nEUROPt

Innovative solutions for brain imaging

Project reference: 201076 - Funded under:  FP7-HEALTH

Advanced non-invasive imaging methodologies for in vivo diagnosis, monitoring and prognosis of major neurological diseases. The integrated approach could revolutionize the diagnosis and monitoring of conditions including stroke and severe brain trauma.

Computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) are imaging techniques that provide extensive anatomical and physiological data of outmost importance for guiding diagnosis and therapy in clinical practice. However, these methods cannot assess systemic parameters such as heart rate or blood pressure, and they cannot be applied at the bedside. Electroencephalography (EEG) constitutes a long-standing technique that can continuously and non-invasively monitor the brain.

The EU-funded “Non-invasive imaging of brain function and disease by pulsed near infrared light” (NEUROPT) consortium was motivated to generate a clinical tool for continuous monitoring of the haemodynamic parameters of cerebral oxygenation and perfusion. This tool should also complement MRI/CT/PET methods and at the same time be compatible with existing neuro-monitoring techniques (EEG, Doppler ultrasound).

To achieve this, partners had to improve spatial resolution of current imaging techniques, remove artefacts and enable the absolute quantification of physiological parameters. To this end, they employed time-resolved techniques that offer greater sensitivity than most optical methods and distinguish between surface tissues (e.g. skin and skull) and brain tissue.

Figure 1 Picture of the fast-gated module designed, assembled and tested for clinical applications.

Novel photonic devices were constructed as well as device prototypes for use in the clinical setting, including a specialised helmet for attaching the optical fibres to the head. Through software development, researchers could also analyse the time-resolved measurements on the head and calculate the oxy- and deoxyhaemoglobin concentrations. NEUROPT researchers worked on realistic modelling and computation, especially with a view to improving light propagation in the human head. The feasibility of this combinatorial approach was tested in separate visual and motor studies in healthy individuals. It was further successfully applied to perform measurements in patients with acute neurological conditions, photosensitive epilepsy or stroke.

 

Project Participants

  • Politecnico di Milano – Project coordinator (Italy)
  • Physikalisch-Technische Bundesanstalt (Germany)
  • University College London (United Kingdom)
  • Institute of Biocybernetics and Biomedical Engineering - Polish Academy of Sciences (Poland)
  • Fondazione IRCSS Istituto Neurologico Carlo Besta (Italy)
  • Charite - Universitaetsmedizin Berlin (Germany)
  • Warszawski Uniwersytet Medyczny (Poland)
  • Institut fur Lasertechnologien in der Medizin und Messtechnik an der Universitat Ulm (Germany)
  • Universita Degli Studi Di Firenze (Italy)
  • University of Bath (United Kingdom)
  • Fianium Ltd (United Kingdom)
  • Micro Photon Devices s.r.l. (Italy)
  • Becker & Hickl Gmbh (Germany)
  • CF Consulting Finanziamenti Unione Europea Srl (Italy)

 

Description of work performed

WP1 was focused on the advancement of a set of novel methodologies aiming at improving sensitivity resolution and quantitation of optical imaging methods. The possibility to strictly interact with photonics devices developers has made it possible to study new methods not achievable with commercial devices.

Figure 2 Functional activation recorded on a healthy subject following a motor task using the developed time-gated setup with a single optode probe (source-detector distance = 0.6 cm)

In WP2 novel ultrafast fiber lasers and photonic crystal fibers have been developed to produce supercontinuum light sources. Detector technology based on fast gated single-photon avalanche diode (SPADs), SPAD detectors operating in counting mode and SPADs arrays have been developed and fabricated. Time-correlated single-photon counting (TCSPC) electronics have been developed and evaluated within diffuse optical imaging instrumentation. The developed technologies offer increased optical power, choice of wavelength, detection speed, sensitivity and data processing capability for diffuse optical imaging.

WP3 was concentrated on improved forward and inverse solutions for realistic modelling of the light propagation in the human head. Investigated inverse models were capable of retrieving successfully the optical properties e.g. of two-layered turbid media. A variety of inverse programs are now available for retrieving the absolute values of physical quantities which are important for use in clinics.

In WP4 new instrumentation, ready for use in a clinical environment, was developed to facilitate novel measurements on the brain. In particular, second-generation 32-channels time-resolved optical tomography system has been built and tested.

In WP5 standardized protocols have been developed to assess the performance of instruments for time-domain optical imaging of the brain. These allow the comparison of various instruments and to estimate the technological and methodological advances. Liquid phantoms with known optical properties have been provided as a basis for the implementation of the protocols.

In WP6 a software package for analysis of the time-resolved measurements on the head was developed. This has been used to process signals acquired during clinical measurement campaigns and physical phantom measurements. Furthermore, software tools were developed to visualize and correlate data from optical brain imaging methods and other modalities (EEG, fMRI, SPECT).

Figure 3 Activation in the infant brain reconstructed using cortical mapping

WP7 aims at transferring time-domain optical imaging from a methodological and technical ground into the field of application. Measurements on healthy subjects showed the feasibility to study functional activation during simple motor and visual tasks with NIRS and successfully demonstrated the simultaneous recording with other physiologic parameters (EEG; Doppler fluometry). Measurement campaign on patients with circumscribed diseases, clinically validated these advanced non-invasive time-domain optical imaging techniques. 

In WP8 a systematic review of papers regarding the NIRS application on selected clinical fields has been performed to provide a survey on the use of diffuse optical imaging of brain. As compared to the continuous wave NIRS data reported in the literature, the results obtained by time-domain NIRS evidenced a better quantification of physiological parameters, improved spatial resolution and overall robustness of the NIRS measurements.

Given the non-invasive nature of the NEUROPT approach and its potential to be continuously applied at the bedside, it should facilitate the diagnosis of functional brain impairment and monitor its progress. As a result, it should improve the prognosis of patients with serious neurological conditions and could also be applied for imaging the brain of infants.

Selected publications

A. Pifferi, A. Torricelli, L. Spinelli, D. Contini, R. Cubeddu, F. Martelli, G. Zaccanti, A. Tosi, A. Dalla Mora, F. Zappa, and S. Cova, “Time-Resolved Diffuse Reflectance Using Small Source-Detector Separation and Fast Single-Photon Gating”, Physical Review Letters, vol. 100, pp. 138101, Mar. 2008.

A. Dalla Mora, A. Tosi, F. Zappa, S. Cova, D. Contini, A. Pifferi, L. Spinelli, A. Torricelli, and R. Cubeddu, “Fast-Gated Single-Photon Avalanche Diode for Wide Dynamic Range Near Infrared Spectroscopy”, IEEE Journal of Selected Topics in Quantum Electronics, vol. 16, no. 4, pp. 1023-1030, July-Aug. 2010.

M. Mazurenka, L. Di Sieno, G. Boso, D. Contini, A. Pifferi, A. Dalla Mora, A. Tosi, H. Wabnitz, and R. Macdonald, “Non-contact in vivo diffuse optical imaging using a time-gated scanning system”, Biomedical Optics Express, vol. 4, iss. 10, pp. 2257-2268, Sept. 2013.

 S. Koch, C. Habermehl, J. Mehnert, C. H. Schmitz, S. Holtze, A. Villringer, J. Steinbrink, and H. Obrig, “High-Resolution Optical Functional Mapping of the Human Somatosensory Cortex”, Frontiers in Neuroenergetics, vol. 2, no. 12, Jun. 2010.

A. Torricelli, D. Contini, A. Pifferi, M. Caffini, R. Re, L. Zucchelli, and L. Spinelli, “Time domain functional NIRS imaging for human brain mapping”, NeuroImage,  vol. 85, iss. 1, pp. 28-50, Jan. 2014.

M. Mazurenka, A. Jelzow, H. Wabnitz, D. Contini, L. Spinelli, A. Pifferi, R. Cubeddu, A. Dalla Mora, A. Tosi, F. Zappa, and R. Macdonald, “Non-contact time-resolved diffuse reflectance imaging at null source-detector separation”, Optics Express vol. 20, iss. 1, pp. 283-290, Jan. 2012.