Rupesh Kotecha

Frequency and spatial characteristics of high-frequency neuromagnetic signals in childhood epilepsy

PURPOSE Invasive intracranial recordings have suggested that high-frequency oscillation is involved in epileptogenesis and is highly localized to epileptogenic zones. The aim of the present study is to characterize the frequency and spatial patterns of high-frequency brain signals in childhood epilepsy using a non-invasive technology. METHODS Thirty children with clinically diagnosed epilepsy were studied using a whole head magnetoencephalography (MEG) system. MEG data were digitized at 4,000 Hz. The frequency and spatial characteristics of high-frequency neuromagnetic signals were analyzed using continuous wavelet transform and beamformer. Three-dimensional magnetic resonance imaging (MRI) was obtained for each patient to localize magnetic sources. RESULTS Twenty-six patients showed high-frequency (100-1,000 Hz) components (26/30, 86%). Nineteen patients showed more than one high-frequency component (19/30, 63%). The frequency range of high-frequency components varied across patients. The highest frequency band was identified around 910 Hz. The loci of high-frequency epileptic activities were concordant with the lesions identified by magnetic resonance imaging for 21 patients (21/30, 70%). The MEG source localizations of high-frequency components were found to be concordant with intracranial recordings for nine of the eleven patients who underwent epilepsy surgery (9/11, 82%). CONCLUSION The results have demonstrated that childhood epilepsy was associated with high-frequency epileptic activity in a wide frequency range. The concordance of MEG source localization, MRI and intracranial recordings suggests that measurement of high-frequency neuromagnetic signals might provide a novel approach for clinical management of childhood epilepsy.

Modeling the Developmental Patterns of Auditory Evoked Magnetic Fields in Children

Background As magnetoencephalography (MEG) is of increasing utility in the assessment of deficits and development delays in brain disorders in pediatrics, it becomes imperative to fully understand the functional development of the brain in children. Methodology The present study was designed to characterize the developmental patterns of auditory evoked magnetic responses with respect to age and gender. Sixty children and twenty adults were studied with a 275-channel MEG system. Conclusions Three main responses were identified at approximately 46 ms (M50), 71 ms (M70) and 106 ms (M100) in latency for children. The latencies of M70 and M100 shortened with age in both hemispheres; the latency of M50 shortened with age only in the right hemisphere. Analysis of developmental lateralization patterns in children showed that the latency of the right hemispheric evoked responses shortened faster than the corresponding left hemispheric responses. The latency of M70 in the right hemisphere highly correlated to the age of the child. The amplitudes of the M70 responses increased with age and reached their peaks in children 12–14 years of age, after which they decreased with age. The source estimates for the M50 and M70 responses indicated that they were generated in different subareas in the Heschls gyrus in children, while not localizable in adults. Furthermore, gender also affected developmental patterns. The latency of M70 in the right hemisphere was proposed to be an index of auditory development in children, the modeling equation is 85.72-1.240xAge (yrs). Our results demonstrate that there is a clear developmental pattern in the auditory cortex and underscore the importance of M50 and M70 in the developing brain.

Noninvasive localization of epileptogenic zones with ictal high-frequency neuromagnetic signals

OBJECT Recent reports suggest that high-frequency epileptic activity is highly localized to epileptogenic zones. The goal of the present study was to investigate the potential usefulness of noninvasive localization of high-frequency epileptic activity for epilepsy surgery. METHODS Data obtained in 4 patients, who had seizures during routine magnetoencephalography (MEG) tests, were retrospectively studied. The MEG data were digitized at 4000 Hz, and 3D MR images were obtained. The magnetic sources were volumetrically localized with wavelet-based beamformer. The MEG results were subsequently compared with clinical data. RESULTS The 4 patients had 1-4 high-frequency neuromagnetic components (110-910 Hz) in ictal and interictal activities. The loci of high-frequency activities were concordant with intracranial recordings therein 3 patients, who underwent presurgical evaluation. The loci of high-frequency ictal activities were in line with semiology and neuroimaging in all 4 of the patients. High-frequency epileptic activity was highly localized to the epileptogenic zones. CONCLUSIONS High-frequency epileptic activity can be volumetrically localized with MEG. Source analysis of high-frequency neuromagnetic signals has the potential to determine epileptogenic zones noninvasively and preoperatively for epilepsy surgery.

Accumulated source imaging of brain activity with both low and high-frequency neuromagnetic signals

Recent studies have revealed the importance of high-frequency brain signals (>70 Hz). One challenge of high-frequency signal analysis is that the size of time-frequency representation of high-frequency brain signals could be larger than 1 terabytes (TB), which is beyond the upper limits of a typical computer workstations memory (<196 GB). The aim of the present study is to develop a new method to provide greater sensitivity in detecting high-frequency magnetoencephalography (MEG) signals in a single automated and versatile interface, rather than the more traditional, time-intensive visual inspection methods, which may take up to several days. To address the aim, we developed a new method, accumulated source imaging, defined as the volumetric summation of source activity over a period of time. This method analyzes signals in both low- (1~70 Hz) and high-frequency (70~200 Hz) ranges at source levels. To extract meaningful information from MEG signals at sensor space, the signals were decomposed to channel-cross-channel matrix (CxC) representing the spatiotemporal patterns of every possible sensor-pair. A new algorithm was developed and tested by calculating the optimal CxC and source location-orientation weights for volumetric source imaging, thereby minimizing multi-source interference and reducing computational cost. The new method was implemented in C/C++ and tested with MEG data recorded from clinical epilepsy patients. The results of experimental data demonstrated that accumulated source imaging could effectively summarize and visualize MEG recordings within 12.7 h by using approximately 10 GB of computer memory. In contrast to the conventional method of visually identifying multi-frequency epileptic activities that traditionally took 2–3 days and used 1–2 TB storage, the new approach can quantify epileptic abnormalities in both low- and high-frequency ranges at source levels, using much less time and computer memory.

Gamma oscillations in the primary motor cortex studied with MEG

In recent years, there has been a growing interest on the role of gamma band (>30 Hz) neural oscillations in motor control, although the function of this activity in motor control is unknown clearly. With the goal of discussing the high frequency sources non-invasively and precisely during unilateral index finger movement, we investigated gamma band oscillations in 20 right-handed normal adults with magnetoencephalography (MEG). The results showed that gamma band activity appeared only during finger movement. Nineteen subjects displayed consistently contralateral event-related synchronization (C-ERS) within high gamma band (70-150 Hz) in primary motor cortex (M1) of both hemispheres. Interestingly, 15 subjects displayed ipsilateral event-related desynchronization (I-ERD) and C-ERS within broad gamma band (30-150 Hz). The locations of the broad gamma band I-ERD and C-ERS revealed hemispherical symmetry in M1. These findings demonstrate that there are consistent high gamma C-ERS and inconsistent low gamma I-ERD during a simple finger movement in the motor cortex. This study provides new evidence for the use of high gamma frequency oscillations as biomarkers in the analyses of functional brain activity and the localization of the motor cortex.

Time, frequency and volumetric differences of high-frequency neuromagnetic oscillation between left and right somatosensory cortices.

Hemispheric specialization or asymmetry in higher brain functions such as language is well accepted. This study was designed to quantitatively determine if the hemispheric asymmetry is measurable in the somatosensory system. Twenty-two participants were studied with magnetoencephalography (MEG) while their left and right index fingers were stimulated in randomized order. The finger representation in the cortex was volumetrically localized using a wavelet based beamformer. The strength of functional activity was estimated with an intensity volume while the waveforms of the virtual sensors were computed with a virtual sensor placed in the center of localized finger area. The results showed that the latency of the first identifiable response evoked by left finger stimulation was significantly shorter than that evoked by right finger stimulation (p<0.05). The left somatosensory cortex generated higher frequency neuromagnetic signals than did the right somatosensory cortex (p<0.05). Moreover, the volume of neuromagnetic activation elicited by right finger stimulation was significantly larger than that elicited by left finger stimulation in males (p<0.001). The neuromagnetic activation revealed by virtual sensors was more consistent than that revealed by physical sensors across participants. We conclude that neuromagnetic activities in the left and right somatosensory cortices have significant differences in terms of response latency, oscillation frequency and activation volume in high-frequency neuromagnetic signals. An investigation of the hemispheric specific features of neuromagnetic activation in the somatosensory cortex lays a foundation for the study of psychophysiologic asymmetries in the brain.

Clinical outcomes of radiation therapy in the management of Langerhans cell histiocytosis.

Objectives:Langerhans cell histiocytosis (LCH) is a rare disease with variable clinical presentation. In the present study, we report on the effectiveness and clinical complications of radiation therapy in children with LCH. Materials and Methods:We retrospectively reviewed all patients with LCH treated with radiation therapy over a 6-decade period at a single institution. Radiotherapy data, clinical features, radiographic data, and vital status were analyzed. Results:The mean age at diagnosis for 69 patients was 5.3 years (3 mo to 37 y) and the median duration of follow-up was 6 years (7 d to 32 y). Radiation therapy was performed for 169 sites, primarily bone lesions. The median radiotherapy dose was 10 Gy (2.5 to 45 Gy). Radiographic follow-up data were available for 139 of the sites treated and clinical follow-up was available for 156 of sites treated. The radiographic local control was 91.4%, and 13% of lesions showed complete sclerosis or reconstitution of bone. A total of 90.4% of patients reported stabilization or improvement in lesion-related symptoms, most often pain. Twelve patients had diabetes insipidus at diagnosis or during follow-up. Eight of these patients received radiation treatment to the pituitary and none experienced a reduction in desmopressin dosage posttreatment. Radiation complications were few, including femoral neck fracture in 1 patient and facial asymmetry in 3 patients. No secondary malignancies were observed. Conclusions:Radiotherapy for LCH has high rates of local control and symptomatic improvement. Importantly, however, there is evidence of short-term and long-term morbidity when children are treated with low-dose irradiation.

Neuromagnetic correlates of developmental changes in endogenous high-frequency brain oscillations in children: A wavelet-based beamformer study

Recent studies have found that the brain generates very fast oscillations. The objective of the present study was to investigate the spectral, spatial and coherent features of high-frequency brain oscillations in the developing brain. Sixty healthy children and 20 healthy adults were studied using a 275-channel magnetoencephalography (MEG) system. MEG data were digitized at 12,000 Hz. The frequency characteristics of neuromagnetic signals in 0.5-2000 Hz were quantitatively determined with Morlet wavelet transform. The magnetic sources were volumetrically estimated with wavelet-based beamformer at 2.5 mm resolution. The neural networks of endogenous brain oscillations were analyzed with coherent imaging. Neuromagnetic activities in 8-12 Hz and 800-900 Hz were found to be the most reliable frequency bands in healthy children. The neuromagnetic signals were localized in the occipital, temporal and frontal cortices. The activities in the occipital and temporal cortices were strongly correlated in 8-12 Hz but not in 800-900 Hz. In comparison to adults, children had brain oscillations in intermingled frequency bands. Developmental changes in children were identified for both low- and high-frequency brain activities. The results of the present study suggest that the development of the brain is associated with spatial and coherent changes of endogenous brain activities in both low- and high-frequency ranges. Analysis of high-frequency neuromagnetic oscillation may provide novel insights into cerebral mechanisms of brain function. The noninvasive measurement of neuromagnetic brain oscillations in the developing brain may open a new window for analysis of brain function.

Neuromagnetic biomarkers of visuocortical development in healthy children

OBJECTIVE The objective of the present study was to investigate noninvasive biomarkers for visuocortical development in healthy children. METHODS Sixty healthy children and 20 adults were studied with a whole-head magnetoencephalography (MEG) system. The adults were included to find out when the markers stabilize. Visual evoked magnetic fields (VEFs) were evoked with full-field pattern-reversal checks. RESULTS Three response peaks were identified at 77+/-8 ms (M75), 111+/-9 ms (M100) and 150+/-11 ms (M145) for children. The latency of M75 and M100 decreased with age (p<0.01). The amplitude ratio of M100/M75 increased significantly with age (p<0.001). The differences of MEG source images between the left and right occipital cortices for M75 and M145 increased significantly with age (r=0.47 and 0.46, respectively, p<0.01). CONCLUSIONS The latency of M75 and M100 and the amplitude ratio of M100/M75 are robust biomarkers for the development of visual function in children. SIGNIFICANCE The development of visual function in childhood is noninvasively measurable. The results lay a foundation for quantitative identification of developmental delay and/or abnormalities of visual function in children with brain disorders.

Overall survival and the response to radiotherapy among molecular subtypes of breast cancer brain metastases treated with targeted therapies

The current study was conducted to investigate survival and the response to radiotherapy among patients with molecular subtypes of breast cancer brain metastases treated with or without targeted therapies.