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Analysis of Multifrequency and Phase Keying Strategies for Focusing Ultrasound to the Human Vertebral Canal

Focused ultrasound has been shown to increase the permeability of the blood–brain barrier and its feasibility for opening the blood–spinal cord barrier has also been demonstrated in small animal models, with great potential to impact the treatment of spinal cord (SC) disorders. For clinical translation, challenges to transvertebral focusing of ultrasound energy on the human spinal canal, such as a focal depth of field and standing-wave formation, must be addressed. A dual-aperture approach using multifrequency and phase-shift keying (PSK) strategies for achieving a controlled focus in human thoracic vertebrae was investigated through numerical simulations and benchtop experiments in ex vivo human vertebrae. An ~85% reduction in the focal depth of field was achieved compared to a single-aperture approach at 564 kHz. Short-burst (two-cycle) excitations in combination with PSK were found to suppress the formation of standing waves in ex vivo human thoracic vertebrae when focusing through the vertebral laminae. The results make an important contribution toward the development of a clinical-scale approach for targeting ultrasound therapy to the SC.