Fluorescence imaging, diagnosis, and photodynamic therapy for brain tumours

Lead Research Organisation: University of St Andrews
Department Name: Physics and Astronomy

Abstract

Glioblastoma multiforme (GBM) is an aggressive malignant brain tumour with a median survival for adults of only 11 - 15 months. Published studies have shown that prognosis can be improved if near-complete removal of the tumour can be achieved in surgery [do we need to put references?]. To aid resection, fluorescence guidance is used, utilising blue light excitation of a red fluorescing photosensitiser to highlight diseased cells. There is a need to better understand the light-tissue interactions during fluorescence guided resection, investigating the depth in tissue information present in the returned image and whether photodynamic therapy can be successfully performed with the existing photosensitiser. Building upon the knowledge accumulated over 13 years of collaboration on light interaction with skin, Monte Carlo Radiative Transfer will be used to investigate these clinical challenges in the brain and to continue our research on the impact of light on skin for both therapy and public health.

The student will adapt our Monte Carlo radiation transfer codes to model the propagation of therapeutic light in brain tissue with goals of determining depth penetration of light, appropriate optical properties for scattering and absorption in brain tissue, diffusion of the pro-drug, cell kill due top PDT action, and production of fluorescent light indicating which areas have cancer cells. The research will help inform clinicians as to the efficacy of PDT in the brain and also using fluorescence as a diagnostic of cancer for surgery to remove diseased tissue.

Planned Impact

Complementing our Pathways to Impact document, here we state the expected real-world impact, which is of course the leading priority for our industrial partners. Their confidence that the proposed CDT will deliver valuable scientific, engineering and commercial impact is emphasized by their overwhelming financial support (£4.38M from industry in the form of cash contributions, and further in-kind support of £5.56M).

Here we summarize what will be the impacts expected from the proposed CDT.

(1) Impact on People
(a) Students
The CDT will have its major impact on the students themselves, by providing them with new understanding, skills and abilities (technical, business, professional), and by enhancing their employability.
(b) The UK public
The engagement planned in the CDT will educate and inform the general public about the high quality science and engineering being pursued by researchers in the CDT, and will also contribute to raising the profile of this mode of doctoral training -- particularly important since the public have limited awareness of the mechanisms through which research scientists are trained.

(2) Impact on Knowledge
New scientific knowledge and engineering know-how will be generated by the CDT. Theses, conference / journal papers and patents will be published to disseminate this knowledge.

(3) Impact on UK industry and economy
UK companies will gain a competitive advantage by using know-how and new techniques generated by CDT researchers.
Companies will also gain from improved recruitment and retention of high quality staff.
Longer term economic impacts will be felt as increased turnover and profitability for companies, and perhaps other impacts such as the generation / segmentation of new markets, and companies receiving inward investment for new products.

(4) Impact on Society
Photonic imaging, sensing and related devices and analytical techniques underpin many of products and services that UK industry markets either to consumers or to other businesses. Reskilling of the workforce with an emphasis on promoting technical leadership is central to EPSRC's Productive Nation prosperity outcome, and our CDT will achieve exactly this through its development of future industrially engaged scientists, engineers and innovators. The impact that these individuals will have on society will be manifested through their contribution to the creation of new products and services that improve the quality of life in sectors like transport, dependable energy networks, security and communications.

Greater internationalisation of the cohort of CDT researchers is expected from some of the CDT activities (e.g. international summer schools), with the potential impact of greater collaboration in the future between the next generations of UK and international researchers.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/S022821/1 01/10/2019 31/03/2028
2262922 Studentship EP/S022821/1 01/09/2019 30/08/2024 Louise Finlayson
 
Description A significant element of the research that has been developed so far is the adaptations made to a pre-existing code. We are using Monte Carlo Radiative Transfer methods to model the path of light in biological tissue. A 'blank' Monte Carlo code was first used to recreate a previous students 5-layer skin model in order to model light transport in skin. An extra layer was added to this, and a variable resolution grid was used to allow more detail to be seen in the thinner, upper layers of the skin. The code was also adapted to run on a HPC cluster within the University of St Andrews, which significantly reduced its running time as it allowed the code to run over several hundred cores. An in-depth literature search allowed a wide range of optical properties from 200 - 1000nm to be identified for each skin layer, allowing results from the code to be extended from the ultraviolet (UV) range into the visible light and infrared (IR) range. These results were then used to write the paper 'Depth penetration of light into skin as a function of wavelength from 200 - 1000 nm' and to develop an online data sharing tool.
The skin model was also used in collaboration with several researchers within St Andrews University and Ninewells Hospital to study the safety of far-UVC germicidal lamps by looking how much skin damage they cause compared to other light sources. The finding here showed that minimal damage occurred in filtered sources that reduced the intensity of larger wavelengths.
The research is now beginning to focus on creating a Monte Carlo simulation to look at light transport in the brain. The ability to simulate photodynamic therapy has been added to the code and this will be used to simulate intra-operative photodynamic treatment of glioblastoma multiforme brain tumours. The next goal is for several different treatment methods to be virtually recreated and their efficacy compared, as laid out in the award objectives.
Exploitation Route It is expected that the data sharing app as well as the outcomes of the skin penetration depth research will be used by clinicians and other researchers to aid the design and understanding of light-based dermatological treatments as well as increase understanding of risks associated with sources such as sun light and ultraviolet lamps.
It is hoped that the skin model will be further improved by adapting it for different Fitzpatrick phototypes and using it to understand more about the effect of sunscreens. This work will likely be carried out by a future PhD student.
Sectors Healthcare

 
Title Depth Penetration of Light into Skin 
Description A web app was developed to allow clinicians and other researchers to easily access the data from my skin model Monte Carlo simulations. The app was built through 'Shinyapps' and allows users to upload a light spectrum and be given a data set showing the penetration depth into skin of each wavelength of light within the uploaded spectrum. 
Type Of Technology Webtool/Application 
Year Produced 2021 
Impact This app makes penetration depth information easily accessible to those who need it. It has been used by a several people since its release, including researchers from Public Health England. 
URL https://loufin.shinyapps.io/Depth_Pen_App/