A key competence of the PTB department Biomedical Optics is the development and application of optical imaging techniques with sub-nanosecond time resolution.

Recording of time-resolved diffuse near-infrared reflectance or fluorescence on the head allows to achieve depth selectivity in the detection of concentration changes of tissue constituents or exogenous chromophores. Thus intra- and extracerebral contributions to the signal can be separated. The technique has been applied in functional stimulation experiments and in bedside perfusion measurements that are based on monitoring absorption changes following a dye bolus. A time-domain brain imager has been developed and is available for application in various projects within BNIC. Simultaneously, algorithms for depth-selective assessment of changes in oxy- and deoxyhaemoglobin concentrations are being developed and optimized.

Neuroimaging applications

• Recording of cerebral haemodynamic response to functional stimulation, in particular if fMRI is not applicable

• Functional stimulation experiments, in part simultaneously with MEG or fMRI to study neurovascular coupling
• Assessment of cerebral perfusion following a dye bolus, in particular in stroke patients
• Recording of fluorescence of a contrast agent from the human cortex

Method

Short (~ 100 ps) laser pulses are delivered to a certain position of the head via an optical fibre. Photons exiting the tissue after multiple scattering at a distance of, e.g., 3 cm from the source ("diffuse reflectance") are collected by an optical fibre bundle and fed to a fast detector. By time-correlated single photon counting the time of flight of each detected photon is measured and the distribution of times of flight is accumulated.

The spread of times of flight of photons depends on the optical properties (scattering and absorption coefficient) of the traversed tissue. By analysing the shape of the distribution of times of flight, depth-resolved assessment of optical properties is possible: Photons arriving after short times of flight ("early photons") on average penetrate less deeply into the tissue than photons with long times of flight ("late photons"). Simultaneous measurement at several wavelengths allows to investigate changes in the concentrations of oxy- and deoxyhaemoglobin.

Instrument

Our recently developed prototype time-domain NIR brain imager [Wabnitz et al. 2005] relies on picosecond diode lasers emitting at various wavelengths, an optical fibre switch and multi-channel time-correlated single photon counting. The configuration of the instrument is flexible and allows for, e.g.,

• 16-pixel imaging obtained by switching through 9 source fibres while simultaneously recording in 4 detection channels
• simultanous recording at four sites
• simultaneous recording of diffuse reflectance and fluorescence at two sites

Applications in progress

• Assessment of cerebral perfusion by ICG bolus tracking (diffuse reflectance, fluorescence)

  together with J. Steinbrink, H. Obrig (Charité) (S8)

• Concurrent time-resolved near-infrared spectroscopy and DC magnetoencephalography (motor stimulation)

  together with T. Sander (PTB, 8.2), S. Leistner, B.-M. Mackert (Charité) (Core 3, P3)

• Depth-selective imaging of responses to motor stimulation in healthy volunteers

  together with C. Drenckhahn, J.P. Dreier (Charité) (P4)

• Concurrent time-resolved near-infrared spectroscopy and fMRI

  together with R. Brühl (PTB, 8.1) (Core 2)

External collaboration

• A. Liebert (Institute of Biocybernetics and Biomedical Engineering, Warsaw)

• A. Torricelli (Politecnico di Milano, Dept. of Physics, Milan)
• T. Durduran (University of Pennsylvania, Philadelphia)