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Papers by Michael Bindschadler

Medical Imaging 2015: Physics of Medical Imaging, 2015

Medical Imaging 2015: Image Processing, 2015

Journal of medical imaging (Bellingham, Wash.), Jan 3, 2014

Dynamic contrast-enhanced computed tomography (CT) could provide an accurate and widely available... more Dynamic contrast-enhanced computed tomography (CT) could provide an accurate and widely available technique for myocardial blood flow (MBF) estimation to aid in the diagnosis and treatment of coronary artery disease. However, one of its primary limitations is the radiation dose imparted to the patient. We are exploring techniques to reduce the patient dose by either reducing the tube current or by reducing the number of temporal frames in the dynamic CT sequence. Both of these dose reduction techniques result in noisy data. In order to extract the MBF information from the noisy acquisitions, we have explored several data-domain smoothing techniques. In this work, we investigate two specific smoothing techniques: the sinogram restoration technique in both the spatial and temporal domains and the use of the Karhunen-Loeve (KL) transform to provide temporal smoothing in the sinogram domain. The KL transform smoothing technique has been previously applied to dynamic image sequences in p...

Proceedings of the National Academy of Sciences of the United States of America, Jan 12, 2004

University of Rochester nonmotile and surrounded by diffuse actin clouds or found in one of sever... more University of Rochester nonmotile and surrounded by diffuse actin clouds or found in one of several motile configurations (Figure 601 Elmwood Avenue P.O. Box 639 2A).

Medical Imaging 2014: Physics of Medical Imaging, 2014

Contrast enhancement on cardiac CT provides valuable information about myocardial perfusion and m... more Contrast enhancement on cardiac CT provides valuable information about myocardial perfusion and methods have been proposed to assess perfusion with static and dynamic acquisitions. There is a lack of knowledge and consensus on the appropriate approach to ensure 1) sufficient diagnostic accuracy for clinical decisions and 2) low radiation doses for patient safety. This work developed a thorough dynamic CT simulation and several accepted blood flow estimation techniques to evaluate the performance of perfusion assessment across a range of acquisition and estimation scenarios. Cardiac CT acquisitions were simulated for a range of flow states (Flow = 0.5, 1, 2, 3 ml/g/min, cardiac output = 3,5,8 L/min). CT acquisitions were simulated with a validated CT simulator incorporating polyenergetic data acquisition and realistic x-ray flux levels for dynamic acquisitions with a range of scenarios including 1, 2, 3 sec sampling for 30 sec with 25, 70, 140 mAs. Images were generated using conventional image reconstruction with additional image-based beam hardening correction to account for iodine content. Time attenuation curves were extracted for multiple regions around the myocardium and used to estimate flow. In total, 2,700 independent realizations of dynamic sequences were generated and multiple MBF estimation methods were applied to each of these. Evaluation of quantitative kinetic modeling yielded blood flow estimates with an root mean square error (RMSE) of ∼0.6 ml/g/min averaged across multiple scenarios. Semi-quantitative modeling and qualitative static imaging resulted in significantly more error (RMSE = ∼1.2 and ∼1.2 ml/min/g respectively). For quantitative methods, dose reduction through reduced temporal sampling or reduced tube current had comparable impact on the MBF estimate fidelity. On average, half dose acquisitions increased the RMSE of estimates by only 18% suggesting that substantial dose reductions can be employed in the context of quantitative myocardial blood flow estimation. In conclusion, quantitative model-based dynamic cardiac CT perfusion assessment is capable of accurately estimating MBF across a range of cardiac outputs and tissue perfusion states, outperforms comparable static perfusion estimates, and is relatively robust to noise and temporal subsampling.

Physics in Medicine and Biology, 2014

Myocardial blood flow (MBF) can be estimated from dynamic contrast enhanced (DCE) cardiac CT acqu... more Myocardial blood flow (MBF) can be estimated from dynamic contrast enhanced (DCE) cardiac CT acquisitions, leading to quantitative assessment of regional perfusion. The need for low radiation dose and the lack of consensus on MBF estimation methods motivates this study to refine the selection of acquisition protocols and models for CT-derived MBF. DCE cardiac CT acquisitions were simulated for a range of flow states (MBF = 0.5, 1, 2, 3 ml (min g)(-1), cardiac output = 3, 5, 8 L min(-1)). Patient kinetics were generated by a mathematical model of iodine exchange incorporating numerous physiological features including heterogenenous microvascular flow, permeability and capillary contrast gradients. CT acquisitions were simulated for multiple realizations of realistic x-ray flux levels. CT acquisitions that reduce radiation exposure were implemented by varying both temporal sampling (1, 2, and 3 s sampling intervals) and tube currents (140, 70, and 25 mAs). For all acquisitions, we compared three quantitative MBF estimation methods (two-compartment model, an axially-distributed model, and the adiabatic approximation to the tissue homogeneous model) and a qualitative slope-based method. In total, over 11 000 time attenuation curves were used to evaluate MBF estimation in multiple patient and imaging scenarios. After iodine-based beam hardening correction, the slope method consistently underestimated flow by on average 47.5% and the quantitative models provided estimates with less than 6.5% average bias and increasing variance with increasing dose reductions. The three quantitative models performed equally well, offering estimates with essentially identical root mean squared error (RMSE) for matched acquisitions. MBF estimates using the qualitative slope method were inferior in terms of bias and RMSE compared to the quantitative methods. MBF estimate error was equal at matched dose reductions for all quantitative methods and range of techniques evaluated. This suggests that there is no particular advantage between quantitative estimation methods nor to performing dose reduction via tube current reduction compared to temporal sampling reduction. These data are important for optimizing implementation of cardiac dynamic CT in clinical practice and in prospective CT MBF trials.

Journal of Cell Science, 2007

Current Biology, 2004

Chaos: An Interdisciplinary Journal of Nonlinear Science, 2001

In many cell types, asynchronous or synchronous oscillations in the concentration of intracellula... more In many cell types, asynchronous or synchronous oscillations in the concentration of intracellular free calcium occur in adjacent cells that are coupled by gap junctions. Such oscillations are believed to underlie oscillatory intercellular calcium waves in some cell types, and thus it is important to understand how they occur and are modified by intercellular coupling. Using a previous model of intracellular calcium oscillations in pancreatic acinar cells, this article explores the effects of coupling two cells with a simple linear diffusion term. Depending on the concentration of a signal molecule, inositol ͑1,4,5͒-trisphosphate, coupling two identical cells by diffusion can give rise to synchronized in-phase oscillations, as well as different-amplitude in-phase oscillations and same-amplitude antiphase oscillations. Coupling two nonidentical cells leads to more complex behaviors such as cascades of period doubling and multiply periodic solutions. This study is a first step towards understanding the role and significance of the diffusion of calcium through gap junctions in the coordination of oscillatory calcium waves in a variety of cell types.

Biophysical Journal, 2004

We have derived a broad, deterministic model of the steady-state actin cycle that includes its ma... more We have derived a broad, deterministic model of the steady-state actin cycle that includes its major regulatory mechanisms. Ours is the first model to solve the complete nucleotide profile within filaments, a feature that determines the dynamics and geometry of actin networks at the leading edges of motile cells, and one that has challenged investigators developing models to interpret steady-state experiments. We arrived at the nucleotide profile through analytic and numerical approaches that completely agree. Our model reproduces behaviors seen in numerous experiments with purified proteins, but allows a detailed inspection of the concentrations and fluxes that might exist in these experiments. These inspections provide new insight into the mechanisms that determine the rate of actin filament treadmilling. Specifically, we find that mechanisms for enhancing Pi release from the ADPÁPi intermediate on filaments, for increasing the off rate of ADP-bound subunits at pointed ends, and the multiple, simultaneous functions of profilin, make unique and essential contributions to increased treadmilling. In combination, these mechanisms have a theoretical capacity to increase treadmilling to levels limited only by the amount of available actin. This limitation arises because as the cycle becomes more dynamic, it tends toward the unpolymerized state.

Annals of Biomedical Engineering, 2007

In this report we extend our recent mathematical formulation of the actin cycle model [Bindschadl... more In this report we extend our recent mathematical formulation of the actin cycle model [Bindschadler et al. Biophys. J. 86 (2004) 2720] to predict the influence of key regulatory mechanisms on network-scale state variables estimable in live cell experiments. Specifically, we examine the influence of regulation by cofilin, profilin, capping protein and proteins that adjust filament number through nucleation and/or filament severing, on the higher order variables of average filament length, polymer fraction, and filament turnover rate. Importantly, we find that severing/ nucleation, the acceleration of ADP-subunit disassembly by cofilin, and the catalytic and shuttle functions of profilin have Ôsignature' effects on the higher order state variables. In this way, measurement of the state variables in live cells can allow inference of regulatory mechanism(s) underlying changes in cell state. Our results compare favorably to published data for endothelial cells undergoing a transition from non-motile confluent cells to highly motile subconfluent cells. The extension of our model to higher order state variables allows us to investigate other important issues such as the distinction between basic and higher order measures of filament dynamics, the influence of thymosin b4 on network state variables, the interplay between thymosin b4 and profilin, and the synergystic effects of cofilin and profilin.

Medical Imaging 2014: Image Processing, 2014

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