Duffy, Mitchell J.; Duffy, Mitchell James: Development of translational optical imaging strategies to assess inflammatory biomarkers in rheumatoid arthritis. 2018
Inhalt
- Content
- Abstract
- Introduction
- List of Figures
- Inflammation
- Cartilage and Bone Destruction
- Diagnosis
- Management
- Role of Imaging in Arthritis
- Imaging Modalities
- Optical Imaging
- Fluorescence Reflectance Imaging
- Biomarkers for imaging of inflammation in RA
- S100A9
- Matrix Metalloproteinases
- Animal Models of Rheumatoid Arthritis
- Aim
- Materials and Methods
- Results
- Curriculum Vitae
- Onset phase
- Imaging results show individual inflammation of paws in CIA
- Two subtypes of disease progression identified
- Both fast and slow responders show statistically elevated S100A8/A9 and MMP levels on the day of peak inflammation
- S100A8/A9 and MMP SBRs correlate and are elevated in paws with high clinical scores
- Resolution phase
- Imaging results show inflammation resolution and low SBRs at late time point regardless of paw clenching
- Imaging of the resolution of a highly inflamed state shows decreasing levels of inflammatory biomarkers.
- Histology
- Morphological findings
- Analysis Methods
- Immunohistochemistry corroborates target presence beginning at clinical score 2
- Late stage disease shows little S100A8/A9 and MMP expression despite high clinical scores
- Single joint inflammation case study
- Why employ the signal to background ratio?
- Thresholded SBR Inflammatory Area Analysis Method
- Thresholded SBR Inflammatory Fraction Analysis Method
- Receiver Operating Characteristic for optimal threshold determination
- Discussion
- Multiplexing small molecule probes provided novel insight into concurrent expression of MMPs and S100A8/A9
- No time shift between the expression of S100A8/A9 and MMPs was found
- Histology corroborated S100A9 and MMP-9 imaging data
- Division of onset phase CIA mice into fast and slow responding groups
- The clinical score reflects externally observable markers of inflammation
- Choice of analysis method and use of signal to background ratio
- Blood concentration of tracer is lower in CIA mice
- Thresholded SBR Area and Fraction analyses considered
- ROC curves indicate limited applicability of thresholding methods
- FRI in the clinic
- Photoacoustic imaging of Naphthalocyanine labelled ligands presents a 3D diagnostic opportunity
- Conclusions and Outlook
- References
- Appendix
- A Abbreviations