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Ultrasound to Diagnose and Treat Heterotopic Ossification


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The purpose of the project is to investigate Doppler ultrasound imaging and therapeutic ultrasound histotripsy for the diagnosis and treatment of acquired heterotopic ossification (HO). Thus far, we have imaged four rounds of ossified and control stem cells with color Doppler ultrasound and have found that imaging at 5 MHz with 12 cycles repeated at 3000 Hz and acoustic pressures of 2 MPa positive and 1 MPa negative produces the most twinkling. We continue to evaluate which metrics of mineralization best match Doppler ultrasound power and/or variance; a manuscript of these results is in preparation. We have also shown that therapeutic ultrasound histotripsy at 1.07 MHz with acoustic pressures of 12 MPa positive and 6 MPa negative successfully fractionates lab-grown calcium phosphate crystals less than 1 mm in size with minimal damage to the surrounding tissue-mimicking phantom. We are currently refining these parameters in ossified stem cells embedded in tissue-mimicking phantoms. Animal studies for imaging HO and treating HO are poised to begin pending receipt of the backordered Matrigel, abasement membrane needed to induce HO in the chosen murine animal model. On the benchtop, we have shown very promising results in detecting and treating HO that we will use to finalize imaging and therapy parameters before translating to the murine animal model of HO in the second year of the project.



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