  H. Drexler,et al.  Effects of Anesthesia on Diastolic Function in Mice Assessed by Echocardiography , 2005, Echocardiography.

[22]  Stefan Neubauer,et al.  Quantitative 3-Dimensional Echocardiography for Accurate and Rapid Cardiac Phenotype Characterization in Mice , 2004, Circulation.

[23]  Marco Nolden,et al.  The Medical Imaging Interaction Toolkit , 2005, Medical Image Anal..

[24]  Wolfhard Semmler,et al.  Small Animal Computed Tomography Imaging , 2007 .

[25]  A. S. Hedayat,et al.  A Unified Approach for Assessing Agreement for Continuous and Categorical Data , 2007, Journal of biopharmaceutical statistics.

[26]  Michael Grasruck,et al.  Ultra-high resolution flat-panel volume CT: fundamental principles, design architecture, and system characterization , 2006, European Radiology.

[27]  Pierre Croisille,et al.  Cardiac and respiratory double self‐gated cine MRI in the mouse at 7 T , 2006, Magnetic resonance in medicine.

[28]  J. Boone,et al.  Small-animal X-ray dose from micro-CT. , 2004, Molecular imaging.

[29]  Marc Kachelrieß,et al.  Validation of a raw data-based synchronization signal (kymogram) for phase-correlated cardiac image reconstruction , 2007, European Radiology.