Correlation of fetal heart rate dynamics to inflammatory markers and brain-derived neurotrophic factor during pregnancy.

OBJECTIVES: This study aims to show the relation between biomarkers in maternal and cord-blood samples and fetal heart rate variability (fHRV) metrics through a non-invasive fetal magnetocardiography (fMCG) technique. METHODS: Twenty-three women were enrolled for collection of maternal serum and fMCG tracings immediately prior to their scheduled cesarean delivery. The umbilical cord blood was collected for measurement of biomarker levels. The fMCG metrics were then correlated to the biomarker levels from the maternal serum and cord blood. RESULTS: Brain-derived neurotrophic factor (BDNF) had a moderate correlation with fetal parasympathetic activity (0.416) and fetal sympathovagal ratios (-0.309; -0.356). Interleukin (IL)-6 also had moderate-sized correlations but with an inverse relationship as compared to BDNF. These correlations were primarily in cord-blood samples and not in the maternal blood. CONCLUSIONS: In this small sample-sized exploratory study, we observed a moderate correlation between fHRV and cord-blood BDNF and IL-6 immediately preceding scheduled cesarean delivery at term. These findings need to be validated in a larger population.

Application of Magnetocardiography to Screen for Inflammatory Cardiomyopathy and Monitor Treatment Response.

Background Inflammatory cardiomyopathy is one of the most common causes of sudden cardiac death in young adults. Diagnosis of inflammatory cardiomyopathy remains challenging, and better monitoring tools are needed. We present magnetocardiography as a method to diagnose myocardial inflammation and monitor treatment response. Methods and Results A total of 233 patients were enrolled, with a mean age of 45 (±18) years, and 105 (45%) were women. The primary analysis included 209 adult subjects, of whom 66 (32%) were diagnosed with inflammatory cardiomyopathy, 17 (8%) were diagnosed with cardiac amyloidosis, and 35 (17%) were diagnosed with other types of nonischemic cardiomyopathy; 91 (44%) did not have cardiomyopathy. The second analysis included 13 patients with inflammatory cardiomyopathy who underwent immunosuppressive therapy after baseline magnetocardiography measurement. Finally, diagnostic accuracy of magnetocardiography was tested in 3 independent cohorts (total n=23) and 1 patient, who developed vaccine-related myocarditis. First, we identified a magnetocardiography vector to differentiate between patients with cardiomyopathy versus patients without cardiomyopathy (vector of ≥0.051; sensitivity, 0.59; specificity, 0.95; positive predictive value, 93%; and negative predictive value, 64%). All patients with inflammatory cardiomyopathy, including a patient with mRNA vaccine-related myocarditis, had a magnetocardiography vector ≥0.051. Second, we evaluated the ability of the magnetocardiography vector to reflect treatment response. We observed a decrease of the pathologic magnetocardiography vector toward normal in all 13 patients who were clinically improving under immunosuppressive therapy. Magnetocardiography detected treatment response as early as day 7, whereas echocardiographic detection of treatment response occurred after 1 month. The magnetocardiography vector decreased from 0.10 at baseline to 0.07 within 7 days (P=0.010) and to 0.03 within 30 days (P<0.001). After 30 days, left ventricular ejection fraction improved from 42.2% at baseline to 53.8% (P<0.001). Conclusions Magnetocardiography has the potential to be used for diagnostic screening and to monitor early treatment response. The method is valuable in inflammatory cardiomyopathy, where there is a major unmet need for early diagnosis and monitoring response to immunosuppressive therapy.

Noninvasive Fetal Electrocardiography in the Diagnosis of Long QT Syndrome: A Case Series.

INTRODUCTION: Early detection and monitoring for malignant arrhythmias is fundamental to prenatal care in long QT syndrome (LQTS). Recently, we studied the feasibility of isolating the fetal electrocardiogram (fECG) and measuring electrocardiographic intervals with a noninvasive fECG device using blind source separation with reference signal. Our aim was to evaluate the ability of fECG to diagnose LQTS. CASE PRESENTATIONS: We identified 3 cases of clinically suspected LQTS based on fetal echocardiogram (2 had sinus bradycardia, 1 had second-degree atrioventricular block with negative maternal anti-SSA/SSB antibody titers). With institutional review board approval, these patients were prospectively enrolled for fECG acquisition. Offline post-processing generated fECG waveforms and calculated QT intervals. Case 1 and 3 had a maternal history of LQTS. Two of the three fetuses with suspected LQTS had confirmed LQTS by postnatal ECG and genetic testing. FECG was able to identify a prolonged corrected QT interval in both cases. One of these also had fetal magnetocardiography (fMCG), which yielded similar findings to the fECG. The third fetus had a normal fECG; fMCG and postnatal ECG were also normal. CONCLUSIONS: In 3 cases, fECG findings corroborated the diagnosis of LQTS. Noninvasive fECG may offer a novel method for fECG that is portable and more clinically accessible.

Complex and Novel Arrhythmias Precede Stillbirth in Fetuses With De Novo Long QT Syndrome.

BACKGROUND: Long QT syndrome (LQTS) is a leading cause of sudden cardiac death in early life and has been implicated in ≈10% of sudden infant deaths and unexplained stillbirths. The purpose of our study was to use fetal magnetocardiography to characterize the electrophysiology and rhythm phenotypes of fetuses with de novo and inherited LQTS variants and identify risk factors for sudden death before birth. METHODS: We reviewed the fetal magnetocardiography database from the University of Wisconsin Biomagnetism Laboratory for fetuses with confirmed LQTS. We assessed waveform intervals, heart rate, and rhythm, including the signature LQTS rhythms: functional 2° atrioventricular block, T-wave alternans, and torsade de pointes (TdP). RESULTS: Thirty-nine fetuses had pathogenic variants in LQTS genes: 27 carried the family variant, 11 had de novo variants, and 1 was indeterminate. De novo variants, especially de novo SCN5A variants, were strongly associated with a severe rhythm phenotype and perinatal death: 9 (82%) showed signature LQTS rhythms, 6 (55%) showed TdP, 5 (45%) were stillborn, and 1 (9%) died in infancy. Those that died exhibited novel fetal rhythms, including atrioventricular block with 3:1 conduction ratio, QRS alternans in 2:1 atrioventricular block, long-cycle length TdP, and slow monomorphic ventricular tachycardia. Premature ventricular contractions were also strongly associated with TdP and perinatal death. Fetuses with familial variants showed a lower incidence of signature LQTS rhythm (6/27=22%), including TdP (3/27=11%). All were live born. CONCLUSIONS: The malignancy of de novo LQTS variants was remarkably high and demonstrate that these mutations are a significant cause of stillbirth. Their ability to manifest rhythms not known to be associated with LQTS increases the difficulty of echocardiographic diagnosis and decreases the likelihood that a resultant fetal loss is attributed to LQTS. Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03047161.

Identification of malignant early repolarization pattern by late QRS activity in high-resolution magnetocardiography.

BACKGROUND: The early repolarization pattern (ERP) in electrocardiography (ECG) has been considered as a risk for ventricular fibrillation (VF), but effective methods for identification of malignant ERP are still required. We investigated whether high spatiotemporal resolution 64-channel magnetocardiography (MCG) would enable distinction between benign and malignant ERPs. METHODS: Among all 2,636 subjects who received MCG in our facility, we identified 116 subjects (43 ± 18 years old, 54% male) with inferior and/or lateral ERP in ECG and without structural heart disease, including 13 survivors of VF (ERP-VF(+)) and 103 with no history of VF (ERP-VF(-)). We measured the following MCG parameters in a time-domain waveform of relative current magnitude: (a) QRS duration (MCG-QRSD), (b) root-mean-square of the last 40 ms (MCG-RMS40), and (c) low amplitude (<10% of maximal) signal duration (MCG-LAS). RESULTS: Compared to ERP-VF(-), ERP-VF(+) subjects presented a significantly longer MCG-QRS (108 ± 24 vs. 91 ± 23 ms, p = .02) and lower MCG-RMS40 (0.10 ± 0.08 vs. 0.25 ± 0.20, p = .01) but no difference in MCG-LAS (38 ± 22 vs. 29 ± 23 ms, p = .17). MCG-QRSD and MCG-RMS40 showed significantly larger area under the ROC curve compared to J-peak amplitude in ECG (0.72 and 0.71 vs. 0.50; p = .04 and 0.03). The sensitivity, specificity, and odds ratio for identifying VF(+) based on MCG-QRSD ≥ 100 ms and MCG-RMS40 ≤ 0.24 were 69%, 74%, and 6.33 (95% CI, 1.80-22.3), and 92%, 48%, and 10.9 (95% CI, 1.37-86.8), respectively. CONCLUSION: Magnetocardiography is an effective tool to distinguish malignant and benign ERPs.

Mechanism of Recurrence of Atrial Tachycardia: Comparison Between First Versus Redo Procedures in a High-Resolution Mapping System.

BACKGROUND: Atrial fibrillation ablation-related atrial tachycardia (AT) is complex and may demonstrate several forms: anatomic macroreentrant AT (AMAT), non-AMAT, and focal AT. We aimed to elucidate the recurrence rate and mechanisms of atrial fibrillation ablation-related AT recurrence. METHODS: Among 147 patients with ATs treated with the Rhythmia system, 68 (46.3%) had recurrence at mean 4.2 (2.9-11.6) months, and 44 patients received a redo procedure. AT circuits in the first procedure were compared with those in the redo procedure. RESULTS: Although mappable ATs were not observed in 7 patients, 68 ATs were observed in 37 patients during the first procedure: perimitral flutter (PMF) in 26 patients, roof-dependent macroreentrant AT (RMAT) in 18, peritricuspid flutter in 10, non-AMAT in 14, and focal AT in 3. During the redo AT ablation procedure, 54 ATs were observed in 41/44 patients: PMF in 24, RMAT in 14, peritricuspid flutter in 1, non-AMAT in 14, and focal AT in 1. Recurrence of PMF and RMAT was observed in 15 of 26 (57.7%) and 8 of 18 (44.4%) patients, respectively, while peritricuspid flutter did not recur. Neither the same focal AT nor the same non-AMAT were observed except in 1 case with septal scar-related biatrial AT. Epicardial structure-related ATs were involved in 18 of 24 (75.0%) patients in PMF, 4 of 14 (28.6%) in RMAT, and 4 of 14 (28.6%) in non-AMAT. Of 21 patients with a circuit including epicardial structures, 6 patients treated with ethanol infusion in the vein of Marshall did not show any AT recurrence, although 8 of 15 (53.3%) treated with radiofrequency showed AT recurrence (P=0.04). CONCLUSIONS: Although high-resolution mapping may lead to correct diagnosis and appropriate ablation in the first procedure, the recurrence rate is still high. The main mechanism of atrial fibrillation ablation-related AT is the recurrence of PMF and RMAT or non-AMAT different from the first procedure. Epicardial structures (eg, coronary sinus/vein of Marshall system) are often involved, and ethanol infusion in the vein of Marshall may be an additional treatment.

Magnetocardiographic identification of prolonged fetal corrected QT interval in women receiving treatment for opioid use disorder.

AIM: Pregnant women undergoing treatment for opioid use disorder (OUD) may be exposed to multiple QT prolonging agents. We used magnetocardiography to measure fetal QT intervals in mothers with OUD on buprenorphine therapy. METHODS: Fetal and maternal magnetocardiography was performed in pregnant women receiving buprenorphine-assisted treatment (Disorder group); these were matched by gestational age to pregnant women who were opiate naïve (Reference group). Corrected QT intervals were determined using Bazett's formula and compared between groups. RESULTS: A total of eight women in the Disorder group matched to eight in the Reference group. Seven of the mothers (88%) in the Disorder group were smokers; there were no smokers in the Reference group. The average fetal corrected QT was significantly longer (P = 0.022) in the Disorder group than that in the Reference group (505 milliseconds [ms] ± 68.6 [standard deviation] vs 383 ms ± 70.3 [standard deviation]). CONCLUSION: Novel data from this small sample demonstrate prolongation of fetal corrected QT in women with OUD participating in buprenorphine assisted therapy. Additional investigation from a larger sample is needed to clarify if fetal buprenorphine and/or tobacco exposure is associated with changes in fetal QT which would warrant further prenatal and postnatal testing.

Prediction of postnatal arrhythmia in fetuses with cardiac rhabdomyoma.

OBJECTIVES: Fetal cardiac rhabdomyomas are rare but well-known to be associated with arrhythmia or conduction abnormalities. However, since in utero electrophysiological information is quite limited, it remains unclear which type of rhabdomyoma will develop arrhythmia after birth. The aim of this study is to identify factors that predict postnatal arrhythmia requiring therapy in fetuses with cardiac rhabdomyoma. STUDY DESIGN: A retrospective review of infants prenatally diagnosed with cardiac rhabdomyoma was performed at our tertiary pediatric cardiac center between 1990 and 2016. Fetal arrhythmia was diagnosed using fetal echocardiography and magnetocardiography. We compared the characteristics of cases with and without antiarrhythmic therapy after birth. Cases without antiarrhythmic therapy after birth consisted of those who had postnatal arrhythmia but did not require antiarrhythmic therapy and those who had no postnatal arrhythmia. RESULTS: A total of 20 fetuses with cardiac rhabdomyoma were included in this study. Ten cases (50%) were confirmed as having tuberous sclerosis after birth. The mean gestational week at diagnosis and delivery were 32.1 ± 2.7 and 37.6 ± 2.8 weeks, respectively. Mean cardiac tumor size in utero was 21 ± 11 mm (range, 7-54 mm) in diameter. Fetal arrhythmia was found in six cases; three resolved in utero with transplacental antiarrhythmic therapy. Postnatal arrhythmia or conduction abnormalities were found in 12 cases; 7 required antiarrhythmic therapy. Cases with antiarrhythmic therapy after birth had larger cardiac tumor in utero than those without therapy (29.6 ± 12.8 mm versus 16.3 ± 5.8 mm, p < .01). Cardiac tumor size >30 mm in diameter predicted postnatal arrhythmia requiring therapy with sensitivity of 57.1% and specificity of 100%. Location and number of cardiac tumor and presence of arrhythmia or conduction abnormalities in utero were similar between the two groups. CONCLUSIONS: Cardiac rhabdomyomas >30 mm in diameter are associated with postnatal arrhythmia requiring therapy regardless of number and location.

Isolated Late Activation Detected by Magnetocardiography Predicts Future Lethal Ventricular Arrhythmic Events in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.

BACKGROUND: Risk stratification of ventricular arrhythmias is vital to the optimal management in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). We hypothesized that 64-channel magnetocardiography (MCG) would be useful to detect isolated late activation (ILA) by overcoming the limitations of conventional noninvasive predictors of ventricular tachyarrhythmias, including epsilon waves, late potential (LP), and right ventricular ejection fraction (RVEF), in ARVC patients.Methods and Results:We evaluated ILA on MCG, defined as discrete activations re-emerging after the decay of main RV activation (%magnitude >5%), and conventional noninvasive predictors of ventricular tachyarrhythmias (epsilon waves, LP, and RVEF) in 40 patients with ARVC. ILA was noted in 24 (60%) patients. Most ILAs were found in RV lateral or inferior areas (17/24, 71%). We defined "delayed ILA" as ILA in which the conduction delay exceeded its median (50 ms). During a median follow-up of 42.5 months, major arrhythmic events (MAEs: 1 sudden cardiac death, 3 sustained ventricular tachycardias, and 4 appropriate implantable cardioverter defibrillator discharges) occurred more frequently in patients with delayed ILA (6/12) than in those without (2/28; log-rank: P=0.004). Cox regression analysis identified delayed ILA as the only independent predictor of MAEs (hazard ratio 7.63, 95% confidence interval 1.72-52.6, P=0.007), and other noninvasive parameters were not significant predictors. CONCLUSIONS: MCG is useful to identify ARVC patients at high risk of future lethal ventricular arrhythmias.

Biomagnetic activity and non linear analysis in obstetrics and gynecology in a Greek population.

This article reports the application of non-linear analysis to biomagnetic signals recorded from fetal growth restriction, fetal brain activity, ovarian lesions, breast lesions, umbilical arteries, uterine myomas, and uterine arteries in a Greek population. The results were correlated with clinical findings. The biomagnetic measurements and the application of non-linear analysis are promising procedures in Obstetrics and Gynecology.

Early Myocardial Repolarization Heterogeneity Is Detected by Magnetocardiography in Diabetic Patients with Cardiovascular Risk Factors.

Multi-channel magnetocardiography (MCG) is a sensitive technique to map spatial ventricular repolarization with high resolution and reproducibility. Spatial ventricular repolarization heterogeneity measured by MCG has been shown to accurately detect and localize myocardial ischemia. Here, we explored whether these measurements correlated with cardiovascular risk factors in patients with type 2 diabetes. Two hundreds and seventy-seven type 2 diabetic patients without known coronary artery disease (CAD) and arrhythmia were recruited consecutively from the outpatient clinic of National Taiwan University Hospital. The spatially distributed QTc contour maps were constructed with 64-channel MCG using the superconducting quantum interference device (SQUID) system. Indices of myocardial repolarization heterogeneity including the smoothness index of QTc (SI-QTc) and QTc dispersion were derived and analyzed for association with conventional cardiovascular risk factors. SI-QTc correlated strongly with the QTc dispersion (r = 0.70, p <0.0001). SI-QTc was significantly higher in patients with presence of metabolic syndrome in comparison to those without metabolic syndrome (8.56 vs. 7.96 ms, p = 0.02). In univariate correlation analyses, QTc dispersion was associated with smoking status (average 79.90, 83.83, 86.51, and 86.00 ms for never smokers, ex-smokers, current smokers reporting less than 10 cigarettes daily, and current smoker reporting more than 10 cigarettes daily, respectively, p = 0.03), body weight (r = 0.15, p = 0.01), and hemoglobin A1c (r = 0.12, p = 0.04). In stepwise multivariate regression analyses, QTc dispersion was associated with smoking (p = 0.02), body weight (p = 0.04), total cholesterol levels (p = 0.05), and possibly estimated glomerular filtration rate (p = 0.07). In summary, spatial heterogeneity of myocardial repolarization measured by MCG is positively associated cardiovascular risk factors including adiposity, smoking, and total cholesterol levels.

Spatial repolarization heterogeneity detected by magnetocardiography correlates with cardiac iron overload and adverse cardiac events in beta-thalassemia major.

BACKGROUND: Patients with transfusion-dependent beta-thalassemia major (TM) are at risk for myocardial iron overload and cardiac complications. Spatial repolarization heterogeneity is known to be elevated in patients with certain cardiac diseases, but little is known in TM patients. The purpose of this study was to evaluate spatial repolarization heterogeneity in patients with TM, and to investigate the relationships between spatial repolarization heterogeneity, cardiac iron load, and adverse cardiac events. METHODS AND RESULTS: Fifty patients with TM and 55 control subjects received 64-channel magnetocardiography (MCG) to determine spatial repolarization heterogeneity, which was evaluated by a smoothness index of QTc (SI-QTc), a standard deviation of QTc (SD-QTc), and a QTc dispersion. Left ventricular function and myocardial T2* values were assessed by cardiac magnetic resonance. Patients with TM had significantly greater SI-QTc, SD-QTc, and QTc dispersion compared to the control subjects (all p values<0.001). Spatial repolarization heterogeneity was even more pronounced in patients with significant iron overload (T2*<20 ms, n = 20) compared to those with normal T2* (all p values<0.001). Loge cardiac T2* correlated with SI-QTc (r = -0.609, p<0.001), SD-QTc (r = -0.572, p<0.001), and QTc dispersion (r = -0.622, p<0.001), while all these indices had no relationship with measurements of the left ventricular geometry or function. At the time of study, 10 patients had either heart failure or arrhythmia. All 3 indices of repolarization heterogeneity were related to the presence of adverse cardiac events, with areas under the receiver operating characteristic curves (ranged between 0.79 and 0.86), similar to that of cardiac T2*. CONCLUSIONS: Multichannel MCG demonstrated that patients with TM had increased spatial repolarization heterogeneity, which is related to myocardial iron load and adverse cardiac events.

Fetal arrhythmias associated with cardiac rhabdomyomas.

BACKGROUND: Primary heart tumors in fetuses are rare and mainly represent rhabdomyomas. The tumors have a variable expression and can be associated with arrhythmias, including both wide and narrow QRS tachycardia. Although multiple Doppler techniques exist to assess fetal heart rhythm, it can be difficult to record precise electrophysiological abnormalities in fetal life. OBJECTIVE: Investigations defining precise electrophysiological diagnosis were performed by using fetal magnetocardiography (fMCG). METHODS: In addition to routine fetal echocardiography, fMCG was used to investigate electrophysiological rhythm patterns in a series of 10 fetuses with cardiac rhabdomyomas. RESULTS: The mean gestational age of the fetuses was 28.6 ± 4.7 weeks. The multiple rhabdomyomas were mainly located in the right and left ventricles as well as around the atrioventricular groove. Arrhythmias or conduction abnormalities were diagnosed in all 10 patients, although only 6 of them were referred due to that indication. Remarkably, 80% (8 of 10) had associated Wolff-Parkinson-White pre-excitation. In addition, we found prominent P waves in 4 fetuses. CONCLUSION: In fetuses with rhabdomyomas, a disease where rhythm pathology is common, precise electrophysiological diagnosis can now be made by fMCG. fMCG is complimentary to echocardiography for rhythm assessment and can detect conduction abnormalities that are not possible to diagnose prenatally with M-mode or pulsed Doppler ultrasound. Risk factor assessment using fMCG can support pregnancy management and postnatal treatment and follow-up.

Noninvasive diagnosis of coronary artery disease using two parameters extracted in an extrema circle of magnetocardiogram.

Magnetocardiography (MCG) is a complementary or alternative tool for noninvasive detection of coronary artery disease (CAD). The effectiveness of the tool for CAD diagnosis is generally evaluated by statistical analysis. In this study, we present a new method for screening CAD, in which two parameters including the curvature of magnetic field zero line and the area ratio of the extrema circle are extracted in magnetic field maps. 50 normal and 28 CAD subjects, whose signals were recorded by a 4-channel superconducting quantum interference device system, are analyzed with this method. The statistical results show a sensitivity and specificity of 71.4% and 72.0% respectively.

Surgical treatment for epilepsy involving language cortices: a combined process of electrical cortical stimulation mapping and intra-operative continuous language assessment.

OBJECTIVE: The purpose of this study was to improve the surgical treatment of epilepsy by maximising seizure control while protecting language function. METHODS: A combined process of extra-operative electrical cortical stimulation (ECS) mapping, direct ECS and intra-operative continuous language assessment was performed during complicated operative cases. Of the 24 epilepsy patients, nine had a complex relationship between the seizure onset zone and the language cortices. The combined process was used in these nine patients. In the other 15 patients, surgical resection was completed based on extra-operative ECS results alone. Evaluations were performed before and after surgery to assess language function and seizure control. RESULTS: The intra-operative continuous language assessment provided important information at the time of the resection. Seven extra-operative ECS positive language sites were resected without obvious language deficits in two patients. Resection was interrupted by language disturbances in an area where no extra-operative ECS positive site was identified in one patient. In three other patients, functional boundary was undefined in extra-operative ECS result, epileptogenic cortices were maximally resected during the continuous language assessment. In terms of seizure control, 18 of 24 (75%) patients reached Engel's class I, including all nine patients who underwent intra-operative continuous language assessment. One patient had minor surgery-related language deficits three months after resection. CONCLUSIONS: Intra-operative continuous language assessment proved to be complementary to extra-operative ECS mappings. The combination of ECS mappings and intra-operative continuous language assessment can maximise the resection of epileptogenic cortices and preserve language function in difficult cases involving the language cortex.

Depression of cortical activity in humans by mild hypercapnia.

The effects of neural activity on cerebral hemodynamics underlie human brain imaging with functional magnetic resonance imaging and positron emission tomography. However, the threshold and characteristics of the converse effects, wherein the cerebral hemodynamic and metabolic milieu influence neural activity, remain unclear. We tested whether mild hypercapnia (5% CO2 ) decreases the magnetoencephalogram response to auditory pattern recognition and visual semantic tasks. Hypercapnia induced statistically significant decreases in event-related fields without affecting behavioral performance. Decreases were observed in early sensory components in both auditory and visual modalities as well as later cognitive components related to memory and language. Effects were distributed across cortical regions. Decreases were comparable in evoked versus spontaneous spectral power. Hypercapnia is commonly used with hemodynamic models to calibrate the blood oxygenation level-dependent response. Modifying model assumptions to incorporate the current findings produce a modest but measurable decrease in the estimated cerebral metabolic rate for oxygen change with activation. Because under normal conditions, low cerebral pH would arise when bloodflow is unable to keep pace with neuronal activity, the cortical depression observed here may reflect a homeostatic mechanism by which neuronal activity is adjusted to a level that can be sustained by available bloodflow. Animal studies suggest that these effects may be mediated by pH-modulating presynaptic adenosine receptors. Although the data is not clear, comparable changes in cortical pH to those induced here may occur during sleep apnea, sleep, and exercise. If so, these results suggest that such activities may in turn have generalized depressive effects on cortical activity.

Minimally invasive magnetic resonance imaging-guided stereotactic radiofrequency thermocoagulation for epileptogenic hypothalamic hamartomas.

OBJECTIVE: To validate the safety and efficacy of magnetic resonance imaging (MRI)-guided stereotactic radiofrequency thermocoagulation (SRT) for epileptogenic hypothalamic hamartoma (HH), we evaluated surgical outcomes and revised the MRI classification. METHODS: We retrospectively reviewed 25 consecutive patients with HH (age range, 2-36 years; mean age, 14.8 years) with gelastic seizures. Other seizure types were exhibited in 22 patients (88.0%), precocious puberty in 8 (32.0%), behavioral disorder in 10 (40.0%), and mental retardation in 14 (56.0%). We classified HH into 3 subtypes according to coronal MRI: intrahypothalamic, parahypothalamic, and mixed hypothalamic type. Maximum diameter ranged from 8 to 30 mm (mean, 15.3 mm). All patients underwent SRT (74 degrees C, 60 seconds) for HH. RESULTS: HH subtype and size were correlated with precocious puberty, mental retardation, and behavioral disorder. Thirty-one SRT procedures were performed, requiring 1 to 8 tracks (mean, 3.8 tracks) and involving 1 to 18 lesions (mean, 7.2 lesions). There were no adaptive limitations, regardless of size or subtype. Mixed-type HHs needed more tracks and more lesions. No permanent complications persisted after SRT, and gelastic seizures disappeared in all but 2 patients. Complete seizure freedom was achieved in 19 patients (76.0%). These patients had not only disappearance of all seizure types and behavioral disorder but also intellectual improvement. CONCLUSION: The present SRT procedure has favorable efficacy and invasiveness and has no adaptive limitations. SRT should therefore be considered before adulthood. The new HH classification is useful to understand clinical symptoms and to determine surgical strategies.

Spatiotemporal patterns of brain activation during an action naming task using magnetoencephalography.

Eight right-handed subjects were asked to silently generate a verb to a visual stimulus while the magnetic flux normal to the scalp surface was recorded with a whole-head neuromagnetometer. The spatiotemporal patterns of activation in lateral occipital, inferior parietal, superior temporal, basal temporal, and inferior frontal cortices were estimated using minimum estimation, a distributed source analysis methodology. Although there was significant variability among subjects, averaged data indicated that latencies of peak activation in these regions of interest progressed from posterior to anterior. Peak latencies were earliest in lateral occipital cortex and latest in pars opercularis and pars triangularis in the inferior frontal gyrus. Lateralization of activation was strongest in pars opercularis, which is part of classical Broca's area, with activation being stronger in this area within the left hemisphere in every subject. Results provide support for the use of magnetoencephalography in conjunction with MNE analysis for the purpose of lateralizing and localizing language-specific activation in frontal areas as well as the study of the spatiotemporal parameters of brain activation associated with cognitive function.

Detection of atrial arrhythmia in superconducting quantum interference device magnetocardiography; preliminary result of a totally-noninvasive localization method for atrial current mapping.

Map-guided surgery is the goal for treatment of atrial fibrillation (AF), because it minimizes unnecessary incisions or procedures. We propose a totally-noninvasive and even non-contact method to detect atrial arrhythmia with a superconducting quantum interference device magnetocardiography (MCG) system, and report the first clinical application case of MCG map-guided AF surgery. To detect weak atrial excitation, we utilized a high sensitive 64-channel MCG system measuring tangential magnetic field components, which is known to be more sensitive to a deeper current source. We measured the MCG signals from eight patients with chronic AF. Then, we separated the f-wave from the other components by using independent component analysis. The extracted f-wave caused by reentrant myocardial excitation was three-dimensionally localized on the mesh model of a human heart by a novel beamformer technique having a surface action potential activity as its filter output. We localized the abnormal stimulation source of an atrial arrhythmia non-invasively and visualized the current source distribution corresponding to the atrial excitation successfully on the three-dimensional atrial surface, which was separated from the ventricular excitation. Using this atrial mapping, we underwent minimal AF surgery in three patients and converted their AF to sinus rhythm successfully.