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Implications of Transvascular Fluid Exchange in Nonlinear, Biphasic Analyses of Flow-Controlled Infusion in Brain

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Abstract

A nonlinear, coupled biphasic-mass transport model that includes transvascular fluid exchange is proposed for flow-controlled infusions in brain tissue. The model accounts for geometric and material nonlinearities, a hydraulic conductivity dependent on deformation, and transvascular fluid exchange according to Starling’s law. The governing equations were implemented in a custom-written code assuming spherical symmetry and using an updated Lagrangian finite-element algorithm. Results of the model indicate that, using normal physiological values of vascular permeability, transvascular fluid exchange has negligible effects on tissue deformation, fluid pressure, and transport of the infused agent. As vascular permeability may be increased artificially through methods such as administering nitric oxide, a parametric study was conducted to determine how increased vascular permeability affects flow-controlled infusion. Increased vascular permeability reduced both tissue deformation and fluid pressure, possibly reducing damage to tissue adjacent to the infusion catheter. Furthermore, the loss of fluid to the vasculature resulted in a significantly increased interstitial fluid concentration but a modestly increased tissue concentration. From a clinical point of view, this increase in concentration could be beneficial if limited to levels below which toxicity would not occur. However, the modestly increased tissue concentration may make the increase in interstitial fluid concentration difficult to assess in vivo using co-infused radiolabeled agents.

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References

  • Almeida, E. S., & Spilker, R. L. (1997). Mixed and penalty finite element models for the nonlinear behavior of biphasic soft tissues in finite deformations: Part I—alternate formulations. Comput. Methods Biomech. Biomed. Eng., 1, 25–46.

    Article  Google Scholar 

  • Barry, S. I., & Aldis, G. K. (1992). Flow-induced deformation from pressurized cavities in absorbing porous tissues. Bull. Math. Biol., 54, 977–997.

    MATH  Google Scholar 

  • Bartus, R. T., Snodgrass, P., Marsh, J., Agostino, M., Perkins, A., & Emerich, D. F. (2000). Intravenous cereport (RMP-7) modifies topographic uptake profile of carboplatin within rat glioma and brain surrounding tumor, elevates platinum levels, and enhance survival. J. Pharmacol. Exp. Ther., 293, 903–911.

    Google Scholar 

  • Basser, P. J. (1992). Interstitial pressure, volume, and flow during infusion into brain tissue. Microvasc. Res., 44, 143–165.

    Article  Google Scholar 

  • Baxter, L. T., & Jain, R. K. (1989). Transport of fluid and macromolecules in tumors I. Role of interstitial pressure and convection. Microvasc. Res., 37, 77–104.

    Article  Google Scholar 

  • Baxter, L. T., & Jain, R. K. (1990). Transport of fluid and macromolecules in tumors II. Role of heterogeneous perfusion and lymphatics. Microvasc. Res., 37, 246–263.

    Article  Google Scholar 

  • Belytschko, T., Liu, W. K., & Moran, B. (2000). Nonlinear finite element for continua and structures. Chichester: Wiley.

    Google Scholar 

  • Bobo, R. H., Laske, D. W., Akbasak, A., Morrison, P. F., Dedrick, R. L., & Oldfield, O. H. (1994). Convection-enhanced delivery of macromolecules in the brain. Proc. Natl. Acad. Sci. USA, 91, 2076–2080.

    Article  Google Scholar 

  • Bruehlmeier, M., Roelcke, U., Blauenstein, P., Missimer, J., Schubiger, P. A., Locher, J. T., Pellikka, R., & Ametamey, S. M. (2003). Measurement of the extracellular space in brain tumors using 76Br-bromide and PET. J. Nucl. Med., 44, 1210–1218.

    Google Scholar 

  • Chen, X., & Sarntinoranont, M. (2007). Biphasic finite element model of solute transport for direction infusion into nervous tissue. Ann. Biomed. Eng., 35, 2145–2158.

    Article  Google Scholar 

  • Chen, Z.-J., Broaddus, W. C., Viswanathan, R. R., Raghavan, R., & Gillies, G. T. (2002). Intraparenchymal drug delivery via positive-pressure infusion: experimental and modeling studies of poroelasticity in brain phantom gels. IEEE Trans. Biomed. Eng., 49, 85–96.

    Article  Google Scholar 

  • Chen, Z.-J., Gillies, G. T., Broaddus, W. C., Prabhu, S. S., Fillmore, H., Mitchell, R. M., Corwin, F. D., & Fatouros, P. P. (2004). A realistic brain tissue phantom for intraparenchymal infusion studies. J. Neurosurg., 101, 314–322.

    Article  Google Scholar 

  • Chen, X., Astary, G. W., Sepulveda, H., Mareci, T. H., & Sarntinoranont, M. (2008). Quantitative assessment of macromolecular concentration during direct infusion into an agarose hydrogel phantom using contrast-enhanced MRI. J. Magn. Reson. Imaging, 26, 1433–1441.

    Article  Google Scholar 

  • Cheng, S., & Bilston, L. E. (2007). Unconfined compression of white matter. J. Biomech., 40, 117–124.

    Article  Google Scholar 

  • Franceschini, G., Bigoni, D., Regitnig, P., & Holzapfel, G. A. (2006). Brain tissue deforms similarly to filled elastomers and follows consolidation theory. J. Mech. Phys. Solids, 54, 2592–2620.

    Article  MATH  Google Scholar 

  • García, J. J., & Smith, J. H. (2009). A biphasic hyperelastic model for the analysis of fluid and mass transport in brain tissue. Ann. Biomed. Eng., 37, 375–386.

    Article  Google Scholar 

  • García, J. J., & Smith, J. H. (2010). A biphasic hyperelastic model for hydrocephalus. Lat. Am. Appl. Res., 40, 295–302.

    Google Scholar 

  • Ivanchenko, O., & Ivanchenko, V. (2011). Designing and testing of backflow-free catheters. J. Biomech. Eng., 133, 061003.

    Article  Google Scholar 

  • Ivanchenko, O., Sindhwani, N., & Linninger, A. (2010). Experimental techniques for studying poroelasticity in brain phantom gels under high flow microinfusion. J. Biomech. Eng., 132, 051008.

    Article  Google Scholar 

  • Jain, R. K. (1987). Transport of molecules across tumor vasculature. Cancer Metastasis Rev., 6, 559–593.

    Article  Google Scholar 

  • Kim, J. H., Astary, G. W., Chen, X., Mareci, T. H., & Sarntinoranont, M. (2009). Voxelized model of interstitial transport in the rat spinal cord following direct infusion into white matter. J. Biomech. Eng., 131, 071007.

    Article  Google Scholar 

  • Kim, J. H., Mareci, T. H., & Sarntinoranont, M. (2010). A voxelized model of direct infusion into the corpus callosum and hippocampus of the rat brain: Model development and parameter analysis. Med. Biol. Eng. Comput., 48, 203–214.

    Article  Google Scholar 

  • Kimura, M., Dietrich, H. H., Huxley, V. H., Reichner, D. R., & Dacey, R. G., Jr. (1993). Measurement of hydraulic conductivity in isolated arterioles of rat brain cortex. Am. J. Physiol., 264, H1788–H1797.

    Google Scholar 

  • Kunwar, S., Chang, S. M., Prados, M. D., Berger, M. S., Sampson, J. H., Croteau, D., Sherman, J. W., Grahn, A. Y., Shu, V. S., Dul, J. L., Husain, S. R., Joshi, B. H., Pedain, C., & Puri, R. K. (2006). Safety of intraparenchymal convection-enhanced delivery of cintredekin besudotox in early-phase studies. Neurosurg. Focus, 20, E15.

    Google Scholar 

  • Kunwar, S., Prados, M. D., Chang, S. M., Berger, M. S., Lang, F. F., Piepmeier, J. M., Sampson, J. H., Ram, Z., Gutin, P. H., Gibbons, R. D., Aldape, K. D., Croteau, D. J., Sherman, J. W., & Puri, R. K. (2007). Direct intracerebral delivery of cintredekin besudotox (IL13-PE38QQR) in recurrent malignant glioma: a report by the cintredekin besudotox intraparenchymal study group. J. Clin. Oncol., 25, 837–844.

    Article  Google Scholar 

  • Lee, S. J., Pishko, G. L., Astary, G. W., Mareci, T. H., & Sarntinoranont, M. (2009). Characterization of an anisotropic hydrogel tissue substrate for infusion testing. J. Appl. Polym. Sci., 114, 1992–2002.

    Article  Google Scholar 

  • Lieberman, D. M., Laske, D. W., Morrison, P. F., Bankiewicz, K. S., & Oldfield, E. H. (1995). Convection-enhanced distribution of large molecules in gray matter during interstitial drug infusion. J. Neurosurg., 82, 1021–1029.

    Article  Google Scholar 

  • Lidar, Z., Mardor, Y., Jonas, T., Pfeffer, R., Faibel, M., Nass, D., Hadani, M., & Ram, Z. (2004). Convection-enhanced delivery of paclitaxel for the study of treatment of recurrent malignant glioma: a Phase I/II clinical study. J. Neurosurg., 100, 472–479.

    Article  Google Scholar 

  • Linninger, A. A., Somayaji, M. R., Erickson, T., Guo, X., & Penn, R. D. (2008a). Computational methods for predicting drug transport in anisotropic and heterogeneous brain tissue. J. Biomech., 41, 2176–2187.

    Article  Google Scholar 

  • Linninger, A. A., Somayaji, M. R., Mekarski, M., & Zhang, L. (2008b). Prediction of convection-enhanced drug delivery to the human brain. J. Theor. Biol., 250, 125–138.

    Article  Google Scholar 

  • Linninger, A. A., Somayaji, M. R., Zhang, L., Hariharan, M. S., & Penn, R. D. (2008c). Rigorous mathematical modeling techniques for optimal delivery of macromolecules to the brain. IEEE Trans. Biomed. Eng., 55, 2303–2313.

    Article  Google Scholar 

  • Miller, K., & Chinzei, K. (1997). Constitutive modelling of brain tissue: experiment and theory. J. Biomech., 30, 1115–1121.

    Article  Google Scholar 

  • Miller, K., & Chinzei, K. (2002). Mechanical properties of brain tissue in tension. J. Biomech., 35, 483–490.

    Article  Google Scholar 

  • Morrison, P. F., Laske, D. W., Bobo, H., Oldfield, E. H., & Dedrick, R. L. (1994). High-flow microinfusion: tissue penetration and pharmacodynamics. Am. J. Physiol., 266, R292–R305.

    Google Scholar 

  • Netti, P. A., Baxter, L. T., Boucher, Y., Skalak, R., & Jain, R. K. (1997). Macro- and microscopic fluid transport in living tissues: application to solid Tumors. AIChE J., 43, 818–834.

    Article  Google Scholar 

  • Netti, P. A., Travascio, F., & Jain, R. K. (2003). Coupled macromolecular transport and gel mechanics: poroviscoelastic approach. AIChE J., 49, 1580–1596.

    Article  Google Scholar 

  • Ogden, R. W. (1984). Non-linear elastic deformations. Mineola: Dover.

    Google Scholar 

  • Paulson, O. B., Hertz, M. M., Bolwig, T. G., & Lassen, N. A. (1977). Filtration and diffusion of water across the blood–brain barrier. Microvasc. Res., 13, 113–124.

    Article  Google Scholar 

  • Pishko, G. L., Astary, G. W., Mareci, T. H., & Sarntinoranont, M. (2011). Sensitivity analysis of an image-based solid tumor computational model with heterogeneous vasculature and porosity. Ann. Biomed. Eng., 39, 2360–2373. doi:10.1007/s10439-011-0349-7.

    Article  Google Scholar 

  • Prabhu, S. S., Broaddus, W. C., Gillies, G. T., Loudon, W. G., Chen, Z.-J., & Smith, B. (1998). Distribution of macromolecular dyes in brain using positive pressure infusion: a model for direct controlled delivery of therapeutic agents. Surg. Neurol., 50, 367–375.

    Article  Google Scholar 

  • Prados, M. D., Schold, S. C., Jr., Fine, H. A., Jaeckle, K., Hochberg, F., Mechtler, L., Fetell, M. R., Phuphanich, S., Feun, L., Janus, T. J., Ford, K., & Graney, W. (2003). A randomized, double-blind, placebo-controlled, phase 2 study of RMP-7 in combination with carboplatin administered intravenously for the treatment of recurrent malignant glioma. Neuro-Oncology, 5, 96–103.

    Google Scholar 

  • Sampson, J. H., Brady, M. L., Petry, N. A., Croteau, D., Friedman, A. H., Friedman, H. S., Wong, T., Bigner, D. D., Pastan, I., Puri, R. K., & Pedain, C. (2007a). Intracerebral infusate distribution by convection-enhanced delivery in humans with malignant gliomas: descriptive effects of target anatomy and catheter positioning. Neurosurgery, 60, ONS-89–ONS-99.

    Article  Google Scholar 

  • Sampson, J. H., Raghavan, R., Brady, M. L., Provenzale, J. M., Herndon, J. E., II, Croteau, D., Friedman, A. H., Reardon, D. A., Coleman, R. E., Wong, T., Bigner, D. D., Pastan, I., Rodríguez-Ponce, M. I., Tanner, P., Puri, R., & Pedain, C. (2007b). Clinical utility of a patient-specific algorithm for simulating intracerebral drug infusions. Neuro-Oncology, 9, 343–353.

    Article  Google Scholar 

  • Sampson, J. H., Raghavan, R., Provenzale, J. M., Croteau, D., Reardon, D. A., Coleman, R. E., Rodríguez Ponce, I., Pastan, I., Puri, R. K., & Pedain, C. (2007c). Induction of hyperintense signal on T2-weighted MR images correlates with infusion distribution from intracerebral convection-enhanced delivery of a tumor-targeted cytotoxin. Am. J. Rentgenol., 188, 703–709.

    Article  Google Scholar 

  • Sampson, J. H., Archer, G., Pedain, C., Wembacher-Schröder, E., Westphal, M., Kunwar, S., Vogelbaum, M. A., Coan, A., Herndon, J. E., II, Raghavan, R., Brady, M. L., Reardon, D. A., Friedman, A. H., Friedman, H. S., Rodríguez-Ponce, M. I., Chang, S. M., Mittermeyer, S., Croteau, D., & Puri, R. K. (2010). Poor drug distribution as a possible explanation for the results of the PRECISE trial. J. Neurosurg., 113, 301–309.

    Article  Google Scholar 

  • Sarntinoranont, M., Banerjee, R. K., Lonser, R. R., & Morrison, P. F. (2003). A computational model of direct interstitial infusion of macromolecules into the spinal cord. Ann. Biomed. Eng., 31, 448–461.

    Article  Google Scholar 

  • Sarntinoranont, M., Chen, X., Zhao, J., & Mareci, T. H. (2006). Computational model of interstitial transport in the spinal cord using diffusion tensor imaging. Ann. Biomed. Eng., 34, 1304–1321.

    Article  Google Scholar 

  • Sevick, E. M., & Jain, R. K. (1991). Measurement of capillary filtration coefficient in a solid tumor. Cancer Res., 51, 1352–1355.

    Google Scholar 

  • Smith, J. H., & García, J. J. (2009). A nonlinear biphasic model of flow-controlled infusion in brain: fluid transport and tissue deformation analyses. J. Biomech., 42, 2017–2025.

    Article  Google Scholar 

  • Smith, J. H., & García, J. J. (2011). A nonlinear biphasic model of flow-controlled infusion in brain: mass transport analyses. J. Biomech., 44, 524–531.

    Article  Google Scholar 

  • Smith, J. H., & Humphrey, J. A. C. (2007). Interstitial transport and transvascular fluid exchange during infusion into brain and tumor tissue. Microvasc. Res., 73, 58–73.

    Article  Google Scholar 

  • Sobey, I., & Wirth, B. (2006). Effect of non-linear permeability in a spherically symmetric model of hydrocephalus. Math. Med. Biol., 23, 339–361.

    Article  MATH  Google Scholar 

  • Starling, E. H. (1896). On the absorption of fluids from the connective tissue spaces. J. Physiol., 19, 312–326.

    Google Scholar 

  • Truskey, G. A., Yuan, F., & Katz, D. F. (2004). Transport phenomena in biological systems. Upper Saddle River: Pearson Prentice Hall.

    Google Scholar 

  • Varenika, V., Dickinson, P., Bringas, J., LeCouteur, R., Higgins, R., Park, J., Fiandaca, M., Berger, M., Sampson, J., & Bankiewicz, K. (2008). Detection of infusate leakage in the brain using real-time imaging of convection-enhanced delivery. J. Neurosurg., 109, 874–880.

    Article  Google Scholar 

  • Weyerbrock, A., Walbridge, S., Saavedra, J. E., Keefer, L. K., & Oldfield, E. H. (2011). Differential effects of nitric oxide on blood-brain barrier integrity and cerebral blood flow in intracerebral C6 gliomas. Neuro-Oncology, 13, 203–211.

    Article  Google Scholar 

  • Zhao, J., Salmon, H., & Sarntinoranont, M. (2007). Effect of heterogeneous vasculature on interstitial transport within a solid tumor. Microvasc. Res., 73, 224–236.

    Article  Google Scholar 

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Smith, J.H., Starkweather, K.A. & García, J.J. Implications of Transvascular Fluid Exchange in Nonlinear, Biphasic Analyses of Flow-Controlled Infusion in Brain. Bull Math Biol 74, 881–907 (2012). https://doi.org/10.1007/s11538-011-9696-7

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  • DOI: https://doi.org/10.1007/s11538-011-9696-7

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