Related Experiment Video
Updated: Aug 16, 2026

Quantitative Autoradiographic Method for Determination of Regional Rates of Cerebral Protein Synthesis In Vivo
Published on: June 28, 2019
A unique method by which to quantitate synchrony with equilibrium radionuclide angiography
J William O'Connell1, Carole Schreck, Michael Moles
1Departments of Medicine (Cardiovascular Division) and Radiology (Nuclear Medicine Section), University of California-San Francisco, UCSF Medical Center, San Francisco, CA, USA.
Insights
New quantitative parameters, synchrony (S) and entropy (E), were developed to better assess ventricular synchrony in patients undergoing cardiac resynchronization therapy (CRT). These novel measures demonstrated superior reproducibility and differentiation compared to existing methods, offering potential for personalized CRT.
Area of Science:
- Cardiovascular Imaging and Nuclear Medicine
- Biomedical Engineering
- Heart Failure Management
Background:
- Cardiac resynchronization therapy (CRT) improves outcomes in heart failure but lacks individualization due to the absence of specific synchrony measures.
- Existing methods for assessing ventricular synchrony, such as standard deviation of phase angle (SD Ø), have limitations in reproducibility and differentiation.
- There is a critical need for accurate, reproducible, and quantitative methods to evaluate ventricular synchrony for personalized CRT.
Purpose of the Study:
- To derive and evaluate novel quantitative parameters for assessing ventricular synchrony: synchrony (S) and entropy (E).
- To compare the performance of these new parameters against established measures like SD Ø.
- To determine the added value of S and E in differentiating various patterns of ventricular contraction.
Main Methods:
- Utilized equilibrium radionuclide angiography (ERNA) to derive new synchrony (S) and entropy (E) parameters based on phase angle (Ø) and amplitude.
- Defined S as the vector sum of amplitudes divided by the scalar sum of vector lengths, with complete synchrony equaling 1.
- Defined E as a measure of contraction disorder, ranging from 0 (full synchrony) to 1 (random contraction), and applied these parameters to simulated and clinical datasets.
Main Results:
- The new synchrony (S) and entropy (E) parameters demonstrated high reproducibility.
- S and E effectively differentiated between normal (N), aneurysmal (An), severely diffuse (Diff), and severely regional (Reg) ventricular dysfunction models.
- Established SD Ø failed to differentiate these distinct contraction patterns, highlighting the limitations of current methods.
Conclusions:
- Novel scintigraphic parameters, S and E, provide a unique and valuable method for evaluating ventricular synchrony.
- These parameters offer improved differentiation of contraction patterns compared to SD Ø, addressing a key limitation in current practice.
- The derived parameters have the potential to enable more individualized and effective application of cardiac resynchronization therapy.
Background:
Cardiac resynchronization therapy (CRT) improves symptoms and the survival rate in patients with advanced heart failure by improving synchrony. However, CRT is not always successful, is costly, and is applied without individualization. There is no specific measure of synchrony. The goal of this study was to analyze new quantitative parameters of synchrony and compare them with established measures.
Methods And Results:
Equilibrium radionuclide angiography, phase angle (Ø), and amplitude quantitate regional contraction timing and magnitude and are the basis for new synchrony (S) and entropy (E) parameters. S is the vector sum of all amplitudes based on the angular distribution of Ø divided by the scalar sum of the length of all vectors. Complete S equals 1, and its absence equals 0. E measures the disorder in the region of interest, is 1 with random contraction and 0 with full synchrony, and differentiates among differing contraction patterns. Left ventricular S and E were measured in 22 normal equilibrium radionuclide angiography studies, where regions of interest were drawn from the left ventricle, left atrium, and background to analyze model ventricles with normal wall motion (N), ventricles with aneurysm (An), ventricles with severe diffuse dysfunction (Diff), and ventricles with severe regional dysfunction (Reg). The new S and E parameters were highly reproducible and well differentiated among N, An, Diff, and Reg, which were not separated by SD Ø (SD of ventricular phase), which has gained popularity as a measure of synchrony.
Conclusion:
Unique scintigraphic parameters for the evaluation of ventricular synchrony were derived, and their added value was determine compared with established measures. Indications for pacemaker therapy now include the treatment of severe congestive heart failure (CHF). Atrial triggered biventricular pacemakers reduce CHF symptoms and prolong life in patients with cardiomyopathy, severe CHF, left ventricular (LV) ejection fraction (EF) lower than 35%, and QRS greater than 120 milliseconds. Such pacing, or cardiac resynchronization therapy (CRT), seeks to reduce the heterogeneity and increase the synchrony of ventricular activation, conduction, and contraction. CRT has improved hemodynamics, increased exercise tolerance, reduced symptoms and the need for hospitalization, reversed ventricular remodeling, and reduced the all-cause mortality rate in CHF. However, CRT is costly, fails to improve symptoms or activity level in more than 30% of patients, and is applied blindly without individualization or consideration of lead placement sight. A variety of echocardiographic methods have sought to measure synchrony and its serial changes with CRT. A recent study presented evidence of the poor reproducibility of several widely applied echocardiographic measurements by which to determine ventricular synchrony. Magnetic resonance imaging has excellent resolution of regional wall motion and has been applied to assess ventricular synchrony and its response to pacing therapy. However, these methods are complex and are not well established or widely available, and magnetic resonance imaging has not been widely applied after pacing. An accurate and reproducible method is needed by which to objectively measure regional ventricular synchrony. Phase image analysis, a functional method based on the first Fourier harmonic fit of the gated blood pool time versus radioactivity curve, generates the parameters of amplitude (A), which parallels the extent of regional ventricular contraction or stroke volume, and phase angle (Ø), which represents the timing of regional contraction. It was applied early with demonstrated reproducibility to show the linkage between electrical and mechanical dyssynchrony and to characterize the contraction pattern in heart failure and its alteration with CRT. The SD of ventricular Ø, applied as a marker of synchrony, has been shown to demonstrate the beneficial effects of biventricular pacing, and its strong prognostic value has been shown in patients with congestive cardiomyopathy and CHF, superior to LVEF. The SD Ø may not be optimal for synchrony evaluation. We sought improved, more sensitive parameters to better differentiate synchrony among the spectrum of possible patterns of dyssynergy. We derived, initially evaluated, and here present new synchrony (S) and entropy (E) parameters, based on the phase method, to quantitate regional and global ventricular synchrony and applied them in simulation and clinical protocols.