Scholarly Works, School of Biomedical Engineering and Sciences

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https://hdl.handle.net/10919/23275

Research articles, presentations, and other scholarship

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Heat transfer model to characterize the focal cooling necessary to suppress spontaneous epileptiform activity
Guerra, Reynaldo G.; Davalos, Rafael V.; Garcia, Paulo A.; Rubinsky, Boris; Berger, Mitchel (SPIE, 2005-04-14)
Epilepsy is characterized by paroxysmal transient disturbances of the electrical activity of the brain. Symptoms are manifested as impairment of motor, sensory, or psychic function with or without loss of consciousness or convulsive seizures. This paper presents an initial post-operative heat transfer analysis of surgery performed on a 41 year-old man with medically intractable Epilepsy. The surgery involved tumor removal and the resection of adjacent epileptogenic tissue. Electrocorticography was performed before resection. Cold saline was applied to the resulting interictal spike foci resulting in transient, complete cessation of spiking. A transient one dimensional semi-infinite finite element model of the surface of the brain was developed to simulate the surgery. An approximate temperature distribution of the perfused brain was developed by applying the bioheat equation. The model quantifies the surface heat flux reached in achieving seizure cessation to within an order of magnitude. Rat models have previously shown that the brain surface temperature range to rapidly terminate epileptogenic activity is 20-24°C. The developed model predicts that a constant heat flux of approximately -13,000W/m², applied at the surface of the human brain, would achieve a surface temperature in this range in approximately 3 seconds. A parametric study was subsequently performed to characterize the effects of brain metabolism and brain blood perfusion as a function of the determined heat flux. The results of these findings can be used as a first approximation in defining the specifications of a cooling device to suppress seizures in human models.
Effects of receptor clustering on ligand dissociation kinetics: Theory and simulations
Gopalakrishnan, Mahima; Forsten-Williams, Kimberly; Nugent, Matthew A.; Täuber, Uwe C. (Cell Press, 2005-12-01)
Receptor-ligand binding is a critical first step in signal transduction and the duration of the interaction can impact signal generation. In mammalian cells, clustering of receptors may be facilitated by heterogeneous zones of lipids, known as lipid rafts. In vitro experiments show that disruption of rafts significantly alters the dissociation of fibrbroblast growth factor-2 (FGF2) from heparan sulfate proteoglycans (HSPGs), co-receptors for FGF-2. In this article, we develop a continuum stochastic formalism to address how receptor clustering might influence ligand rebinding. We find that clusters reduce the effective dissociation rate dramatically when the clusters are dense and the overall surface density of receptors is low. The effect is much less pronounced in the case of high receptor density and shows nonmonotonic behavior with time. These predictions are verified via lattice Monte Carlo simulations. Comparison with FGF-2-HSPG experimental results is made and suggests that the theory could be used to analyze similar biological systems. We further present an analysis of an additional cooperative internal-diffusion model that might be used by other systems to increase ligand retention when simple rebinding is insufficient.
Mathematical Study and Numerical Simulation of Multispectral Bioluminescence Tomography
Han, Weimin; Cong, Wenxiang; Wang, Ge (Hindawi, 2006-12-12)
Multispectral bioluminescence tomography (BLT) attracts increasinglymore attention in the area of optical molecular imaging. In this paper, we analyzethe properties of the solutions to the regularized and discretized multispectralBLT problems. First, we show the solution existence, uniqueness, and itscontinuous dependence on the data. Then, we introduce stable numerical schemes andderive error estimates for numerical solutions. We report some numerical resultsto illustrate the performance of the numerical methods on the quality of multispectralBLT reconstruction.
Canine Cancer Screening Via Ultraviolet Absorbance And Fluorescence Spectroscopy Of Serum Proteins
Dickerson, Bryan Douglas; Geist, Brian L.; Spillman, William B. Jr.; Robertson, John L. (Optical Society of America, 2007-01-01)
A cost-effective optical cancer screening and monitoring technique was demonstrated in a pilot study of canine serum samples and was patented for commercialization. Compared to conventional blood chemistry analysis methods, more accurate estimations of the concentrations of albumin, globulins, and hemoglobin in serum were obtained by fitting the near UV absorbance and photoluminescence spectra of diluted serum as a linear combination of component reference spectra. Tracking these serum proteins over the course of treatment helped to monitor patient immune response to carcinoma and therapy. For cancer screening, 70% of dogs with clinical presentation of cancer displayed suppressed serum hemoglobin levels (below 20 mg/dL) in combination with atypical serum protein compositions, that is, albumin levels outside of a safe range (from 4 to 8 g/dL) and globulin levels above or below a more normal range (from 1.7 to 3.7 g/dL). Of the dogs that met these criteria, only 20% were given a false positive label by this cancer screening test. (C) 2007 Optical Society of America.
A General Local Reconstruction Approach Based on a Truncated Hilbert Transform
Ye, Yangbo; Yu, Hengyong; Wei, Yuchuan; Wang, Ge (Hindawi, 2007-06-17)
Exact image reconstruction from limited projection data has been a central topic in the computed tomography (CT) field. In this paper, we present a general region-of-interest/volume-of-interest (ROI/VOI) reconstruction approach using a truly truncated Hilbert transform on a line-segment inside a compactly supported object aided by partial knowledge on one or both neighboring intervals of that segment. Our approach and associated new data sufficient condition allows the most flexible ROI/VOI image reconstruction from the minimum account of data in both the fan-beam and cone-beam geometry. We also report primary numerical simulation results to demonstrate the correctness and merits of our finding. Our work has major theoretical potentials and innovative practical applications.
A Fast CT Reconstruction Scheme for a General Multi-Core PC
Zeng, Kai; Bai, Erwei; Wang, Ge (Hindawi, 2007-07-04)
Expensive computational cost is a severe limitation in CT reconstruction for clinical applications that need real-time feedback. A primary example is bolus-chasing computed tomography (CT) angiography (BCA) that we have been developing for the past several years. To accelerate the reconstruction process using the filtered backprojection (FBP) method, specialized hardware or graphics cards can be used. However, specialized hardware is expensive and not flexible. The graphics processing unit (GPU) in a current graphic card can only reconstruct images in a reduced precision and is not easy to program. In this paper, an acceleration scheme is proposed based on a multi-core PC. In the proposed scheme, several techniques are integrated, including utilization of geometric symmetry, optimization of data structures, single-instruction multiple-data (SIMD) processing, multithreaded computation, and an Intel C++ compilier. Our scheme maintains the original precision and involves no data exchange between the GPU and CPU. The merits of our scheme are demonstrated in numerical experiments against the traditional implementation. Our scheme achieves a speedup of about 40, which can be further improved by several folds using the latest quad-core processors.
Mathematical Modeling of Irreversible Electroporation for Treatment Planning
Edd, Jon F.; Davalos, Rafael V. (Sage, 2007-08)
Irreversible Electroporation (IRE) is a new drug-free method to ablate undesirable tissue of particular use in cancer therapy. IRE achieves cell death within the targeted tissue through a series of electric pulses that elevate the transmembrane potentials to an extent that permanently damages the lipid bilayers throughout the treated region. Although the IRE procedure is easy to perform, treatment planning is complicated by the fact that the electric field distribution within the tissue, the greatest single factor controlling the extents of IRE, depends non-trivially on the electrode configuration, pulse parameters and any tissue heterogeneities. To address this difficulty, we instruct on how to properly model IRE and discuss the benefit of modeling in designing treatment protocols. The necessary theoretical basis is introduced and discussed through the detailed analysis of two classic dual-electrode configurations from electrochemotherapy: coaxial disk electrodes and parallel needle electrodes. Dimensionless figures for these cases are also provided that allow cell constants, treated areas, and the details of heating to be determined for a wide range of conditions, for uniform tissues, simply by plugging in the appropriate physical property values and pulse parameters such as electrode spacing, size, and pulse amplitude. Complexities, such as heterogeneous tissues and changes in conductivity due to electroporation, are also discussed. The synthesis of these details can be used directly by surgeons in treatment planning. Irreversible electroporation is a promising new technique to treat cancer in a targeted manner without the use of drugs; however, it does require a detailed understanding of how electric currents flow within biological tissues. By providing the understanding and tools necessary to design an IRE protocol, this study seeks to facilitate the translation of this new and exciting cancer therapy into clinical practice.
A General Formula for Fan-Beam Lambda Tomography
Yu, Hengyong; Wang, Ge (Hindawi, 2007-08-23)
Improving the Accuracy of the Diffusion Model in Highly Absorbing Media
Cong, Alexander X.; Shen, Haiou; Cong, Wenxiang; Wang, Ge (Hindawi, 2007-08-29)
The diffusion approximation of the Boltzmann transport equation is most commonly used for describing the photon propagation in turbid media. It produces satisfactory results in weakly absorbing and highly scattering media, but the accuracy lessens with the decreasing albedo. In this paper, we presented a method to improve the accuracy of the diffusion model in strongly absorbing media by adjusting the optical parameters. Genetic algorithm-based optimization tool is used to find the optimal optical parameters. The diffusion model behaves more closely to the physical model with the actual optical parameters substituted by the optimized optical parameters. The effectiveness of the proposed technique was demonstrated by the numerical experiments using the Monte Carlosimulation data as measurements.
Image Reconstruction For Bioluminescence Tomography From Partial Measurement
Jiang, Ming; Zhou, Tie; Cheng, Jiantao; Cong, Wenxiang; Wang, Ge (Optical Society of America, 2007-09-01)
The bioluminescence tomography is a novel molecular imaging technology for small animal studies. Known reconstruction methods require the completely measured data on the external surface, although only partially measured data is available in practice. In this work, we formulate a mathematical model for BLT from partial data and generalize our previous results on the solution uniqueness to the partial data case. Then we extend two of our reconstruction methods for BLT to this case. The first method is a variant of the well-known EM algorithm. The second one is based on the Landweber scheme. Both methods allow the incorporation of knowledge-based constraints. Two practical constraints, the source non-negativity and support constraints, are introduced to regularize the BLT problem and produce stability. The initial choice of both methods and its influence on the regularization and stability are also discussed. The proposed algorithms are evaluated and validated with intensive numerical simulation and a physical phantom experiment. Quantitative results including the location and source power accuracy are reported. Various algorithmic issues are investigated, especially how to avoid the inverse crime in numerical simulations. (c) 2007 Optical Society of America.
Experimental Study on Bioluminescence Tomography with Multimodality Fusion
Lv, Yujie; Tian, Jie; Cong, Wenxiang; Wang, Ge (Hindawi, 2007-09-10)
To verify the influence of a priori information on the nonuniqueness problem of bioluminescence tomography (BLT), the multimodality imaging fusion based BLT experiment is performed by multiview noncontact detection mode, which incorporates the anatomical information obtained by the microCT scanner and the background optical properties based on diffuse reflectance measurements. In the reconstruction procedure, the utilization of adaptive finite element methods (FEMs) and a priori permissible source region refines the reconstructed results and improves numerical robustness and efficiency. The comparison between the absence and employment of a priori information shows that multimodality imaging fusion is essential to quantitative BLT reconstruction.
Tumor Ablation with Irreversible Electroporation
Al-Sakere, Bassim; Andre, Franck; Bernat, Claire; Connault, Elisabeth; Opolon, Paule; Davalos, Rafael V.; Rubinsky, Boris; Mir, Lluis M. (PLOS, 2007-11-07)
We report the first successful use of irreversible electroporation for the minimally invasive treatment of aggressive cutaneous tumors implanted in mice. Irreversible electroporation is a newly developed non-thermal tissue ablation technique in which certain short duration electrical fields are used to permanently permeabilize the cell membrane, presumably through the formation of nanoscale defects in the cell membrane. Mathematical models of the electrical and thermal fields that develop during the application of the pulses were used to design an efficient treatment protocol with minimal heating of the tissue. Tumor regression was confirmed by histological studies which also revealed that it occurred as a direct result of irreversible cell membrane permeabilization. Parametric studies show that the successful outcome of the procedure is related to the applied electric field strength, the total pulse duration as well as the temporal mode of delivery of the pulses. Our best results were obtained using plate electrodes to deliver across the tumor 80 pulses of 100 µs at 0.3 Hz with an electrical field magnitude of 2500 V/cm. These conditions induced complete regression in 12 out of 13 treated tumors, (92%), in the absence of tissue heating. Irreversible electroporation is thus a new effective modality for non-thermal tumor ablation.
Digital Spectral Separation Methods And Systems For Bioluminescence Imaging
Wang, Ge; Shen, Haiou; Liu, Y.; Cong, A.; Cong, W. X.; Wang, Y.; Dubey, P. (Optical Society of America, 2008-01-01)
We propose a digital spectral separation (DSS) system and methods to extract spectral information optimally from a weak multispectral signal such as in the bioluminescent imaging (BLI) studies. This system utilizes our newly invented spatially-translated spectral-image mixer (SSM), which consists of dichroic beam splitters, a mirror, and a DSS algorithm. The DSS approach overcomes the shortcomings of the data acquisition scheme used for the current BLI systems. Primarily, using our DSS scheme, spectral information will not be filtered out. Accordingly, truly parallel multi-spectral multi-view acquisition is enabled for the first time to minimize experimental time and optimize data quality. This approach also permits recovery of the bioluminescent signal time course, which is useful to study the kinetics of multiple bioluminescent probes using multi-spectral bioluminescence tomography (MSBT).
Exact Interior Reconstruction with Cone-Beam CT
Ye, Yangbo; Yu, Hengyong; Wang, Ge (Hindawi, 2008-01-23)
Using the backprojection filtration (BPF) and filtered backprojection (FBP) approaches, respectively, we prove that with cone-beam CT the interior problem can be exactly solved by analytic continuation. The prior knowledge we assume is that a volume of interest (VOI) in an object to be reconstructed is known in a subregion of the VOI. Our derivations are based on the so-called generalized PI-segment (chord). The available projection onto convex set (POCS) algorithm and singular value decomposition (SVD) method can be applied to perform the exact interior reconstruction. These results have many implications in the CT field and can be extended to other tomographic modalities, such as SPECT/PET, MRI.
Cone-Beam Composite-Circling Scan and Exact Image Reconstruction for a Quasi-Short Object
Yu, Hengyong; Wang, Ge (Hindawi, 2008-02-03)
Here we propose a cone-beam composite-circling mode to solve the quasi-short object problem, which is to reconstruct a short portion of a long object from longitudinally truncated cone-beam data involving the short object. In contrast to the saddle curve cone-beam scanning, the proposed scanning mode requires that the X-ray focal spot undergoes a circular motion in a plane facing the short object, while the X-ray source is rotated in the gantry main plane. Because of the symmetry of the proposed mechanical rotations and the compatibility with the physiological conditions, this new mode has significant advantages over the saddle curve from perspectives of both engineering implementation and clinical applications. As a feasibility study, a backprojection filtration (BPF) algorithm is developed to reconstruct images from data collected along a composite-circling trajectory. The initial simulation results demonstrate the correctness of the proposed exact reconstruction method and the merits of the proposed mode.
X-Ray Phase-Contrast Imaging with Three 2D Gratings
Jiang, Ming; Wyatt, Christopher Lee; Wang, Ge (Hindawi, 2008-03-24)
X-ray imaging is of paramount importance for clinical and preclinical imaging but it is fundamentally restricted by the attenuation-based contrast mechanism, which has remained essentially the same since Roentgen's discovery a century ago. Recently, based on the Talbot effect, groundbreaking work was reported using 1D gratings for X-ray phase-contrast imaging with a hospital-grade X-ray tube instead of a synchrotron or microfocused source. In this paper, we report an extension using 2D gratings that reduces the imaging time and increases the accuracy and robustness of phase retrieval compared to current grating-based phase-contrast techniques. Feasibility is demonstrated via numerical simulation.
Exact Interior Reconstruction from Truncated Limited-Angle Projection Data
Ye, Yangbo; Yu, Hengyong; Wang, Ge (Hindawi, 2008-05-06)
Using filtered backprojection (FBP) and an analytic continuation approach, we prove that exact interior reconstruction is possible and unique from truncated limited-angle projection data, if we assume a prior knowledge on a subregion or subvolume within an object to be reconstructed. Our results show that (i) the interior region-of-interest (ROI) problem and interior volume-of-interest (VOI) problem can be exactly reconstructed from a limited-angle scan of the ROI/VOI and a 180 degree PI-scan of the subregion or subvolume and (ii) the whole object function can be exactly reconstructed from nontruncated projections from a limited-angle scan. These results improve the classical theory of Hamaker et al. (1980).
Digital Eversion of a Hollow Structure: An Application in Virtual Colonography
Zhao, Jun; Cao, Liji; Zhuang, Tiange; Wang, Ge (Hindawi, 2008-07-22)
A new methodology is presented for digital eversion of a hollow structure. The digital eversion is advantageous for better visualization of a larger portion of the inner surface with preservation of geometric relationship and without time-consuming navigation. Together with other techniques, digital eversion may help improve screening, diagnosis, surgical planning, and medical education. Two eversion algorithms are proposed and evaluated in numerical simulation to demonstrate the feasibility of the approach.
In Situ Real-Time Chemiluminescence Imaging of Reactive Oxygen Species Formation from Cardiomyocytes
Li, Yunbo; Shen, Haiou; Zhu, Hong; Trush, Michael A.; Jiang, Ming; Wang, Ge (Hindawi, 2009-02-25)
We have applied the highly sensitive chemiluminescence (CL) imagingtechnique to investigate the in situ ROS formation in cultured monolayers of rat H9c2 cardiomyocytes. Photon emission was detected via an innovative imaging system after incubation of H9c2 cells in culture with luminol and horseradish peroxidase (HRP), suggesting constitutive formation of ROS by the cardiomyocytes. Addition of benzo(a)pyrene-1,6-quinone(BPQ) to cultured H9c2 cells resulted in a 4-5-fold increase in the formation of ROS, as detected by the CL imaging. Both constitutive and BPQ-stimulated CL responses in cultured H9c2 cells were sustained for up to 1 hour. The CL responses were completely abolished in the presence of superoxide dismutase and catalase, suggesting the primary involvement of superoxide and hydrogen peroxide (). In contrast to BPQ-mediated redox cycling, blockage of mitochondrial electron transport chain by either antimycin A or rotenone exerted marginal effects on the ROS formation by cultured H9c2 cells. Upregulation of cellular antioxidants fordetoxifying both superoxide and by 3-1,2-dithiole-3-thione resulted in marked inhibition of both constitutive and BPQ-augmented ROS formation in cultured H9c2 cells. Taken together, we demonstrate the sensitive detection of ROS by CL imaging in cultured cardiomyocytes.
Line-Source Based X-Ray Tomography
Bharkhada, Deepak; Yu, Hengyong; Liu, Hong; Plemmons, Robert; Wang, Ge (Hindawi, 2009-04-27)
Current computed tomography (CT) scanners, including micro-CT scanners, utilize a point x-ray source. As we target higher and higher spatial resolutions, the reduced x-ray focal spot size limits the temporal and contrast resolutions achievable. To overcome this limitation, in this paper we propose to use a line-shaped x-ray source so that many more photons can be generated, given a data acquisition interval. In reference to the simultaneous algebraic reconstruction technique (SART) algorithm for image reconstruction from projection data generated by an x-ray point source, here we develop a generalized SART algorithm for image reconstruction from projection data generated by an x-ray line source. Our numerical simulation results demonstrate the feasibility of our novel line-source based x-ray CT approach and the proposed generalized SART algorithm.

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