We developed a 375-channel, whole-head magnetoencephalography (MEG) system ("BabyMEG") for studying the electrophysiological development of human brain during the first years of life. The helmet accommodates heads up to 95% of 36-month old boys in the USA. The unique two-layer sensor array consists of: (1) 270 magnetometers (10 mm diameter, ∼15 mm coil-to-coil spacing) in the inner layer, (2) thirty-five three-axis magnetometers (20 mm × 20 mm) in the outer layer 4 cm away from the inner layer. Additionally, there are three three-axis reference magnetometers. With the help of a remotely operated position adjustment mechanism, the sensor array can be positioned to provide a uniform short spacing (mean 8.5 mm) between the sensor array and room temperature surface of the dewar. The sensors are connected to superconducting quantum interference devices (SQUIDs) operating at 4.2 K with median sensitivity levels of 7.5 fT/√Hz for the inner and 4 fT/√Hz for the outer layer sensors. SQUID outputs are digitized by a 24-bit acquisition system. A closed-cycle helium recycler provides maintenance-free continuous operation, eliminating the need for helium, with no interruption needed during MEG measurements. BabyMEG with the recycler has been fully operational from March, 2015. Ongoing spontaneous brain activity can be monitored in real time without interference from external magnetic noise sources including the recycler, using a combination of a lightly shielded two-layer magnetically shielded room, an external active shielding, a signal-space projection method, and a synthetic gradiometer approach. Evoked responses in the cortex can be clearly detected without averaging. These new design features and capabilities represent several advances in MEG, increasing the utility of this technique in basic neuroscience as well as in clinical research and patient studies.

We developed a prototype of a mobile, high-resolution, multichannel magnetoencephalography ͑MEG͒ system, called babySQUID, for assessing brain functions in newborns and infants. Unlike electroencephalography, MEG signals are not distorted by the scalp or the fontanels and sutures in the skull. Thus, brain activity can be measured and localized with MEG as if the sensors were above an exposed brain. The babySQUID is housed in a moveable cart small enough to be transported from one room to another. To assess brain functions, one places the baby on the bed of the cart and the head on its headrest with MEG sensors just below. The sensor array consists of 76 first-order axial gradiometers, each with a pickup coil diameter of 6 mm and a baseline of 30 mm, in a high-density array with a spacing of 12-14 mm center-to-center. The pickup coils are 6 ± 1 mm below the outer surface of the headrest. The short gap provides unprecedented sensitivity since the scalp and skull are thin ͑as little as 3 -4 mm altogether͒ in babies. In an electromagnetically unshielded room in a hospital, the field sensitivity at 1 kHz was ϳ17 fT/ ͱ Hz. The noise was reduced from ϳ400 to 200 fT/ ͱ Hz at 1 Hz using a reference cancellation technique and further to ϳ40 fT/ ͱ Hz using a gradient common mode rejection technique. Although the residual environmental magnetic noise interfered with the operation of the babySQUID, the instrument functioned sufficiently well to detect spontaneous brain signals from babies with a signal to noise ratio ͑SNR͒ of as much as 7.6:1. In a magnetically shielded room, the field sensitivity was 17 fT/ ͱ Hz at 20 Hz and 30 fT/ ͱ Hz at 1 Hz without implementation of reference or gradient cancellation. The sensitivity was sufficiently high to detect spontaneous brain activity from a 7 month old baby with a SNR as much as 40:1 and evoked somatosensory responses with a 50 Hz bandwidth after as little as four averages. We expect that both the noise and the sensor gap can be reduced further by approximately half with a gain in SNR of about four. Thus, we conclude from the performance of the prototype that it should be feasible to improve the babySQUID to detect cortical activity in infants in real time with high spatial resolution.

Background: A major motivation in designing the new infant and child magnetoencephalography (MEG) system described in this manuscript is the premise that electrophysiological signatures (resting activity and evoked responses) may serve as biomarkers of neurodevelopmental disorders, with neuronal abnormalities in conditions such as autism spectrum disorder (ASD) potentially detectable early in development. Whole-head MEG systems are generally optimized/sized for adults. Since magnetic field produced by neuronal currents decreases as a function of distance2 and infants and young children have smaller head sizes (and thus increased brain-to-sensor distance), whole-head adult MEG systems do not provide optimal signal-to-noise in younger individuals. This spurred development of a whole-head infant and young child MEG system – Artemis 123.Methods:In addition to describing the design of the Artemis 123, the focus of this manuscript is the use of Artemis 123 to obtain auditory evoked neuromagnetic recordings and resting-state data in young children. Data were collected from a 14-month-old female, an 18-month-old female, and a 48-month-old male. Phantom data are also provided to show localization accuracy.Results:Examination of Artemis 123 auditory data showed generalizability and reproducibility, with auditory responses observed in all participants. The auditory MEG measures were also found to be manipulable, exhibiting sensitivity to tone frequency. Furthermore, there appeared to be a predictable sensitivity of evoked components to development, with latencies decreasing with age. Examination of resting-state data showed characteristic oscillatory activity. Finally, phantom data showed that dipole sources could be localized with an error less than 0.5 cm.Conclusions:Artemis 123 allows efficient recording of high-quality whole-head MEG in infants four years and younger. Future work will involve examining the feasibility of obtaining somatosensory and visual recordings in similar-age children as well as obtaining recordings from younger infants. Thus, the Artemis 123 offers the promise of detecting earlier diagnostic signatures in such neurodevelopmental disorders.

Purpose: Multichannel Transcranial Magnetic Stimulation (mTMS) arrays enable multiple sites to be stimulated simultaneously or sequentially under electronic control without moving the system’s stimulation coils. Here, we build and characterize the performance of a novel modular 3-axis TMS coil that can be utilized as a unit element in large-scale multichannel TMS arrays. Methods: We determined the basic physical characteristics of the 3-axis TMS coil x -, y - and z -elements using a custom 2-channel programmable stimulator prototype. We mapped the temporal rate-of-change of the induced magnetic field ( dB/dt ) on a 2D plane parallel to the coil surface (including an extended line for full spatial coverage) and compared those values with predictions from magnetic field simulations. Temperature measurements were carried out to assess the incorporated air-cooling method. We measured the mutual and self-inductances of the x/y/z -elements to assess coupling between them. Additionally, we measured and calculated the coupling between z -elements in the array configuration. Finally, we performed electric field simulations to evaluate the stimulation intensity and focality of the coil and compared the results to conventional TMS coils as well as demonstrated suitability of the 3-axis coil for a multichannel array configuration. Results: The experimentally obtained dB/dt values validated the computational model of the 3-axis coil and therefore confirmed that both the coil and stimulator system are operating as intended. The air-cooling system was effective for brief high-frequency pulse trains and extended single- and paired-pulse TMS protocols. The electromagnetic simulations suggested that an array of the 3-axis coils would have comparable stimulation intensity to conventional TMS coils, therefore enabling clearly suprathreshold stimulation of the human brain. The recorded coil coupling between the x/y/z -elements was < 1% and the maximal coupling between z -elements in the array configuration was 1.8% and 3.4% for the measured and calculated values, respectively. Conclusion: We presented a 3-axis coil intended for multichannel TMS arrays. The electromagnetic measurements and simulations verified that the coil fabrication met the desired specifications and that the inductive coupling between the elements was negligible. The air-cooled 3-axis TMS coil appears suitable to be used as an element in multichannel TMS arrays.

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