Reducing Flow Resistance via Introduction and Enlargement of Microcracks in Convection Enhanced Delivery (CED) in Porous Tumors †
<p>Three models generated in this study for simulation. (<b>Left</b>): the first model without a crack; (<b>middle</b>): the second model with a cylindrical microcrack; and (<b>right</b>): the third model with an enlarged microcrack.</p> "> Figure 2
<p>Simulated pressure field (<b>left</b>) and velocity field (<b>right</b>) in the tumor without a microcrack. The inset images are the enlarged pressure and velocity fields near the infusion surface.</p> "> Figure 3
<p>Simulated pressure field (<b>left</b>) and velocity field (<b>right</b>) in the tumor with a cylindrical microcrack. The inset images are the enlarged pressure and velocity fields near the infusion surface and along the microcrack.</p> "> Figure 4
<p>Components of the displacement vector in the lateral (<b>Left</b>) and axial (<b>Right</b>) directions of the microcrack in the tumor with a cylindrical microcrack.</p> "> Figure 5
<p>The original (green dots) interface and post-deformation (red dots) interface of the microcrack and tissue plotted in Excel. A frustum-shaped microcrack is generated using curve fitting.</p> "> Figure 6
<p>Simulated pressure field (<b>left</b>) and velocity field (<b>right</b>) in the tumor with an enlarged frustum microcrack. The inset images are the enlarged pressure and velocity fields near the infusion surface and along the microcrack after deformation.</p> "> Figure 7
<p>The original (blue dots) and post-deformation (orange dots) interfaces between the microcrack and tumor region, as affected by the length of the microcrack.</p> "> Figure 8
<p>The original (blue dots) and post-deformation (orange dots) interfaces between the microcrack and tumor region, as affected by the radius of the original cylindrical microcrack.</p> "> Figure 9
<p>Details of the pressure field near the infusion surface and along the microcrack as influenced by the permeability of the microcrack: (<b>a</b>) <span class="html-italic">Κ</span><sub>2</sub> = 1 × 10<sup>−13</sup> m<sup>2</sup>, (<b>b</b>) <span class="html-italic">Κ</span><sub>2</sub> = 2.0173 × 10<sup>−13</sup> m<sup>2</sup>, and (<b>c</b>) <span class="html-italic">Κ</span><sub>2</sub> = 3 × 10<sup>−13</sup> m<sup>2</sup>.</p> "> Figure 10
<p>The original (blue dots) and post-deformation (orange dots) interfaces between the microcrack and tumor region, as affected by the permeability of the microcrack: (<b>a</b>) <span class="html-italic">Κ</span><sub>2</sub> = 1 × 10<sup>−13</sup> m<sup>2</sup>, (<b>b</b>) <span class="html-italic">Κ</span><sub>2</sub> = 2.0173 × 10<sup>−13</sup> m<sup>2</sup>, and (<b>c</b>) <span class="html-italic">Κ</span><sub>2</sub> = 3 × 10<sup>−13</sup> m<sup>2</sup>.</p> "> Figure 11
<p>Obtained enlargements of the microcrack from the original locations (blue dots) to later locations (orange dots) at different infusion pressures.</p> ">
Abstract
:1. Introduction
2. Materials and Methods
2.1. Model Setup
2.2. Governing Equations
2.3. Solving Procedures
2.4. Numerical Simulation Methods
3. Results
3.1. Parameters
3.2. Baseline Case Simulation Results
3.2.1. Pressure and Velocity Fields without Introduction of Microcrack [36]
3.2.2. Microcrack Introduction and Tissue Deformation by the Poroelastic Model
3.2.3. The Enlarged Microcrack Constructed in the Third Model
3.2.4. Flow Rate and Flow Resistance
3.3. Parametric Studies
3.3.1. Changing the Axial Length of the Microcrack
3.3.2. Changing the Radius of the Initial Cylindrical Microcrack
3.3.3. Influence of the Transport Properties in the Microcrack
3.3.4. Changing the Interstitial Fluid Pressure at the Infusion Surface
4. Discussion
5. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
- Wilhelm, S.; Tavares, A.J.; Dai, Q.; Ohta, S.; Audet, J.; Dvorak, H.F.; Chan, W.C.W. Analysis of nanoparticle delivery to tumours. Nat. Rev. Mater. 2016, 1, 16014. [Google Scholar] [CrossRef]
- Begg, K.; Tavassoli, M. Inside the hypoxic tumour: Reprogramming of the DDR and radioresistance. Cell Death Discov. 2020, 6, 77. [Google Scholar] [CrossRef] [PubMed]
- Bauer, H.-C.; Krizbai, I.A.; Bauer, H.; Traweger, A. You shall not pass”—Tight junctions of the blood brain barrier. Front. Neurosci. 2014, 8, 392. [Google Scholar] [CrossRef] [PubMed]
- McGuire, S.; Zaharoff, D.; Yuan, F. Nonlinear dependence of hydraulic conductivity on tissue deformation during intratumoral infusion. Ann. Biomed. Eng. 2006, 34, 1173–1181. [Google Scholar] [CrossRef] [PubMed]
- Jahangiri, A.; Chin, A.T.; Flanigan, P.M.; Chen, R.; Bankiewicz, K.; Aghi, M.K. Convection-enhanced delivery in glioblastoma: A review of preclinical and clinical studies. J. Neurosurg. 2017, 126, 191–200. [Google Scholar] [CrossRef]
- Zhou, Z.; Singh, R.; Souweidane, M.M. Convection-enhanced delivery for diffuse intrinsic pontine glioma treatment. Curr. Neuropharmacol. 2017, 15, 116–128. [Google Scholar] [CrossRef]
- Mehta, A.I.; Choi, B.D.; Raghavan, R.; Brady, M.; Friedman, A.H.; Bigner, D.D.; Pastan, I.; Sampson, J.H. Imaging of convection enhanced delivery of toxins in humans. Toxins 2011, 3, 201–206. [Google Scholar] [CrossRef]
- Lonser, R.R.; Sarntinoranont, M.; Morrison, P.F.; Oldfield, E.H. Convection-enhanced delivery to the central nervous system. J. Neurosurg. 2015, 122, 697–706. [Google Scholar] [CrossRef]
- Raghavan, R.; Brady, M.L.; Rodríguez-Ponce, M.I.; Hartlep, A.; Pedain, C.; Sampson, J.H. Convection-enhanced delivery of therapeutics for brain disease, and its optimization. Neurosurg. Focus 2006, 20, E12. [Google Scholar] [CrossRef]
- Casanova, F.; Carney, P.R.; Sarntinoranont, M. Effect of needle insertion speed on tissue injury, stress, and backflow distribution for convection-enhanced delivery in the rat brain. PLoS ONE 2014, 9, e94919. [Google Scholar] [CrossRef]
- Hines-Peralta, A.; Liu, Z.-J.; Horkan, C.; Solazzo, S.; Goldberg, S.N. Chemical tumor ablation with use of a novel multiple-tine infusion system in a canine sarcoma model. J. Vasc. Interv. Radiol. 2006, 17, 351–358. [Google Scholar] [CrossRef] [PubMed]
- Orozco, G.A.; Smith, J.H.; García, J.J. Three-dimensional nonlinear finite element model to estimate backflow during flow-controlled infusions into the brain. Proc. Inst. Mech. Eng. Part H J. Eng. Med. 2020, 234, 1018–1028. [Google Scholar] [CrossRef] [PubMed]
- Orozco, G.; Córdoba, G.; Urrea, F.; Casanova, F.; Smith, J.; García, J. Finite element model to reproduce the effect of pre-stress and needle insertion velocity during infusions into brain phantom gel. IRBM 2021, 42, 180–188. [Google Scholar] [CrossRef]
- Ayers, A.D.; Smith, J.H. A biphasic fluid–structure interaction model of backflow during infusion into agarose gel. J. Biomech. Eng. 2023, 145, 121009. [Google Scholar] [CrossRef]
- Su, D.; Ma, R.; Zhu, L. Numerical study of nanofluid infusion in deformable tissues in hyperthermia cancer treatment. Med. Biol. Eng. Comput. 2011, 11, 1233–1240. [Google Scholar] [CrossRef]
- Sillay, K.A.; McClatchy, S.G.; Shepherd, B.A.; Venable, G.T.; Fuehrer, T.S. Image-guided convection-enhanced delivery into agarose gel models of the brain. J. Vis. Exp. 2014, 14, 51466. [Google Scholar] [CrossRef]
- Lonser, R.R.; Walbridge, S.; Garmestani, K.; Butman, J.A.; Walters, H.A.; Vortmeyer, A.O.; Morrison, P.F.; Brechbiel, M.W.; Oldfield, E.H. Successful and safe perfusion of the primate brainstem: In vivo magnetic resonance imaging of macromolecular distribution during infusion. J. Neurosurg. 2002, 97, 905–913. [Google Scholar] [CrossRef]
- Krauze, M.T.; Saito, R.; Noble, C.; Tamas, M.; Bringas, J.; Park, J.W.; Berger, M.S.; Bankiewicz, K. Reflux-free cannula for convection-enhanced high-speed delivery of therapeutic agents. J. Neurosurg. 2005, 103, 923–929. [Google Scholar] [CrossRef]
- Morrison, P.F.; Chen, M.Y.; Chadwick, R.S.; Lonser, R.R.; Oldfield, E.H. Focal delivery during direct infusion to brain: Role of flow rate, catheter diameter, and tissue mechanics. Am. J. Physiol.-Regul. Integr. Comp. Physiol. 1999, 277, R1218–R1229. [Google Scholar] [CrossRef]
- Chen, M.Y.; Lonser, R.R.; Morrison, P.F.; Governale, L.S.; Oldfield, E.H. Variables affecting convection-enhanced delivery to the striatum: A systematic examination of rate of infusion, cannula size, infusate concentration, and tissue—Cannula sealing time. J. Neurosurg. 1999, 90, 315–320. [Google Scholar] [CrossRef]
- Debinski, W.; Tatter, S. Convection-enhanced delivery for the treatment of brain tumors. Expert Rev. Neurother. 2009, 9, 1519–1527. [Google Scholar] [CrossRef] [PubMed]
- Bidros, D.S.; Liu, J.K.; Vogelbaum, M.A. Future of convection-enhanced delivery in the treatment of brain tumors. Future Oncol. 2010, 6, 117–125. [Google Scholar] [CrossRef] [PubMed]
- Seunguk, O.; Odland, R.; Wilson, S.R.; Kroeger, K.M.; Liu, C.; Lowenstein, P.R.; Castro, M.G.; Hall, W.A.; Ohlfest, J.R. Improved distribution of small molecules and viral vectors in the murine brain using a hollow fiber catheter. J. Neurosurg. 2007, 107, 568–577. [Google Scholar]
- Kuang, M.; Lu, M.-D.; Xie, X.-Y.; Xu, H.-X.; Xu, Z.-F.; Liu, G.-J.; Yin, X.-Y.; Huang, J.-F.; Lencioni, R. Ethanol ablation of hepatocellular carcinoma Up to 5.0 cm by using a multipronged injection needle with high-dose strategy. Radiology 2009, 253, 552–561. [Google Scholar] [CrossRef]
- Khaled, A.-R.; Vafai, K. The role of porous media in modeling flow and heat transfer in biological tissues. Int. J. Heat Mass Transf. 2003, 46, 4989–5003. [Google Scholar] [CrossRef]
- Truskey, G.A.; Yuan, F.; Katz, D.F. Transport Phenomena in Biological Systems, 2nd ed.; Pearson Prentice Hall: Upper Saddle River, NJ, USA, 2009. [Google Scholar]
- Chen, Z.-J.; Broaddus, W.C.; Viswanathan, R.R.; Raghavan, R.; Gillies, G.T. Intraparenchymal drug delivery via positive-pressure infusion: Experimental and modeling studies of poroelasticity in brain phantom gels. IEEE Trans. Biomed. Eng. 2002, 49, 85–96. [Google Scholar] [CrossRef]
- Chen, X.; Sarntinoranont, M. Biphasic finite element model of solute transport for direct infusion into nervous tissue. Ann. Biomed. Eng. 2007, 35, 2145–2158. [Google Scholar] [CrossRef]
- Lai, W.M.; Mow, V.C. Drag-induced compression of articular cartilage during a permeation experiment. Biorheology 1980, 17, 111–123. [Google Scholar] [CrossRef]
- Sobey, I.; Wirth, B. Effect of non-linear permeability in a spherically symmetric model of hydrocephalus. Math. Med. Biol. 2006, 23, 339–361. [Google Scholar] [CrossRef]
- Stylianopoulos, T.; Martin, J.D.; Chauhan, V.P.; Jain, S.R.; Diop-Frimpong, B.; Bardeesy, N.; Smith, B.L.; Ferrone, C.R.; Hornicek, F.J.; Boucher, Y. Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors. Proc. Natl. Acad. Sci. USA 2012, 109, 15101–15108. [Google Scholar] [CrossRef]
- Skalak, R.; Zargaryan, S.; Jain, R.K.; Netti, P.A.; Hoger, A. Compatibility and the genesis of residual stress by volumetric growth. J. Math. Biol. 1996, 34, 889–914. [Google Scholar] [CrossRef] [PubMed]
- Basser, P.J. Interstitial pressure, volume, and flow during infusion into brain tissue. Microvasc. Res. 1992, 44, 143–165. [Google Scholar] [CrossRef] [PubMed]
- Netti, P.A.; Baxter, L.T.; Boucher, Y.; Skalak, R.; Jain, R.K. Macro-and microscopic fluid transport in living tissues: Application to solid tumors. AIChE J. 1997, 43, 818–834. [Google Scholar] [CrossRef]
- Singh, M.; Ma, R.; Zhu, L. Theoretical evaluation of enhanced gold nanoparticle delivery to pc3 tumors due to increased hydraulic conductivity or recovered lymphatic function after mild whole body hyperthermia. Med. Biol. Eng. Comput. 2021, 59, 301–313. [Google Scholar] [CrossRef]
- Naseem, M.J.; Ma, R.; Zhu, L. Enhancing fluid infusion via introduction and enlargement of microcrack in tumors—Theoretical simulations. In Proceedings of the Summer Biomechanics, Bioengineering and Biotransport Conference, Lake Geneva, WI, USA, 11–14 June 2024. Submission ID: 243. [Google Scholar]
- Yuan, T.; Shen, L.; Dini, D. Porosity-permeability tensor relationship of closely and randomly packed fibrous biomaterials and biological tissues: Application to the brain white matter. Acta Biomater. 2024, 173, 123–134. [Google Scholar] [CrossRef] [PubMed]
Mesh Type | # of Triangular Elements | Qouter m3/s |
---|---|---|
Extremely fine | 12,879 | 9.451 × 10−10 |
Extra fine | 3845 | 9.4475 × 10−10 |
Finer | 1764 | 9.4348 × 10−10 |
Fine | 1160 | 9.413 × 10−10 |
Geometrical Parameter | Value |
---|---|
Infusion surface radius | 0.64 mm |
Tumor outer radius | 10 mm |
Microcrack radius without enlargement | 0.025 or 0.05 mm |
Microcrack length | 3 mm, 4.5 mm, 6 mm, 7.5 mm, or 9 mm |
Fluid Property | Mechanical Property | ||
---|---|---|---|
Density of tumor ρ | 1000 kg/m3 | Tumor Young’s module E1 | 0.3 MPa [28,33] |
Tumor porosity ϕ1 | 0.2 [34,35] | Crack Young’s module E2 | 0.003 MPa |
Crack porosity ϕ2 | 0.78, 0.8, 0.81 | Tissue Poisson’s ratio ν1 | 0.4 [4,28] |
Tumor permeability Κ1 | 5 × 10−16 m2 [28,34] | Crack Poisson’s ratio ν2 | 0.4 [4,28] |
Crack permeability Κ2 | 1 × 10−13, 2.0173 × 10−13, 3 × 10−13 m2 | ||
Infusion pressure P0 | 105, 2 × 105, 4 × 105 Pa [15] | ||
Dynamic viscosity μ | 10−3 Pa s [15] |
The 1st Model | The 2nd Model | The 3rd Model | |
---|---|---|---|
Qouter, m3/s | 8.592 × 10−10 | 9.451 × 10−10 | 1.000 × 10−9 |
Rflow, Pa s/m3 | 2.328 × 1014 | 2.116 × 1014 | 1.999 × 1014 |
Crack Length | Volumetric Flow Rate Qouter (m3/s) | Change from the Baseline Case | |||
---|---|---|---|---|---|
The 1st Model | The 2nd Model | The 3rd Model | The 2nd Model | The 3rd Model | |
3 mm | 8.592 × 10−10 | 9.451 × 10−10 | 1.000 × 10−9 | NA | NA |
4.5 mm | 8.592 × 10−10 | 9.568 × 10−10 | 1.028 × 10−9 | 1.3% | 2.7% |
6 mm | 8.592 × 10−10 | 9.596 × 10−10 | 1.034 × 10−9 | 1.5% | 3.4% |
7.5 mm | 8.592 × 10−10 | 9.604 × 10−10 | 1.034 × 10−9 | 1.6% | 3.4% |
9 mm | 8.592 × 10−10 | 9.607 × 10−10 | 1.034 × 10−9 | 1.7% | 3.4% |
Crack Length | Flow Resistance Rflow (Pa s/m3) | Change from the Baseline Case | |||
---|---|---|---|---|---|
The 1st Model | The 2nd Model | The 3rd Model | The 2nd Model | The 3rd Model | |
3 mm | 2.328 × 1014 | 2.116 × 1014 | 1.999 × 1014 | NA | NA |
4.5 mm | 2.328 × 1014 | 2.090 × 1014 | 1.946 × 1014 | −1.2% | −2.7% |
6 mm | 2.328 × 1014 | 2.084 × 1014 | 1.934 × 1014 | −1.5% | −3.2% |
7.5 mm | 2.328 × 1014 | 2.082 × 1014 | 1.933 × 1014 | −1.6% | −3.3% |
9 mm | 2.328 × 1014 | 2.081 × 1014 | 1.934 × 1014 | −1.7% | −3.3% |
Crack Radius | Flow Resistance (Pa s/m3) | Reduction in Flow Resistance | ||||
---|---|---|---|---|---|---|
1st Model | 2nd Model | 3rd Model | 1st Model | 2nd Model | 3rd Model | |
0.025 mm | 2.33 × 1014 | 2.25 × 1014 | 2.18 × 1014 | N/A | 3.5% | 6.5% |
0.05 mm | 2.33 × 1014 | 2.12 × 1014 | 2.00 × 1014 | N/A | 9% | 14% |
Permeability (m2) | Flow Resistance (Pa s/m3) | Reduction in Flow Resistance | ||||
---|---|---|---|---|---|---|
1st Model | 2nd Model | 3rd Model | 1st Model | 2nd Model | 3rd Model | |
1 × 10−13 | 2.33 × 1014 | 2.19 × 1014 | 2.09 × 1014 | N/A | N/A | N/A |
2.0173 × 10−13 | 2.33 × 1014 | 2.12 × 1014 | 2.00 × 1014 | 0% | 3.2% | 4.3% |
3 × 10−13 | 2.33 × 1014 | 2.08 × 1014 | 1.94 × 1014 | 0% | 5.0% | 7.2% |
Pressure (Pa) | Flow Resistance (Pa s/m3) | Reduction in Flow Resistance | ||||
---|---|---|---|---|---|---|
1st Model | 2nd Model | 3rd Model | 1st Model | 2nd Model | 3rd Model | |
1 × 105 | 2.33 × 1014 | 2.12 × 1014 | 2.05 × 1014 | N/A | N/A | N/A |
2 × 105 | 2.33 × 1014 | 2.12 × 1014 | 2.00 × 1014 | 0% | 0% | 2.5% |
4 × 105 | 2.33 × 1014 | 2.12 × 1014 | 1.91 × 1014 | 0% | 0% | 6.8% |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Naseem, M.J.; Ma, R.; Zhu, L. Reducing Flow Resistance via Introduction and Enlargement of Microcracks in Convection Enhanced Delivery (CED) in Porous Tumors. Fluids 2024, 9, 215. https://doi.org/10.3390/fluids9090215
Naseem MJ, Ma R, Zhu L. Reducing Flow Resistance via Introduction and Enlargement of Microcracks in Convection Enhanced Delivery (CED) in Porous Tumors. Fluids. 2024; 9(9):215. https://doi.org/10.3390/fluids9090215
Chicago/Turabian StyleNaseem, Md Jawed, Ronghui Ma, and Liang Zhu. 2024. "Reducing Flow Resistance via Introduction and Enlargement of Microcracks in Convection Enhanced Delivery (CED) in Porous Tumors" Fluids 9, no. 9: 215. https://doi.org/10.3390/fluids9090215