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January 4, 2024Journal of Nuclear Medicine8 citationsOpen Access

Toward Quantitative Multisite Preclinical Imaging Studies in Acute Myocardial Infarction: Evaluation of the Immune-Fibrosis Axis

MSMaja StrunkGHGyu Seong HeoAHAnnika Hess

Key Result

A standardized consensus acquisition protocol yielded higher 68Ga-DOTA-ECL1i uptake in the infarct territory (P=0.03) and decreased variability between individual animals compared with a local protocol.

Structured PICO

P
Population
33 mice with induced acute myocardial infarction evaluated using standardized versus local PET imaging protocols over 7 days.
I
Intervention
Consensus imaging protocol (lower tracer dose, continuous isoflurane anesthesia, low-dose CT for attenuation correction) with 68Ga-DOTA-ECL1i at 3 days and 68Ga-FAPI-46 at 7 days post-myocardial infarction.
C
Comparator
Local imaging protocol (higher tracer dose, interrupted anesthesia, transmission scan for attenuation correction).
O
Outcome
Reproducibility and variability of quantitative radiotracer uptake (%ID/g and SUV) in the infarct territory.surrogate

Standardized acquisition protocols and centralized core-lab image analysis are necessary to maximize reproducibility in multicenter preclinical molecular imaging studies.

Main Result

p-value: p=0.03

Limitations

  • Biological factors could not be standardized between centers
  • Differences in mouse strains and sex may have influenced post-infarction healing
  • Differences in pain management post-surgery
  • Different commercial scanners prevented complete standardization of image reconstruction
  • Lack of ex vivo validation
  • Biologic factors could not be standardized between centers (different mouse strains, body weights, and infarct sizes).
  • Potential influence of sex on uptake patterns not fully analyzed.
  • Differences in postoperative pain management (carprofen vs tramadol) between sites.

Abstract

The immune-fibrosis axis plays a critical role in cardiac remodeling after acute myocardial infarction. Imaging approaches to monitor temporal inflammation and fibroblast activation in mice have seen wide application in recent years. However, the repeatability of quantitative measurements remains challenging, particularly across multiple imaging centers. We aimed to determine reproducibility of quantitative inflammation and fibroblast activation images acquired at 2 facilities after myocardial infarction in mice. Methods: Mice underwent coronary artery ligation and sequential imaging with 68Ga-DOTA-ECL1i to assess chemokine receptor type 2 expression at 3 d after myocardial infarction and 68Ga-FAPI-46 to assess fibroblast activation protein expression at 7 d after myocardial infarction. Images were acquired at 1 center using either a local or a consensus protocol developed with the second center; the protocols differed in the duration of isoflurane anesthesia and the injected tracer dose. A second group of animals were scanned at the second site using the consensus protocol. Image analyses performed by each site and just by 1 site were also compared. Results: The uptake of 68Ga-DOTA-ECL1i in the infarct territory tended to be higher when the consensus protocol was used (P = 0.03). No difference was observed between protocol acquisitions for 68Ga-FAPI-46. Compared with the local protocol, the consensus protocol decreased variability between individual animals. When a matched consensus protocol was used, the 68Ga-DOTA-ECL1i infarct territory percentage injected dose per gram of tissue was higher on images acquired at site B than on those acquired at site A (P = 0.006). When normalized to body weight as SUV, this difference was mitigated. Both the percentage injected dose per gram of tissue and the SUV were comparable between sites for 68Ga-FAPI-46. Image analyses at the sites differed significantly, but this difference was mitigated when all images were analyzed at site A. Conclusion: The application of a standardized acquisition protocol may lower variability within datasets and facilitate comparison of molecular radiotracer distribution between preclinical imaging centers. Like clinical studies, multicenter preclinical studies should use centralized core-based image analysis to maximize reproducibility across sites.

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Cite This Study

Strunk et al. (2024) studied Acute Myocardial Infarction (n=33). Consensus imaging protocol vs. Local imaging protocol was evaluated on 68Ga-DOTA-ECL1i uptake in the infarct territory (p=0.03). A standardized consensus acquisition protocol yielded higher 68Ga-DOTA-ECL1i uptake in the infarct territory (P=0.03) and decreased variability between individual animals compared with a local protocol.

synapsesocial.com/papers/6a35d97d1cf1489100f6a921https://doi.org/10.2967/jnumed.123.266526
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