Improved sensitivity to cerebral hemodynamics during brain activation with a time-gated optical system: analytical model and experimental validation.

Time domain (TD) diffuse optical measurement systems are being applied to neuroimaging, where they can detect hemodynamics changes associated with cerebral activity. We show that TD systems can provide better depth sensitivity than the more traditional continuous wave (CW) systems by gating late photons, which carry information about deep layers of the brain, and rejecting early light, which is sensitive to the superficial physiological signal clutter. We use an analytical model to estimate the contrast due to an activated region of the brain, the instrumental noise of the systems, and the background signal resulting from superficial physiological signal clutter. We study the contrast-to-noise ratio and the contrast-to-background ratio as a function of the activation depth and of the source-detector separation. We then present experimental results obtained with a time-gated instrument on the motor cortex during finger-tapping exercises. Both the model and the experimental results show a similar contrast-to-noise ratio for CW and TD, but that estimation of the contrast is experimentally limited by background fluctuations and that a better contrast-to-background ratio is obtained in the TD case. Finally, we use the time-gated measurements to resolve in depth the brain activation during the motor stimulus.

Coregistered tomographic x-ray and optical breast imaging: initial results.

We describe what is, to the best of our knowledge, the first pilot study of coregistered tomographic x-ray and optical breast imaging. The purpose of this pilot study is to develop both hardware and data processing algorithms for a multimodality imaging method that provides information that neither x-ray nor diffuse optical tomography (DOT) can provide alone. We present in detail the instrumentation and algorithms developed for this multimodality imaging. We also present results from our initial pilot clinical tests. These results demonstrate that strictly coregistered x-ray and optical images enable a detailed comparison of the two images. This comparison will ultimately lead to a better understanding of the relationship between the functional contrast afforded by optical imaging and the structural contrast provided by x-ray imaging.

Optode positional calibration in diffuse optical tomography.

Although diffuse optical tomography is a highly promising technique used to noninvasively image blood volume and oxygenation, the reconstructed data are sensitive to systemic difference between the forward model and the actual experimental conditions. In particular, small changes in optode location or in the optode-tissue coupling coefficient significantly degrade the quality of the reconstruction images. Accurate system calibration therefore is an essential part of any experimental protocol. We present a technique for simultaneously calibrating optode positions and reconstructing images that significantly improves image quality, as we demonstrate with simulations and phantom experiments.

Volumetric diffuse optical tomography of brain activity.

We present three-dimensional diffuse optical tomography of the hemodynamic response to somatosensory stimulation in a rat. These images show the feasibility of volumetrically imaging the functional response to brain activity with diffuse light. A combination of positional optode calibration and contrast-to-noise ratio weighting was found to improve imaging performance.

Fluorescence optical diffusion tomography using multiple-frequency data.

A method is presented for fluorescence optical diffusion tomography in turbid media using multiple-frequency data. The method uses a frequency-domain diffusion equation model to reconstruct the fluorescent yield and lifetime by means of a Bayesian framework and an efficient, nonlinear optimizer. The method is demonstrated by using simulations and laboratory experiments to show that reconstruction quality can be improved in certain problems through the use of more than one frequency. A broadly applicable mutual information performance metric is also presented and used to investigate the advantages of using multiple modulation frequencies compared with using only one.