Clare E. Elwell

OPTICAL PATHLENGTH MEASUREMENTS ON ADULT HEAD, CALF AND FOREARM AND THE HEAD OF THE NEWBORN-INFANT USING PHASE-RESOLVED OPTICAL SPECTROSCOPY

We have used an intensity modulated optical spectrometer, which measures the phase shift across tissue experienced by intensity modulated near-infrared light, to determine the absolute optical pathlength through tissue. The instrument is portable and takes only 5 s to record pathlength at four wavelengths (690 nm, 744 nm, 807 nm and 832 nm). The absolute pathlength divided by the known spacing between the light source and detector on the skin is the differential pathlength factor (DPF) which previous studies have shown is approximately constant for spacings greater than 2.5 cm. DPF results are presented for measurements on 100 adults and 35 newborn infants to determine the statistical variation on the DPF. All measurements were made at a frequency of 200 MHz with source-detector spacings of > 4 cm. Results at 807 nm show a DPF of 4.16(+/- 18.8%) for adult arm, 5.51(+/- 18%) for adult leg, 6.26(+/- 14.1%) for adult head and 4.99(+/- 9%) for the head of a newborn infant. A wavelength dependence was obtained for DPF on all tissues and a difference in DPF between male and female was observed for both the adult arm and leg. The results can be used to improve the quantitation of chromophore concentration changes in adults and newborn infants.

Illuminating the developing brain: The past, present and future of functional near infrared spectroscopy

A decade has passed since near infrared spectroscopy (NIRS) was first applied to functional brain imaging in infants. As part of the team that published the first functional near infrared spectroscopy (fNIRS) infant study in 1998, we have continued to develop and refine both the technology and methods associated with these measurements. The increasing international interest that this technology is generating among neurodevelopmental researchers and the recent technical developments in biomedical optics have prompted us to compile this review of the challenges that have been overcome in this field, and the practicalities of performing fNIRS in infants. We highlight the increasingly diverse and ambitious studies that have been undertaken and review the technological and methodological advances that have been made in the study design, optical probe development, and interpretation and analyses of the haemodynamic response. A strong emphasis is placed on the potential of the technology and future prospects of fNIRS in the field of developmental neuroscience.

Measurement of cranial optical path length as a function of age using phase resolved near infrared spectroscopy

Near infrared spectroscopy (NIRS) has been used to measure concentration changes of cerebral hemoglobin and cytochrome in neonates, children, and adults, to study cerebral oxygenation and hemodynamics. To derive quantitative concentration changes from measurements of light attenuation, the optical path length must be known. This is obtained by multiplying the source/detector separation by a laboratory measured differential path length factor (DPF) which accounts for the increased distance traveled by light due to scattering. DPF has been measured by time of flight techniques on small populations of adults and postmortem infants. The values for adults are greater than those for newborns, and it is not clear how to interpolate the present data for studies on children. Recent developments in instrumentation using phase resolved spectroscopy techniques have produced a bedside unit which can measure optical path length on any subject. We have developed an intensity modulated optical spectrometer which measures path length at four wavelengths. Two hundred and eighty three subjects from 1 d of age to 50 y were studied. Measurements were made at a fixed frequency of 200 MHz and a source detector separation of 4.5 cm. Results suggest a slowly varying age dependence of DPF, following the relation DPF690 = 5.38 + 0.049A0.877, DPF744 = 5.11 + 0.106A0.723, DPF807 = 4.99 + 0.067A0.814, and DPF832 = 4.67 + 0.062A0.819, where DPF690 is the DPF measured at 690 nm and A is age is expressed in years from full term. There was a wide scatter of values, however, implying that ideally DPF should be measured at the time of each study.

Quantitative spatially resolved measurement of tissue chromophore concentrations using photoacoustic spectroscopy: application to the measurement of blood oxygenation and haemoglobin concentration

A new approach based on pulsed photoacoustic spectroscopy for non-invasively quantifying tissue chromophore concentrations with high spatial resolution has been developed. The technique is applicable to the quantification of tissue chromophores such as oxyhaemoglobin (HbO(2)) and deoxyhaemoglobin (HHb) for the measurement of physiological parameters such as blood oxygen saturation (SO(2)) and total haemoglobin concentration. It can also be used to quantify the local accumulation of targeted contrast agents used in photoacoustic molecular imaging. The technique employs a model-based inversion scheme to recover the chromophore concentrations from photoacoustic measurements. This comprises a numerical forward model of the detected time-dependent photoacoustic signal that incorporates a multiwavelength diffusion-based finite element light propagation model to describe the light transport and a time-domain acoustic model to describe the generation, propagation and detection of the photoacoustic wave. The forward model is then inverted by iteratively fitting it to measurements of photoacoustic signals acquired at different wavelengths to recover the chromophore concentrations. To validate this approach, photoacoustic signals were generated in a tissue phantom using nanosecond laser pulses between 740 nm and 1040 nm. The tissue phantom comprised a suspension of intralipid, blood and a near-infrared dye in which three tubes were immersed. Blood at physiological haemoglobin concentrations and oxygen saturation levels ranging from 2% to 100% was circulated through the tubes. The signal amplitude from different temporal sections of the detected photoacoustic waveforms was plotted as a function of wavelength and the forward model fitted to these data to recover the concentrations of HbO(2) and HHb, total haemoglobin concentration and SO(2). The performance was found to compare favourably to that of a laboratory CO-oximeter with measurement resolutions of +/-3.8 g l(-1) (+/-58 microM) and +/-4.4 g l(-1) (+/-68 microM) for the HbO(2) and HHb concentrations respectively and +/-4% for SO(2) with an accuracy in the latter in the range -6%-+7%.

Regional Hemodynamic Responses to Visual Stimulation in Awake Infants

This study presents the first measurements using near infrared spectroscopy of changes in regional hemodynamics as a response to a visual stimulus in awake infants. Ten infants aged 3 d to 14 wk viewed a checkerboard with a 5-Hz pattern reversal. The emitter and detector (optodes) of a near infrared spectrophotometer were placed over the occipital region of the head. Changes in concentration of oxy- and deoxyhemoglobin (Hbo2 and Hb) were measured and compared during 10-s epochs of stimulus on and off. A control group of 10 infants aged 18 d to 13 wk were examined with the same setup, but with the optodes over the frontoparietal region. In the test group the total hemoglobin concentration (Hbo2 + Hb) increased while the stimulus was on by a mean (±SD) of 2.51 (±1.48) μmol·L-1. Nine out of 10 infants showed an Hbo2 increase, and 9 out of 10 an Hb increase related to the stimulus. There was no significant change in any of these parameters in the control group. The results imply that there is increased cerebral blood flow due to stimulation that is specific to the visual cortex and that infants, unlike adults, show increased cerebral oxygen utilization during activation that outstrips this hemodynamic effect. The study demonstrates that near infrared spectroscopy can be used as a practical and noninvasive method of measuring visual functional activation and its hemodynamic correlates in the awake infant.

Spectral dependence of temporal point spread functions in human tissues

We have determined the spectral dependence of the temporal point spread functions of human tissues experimentally between 740 and 840 nm in transmittance measurements on the adult head, forearm, and calf (in vivo) and the infant head (post mortem) by using picosecond laser pulses and a streak camera detector. Two parameters are extracted from the temporal point spread function; the differential path-length factor (DPF), calculated from the mean time, and the slope of the logarithmic intensity decay. In all tissues the DPF and the logarithmic slope show a reciprocal relationship and exhibit characteristics of the absorption spectra of hemoglobin. The DPF falls with increasing wavelength, the variation being typically 12%, while the logarithmic slope increases with wavelength. A quantitative analysis of the logarithmic slope spectrum significantly underestimated expected tissue chromophore concentrations. The absolute magnitudes of the DPF showed considerable intersubject variation, but the variation with wavelength was consistent and thus may be used in the correction of tissue attenuation spectra.

Noninvasive measurement of human forearm oxygen consumption by near infrared spectroscopy

SummaryThis study reported on the application of near infrared spectroscopy (NIRS) to noninvasive measurements of forearm brachio-radial muscle oxygen consumption (

Assessment of the cerebral cortex during motor task behaviours in adults: a systematic review of functional near infrared spectroscopy (fNIRS) studies.

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