Mesoscale Brain Mapping: Bridging Scales and Modalities in Neuroimaging - A Symposium Review.

Advances in the spatiotemporal resolution and field-of-view of neuroimaging tools are driving mesoscale studies for translational neuroscience. On October 10, 2023, the Center for Mesoscale Mapping (CMM) at the Massachusetts General Hospital (MGH) Athinoula A. Martinos Center for Biomedical Imaging and the Massachusetts Institute of Technology (MIT) Health Sciences Technology based Neuroimaging Training Program (NTP) hosted a symposium exploring the state-of-the-art in this rapidly growing area of research. "Mesoscale Brain Mapping: Bridging Scales and Modalities in Neuroimaging" brought together researchers who use a broad range of imaging techniques to study brain structure and function at the convergence of the microscopic and macroscopic scales. The day-long event centered on areas in which the CMM has established expertise, including the development of emerging technologies and their application to clinical translational needs and basic neuroscience questions. The in-person symposium welcomed more than 150 attendees, including 57 faculty members, 61 postdoctoral fellows, 35 students, and four industry professionals, who represented institutions at the local, regional, and international levels. The symposium also served the training goals of both the CMM and the NTP. The event content, organization, and format were planned collaboratively by the faculty and trainees. Many CMM faculty presented or participated in a panel discussion, thus contributing to the dissemination of both the technologies they have developed under the auspices of the CMM and the findings they have obtained using those technologies. NTP trainees who benefited from the symposium included those who helped to organize the symposium and/or presented posters and gave "flash" oral presentations. In addition to gaining experience from presenting their work, they had opportunities throughout the day to engage in one-on-one discussions with visiting scientists and other faculty, potentially opening the door to future collaborations. The symposium presentations provided a deep exploration of the many technological advances enabling progress in structural and functional mesoscale brain imaging. Finally, students worked closely with the presenting faculty to develop this report summarizing the content of the symposium and putting it in the broader context of the current state of the field to share with the scientific community. We note that the references cited here include conference abstracts corresponding to the symposium poster presentations.

Influence of peripheral axon geometry and local anatomy on magnetostimulation chronaxie.

Objective.Rapid switching of magnetic resonance imaging (MRI) gradient fields induces electric fields that can cause peripheral nerve stimulation (PNS) and so accurate characterization of PNS is required to maintain patient safety and comfort while maximizing MRI performance. The minimum magnetic gradient amplitude that causes stimulation, the PNS threshold, depends on intrinsic axon properties and the spatial and temporal properties of the induced electric field. The PNS strength-duration curve is widely used to characterize simulation thresholds for periodic waveforms and is parameterized by the chronaxie and rheobase. Safety limits to avoid unwanted PNS in MRI rely on a single chronaxie value to characterize the response of all nerves. However, experimental magnetostimulation peripheral nerve chronaxie values vary by an order of magnitude. Given the diverse range of chronaxies observed and the importance of this number in MRI safety models, we seek a deeper understanding of the mechanisms contributing to chronaxie variability.Approach.We use a coupled electromagnetic-neurodynamic PNS model to assess geometric sources of chronaxie variability. We study the impact of the position of the stimulating magnetic field coil relative to the body, along with the effect of local anatomical features and nerve trajectories on the driving function and the resulting chronaxie.Main results.We find realistic variation of local axon and tissue geometry can modulate a given axon's chronaxie by up to two-fold. Our results identify the temporal rate of charge redistribution as the underlying determinant of the chronaxie.Significance.This charge distribution is a function of both intrinsic axon properties and the spatial stimulus along the nerve; thus, examination of the local tissue topology, which shapes the electric fields, as well as the nerve trajectory, are critical for better understanding chronaxie variations and defining more biologically informed MRI safety guidelines.

Prediction of experimental cardiac magnetostimulation thresholds using pig-specific body models.

PURPOSE: Modern high-amplitude gradient systems can be limited by the International Electrotechnical Commission 60601-2-33 cardiac stimulation (CS) limit, which was set in a conservative manner based on electrode experiments and E-field simulations in uniform ellipsoidal body models. Here, we show that coupled electromagnetic-electrophysiological modeling in detailed body and heart models can predict CS thresholds, suggesting that such modeling might lead to more detailed threshold estimates in humans. Specifically, we compare measured and predicted CS thresholds in eight pigs. METHODS: We created individualized porcine body models using MRI (Dixon for the whole body, CINE for the heart) that replicate the anatomy and posture of the animals used in our previous experimental CS study. We model the electric fields induced along cardiac Purkinje and ventricular muscle fibers and predict the electrophysiological response of these fibers, yielding CS threshold predictions in absolute units for each animal. Additionally, we assess the total modeling uncertainty through a variability analysis of the 25 main model parameters. RESULTS: Predicted and experimental CS thresholds agree within 19% on average (normalized RMS error), which is smaller than the 27% modeling uncertainty. No significant difference was found between the modeling predictions and experiments (p < 0.05, paired t-test). CONCLUSION: Predicted thresholds matched the experimental data within the modeling uncertainty, supporting the model validity. We believe that our modeling approach can be applied to study CS thresholds in humans for various gradient coils, body shapes/postures, and waveforms, which is difficult to do experimentally.

Measurement of magnetostimulation thresholds in the porcine heart.

PURPOSE: Powerful MRI gradient systems can surpass the International Electrotechnical Commission (IEC) 60601-2-33 limit for cardiac stimulation (CS), which was determined by simple electromagnetic simulations and electrode stimulation experiments. Only a few canine studies measured magnetically induced CS thresholds in vivo and extrapolating them to human safety limits can be challenging. METHODS: We measured cardiac magnetostimulation thresholds in 10 healthy, anesthetized pigs using capacitors discharged into a flat spiral coil to produce damped sinusoidal waveforms with effective stimulus duration ts,eff  = 0.45 ms. Electrocardiography (ECG), blood pressure, and peripheral oximetry signals were recorded to determine threshold coil currents yielding cardiac capture. Dixon and CINE MR volumes from each animal were segmented to generate porcine-specific electromagnetic models to calculate dB/dt and E-field values in the porcine heart at threshold. For comparison, we also simulated maximum dB/dt and E-field values created by three MRI gradient systems in the heart of a human body model. RESULTS: The average dB/dt threshold estimated in the porcine heart was 1.66 ± 0.23 kT/s, which is 11-fold greater than the IEC dB/dt limit at ts,eff  = 0.45 ms, and 31-fold greater than the maximum value created by the investigated MRI gradients in the human heart. The average E-field threshold estimated in the porcine heart was 92.9 ± 13.5 V/m, which is 6-fold greater than the IEC E-field limit at ts,eff  = 0.45 ms and 37-fold greater than the maximum gradient-induced E-field in the human heart. CONCLUSION: This first measurement of cardiac magnetostimulation thresholds in pigs indicates that the IEC cardiac safety limit is conservative for the investigated stimulus duration (ts,eff  = 0.45 ms).

Forward multiple scattering dominates speckle decorrelation in whole-blood flowmetry using optical coherence tomography.

Quantitative blood flow measurements using optical coherence tomography (OCT) have a wide potential range of medical research and clinical applications. Flowmetry based on the temporal dynamics of the OCT signal may have the ability to measure three-dimensional flow profiles regardless of the flow direction. State-of-the-art models describing the OCT signal temporal statistics are based on dynamic light scattering (DLS), a model which is inherently limited to single scattering regimes. DLS methods continue to be applied to OCT despite the knowledge that red blood cells produce strong forward multiple scattering. Here, we postulate that forward multiple scattering is the primary mechanism causing the rate of speckle-decorrelation derived from data acquired in vivo to deviate from the rate of decorrelation determined in phantom experiments. We also postulate that multiple scattering contributions to decorrelation are only present when the sample exhibits velocity field inhomogeneities larger than the scale of a resolution volume and are thus absent in rigid bulk motion. To test these hypotheses, we performed a systematic study of the effects of forward multiple scattering on OCT signal decorrelation with phantom experiments under physiologically relevant flow conditions and relative bulk motion. Our experimental results confirm that the amount of forward multiple scattering affects the proportionality between lateral flow and decorrelation. We propose that multiply scattered light carries information from different locations in the sample and each location imprints scattering dynamics on the scattered light causing increased decorrelation rates. Our analysis confirms that the detection of forward scattered light inside the vessel lumen causes an increase in the rate of decorrelation which results in an overestimation of blood flow velocities at depths as shallow as 40 µm into whole blood for OCT systems with typical numerical apertures used in retinal imaging.