Research Interests
• Structural and statistical modeling of biological systems;
• Pharmacokinetics and pharmacodynamics;
• Glucose and insulin metabolism
• Parameter estimation and input reconstruction methods
Contact Information
Department of Bioengineering
University of Washington
Box 355061
William H. Foege Building, Room N410G
Seattle, WA 98195-2255
Phone: 206-616-1133
Fax: 206-543-3081
E-mail: vicini@u.washington.edu
Web Site: http://depts.washington.edu/rfpk
Research Description
The research conducted in our group, the Resource Facility for Population Kinetics, has two important components:
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Mathematical models of biological systems. The concentration in blood of hormones, drugs, and toxic substances is the result of many processes, like secretion, distribution, and utilization. The measurement in the intact organism of these fluxes is important to understand physiological systems and allow early failure detection of critical regulatory mechanisms. However, an indirect measurement approach is necessary in vivo. Dynamic data must be generated by a suitable experiment design and interpreted with an appropriate model of the system ("kinetic model"). Both the choices of the experimental design and the mathematical model are of utmost importance. Paradigms in this field are the modalities of local distribution and metabolism of substrates at organ level, the disposition of toxicants in the body and the distribution and effect of drugs (pharmacokinetics and pharmacodynamics). We are applying state-of-the-art techniques of parameter estimation and input reconstruction to enhance our understanding of several biological systems, such as glucose-insulin interaction in normal and disease states, the distribution and metabolism of glucose in skeletal muscle, workplace assessment of exposure to toxicants, various drug biodistribution and efficacy.
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Population kinetic analysis. Reliably determining the distribution of the parameters that describe the kinetics of substrates in a population is a major advance in understanding their behavior, with impact on both clinical and pharmacological applications. A major obstacle has been handling all the sources of uncertainty (between-individual and within-individual) in the mathematical modeling of a population of subjects. Population kinetics can be defined as the discipline that models these sources of variability, based on a collection of individual data (the population data). We are trying to develop approaches to population kinetic analysis and apply them to metabolic, pharmacological and toxicokinetic studies.
Teaching Activities
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BIOEN 303: Bioengineering Signal Processing
Introduction of signal processing techniques necessary to record and analyze medical and biological data. Students use transform calculus to analyze differential equations and develop approximations to functions. Introduces sampling and applies it to biological data. Prerequisite: BIOEN 302.
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BIOEN 485: Computational Bioengineering
Introduction to computational, mathematical, and statistical approaches to the analysis of biological systems, including systems and control theory, molecular models and bioinformatics. Lectures and laboratory sessions emphasize practical problems in kinetics, metabolism, and genomics. Prerequisite: CSE 143; BIOEN 305; MATH 308.
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BIOEN 540: Biosystem Identification
Fundamentals of mathematical modeling in medicine and biology. Introduction to compartmental models: a priori and a postpriori identifiability. Data measurement error and parameter estimation. Maximum likelihood and least squares. Introduction to tracer-tracee models, pharmacokinetics, and pharmacodynamics. Use of models to test hypotheses. Hands-on computer experience. Prerequisite: consent of instructor.
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BIOEN 584: Computational and Integrative Bioengineering
Advanced computational, mathematical, and statistical approaches to the analysis of biological systems, including molecular models, time series, fractal systems, population kinetic analysis, and stochastic simulation. Lectures and laboratory sessions emphasize practical problems in kinetic analysis, metabolism, and genomics. Final project, written and oral reports. Prerequisite: BIOEN 485.
- BIOEN 599M: Bioengineering Statistics
Application of quantitative and inferential tools to the analysis of
biological and biomedical data. Fundamentals of probability. The Central
Limit Theorem. Estimators: sample mean, sample variance. Hypothesis testing.
Least squares and maximum likelihood. Covariance and correlation. Linear and
nonlinear regression. One-way and two-way analysis of variance. Model
selection principles. Introduction to Bayesian statistics. Maximum a
posteriori estimation. Monte Carlo Markov Chain. Linear and nonlinear mixed
effects models.
Honors, Awards, and Society Activities
- 1994: IFAC Student Award, Symposium on Modeling and Control in Biomedical Systems
- 1996: Open Competition Finalist, Whitaker Foundation and Engineering in Medicine and Biology Society of the IEEE Student Paper Competition, IEEE/EMBS Conference
- 1996: Prize "Friends of the University of Padova Bressanone-Brixen" for the best Bioengineering PhD dissertation. Given during the IVI Convegno-Scuola del Gruppo Nazionale di Bioingegneria del CNR, Bressanone, Italy, 1997.
- 2003: IEEE/EMBS Early Career Achievement Award for innovative developments in the theory and application of engineering software design, modeling, and simulation methods to an extensive array of relevant problems in modern biomedical research.
Selected Publications
- P Vicini, A Caumo, and C Cobelli, "Glucose effectiveness and insulin sensitivity from the single compartment minimal models of glucose disappearance: Consequences of undermodeling assessed by Monte Carlo simulation", IEEE Trans. Biomed. Eng. 46: 130-137, 1999.
- P Vicini, JJ Zachwieja, K Yarasheski, DM Bier, A Caumo, C Cobelli, "Glucose production during an IVGTT by deconvolution: validation with the tracer-to-tracee clamp technique", Am. J. Physiol. 276: E285-E294, 1999.
- T Konrad, P Vicini, K Kusterer, A Höflich, A Assadkhani, HJ Bohles, A Sewell, HJ Tritschler, C Cobelli, KH Usadel, "a-lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with type 2 diabetes", Diabetes Care 22: 280-287, 1999.
- P Vicini, C Cobelli, "A priori identifiability of distributed models of blood-tissue exchange", Ann. Biomed. Eng. 27: 200-207, 1999.
- P Vicini, CH Pierce, RL Dills, MS Morgan and DA Kalman, "Individual prior information in a physiological model of 2H8-toluene kinetics: an empirical Bayes estimation strategy", Risk Analysis 19: 1127-1134, 1999.
- P Vicini and MJ Kushmerick, "Analysis of cellular energetics by a mathematical model of biochemical energy balance: parametric identification in human skeletal muscle", American Journal of Physiology 279: C213-C224, 2000.
- RP Hoffman, P Vicini, WI Sivitz, and C Cobelli, "Pubertal adolescent male-female differences in insulin sensitivity and glucose effectiveness determined by the one compartment minimal model", Pediatric Research 48: 384-388, 2000.
- P Vicini, H-T Su and JJ DiStefano, III, "Identifiability and interval identifiability of mammillary and catenary compartmental models with some known rate constants", Mathematical Biosciences 167: 145-161, 2000.
- P Vicini and C Cobelli, "The iterative two-stage population approach to IVGTT minimal modeling: improved precision with reduced sampling", American Journal of Physiology 280: E179-E186, 2001.
- S Rashid, KD Uffelman, PH Barrett, P Vicini, K Adeli, and GF Lewis, "Triglyceride enrichment of HDL does not alter HDL-selective cholesteryl ester clearance in rabbits", Journal of Lipid Research 42: 265-271, 2001.
- Vicini P, Gastonguay MR, Foster DM, "Model-based approaches to biomarker discovery and evaluation: a multidisciplinary integrated review", Crit RevBiomed Eng 30: 379-418, 2002.
- Hooker AC, Foracchia M, Dodds MG, Vicini P, "An evaluation of population D-optimal designs via pharmacokinetic simulations", Ann Biomed Eng 31:98-111, 2003.
- Kerwin W, Hooker A, Spilker M, Vicini P, Ferguson M, Hatsukami T, Yuan C, "Quantitative magnetic resonance imaging analysis of neovasculature volume in carotid atherosclerotic plaque", Circulation 18;107:851-856, 2003.
- Osterberg O, Erichsen L, Ingwersen SH, Plum A, Poulsen HE, Vicini P, "Pharmacokinetic and pharmacodynamic properties of insulin aspart and human insulin", J Pharmacokinet Pharmacodyn 30: 221-235, 2003.
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