Time domain optical imaging device based on a commercial time-to-digital converter

Time-domain diffuse optical imaging is a noninvasive technique that uses pulsed near-infrared light as the interrogation source to produce quantitative images displaying the variation in blood volume and oxygenation in the human brain. Measuring the times of flights of photons provides information on the photon pathlengths in tissue, which enables absolute concentrations of the oxygenated and deoxygenated forms of hemoglobin to be estimated. Recent advances in silicon electronics have enabled the development of time-domain systems, which are lightweight and low cost, potentially enabling the imaging technique to be applied to a far greater cohort of subjects in a variety of environments. While such technology usually depends on customized circuits, in this article, we present a system assembled from commercially available components, including a low-cost time-to-digital converter and a silicon photomultiplier detector. The system is able to generate histograms of photon flight times at a rate of 81–90 kS/s and with a sampled bin width of 54 ps. The linearity and performance of the system are presented, and its potential as the basis for a modular multi-detector imaging system is explored

Three dimensional optical imaging of blood volume and oxygenation in the neonatal brain

Optical methods provide a means of monitoring cerebral oxygenation in newborn infants at risk of brain injury. A 32-channel optical imaging system has been developed with the aim of reconstructing three-dimensional images of regional blood volume and oxygenation. Full image data sets were acquired from 14 out of 24 infants studied; successful images have been reconstructed in 8 of these infants. Regional variations in cerebral blood volume and tissue oxygen saturation are present in healthy preterm infants. In an infant with a large unilateral intraventricular haemorrhage, a corresponding region of low oxygen saturation was detected. These results suggest that optical tomography may provide an appropriate technique for investigating regional cerebral haemodynamics and oxygenation at the cotside. (c) 2006 Elsevier Inc. All rights reserved

The reproducibility of optical mammography in healthy volunteers.

This study was designed to determine the reproducibility of optical mammography. Eight healthy pre-menopausal volunteers were scanned at different time intervals (minutes, weeks and months apart) to investigate the effects of within-subject variation, between-subject variation and systematic variations on both the raw data and images. The study shows that the greatest source of variation in optical mammography raw data and images is between different subjects, and scans of the same subject are very reproducible. The averaged total haemoglobin concentration from the eight volunteers was (24 ± 10) µM, and the average tissue oxygen saturation was (70 ± 10)%, which is comparable with other data in the literature. The average absorption coefficient at 780 nm was (0.0048 ± 0.0017) mm(-1) and the average reduced scatter coefficient at 780 nm was (0.80 ± 0.12) mm(-1). Again, this is comparable with published values. When our data are combined with the published values, the weighted average total haemoglobin concentration and tissue oxygen saturation for pre-menopausal breasts are (29 ± 8) µM and (73 ± 3)%, respectively. The results of our study show that we can be reassured that any changes within the tumour region seen during neoadjuvant therapy are likely to be due to a real physiological response to treatment, as the physiological properties of the breast remain relatively constant. However, in this study, we cannot distinguish between a tumour response to treatment and systemic changes in the healthy breast

Data-driven approach to optimum wavelength selection for diffuse optical imaging

The production of accurate and independent images of the changes in concentration of oxyhemoglobin and deoxyhemoglobin by diffuse optical imaging is heavily dependent on which wavelengths of near-infrared light are chosen to interrogate the target tissue. Although wavelengths can be selected by theoretical methods, in practice the accuracy of reconstructed images will be affected by wavelength-specific and system-specific factors such as laser source power and detector sensitivity. We describe the application of a data-driven approach to optimum wavelength selection for the second generation of University College London's multichannel, time-domain optical tomography system (MONSTIR II). By performing a functional activation experiment using 12 different wavelengths between 690 and 870 nm, we were able to identify the combinations of 2, 3, and 4 wavelengths which most accurately reproduced the results obtained using all 12 wavelengths via an imaging approach. Our results show that the set of 2, 3, and 4 wavelengths which produce the most accurate images of functional activation are [770, 810], [770, 790, 850], and [730, 770, 810, 850] respectively, but also that the system is relatively robust to wavelength selection within certain limits. Although these results are specific to MONSTIR II, the approach we developed can be applied to other multispectral near-infrared spectroscopy and optical imaging systems

Construction and validation of a database of head models for functional imaging of the neonatal brain

The neonatal brain undergoes dramatic structural and functional changes over the last trimester of gestation. The accuracy of source localisation of brain activity recorded from the scalp therefore relies on accurate age-specific head models. Although an age-appropriate population-level atlas could be used, detail is lost in the construction of such atlases, in particular with regard to the smoothing of the cortical surface, and so such a model is not representative of anatomy at an individual level. In this work, we describe the construction of a database of individual structural priors of the neonatal head using 215 individual-level datasets at ages 29-44 weeks postmenstrual age from the Developing Human Connectome Project. We have validated a method to segment the extra-cerebral tissue against manual segmentation. We have also conducted a leave-one-out analysis to quantify the expected spatial error incurred with regard to localising functional activation when using a best-matching individual from the database in place of a subject-specific model; the median error was calculated to be 8.3 mm (median absolute deviation 3.8 mm). The database can be applied for any functional neuroimaging modality which requires structural data whereby the physical parameters associated with that modality vary with tissue type and is freely available at www.ucl.ac.uk/dot-hub

Diffuse optical tomography for the detection of perinatal stroke at the cot side: a pilot study

BACKGROUND: Perinatal stroke is a potentially debilitating injury, often under-diagnosed in the neonatal period. We conducted a pilot study investigating the role of the portable, non-invasive brain monitoring technique, diffuse optical tomography (DOT), as an early detection tool for infants with perinatal stroke. METHODS: Four stroke-affected infants were scanned with a DOT system within the first 3 days of life and compared to four healthy control subjects. Spectral power, correlation, and phase lag between interhemispheric low frequency (0.0055–0.3 Hz) hemoglobin signals were assessed. Optical data analyses were conducted with and without magnetic resonance imaging (MRI)- guided stroke localization to assess the efficacy of DOT when used without stroke anatomical information. RESULTS: Interhemispheric correlations of both oxyhemoglobin and deoxyhemoglobin concentration were significantly reduced in the stroke-affected group within the very low (0.0055–0.0095 Hz) and resting state (0.01–0.08 Hz) frequencies (p < 0.003). There were no interhemispheric differences for spectral power. These results were observed even without MRI stroke localization. CONCLUSION: This suggests that DOT and correlation-based analyses in the low-frequency range can potentially aid the early detection of perinatal stroke, prior to MRI acquisition. Additional methodological advances are required to increase the sensitivity and specificity of this technique

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

Imaging in breast cancer: Diffuse optics in breast cancer: detecting tumors in pre-menopausal women and monitoring neoadjuvant chemotherapy

Diffuse optical spectroscopy (DOS) and diffuse optical imaging (DOI) are non-invasive diagnostic techniques that employ near-infrared (NIR) light to quantitatively characterize the optical properties of centimeter-thick, multiple-scattering tissues. Although NIR was first applied to breast diaphanography more than 70 years ago, quantitative optical methods employing time- or frequency-domain 'photon migration' technologies have only recently been used for breast imaging. Because their performance is not limited by mammographic density, optical methods can provide new insight regarding tissue functional changes associated with the appearance, progression, and treatment of breast cancer, particularly for younger women and high-risk subjects who may not benefit from conventional imaging methods. This paper reviews the principles of diffuse optics and describes the development of broadband DOS for quantitatively measuring the optical and physiological properties of thick tissues. Clinical results are shown highlighting the sensitivity of diffuse optics to malignant breast tumors in 12 pre-menopausal subjects ranging in age from 30 to 39 years and a patient undergoing neoadjuvant chemotherapy for locally advanced breast cancer. Significant contrast was observed between normal and tumor regions of tissue for deoxy-hemoglobin (p = 0.005), oxy-hemoglobin (p = 0.002), water (p = 0.014), and lipids (p = 0.0003). Tissue hemoglobin saturation was not found to be a reliable parameter for distinguishing between tumor and normal tissues. Optical data were converted into a tissue optical index that decreased 50% within 1 week in response to neoadjuvant chemotherapy. These results suggest a potential role for diffuse optics as a bedside monitoring tool that could aid the development of new strategies for individualized patient care