A Preliminary Study of Contrast-Enhanced Ultrasound (CEUS) and Cytokine Expression Analysis (CEA) as Early Predictors for the Outcome of Tibial Non-Union Therapy

Abstract

The current study investigates if contrast-enhanced ultrasound (CEUS) or cytokine expression analysis (CEA) evaluating vascularization are capable of predicting the outcome of non-union therapy. Patients with tibial non-unions were surgically treated and participated in our follow-up program including perioperative collection of blood as well as CEUS analysis. Two groups were formed: Responders in group 1 (G1, N = 8) and Non-Responders in group 2 (G2, N = 5). Serum cytokine expression and local microperfusion were compared and correlated to the radiologic outcome. Evaluation of TNF-α expression revealed significantly lower values prior to first surgery in G1 (G1: 9.66 ± 0.96 pg/mL versus G2: 12.63 ± 1.2 pg/mL; p = 0.045); whereas after treatment both CEA and CEUS indicated a higher potential for angiogenesis in Responders. Logistic regression modelling revealed the highest predictive power regarding eventual osseous consolidation for the combination of both CEUS and serum CEA. The results provide first evidence regarding a link between changes in the serum expression of distinct pro-angiogenic cytokines and alterations in the local microperfusion assessed via both non-invasive and radiation-free diagnostic modalities. In addition, a combination of CEUS and CEA is a promising novel tool in early prediction of the outcome of non-union therapy.

Studies of Superb Microvascular Imaging and Contrast‐Enhanced Ultrasonography in the Evaluation of Vascularization in Early Bone Regeneration

“…Krammer et al reported that early evaluation (examination at 12 week) of successful recovery after tibial non‐union can be realized with CEUS. A study by Haubruck et al reported that a combination of CEUS and peripheral cytokine expression analysis is a promising novel tool in early prediction of the outcome of nonunion therapy. As an improved Doppler technology, SMI technology can display the blood flow in microvessels.…”

Métodos de avaliação do regenerado ósseo

“…1,30 A ultrassonografia com contraste (USC) pode fornecer uma indicação precoce de neovascularização e uma base diagnóstica para a regeneração óssea deficiente. 31 A ultrassonografia também pode predizer a formação de calo ósseo ao revelar mudanças no fluxo sanguíneo ao redor do osso novo, o que pode compensar a má visualização precoce do calo na radiografia. 32 A ultrassonografia é um método não invasivo, eficaz, barato e livre de radiação ionizante para avaliar a cicatrização óssea, que pode detectar formação óssea nova quatro a seis semanas antes da radiografia, 26 além de indicar a taxa de formação de osso novo nos estágios iniciais de distração.…”

The progress in quantitative evaluation of callus during distraction osteogenesis

“…However, new bone with incomplete remodeling and calcification can be well evaluated by high-resolution linear ultrasound [ 35 ]. Contrast-enhanced ultrasound (CEUS) can provide an early indication of neovascularization and provide a diagnostic basis for poor bone regeneration [ 36 ]. Ultrasound can also predict bone callus formation by observing changes in blood flow around the new bone [ 37 ], which can compensate for the poor early visualization of the callus on X-ray.…”

“…CEUS can show the microperfusion of local tissue at the capillary level. Through the study of patients with tibial nonunion, Haubruck et al [ 36 ] found a relationship between the expression of different angiogenic cytokines in serum and the change in local microperfusion. They believe that the combined detection of CEUS and cytokine expression analysis (CEA) is a promising new tool for the early prediction of tibial nonunion.…”