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More about ... biomedical engineering and medical imaging: shedding light on the brain with near-infrared spectroscopy.

In 1977 it was first shown that light in the near-infrared region of the spectrum penetrates biological materials sufficiently to measure changes in cerebral oxygenation, a completely non-invasive technique. (1) Since then, near-infrared spectroscopy (NIRS) has been used to monitor oxyhaemoglobin, deoxyhaemoglobin, blood volume and cytochrome oxidase for a variety of clinical and research applications.

Imaging with near-infrared light

Oxyhaemoglobin and deoxyhaemoglobin absorb light in the 650 - 1 000 nm wavelength range, and attenuate measurements of light transmitted through tissue. In a non-scattering medium, the concentration of an absorbing compound is proportional to the ratio of light attenuation through the medium, and the distance between the source and the detector. In the case of two absorbing compounds, the concentrations of each can be calculated from measurements of light attenuation at two different wavelengths using the Beer Lambert law - the same principle used in pulse oximetry.

However, because biological tissue is highly scattering, an unknown amount of light attenuation results from scatter rather than absorption. Because of this, continuous wave NIRS - the simplest and most commonly used technique - is able to provide quantified concentration changes relative to an arbitrary baseline, but not absolute haemoglobin concentrations.

Clinically and in neuroscience research, NIRS measurements from a single source and detector are commonly used. An emerging imaging technique, which is an area of current research in physics and engineering, is diffuse optical tomography (DOT), which requires surface measurements from multiple overlapping source-detector pairs. Three-dimensional tomographic images of the interior of a small area can then be reconstructed using mathematical models of light propagation through tissue.

Applications of NIRS

The principal clinical application of NIRS is for monitoring brain oxygenation in neonatal intensive care. (2) Attempts have also been made to monitor fetal cerebral oxygenation, both transabdominally and during delivery. (3) Other pregnancy-related applications include transabdominal measurement of placental oxygenation (4) and assessment of embryo viability for in vitro fertilisation. (5) NIRS and DOT are also used, often in conjunction with mammography or ultrasound, to detect changes in haemodynamics related to tumours in the breast. (2)

Perhaps the fastest-growing application area is in the study of brain function, where, as an alternative to functional magnetic resonance imaging (fMRI), NIRS is used to measure changes in cerebral oxygenation in response to a stimulus. A localised increase in metabolic demand in a cortical region results in an increase in oxyhaemoglobin and a decrease in deoxyhaemoglobin which can be measured by detectors placed on the scalp, as shown in Fig. 1.

[FIGURE 1 OMITTED]

In sports science research, NIRS can be used to measure oxygenation in the brain and muscles simultaneously, for example to investigate the relationship between the two and perceived exertion during an exhaustive cycling test. (6)

NIRS has several advantages which makes it useful in clinical and research settings. It is portable, allows for long-term monitoring, and is relatively inexpensive. (7) Although NIRS has lower spatial sensitivity than fMRI and positron emission tomography (PET), and is limited to detecting cortical activation (8) it does not expose subjects to harmful radiation, (9) which makes it safe for use in studies of infants and pregnant women.

[FIGURE 2 OMITTED]

NIRS in cognitive-affective neuroscience of pregnancy

Recently, NIRS has been used to investigate the regulation of emotion in pregnancy. (10) This is important as there is a high prevalence of mood and anxiety disorders in pregnancy, but it is not clear why pregnant women are at increased risk for developing these disorders. Pregnant women underwent an imaging session with NIRS to investigate prefrontal cortex (PFC) activation in response to emotional facial stimuli including fear, and completed self-report questionnaires on distress and anxiety at each trimester. Non-pregnant controls completed these assessments at a once-off session. There was significant PFC activation in response to fearful faces in both pregnant women and controls, compared with a resting phase. However, women in the second trimester of pregnancy showed greater right PFC activation than controls in response to fearful faces (Fig. 2). In pregnant women, this increased PFC activation was significantly associated with increased distress and anxiety at all trimesters. This suggests that PFC processing of threat stimuli is altered in pregnancy, which may help explain why pregnant women have an increased vulnerability for developing mood and anxiety problems.

Conclusion

Because of its biochemical specificity and non-invasiveness NIRS has a wide variety of applications. Although it lacks the spatial resolution of fMRI and cannot detect activation in subcortical structures, in neuroscience research NIRS and DOT can be used in situations where for ethical or practical reasons fMRI can not. NIRS therefore holds particular promise for investigating cortical brain activity in pregnant women and infants, as well as in ambulatory tasks which cannot be performed inside an MRI scanner. Advances in imaging and analysis methods and fusion with other imaging modalities will increase the accuracy of spatial localisation and provide further information about the metabolic dynamics of the brain, as well as of other organs.

Acknowledgements

Financial assistance was provided by the Medical Research Council of SA, Harry Crossley Foundation and National Research Foundation.

References available at www.cmej.org.za

References

(1.) Jobsis FF. Noninvasive infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters. Science 1977;198(4323):1264-1267.

(2.) Gibson A, Dehghani H. Diffuse optical imaging. Philos Transact A Math Phys Eng Sci 2009;367(1900):3055-3072.

(3.) Rolfe P. In vivo near-infrared spectroscopy. Annu Rev Biomed Eng 2000;2:715-754.

(4.) Kawamura T, Kakogawa J, Takeuchi Y, et al. Measurement of placental oxygenation by transabdominal near-infrared spectroscopy. Am J Perinatol 2007;24(3):161-166.

(5.) Nagy ZP, Sakkas D, Behr B. Symposium: innovative techniques in human embryo viability assessment. Non-invasive assessment of embryo viability by metabolomic profiling of culture media ('metabolomics'). Reprod Biomed Online 2008;17(4):502-507.

(6.) Fontes E, Smirmaul B, Roos A, et al. The relationship between perceived exertion versus muscle and cerebral oxygenation during fatiguing exercise performed at normoxia and hypoxia. 15th Annual Congress of ECSS, 23-26 June 2010 Antalya, Turkey.

(7.) Leon-Carrion J, Martin-Rodriguez JF, Damas-Lopez J, et al. A lasting post-stimulus activation on dorsolateral prefrontal cortex is produced when processing valence and arousal in visual affective stimuli. Neurosci Lett 2007;422(3):147-152.

(8.) Yang H, Zhou Z, Liu Y, et al. Gender difference in hemodynamic responses of prefrontal area to emotional stress by near-infrared spectroscopy. Behav Brain Res 2007;178(1):172-176.

(9.) Hoshi Y. Functional near-infrared spectroscopy: current status and future prospects. J Biomed Opt 2007;12(6):062106.

(10.) Roos A, Robertson F, Lochner C, Vythilingum B, Stein DJ. The association between prefrontal cortex activation to affective stimuli in pregnant women and distress. International Anxiety Disorder Symposium, 1-2 May 2010 Stellenbosch, South Africa.

ANNERINE ROOS, BSc, BSc Hon, MSc, PhD

MRC Research Unit on Anxiety and Stress Disorders, Department of Psychiatry, Stellenbosch University

FRANCES ROBERTSON, BSc, MSc

MRC/UCT Biomedical Imaging Research Unit, Department of Human Biology, University of Cape Town

Correspondence to: Annerine Roos (aroos@sun.ac.za)
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Author:Roos, Annerine; Robertson, Frances
Publication:CME: Your SA Journal of CPD
Date:Mar 1, 2011
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