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165 Label-free autofluorescence lifetime to assess changes in myocardial fibrosis and metabolism in vivo in a doxorubicin cardiomyopathy heart failure model
  1. BT Dyer1,
  2. JM Elder2,
  3. J Lagarto1,
  4. SE Harding2,
  5. PMW French3,
  6. NS Peters2,
  7. C Dunsby3,
  8. AR Lyon2
  1. 1Imperial College London
  2. 2NHLI, Imperial College London
  3. 3Photonics Group, Department of Physics, Imperial College London

Abstract

We are developing an autofluorescence (AFL) lifetime-based technique to characterise the signatures associated with histological, metabolic and functional changes in myocardial disease. AFL spectroscopy exploits the properties of a number of endogenous molecules and offers the potential to avoid exogenous label use that could potentially alter the physiological environment. AFL measurements of molecules such as NADH and flavins may report energetic state changes, whilst signatures from matrix such as collagen inform of structural alterations. We investigated the application of a fibre-optic based single-point instrument combining time-resolved spectrofluorometry and diffuse reflectance spectroscopy to a doxorubicin cardiomyopathy heart failure model (DOX-HF) in vivo.

Sprague-Dawley male rats received 1.25 mg/kg doxorubicin or vehicle (0.9% NaCl) via tail vein injection weekly for 8 weeks. AFL signals were measured in vivo in week 11, once heart failure phenotype was well established. DOX-HF(n = 8) LVEF 49.6% vs. 80.4% in controls (n = 4)(**p = 0.006). At 11 weeks, significant differences in AFL signals between DOX-HF(n = 6) and control (n = 3) in LV, RV and LV posterior wall were observed (*p < 0.05). A significantly increased proportion of collagen AFL was seen across all areas in DOX-HF (n = 6) vs. control (n = 3)(*p < 0.05). AFL-predicted collagen content was previously highly correlated with quantitative histology (r = 0.984,*p < 0.05).

Our instrument has sensitivity to characterise in vivo changes in DOX-HF model without use of exogenous compounds. Incorporation into coronary catheters or pacing leads could offer additional diagnostic information and monitoring. Identification of earlier changes could permit development of a screening strategy to identify cancer patients developing cardiomyopathy to permit judicious adjustment of chemotherapy.

  • Autofluorescence Lifetime
  • Doxorubicin cardiotoxicity
  • Chemotherapy cardiomyopathy

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