Microscale characterisation of the time-dependent mechanical behaviour of brain white matter

Jamal, Asad; Bernardini, Andrea; Dini, Daniele

doi:10.1016/j.jmbbm.2021.104917

Cited by 15 publications

(18 citation statements)

References 80 publications

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“…The results in Fig. 4 indicate that the model is nearly isotropic in the x and y directions as the slopes are nearly the same, confirming the tissue behaves as a transversely isotropic material [ 66 ]. Thus, the values of D in the x and y directions are averaged to represent the D in the direction perpendicular to the axons.…”

Section: Resultsmentioning

confidence: 84%

Effect of Particle Size and Surface Charge on Nanoparticles Diffusion in the Brain White Matter

et al. 2022

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Purpose Brain disorders have become a serious problem for healthcare worldwide. Nanoparticle-based drugs are one of the emerging therapies and have shown great promise to treat brain diseases. Modifications on particle size and surface charge are two efficient ways to increase the transport efficiency of nanoparticles through brain-blood barrier; however, partly due to the high complexity of brain microstructure and limited visibility of Nanoparticles (NPs), our understanding of how these two modifications can affect the transport of NPs in the brain is insufficient. Methods In this study, a framework, which contains a stochastic geometric model of brain white matter (WM) and a mathematical particle tracing model, was developed to investigate the relationship between particle size/surface charge of the NPs and their effective diffusion coefficients (D) in WM. Results The predictive capabilities of this method have been validated using published experimental tests. For negatively charged NPs, both particle size and surface charge are positively correlated with D before reaching a size threshold. When Zeta potential (Zp) is less negative than -10 mV, the difference between NPs’ D in WM and pure interstitial fluid (IF) is limited. Conclusion A deeper understanding on the relationships between particle size/surface charge of NPs and their D in WM has been obtained. The results from this study and the developed modelling framework provide important tools for the development of nano-drugs and nano-carriers to cure brain diseases.

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Section: Resultsmentioning

confidence: 84%

Effect of Particle Size and Surface Charge on Nanoparticles Diffusion in the Brain White Matter

et al. 2022

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“…The mechanical characteristics of CNS tissue have been widely investigated using both macro and microscale experimental approaches [ 33 ]. Most of such characterisation is focused on the viscoelastic solid phase [ 61 ]; however, experimental investigations at the relevant length scale were able to capture the poroelastic effect as well [ 31 , 47 , 62 ]. Such experimental results are explained by treating brain tissue as a biphasic material.…”

Section: Infusion-based Drug Delivery In Cns Tissuementioning

confidence: 99%

“…Additionally, our recent study has revealed this difference when these components are in their natural environment. The stiffness of ECM is lower than that of axons, and the E of ECM when compared to axons is

47%,

42% and

25.6% lower in corpus callosum, corona radiata and fornix, respectively [ 61 ]. Furthermore, the existing trend in the literature can also be attributed to the absence of evidence that heterogeneities in the micromechanical environment affect flow behaviour.…”

Section: Infusion-based Drug Delivery In Cns Tissuementioning

confidence: 99%

“…For example, Forte et al [ 203 ] developed a numerical model for the prediction of brain shift during surgical procedures and employed a phantom made of a composite hydrogel [ 204 , 205 ] to validate their findings. Such studies, combined with the use of advanced experimental investigations [ 41 , 61 , 206 ], highlight the importance of modelling using robust and fully validated constitutive laws for the simulations of brain deformation [ 42 , 47 , 207 ]. The use of reduced-order models derived from more complex descriptions of the tissue deformation has also been pursued and holds promise in the context of guiding intra-operative adjustment and helping clinicians during surgical procedures [ 208 , 209 ].…”

Section: Robotics Solutionsmentioning

confidence: 99%

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Insights into Infusion-Based Targeted Drug Delivery in the Brain: Perspectives, Challenges and Opportunities

Jamal

Yuan

Galvan

et al. 2022

IJMS

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Targeted drug delivery in the brain is instrumental in the treatment of lethal brain diseases, such as glioblastoma multiforme, the most aggressive primary central nervous system tumour in adults. Infusion-based drug delivery techniques, which directly administer to the tissue for local treatment, as in convection-enhanced delivery (CED), provide an important opportunity; however, poor understanding of the pressure-driven drug transport mechanisms in the brain has hindered its ultimate success in clinical applications. In this review, we focus on the biomechanical and biochemical aspects of infusion-based targeted drug delivery in the brain and look into the underlying molecular level mechanisms. We discuss recent advances and challenges in the complementary field of medical robotics and its use in targeted drug delivery in the brain. A critical overview of current research in these areas and their clinical implications is provided. This review delivers new ideas and perspectives for further studies of targeted drug delivery in the brain.

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“…3. Permeability in white matter is anisotropic in nature because of the directionality of the axons (Jamal et al 2022a) and should therefore be described as a tensor. However, in this study our focus is to obtain a better understanding of the microstructural origin (axonal deformation) of the macroscopic response of the tissue to infusion pressure, which results in permeability changes.…”

Section: Boundary Conditions: Microscopic Modelmentioning

confidence: 99%

On the microstructurally driven heterogeneous response of brain white matter to drug infusion pressure

Yuan

Zhan

Jamal

et al. 2022

Biomech Model Mechanobiol

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Delivering therapeutic agents into the brain via convection-enhanced delivery (CED), a mechanically controlled infusion method, provides an efficient approach to bypass the blood–brain barrier and deliver drugs directly to the targeted focus in the brain. Mathematical methods based on Darcy’s law have been widely adopted to predict drug distribution in the brain to improve the accuracy and reduce the side effects of this technique. However, most of the current studies assume that the hydraulic permeability and porosity of brain tissue are homogeneous and constant during the infusion process, which is less accurate due to the deformability of the axonal structures and the extracellular matrix in brain white matter. To solve this problem, a multiscale model was established in this study, which takes into account the pressure-driven deformation of brain microstructure to quantify the change of local permeability and porosity. The simulation results were corroborated using experiments measuring hydraulic permeability in ovine brain samples. Results show that both hydraulic pressure and drug concentration in the brain would be significantly underestimated by classical Darcy’s law, thus highlighting the great importance of the present multiscale model in providing a better understanding of how drugs transport inside the brain and how brain tissue responds to the infusion pressure. This new method can assist the development of both new drugs for brain diseases and preoperative evaluation techniques for CED surgery, thus helping to improve the efficiency and precision of treatments for brain diseases.

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Microscale characterisation of the time-dependent mechanical behaviour of brain white matter

Cited by 15 publications

References 80 publications

Effect of Particle Size and Surface Charge on Nanoparticles Diffusion in the Brain White Matter

Effect of Particle Size and Surface Charge on Nanoparticles Diffusion in the Brain White Matter

Insights into Infusion-Based Targeted Drug Delivery in the Brain: Perspectives, Challenges and Opportunities

On the microstructurally driven heterogeneous response of brain white matter to drug infusion pressure

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