Nick Everdell

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.

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 whole-head optical tomography of passive motor evoked responses in the neonate

Optical tomography has been used to reconstruct three-dimensional images of the entire neonatal head during motor evoked responses. Data were successfully acquired during passive movement of each arm on four out of six infants examined, from which eight sets of bilateral images of hemodynamic parameters were reconstructed. Six out of the eight images showed the largest change in total hemoglobin in the region of the contralateral motor cortex. The mean distance between the peak response in the image and the estimated position of the contralateral motor cortex was 10.8 mm. These results suggest that optical tomography may provide an appropriate technique for non-invasive cot-side imaging of brain function.

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.

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.

Three-dimensional time-resolved optical mammography of the uncompressed breast

Optical tomography is being developed as a means of detecting and specifying disease in the adult female breast. We present a series of clinical three-dimensional optical images obtained with a 32-channel time-resolved system and a liquid-coupled interface. Patients place their breasts in a hemispherical cup to which sources and detectors are coupled, and the remaining space is filled with a highly scattering fluid. A cohort of 38 patients has been scanned, with a variety of benign and malignant lesions. Images show that hypervascularization associated with tumors provides very high contrast due to increased absorption by hemoglobin. Only half of the fibroadenomas scanned could be observed, but of those that could be detected, all but one revealed an apparent increase in blood volume and a decrease in scatter and oxygen saturation.

A frequency multiplexed near-infrared topography system for imaging functional activation in the brain

We have developed a novel near-infrared optical topography system that can acquire images of functional activation in the human brain at 10 frames per second using 32 detectors. The image acquisition rate is inversely proportional to the number of detectors, so the maximum acquisition rate using four detectors is 80Hz. 16 laser diode sources (8 at 785 and 8 at 850nm) are illuminated simultaneously, and each of 8 avalanche photodiode detectors records light from several sources at the same time. The contribution from each source is demultiplexed in software using fast Fourier transforms. This allows for a more flexible, smaller, and less complex system than is achievable using traditional hardware demodulation techniques, such as lock-in amplifiers. The system will eventually incorporate a total of 64 sources and 32 detectors, enabling the entire adult cortex to be imaged. The system is designed to be as flexible as possible, and to be applicable to a wide variety of experimental and clinical needs. To thi...

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.

Investigation of depth dependent changes in cerebral haemodynamics during face perception in infants

Near-infrared spectroscopy has been used to record oxygenation changes in the visual cortex of 4 month old infants. Our in-house topography system, with 30 channels and 3 different source-detector separations, recorded changes in the concentration of oxy-, deoxy- and total haemoglobin (HbO2, HHb and HbT) in response to visual stimuli (face, scrambled visual noise and cartoons as rest). The aim of this work was to demonstrate the capability of the system to spatially localize functional activation and study the possibility of depth discrimination in the haemodynamic response. The group data show both face stimulation and visual noise stimulation induced significant increases in HbO2 from rest, but the increase in HbO2 with face stimulation was not significantly different from that seen with visual noise stimulation. The face stimuli induced increases in HbO2 were spread across a greater area across all depths than visual noise induced changes. In results from a single subject there was a significant increase of HbO2 in the inferior area of the visual cortex in response to both types of stimuli, and a larger number of channels (source-detector pairs) showed HbO2 increase to face stimuli, especially at the greatest depth. Activation maps were obtained using 3D reconstruction methods on multi source-detector separation optical topography data.

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.