Comparison of current density viability imaging at rest with FDG-PET in patients after myocardial infarction.

The assessment of myocardial viability is a major diagnostic challenge in patients with coronary artery disease (CAD) after myocardial infarction. Novel threedimensional current density (CD) imaging algorithms use high-resolution magnetic field mapping to determine the electrical activity of myocardial segments at rest. We, for the first time, compared CD activity obtained with several algorithms to 18-F-fluoro-deoxyglucose positron emission tomography (FDG-PET) in evaluation of myocardial viability. Magnetic field maps were obtained in nine adult patients (pt) with CAD and a history of infarction. The criterion for non-viable myocardium was an FDG-PET uptake with less than 45% of the maximum in the respective segments. CD imaging was applied to the left ventricle by using six different methods to solve the inverse problem. Mean CD activity was calculated for a close meshed grid of 90 locations of the left ventricle. A cardiologist compared bull's eye plots of CD and FDG-PET activity by eye. Spearman's correlation coefficients and specificity at a given level of sensitivity (70%) were calculated. Bull's eye plots revealed a significant correlation of CD/PET in 5 pt and no correlation in 3 pt. One pt had a negative correlation. The six different CD reconstruction methods performed similar. While CD reconstruction has the principal potential to image viable myocardium, we found that the reconstructed CD magnitude was low in scar segments but also reduced in some segments with preserved metabolic activity under resting conditions. New vector measurement techniques, the use of additional stress testing and advances in mathematical methodology are expected to improve CD imaging in future.

A Matlab library for solving quasi-static volume conduction problems using the boundary element method.

The boundary element method (BEM) is commonly used in the modeling of bioelectromagnetic phenomena. The Matlab language is increasingly popular among students and researchers, but there is no free, easy-to-use Matlab library for boundary element computations. We present a hands-on, freely available Matlab BEM source code for solving bioelectromagnetic volume conduction problems and any (quasi-)static potential problems that obey the Laplace equation. The basic principle of the BEM is presented and discretization of the surface integral equation for electric potential is worked through in detail. Contents and design of the library are described, and results of example computations in spherical volume conductors are validated against analytical solutions. Three application examples are also presented. Further information, source code for application examples, and information on obtaining the library are available in the WWW-page of the library: (http://biomed.tkk.fi/BEM).

Imaging characteristics of different multichannel magnetocardiographic systems.

In this study a comparison of multichannel magnetocardiographic systems is performed with respect to the "detectable" information content. We investigate the lead-field matrices, the slope of the singular values and the source spaces of three different devices: the VectorView (Neuromag: magnetometer-gradiometer mixed device) of the BioMag Laboratory, Helsinki University Central Hospital (HUCH), the arrangement of electronically coupled magnetometers of the Physikalisch-Technische Bundesanstalt Berlin (PTB) and a virtual sensor geometry which was optimized for an improved slope of the singular values at the Institute of Biomedical Engineering, Karlsruhe.

Heart rate adjustment of magnetic field map rotation in detection of myocardial ischemia in exercise magnetocardiography.

AIMS: We studied the capability of heart rate (HR) adjusted change in multichannel magnetocardiogram (MCG) to detect exercise-induced ischemia. METHODS AND RESULTS: The MCG and 12-lead ECG were recorded simultaneously during supine exercise testing in 17 healthy controls and 24 patients with single vessel coronary artery disease (CAD). In the MCG analysis, we plotted the orientation of the magnetic field map (MFM) against the HR in each cardiac cycle during recovery. A regression line was fitted to the data and the line slope (degrees/bpm) was determined. In the ECG, the ST-segment depression vs HR (ST/HR) slope was evaluated. The HR adjusted MFM rotation was more extensive in the pooled CAD group, and in all subgroups with different stenosed vessel, than in the control group at the ST-segment (1.5 +/- 2.1 degrees/bpm vs 0.29 +/- 0.25 degrees/bpm, p < 0.0005) and at the T-wave apex (0.95 +/- 0.81 degrees/bpm vs 0.24 +/- 0.25 degrees/bpm, p < 0.0005). Areas under the receiver operating characteristic curves of the HR adjusted MFM rotation at the ST-segment (88.5%) and the T-wave (86.0%) were higher than the ones without HR adjustment (75.5% and 68.1%, respectively), and higher than the area of ST/HR slope in the ECG (80.2%). CONCLUSION: HR adjusted MFM rotation detects transient ischemia independent of the stenosed vessel. HR adjustment improves the performance of the MCG in ischemia detection by the analysis of the ST-segment and the T-wave. The MCG was superior to the 12-lead ECG.

ST-segment level and slope in exercise-induced myocardial ischemia evaluated with body surface potential mapping.

Body surface potential mapping (BSPM) is superior to 12-lead electrocardiography for detection of acute and old myocardial infarctions (MIs). We used BSPM to examine electrocardiographic criteria for acute reversible myocardial ischemia. BSPM with 123 channels was performed in 45 patients with coronary artery disease (CAD) and 25 healthy controls during supine bicycle exercise testing. Of the 45 patients, 18 patients had anterior, 14 had posterior, and 13 had inferior ischemia documented by coronary angiography and thallium scintigraphy. The ST amplitude was measured 60 ms after the J-point and the ST slope calculated by fitting a regression line from the J-point to 60 ms after it. The optimal locations for detecting ST depression and ST-slope decrease were identified. In the pooled CAD patient group, the optimal location for ST depression was 5 cm below standard lead V(5) (CAD group: -70 +/- 70 microV; controls: 70 +/- 80 microV, p <0.001). Using a cut-off value of -10 microV, the ST depression separated the patients with CAD from controls with a sensitivity of 84% and a specificity of 96%. The ST slope became more horizontal in the patient group than in the control group. The optimal location for ST-slope decrease was over the left side (CAD group: 20 +/- 20 microV/s; controls: 720 +/- 320 microV/s, p <0.001). Using a cut-off value of 320 microV/s, the ST slope separated patients with CAD from controls with a sensitivity of 93% at a specificity level of 88%. The area under the receiver operating characteristic curve of ST slope tended to be higher than the one of ST depression (97% vs 93%; p = 0.097). In conclusion, regions sensitive for ST depression and for ST-slope decrease could be identified in BSPM, despite variation in the location of ischemia and the presence or absence of a history of MI. ST slope is a sensitive and specific marker of transient myocardial ischemia, and might perform even better than ST depression.

Recording locations in multichannel magnetocardiography and body surface potential mapping sensitive for regional exercise-induced myocardial ischemia.

INTRODUCTION: This study aimed to identify the optimal locations in multichannel magnetocardiography (MCG) and body surface potential mapping (BSPM) to detect exercise-induced myocardial ischemia. METHODS: We studied 17 healthy controls and 24 coronary artery disease (CAD) patients with stenosis in one of the main coronary artery branches: left anterior descending (LAD) in 11 patients, right (RCA) in 7 patients, and left circumflex (LCX) in 6 patients. MCG and BSPM signals were recorded during a supine bicycle stress test. The capability of a recording location to separate the groups was quantified by subtracting the mean signal amplitude of the normal group from that of the patient group during the ST segment and at the T-wave apex, and dividing the resulting amplitude difference by the corresponding standard deviation within all subjects. RESULTS: In MCG the optimal location for ST depression was at the right inferior grid for the RCA, at the mid-inferior grid for the LCX, and in the middle of these locations for the LAD subgroup (mean ST amplitudes: CAD -80 +/- 360fT, controls 610 +/- 660fT; p < 0.001). In BSPM it was on the left upper anterior thorax for the LAD, left lower anterior thorax for the RCA, and on the lower back for the LCX subgroup (mean ST amplitudes: CAD -39 +/- 61 microV and controls 38 +/- 38 microV; p < 0.001). In MCG the optimal site for T-wave amplitude decrease was the same as the one for the ST depression. In BSPM it was on the middle front for the LAD, on the back for the LCX and on the left abdominal area for the RCA group. In accordance with electromagnetic theory, the largest ST segment and T-wave amplitude changes took place in MCG in locations orthogonal to those in BSPM. CONCLUSION: This study identified magnetocardiographic and BSPM recording locations which are sensitive for detecting transient myocardial ischemia by evaluation of the ST segment as well as the T-wave. These locations strongly depend on ischemic regions and are outside the conventional 12-lead ECG recording sites.

Magnetocardiographic and electrocardiographic exercise mapping in healthy subjects.

In 12-lead electrocardiography (ECG), detection of myocardial ischemia is based on ST-segment changes in exercise testing. Magnetocardiography (MCG) is a complementary method to the ECG for a noninvasive study of the electric activity of the heart. In the MCG, ST-segment changes due to stress have also been found in healthy subjects. To further study the normal response to exercise, we performed MCG mappings in 12 healthy volunteers during supine bicycle ergometry. We also recorded body surface potential mapping (BSPM) with 123 channels using the same protocol. In this paper we compare, for the first time, multichannel MCG recorded in bicycle exercise testing with BSPM over the whole thorax in middle-aged healthy subjects. We quantified changes induced by the exercise in the MCG and BSPM with parameters based on signal amplitude, and correlation between signal distributions at rest and after exercise. At the ST-segment and T-wave apex, the exercise induced a magnetic field component outward the precordium and the minimum value of the MCG signal over the mapped area was found to be amplified. The response to exercise was smaller in the BSPM than in the MCG. A negative component in the MCG signal at the repolarization period of the cardiac cycle should be considered as a normal response to exercise. Therefore, maximum ST-segment depression over the mapped area in the MCG may not be an eligible parameter when evaluating the presence of ischemia.

Beat-to-beat analysis method for magnetocardiographic recordings during interventions.

Multichannel magnetocardiography (MCG) during exercise testing has been shown to detect myocardial ischaemia in patients with coronary artery disease. Previous studies on exercise MCG have focused on one or few time intervals during the recovery period and only a fragment of the data available has been utilized. We present a method for beat-to-beat analysis and parametrization of the MCG signal. The method can be used for studying and quantifying the changes induced in the MCG by interventions. We test the method with data recorded in bicycle exercise testing in healthy volunteers and patients with coronary artery disease. Information in all cardiac cycles recorded during the recovery period of exercise MCG testing is, for the first time, utilized in the signal analysis. Exercise-induced myocardial ischaemia was detected by heart rate adjustment of change in magnetic field map orientation. In addition to the ST segment, the T wave in the MCG was also found to provide information related to myocardial ischaemia. The method of analysis efficiently utilizes the spatial and temporal properties of multichannel MCG mapping, providing a new tool for detecting and quantifying fast phenomena during interventional MCG studies. The method can also be applied to an on-line analysis of MCG data.

Current-density estimation of exercise-induced ischemia in patients with multivessel coronary artery disease.

Magnetocardiographic and body surface potential mapping data measured in 6 patients with multivessel coronary artery disease were used in equivalent current-density estimation (CDE). Patient-specific boundary-element torso models were acquired from magnetic resonance images. Positron emission tomography data registrated with anatomical magnetic resonance imaging data provided the gold standard. Discrete current-density estimation values were computed on the epicardial surface of the left ventricle from difference (stress-rest) ST-segment maps. The ill-posed inverse problem was regularized with 3 different methods (Tikhonov regularization with an identity or a surface Laplacian operator and a maximum a posteriori estimator). Comparisons with positron emission tomography studies showed that the maximum a posteriori estimator is superior to other regularizations, provided that a suitable a priori information is available. In general, good correspondence was found for segments of high and low amplitude in current-density estimations, and the viable and scar areas in positron emission tomography, respectively.

The effect of geometric and topologic differences in boundary element models on magnetocardiographic localization accuracy.

This study was performed to evaluate the changes in magnetocardiographic (MCG) source localization results when the geometry and the topology of the volume conductor model were altered. Boundary element volume conductor models of three patients were first constructed. These so-called reference torso models were then manipulated to mimic various sources of error in the measurement and analysis procedures. Next, equivalent current dipole localizations were calculated from simulated and measured multichannel MCG data. The localizations obtained with the reference models were regarded as the "gold standard." The effect of each modification was investigated by calculating three-dimensional distances from the gold standard localizations to the locations obtained with the modified model. The results show that the effect of the lungs and the intra-ventricular blood masses is significant for deep source locations and, therefore, the torso model should preferably contain internal inhomogeneities. However, superficial sources could be localized within a few millimeters even with nonindividual, so called standard torso models. In addition, the torso model should extend long enough in the pelvic region, and the positions of the lungs and the ventricles inside the model should be known in order to obtain accurate localizations.

Conversion of magnetocardiographic recordings between two different multichannel SQUID devices.

Comparison of biomagnetic measurements performed with different multichannel magnetometers is difficult, because differing sensor types and locations do not allow measurements from the same locations in respect to the body. In this study, two transformation procedures were utilized to compare magnetocardiograms (MCG) recorded with two different multisensor systems. Signals from one sensor array were used to compute parameters of a multipole expansion or minimum-norm estimates at 1-ms steps over the cardiac cycle. The signals of the second sensor array were then simulated from the computed estimates and compared against measured data. Both the multipole- and the minimum-norm-based transformation method yielded good results; the average correlation between simulated and measured signals was 93%. Thus, the methods are useful to compare MCG recordings performed using differing sensor configurations, e.g., for multicenter patient studies. This study provides the first empirical basis for assessing the transformation of MCG data of differing devices by general model-based field reconstructions.

Identification of post-myocardial infarction patients with ventricular tachycardia by time-domain intra-QRS analysis of signal-averaged electrocardiogram and magnetocardiogram.

A new time-domain analysis method, which quantifies ECG/MCG intra-QRS fragmentation, is applied to parts of the QRS complex to identify post-myocardial infarction patients with ventricular tachycardia. Three leads of signal-averaged electrocardiograms and nine leads of magnetocardiograms were band-pass filtered (74 Hz to 180 Hz). The filtered signals showed fragmentation in the QRS region, which was quantified by the number of peaks M and a score S, that is the product of M and the sum of the peak amplitudes. Both parameters were determined for the first 80 ms of the QRS complex and the total QRS complex in each channel. For classification, the mean-values of the parameters M and S of the three electrical leads and the nine magnetic leads were calculated. Late potential and late field analyses were performed for the same signals. 31 myocardial infarction patients were included, 20 of them with a history of documented ventricular tachycardia (VT). Identification of VT patients using the SAECG led to better results (sensitivity 95%, specificity 91%) considering the entire QRS complex than with the standard late potential analysis suggested by Simson (sensitivity 90%, specificity 73%). For the SAMCG and the entire QRS complex results using the parameters S and M are also better (sensitivity 95%, specificity 100%) than for the late field analysis (sensitivity 90% and specificity 100%). For the first 80 ms, the performance of the parameters M and S is only slightly decreased.

Non-invasive arrhythmia risk evaluation in clinical environment.

We have applied various methods to extract parameters from high-resolution magnetocardiographic (MCG) and electrocardiographic (ECG) recordings for characterizing the risk of life-threatening arrhythmias. The methods include detection of late fields and late potentials at the end of the QRS, abnormalities in spectral variability and signal fragmentation during the QRS, and variability in the heart rate. In addition, we have developed methods to convert MCG signals measured with any sensor configurations to a common presentation form. The signal processing methods have been implemented on a user-friendly interface which allows fast and easy use in a clinical environment.

Bioelectromagnetic localization of a pacing catheter in the heart.

The accuracy of localizing source currents within the human heart by non-invasive magneto- and electrocardiographic methods was investigated in 10 patients. A non-magnetic stimulation catheter inside the heart served as a reference current source. Biplane fluoroscopic imaging with lead ball markers was used to record the catheter position. Simultaneous multichannel magnetocardiographic (MCG) and body surface potential mapping (BSPM) recordings were performed during catheter pacing. Equivalent current dipole localizations were computed from MCG and BSPM data, employing standard and patient-specific boundary element torso models. Using individual models with the lungs included, the average MCG localization error was 7+/-3 mm, whereas the average BSPM localization error was 25+/-4 mm. In the simplified case of a single homogeneous standard torso model, an average error of 9+/-3 mm was obtained from MCG recordings. The MCG localization accuracies obtained in this study imply that the capability of multichannel MCG to locate dipolar sources is sufficient for clinical purposes, even without constructing individual torso models from x-ray or from magnetic resonance images.

Nonfluoroscopic localization of an amagnetic stimulation catheter by multichannel magnetocardiography.

This study was performed to: (1) evaluate the accuracy of noninvasive magnetocardiographic (MCG) localization of an amagnetic stimulation catheter; (2) validate the feasibility of this multipurpose catheter; and (3) study the characteristics of cardiac evoked fields. A stimulation catheter specially designed to produce no magnetic disturbances was inserted into the heart of five patients after routine electrophysiological studies. The catheter position was documented on biplane cine x-ray images. MCG signals were then recorded in a magnetically shielded room during cardiac pacing. Noninvasive localization of the catheter's tip and stimulated depolarization was computed from measured MCG data using a moving equivalent current-dipole source in patient-specific boundary element torso models. In all five patients, the MCG localizations were anatomically in good agreement with the catheter positions defined from the x-ray images. The mean distance between the position of the tip of the catheter defined from x-ray fluoroscopy and the MCG localization was 11 +/- 4 mm. The mean three-dimensional difference between the MCG localization at the peak stimulus and the MCG localization, during the ventricular evoked response about 3 ms later, was 4 +/- 1 mm calculated from signal-averaged data. The 95% confidence interval of beat-to-beat localization of the tip of the stimulation catheter from ten consecutive beats in the patients was 4 +/- 2 mm. The propagation velocity of the equivalent current dipole between 5 and 10 ms after the peak stimulus was 0.9 +/- 0.2 m/s. The results show that the use of the amagnetic catheter is technically feasible and reliable in clinical studies. The accurate three-dimensional localization of this multipurpose catheter by multichannel MCG suggests that the method could be developed toward a useful clinical tool during electrophysiological studies.

Multichannel magnetocardiographic measurements with a physical thorax phantom.

Artificial dipolar sources were applied inside a physical thorax phantom to experimentally investigate the accuracy obtainable for non-invasive magnetocardiographic equivalent current dipole localisation. For the measurements, the phantom was filled with saline solution of electrical conductivity 0.21 S m-1. A multichannel cardiomagnetometer was employed to record the magnetic fields generated by seven dipolar sources at distances from 25 mm to 145 mm below the surface of the phantom. The inverse problem was solved using an equivalent current dipole in a homogeneous boundary element torso model. The dipole parameters were determined with a non-linear least squares fitting algorithm. The signal-to-noise ratio (SNR) and the goodness of fit of the calculated localisations were used in assessing the quality of the results. The dependence between the SNR and the goodness of fit was derived, and the results were found to correspond to the model. With SNR between 5 and 10, the average localisation error was found to be 9 +/- 8 mm, while for SNR between 30 and 40 and goodness of fit between 99.5% and 100%, the average error reduced to 3.2 +/- 0.3 mm. The SNR values obtained in this study were also compared with typical clinical values of SNR.

Reconstruction of 3-D geometry using 2-D profiles and a geometric prior model.

A method has been developed to reconstruct three-dimensional (3-D) surfaces from two-dimensional (2-D) projection data. It is used to produce individualized boundary element models, consisting of thorax and lung surfaces, for electro- and magnetocardiographic inverse problems. Two orthogonal projections are utilized. A geometrical prior model, built using segmented magnetic resonance images, is deformed according to profiles segmented from projection images. In our method, virtual X-ray images of the prior model are first constructed by simulating real X-ray imaging. The 2-D profiles of the model are segmented from the projections and elastically matched with the profiles segmented from patient data. The displacement vectors produced by the elastic 2-D matching are back projected onto the 3-D surface of the prior model. Finally, the model is deformed, using the back-projected vectors. Two different deformation methods are proposed. The accuracy of the method is validated by a simulation. The average reconstruction error of a thorax and lungs was 1.22 voxels, corresponding to about 5 mm.

Simulated epicardial potential maps during paced activation reflect myocardial fibrous structure.

Using a three-dimensional propagation model of the human ventricular myocardium, we studied the role of fibrous structure in generating epicardial potential maps. This model represents the myocardium as an anisotropic bidomain with an equal anisotropy ratio, and it incorporates a realistic representation of anatomical features, including epi-endocardial fiber rotation in the compact portion of the wall (compacta) and a distinct fiber arrangement of the trabeculated portion (trabeculata). Activation sequences were elicited at various intramural depths, and maps were calculated throughout a 60 ms sequence. The simulated maps closely resembled those measured by others in the canine heart. During the early stages of activation, a typical map featuring a central minimum flanked by two maxima emerged, with the axis joining these extrema approximately parallel to the fibers near the pacing site, and the axis joining the maxima rotated in the same direction as the fibers for different pacing depths; for endocardial and subendocardial pacing this map changed into one with an oblong positive area. During the later stages of activation, the positive areas of the maps expanded and rotated with the transmural fiber rotation. In concurrence with experiments, we saw a fragmentation and asymmetry of expanding and rotating positive areas. The latter features-apparently caused by the interface between the compacta and trabeculata, variable local thickness of the wall, or local undulations of the vetricular surface-could not be reproduced by more idealized, slab models.

Nonfluoroscopic localization of an amagnetic catheter in a realistic torso phantom by magnetocardiographic and body surface potential mapping.

This study was performed to evaluate the accuracy of multichannel magnetocardiographic (MCG) and body surface potential mapping (BSPM) in localizing three-dimensionally the tip of an amagnetic catheter for electrophysiology without fluoroscopy. An amagnetic catheter (AC), specially designed to produce dipolar sources of different geometry without magnetic disturbances, was placed inside a physical thorax phantom at two different depths, 38 mm and 88 mm below the frontal surface of the phantom. Sixty-seven MCG and 123 BSPM signals generated by the 10 mA current stimuli fed into the catheter were then recorded in a magnetically shielded room. Non-invasive localization of the tip of the catheter was computed from measured MCG and BSPM data using an equivalent current dipole source in a phantom-specific boundary element torso model. The mean 3-dimensional error of the MCG localization at the closer level was 2 +/- 1 mm. The corresponding error calculated from the BSPM measurements was 4 +/- 1 mm. At the deeper level, the mean localization errors of MCG and BSPM were 7 +/- 4 mm and 10 +/- 2 mm, respectively. The results showed that MCG and BSPM localization of the tip of the AC is accurate and reproducible provided that the signal-to-noise ratio is sufficiently high. In our study, the MCG method was found to be more accurate than BSPM. This suggests that both methods could be developed towards a useful clinical tool for nonfluoroscopic 3-dimensional electroanatomical imaging during electrophysiological studies, thus minimizing radiation exposure to patients and operators.

Magnetocardiographic pacemapping for nonfluoroscopic localization of intracardiac electrophysiology catheters.

The purpose of the study was to validate, in patients, the accuracy of magnetocardiography (MCG) for three-dimensional localization of an amagnetic catheter (AC) for multiple monophasic action potential (MAP) with a spatial resolution of 4 mm2. The AC was inserted in five patients after routine electrophysiological study. Four MAPs were simultaneously recorded to monitor the stability of endocardial contact of the AC during the MCG localization. MAP signals were band-pass filtered DC-500 Hz and digitized at 2 KHz. The position of the AC was also imaged by biplane fluoroscopy (XR), along with lead markers. MCG studies were performed with a multichannel SQUID system in the Helsinki BioMag shielded room. Current dipoles (5 mm; 10 mA), activated at the tip of the AC, were localized using the equivalent current dipole (ECD) model in patient-specific boundary element torso. The accuracy of the MCG localizations was evaluated by: (1) anatomic location of ECD in the MRI, (2) mismatch with XR. The AC was correctly localized in the right ventricle of all patients using MRI. The mean three-dimensional mismatch between XR and MCG localizations was 6 +/- 2 mm (beat-to-beat analysis). The co efficient of variation of three-dimensional localization of the AC was 1.37% and the coefficient of reproducibility was 2.6 mm. In patients, in the absence of arrhythmias, average local variation coefficients of right ventricular MAP duration at 50% and 90% of repolarization, were 7.4% and 3.1%, respectively. This study demonstrates that with adequate signal-to-noise ratio, MCG three-dimensional localizations are accurate and reproducible enough to provide nonfluoroscopy dependant multimodal imaging for high resolution endocardial mapping of monophasic action potentials.