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Imaging the neonatal brain with optical tomography

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Optical topography is able to measure and display haemodynamic changes occurring in the cortex, but is far less sensitive to deeper tissues. Optical tomography, however, uses widely spaced sources and detectors to measure light which has passed through central regions of the brain, which can be affected by disruption to the supply of blood and oxygen around birth. Light travelling through these regions is heavily attenuated and therefore more intense light sources and more sensitive detectors are required. Even so, the acquisition time is typically a few minutes compared to less than a second in the case of optical topography.

Brain injury in preterm and term infants is a major cause of permanent disability and death. Several groups have developed optical tomography of the infant brain with the aim of providing diagnostic and therapeutic information about the more important types of brain injury. Intraventricular haemorrhage may occur in premature infants whose cerebral vasculature is too weak to withstand the fluctuations in blood pressure which occur during birth (Whitelaw 2001), while periventricular leucomalacia is damage to the white matter which is common in premature infants (Volpe 2001). Hypoxic-ischaemic brain injury around the time of birth is a major cause of brain injury in the term infant (Wyatt 2002). These three mechanisms of brain injury all manifest themselves as disruption to the supply of blood and oxygen to vulnerable areas of the brain. Currently, they are either diagnosed clinically, by ultrasound (which gives only anatomical information) or MRI (which clinicians may be reluctant to request if it means moving a very ill infant out of an intensive care environment). Optical tomography may provide a bedside system to identify infants at risk, to diagnose injury and to monitor treatment (Thoresen 2000). For a detailed review of optical imaging of the neonatal brain, see Hebden (2003).

The first tomographic images of the neonatal were recorded by the group of Benaron, by reconstructing measurements of mean photon flight time made across the neonatal head. Thirty-four pairs of sources and detectors were attached to the head using a headband (Hintz et al. 1998) and were used to obtain 2D tomographic slice images of anatomical disorders (Hintz et al. 1999, Benaron et al. 2000) and functional activation (Benaron et al. 2000). Eight optical images were generated from six infants in the first month of life, four of whom had IVH. Six of the eight images compared favourably with CT, ultrasound and MRI images. Later, Benaron et al. (2000) generated images from two neonatal subjects, one a control and the other with a stroke. They detected a significant difference between the two subjects, and the location of the stroke agreed with a CT image. Images were also presented, using the same approach, of functional motor activity. The images obtained in these studies were remarkable, given the relatively simple instrumentation (Benaron et al. 1994b) and crude reconstruction techniques (Benaron et al. 1994a), and encouraged the suggestion that optical tomography could play a major diagnostic role in neonatology.

More recently, the group at University College London has used a purpose-built 32 channel time-resolved imaging system (Schmidt et al. 2000) and a non-linear image reconstruction approach based on finite element modelling (Arridge et al. 2000) to generate 3D images of the neonatal head. Sources and detectors are coupled to the head using a foam-lined helmet which is custom built for each infant. The positions of the connectors within the helmet are used to define the outer surface of a finite element mesh (Gibson et al. 2003) which is used for image reconstruction. The first published results were images of the brain of an infant with IVH, which revealed an increase in blood volume in the region of the haemorrhage as shown on an ultrasound examination (Hebden et al. 2002). Another of the babies studied so far was mechanically ventilated, allowing images to be reconstructed from data acquired at two wavelengths during changes in inspired oxygen and carbon dioxide (Hebden et al. 2004). The reconstructed images of [HHb] and [HbO] agreed qualitatively with physiological predictions. Recently, images have been obtained from a pair of twins, recorded consecutively on the same day. One twin was anatomically normal while the other had an IVH which had caused additional bleeding into the brain tissue. Images of blood volume and oxygenation in the baby with the normal brain (Figure 4a) are symmetrical about the midline and appear to show a decrease in blood volume in the white matter. The haemorrhage (Figure 4b) can be seen as an increase in blood volume and, a decrease in oxygenation (from about 65% to about 10%). The location of the increase in blood volume correlated well with the site of the IVH determined from an ultrasound image, but interestingly, the location of the increase in oxygenation appeared to correlate more closely with the infarct of the haemorrhage into the brain tissue.

Encouraging results have been obtained by neonatal optical tomography, although so far the application is not as widely used as optical topography. This is partly due to the additional complexity of the instrumentation and the practical difficulties of acquiring data from premature babies who may be very ill. A further difficulty is obtaining an adequate reference measurement for data calibration. Theoretical advances such as solving for the coupling coefficients and the incorporation of prior anatomical information from MRI and improvements to instrumentation are expected to lead to significant improvements in image quality and clinical acceptance.

ReferencesEdit

  • Arridge S R, J C Hebden, M Schweiger, F E W Schmidt, M E Fry, E M C Hillman, H Dehghani, and D T Delpy (2000), "A method for 3D time-resolved optical tomography" Int. J. Imag. Sys. Tech 11 2-11.
  • Benaron D A, S R Hintz, A Villringer, D A Boas, A Kleinschmidt, J Frahm, C Hirth, H Obrig, J C van Houten, E L Kermit, W-F Cheong, and D K Stevenson (2000), "Noninvasive functional imaging of human brain using light" J. Cerebr. Blood Flow Metab. 20 469-477.
  • Benaron D A, D C Ho, S D Spilman, J C van Houten, and D K Stevenson (1994a), "Non-recursive linear algorithms for optical imaging in diffusive media" Adv. Exp. Med. Biol. 361 215-222.
  • Benaron D A, D C Ho, S D Spilman, J C van Houten, and D K Stevenson (1994b), "Tomographic time-of-flight optical imaging device" Adv. Exp. Med. Biol. 361 207-214.
  • Gibson A P, J Riley, M Schweiger, J C Hebden, S R Arridge, and D T Delpy (2003), "A method for generating patient-specific finite element meshes for head modelling" Phys. Med. Biol. 48 481-495.
  • Hebden J C (2003), "Advances in optical imaging of the newborn infant brain" Psychophysiology 40 501-510.
  • Hebden J C, A P Gibson, T Austin, R M Yusof, N Everdell, D T Delpy, S R Arridge, J H Meek, and J S Wyatt (2004), "Imaging changes in blood volume and oxygenation in the newborn infant brain using three-dimensional optical tomography" Phys. Med. Biol. 49(7) 1117-1130.
  • Hebden J C, A P Gibson, R M Yusof, N Everdell, E M Hillman, D T Delpy, T Austin, J Meek, and J S Wyatt (2002), "Three-dimensional optical tomography of the premature infant brain" Phys. Med. Biol. 47 4155-4166.
  • Hintz S R, D A Benaron, J P v Houten, J L Duckworth, F W H Liu, S D Spilman, D K Stevenson, and W-F Cheong (1998), "Stationary headband for clinical time-of-flight optical imaging at the bedside" Photochem. Photobiol. 68 361-369.
  • Hintz S R, W F Cheong, J P van Houten, D K Stevenson, and D A Benaron (1999), "Bedside imaging of intracranial hemorrhage in the neonate using light: Comparison with ultrasound, computed tomography, and magnetic resonance imaging" Pediatr. Res. 45(1) 54-59.
  • Schmidt F E W, M E Fry, E M C Hillman, J C Hebden, and D T Delpy (2000), "A 32-channel time-resolved instrument for medical optical tomography" Rev. Sci. Instrum. 71(1) 256-265.
  • Thoresen M (2000), "Cooling the newborn after asphyxia - physiological and experimental background and its clinical use" Semin. Neonatol. 5 61-73.
  • Volpe J J (2001), "Neurobiology of periventricular leukomalacia in the premature infant" Pediatr. Res. 50(5) 553-562.
  • Whitelaw A (2001), "Intraventricular haemorrhage and post haemorrhagic hydrocephalus: pathogenesis, prevention and future interventions" Semin. Neonatol. 6 135-146.
  • Wyatt J S (2002), "Applied physiology: brain metabolism following perinatal asphyxia" Current Paediatrics 12 227-231.

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