Quantitative Imaging of Cerebral Thromboemboli in Vivo: The Effects of Tissue-Type Plasminogen Activator

Dong Eog Kim, Jeong Yeon Kim, Dawid Schellingerhout, Ju Hee Ryu, Su Kyoung Lee, Sangmin Jeon, Ji Sung Lee, Jiwon Kim, Hee Jeong Jang, Jung E. Park, Eo Jin Kim, Ick Chan Kwon, Cheol Hee Ahn, Matthias Nahrendorf, Kwangmeyung Kim

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15 Scopus citations


Background and Purpose - Quantitative imaging for the noninvasive assessment of thrombolysis is needed to advance basic and clinical thrombosis-related research and tailor tissue-type plasminogen activator (tPA) treatment for stroke patients. We quantified the evolution of cerebral thromboemboli using fibrin-targeted glycol chitosan-coated gold nanoparticles and microcomputed tomography, with/without tPA therapy. Methods - We injected thrombi into the distal internal carotid artery in mice (n=50). Fifty-five minutes later, we injected fibrin-targeted glycol chitosan-coated gold nanoparticles, and 5 minutes after that, we treated animals with tPA or not (25 mg/kg). We acquired serial microcomputed tomography images for 24 hours posttreatment. Results - Thrombus burden at baseline was 784×103±59×103 μm2 for the tPA group (n=42) and 655×103±103×103 μm2 for the saline group (n=8; P=0.37). Thrombus shrinkage began at 0.5 to 1 hour after tPA therapy, with a maximum initial rate of change at 4603±957 μm2/min. The rate of change lowered to ≈61% level of the initial in hours 1 to 2, followed by ≈29% and ≈1% in hours 2 to 3 and 3 to 24, respectively. Thus, 85% of total thrombolysis over 24 hours (≈500 μm2, equivalent to 64% of the baseline thrombus burden) occurred within the first 3 hours of treatment. Thrombus burden at 24 hours could be predicted at around 1.5 to 2 hours. Saline treatment was not associated with significant changes in the thrombus burden. Infarct size was smaller in the tPA group versus saline group (18.1±2.3 versus 45.8±3.3 mm2; P<0.01). Infarct size correlated to final thrombus burden (r=0.71; P<0.01). Time to thrombolysis, completeness of thrombolysis, and tPA therapy were independent predictors of infarct size. Conclusions - Thromboembolic burden and the efficacy of tPA therapy can be assessed serially, noninvasively, and quantitatively using high-resolution microcomputed tomography and a fibrin-binding nanoparticle imaging agent.

Original languageEnglish
Pages (from-to)1376-1385
Number of pages10
Issue number5
StatePublished - 1 May 2017

Bibliographical note

Funding Information:
This work was supported by Global Research Lab (GRL) program (NRF-2015K1A1A2028228) of the National Research Foundation, funded by the Korean government.

Publisher Copyright:
© 2017 American Heart Association, Inc.


  • direct thrombus imaging
  • gold nanoparticles
  • microCT
  • thrombus evolution
  • tissue-type plasminogen activator


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