SignificanceIndocyanine green-based dynamic contrast-enhanced fluorescence imaging (DCE-FI) can objectively assess bone perfusion intraoperatively. However, it is susceptible to motion artifact due to patients’ involuntary respiration and mechanical disturbance. Reducing motion artifacts would significantly improve DCE-FI for orthopedic surgical guidance.AimOur primary objective is to develop an automated correction method to reduce motion artifacts in DCE-FI and improve the accuracy of bone perfusion assessment.ApproachWe developed an automated motion correction approach based on frame-by-frame mutual information (MI) and validated the effectiveness of this approach in various phantom studies and patient images from 45 imaging sessions of fifteen amputees.ResultsThe MI-based correction reduced motion artifacts by 93% for mechanical disturbances and 76% for simulated respiration in phantom studies. Patient images show improved alignment, improved kinetic curves, and restored bone perfusion-related parameters with an average correction of 4.3 and 9.6 mm in x- and y-axes per session.ConclusionsThe automated MI-based motion correction was able to eliminate motion artifacts effectively and significantly improved the quantitative assessment of bone perfusion by DCE-FI.
Following orthopaedic trauma, bone devitalization is a critical determinant of complications such as infection or nonunion. Intraoperative assessment of bone perfusion has thus far been limited. Furthermore, treatment failure for infected fractures is unreasonably high, owing to the propensity of biofilm to form and become entrenched in poorly vascularized bone. Fluorescence-guided surgery and molecularly-guided surgery could be used to evaluate the viability of bone and soft tissue and detect the presence of planktonic and biofilm-forming bacteria. This proceedings paper discusses the motivation behind developing this technology and our most recent preclinical and clinical results.
Indocyanine green (ICG)-based dynamic contrast-enhanced fluorescence imaging (DCE-FI) can objectively assess bone perfusion intraoperatively. However, it is susceptible to motion artifacts due to patient’s involuntary respiration during the 4.5-minute DCE-FI data acquisition. An automated motion correction approach based on mutual information (MI) frame-by-frame was developed to overcome this problem. In this approach, MIs were calculated between the reference and the adjacent frame translated and the maximal MI corresponded to the optimal translation. The images obtained from eighteen amputation cases were utilized to validate the approach and the results show that this correction can significantly reduce the motion artifacts and can improve the accuracy of bone perfusion assessment.
Debridement of the surgical site during open fracture reduction and internal fixation is important for preventing surgical site infection; the risk of subsequent fracture-associated infection for a particular area of tissue is assessed by the surgeon based on multi-level variables, including demographics and laboratory results. Intraoperative fluorescence imaging can contribute additional information at a more localized level. Here we present a fluorescence-based predictive model using features from dynamic contrast enhanced-fluorescence imaging (DCE-FI), as well as patient-level variables associated with infection risk. Regions-of-interest were selected from thirty-eight enrolled open fracture patients. Spatial and kinetic features were extracted from DCE-FI, and combined with patient infection risk factor describing the possibility of getting surgical-site-infection. The model was evaluated for ability to predict composite outcome scores—intra-operative surgeon assessment coupled with post-operative confirmed infection outcome. This proposed model demonstrates high predictive performance with an accuracy of 0.86, evaluated with a cross-validation approach, and is a promising approach for early and quick identification of tissue prone to infection.
Timely assessment of bone perfusion in orthopaedic trauma surgery plays an important role in successful treatment outcome. For guiding accurate debridement of bones with impaired blood supply, fluorescence-guided surgery (FGS) technique have gained increasingly popularity. Compared to other imaging modalities like computed tomography and nuclear magnetic resonance imaging that are time consuming and less practical during surgery, fluorescence imaging can be performed intraoperatively and is able to visualize the bone blood flow in real time. In order to link the blood flow fluorescence imaging to quantitative bone perfusion numbers, in this study we are using a modified fluorescent microsphere (FM) approach called microsphere quantification using imaging cryomacrotome (mQUIC). Bone perfusion is assessed by identifying the density of deposited microspheres in reconstructed imaging volumes, which are proportional to the regional blood flow. In the rabbit model presented here, cryoimaging was used to scan femurs injected with three colors of microspheres corresponding to three conditions: baseline, post-osteotomy and post-periosteal stripping. Image processing, such as top-hat transform and object-based colocalization, was used to enable accurate counting of FMs to produce their 3D-localization within the bones. FM density volumes were converted to bone perfusion units (mL/min/100g) using the reference organ technique. This study provides a groundwork for direct comparison with our DCE-FI technique for measuring bone perfusion in orthopaedic trauma surgery models.
ICG-based dynamic contrast-enhanced fluorescence imaging (DCE-FI) and intraoperative DCE- magnetic resonance imaging (MRI) have been carried out nearly simultaneously in three lower extremity bone infection cases to investigate the relationship between these two imaging modalities for assessing bone blood perfusion during open orthopedic surgeries. Time-intensity curves in the corresponding regions of interest of two modalities were derived for comparison. The results demonstrated that ICG-based DCE-FI has higher sensitivity to perfusion changes while DCE-MRI provides superior and supplemental depth-related perfusion information. Research applying the depth-related perfusion information derived from MRI to improve the overall analytic modeling of intraoperative DCE-FI is ongoing.
In orthopedic trauma surgery, timely assessment of bone tissue perfusion plays a vital role in the successful treatment outcome. Fluorescence-guidance is gaining increased surgical interest, especially with respect to hemodynamic assessment of bone. Intraoperative dynamic contrast-enhanced fluorescence imaging (DCE-FI) not only enables visualization of the perfused areas of the injured bone, but with subsequent analysis using kinetic models, may also provide a valuable quantitative bone blood flow information to a surgeon. In this study, we are validating this quantitative approach with a modified fluorescent microsphere (FM) technique using a custom-built four-channel imaging cryomacrotome. We demonstrate that FMs of four different colors can be accurately detected in controlled phantoms and evaluate their detection accuracy in real blood samples. In a rabbit model of orthopaedic trauma, we show that blood flow measurements using the DCE-FI technique can be compared with the FM technique. This feasibility pilot study provides the groundwork for investigation of the correlation between bone perfusion measurements using DCE-FI and using fluorescent microspheres, in units of ml/min/100g.
This study presents a first clinical translation of bone viability classification technology based on fluorescence imaging and subsequent image texture analysis to provide orthopedic surgeons with intraoperative information for patient treatment optimization.
Forty two patients with high energy open fractures were involved into the study to investigate whether an indocyanine green (ICG)-based dynamic contrast-enhanced fluorescence imaging (DCE-FI) can be used to objectively assess bone perfusion and guide surgical debridement. For each patient, fluorescence images were recorded after 0.1 mg/kg of ICG was administered intravenously. By utilizing a bone-specific kinetic model to the video sequences, the perfusion-related metrics were calculated. The results of this study shown that the quantitative ICG-based DEC-FI can accurately assess the human bone perfusion during the orthopedic surgery.
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