A Novel Design of a Portable Birdcage via Meander Line Antenna (MLA) to Lower Beta Amyloid (Aβ) in Alzheimer’s Disease

Abstract

Late Onset Alzheimer's Disease (LOAD) is the most common cause of dementia, characterized by the deposition of plaques primarily of neurotoxic amyloid-[Formula: see text] ([Formula: see text]) peptide and tau protein. Our objective is to develop a noninvasive therapy to decrease the toxic A[Formula: see text] levels, using repeated electromagnetic field stimulation (REMFS) in the brain of Alzheimer's disease patients. We previously examined the effects of REMFS on [Formula: see text] levels in primary human brain (PHB) cultures at different frequencies, powers, and specific absorption rates (SAR). PHB cultures at day in vitro (DIV7) treated with 64 MHz with a SAR of 0.6 W/Kg, one hour daily for 14 days (DIV 21) had significantly reduced (p =0.001) levels of secreted [Formula: see text]-42 and [Formula: see text]-40 peptide without evidence of toxicity. The EMF frequency and power, and SAR levels used in our work is utilized in MRI's, thus suggesting REMFS can be further developed in clinical settings to lower ([Formula: see text]) levels and improve the memory in AD patients. These findings and numerous studies in rodent AD models prompted us to design a portable RF device, appropriate for human use, that will deliver a homogeneous RF power deposition with a SAR value of 0.4-0.9 W/kg to all human brain memory areas, lower ([Formula: see text]) levels, and potentially improve memory in human AD patients.The research took place at the Indiana University School of Medicine (IUSM) and Purdue University Indianapolis. The first phase was done in PHB cultures at the IUSM. Through this phase, we found that a 64 MHz frequency and an RF power deposition with a SAR of 0.4-0.6 W/kg reduced the (A[Formula: see text]) levels potentially impacting Alzheimer's disease. The second phase of the project was conducted at Purdue University, we used ANSYS HFSS (High Frequency Simulation System) to design the devices that produced an appropriate penetration depth, polarization, and power deposition with a SAR of 0.4-0.9 W/kg to all memory brain areas of several numerical models. In Phase II-B will validate the device in a physical phantom. Phase III will require the FDA approval and application in clinical trials.The research parameters were translated into a designed product that fits comfortably in human head and fed from an external RF source that generates an RF power deposition with a SAR of 0.4-0.9 W/kg to a realistic numerical brain. The engineering design is flexible by varying the leg capacitors of the Meander Line Antenna (MLA) devices. Thermal outcomes of the results guarantee less than 0.5 C temperature increase within one-hour time of exposure, which can be used in clinical trials for AD patients. Design parameters include dimension of the coil, the MLA structure, conducting material, and capacitance values with the produced EM fields. The flexible design was achieved by varying the additive capacitance between conductors, and via a hybrid approach integrating a birdcage with sixteen MLA. A coil antenna size within 16 cm radius and 13 cm length was achieved. A capacitance between 6.9 nF and 9.2 nF were observed when copper materials with 16 conductors were used to achieve the research parameters in focus.The medical project proposed here has three phases: The initial phase of determining the research parameters for reducing A[Formula: see text] levels in human brain cultures and animal studies was completed at the IUSM. The translational engineering design of the REMS device and the numerical head and Antenna devices was successfully completed and presented in this paper by Purdue University and IUSM. Future phases will require manufacture and experimental validation of the REMS device with FDA approval for human application. Clinical impact: Our biological studies in human brain cultures showed that an RF power with a SAR of 0.4-0.9 W/kg at 64 MHz, lowered A[Formula: see text] levels, which potentially will prevent the death of the brain neurons and improve memory in AD. The fact that we found a safe RF power deposition with a SAR value associated with the proposed biological effects in human neurons and that 64 MHz provides a penetration depth of 13.5 cm that reaches all memory areas in a human brain makes the design and manufacture of this device of high clinical impact in the study of these exposures on the treatment of Alzheimer's and other protein associate diseases. Also, 64 MHz and RF power deposition with similar SAR levels are administer routinely in routine MRI for more than 4 decades makes it a safe framework for these novel therapeutic strategy.Clinical and Translational Impact Statement: The basic science work presented previously is both mechanistic and translational, and would advance the field of neuroscience as well as AD. This prompted us to joint efforts between the Indiana University School of Medicine and the electrical and computer engineering at Purdue University to design and develop a suitable EMF device for human treatments. Recently, our engineering team designed a birdcage antenna that generate a homogeneous RF power deposition with the same SAR values of our biological experiments in a realistic numerical human brain. Here, the engineering research has been extended to investigate the design of a portable flexible birdcage antenna that will enable adjustments to fit physical patient's characteristics, such as geometry, head size, and tissue dimensions. This new device is expected to improve SAR uniformity and may reduce the likelihood of untreated regions in the brains of patients during treatments. Also, here we determined that the maximum temperature rise of these exposures was less than 0.5°C, which is a safe level per regulatory agencies. This study considers a portable device system that will achieve the research parameters and patient satisfaction regarding reliability and comfort.