Contrast-enhanced ultrasound (CEUS) can predict treatment failure for bone fractures that fail to heal, according to a German study published August 22 in Ultrasound in Medicine and Biology.
Researchers led by Dr. Julian Doll from Heidelberg University Hospital in Germany found that CEUS can detect perfusion differences between consolidating and persistent nonunion fractures and can predict treatment failure as early as 12 weeks after surgery.
"Our results prove that CEUS can ... predict the outcome of nonunion surgery and that it can do so even earlier [than other methods], at lower costs and with fewer contrast agent-related side effects," Doll and colleagues wrote.
Bone fractures are classified as nonunion when they do not heal after conventional surgical methods. Nonunion fractures occur in 1.9% and 10% of cases, and they often require expensive diagnostics, multiple surgeries, and long follow-up periods. This can put a heavy financial burden on patients, who also suffer from reduced physical well-being.
The researchers said this makes early detection of nonunion fractures "paramount" for better treatment selection. Therefore, they wanted to validate the diagnostic value of CEUS in predicting the outcome of nonunion revision surgery and confirm its significance in bone perfusion diagnostics.
"We hypothesize that patients with consolidated nonunions, 'responders,' have significantly higher micro-perfusion parameters in the CEUS examination as early as 12 weeks after nonunion surgery, as compared with 'nonresponders,' " they said.
The team looked at data from 112 patients, 79 male and 33 female, with long-bone nonunions between 2014 and 2020. Twelve weeks after surgery, patients underwent contrast ultrasound exams, aiming to assess formations in the nonunion gap. X-rays were also performed to determine the progress of bone union.
The group found significantly higher perfusion levels in responders than nonresponders after 12 weeks. Consolidation, a stage of proper bone healing, was achieved within 36 months for 89 patients (responders), whereas 23 patients showed persistent nonunions (nonresponders) and required further surgery.
Persistent-fracture nonunions could be predicted with a sensitivity of 88.7% and specificity of 72.2% in lower-limb nonunions. The study authors said these patients are likely to suffer from persistent nonunion and may benefit from early revision surgery.
For nonunion fractures of the upper limbs, the sensitivity of contrast ultrasound was found to be 66.7% and specificity was 100%. The researchers said these patients will most likely have their fractures consolidate within 36 months.
Doll and colleagues said these results show that contrast-enhanced ultrasound should be integrated into deciding on revision surgery at an early stage and that it could complement current postoperative monitoring strategies of nonunion consolidation.
"Combining information on the patient's history, standard clinical and radiological examinations and microperfusion assessment by means of CEUS can lead to earlier detection of treatment failure, enabling timely revision surgery," the authors wrote.
![Examples of ultrasound findings and techniques. (A) Images in a 39-year-old male patient with a mass in the left thigh. The mass is heterogeneous on the B-mode US image (compared with the patient in D) and showed increased microvascularity (superb microvascular imaging [SMI]) and shear-wave elastography (SWE) values. Undifferentiated pleomorphic sarcoma was diagnosed at biopsy (with pleomorphic rhabdomyosarcoma in surgical specimen). (B) Images in an 18-year-old male patient with a mass in the left leg. The mass is hypoechoic on the B-mode image, with no other findings suggestive of malignancy. The lesion is in contact with the cortex of the tibia, which is slightly irregular. CT revealed a doubtful anteromedial tibial erosion. The microvascular study demonstrated high vascularization, suggestive of malignancy. Periosteal Ewing sarcoma was diagnosed with both histologic and immunohistochemical confirmation. (C) Images in a 69-year-old female patient with a lump growing on the outside of the left leg. Multiple SWE examinations were performed (please note the high values obtained in the measurements, whereas the color map highlights the stiffness relative to adjacent tissues). SMI showed areas of increased vascularization to target for sampling. Undifferentiated spindle cell sarcoma was diagnosed at biopsy, with residual leiomyosarcoma in the surgical specimen after neoadjuvant therapy. (D) Images in a 56-year-old female patient with a mass in the right thigh. The mass is heterogeneous at both B-mode ultrasound (similar to patient A) and MRI (coronal T2-weighted spectral attenuated inversion recovery [SPAIR]; T1-weighted pre-contrast and postcontrast imaging), which even shows uptake after the administration of paramagnetic contrast material, which is traditionally suggestive of malignancy. Low values at SMI and elastography are suggestive of benignity. Spindle cell lipoma was diagnosed at biopsy, with atypical spindle cell lipomatous tumor in the surgical specimen.](https://img.auntminnie.com/mindful/smg/workspaces/default/uploads/2026/08/images-radiol250278fig2.APCFLSvX6p.jpg?auto=format%2Ccompress&fit=crop&h=100&q=70&w=100)
![Examples of ultrasound findings and techniques. (A) Images in a 39-year-old male patient with a mass in the left thigh. The mass is heterogeneous on the B-mode US image (compared with the patient in D) and showed increased microvascularity (superb microvascular imaging [SMI]) and shear-wave elastography (SWE) values. Undifferentiated pleomorphic sarcoma was diagnosed at biopsy (with pleomorphic rhabdomyosarcoma in surgical specimen). (B) Images in an 18-year-old male patient with a mass in the left leg. The mass is hypoechoic on the B-mode image, with no other findings suggestive of malignancy. The lesion is in contact with the cortex of the tibia, which is slightly irregular. CT revealed a doubtful anteromedial tibial erosion. The microvascular study demonstrated high vascularization, suggestive of malignancy. Periosteal Ewing sarcoma was diagnosed with both histologic and immunohistochemical confirmation. (C) Images in a 69-year-old female patient with a lump growing on the outside of the left leg. Multiple SWE examinations were performed (please note the high values obtained in the measurements, whereas the color map highlights the stiffness relative to adjacent tissues). SMI showed areas of increased vascularization to target for sampling. Undifferentiated spindle cell sarcoma was diagnosed at biopsy, with residual leiomyosarcoma in the surgical specimen after neoadjuvant therapy. (D) Images in a 56-year-old female patient with a mass in the right thigh. The mass is heterogeneous at both B-mode ultrasound (similar to patient A) and MRI (coronal T2-weighted spectral attenuated inversion recovery [SPAIR]; T1-weighted pre-contrast and postcontrast imaging), which even shows uptake after the administration of paramagnetic contrast material, which is traditionally suggestive of malignancy. Low values at SMI and elastography are suggestive of benignity. Spindle cell lipoma was diagnosed at biopsy, with atypical spindle cell lipomatous tumor in the surgical specimen.](https://img.auntminnie.com/mindful/smg/workspaces/default/uploads/2026/08/images-radiol250278fig2.APCFLSvX6p.jpg?auto=format%2Ccompress&dpr=2&fit=crop&h=167&q=70&w=250)
