Alexandra K. Diem

Personal Website.
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Publications

Journal articles

Diem AK, Valen-Sendstad K (2019) Timelapsing perfusion: Proof of concept of a novel method to study drug delivery in whole organs.. Biophysical Journal. https://doi.org/10.1016/j.bpj.2019.09.029

Abstract

Perfusion is one of the most important processes maintaining organ health. From a computational perspective, however, perfusion is amongst the least studied physiological processes of the heart. The recent development of novel nanoparticle-based targeted cardiac therapy calls for novel simulation methods that can provide insights into the distribution patterns of therapeutic agents within the heart tissue. Additionally, resolving the distribution patterns of perfusion is crucial for gaining a full understanding of the long-term impacts of cardiovascular diseases that can lead to adverse remodelling, such as myocardial ischemia and heart failure. In this study we have developed and used a novel particle tracking-based method to simulate the perfusion-mediated distribution of nanoparticles or other solutes. To model blood flow through perfused tissue we follow the approach of others and treat the tissue as a porous medium in a continuum model. Classically, solutes are modelled using reaction-advection-diffusion kinetics. However, due to the discrepancy of scales between advection and diffusion in blood vessels, this method becomes practically numerically unstable. Instead, we track a bolus of solutes or nanoparticles using particle tracking based purely on advection in arteries. In capillaries we employ diffusion kinetics, using an effective diffusion coefficient to mimic capillary blood flow. We first demonstrate the numerical validity and computational efficiency of this method on a 2D benchmark problem. Finally, we demonstrate how the method is used to visualise perfusion patterns of a healthy and ischemic human left ventricle geometry. The efficiency of the method allows for nanoparticle tracking over multiple cardiac cycles using a conventional laptop, providing a framework for the simulation of experimentally relevant time frames to advance pre-clinical research.

Agdestein S, Valen-Sendstad K, Diem AK (2018) Artery. FE: An implementation of the 1D blood flow equations in FEniCS. Journal of Open Source Software 3: 1107. https://doi.org/10.5281/zenodo.2383815

Diem AK, Carare RO, Weller RO, Bressloff NW (2018) A control mechanism for intra-mural peri-arterial drainage via astrocytes: How neuronal activity could improve waste clearance from the brain. Plos One 13(10): e0205276. https://doi.org/10.1371/journal.pone.0205276

Rougier NP, Hinsen K, Alexandre F, Arildsen T, Barba LA, et al. including Diem AK (2017) Sustainable computational science: the ReScience initiative. PeerJ Computer Science 3:e142. https://doi.org/10.7717/peerj-cs.142

Diem AK (2017) [Re] A bidirectional model for communication in the neurovascular unit. ReScience 3 (1): 9. https://zenodo.org/record/890901

Diem AK, Bressloff NW, MacGregor Sharp M, Carare RO, Richardson G (2017) Arterial pulsations cannot drive intramural periarterial drainage: Significance for Alzheimer’s disease. Frontiers in Neuroscience 11: 475. https://doi.org/10.3389/fnins.2017.00475

Diem AK, Bressloff NW (2017) VaMpy: A Python Package to Solve 1D Blood Flow Problems. Journal of Open Research Software 5: 17. http://doi.org/10.5334/jors.159

Diem AK, Tan M, Bressloff NW, Hawkes C, Morris AWJ, Weller RO, Carare RO (2016) A Simulation Model of Periarterial Clearance of Amyloid-β from the Brain. Frontiers in Ageing Neuroscience 8: 18. https://doi.org/10.3389/fnagi.2016.00018

Sharp MK, Diem AK, Weller RO, Carare RO (2016) Peristalsis with Oscillating Flow Resistance: A Mechanism for Periarterial Clearance of Amyloid Beta from the Brain. Annals of Biomedical Engineering 44 (5): 1553-65. https://dx.doi.org/10.1007/s10439-015-1457-6

Invited talks

Conference contributions