TY - JOUR
T1 - High Frequency Spectral Ultrasound Imaging Detects Early Heterotopic Ossification in Rodents
AU - Edwards, Nicole J.
AU - Hobson, Eric
AU - Dey, Devaveena
AU - Rhodes, Alisha
AU - Overmann, Archie
AU - Hoyt, Benjamin
AU - Walsh, Sarah A.
AU - Pagani, Chase A.
AU - Strong, Amy L.
AU - Hespe, Geoffrey E.
AU - Padmanabhan, Karthik R.
AU - Huber, Amanda
AU - Deng, Cheri
AU - Davis, Thomas A.
AU - Levi, Benjamin
N1 - Publisher Copyright:
© Copyright 2021, Mary Ann Liebert, Inc., publishers 2021.
PY - 2021/5/1
Y1 - 2021/5/1
N2 - Heterotopic ossification (HO) is a devastating condition in which ectopic bone forms inappropriately in soft tissues following traumatic injuries and orthopedic surgeries as a result of aberrant mesenchymal progenitor cell (MPC) differentiation. HO leads to chronic pain, decreased range of motion, and an overall decrease in quality of life. While several treatments have shown promise in animal models, all must be given during early stages of formation. Methods for early determination of whether and where endochondral ossification/soft tissue mineralization (HO anlagen) develop are lacking. At-risk patients are not identified sufficiently early in the process of MPC differentiation and soft tissue endochondral ossification for potential treatments to be effective. Hence, a critical need exists to develop technologies capable of detecting HO anlagen soon after trauma, when treatments are most effective. In this study, we investigate high frequency spectral ultrasound imaging (SUSI) as a noninvasive strategy to identify HO anlagen at early time points after injury. We show that by determining quantitative parameters based on tissue organization and structure, SUSI identifies HO anlagen as early as 1-week postinjury in a mouse model of burn/tenotomy and 3 days postinjury in a rat model of blast/amputation. We analyze single cell RNA sequencing profiles of the MPCs responsible for HO formation and show that the early tissue changes detected by SUSI match chondrogenic and osteogenic gene expression in this population. SUSI identifies sites of soft tissue endochondral ossification at early stages of HO formation so that effective intervention can be targeted when and where it is needed following trauma-induced injury. Furthermore, we characterize the chondrogenic to osteogenic transition that occurs in the MPCs during HO formation and correlate gene expression to SUSI detection of the HO anlagen.
AB - Heterotopic ossification (HO) is a devastating condition in which ectopic bone forms inappropriately in soft tissues following traumatic injuries and orthopedic surgeries as a result of aberrant mesenchymal progenitor cell (MPC) differentiation. HO leads to chronic pain, decreased range of motion, and an overall decrease in quality of life. While several treatments have shown promise in animal models, all must be given during early stages of formation. Methods for early determination of whether and where endochondral ossification/soft tissue mineralization (HO anlagen) develop are lacking. At-risk patients are not identified sufficiently early in the process of MPC differentiation and soft tissue endochondral ossification for potential treatments to be effective. Hence, a critical need exists to develop technologies capable of detecting HO anlagen soon after trauma, when treatments are most effective. In this study, we investigate high frequency spectral ultrasound imaging (SUSI) as a noninvasive strategy to identify HO anlagen at early time points after injury. We show that by determining quantitative parameters based on tissue organization and structure, SUSI identifies HO anlagen as early as 1-week postinjury in a mouse model of burn/tenotomy and 3 days postinjury in a rat model of blast/amputation. We analyze single cell RNA sequencing profiles of the MPCs responsible for HO formation and show that the early tissue changes detected by SUSI match chondrogenic and osteogenic gene expression in this population. SUSI identifies sites of soft tissue endochondral ossification at early stages of HO formation so that effective intervention can be targeted when and where it is needed following trauma-induced injury. Furthermore, we characterize the chondrogenic to osteogenic transition that occurs in the MPCs during HO formation and correlate gene expression to SUSI detection of the HO anlagen.
KW - heterotopic ossification
KW - high frequency spectral ultrasound imaging
KW - mesenchymal progenitor cells
KW - traumatic injury
UR - http://www.scopus.com/inward/record.url?scp=85105506431&partnerID=8YFLogxK
U2 - 10.1089/scd.2021.0011
DO - 10.1089/scd.2021.0011
M3 - Article
C2 - 33715398
AN - SCOPUS:85105506431
SN - 1547-3287
VL - 30
SP - 473
EP - 484
JO - Stem Cells and Development
JF - Stem Cells and Development
IS - 9
ER -