Jeremy C. Hebden

Recent advances in diffuse optical imaging

We review the current state-of-the-art of diffuse optical imaging, which is an emerging technique for functional imaging of biological tissue. It involves generating images using measurements of visible or near-infrared light scattered across large (greater than several centimetres) thicknesses of tissue. We discuss recent advances in experimental methods and instrumentation, and examine new theoretical techniques applied to modelling and image reconstruction. We review recent work on in vivo applications including imaging the breast and brain, and examine future challenges.

Optical imaging in medicine: II. Modelling and reconstruction

The desire for a diagnostic optical imaging modality has motivated the development of image reconstruction procedures involving solution of the inverse problem. This approach is based on the assumption that, given a set of measurements of transmitted light between pairs of points on the surface of an object, there exists a unique three-dimensional distribution of internal scatterers and absorbers which would yield that set. Thus imaging becomes a task of solving an inverse problem using an appropriate model of photon transport. In this paper we examine the models that have been developed for this task, and review current approaches to image reconstruction. Specifically, we consider models based on radiative transfer theory and its derivatives, which are either stochastic in nature (random walk, Monte Carlo, and Markov processes) or deterministic (partial differential equation models and their solutions). Image reconstruction algorithms are discussed which are based on either direct backprojection, perturbation methods, nonlinear optimization, or Jacobian calculation. Finally we discuss some of the fundamental problems that must be addressed before optical tomography can be considered to be an understood problem, and before its full potential can be realized.

Optical imaging in medicine: I. Experimental techniques

The overwhelming scatter which occurs when optical radiation propagates through tissue severely limits the ability to image internal structure using measurements of transmitted intensity. A broad range of methods has been proposed during the past decade or so in order to improve imaging performance. Direct methods involve isolating an unscattered or least-scattered component of transmitted scattered light. Indirect methods generally involve measuring some characteristic of the temporal distribution of transmitted light, or an equivalent in the frequency domain, and obtaining a computational solution to the inverse problem. In this paper, we review the experimental techniques which have been proposed in order to explore both direct and indirect imaging. The relative merits and limitations of the various experimental methods are discussed, and we consider the future directions and likelihood of success of optical imaging in medicine.

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.

A 32-channel time-resolved instrument for medical optical tomography

A prototype multichannel time-resolved medical optical tomography system is presented, and various instrumental aspects and performance issues are discussed. The instrument has been designed primarily as a continuous bedside monitor for obtaining functional images of premature infants’ brains that are at an increased risk of injury due to dysfunction in cerebral oxygenation or hemodynamics. Separate maps of the internal absorption and scattering properties can be reconstructed from purely temporal measurements of photons transmitted diffusely through the tissue, and without recourse to reference or baseline measurements. The instrument employs 32 source fibers that sequentially deliver near-infrared pulsed laser radiation of picosecond duration. Transit time measurements of very high temporal resolution and stability are made between these sources and 32 detector optodes that are located on the surface. The effectiveness of this instrument is demonstrated by successfully imaging a tissue-equivalent phantom.

Time resolved imaging through a highly scattering medium

Transmission images through a highly scattering medium have been obtained using picosecond pulses of visible light. The imaging method involves recording and discriminating between the times-of-flight of photons that penetrate th medium and using a fraction of the light with the shortest travel times to construct an image. The technique is being developed as a possible alternative method of screening for breast cancer without using potentially harmful x-rays. One- and two-dimensional images are presented of objects whose optical thicknesses are comparable with those of the human breast at visible wavelengths.

Three-dimensional time-resolved optical tomography of a conical breast phantom

A 32-channel time-resolved imaging device for medical optical tomography has been employed to evaluate a scheme for imaging the human female breast. The fully automated instrument and the reconstruction procedure have been tested on a conical phantom with tissue-equivalent optical properties. The imaging protocol has been designed to obviate compression of the breast and the need for coupling fluids. Images are generated from experimental data with an iterative reconstruction algorithm that employs a three-dimensional (3D) finite-element diffusion-based forward model. Embedded regions with twice the background optical properties are revealed in separate 3D absorption and scattering images of the phantom. The implications for 3D time-resolved optical tomography of the breast are discussed.

Time resolved optical tomography of the human forearm

A 32-channel time-resolved optical imaging instrument has been developed principally to study functional parameters of the new-born infant brain. As a prelude to studies on infants, the device and image reconstruction methodology have been evaluated on the adult human forearm. Cross-sectional images were generated using time-resolved measurements of transmitted light at two wavelengths. All data were acquired using a fully automated computer-controlled protocol. Images representing the internal scattering and absorbing properties of the arm are presented, as well as images that reveal physiological changes during a simple finger flexion exercise. The results presented in this paper represent the first simultaneous tomographic reconstruction of the internal scattering and absorbing properties of a clinical subject using purely temporal data, with additional co-registered difference images showing repeatable absorption changes at two wavelengths in response to exercise.

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.