PhD position EIC european project at the Université de Lyon

Intraoperative optical imaging for neurosurgery guidance

As part of a recently awarded EIC Pathfinder european Grant (www.hyperprobe.eu) we are looking for a PhD student. EIC supports projects that research and develop emerging breakthrough technologies. The main goal of our project consists in transforming brain surgery by advancing functional-guided neuronavigational imaging.

Intraoperative neuroimaging is developing as an indispensable means of assistance for surgical procedures. We are
working on the development of innovative optical imaging methods for translational medical applications. These works
are based on clinical collaborations with Jacques Guyotat (Neurosurgery department of Lyon University hospital HCL) and Fabien Schneider (Radiology department of Saint Etienne University hospital) for the development of new intraoperative optical imaging strategies inspired from fMRI (functional Magnetic Resonance Imaging) [1, 2].

Clinical context
Resting state imaging is a new technique of public interest because it can identify functional brain areas without patient
intervention and could be possibly used under general anaesthesia. The development of an optical method would make it
possible to reduce the time of neurosurgery operations and improve the surgeon’s operating comfort while guaranteeing the patient’s well-being. Optical imaging is particularly adapted to an intraoperative context because intrinsic contrasts could be assessed in a non invasive and non ionising way. However, the use of optical imaging faces to several difficulties related to the quantification and understanding of biomarkers for the analysis of brain connectivity at rest.

Scientific Objectives
Brain functionality has to be assessed intraoperatively. This can be done using both approaches of task-based brain areas [3, 4, 5] and resting state brain networks [6]. We have already developed haemodynamics quantification models for intraoperative optical imaging [3], see Fig. 1. However, the brain haemodynamics response is largely impaired due to brain pathologies like gliomas [7][ We need to develop functional models that will integrate the possible impairment of brain haemodynamic response. This will be investigated using also models integrating Cytochrome Oxidase (CCO) brain  response in complement to haemodynamics [8, 9], using the expertise of the UCL team on CCO optical spectroscopy [10]. CCO is linked to cell metabolism and is complementary to haemodynamics. Intraoperative resting state imaging could potentially be used for awake or anesthetised patients. The difficulty lies on the fact that current fMRI methodologies used the entire brain for data processing of cerebral networks. Intraoperative optical resting state only gives access to the part of the brain that is exposed. We will develop ML-based resting state functional models using fMRI data as a priori and to complete the missing data using the expertise of the TUM partner on ML. We will also investigate the integration of the rich spatiotemporal information accessible with intraoperative optical imaging as compared to BOLD fMRI for resting state data processing. BOLD fMRI and electrical stimulation will be used as Clinical gold standard for validation of classificationpipeline of brain functionality [11, 12].

PhD candidate profil
The person recruited will mainly work on modelling, signal/image processing, optical acquisition set up. He/she will perform in vivo experiments on humans in a neurosurgery operating room at the Hospices Civils de Lyon. The prerequisites are therefore those of a physicist and/or engineer with a specialisation in modelling and/or signal processing and/or optical instrumentation with a strong attraction for multidisciplinary in the medical and biomedical fields.

Figure 1 – Identification of the cerebral motor area related to patient’s left hand movement identified by fMRI (blue map) and optical imaging (magenta map). The contour of the surgical window of image A is represented in black in image B. The letter M indicates the motor area identified by the neurosurgeon. C – Neurosurgery operating room in Hospices Civils de Lyon.

Benefits
Salary : 2044€ gross/month first year ; 2100€ second year ; 2200€ third year (Allocation doctorale ; University Collective Agreement) including health insurance 3-year contract with 49 days of holidays per year Flexible working hours Possibility to be involved in entrepreneurial training and activities Possibility to teach in the University departments (gratification 280€ gross/month) International community of young scientists (PhD, postdocs) Research mobility within the EIC project partners (UCL London ; TUM Munich ; UNIFI Florence)

Selection process
The paper documents are continuously assessed and fitting candidates complying with the requirements are invited for interviews as soon as possible. Applicants should provide the following information in their application :
1. Cover Letter (including motivation, qualifications and possible synergy with the project).
2. A detailed CV including technical / analytical skills and a list of publications.
3. Copy of MSc diploma or equivalent and transcript of marks during the academic curriculum
4. Contact information of two referees

Scientific environment
stimulating scientific and technological environment : The PhD will take place at CREATIS, a multidisciplinary research laboratory applied to medical imaging associated with the CNRS and INSERM, in the scientific domain of “la Doua” in Lyon. Close collaboration with clinicians : Experiments in the neurosurgery operating room will be carried out in close collaboration with Jacques Guyotat (Neurosurgery department of Lyon University hospital) pioneer of the 5-ALA fluorescence technique in France and Fabien Schneider (Radiology department of Saint Etienne University hospital) expert in fMRI. Technical support by the optics and computer engineers from CREATIS and experts in setting up clinical trials from the HCL DRCI.
The supervision committee will be composed of specialists in each component of this research subject :
— Clinical medical optical setup (Bruno Montcel and Charly Caredda)
— Data analyses and processing (Michaël Sdika)
— Radiology and resting state connectivity (Fabien Schneider)
— Neurosurgery (Jacques Guyotat and Thiebaud Picart)

Contact
Bruno Montcel bruno.montcel@creatis.insa-lyon.fr

Références
[1] Michael D. Fox and Marcus E. Raichle. Spontaneous fluctuations in brain activity observed with functional magnetic
resonance imaging. Nature Reviews Neuroscience, 8(9) :700–711, September 2007.
[2] Bharat Biswal, F. Zerrin Yetkin, Victor M. Haughton, and James S. Hyde. Functional connectivity in the motor cortex of
resting human brain using echo-planar mri. Magnetic Resonance in Medicine, 34(4) :537–541, October 1995.
[3] Charly Caredda, Laurent Mahieu-Williame, Raphaël Sablong, Michaël Sdika, Laure Alston, Jacques Guyotat, and Bruno
Montcel. Intraoperative quantitative functional brain mapping using an RGB camera. Neurophotonics, 6(4) :1 – 14, 2019.
[4] Charly Caredda, Laurent Mahieu-Williame, Raphaël Sablong, Michaël Sdika, Jacques Guyotat, and Bruno Montcel. Real
time intraoperative functional brain mapping using a RGB camera. In J. Quincy Brown and Ton G. van Leeuwen, editors,
Clinical and Preclinical Optical Diagnostics II, volume 11073, pages 17 – 21. International Society for Optics and Photonics,
SPIE, 2019.
[5] Charly Caredda, Laurent Mahieu-Williame, Raphaël Sablong, Michaël Sdika, Jacques Guyotat, and Bruno Montcel. Optimal
Spectral Combination of a Hyperspectral Camera for Intraoperative Hemodynamic and Metabolic Brain Mapping. Applied
Sciences, 10(15) :5158, July 2020.
[6] Charly Caredda, Laurent Mahieu-Williame, Raphaël Sablong, Michaël Sdika, Fabien C. Schneider, Jacques Guyotat, and
Bruno Montcel. Intraoperative resting-state functional connectivity based on rgb imaging. Diagnostics, 11(11), 2021.
[7] Mary Katherine Montgomery et al. Glioma-induced alterations in neuronal activity and neurovascular coupling during
disease progression. Cell Reports, 31(2) :107500, 2020.
[8] Gemma Bale, Clare E Elwell, and Ilias Tachtsidis. From jöbsis to the present day : a review of clinical near-infrared
spectroscopy measurements of cerebral cytochrome-c-oxidase. Journal of biomedical optics, 21(9) :091307, 2016.
[9] Charly Caredda, Laurent Mahieu-Williame, Raphaël Sablong, Michaël Sdika, Jacques Guyotat, and Bruno Montcel. Intraoperative functional and metabolic brain mapping using hyperspectral imaging. In Steen J. Madsen, Victor X. D. Yang,
and Nitish V. Thakor, editors, Clinical and Translational Neurophotonics 2020, volume 11225, pages 24 – 30. International
Society for Optics and Photonics, SPIE, 2020.
[10] Luca Giannoni, Frédéric Lange, Marija Sajic, Kenneth J. Smith, and Ilias Tachtsidis. A hyperspectral imaging system for
mapping haemoglobin and cytochrome-c-oxidase concentration changes in the exposed cerebral cortex. IEEE Journal of
Selected Topics in Quantum Electronics, 27 :1–11, 2021.
[11] F.C. Schneider, M. Pailler, I. Faillenot, F. Vassal, J. Guyotat, F.-G. Barral, and C. Boutet. Presurgical assessment of the
sensorimotor cortex using resting-state fmri. American Journal of Neuroradiology, 37(1) :101–107, 2016.
[12] Francesco Signorelli, J Guyotat, Fabien Schneider, Jean Isnard, and P Bret. Technical refinements for validating functional
mri-based neuronavigation data by electrical stimulation during cortical language mapping. Minimally invasive neurosurgery : MIN, 46 :265–8, 11 2003.