Tomographic imaging of flow and chromophore concentrations in biological tissue

Understanding the functional makeup of the brain is a holy grail of neuroscience, and imaging tools play a significant role in achieve this aim. Functional imaging is a more difficult goal than anatomical imaging because it depends on establishing a contrast mechanism that relates to physiological function and also can be measured with good accuracy and resolution. Optical techniques are very attractive because of the rich information encoded in the absorption spectra of many different molecules, but they are difficult to use at large scale because of the high degree of scattering that occurs in passing through different tissues of the body.

By using time-resolved measurements of the propagation of light from multiple illumination patterns, diffuse optical tomography (DOT) can produced low-resolution images of absorption and scattering properties, and decorrelate these to produce maps of oxygenation in the brain and other organs. At the same time, diffuse correlation spectroscopy (DCS) examines the way in which coherent light is decorrelated from itself when compared over time. This decorrelation naturally occurs due to the Brownian motion of endogenous scattering particles, and blood flow. Coherent optical techniques thus allow the non-invasive monitoring of blood flow and provide an indication of pathological cerebral auto-regulation during, e.g., stroke. Until recently, limitations in coherent detection technology have prevented significant developments towards diffuse correlation tomography (DCT), wherein volumetric images of blood flow can be produced.

In this project we aim to develop a system for DCT and time-resolved DOT in one device. This will bring the two techniques together to provide images of cerebral blood flow and cerebral metabolic rate of oxygen extraction in the brain for the first time. We propose the development of theoretical and experimental methods which will enable the development of a new generation of optical instruments for portable, low-cost, continuous simultaneous monitoring of blood flow and chromophore concentrations. The rich images produced by our system have the potential to vastly improve our understanding of underlying neurological processes and pathology, and to allow the efficient use of scarce resources in targeted treatments.

Impact in Neuroscience
In combining standard diffuse optical methods with correlation tomography, we introduce two new measurement parameters, namely the cerebral blood flow (CBF) and cerebral metabolic rate of oxygen extraction (CMRO2), which will enable a better understanding of the physiological status of the brain in a complete, accurate, and robust way. The combination of these two techniques will be unique worldwide. The value of the flow measurement is essential, owing to the link between the blood flow and the oxygen consumption: if a cell is using more oxygen it will demand more blood flow. By measuring both, we will be able to determine if the tissue is actually using more oxygen, indicated by an increase in flow, and a decrease in oxygen saturation. In so doing we expect to increase the understanding of the basic functional connectivity of the developing brain which will impact on other areas of cognitive neuroscience.

Impact in Healthcare
According to the global Action Report published by the World Health Organisation in 2012, preterm births are 15 million every year and rising. More than 80% of preterm births occur between 32-37 weeks of gestation and most of these babies can survive with essential newborn care. More than 75% of deaths of preterm births can be prevented without intensive care. Even though the risk of death to preterm infants is reducing, the ongoing potential for brain injury leads to severe disability, both physical and cognitive.
Through enabling the continuous monitoring of babies with existing or suspected impairment, our technology will also allow the targeted use of scarce rehabilitatory resources.
The long term impact of this research will be to improve the knowledge of pathophysiology of brain injury in premature babies in order to reduce the risk of brain impairment.

Impact in Imaging Science
Recent trends in imaging science have also seen the benefit of combining two or more imaging modalities, either from different scanners or on the same system. A well-established method to combine the information from different modalities is to merge them on the image level, i.e. the images are first reconstructed and then the information is combined (image fusion). However, when one or more of the modalities is ill-posed, as is the case here, then image reconstruction should properly be treated as the recovery of joint information simultaneously and entails the proper handling of joint prior information. We expect that the techniques developed in this project will produce impact in other multimodality/multispectral methodologies such as PET-MRI, MRI-EIT, and SPECT-CT, amongst others.

Impact in Data Science
We will develop novel methods for handling big datasets: three dimensions of space, two of time (short correlation time, long physiological time) and multispectrally. This "6D" problem will lead to novelty in compression methods and algorithmic design can be expected to impact on other areas of data science where continuous modelling of long time-series and large data arrays is relevent; notably geosciences and geostatistics, astrophysics, and the communications industry.