[Show abstract][Hide abstract] ABSTRACT: Functional near infrared spectroscopy (fNIRS) is an emerging tool for non-invasively monitoring the haemodynamic response to brain activation. The technique has been widely adopted to investigate cortical responses during motor tasks in health and disease. This systematic review provides a critical analysis of the research findings in the hope of summating relevant information, identifying consistent outcomes acquired using different spectrometers, clarifying data inconsistencies, and learning from the common challenges across disciplines. The spatiotemporal characteristics, reliability, repeatability and modulation of typical cortical response evoked by motor stimulation are all evaluated in detail. The review assesses the contribution of the technique to advancing our understanding of motor skill learning and control in the context of tasks of everyday living, athletic performance, and recovery from neurological illness. Finally, the limitations of current fNIRS technologies are examined and a series of recommendations for future studies are provided based upon the reviewed literature.
[Show abstract][Hide abstract] ABSTRACT: Since its formation in the early 1940s, in addition to its routine task of applying physical sciences to medicine, the Medical Physics Department at University College London has been active in the research and development of medical sensors and instrumentation. In the last 15 years an increasing amount of this development work has been commercially sponsored and the Department has been actively involved in the process of technology transfer from the health-care field to the medical equipment industry.
Journal of Medical Engineering & Technology 07/2009; 11(5). DOI:10.3109/03091908709040976
[Show abstract][Hide abstract] ABSTRACT: The effect of seizures on brain blood flow and metabolism has been extensively studied. However, few studies have focused on mitochondria. We used near infrared spectroscopy (NIRS) to study hemoglobin and cytochrome oxidase changes during seizures, induced by the GABA antagonist bicuculline, in the adult rat. A broadband spectroscopy system was used with the optodes placed across the rat head. We focused on the initial seizures post-bicuculline addition during which oxyhemoglobin (HbO2) increased, deoxyhemoglobin (HHb) decreased and total hemoglobin (Hbtot) increased. The NIRS signal associated with the oxidised CuA centre of mitochondrial cytochrome c oxidase (oxCCO) decreased. At the highest bicuculline doses (0.25 mg/animal) the maximum values recorded were: delta HbO2 = +19 +/- 7 microM; delta HHb = -12 +/- 4 microM; delta Hbtot = +7 +/- 4 microM, delta oxCCO = - 1.7 +/- 0.3 microM. These results are broadly in line with other NIRS studies. However, previous measurements of NADH fluorescence indicate oxidation of the mitochondrial redox chain under these conditions. The changes induced by bicuculline provide an interesting challenge to the physics and biochemistry of using NIRS to study mitochondrial redox states in vivo and we explore the possible spectroscopic and/or biochemical meaning of these apparent anomalies.
Advances in Experimental Medicine and Biology 02/2009; 645:129-34. DOI:10.1007/978-0-387-85998-9_20 · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Optical topography (OT) is a near infrared spectroscopy (NIRS) technique that provides spatial maps of haemodynamic and oxygenation changes. When developing, testing and calibrating OT systems it is often necessary to use tissue simulating phantoms that are capable of providing realistic changes in attenuation properties. We present a novel dynamic tissue phantom that enables spatially and temporally varying tissue properties to be reproduced in a controlled manner.
This new dynamic test phantom consists of a modified liquid crystal display (LCD) (enabling flexible and rapid changes in attenuation across different regions of the phantom) sandwiched between two layers of tissue simulating epoxy resin (providing static and homogeneous optical absorption and scattering). By activating different pixels in the liquid crystal display it is possible to produce highly localised and dynamic changes in attenuation which can be used to simulate the changes associated with the cerebral haemodynamic response to functional activation. The reproducibility of the dynamic phantom will be described with examples of its use with an OT system.
Advances in Experimental Medicine and Biology 02/2009; 645:141-6. DOI:10.1007/978-0-387-85998-9_22 · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Circulating blood volume (BV) is an important, but often unconsidered, variable in newborn infants undergoing intensive care. The data on validation and repeatability of BV measurement are limited.Aim: To validate and test the repeatability of measuring BV in newborn infants using indocyanine green (ICG) and pulse dye densitometry (PDD).Methods: Validation– Paired measurements of BV were made using the fetal hemoglobin (HbF) dilution and the PDD method. Repeatability– The BV was measured twice at an interval of 30–40 min in a second group of infants.Results: Validation– Data from three of 13 infants studied were excluded because of probe dislodgement or ICG injection error. The median (range) birth weight of the 10 infants whose data were analyzed was 1032 g (740–2384 g) and seven (70%) were receiving either mechanical ventilation or nasal CPAP. The median BV measured by HbF dilution was 66.2 ml·kg−1 (43.7–81.0 ml·kg−1) and by the PDD method was 68.9 ml·kg−1 (49.3–101.0 ml·kg−1). The mean difference was 5.92 ml·kg−1 (sd 17.33 ml·kg−1). Repeatability– Twelve infants were studied and three excluded because of probe dislodgement/motion artifact or ICG injection error. The median weight of the nine infants whose data were analyzed was 1208 g (795–2600 g). The median (range) BV1 and BV2 were 70.5 ml·kg−1 (53.1–160 ml·kg−1) and 87.5 ml·kg−1 (38.0–248.0 ml·kg−1), respectively. Mean difference of the two BV estimates (BV1–BV2) was −24.6 ml·kg−1 (sd 33.3 ml·kg−1) and coefficient of repeatability was 66.5 ml·kg−1.Conclusion: Pulse dye densitometry can be used to measure BV in the newborn infant at the cotside but the repeatability measurements suggest that its use is limited.
[Show abstract][Hide abstract] ABSTRACT: Oxy- (HbO2) and deoxy- (HHb) haemoglobin signals measured by near infrared (NIR) spectroscopy over the human frontal lobes frequently contain respiratory and low frequency oscillations (LFOs). It has been suggested previously that venous oxygen saturation (SvO2) can be calculated from these respiratory oscillations. In this paper, we investigated the use of a Fourier transform based algorithm to calculate an oxygen saturation measure known as S(osc)O2 which may be a close estimate of the underlying SvO2. S(osc)O2 was calculated using three different frequency ranges, (1) respiratory oscillations only, (2) LFOs only, and (3) both respiratory oscillations and LFOs. At each frequency range S(osc)O2 was calculated using either (1) the modified Beer-Lambert law (MBL) or (2) spatially resolved spectroscopy (SRS). In total six different measurements of S(osc)O2 were investigated here. Experiments were performed in six adult ventilated patients with traumatic brain injury. The patients' inspired oxygen fraction (FiO2) was raised in two hyperoxic phases. The calculated S(osc)O2 values were compared with other cerebral oxygenation measures including an intraparenchymal catheter based brain tissue oxygen tension (PbrO2) and the NIR based tissue oxygenation index (TOI). It was found that the S(osc)O2 calculated using the combined respiratory and LFO frequency range and the SRS method resulted in the highest detection rates of hyperoxic changes. This measure of S(osc)O2 may provide a viable, continuous, non invasive, bedside measure of cerebral venous oxygen saturation.
Advances in Experimental Medicine and Biology 02/2008; 614:235-44. DOI:10.1007/978-0-387-74911-2_27 · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate neurocognitive mechanisms associated with task-related expertise development, this paper investigates serial changes in prefrontal activation patterns using functional near infrared spectroscopy (fNIRS). We evaluate cortical function in 62 healthy subjects with varying experience during serial evaluations of a knot-tying task. All tasks were performed bimanually and self paced, with fixed episodes of motor rest for five repetitions. Improvements in technical skill were evaluated using dexterity indices to quantify time, total movements and pathlength required to complete trials. Significant improvements in technical skills were observed in novices between the 2nd and 3rd trials, associated with increasing task familiarity. In trained subjects, minimal fluctuation in task-related oxyhaemoglobin (HbO(2)) and deoxyhaemoglobin (HHb) changes were observed in association with more stable task performance. In contrast, two significant transitions in prefrontal haemodynamic change were observed in novices. Greater task-related increases in HbO(2) and decreases in HHb were identified on the second trial compared to the first. Relative decreases in HbO(2) and increases in HHb change were observed between the third and fourth, and fourth and fifth trials respectively. These data suggest that prefrontal processing across five knot-tying trials is influenced by the level of experience on a task. Modifications in prefrontal activation appear to confer technical performance adaptation in novices.
[Show abstract][Hide abstract] ABSTRACT: Recent advances in near-infrared spectroscopy (NIRS) allow measurements of absolute tissue oxygen saturation (TOI) using spatially resolved spectroscopy (SRS), while enabling better depth sensitivity. However concerns remain regarding the relative contribution of the extracranial circulation to the cerebral NIRS TOI signal. In this study we investigated this during a period of selective rise in cerebral blood flow (CBF) produced by the administration of acetazolamide (ACZ) in 10 healthy volunteers. A two channel spectrometer (NIRO 300, Hamamatsu Photonics KK) was used to measure absolute cerebral TOI over the frontal cortex using the SRS technique using an optode spacing of 5 cm and 1.5 cm for channel 1 and 2 respectively. After ACZ administration we were able to observe a significant increase in the velocity of middle cerebral artery (V(mca), measured with the transcranial Doppler (TCD)) which was accompanied by an increase in TOI as monitored by the NIRO 300 with an optode spacing of 5 cm but not with an optode spacing of 1.5 cm. Furthermore a direct relationship was seen between the V(mca) and the TOI measured at 5 cm optode spacing. This work suggests that using this commercial NIRS instrument with an optode spacing of 5 cm one is able to detect the intracranial changes.
Advances in Experimental Medicine and Biology 02/2008; 614:389-96. DOI:10.1007/978-0-387-74911-2_43 · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Near-infrared spectroscopy (NIRS) has been used to measure changes in cerebral oxy- and deoxy- haemoglobin (delta[HbO2], delta[HHb]) in response to functional activation. It has been previously reported that during functional activation of the motor cortex heart rate increases. The aim of this study was to investigate systemic changes during functional activation of the frontal cortex. The responses to anagram presentations with varying difficulty (4-Letters and 7-Letters) over a 6 minute period were recorded. A Hamamatsu NIRO 200 NIRS system recorded delta[HbO2] and delta[HHb] using the modified Beer Lambert law (MBL) and tissue oxygenation index (TOI) employing spatial resolved spectroscopy (SRS) over the left and right frontal hemisphere. Mean blood pressure (MBP) and heart rate (HR) were measured continuously. Nine young healthy volunteers (mean age 23) were included in the analysis. Significant task related changes were observed in both the NIRS and systemic signals during the anagram solving with increases in [HbO2] and [HHb] accompanied by changes in MBP and HR. The [HbO2] and [HHb] signals measured over the frontal region were found to have a varying association with the MBP signal across different volunteers. The effect of these systemic changes on measured NIRS signals must be considered
Advances in Experimental Medicine and Biology 02/2008; 614:397-403. DOI:10.1007/978-0-387-74911-2_44 · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A time domain optical coherence tomography (OCT) system is described that uses mid-infrared light (6-8 microm). To the best of our knowledge, this is the first OCT system that operates in the mid-infrared spectral region. It has been designed to characterize bioengineered tissues in terms of their structure and biochemical composition. The system is based upon a free-space Michelson interferometer with a germanium beam splitter and a liquid nitrogen cooled HgCdTe detector. A key component of this work has been the development of a broadband quantum cascade laser source (InGaAs/AlInAs containing 11 different active regions of the three well vertical transition type) that emits continuously over the 6-8 microm wavelength range. This wavelength range corresponds to the so called "mid-infrared fingerprint region" which exhibits well-defined absorption bands that are specifically attributable to the absorbing molecules. Therefore, this technology provides an opportunity for optical coherence molecular imaging without the need for molecular contrast agents. Preliminary measurements are presented.
[Show abstract][Hide abstract] ABSTRACT: We have previously reported changes in the concentrations of oxy-(delta[HbO2]) deoxy- (delta[HHb]) and total haemoglobin (delta[HbT] = delta[HbO2] + delta[HHb]) measured using near infrared spectroscopy (NIRS) over the frontal cortex (FC) during an anagram solving task. These changes were associated with a significant increase in both mean blood pressure (MBP) and heart rate (HR). The aim of this study was to investigate whether the changes in MBP previously recorded during an anagram solving task produces associated changes in scalp blood flow (flux) measured by laser Doppler and whether any changes are seen in NIRS haemodynamic measurements over a control region of the brain (motor cortex: MC). During the 4-Letter anagram task significant changes were observed in the delta[HbO2], delta[HHb] and delta[HbT] in both the frontal and motor cortex (n = 11, FC p < 0.01, MC p < 0.01). These changes were accompanied by significant changes in both MBP (n = 11, p < 0.01) and scalp flux (n = 9, p = 0.01). During the 7-Letter anagram task significant changes were observed in the delta[HbO2] and delta[HbT] (n = 11, FC p < 0.01, MC p < 0.01), which were accompanied by significant changes in both MBP (n = 11, p = 0.05) and flux (n = 9, p = 0.05). The task-related changes seen in MBP and flux in this study appear to contribute to the changes in the NIRS signals over both the activated and control regions of the cortex.
Advances in Experimental Medicine and Biology 01/2008; 614:21-8. DOI:10.1007/978-0-387-74911-2_3 · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: One hertz transcranial magnetic stimulation (TMS) over the motor cortex has been reported to increase activity in the motor cortex contralateral to stimulation, as evidenced by the elevated motor evoked potential on the corresponding hand muscle. Little research, however, has assessed concomitant changes in the haemoglobin level in the unstimulated motor cortex. An aim of this study was to measure the change of oxy- and deoxy-haemoglobin levels in the left motor cortex after 20 min of 1 Hz TMS over the right motor cortex. Subjects carried out a finger to thumb tapping task sequentially with six blocks of ten cycles (30 s on and 60 s off). One block was performed before TMS and five after TMS. The results show that the level of oxyhaemoglobin in the unstimulated cortex increased after TMS over the contralateral hemisphere and that the increase lasted 40 min after 1 Hz stimulation. Deoxy-haemoglobin was slightly decreased during the first 15 min after stimulation. The results identify long term physiological changes resulting from 1 Hz stimulation and help to inform our understanding of interhemispheric interactions in TMS studies.
Experimental Brain Research 09/2007; 181(4):555-60. DOI:10.1007/s00221-007-0952-x · 2.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Optical tomography is being developed as a means of detecting and specifying disease in the adult female breast. We present a series of clinical three-dimensional optical images obtained with a 32-channel time-resolved system and a liquid-coupled interface. Patients place their breasts in a hemispherical cup to which sources and detectors are coupled, and the remaining space is filled with a highly scattering fluid. A cohort of 38 patients has been scanned, with a variety of benign and malignant lesions. Images show that hypervascularization associated with tumors provides very high contrast due to increased absorption by hemoglobin. Only half of the fibroadenomas scanned could be observed, but of those that could be detected, all but one revealed an apparent increase in blood volume and a decrease in scatter and oxygen saturation.
[Show abstract][Hide abstract] ABSTRACT: To investigate the accuracy of measuring cerebral blood flow (CBF) using a bolus injection of Indocyanine Green (ICG) detected by near-infrared spectroscopy in adult human heads, simulations were performed using a two-layered model representing the extracerebral and intracerebral layers. Modeled optical data were converted into tissue ICG concentration using either the one-detector modified Beer-Lambert law (MBLL) method, or the two-detector partial path-length (PPL) method. The CBFs were estimated using deconvolution and blood flow index techniques. Using the MBLL method, the CBFs were significantly underestimated but the PPL method improved their accuracy and robustness, especially when used as relative measures. The dispersion of the arterial input function also affected the CBF estimates.
[Show abstract][Hide abstract] ABSTRACT: We have previously used a continuous four-wavelength near-infrared spectrometer to measure changes in the cerebral concentrations of oxy-haemoglobin (Delta[HbO(2)] and deoxy-haemoglobin (Delta[HHb]) during head-up tilt in patients with primary autonomic failure. The measured changes in light attenuation also allow calculation of changes in the concentration of oxidized cytochrome-c-oxidase (Delta[(ox)CCO]), and this paper analyses the Delta[(ox)CCO] during the severe episodes of orthostatic hypotension produced by this experimental protocol. We studied 12 patients during a passive change in position from supine to a 60 degrees head-up tilt. The challenge caused a reduction in mean blood pressure of 59.93 (+/-26.12) mmHg (Mean (+/-SD), p < 0.0001), which was associated with a reduction in the total concentration of haemoglobin (Delta[HbT] = Delta[HbO(2)] + Delta[HHb]) of 5.02 (+/-3.81) microM (p < 0.0001) and a reduction in the haemoglobin difference concentration (Delta[Hb(diff)] = Delta[HbO(2)] - Delta[HHb]) of 14.4 (+/-6.73) microM (p < 0.0001). We observed a wide range of responses in Delta[(ox)CCO]. Six patients demonstrated a drop in Delta[(ox)CCO] (0.17 +/- 0.15 microM); four patients demonstrated no change (0.01 +/- 0.12 microM) and two patients showed an increase in Delta[(ox)CCO] (0.21 +/- 0.01 microM). Investigation of the association between the changes in concentrations of haemoglobin species and the Delta[(ox)CCO] for each patient show a range of relationships. This suggests that a simple mechanism for crosstalk, which might produce artefactual changes in [(ox)CCO], is not present between the haemoglobin and the (ox)CCO NIRS signals. Further investigation is required to determine the clinical significance of the changes in [(ox)CCO].
[Show abstract][Hide abstract] ABSTRACT: Wavelet cross-correlation (WCC) is used to analyse the relationship between low-frequency oscillations in near-infrared spectroscopy (NIRS) measured cerebral oxyhaemoglobin (O(2)Hb) and mean arterial blood pressure (MAP) in patients suffering from autonomic failure and age-matched controls. Statistically significant differences are found in the wavelet scale of maximum cross-correlation upon posture change in patients, but not in controls. We propose that WCC analysis of the relationship between O(2)Hb and MAP provides a useful method of investigating the dynamics of cerebral autoregulation using the spontaneous low-frequency oscillations that are typically observed in both variables without having to make the assumption of stationarity of the time series. It is suggested that for a short-duration clinical test previous transfer-function-based approaches to analyse this relationship may suffer due to the inherent nonstationarity of low-frequency oscillations that are observed in the resting brain.
[Show abstract][Hide abstract] ABSTRACT: One hertz transcranial magnetic stimulation (TMS) over the motor cortex has been reported to increase activity in the motor cortex contralateral to stimulation, as evidenced by the elevated motor evoked potential on the corresponding hand muscle. Little research, however, has assessed concomitant changes in the haemoglobin level in the unstimulated motor cortex. An aim of this study was to measure the change of oxy-and deoxy-haemoglobin levels in the left motor cortex after 20 min of 1 Hz TMS over the right motor cortex. Subjects carried out a Wnger to thumb tapping task sequentially with six blocks of ten cycles (30 s on and 60 s oV). One block was performed before TMS and Wve after TMS. The results show that the level of oxyhae-moglobin in the unstimulated cortex increased after TMS over the contralateral hemisphere and that the increase lasted 40 min after 1 Hz stimulation. Deoxy-haemoglobin was slightly decreased during the Wrst 15 min after stimula-tion. The results identify long term physiological changes resulting from 1 Hz stimulation and help to inform our understanding of interhemispheric interactions in TMS studies.