Imaging Cerebral Energy Metabolism in Healthy Infants.

Broadband near-infrared spectroscopy (bNIRS) has the potential to provide non-invasive measures of cerebral haemodynamic changes alongside changes in cellular oxygen utilisation through the measurement of mitochondrial enzyme cytochrome-c-oxidase (oxCCO). It therefore provides the opportunity to explore brain function and specialisation, which remains largely unexplored in infancy. We used bNIRS to measure changes in haemodynamics and changes in oxCCO in 4-to-7-month-old infants over the occipital and right temporal and parietal cortices in response to social and non-social visual and auditory stimuli. Changes in concentration of oxygenated-haemoglobin (Δ[HbO2]), deoxygenated haemoglobin (Δ[HHb]) and change in the oxidation state of oxCCO (Δ[oxCCO]) were calculated using changes in attenuation of light at 120 wavelengths between 780 and900 nm, using the UCLn algorithm. For 4 infants, the attenuation changes in a subset of wavelengths were used to perform image reconstruction, in an age-matched infant model, for channels over the right parietal and temporal cortices, using a multispectral approach which allows direct reconstruction of concentration change data. The volumetric reconstructed images were mapped onto the cortical surface to visualise the reconstructed changes in concentration of HbO2 and HHb and changes in metabolism for both social and non-social stimuli. Spatially localised activation was observed for Δ[oxCCO] and Δ[HbO2] over the temporo-parietal region, in response to the social stimulus. This study provides the first reconstructed images of changes in metabolism in healthy, awake infants.

Multishell Diffusion MRI-Based Tractography of the Facial Nerve in Vestibular Schwannoma.

BACKGROUND AND PURPOSE: Tractography of the facial nerve based on single-shell diffusion MR imaging is thought to be helpful before surgery for resection of vestibular schwannoma. However, this paradigm can be vitiated by the isotropic diffusion of the CSF, the convoluted path of the facial nerve, and its crossing with other bundles. Here we propose a multishell diffusion MR imaging acquisition scheme combined with probabilistic tractography that has the potential to provide a presurgical facial nerve reconstruction uncontaminated by such effects. MATERIALS AND METHODS: Five patients scheduled for vestibular schwannoma resection underwent multishell diffusion MR imaging (b-values = 0, 300, 1000, 2000 s/mm2). Facial nerve tractography was performed with a probabilistic algorithm and anatomic seeds located in the brain stem, cerebellopontine cistern, and internal auditory canal. A single-shell diffusion MR imaging (b-value = 0, 1000 s/mm2) subset was extrapolated from the multishell diffusion MR imaging data. The quality of the facial nerve reconstruction based on both multishell diffusion MR imaging and single-shell diffusion MR imaging sequences was assessed against intraoperative videos recorded during the operation. RESULTS: Single-shell diffusion MR imaging-based tractography was characterized by failures in facial nerve tracking (2/5 cases) and inaccurate facial nerve reconstructions displaying false-positives and partial volume effects. In contrast, multishell diffusion MR imaging-based tractography provided accurate facial nerve reconstructions (4/5 cases), even in the presence of ostensibly complex patterns. CONCLUSIONS: In comparison with single-shell diffusion MR imaging, the combination of multishell diffusion MR imaging-based tractography and probabilistic algorithms is a more valuable aid for surgeons before vestibular schwannoma resection, providing more accurate facial nerve reconstructions, which may ultimately improve the postsurgical patient's outcome.

A Fibreless Multiwavelength NIRS System for Imaging Localised Changes in Cerebral Oxidised Cytochrome C Oxidase.

Measurement of the oxidation state of cytochrome c oxidase (oxCCO) can inform directly on neuronal metabolism. Conventionally this has been measured in vivo using benchtop broadband near infrared spectroscopy (NIRS) systems. Spatially resolved measures of oxCCO have recently been made possible using a multichannel fibre-based broadband NIRS system. We describe the use of a fibreless multiwavelength NIRS system using light emitting diodes (LED) designed specifically to image localised changes in oxCCO and hence neuronal metabolism. A fibreless system consisting of four modules, each containing two LED sources and four photodiode detectors, was developed. Each LED source contained eight LED dies (780, 811, 818, 842, 850, 882, 891 and 901 nm) assembled in an area of 1.5 × 1.5 mm. A well-established hyperoxia protocol was used to evaluate the oxCCO spatially resolved measurement capabilities of the system and, subsequently, its imaging capabilities were tested using a functional activation paradigm. A multi-spectral image reconstruction approach was used to provide images of Δ[HbO2], Δ[HHb] and Δ[oxCCO] from the multi-distance, multi-channel optical datasets. This novel fibreless multiwavelength NIRS system allows imaging of localised changes in oxCCO in the human brain, and has potential for development as an inexpensive, wearable, continuous monitor of cerebral energetics in a range of experimental and clinical scenarios.

N2pc reflects two modes for coding the number of visual targets.

Humans share with a variety of animal species the spontaneous ability to detect the numerical correspondence between limited quantities of visual objects and discrete auditory events. Here, we explored how such mental representation is generated in the visual modality by monitoring a parieto-occipital ERP component, N2pc, whose amplitude covaries with the number of visual targets in explicit enumeration. Participants listened to an auditory sequence of one to three tones followed by a visual search display containing one to three targets. In Experiment 1, participants were asked to respond based on the numerical correspondence between tones and visual targets. In Experiment 2, participants were asked to ignore the tones and detect a target presence in the search display. The results of Experiment 1 showed an N2pc amplitude increase determined by the number of visual targets followed by a centroparietal ERP component modulated by the numerical correspondence between tones and visual targets. The results of Experiment 2 did not show an N2pc amplitude increase as a function of the number of visual targets. However, the numerical correspondence between tones and visual targets influenced N2pc amplitude. By comparing a subset of amplitude/latency parameters between Experiment 1 and 2, the present results suggest N2pc reflects two modes for representing the number of visual targets. One mode, susceptible to subjective control, relies on visual target segregation for exact target individuation, whereas a different mode, likely enabling spontaneous cross-modal matching, relies on the extraction of rough information about number of targets from visual input.

Spatial Distribution of Changes in Oxidised Cytochrome C Oxidase During Visual Stimulation Using Broadband Near Infrared Spectroscopy Imaging.

Functional hyperaemia, characterised as an increase in concentration of oxyhaemoglobin [HbO2] and a decrease in concentration of deoxyhaemoglobin [HHb] in response to neuronal activity, can be precisely mapped using diffuse optical spectroscopy. However, such techniques do not directly measure changes in metabolic activity during neuronal activation. Changes in the redox state of cerebral oxidised cytochrome c oxidase Δ[oxCCO] measured by broadband spectroscopy may be a more specific marker of neuronal metabolic activity. This study aims to investigate the spatial distribution of Δ[oxCCO] responses during the activation of the visual cortex in the healthy adult human brain, and reconstruct images of these changes.Multi-channel broadband NIRS measurements were collected from the left visual cortex of four healthy volunteers using an in-house broadband spectrometer during an inverting checkerboard visual stimulation paradigm. Δ[HbO2], Δ[HHb] and Δ[oxCCO] were calculated by fitting the broadband spectra between 780 and 900 nm using the UCLn algorithm. Centre of gravity analysis was applied to the concentration data to determine the centres of activation for [HbO2], [HHb] and [oxCCO].All four subjects showed similar changes in [oxCCO] in the presence of a typical visual-evoked haemodynamic response in channels overlying the visual cortex. Image reconstruction of the optical data showed a clear and spatially localized activation for all three chromophores. Centre of gravity analysis showed different localisation of the changes in each of the three chromophores across the visual cortex with the x-y coordinates of the mean centres of gravity (across 4 subjects) of HbO2, HHb and oxCCO at (63.1 mm; 24.8 mm), (56.2 mm; 21.0 mm) and (63.7 mm; 23.8 mm), respectively.The spatial distribution of Δ[oxCCO] response appears distinct from the haemodynamic response in the human visual cortex. Image reconstruction of Δ[oxCCO] shows considerable promise as a technique to visualise regional variation in [oxCCO] in a range of scenarios.

Neurovascular Interactions in the Neurologically Compromised Neonatal Brain.

Neurological brain injuries such as hypoxic ischaemic encephalopathy (HIE) and associated conditions such as seizures have been associated with poor developmental outcome in neonates. Our limited knowledge of the neurological and cerebrovascular processes underlying seizures limits their diagnosis and timely treatment. Diffuse optical tomography (DOT) provides haemodynamic information in the form of changes in concentration of de/oxygenated haemoglobin, which can improve our understanding of seizures and the relationship between neural and vascular processes. Using simultaneous EEG-DOT, we observed distinct haemodynamic changes which are temporally correlated with electrographic seizures. Here, we present DOT-EEG data from two neonates clinically diagnosed as HIE. Our results highlight the wealth of mutually-informative data that can be obtained using DOT-EEG techniques to understand neurovascular coupling in HIE neonates.

Idiosyncratic control of the center of mass in expert climbers.

Here, we studied posture and movement coordination adopted by expert climbers. The investigation of such expertise might be of particular interest to gain understanding about the mechanisms underlying the biomechanical control of vertical quadrupedal locomotion. A novel custom setup was developed to analyze the motion of the center-of-mass (COM) and complementary information about the dynamic distribution of vertical reaction forces under the feet during climbing in nine elite climbers (EC) and nine control subjects. Two adaptive features were found in EC. First, unexpectedly they tended to maintain larger COM distances from the wall relative to controls, during both the static and dynamic phases of vertical motion (by ∼5 cm in both cases). Second, while the control subjects tended to restrain the lateral motion of the COM, all EC demonstrated systematic COM oscillations (∼1.3 times larger) associated with a significant alternating dynamic redistribution of the body weight between the limbs during the double support phase. The latter phenomenon likely reflects an adopted basic climbing strategy in experts. Furthermore, a convergence of the optimal solution towards a more diagonal climbing strategy in EC may shed light on the origin of the diagonal gait in primates and early hominids habituated to quadrupedal vertical locomotion.

A methodology to improve estimation of stimulus-evoked hemodynamic response from fNIRS measurements.

Functional near-infrared spectroscopy (fNIRS) is a non-invasive optical neuroimaging method used to investigate functional activity of the cerebral cortex evoked by cognitive, visual, auditory and motor tasks, detecting regional changes of oxy- and deoxy-hemoglobin concentration. Accurate estimation of the stimulus-evoked hemodynamic response (HR) from fNIRS signals in order to quantitatively investigate cognitive functions requires to cope with several noise components. Some of them appear as random disturbances (typically tackled through averaging techniques), while others are due to physiological sources, such as heart beat, respiration, vasomotor waves, and are particularly challenging to be dealt with because they lie in the same frequency band of HR. In this work we present a new two-steps methodology for the HR estimation from fNIRS data. The first step is a pre-processing stage where physiological trends in fNIRS data are reduced by exploiting a mathematical model identified from the signal of a reference channel. In the second step, the pre-processed data of the other channels are filtered with a recently presented non-parametric Bayesian approach (Scarpa et al., Optics Express, 2010). The presented method for HR estimation is compared with widely used methods: conventional averaging, band-pass filtering and principal component analysis (PCA). Results on simulated data reveal the ability of the proposed method to improve the accuracy of the estimates of the functional hemodynamic response, as well as the estimate of peak amplitude and latency. Encouraging preliminary results in a representative real data set showing an improvement of contrast to noise ratio are also reported.