Elsevier

NeuroImage

Volume 21, Issue 4, April 2004, Pages 1464-1471
NeuroImage

Evoked-cerebral blood oxygenation changes in false-negative activations in BOLD contrast functional MRI of patients with brain tumors

https://doi.org/10.1016/j.neuroimage.2003.10.042Get rights and content

Abstract

Blood oxygenation level dependent contrast functional MRI (BOLD-fMRI) has been used to define the functional cortices of the brain in preoperative planning for tumor removal. However, some studies have demonstrated false-negative activations in such patients. We compared the evoked-cerebral blood oxygenation (CBO) changes measured by near-infrared spectroscopy (NIRS) and activation mapping of BOLD-fMRI in 12 patients with brain tumors who had no paresis of the upper extremities. On the nonlesion side, NIRS demonstrated a decrease in deoxyhemoglobin (Deoxy-Hb) with increases in oxyhemoglobin (Oxy-Hb) and total hemoglobin (Total-Hb) during a contralateral hand grasping task in the primary sensorimotor cortex (PSMC) of all patients. On the lesion side, NIRS revealed a decrease in Deoxy-Hb in five patients (Deoxy-decrease group), and an increase in Deoxy-Hb in seven patients (Deoxy-increase group); the Oxy-Hb and Total-Hb were increased during activation in both groups, indicating the occurrence of rCBF increases in response to neuronal activation. BOLD-fMRI demonstrated clear activation areas in the PSMC on the nonlesion side of all patients and on the lesion side of the Deoxy-decrease group. However, in the Deoxy-increase group, BOLD-fMRI revealed only a small activation area or no activation on the lesion side. Intraoperative brain mapping identified the PSMC on the lesion side that was not demonstrated by BOLD-fMRI. The false-negative activations might have been caused by the atypical evoked-CBO changes (i.e. increases in Deoxy-Hb) and the software employed to calculate the activation maps, which does not regard an increase of Deoxy-Hb (i.e., a decrease in BOLD-fMRI signal) as neuronal activation.

Introduction

Blood oxygenation level dependent contrast functional MRI (BOLD-fMRI) is regarded as a well-established noninvasive diagnostic method for imaging activated cortical areas. BOLD-fMRI images the activated areas by detecting the reduced concentration of deoxyhemoglobin (Deoxy-Hb) Kwong et al., 1992, Ogawa et al., 1990, Ogawa et al., 1992, which is caused by a larger increase in regional cerebral blood flow (rCBF) as compared to the cerebral metabolic rate for oxygen (CMRO2) in normal adults Fox and Raichle, 1986, Fox et al., 1988. Based on the assumption that normal adults and patients with brain tumors exhibit similar cerebral blood oxygenation (CBO) changes in the activated areas, BOLD-fMRI has been used to define the functional cortices of the brain in preoperative planning for tumor removal Atlas et al., 1996, Mueller et al., 1996, Nelson et al., 2002.

Several BOLD-fMRI studies have, however, cast doubt on the reliability of its functional imaging in patients with brain tumors Holodny et al., 1999, Holodny et al., 2000, Inoue et al., 1999, Lurito et al., 2000, Schreiber et al., 2000. Holodny et al., 1999, Holodny et al., 2000 reported that BOLD-fMRI indicated that patients with brain tumors in or adjacent to the primary sensorimotor cortex (PSMC) displayed significantly less activation of the PSMC on the lesion side than on the nonlesion side, although these patients had only mild sensorimotor deficits. Inoue et al. (1999) found that the fMRI-defined central sulcus did not coincide with the central sulcus as defined by magnetoencephalography. These observations suggest that BOLD-fMRI cannot image activated areas accurately in some patients with brain tumors. However, the underlying mechanism of such false-negative activations remains unclear.

Near-infrared spectroscopy (NIRS) is an optical method for measuring changes of oxyhemoglobin (Oxy-Hb) and Deoxy-Hb concentration in cerebral vessels with the characteristic absorption spectra of hemoglobin in the near-infrared range Jöbsis, 1977, Reynolds et al., 1988. Changes in total hemoglobin (sum of Oxy-Hb and Deoxy-Hb; Total-Hb) indicate blood volume (CBV) changes and correlate with CBF changes under conditions of constant hematocrit and perfusion pressure Ferrari et al., 1992, Pryds et al., 1990, Sakatani et al., 1995. NIRS thus allows us to measure changes of CBO and hemodynamics noninvasively. NIRS has been applied to the evaluation of evoked-CBO changes in normal adults Hock et al., 1995, Hock et al., 1997, Hoshi and Tamura, 1993a, Hoshi et al., 1994, Kato et al., 1993 Kleinschmidt et al., 1996, Sakatani et al., 1999a and patients with brain disorders Hock et al., 1997, Murata et al., 2002, Sakatani et al., 1998, Sakatani et al., 1999b.

NIRS activation studies on normal adults have demonstrated that neuronal activation generally causes a decrease of Deoxy-Hb with increases of Oxy-Hb and Total-Hb in the activated cortical area Hock et al., 1995, Hoshi and Tamura, 1993a, Hoshi and Tamura, 1993b, Hoshi and Tamura, 1997, Hoshi et al., 1994, Kleinschmidt et al., 1996, Sakatani et al., 1999a; this CBO change is consistent with that obtained by PET Fox and Raichle, 1986, Fox et al., 1988. However, the evoked-CBO changes occurring in brain disorders differ from those of normal adults Hock et al., 1997, Murata et al., 2002, Sakatani et al., 1998. Recently, in patients with cerebral ischemia, we compared the evoked-CBO changes measured by NIRS and the activation maps of BOLD-fMRI (Murata et al., 2002). We found that the focal concentration of Deoxy-Hb in the PSMC on the lesion side was increased during activation in the patients. In addition, BOLD-fMRI failed to image the activated areas in the PSMC of the patients. These observations suggested that the evoked-CBO changes occurring in brain disorders differ from those of normal adults resulting in false-negative activations on BOLD-fMRI.

In the present study, employing NIRS, we evaluated the evoked-CBO changes in the PSMC of patients with brain tumors who had no paresis of the upper extremities. We compared the evoked-CBO changes and the activation maps of BOLD-fMRI.

Section snippets

Subjects

We investigated 12 patients (five males and seven females) ranging in age from 27 to 65 years (mean, 48 years). All patients had suffered from brain tumors; eight cases had glioma (five cases of astrocytoma, two cases of glioblastoma, and one case of oligodendroglioma) and four cases had meningioma. We classified the relations between the tumors and the PSMC into three categories. First, the tumor was located within the PSMC (three cases). Second, the tumor was located close to the PSMC, which

Comparison of evoked-CBO changes and activation maps of BOLD-fMRI

On the nonlesion side, the contralateral motor task consistently caused a decrease of Deoxy-Hb with increases of Oxy-Hb and Total-Hb in the PSMC of all patients. After the beginning of the task, the Oxy-Hb and Total-Hb were increased during the task, and Deoxy-Hb decreased below the baseline. These changes showed a return to the control level after the end of the task (Fig. 1A). BOLD-fMRI demonstrated robust activation areas in the PSMC on the nonlesion side during the task (Fig. 1B).

In

Technical considerations regarding NIRS and BOLD-fMRI

The present study is the first NIRS activation study to be performed on patients with brain tumors. We compared the evoked-CBO changes measured by NIRS and the activation maps of BOLD-fMRI in the patients. When comparing such data, the following technical differences between NIRS and BOLD-fMRI need to be considered.

First, NIRS provides more information about the evoked-CBO changes than does BOLD-fMRI. NIRS measures the concentration changes of both Oxy-Hb and Deoxy-Hb in the cerebral vessels by

Acknowledgements

This work was supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Sciences and Technology of Japan (A12307029, A15209047, C15591553, and a grant for the promotion of the industry–university collaboration at Nihon University) and by Hamamatsu Photonics K.K. (Hamamatsu, Japan).

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