P145 Biophysical thalamic neuron models to probe the impact of ultrasound induced heating in the brain
Rikinder Kour1, Ayesha Jameel2,3, Joely Smith3,4, Peter Bain5,6, Dipankar Nandi5,6, Brynmor Jones3, Rebecca Quest3,4, Wladyslaw Gedroyc2,3, Roman Borisyuk7,Nada Yousif1*
1School of Physics Engineering and Computer Science, University of Hertfordshire, UK
2Department of Surgery and Cancer, Imperial College London, UK
3Department of Imaging, Imperial College Healthcare NHS Trust, London, UK
4Department of Bioengineering, Imperial College London, UK
5Division of Brain Sciences, Imperial College London, UK
6Department of Neurosciences, Imperial College Healthcare NHS Trust, London, UK
7Department of Mathematics and Statistics, University of Exeter, Exeter, UK
* Email: n.yousif@herts.ac.uk
Introduction
High intensity focussed ultrasound (HIFU) is used for ablating thalamic neurons to treat tremor [1]. Low intensity focussed ultrasound (LIFU) can be used for neuromodulation [2] and previous modelling suggests that LIFU induces neuronal excitation via mechanical modulation of the cell membrane [3,4]. Although modelling of neural effects of HIFU is limited, understanding the effects of heating during HIFU at sub-ablative temperatures is important, as this is used for monitoring side effects and clinical improvement during tremor treatment [5]. Here we modified biophysical thalamocortical neuron models [6,7] to look at the change in firing patterns as HIFU induced heating approaches ablative temperatures.
Methods
First, we used data from magnetic resonance thermography performed during a HIFU treatment to select the temperature value for the ‘celsius’ parameter in NEURON [8]. We then examined the effect of temperature on the neuronal firing, as mediated by the parameters of gating equations [9]. Next, we added temperature dependence for the membrane capacitance, as shown experimentally [10] and in a previous modelling study [11]. We compared the effect of temperature in single neurons with one, three and 200 compartments under current clamp conditions with different input current levels [6]. Finally, we considered the impact of increasing temperature on a small network of two excitatory thalamic neurons [7] and two inhibitory reticular neurons.
Results
The thermography data (Fig. 1A) shows that at the HIFU target site, the temperature increased up to 62°C for a treatment sonication. With temperature dependent parameters of the gating equations, increasing temperatures lead to inhibition of the neuron (Fig. 1B). Interestingly, when including a temperature dependent membrane capacitance, we observed a similar pattern of results. Furthermore, we also saw the same effect of temperature on firing rate regardless of the number of compartments modelled. Finally, the network model showed that although with changing temperature the firing of the individual neurons both increased and decreased, we still observe an overall termination of firing in all neurons as the temperature exceeds 40°C.
Discussion
HIFU is commonly used to thermally ablate the thalamus and suppress tremor, via application of ultrasound energy called sonications. Test sonications are used to heat the tissue to sub-ablative temperatures to confirm targeting and test for adverse effects. This study looked at the impact of such sub-ablative heating on single neuron models and a small network representative of the target region. Our results indicate that once temperatures exceed 40°C neuronal firing is completely inhibited. Future work will extend the network model to look at downstream effects of heating. Such work will allow us to better understand the link between subablative temperature increases, suppression of tremor and adverse effects for optimising treatment.
Figure 1. Figure1: (A) The heating induced in by a HIFU treatment sonication. The target is at the centre of the image and the temperature reaches 62°C. (B) The results from simulating a single compartment thalamocortical neuron at different temperatures, when the neuron has only temperature dependent gating equations (black) and when the membrane capacitance has temperature dependence (red).
Acknowledgements
NY is funded by the Royal Academy of Engineering and the Leverhulme Trust and AJ is partially funded by Funding Neuro.
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