1. Joshua Li, MD, PhD David B. Weiss, MD Orthopaedic Surgery May 9, 2015

2. University of Virginia Orthopaedic Surgery Pilon fracture

3. University of Virginia Orthopaedic Surgery Pilon fracture

4. University of Virginia Orthopaedic Surgery Pilon fracture – Hardware removal

5. University of Virginia Orthopaedic Surgery MRI with contrast 1 year S/P I&D

6. University of Virginia Orthopaedic Surgery Tagged WBC scan ~18 mos S/P I&D

7. University of Virginia Orthopaedic Surgery Laminoplasty 1 Week Postop

8. University of Virginia Orthopaedic Surgery Degenerative inflammation vs. infection

9. University of Virginia Orthopaedic Surgery Current Diagnosis History and examination History and examination Bone culture Bone culture Radiographs Radiographs CT CT Nuclear medicine Nuclear medicine MRI MRI

10. University of Virginia Orthopaedic Surgery MRI High sensitivity >90% High sensitivity >90% Low specificity 50-60% Low specificity 50-60% Difficult to Difficult to differentiate from sterile inflammation

11. University of Virginia Orthopaedic Surgery Macrophages in chronic osteomyelitis High number in osteomyelitis – – the most frequent cell type Low incidence of macrophages at the aseptic inflammatory site – – in aseptic inflammation, macrophages represent less than 10% of cells – – the major cellular infiltrations are fibroblasts

12. University of Virginia Orthopaedic Surgery Identification of macrophages in osteomyelitis CD68 CD14 CD36 – – CD36, a pattern recognition receptor mediating innate immune responses to pathogens present in macrophages, participates in innate sensing and the phagocytic clearance of both Gram-positive and Gram-negative bacteria

13. University of Virginia Orthopaedic Surgery MRI contrast agent on Fullerene platform Stable encapsulation of metal ions More Gadolinium atoms and incr sensitivity Low Concentration and Molecular Targeting Safe

14. University of Virginia Orthopaedic Surgery Specific aims Aim 1: To characterize the binding and the imaging activity of a functionalized CD36 targeted nanofullerene Gd 3 N@C 80 - CD36Ligand compound in macrophages in vitro. Aim 2: To detect the presence of infection using Gd 3 N@C 80 -CD36Ligand compound in a chronic mouse post-traumatic tibia osteomyelitis model.

15. University of Virginia Orthopaedic Surgery In Vivo Experiment In Vivo Experiment

16. University of Virginia Orthopaedic Surgery Hypothesis

17. Funding Awarded grant from Orthoapedic Trauma Association in 2015 Awarded grant from Orthoapedic Trauma Association in 2015 $20,000 $20,000 Applied for R21 grant from NIH Applied for R21 grant from NIH