Simultaneous measurement of neuronal activity and cortical hemodynamics by unshielded magnetoencephalography and near-infrared spectroscopy.

The correlation between neuronal activity and cortical hemodynamics, namely, neurovascular coupling (NVC), is important to shed light on the mechanism of a variety of brain functions or neuronal diseases. NVC can be studied by simultaneously measuring neuronal activity and cortical hemodynamics. Consequently, noninvasive measurements of the NVC have been widely studied using both electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). However, electromagnetic interference between EEG and fMRI is still a major problem. On the other hand, near-infrared spectroscopy (NIRS) is another promising tool for detecting cortical hemodynamics because it can be combined with EEG or magnetoencephalography (MEG) without any electromagnetic interference. Accordingly, in the present study, a simultaneous measurement system-combining an unshielded MEG using a two-dimensional gradiometer based on a low-Tc superconducting quantum interference device (SQUID) and an NIRS using nonmagnetic thin probes-was developed. This combined system was used to simultaneously measure both an auditory-evoked magnetic field and blood flow change in the auditory cortex. It was experimentally demonstrated that the combined unshielded MEG/NIRS system can simultaneously measure neuronal activity and cortical hemodynamics.

Note: Unshielded bilateral magnetoencephalography system using two-dimensional gradiometers.

Magnetoencephalography (MEG) noninvasively measures neuronal activity with high temporal resolution. The aim of this study was to develop a new type of MEG system that can measure bilateral MEG waveforms without a magnetically shielded room, which is an obstacle to reducing both the cost and size of an MEG system. An unshielded bilateral MEG system was developed using four two-dimensional (2D) gradiometers and two symmetric cryostats. The 2D gradiometer, which is based on a low-T(c) superconducting quantum interference device and wire-wound pickup coil detects a magnetic-field gradient in two orthogonal directions, or ∂/∂x(∂(2)B(z)/∂z(2)), and reduces environmental magnetic-field noise by more than 50 dB. The cryostats can be symmetrically positioned in three directions: vertical, horizontal, and rotational. This makes it possible to detect bilateral neuronal activity in the cerebral cortex simultaneously. Bilateral auditory-evoked fields (AEF) of 18 elderly subjects were measured in an unshielded hospital environment using the MEG system. As a result, both the ipsilateral and the contralateral AEF component N100m, which is the magnetic counterpart of electric N100 in electroencephalography and appears about 100 ms after the onset of an auditory stimulus, were successfully detected for all the subjects. Moreover, the ipsilateral P50m and the contralateral P50m were also detected for 12 (67%) and 16 (89%) subjects, respectively. Experimental results demonstrate that the unshielded bilateral MEG system can detect MEG waveforms, which are associated with brain dysfunction such as epilepsy, Alzheimer's disease, and Down syndrome.

Subtraction magnetocardiogram for detecting coronary heart disease.

BACKGROUND: A large-scale magnetocardiogram (MCG) database was produced, and standard MCG waveforms of healthy patients were calculated by using this database. It was clarified that the standard MCG waveforms are formed with the same shape and current distribution in healthy patients. A new subtraction method for detecting abnormal ST-T waveforms in coronary heart disease (CHD) patients by using the standard MCG waveform was developed. METHODS: We used MCGs of 56 CHD patients (63 ± 3 years old) and 101 age-matched normal control patients (65 ± 5 years old). To construct a subtracted ST-T waveform, we used standard MCG waveforms produced from 464 normal MCGs (male: 268, female: 196). The standard MCG waveforms were subtracted from each subject's measured MCGs, which were shortened or lengthened and normalized to adjust to the data length and magnitude of the standard waveform. We evaluated the maximum amplitude and maximum current-arrow magnitude of the subtracted ST-T waveform. RESULTS: The maximum magnetic field, maximum magnitude of current arrows, and maximum magnitude of total current vector increased according to the number of coronary artery lesions. The sensitivity and specificity of detecting CHD and normal control patients were 74.6% and 84.1%, respectively. CONCLUSIONS: The subtraction MCG method can be used to detect CHD with high accuracy, namely, sensitivity of 74.6% and specificity of 84.1% (in the case of maximum amplitude of total current vector). Furthermore, the subtraction MCG magnitude and its current distribution can reflect the expanse of the ischemic lesion area and the progress from ischemia to myocardial infarction.

Estimation method of finger tapping dynamics using simple magnetic detection system.

We have developed the simple estimation method of a finger tapping dynamics model for investigating muscle resistance and stiffness during tapping movement in normal subjects. We measured finger tapping movements of 207 normal subjects using a magnetic finger tapping detection system. Each subject tapped two fingers in time with a metronome at 1, 2, 3, 4, and 5 Hz. The velocity and acceleration values for both the closing and opening tapping data were used to estimate a finger tapping dynamics model. Using the frequency response of the ratio of acceleration to velocity of the mechanical impedance parameters, we estimated the resistance (friction coefficient) and compliance (stiffness). We found two dynamics models for the maximum open position and tap position. In the maximum open position, the extensor muscle resistance was twice as high as the flexor muscle resistance and males had a higher spring constant. In the tap position, the flexor muscle resistance was much higher than the extensor muscle resistance. This indicates that the tapping dynamics in the maximum open position are controlled by the balance of extensor and flexor muscle friction resistances and the flexor stiffness, and the flexor friction resistance is the main component in the tap position. It can be concluded that our estimation method makes it possible to understand the tapping dynamics.

Repolarization spatial-time current abnormalities in patients with coronary heart disease.

BACKGROUND: Magnetocardiography (MCG) is a new technique for visualizing a current distribution in the myocardium. In recent years, current distribution parameters (CDPs) have been developed based on the distribution. The CDPs reflect spatial-time current abnormalities in patients with coronary heart disease (CHD). However, the criteria and scoring method of the abnormalities using CDPs are still controversial. METHOD: We measured MCG signals for 101 normal controls and 56 CHD patients (single-, double-, and triple-vessel diseases) using a MCG system. The CDPs (maximum current vector [MCV], total current vector [TCV], current integral map, and current rotation) during ventricular repolarization were analyzed. To evaluate the CDPs that are effective in distinguishing between normal controls and CHD patients, the areas under the receiver operating characteristic curve (A(z)) are calculated. Furthermore, the total scores ("0" to "4") of four CDPs with high A(z) values are also calculated. RESULTS: MCV and TCV angles at the T-wave peak had the highest A(z) value. Furthermore, TCV angular differences between the ST-T segment also had high A(z) values. Using the four CDPs, the averaged total score for patients with triple-vessel disease was the highest ("2.67") compared to the other groups (normal controls: 0.53). Furthermore, based on the assumption that subjects with a total score over "1" were suspected of having CHD, sensitivity and specificity were 85.7% and 74.3%, respectively. CONCLUSION: We concluded that the score and criteria using MCV and TCV during repolarization in CHD patients can reflect lesion areas and time changes of electrical activation dispersion due to ischemia.

Standard template of adult magnetocardiogram.

BACKGROUND: We need to know the magnetocardiogram (MCG) features regarding waveform and two-dimensional current distribution in normal subjects in order to classify the abnormal waveform in patients with heart disease. However, a standard MCG waveform has not been produced yet, therefore, we have first made the standard template MCG waveform. METHODS AND RESULTS: We used data from 464 normal control subjects' 64-channel MCGs (268 males, 196 females) to produce a template MCG waveform. The measured data were averaged after shortening or lengthening and normalization. The time interval and amplitude of the averaged data were adjusted to mean values obtained from a database. Furthermore, the current distributions (current arrow maps [CAMs]) were calculated from the produced templates to determine the current distribution pattern. The produced template of the QRS complex had a typical shape in six regions that we defined (M1, M2, M3, M4, M5, and M6). In the P wave, the main current arrow in CAMs pointing in a lower-left direction appeared in M1. In the QRS complex, the typical wave appeared in each region, and there were two main current arrows in M2 and M5. There were negative T waves in M1, M4, and M5, and positive T waves in M3 and M6, and the main current arrow pointing in a lower-left direction appeared in M2. CONCLUSION: Template MCG waveforms were produced. These morphologic features were classified into six regions, and the current distribution was characterized in each region. Consequently, the templates and classifications enable understanding MCG features and writing clinical reports.

Space-time database for standardization of adult magnetocardiogram-making standard MCG parameters.

BACKGROUND: The magnetocardiogram (MCG) is a promising medical tool for detecting and visualizing abnormal cardiac electrical activation in heart-disease patients. However, there is no large-scale MCG database of healthy subjects, and there is little knowledge of gender- and age-related influences on MCG data. METHODS AND RESULTS: We obtained MCG data from 869 subjects (554 men, 315 women) using a conventional 64-channel MCG system, which covers the whole heart. Electrocardiogram (ECG) data were also obtained; 464 people (268 men, 196 women) were identified as a normal group using ECG data. Time intervals (PQ, QRS, QT, and QTc), current distributions (maximum current vector (MCV), and the total current vector (TCV)) of MCG data of the 464 normal subjects were analyzed to obtain basic MCG parameters. Although mean values of PQ and QRS intervals of the male subjects were slightly longer than those of the female subjects, no intervals were correlated with gender or age. The correlation between PQ intervals of ECG and those of MCG was better than the correlation between QRS and QT intervals of ECG and those of MCG. Both MCV and TCV angles were much smaller than the electrical-axis angle in ECG. Although TCVs of the QRS and T waves were stable, the women's mean T-wave-TCV angles significantly increased with age. The maximum amplitude of the P wave was about 1.7 pT, and the value of the QRS complex was about 20-25 pT. Moreover, the T-wave amplitude decreases with age. CONCLUSION: The MCG standard space-time parameters determined here provide a normal range for MCG parameters.

Integral value of JT interval in magnetocardiography is sensitive to coronary stenosis and improves soon after coronary revascularization.

BACKGROUND: Magnetocardiography (MCG) is sensitive to minute cardiac electric abnormalities, but its clinical utility in diagnosing ischemic heart disease (IHD) has not been established. The present study examined the usefulness of an integral MCG value of ventricular repolarization in patients with IHD. METHODS AND RESULTS: MCG was performed at rest in 14 patients with coronary stenosis >75% confirmed by coronary angiography (IHD group) using a 64-channel system, and then the sum of the 64-channel integral values of the QRS or JT intervals (QRSi and JTi, respectively) was calculated. The JTi/QRSi value indicated the total power of currents in JT compared with those in QRS. These measurements were repeated within 2 weeks after coronary revascularization. The Control group comprised 30 healthy volunteers. The baseline value of JTi/QRSi was significantly smaller in the IHD than in the Control group, but after revascularization it increased and did not significantly differ from the Control group. No significant difference in ST deviation was identified by electrocardiography (ECG) before and after coronary revascularization. Analysis of the Control group revealed that JTi/QRSi was not affected by age. CONCLUSIONS: The JTi/QRSi of the MCG is more sensitive to coronary stenosis than ECG, and this parameter improves soon after coronary revascularization.

Motion analysis of grip and release with fingers using simple magnetic detection system.

We have developed a magnetic grip-and-release motion detection system to measure time differences among fingers during motion. We designed a magnetic sensing system consisting of a magnetic oscillation coil, sensing coil, and circuit unit. We measured wave forms of grip-and-release motion (15 s) of seven healthy volunteers using the system. To provide the grip-and-release timing of each finger, we used the reference voltage of each subject in the state of grasping a rod with a 30 mm diameter. Using the reference voltage, the time differences in the finger movements of all volunteers were detected. The detected grip-and-release time difference of both dominant and nondominant hands had a main tendency in which the closing movement of the little finger is fast, within 10 ms, and the opening movement is slow, within 13 ms. Our data suggest that the new magnetic sensing system has the potential to detect the quantitative value of the time difference in grip-and-release motion among fingers.

Visualization of three-dimensional cardiac electrical excitation using standard heart model and anterior and posterior magnetocardiogram.

Our aim in this study is to obtain novel three-dimensional (3-D) images of cardiac electrical excitation that include morphological information on the whole heart. We obtain these 3-D images by projecting anterior and posterior two-dimensional (2-D) current-arrow maps (CAMs) onto a 3-D standard heart model. This standard heart model is adjusted to the individual subject's heart position by using the coordinates of the sinus node, which are obtained from magnetocardiogram (MCG) signals. The anterior and posterior CAMs are calculated by taking the orthogonal partial derivatives of the normal component of the anterior and posterior MCGs. After adjusting the base current values of the anterior and posterior CAMs, the adjusted CAMs are projected onto the standard heart model. We generated the projected CAMs (PCAMs) of the six phases (atrial, and ventricular, excitation) for seven healthy subjects. The validity of PCAM was evaluated by extracting the maximal current directions and positions from the PCAMs. The maximal current directions and positions during each excitation phase were almost in the same in the seven healthy subjects. Therefore, the PCAMs give us a clear view of the anterior and posterior myocardial excitation for the respective electrophysiological phases.

Electrical space-time abnormalities of ventricular depolarization in patients with Brugada syndrome and patients with complete right-bundle branch blocks studied by magnetocardiography.

BACKGROUND: Both ventricular depolarization abnormalities (QRS complex) and repolarization ones (ST/T) are still controversial in literature. The objective of this study was to clarify the space-time variations that occur in patients carriers of Brugada syndrome using Magnetocardiography and also compare them with cases of complete right-bundle branch block (CRBBB) and individuals without any dromotropic disorder (control group). METHODS AND RESULTS: Magnetocardiograms (MCGs) of Brugada syndrome patients (n = 16), CRBBB patients (n = 14), and members of a control group (n = 46) at rest were recorded. The MCGs were used to produce a whole-heart electrical-activation diagram (W-HEAD), which can visualize the spatial time-variant activation in the whole heart. In the W-HEAD pattern, three activations were located in the left ventricle, and CRBBB patients had a wide peak with about 65-ms delay on the right anterior side. While the Brugada syndrome pattern has a posteromedian left-ventricle excitation, that is half the amplitude that occurs in CRBBB patients, the electrical conduction rate to the posterosuperior septum area was low. CONCLUSIONS: The W-HEAD data made it possible to visualize space-time depolarization abnormalities. These findings suggest that the electrical conduction rate to the posterosuperior septum area in Brugada syndrome cases is low, and this low activation may be a feature of typical Brugada syndrome.

Standardization of the PQRST waveform and analysis of arrhythmias in the fetus using vector magnetocardiography.

Fetal magnetocardiography (fMCG) is useful for analysis of fetal cardiac events. However, fetal presentation and movement affect the fMCG waveform, making it difficult to standardize the waveform. The aim of this study was to investigate whether the use of vector magnetometers can compensate for these limitations. We studied 59 fetuses (gestational age, 22-40 wk, median, 32), including 41 with uncomplicated pregnancies and 18 with fetal cardiac disease. fMCG was recorded twice in each case, and the two waveforms were compared with each other in uncomplicated subjects to investigate the effects of fetal presentation. The superconducting quantum interference device (SQUID) system used in this study was a 12-channel vector magnetometer, by which the three components of the magnetic field (Bx, By, Bz) could be detected simultaneously at four recording points. By constructing the three components, a composite waveform (Bxyz) was obtained. The configuration of the composite waveforms was similar among normal fetuses always with positive polarity, independent of fetal presentation and movement. The difference in the time intervals (PR, QRS, and ventricular activation time [VAT]) between the first and second measurements was minimal in the composite waveforms (Bxyz) compared with that in each channel (Bx, By, Bz). Even before signal averaging, waveforms with high time resolution were recorded in at least one of the three components, making it possible to analyze fetal arrhythmias precisely. Our results indicate that vector magnetocardiography is potentially useful for standardization of the fMCG waveforms and to provide a more complete and accurate analysis of fetal arrhythmias.

Magnetocardiography study on ventricular depolarization-current pattern in patients with brugada syndrome and complete right-bundle branch blocks.

BACKGROUND: The objective of this study is to use magnetocardiography to determine the existence of a small abnormal current during ventricular depolarization in patients with Brugada syndrome. To understand this small difference in abnormal current during ventricular depolarization, we compared abnormal currents of patients with cases of complete right-bundle-branch block (CRBBB). METHODS AND RESULTS: We developed a whole-heart electrical bull's eye map (WHEBEM) that uses magnetocardiograms (MCGs) to visualize the current distribution in a circular map. MCGs of Brugada syndrome patients (n = 16), CRBBB patients (n = 10), and controls (n = 12) at rest were recorded. In the WHEBEMs of Brugada syndrome patients, the magnitude of the S-wave current in the upper-right direction of the anterior side is larger than that of the controls. In addition, the R-wave current direction is similar to that of the controls, and the R-wave vector is distributed over a larger area than that of the controls. On the other hand, the CRBBB patients have a distribution of R-wave currents over a larger area in the left anteromedian region and the left posteromedian region. Moreover, in all CRBBB patients, S-wave currents with a large magnitude have the same direction distributed over a small area. CONCLUSIONS: The WHEBEM findings suggest that there is an abnormal current in the direction to the upper right (in the S-wave) in the anterosuperior region of Brugada syndrome patients. We thus conclude that a WHEBEM has the potential to detect characteristics of heart disease.

Reconstruction of action potential of repolarization in patients with congenital long-QT syndrome.

A method for reconstructing an action potential during the repolarization period was developed. This method uses a current distribution-plotted as a current-arrow map (CAM)--calculated using magnetocardiogram (MCG) signals. The current arrows are summarized during the QRS complex period and subtracted during the ST-T wave period in order to reconstruct the action-potential waveform. To ensure the similarity between a real action potential and the reconstructed action potential using CAM, a monophasic action potential (MAP) and an MCG of the same patient with type-I long-QT syndrome were measured. Although the MAP had one notch that was associated with early afterdepolarization (EAD), the reconstructed action potential had two large and small notches. The small notch timing agreed with the occurrence of the EAD in the MAP. On the other hand, the initiation time of an abnormal current distribution coincides with the appearance timing of the first large notch, and its end time coincides with that of the second small notch. These results suggest that a simple reconstruction method using a CAM based on MCG data can provide a similar action-potential waveform to a MAP waveform without having to introduce a catheter.

Quantitative magnetic detection of finger movements in patients with Parkinson's disease.

To develop a new measurement tool for quantitatively detecting the finger movement of a patient with Parkinson's disease (PD), we designed a magnetic sensing system consisting of a magnetic induction coil, a sensing coil, and a circuit unit. The sensing coil detects the inducted magnetic field that varies with the distance between the two coils, and the detected signals are demodulated in the circuit unit in order to obtain the variation voltage from the oscillation frequency. To obtain a coefficient for converting voltage to distance, we measured the output voltages for seven fixed finger positions of 12 normal volunteers. The voltage differences corresponding to the finger movement in 20 PD patients, six age-matched controls, and 12 normal volunteers were then recorded for 30s. To investigate the velocity and acceleration of the finger movement, we calculated their waveforms from the measured displacement waveform. We also detected the main frequency of the tapping rhythm by using a fast Fourier transform (FFT). The averaged amplitude of each waveform decreased with the disorder in the Hoehn-Yahr (HY) stage, while the averaged tapping frequency of PD patients did not have any correlation with this stage. It can be concluded that this magnetic sensing system can assess finger movement quantitatively.

Magneto-encephalographic measurement of neural activity during period of vertigo induced by cold caloric stimulation.

The aim of this study was to investigate neural activity during period of vertiginous sensation, induced by caloric stimulation. After caloric vestibular stimulation (CVS) by cold water of five volunteers (n=5, age: 30+/-10), auditory evoked magnetic fields (AEFs) during the subsequent period of vertiginous sensations were measured by magnetoencephalography (MEG). Current-arrow maps (CAMs) were produced to estimate the spatial current distribution of the AEF responses, and a rotation value (dI(rot)) was calculated from the CAM. The worth of the dI(rot) values as indicators of vertigo was evaluated by comparing them with earlier reported values for elderly control (n=11, age: 67+/-5) and chronic dizziness (CD) (n=27, age: 68+/-8) groups (obtained from AEF responses with no the CVS). Although all volunteers felt vertigo during the AEF measurements, the AEF waveforms and CAM pattern only showed slight changes. While the dI(rot) values (1.43+/-0.73) just after CVS were not significantly different from those (1.59+/-0.46) for the elderly controls, they were significantly different from those (3.54+/-1.34) for the CD patients. These findings suggest that (i) the new parameter (dI(rot)) is more sensitively indicates dizziness (non-rotatory sensation) than vertigo (ii) the auditory cortical region may play an important role in body-balance perception of floating sensations.

Detection of repolarization abnormalities in patients with cardiomyopathy using current vector mapping technique on magnetocardiogram.

OBJECTIVES: We have previously developed current vector maps of tangential components on the magnetocardiogram (MCG) to obtain cardiac current distribution images. The present study was conducted to detect repolarization abnormalities in patients with cardiomyopathy using the current vector map. SUBJECTS AND METHODS: Thirteen patients with cardiomyopathy (nine males and four females aged 7-16 years, mean, 11.5 +/- 3.1 years, +/- SD), and 15 age- and sex-matched normal subjects were studied. Normal components (Bz) of MCG were measured at rest with a multi-channel superconducting quantum interface device (SQUID) system, and differentiated in the tangential direction to obtain current vector maps. Homogeneity of current in the heart during repolarization was investigated. The direction of the maximum current vector was also calculated in each case. RESULTS: In all normal subjects, the current vector consistently showed a left downward direction on the frontal chest plane during the repolarization process. On the other hand, 8 out of 13 patients with cardiomyopathy showed different patterns; four of these patients showed multi-dipoles, and the other four showed a shift in the current vector direction. One of the eight cases showed no abnormality on electrocardiogram (ECG). CONCLUSIONS: Repolarization process in patients with cardiomyopathy was apparently different from those in normal subjects on the current vector map. It was easy to visualize the repolarization process as a projection to the frontal plane, including regional abnormalities, by the current vector maps, which might be more useful for early detection of repolarization abnormalities than ECG.

Noninvasive diagnosis of partial atrial standstill using magnetocardiograms.

A 59-year-old woman with partial atrial standstill was studied using magnetocardiograms (MCGs), which revealed through QRS-T subtraction and time-frequency analysis that there was a high-frequency (6 Hz) magnetic source at the low atrial septum. MCGs are useful for noninvasively evaluating the clinical course of patients with atrial fibrillation.

Abnormal auditory neural networks in patients with right hemispheric infarction, chronic dizziness, and moyamoya disease: a magnetoencephalogram study.

The purpose of this study was to determine whether the auditory cortex is sensitive to cortical insults and to determine the specificity of the insults in three clinical situations with different cortical involvement. Auditory-evoked magnetic fields of ten normal subjects, 8 patients with right hemispheric infarction, 11 with chronic dizziness, and 2 with moyamoya disease were measured. To analyze the abnormality of auditory neural networks, the magnitude ratio and the angle difference (Deltatheta) between response vectors, which were determined from maximum current arrows corresponding to the N100m peak for contralateral and ipsilateral stimuli were used. A normal range of the parameters was defined so that abnormal values could be determined. Of the three parameters, Deltatheta was the most sensitive: 4 patients with right hemispheric infarction, 4 with chronic dizziness, and 1 with moyamoya disease had abnormal Deltatheta. The electrical activity in the patients with such abnormal Deltathetas had a circular current pattern. These findings suggest that right infarction lesions sometime affect the left auditory neural network, dizziness is caused by abnormal neural networks between the vestibular cortical area and the auditory cortex or by an imbalance between left and right auditory-cortex activities, and moyamoya-disease patients have almost normal auditory-electrical activity.

Detection of spatial repolarization abnormalities in patients with LQT1 and LQT2 forms of congenital long-QT syndrome.

The aim of this study is to detect the spatial current dispersion that appears in the T-wave of patients with congenital long-QT syndrome (LQTS). To observe this dispersion, magnetocardiograms (MCGs)--which have a high spatial resolution--of LQT1 patients (n = 7), LQT2 patients (n = 9) and a control group (n = 33) were recorded. The dispersion was evaluated by plotting current-arrow maps (CAMs) calculated from the MCG signals. In the case of LQT1, abnormal current arrows in the CAMs appeared above the inferior part of the heart in two LQT1 patients with a long corrected QT interval (QTc) (>0.6), and the current direction was from the left (origin side) to the right ventricular muscle (110 degrees). In six out of nine LQT2 patients, abnormal current arrows with angles below 20 degrees were observed above the right inferior part or lower septum; the current direction was from the right (origin side) to the left ventricular muscle. However, in the case of the LQT2 patients, the QTc values did not correlate with the abnormal current. These findings suggest that the origin of abnormal repolarization in LQT1 is the left ventricular muscle and the origin of that in LQT2 is the right ventricular muscle or lower septum. The estimation of the origin in LQTS patients can provide important information such as the risk factor of sudden death.