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The Effect of Pulsatile Flow on Intrathecal Drug Delivery in the Spinal Canal

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An Erratum to this article was published on 05 August 2011

Abstract

Clinical studies have shown that drugs delivered intrathecally distribute much faster than can be accounted for by pure molecular diffusion. However, drug transport inside the cerebrospinal fluid (CSF)-filled spinal canal is poorly understood. In this study, comprehensive experimental and computational studies were conducted to quantify the effect of pulsatile CSF flow on the accelerated drug dispersion in the spinal canal. Infusion tests with a radionucleotide and fluorescent dye under stagnant and pulsatile flow conditions were conducted inside an experimental surrogate model of the human spinal canal. The tracer distributions were quantified optically and by single photon emission computed tomography (SPECT). The experimental results show that CSF flow oscillations substantially enhance fluorescent dye and radionucleotide dispersion in the spinal canal experiment. The experimental observations were interpreted by rigorous computer simulations. To demonstrate the clinical significance, the dispersion of intrathecally infused baclofen, an anti-spasticity drug, was predicted by using patient-specific spinal data and CSF flow measurements. The computational predictions are expected to enable the rational design of intrathecal drug therapies.

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Acknowledgments

The authors would like to thank Dr. Amjad Ali at the Nuclear Medicine Department, Rush University medical center for facilitating the SPECT nuclear medicine experiments. We also appreciate the useful discussions on baclofen with Dr. R. Penn. Timothy J. Harris Jr. is gratefully indebted to NSF REU program (NSF EEC 0754590, PI A.A. Linninger) for having supported his undergraduate research during the summer of 2010.

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Authors and Affiliations

  1. Laboratory for Product and Process Design (LPPD), Department of Bioengineering, University of Illinois at Chicago, 851 S. Morgan Street, 218 SEO, Chicago, IL, 60607, USA

    H. D. M. Hettiarachchi, Ying Hsu, Timothy J. Harris Jr. & Andreas A. Linninger

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  1. H. D. M. Hettiarachchi
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  2. Ying Hsu
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  3. Timothy J. Harris Jr.
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  4. Andreas A. Linninger
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Correspondence to Andreas A. Linninger.

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Associate Editor Peter E. McHugh oversaw the review of this article.

An erratum to this article can be found at http://dx.doi.org/10.1007/s10439-011-0376-4

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Hettiarachchi, H.D.M., Hsu, Y., Harris, T.J. et al. The Effect of Pulsatile Flow on Intrathecal Drug Delivery in the Spinal Canal. Ann Biomed Eng 39, 2592–2602 (2011). https://doi.org/10.1007/s10439-011-0346-x

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