Ultrasound diagnosis and treatment of heterotopic ossification

Abstract

Heterotopic ossification (HO), or the presence of bone in soft tissues, can occur after musculoskeletal trauma, causing pain and reduced mobility. However, even the most sensitive diagnostic modality requires 2–3 weeks after initiation to detect HO, and the only treatment is surgical resection after HO matures (>2 years). Here, we evaluate the color Doppler ultrasound twinkling artifact for early diagnosis of HO and focused ultrasound (fUS) for treatment of early HO. We began by evaluating twinkling and fUS parameters in ossified cell culture. We then evaluated imaging and treatment parameters in mice with HO. Results show that twinkling correlated well with the presence of ossified cells; although the exact size/number of ossified cells required for twinkling was unclear. In mice, twinkling was found to detect HO in some mice as early as 3 days-post-injection, which is earlier than other imaging modalities. For treatment, fUS at 1.07-MHz and 0.2% duty-cycle with p + /p− = 17/7 MPa was found to be most successful at disrupting mineralizations with little damage to surrounding cells. Mice treated with fUS were found to have less advanced HO compared to sham mice. These results highlight the promise of ultrasound for the diagnosis and treatment of early HO. [Work supported by CDMRP PR201164].