Elsevier

NeuroImage

Volume 29, Issue 3, 1 February 2006, Pages 697-705
NeuroImage

Cerebral hemodynamics evaluation by near-infrared time-resolved spectroscopy: Correlation with simultaneous positron emission tomography measurements

https://doi.org/10.1016/j.neuroimage.2005.08.008Get rights and content

Abstract

We compared pharmacologically-perturbed hemodynamic parameters (cerebral blood volume; CBV, and flow; CBF) by acetazolamide administration in six healthy human subjects studied with positron emission tomography (PET) and near-infrared (NIR) time-resolved spectroscopy (TRS) simultaneously to investigate whether NIR-TRS could measure in vivo hemodynamics in the brain tissue quantitatively. Simultaneously with the PET measurements, TRS measurements were performed at the forehead with four different optode spacing from 2 cm to 5 cm. Total hemoglobin and oxygen saturation (SO2) measured by TRS significantly increased after administration of acetazolamide at any optode spacing in all subjects. In PET study, CBV and CBF were estimated in the following three volumes of interest (VOIs) determined on magnetic resonance images, VOI1: scalp and skull, VOI2: gray matter region, VOI3: gray and white matter regions. Acetazolamide treatment elevated CBF and CBV significantly in VOI2 and VOI3 but VOI1. TRS-derived CBV was more strongly correlated with PET-derived counterpart in VOI2 and VOI3 when the optode spacing was above 4 cm, although optical signal from cerebral tissue could be caught with any optode spacing. As to increase of the CBV, 4 cm of optode spacing correlated best with VOI2. To support the result of TRS-PET experiment, we also estimated the contribution ratios of intracerebral tissue to observed absorption change based on diffusion theory. The contribution ratios at 4 cm were estimated as follows: 761 nm: 50%, 791 nm: 72%, 836 nm: 70%. These results demonstrated that NIR-TRS with 4 cm of optode spacing could measure cerebral hemodynamic responses optimally and quantitatively.

Introduction

Near-infrared spectroscopy (NIRS) allows simple, non-invasive measurement of the oxygenation state and hemodynamics in living tissue by utilizing the differential in absorption spectrum between oxygenated and deoxygenated hemoglobin. This field got its start from the finding by Jobsis (1977) that when a cat's head is irradiated with near-infrared (NIR) light, the intensity of the transmitted light shows changes according to the oxygen metabolic state in the tissues. Since then, there has been growing study and technique of NIRS measurement.

Making that advantage, this method has been expected for use in surgical operations (Kakihana et al., 1996, De Blasi et al., 1997) and neonate respiration care (Meek et al., 1999, Isobe et al., 2000). Besides the clinical field, topographical imaging by multi-channels measurement is being performed to observe brain activity on the cortex (Watanabe et al., 2000, Tanosaki et al., 2001).

NIRS encompasses some different techniques and analysis, and we are adopting approaches of time-resolved spectroscopy (TRS; Oda et al., 1996, Yamashita et al., 1998), phase modulated spectroscopy (PMS; Tuchiya and Urakami, 1996, Iwai et al., 2001) or spatially resolves spectroscopy (SRS; Suzuki et al., 1999) method, etc. to quantification.

In contrast to the wide applicability of NIRS to brain monitoring, fundamental and critical questions still remain to be clarified, one of which is light propagation in the human head. The effect of the various external tissues of the head such as skin, skull and cerebrospinal fluid (CSF) on photon propagation in the internal cerebral tissue has not yet been fully examined in vivo.

Several researchers (Firbank et al., 1995, Okada et al., 1997) expressed doubts about the use of NIRS on adult human heads due to problems from the multi-layered structure of the scalp, skull, CSF and the cerebral tissue. Firbank first showed that the presence of CSF had a significant effect on the light distribution. It was reported that the NIRS signal from the adult human head was only 10–20% of the total signal due to the effect of CSF from the Monte Carlo simulation. These doubts are related to the essential question of where to measure using the photon, and research studies are being conducted using both simulations (Okada and Delpy, 2000, Okada and Delpy, 2003a, Okada and Delpy, 2003b, Misonoo and Okada, 2001) and experimental measurements. On the contrary, several researchers (McCormick et al., 1992, Harris et al., 1994, Germon et al., 1995, Kohri et al., 2001) have reported that NIRS can detect the brain signals more specifically by increasing the optode spacing from experimental measurements.

In this study, in order to investigate the relation between the optode spacing and light sampling depth, we observed change in the cerebral blood volume (CBV) of six adult subjects by administration of a drug with simultaneous measurement of the TRS system which can measure the blood volume and the oxygen saturation (SO2) quantitatively and positron emission tomography (PET), and we compared the CBV by TRS (TRS CBV) with CBV by PET (PET CBV) and estimated the contribution ratios of intracerebral tissue to the observed absorption change at three different wavelengths.

Section snippets

Subjects

Six healthy male subjects (mean age, 42.6 ± 5.08; range, 37 to 51 years) were studied. Informed consent was obtained from all subjects before experiment. It was confirmed that they had no previous history of intracranial disorders and also that there were no anatomical abnormalities by making a check with a magnetic resonance imaging (MRI; 0.3 T MRP7000AD, Hitachi Ltd., Japan).

Three-wavelength TRS system

We used TRS-10 system (Hamamatsu Photonics K.K., Japan) (Oda et al., 2000) to obtain TRS-CBV in our experiment. This

Physiology

There were no significant changes in physiologic parameters (arterial blood pressure, pulse rates, PaCO2) and psychophysical states (changes in mental activity) between before and after administration of acetazolamide (data is not shown).

TRS

Typical values of TRS tHb and SO2 at each optode spacing during the experiment are shown in Fig. 4. The rise of TRS tHb and SO2 was confirmed at all optode spacings immediately after administering acetazolamide and reached a plateau after about 10 min. These

Discussion

The acetazolamide used in this experiment increases the regional CBF by inhibiting carbonic anhydrase and thereby expanding cerebral blood vessels (Posner and Plum, 1960, Ehrenreich et al., 1961). This drug is therefore generally used to assess the cerebrovascular reserve capacity as an acetazolamide test. Similarly in this study, significant increases of PET CBF and PET CBV by acetazolamide in the intracerebral tissues (VOI2,3) and no significant increase of those in the extracerebral tissues

Conclusion

We observed a change in the CBV by administration of acetazolamide with simultaneous measurement of TRS and PET. These experiments showed that intracerebral hemodynamics response by administering acetazolamide could be captured at optode spacings of 2 cm to 5 cm.

Furthermore, by evaluating the correlation with PET, we concluded that more than 4 cm of optode spacing is preferable for improving quantification of the NIR-TRS measurement to intracerebral hemodynamics. Additionally, 4 cm of optode

Acknowledgments

The authors would like to thank Mr. T. Hiruma for his constant support and encouragement. The authors are also grateful to Drs. Y. Tsuchiya and T. Yamashita for useful discussions.

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