Selective cortical mapping of biological motion processing in young infants.

How specialized is the infant brain for perceiving the facial and manual movements displayed by others? Although there is evidence for a network of regions that process biological motion in adults--including individuated responses to the perception of differing facial and manual movements--how this cortical specialization develops remains unknown. We used functional near-infrared spectroscopy [Lloyd-Fox, S., Blasi, A., & Elwell, C. Illuminating the developing brain: The past, present and future of functional near-infrared spectroscopy. Neuroscience and Biobehavioral Reviews, 34, 269-284, 2010] to investigate the ability of 5-month-old infants to process differing biological movements. Infants watched videos of adult actors moving their hands, their mouth, or their eyes, all in contrast to nonbiological mechanical movements, while hemodynamic responses were recorded over the their frontal and temporal cortices. We observed different regions of the frontal and temporal cortex that responded to these biological movements and different patterns of cortical activation according to the type of movement watched. From an early age, our brains selectively respond to biologically relevant movements, and further, selective patterns of regional specification to different cues occur within what may correspond to a developing "social brain" network. These findings illuminate hitherto undocumented maps of selective cortical activation to biological motion processing in the early postnatal development of the human brain.

Social perception in infancy: a near infrared spectroscopy study.

The capacity to engage and communicate in a social world is one of the defining characteristics of the human species. While the network of regions that compose the social brain have been the subject of extensive research in adults, there are limited techniques available for monitoring young infants. This study used near infrared spectroscopy to investigate functional activation in the social brain network of 36 five-month-old infants. We measured the hemodynamic responses to visually presented stimuli in the temporal lobes. A significant increase in oxyhemoglobin was localized to 2 posterior temporal sites bilaterally, indicating that these areas are involved in the social brain network in young infants.

Optical tomography of the breast using a multi-channel time-resolved imager.

A time-resolved optical tomography system has been used to generate cross-sectional images of the human breast. Images are reconstructed using an iterative, nonlinear algorithm and measurements of mean photon flight time relative to those acquired on a homogeneous reference phantom. Thirty-eight studies have been performed on three healthy volunteers and 21 patients with a variety of breast lesions including cancer. We have successfully detected 17 out of 19 lesions, and shown that optical images of the healthy breast of the same volunteer display a heterogeneity which is repeatable over a period of months. However, results also indicate that the lack of accurate quantitation of optical parameters and limited morphological information limits the ability to characterize different types of lesions and distinguish benign from malignant tissues. Drawbacks of our current methodology and plans for overcoming them are discussed.

Evaluating real-time image reconstruction in diffuse optical tomography using physiologically realistic test data.

In diffuse optical tomography (DOT), real-time image reconstruction of oxy- and deoxy-haemoglobin changes occurring in the brain could give valuable information in clinical care settings. Although non-linear reconstruction techniques could provide more accurate results, their computational burden makes them unsuitable for real-time applications. Linear techniques can be employed under the assumption that the expected change in absorption is small. Several approaches exist, differing primarily in their handling of regularization and the noise statistics. In real experiments, it is impossible to compute the true noise statistics, because of the presence of physiological oscillations in the measured data. This is even more critical in real-time applications, where no off-line filtering and averaging can be performed to reduce the noise level. Therefore, many studies substitute the noise covariance matrix with the identity matrix. In this paper, we examined two questions: does using the noise model with realistic, imperfect data yield an improvement in image quality compared to using the identity matrix; and what is the difference in quality between online and offline reconstructions. Bespoke test data were created using a novel process through which simulated changes in absorption were added to real resting-state DOT data. A realistic multi-layer head model was used as the geometry for the reconstruction. Results validated our assumptions, highlighting the validity of computing the noise statistics from the measured data for online image reconstruction, which was performed at 2 Hz. Our results can be directly extended to a real application where real-time imaging is required.

Assessment of an in situ temporal calibration method for time-resolved optical tomography.

A 32-channel time-resolved optical imaging device is developed at University College London to produce functional images of the neonatal brain and the female breast. Reconstruction of images using time-resolved measurements of transmitted light requires careful calibration of the temporal characteristics of the measurement system. Since they can often vary over a period of time, it is desirable to evaluate these characteristics immediately after, or prior to, the acquisition of image data. A calibration technique is investigated that is based on the measurement of light back-reflected from the surface of the object being imaged. This is facilitated by coupling each detector channel with an individual source fiber. A Monte Carlo model is employed to investigate the influence of the optical properties of the object on the back-reflected signal. The results of simulations indicate that their influence may be small enough to be ignored in some cases, or could be largely accounted for by a small adjustment to the calibrated data. The effectiveness of the method is briefly demonstrated by imaging a solid object with tissue-equivalent optical properties.

Imaging changes in blood volume and oxygenation in the newborn infant brain using three-dimensional optical tomography.

Induced haemodynamic and blood oxygenation changes occurring within the brain of a ventilated newborn infant have been imaged in three dimensions using optical tomography. Noninvasive measurements of the flight times of transmitted light were acquired during illumination of the brain by laser pulses at wavelengths of 780 nm and 815 nm. The oxygen and carbon dioxide partial pressures were adjusted through alterations to the ventilator settings, resulting in changes to the cerebral blood volume and oxygenation. Three-dimensional images were generated using the physiologically associated differences in the measured data, obviating the need for data calibration using a separate reference measurement. The results exhibit large changes in absorption coefficient at both wavelengths. Images corresponding to differences in concentrations of oxy- and deoxyhaemoglobin are in qualitative agreement with known physiological data.

Three-dimensional optical tomography of the premature infant brain.

For the first time, three-dimensional images of the newborn infant brain have been generated using measurements of transmitted light. A 32-channel time-resolved imaging system was employed, and data were acquired using custom-made helmets which couple source fibres and detector bundles to the infant head. Images have been reconstructed using measurements of mean flight time relative to those acquired on a homogeneous reference phantom, and using a head-shaped 3D finite-element-based forward model with an external boundary constrained to match the measured positions of the sources and detectors. Results are presented for a premature infant with a cerebral haemorrhage predominantly located within the left ventricle. Images representing the distribution of absorption at 780 nm and 815 nm reveal an asymmetry consistent with the haemorrhage, and corresponding maps of blood volume and fractional oxygen saturation are generally within expected physiological values.

MONSTIR II: a 32-channel, multispectral, time-resolved optical tomography system for neonatal brain imaging.

We detail the design, construction and performance of the second generation UCL time-resolved optical tomography system, known as MONSTIR II. Intended primarily for the study of the newborn brain, the system employs 32 source fibres that sequentially transmit picosecond pulses of light at any four wavelengths between 650 and 900 nm. The 32 detector channels each contain an independent photo-multiplier tube and temporally correlated photon-counting electronics that allow the photon transit time between each source and each detector position to be measured with high temporal resolution. The system's response time, temporal stability, cross-talk, and spectral characteristics are reported. The efficacy of MONSTIR II is demonstrated by performing multi-spectral imaging of a simple phantom.

Mapping cortical haemodynamics during neonatal seizures using diffuse optical tomography: a case study.

Seizures in the newborn brain represent a major challenge to neonatal medicine. Neonatal seizures are poorly classified, under-diagnosed, difficult to treat and are associated with poor neurodevelopmental outcome. Video-EEG is the current gold-standard approach for seizure detection and monitoring. Interpreting neonatal EEG requires expertise and the impact of seizures on the developing brain remains poorly understood. In this case study we present the first ever images of the haemodynamic impact of seizures on the human infant brain, obtained using simultaneous diffuse optical tomography (DOT) and video-EEG with whole-scalp coverage. Seven discrete periods of ictal electrographic activity were observed during a 60 minute recording of an infant with hypoxic-ischaemic encephalopathy. The resulting DOT images show a remarkably consistent, high-amplitude, biphasic pattern of changes in cortical blood volume and oxygenation in response to each electrographic event. While there is spatial variation across the cortex, the dominant haemodynamic response to seizure activity consists of an initial increase in cortical blood volume prior to a large and extended decrease typically lasting several minutes. This case study demonstrates the wealth of physiologically and clinically relevant information that DOT-EEG techniques can yield. The consistency and scale of the haemodynamic responses observed here also suggest that DOT-EEG has the potential to provide improved detection of neonatal seizures.

Three-dimensional optical topography of brain activity in infants watching videos of human movement.

We present 3D optical topography images reconstructed from data obtained previously while infants observed videos of adults making natural movements of their eyes and hands. The optical topography probe was placed over the temporal cortex, which in adults is responsible for cognitive processing of similar stimuli. Increases in oxyhaemoglobin were measured and reconstructed using a multispectral imaging algorithm with spatially variant regularization to optimize depth discrimination. The 3D optical topography images suggest that similar brain regions are activated in infants and adults. Images were presented showing the distribution of activation in a plane parallel to the surface, as well as changes in activation with depth. The time-course of activation was followed in the pixel which demonstrated the largest change, showing that changes could be measured with high temporal resolution. These results suggest that infants a few months old have regions which are specialized for reacting to human activity, and that these subtle changes can be effectively analysed using 3D optical topography.

Optical tomography of a realistic neonatal head phantom.

We have begun clinical trials of optical tomography of the neonatal brain. To validate this research, we have built and imaged an anatomically realistic, tissue-equivalent neonatal head phantom that is hollow, allowing contrasting objects to be placed inside it. Images were reconstructed by use of two finite-element meshes, one generated from a computed tomography image of the phantom and the other spherical. The phantom was filled with a liquid of the same optical properties as the outer region, and two perturbations were placed inside. These were successfully imaged with good separation between the absorption and scatter coefficients. The phantom was then refilled with a liquid of increased absorption compared with the background to simulate the brain, and the absolute properties of the two regions were found. These were used as a priori information for the complete reconstruction. Both perturbations were visible, superimposed on the increased absorption of the central region. The head-shaped mesh performed slightly better than the spherical mesh, particularly when the absorption of the central region of the phantom was increased.