Faculty Bibliography

BACKGROUND:Achieving non-invasive, targeted modulation of deep brain tissue remains a major challenge in neurotechnology. Current non-invasive brain stimulation methods-such as transcranial electrical (TES), magnetic (TMS), and focused ultrasound (TFUS) stimulation-suffer from limitations in spatial focality, penetration depth, or skull-related distortions. Radio frequency (RF) energy, which penetrates biological tissue effectively, offers an alternative avenue for neural modulation. This study introduces Transcranial Radio Frequency Stimulation (TRFS) as a novel, contactless neuromodulation technique that leverages RF-induced thermal effects to modulate neural activity in vivo. METHODS:We developed a custom RF stimulation system using 945 MHz stub antennas optimized for localized brain heating in mice. Using our unique experimental setup, we developed and tested two operational modes of TRFS:Pristine mode: RF stimulation applied to intact brain tissue.RF-genetics mode: RF stimulation applied to brain regions virally transduced to overexpress the thermosensitive TRPV1 ion channel. Neural activity was recorded using metal-free one-photon fiber photometry with GCaMP calcium indicators. Behavioral effects were assessed through a rotational test in freely moving mice after MK-801-induced hyperlocomotion. Local temperature changes were monitored by optical thermometry RESULTS: In pristine mode, RF exposure induced temperature rises leading to dose-dependent suppression of cortical parvalbumin (PV) interneuron activity. This neural suppression translated behaviorally into a unilateral rotational bias ipsilateral to the stimulated hemisphere in hyperlocomotive freely moving mice.In RF-genetics mode, RF stimulation of TRPV1-overexpressing regions produced temperature-dependent excitation of neural activity once local change in temperatures exceeded ΔT ≈ 1.5 °C. Behaviorally, this excitation reversed the direction of rotation in hyperlocomotive freely moving mice, yielding a contralateral bias. CONCLUSIONS:TRFS represents a conceptual advance in neuromodulation, uniting the inherent capability of RF energy to target deep brain tissue with the biophysical reliability of thermal modulation. TRFS applications are bimodal, capable of influencing the pristine brain by suppressing the activity of specific neuronal populations in targeted regions, or of exciting selectively transfected neural ensembles expressing thermosensitive TRPV1 ion channels. The latter modality, first introduced here, represents a novel concept termed "RF-genetics." TRFS represents a promising platform for next-generation non-invasive brain stimulation with potential translational applications in treating various neurological and psychiatric disorders.

The goal of the MRI4ALL hackathon, which took place in October 2023, was to develop a functional low-field MRI scanner in just one week and to release all created source code and resources as open-source packages. The event was attended by 52 participants from 16 institutions who assembled the scanner on the last day of the hackathon. The scanner's magnetic B₀ field with a strength of 43 mT and a target field-of-view size of 11 cm³ was created with a Halbach array made from 990 N40UH permanent magnets, held in place using 3D printed ring formers. Gradient coils were fabricated by gluing enameled copper wire onto 3D printed holders with imprinted wire patterns. A solenoid coil for RF transmission and reception was built by winding 20 turns of Litz wire around a 3D printed cylinder. A Red Pitaya FPGA prototyping board running the MaRCoS framework was used to control the scanner components, and a GPA-FHDO amplifier board was used to drive the gradients. To simplify the scanner's operation, console software with an intuitive graphical user interface was developed in Python using the PyPulseq package for sequence calculations. Furthermore, the scanner was equipped with a cooling system, as well as options for passive and active shimming. After resolving several technical issues that arose during the assembly, the scanner is now able to acquire MR images with different sequences. While not suitable for real-world clinical applications, it can be utilized for educational purposes or as a low-cost prototyping platform. Moreover, it may serve as a reference design for future MRI development projects. All source code and resources are available on the project website mri4all.org, allowing other groups to replicate the scanner. EVIDENCE LEVEL: n/a TECHNICAL EFFICACY: Stage 1.

Stroke is a leading cause of mortality and disability. Emergent diagnosis and intervention are critical, and predicated upon initial brain imaging; however, existing clinical imaging modalities are generally costly, immobile, and demand highly specialized operation and interpretation. Low-energy microwaves have been explored as a low-cost, small form factor, fast, and safe probe for tissue dielectric properties measurements, with both imaging and diagnostic potential. Nevertheless, challenges inherent to microwave reconstruction have impeded progress, hence conduction of microwave imaging remains an elusive scientific aim. Herein, we introduce a dedicated experimental framework comprising a robotic navigation system to translate blood-mimicking phantoms within a human head model. An 8-element ultra-wideband array of modified antipodal Vivaldi antennas was developed and driven by a two-port vector network analyzer spanning 0.6-9.0 GHz at an operating power of 1 mW. Complex scattering parameters were measured, and dielectric signatures of hemorrhage were learned using a dedicated deep neural network for prediction of hemorrhage classes and localization. An overall sensitivity and specificity for detection >0.99 was observed, with Rayleigh mean localization error of 1.65 mm. The study establishes the feasibility of a robust experimental model and deep learning solution for ultra-wideband microwave stroke detection.

Over the past few decades, daily exposure to radiofrequency (RF) fields has been increasing due to the rapid development of wireless and medical imaging technologies. Under extreme circumstances, exposure to very strong RF energy can lead to heating of body tissue, even resulting in tissue injury. The presence of implanted devices, moreover, can amplify RF effects on surrounding tissue. Therefore, it is important to understand the interactions of RF fields with tissue in the presence of implants, in order to establish appropriate wireless safety protocols, and also to extend the benefits of medical imaging to increasing numbers of people with implanted medical devices. This study explored the neurological effects of RF exposure in rodents implanted with neuronal recording electrodes. We exposed freely moving and anesthetized rats and mice to 950 MHz RF energy while monitoring their brain activity, temperature, and behavior. We found that RF exposure could induce fast onset firing of single neurons without heat injury. In addition, brain implants enhanced the effect of RF stimulation resulting in reversible behavioral changes. Using an optical temperature measurement system, we found greater than tenfold increase in brain temperature in the vicinity of the implant. On the one hand, our results underline the importance of careful safety assessment for brain-implanted devices, but on the other hand, we also show that metal implants may be used for neurostimulation if brain temperature can be kept within safe limits.

Proper animal conditioning is a key factor in the quality and success of preclinical neuroimaging applications. Here, we introduce an open-source easy-to-modify multimodal 3D printable design for rodent conditioning for magnetic resonance imaging (MRI) or other imaging modalities. Our design can be used for brain imaging in anesthetized or awake mice, and in anesthetized rats. We show ease of use and reproducibility of subject conditioning with anatomical T2-weighted imaging for both mice and rats. We also demonstrate the application of our design for awake functional MRI in mice using both visual evoked potential and olfactory stimulation paradigms. In addition, using a combined MRI, positron emission tomography and X-ray computed tomography experiment, we demonstrate that our proposed cradle design can be utilized for multiple imaging modalities.

Stroke is a leading cause of mortality and disability. Emergent diagnosis and intervention are critical, and predicated upon initial brain imaging; however, existing clinical imaging modalities are generally costly, immobile, and demand highly specialized operation and interpretation. Low-energy microwaves have been explored as low-cost, small form factor, fast, and safe probes of tissue dielectric properties, with both imaging and diagnostic potential. Nevertheless, challenges inherent to microwave reconstruction have impeded progress, hence microwave imaging (MWI) remains an elusive scientific aim. Herein, we introduce a dedicated experimental framework comprising a robotic navigation system to translate blood-mimicking phantoms within an anatomically realistic human head model. An 8-element ultra-wideband (UWB) array of modified antipodal Vivaldi antennas was developed and driven by a two-port vector network analyzer spanning 0.6-9.0 GHz at an operating power of 1 mw. Complex scattering parameters were measured, and dielectric signatures of hemorrhage were learned using a dedicated deep neural network for prediction of hemorrhage classes and localization. An overall sensitivity and specificity for detection >0.99 was observed, with Rayliegh mean localization error of 1.65 mm. The study establishes the feasibility of a robust experimental model and deep learning solution for UWB microwave stroke detection.

Temperature is a hallmark parameter influencing almost all magnetic resonance properties (e.g., T\textsubscript{1}, T\textsubscript{2}, proton density, diffusion and more). In the pre-clinical setting, temperature has a large influence on animal physiology (e.g., respiration rate, heart rate, metabolism, cellular stress, and more) and needs to be carefully regulated, especially when the animal is under anesthesia and thermoregulation is disrupted. We present an open-source heating and cooling system capable of stabilizing the temperature of the animal. The system was designed using Peltier modules capable of heating or cooling a circulating water bath with active temperature feedback. Feedback was obtained using a commercial thermistor, placed in the animal rectum, and a proportional{\text -}integral{\text -}derivative (PID) controller capable of locking the temperature. Operation was demonstrated in a phantom as well as mouse and rat animal models, where the standard deviation of the temperature of the animal upon convergence was less than a tenth of a degree. An application where brain temperature of a mouse was modulated was demonstrated using an invasive optical probe and non-invasive magnetic resonance spectroscopic thermometry measurements.

With the development of novel technologies, radio frequency (RF) energy exposure is expanding at various wavelengths and power levels. These developments necessitate updated approaches of RF measurements in complex environments, particularly in live biological tissue. Accurate dosimetry of the absorbed RF electric fields (E-Fields) by the live tissue is the keystone of environmental health considerations for this type of ever-growing non-ionizing radiation energy. In this study, we introduce a technique for direct in-vivo measurement of electric fields in living tissue. Proof of principle in-vivo electric field measurements were conducted in rodent brains using Bismuth Silicon Oxide (BSO) crystals exposed to varying levels of RF energy. Electric field measurements were calibrated and verified using in-vivo temperature measurements using optical temperature fibers alongside electromagnetic field simulations of a transverse electromagnetic (TEM) cell.

Temperature is a hallmark parameter influencing almost all magnetic resonance properties (e.g., T₁ , T₂ , proton density, and diffusion). In the preclinical setting, temperature has a large influence on animal physiology (e.g., respiration rate, heart rate, metabolism, and oxidative stress) and needs to be carefully regulated, especially when the animal is under anesthesia and thermoregulation is disrupted. We present an open-source heating and cooling system capable of regulating the temperature of the animal. The system was designed using Peltier modules capable of heating or cooling a circulating water bath with active temperature feedback. Feedback was obtained using a commercial thermistor, placed in the animal rectum, and a proportional-integral-derivative controller was used to modulate the temperature. Its operation was demonstrated in a phantom as well as in mouse and rat animal models, where the standard deviation of the temperature of the animal upon convergence was less than a 10th of a degree. An application where brain temperature of a mouse was modulated was demonstrated using an invasive optical probe and noninvasive magnetic resonance spectroscopic thermometry measurements.

Nuclear magnetic resonance relaxometry represents a powerful tool for extracting dynamic information. Yet, obtaining links to molecular motion is challenging for many ions that relax through the quadrupolar mechanism, which is mediated by electric field gradient fluctuations and lacks a detailed microscopic description. For sodium ions in aqueous electrolytes, we combine ab initio calculations to account for electron cloud effects with classical molecular dynamics to sample long-time fluctuations, and obtain relaxation rates in good agreement with experiments over broad concentration and temperature ranges. We demonstrate that quadrupolar nuclear relaxation is sensitive to subpicosecond dynamics not captured by previous models based on water reorientation or cluster rotation. While ions affect the overall water retardation, experimental trends are mainly explained by dynamics in the first two solvation shells of sodium, which contain mostly water. This work thus paves the way to the quantitative understanding of quadrupolar relaxation in electrolyte and bioelectrolyte systems.