MEG Frequency Analysis Depicts the Impaired Neurophysiological Condition of Ischemic Brain

<div><p>Purpose</p><p>Quantitative imaging of neuromagnetic fields based on automated region of interest (ROI) setting was analyzed to determine the characteristics of cerebral neural activity in ischemic areas.</p><p>Methods</p><p>Magnetoencephalography (MEG) was used to evaluate spontaneous neuromagnetic fields in the ischemic areas of 37 patients with unilateral internal carotid artery (ICA) occlusive disease. Voxel-based time-averaged intensity of slow waves was obtained in two frequency bands (0.3–4 Hz and 4–8 Hz) using standardized low-resolution brain electromagnetic tomography (sLORETA) modified for a quantifiable method (sLORETA-qm). ROIs were automatically applied to the anterior cerebral artery (ACA), anterior middle cerebral artery (MCAa), posterior middle cerebral artery (MCAp), and posterior cerebral artery (PCA) using statistical parametric mapping (SPM). Positron emission tomography with ¹⁵O-gas inhalation (¹⁵O-PET) was also performed to evaluate cerebral blood flow (CBF) and oxygen extraction fraction (OEF). Statistical analyses were performed using laterality index of MEG and ¹⁵O-PET in each ROI with respect to distribution and intensity.</p><p>Results</p><p>MEG revealed statistically significant laterality in affected MCA regions, including 4–8 Hz waves in MCAa, and 0.3–4 Hz and 4–8 Hz waves in MCAp (95% confidence interval: 0.020–0.190, 0.030–0.207, and 0.034–0.213), respectively. We found that 0.3–4 Hz waves in MCAp were highly correlated with CBF in MCAa and MCAp (<i>r = 0</i>.<i>74</i>, <i>r = 0</i>.<i>68</i>, respectively), whereas 4–8 Hz waves were moderately correlated with CBF in both the MCAa and MCAp (<i>r = 0</i>.<i>60</i>, <i>r = 0</i>.<i>63</i>, respectively). We also found that 4–8 Hz waves in MCAp were statistically significant for misery perfusion identified on ¹⁵O-PET (<i>p<0</i>.<i>05</i>).</p><p>Conclusions</p><p>Quantitatively imaged spontaneous neuromagnetic fields using the automated ROI setting enabled clear depiction of cerebral ischemic areas. Frequency analysis may reveal unique neural activity that is distributed in the impaired vascular metabolic territory, in which the cerebral infarction has not yet been completed.</p></div

Pipelines for automated ROI setting for quantitative images of PET and MEG.

<p>(A) The first step was standardization using SPM. A MEG source image was acquired using a sLORETA-qm spatial filter from the slow spontaneous magnetic fields. MRI-T1WI, CBF in the PET image, and the MEG source image were spatially standardized by SPM using a pre-ordered template of MRI-T1WI and CBF in PET. OEF in the PET image was also standardized by SPM using the template of CBF in PET. (B) The second step was automated ROI constitution using NEUROFLEXER. The pre-ordered ROI template can be applied to the different modalities e.g., MEG and PET, through the normalized MRI.</p

LI from the ¹⁵O-PET and MEG images of the 37 patients using SPM.

<p>These images show the LI of the ¹⁵O-PET and MEG images of the 37 patients included in the present study, showing CBF (a), OEF (b), 0.3- to 4-Hz waves (c), and 4- to 8-Hz waves (d). The averages of the LI are encoded with color (values are shown in the color bars). The images were anatomically standardized by SPM. CBF values are decreased and OEF values are increased in the affected hemisphere. Both 0.3- to 4-Hz and 4- to 8-Hz MEG waves are distributed in the affected hemisphere, predominantly from the posterior temporal to parietal regions. AH: affected hemisphere, nAH: non-affected hemisphere.</p

Imaging differences of theta wave (4–8 Hz) activity between the two groups of ischemic conditions.

<p>MRI overlaid with neuromagnetic slow waves showing differences in theta wave (4–8 Hz) distributions between the two groups of ischemic conditions: Group 1 (n = 30) and Group 2 (n = 7). Blue–green color indicates the distribution of 4- to 8-Hz waves in Group 1, whereas red–yellow color indicates the distribution of 4- to 8-Hz waves in Group 2. We found a significantly greater distribution of 4- to 8-Hz waves in the MCAp of the affected hemisphere in Group 2 compared with Group 1 (<i>p < 0</i>.<i>01</i>; white arrows). The images were anatomically standardized by SPM. AH: affected hemisphere, nAH: non-affected hemisphere.</p

Correlation coefficient between the CBF and MEG in the ROIs of the MCAa and MCAp.

<p>Line plot graph showing absolute values of the correlation coefficient between CBF-LI and MEG-LI in the ROIs of the MCAa and MCAp. We observed a high correlation between 0.3- to 4-Hz wave laterality in the MCAp and CBF-LI in the MCAa (<i>r = 0</i>.<i>68</i>, <i>p < 0</i>.<i>01</i>) and MCAp (<i>r = 0</i>.<i>74</i>, <i>p < 0</i>.<i>01</i>), whereas no significant correlation was recognized between 0.3- to 4-Hz wave laterality in the MCAa and CBF-LI in the MCAa (<i>r = 0</i>.<i>25</i>, <i>p = 0</i>.<i>13</i>) or MCAp (<i>r = 0</i>.<i>37</i>, <i>p = 0</i>.<i>02</i>). We found a moderate correlation between 4- to 8-Hz wave laterality and CBF-LI in the ROIs of the MCAa and MCAp.</p

Automated ROI constitution focusing of the cerebral vascular territory using NEUROSTAT.

<p>ROIs were set to cover the major vascular regions, assuming patients with cerebral vascular disease. ACA, MCAa, MCAp, and PCA regions were generated by NEUROSTAT [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0168588#pone.0168588.ref033" target="_blank">33</a>]. MCAa and MCAp are comparable to M2ant and M2post in this figure, respectively.</p

MRI lesion distribution of 37 patients using SPM.

<p>This image shows the lesion distribution on MRI of the 37 patients included in the present study. The numbers of patients with ischemic lesions are shown by color-coding. Lesions that were hypointense on T1WI are colored blue to green, whereas lesions that were hyperintense on DWI are colored red to yellow. The lesions are seen predominantly in the affected hemisphere, and the distributions show the watershed type of infarction. The images were anatomically standardized by SPM. AH: affected hemisphere, nAH: non-affected hemisphere.</p

Results of investigation with 15O gas PET and MEG.

<p>Results of investigation with 15O gas PET and MEG.</p

Patient characteristics.

<p>Patient characteristics.</p

The absolute values from ¹⁵O-PET and MEG images of the 37 patients using SPM.

<p>These images show the absolute value from ¹⁵O-PET and MEG images of the 37 patients included in the present study, showing CBF (a), OEF (b), 0.3- to 4-Hz waves (c), and 4- to 8-Hz waves (d). The averages of the absolute values are encoded with color (values are shown in the color bars). The images were anatomically standardized by SPM. CBF values are decreased and OEF values are increased predominantly in the affected hemisphere. Both 0.3- to 4-Hz and 4- to 8-Hz waves of MEG are distributed predominantly in the affected hemisphere, from the posterior temporal to parietal regions. The absolute value from MEG images also suggested that the 4- to 8-Hz waves were distributed in the parietal area contralateral to cerebral hemisphere affected by the occlusive ICA lesion (Fig 4d, yellow arrows). AH: affected hemisphere, nAH: non-affected hemisphere.</p