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Spectroscopic Ultrasound Visualizes Early Heterotopic Ossification: A Paradigm Shift Towards Earlier Diagnosis and Treatment
Kavitha Ranganathan, MD, Adeline Hong, PhD, David Cholok, BS, Joe Habbouche, BS, Arminder Kaura, BS, Hsiao Hsin Sung Hsieh, DDS, John Li, MD, Michael Chung, MD, Jonathan Butts, BS, Cheri Deng, PhD, Jan Stegemann, PhD, Steven R. Buchman, MD, Benjamin Levi, MD.
University of Michigan, Ann Arbor, MI, USA.

PURPOSE: The prevention of heterotopic ossification (HO) is limited by inadequate detection of ectopic bone formation at early time points during which prophylaxis must be initiated in order to be effective. Current imaging modalities are costly, invasive, and unable to visualize HO prior to six weeks after bone formation. Therefore, these technologies are not utilized, and patients receive treatment in a delayed fashion as a result of these diagnostic inadequacies. In this study, we validate the use of spectroscopic ultrasound imaging (SUSI) to diagnose HO as early as one week after injury, and five weeks earlier than microCT imaging which is the current gold standard.
METHODS: Concurrent SUSI and microCT were performed after an Achilles tenotomy and 30% total body surface area burn (C57BL6 mice; n=4 per time point). Imaging of the injured limb and skin incision only contra-lateral limb (control) was performed weekly (1-9 weeks post-injury) in a longitudinal fashion. Acoustic concentration (10*log(mm-3)) was calculated for each ultrasound frame. Houndsfield units were used to calculate HO volume on microCT imaging. Histology was used to confirm the presence of HO and to correlate with imaging findings at each time point.
RESULTS: Using SUSI, the acoustic concentration of bone was significantly different than that of muscle, cartilage, and tendon (61.3±7.3 vs. 36.5±8.6 vs. 49.5±5.4 vs. 39.8±0.67; p<0.05). HO was visualized on SUSI as early as 1 week after injury and 5 weeks prior to detection by MicroCT. (Figure 1).The acoustic concentration of HO was significantly greater than that of the control limb (56.9±10.9 vs. 29.0±10.7; p<0.05) at all time points. The surrounding edema also had a significantly lower acoustic concentration than the foci of HO (28.9±5.6 vs. 56.9±10.9; p<0.05), allowing for clear anatomic and structural delineation within this region. Spectroscopic foci of HO present at 1 week within the left limb correlated with the HO present at 9 weeks on microCT and histology.
CONCLUSION: Spectroscopic ultrasound visualizes HO as early as one week after injury. As prophylaxis must be initiated within 1-3 weeks of initial HO formation to prevent the need for surgery, SUSI represents the ideal imaging modality to guide treatment. Additionally, SUSI can be used to monitor the progression of HO to measure when growth has halted in preparation for surgical excision.


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