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Quantitative analysis of peripheral tissue perfusion using spatiotemporal molecular dynamics.

Kang Y, Choi M, Lee J, Koh GY, Kwon K, Choi C - PLoS ONE (2009)

Bottom Line: Because near infrared (NIR) radiation can penetrate relatively deep into tissue, significant attention has been given to intravital NIR fluorescence imaging.Time-series NIR fluorescence images were obtained after injecting ICG intravenously in a murine hindlimb ischemia model.We propose that this novel NIR-imaging-based strategy is a powerful tool for biomedical studies related to the evaluation of therapeutic interventions directed at stimulating angiogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Bio and Brain Engineering, KAIST, Daejeon, Korea.

ABSTRACT

Background: Accurate measurement of peripheral tissue perfusion is challenging but necessary to diagnose peripheral vascular insufficiency. Because near infrared (NIR) radiation can penetrate relatively deep into tissue, significant attention has been given to intravital NIR fluorescence imaging.

Methodology/principal findings: We developed a new optical imaging-based strategy for quantitative measurement of peripheral tissue perfusion by time-series analysis of local pharmacokinetics of the NIR fluorophore, indocyanine green (ICG). Time-series NIR fluorescence images were obtained after injecting ICG intravenously in a murine hindlimb ischemia model. Mathematical modeling and computational simulations were used for translating time-series ICG images into quantitative pixel perfusion rates and a perfusion map. We could successfully predict the prognosis of ischemic hindlimbs based on the perfusion profiles obtained immediately after surgery, which were dependent on the preexisting collaterals. This method also reflected increases in perfusion and improvements in prognosis of ischemic hindlimbs induced by treatment with vascular endothelial growth factor and COMP-angiopoietin-1.

Conclusions/significance: We propose that this novel NIR-imaging-based strategy is a powerful tool for biomedical studies related to the evaluation of therapeutic interventions directed at stimulating angiogenesis.

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Related in: MedlinePlus

Synergistic proangiogenic effects of VEGF and cAng1.(A) Correlations between necrosis probability and regional perfusion rates were determined. (B) Differences in perfusion rates according to the time period are indicated for each group. ANOVA and Bonferroni post hoc test applied to the significant effect of groups on Δ (POD 3 - POD 7), (ANOVA F3,33 = 4.890, P = 0.006). ††, P = 0.004 vs. BSA control. Paired t-tests were performed for each intragroup comparison. (C) Representative examples of BSA control and combined treatment groups.
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pone-0004275-g003: Synergistic proangiogenic effects of VEGF and cAng1.(A) Correlations between necrosis probability and regional perfusion rates were determined. (B) Differences in perfusion rates according to the time period are indicated for each group. ANOVA and Bonferroni post hoc test applied to the significant effect of groups on Δ (POD 3 - POD 7), (ANOVA F3,33 = 4.890, P = 0.006). ††, P = 0.004 vs. BSA control. Paired t-tests were performed for each intragroup comparison. (C) Representative examples of BSA control and combined treatment groups.

Mentions: For therapeutic angiogenesis studies, 70 mice were divided into four groups. The initial perfusion rates of the ischemic limbs were not significantly different among groups (ANOVA, F3,33 = 0.667, p = 0.578, Figure S4). After intramuscular injection of angiogenic factors in the ischemic limbs, follow-up ICG perfusion imaging was serially performed on POD 3 and 7. As expected, the probability of necrosis in regions with low perfusion rates (2–60%/min) was significantly improved by treatment with VEGF, cAng1, or both (Figure 3A). Intergroup comparisons of time-dependent increments in perfusion rates clearly demonstrated synergistic therapeutic effects of VEGF and cAng1, especially between POD 3 and 7 (Figure 3B and Figure S5); this was consistent with results from our previous study [25]. The representative comparison shows that combined treatment with VEGF and cAng1 improved perfusion and the subsequent prognosis of the ischemic hindlimbs (Figure 3C). In the control animals, the amount of necrotic tissue accurately matched the necrosis predicted by postoperative (post-op) perfusion measurements. Slightly diminished perfusion was initially observed in the combined treatment animal, which was predicted to have a poorer prognosis compared to the control; however, the final outcome was much better than that of the control, indicating a protective effect of combined treatment. Histogram analysis showed that the unimodal peak shifted to the right after surgery and was almost completely restored to the level of the normal hindlimb, suggesting a dominant effect of proangiogenic factors on the microvasculature.


Quantitative analysis of peripheral tissue perfusion using spatiotemporal molecular dynamics.

Kang Y, Choi M, Lee J, Koh GY, Kwon K, Choi C - PLoS ONE (2009)

Synergistic proangiogenic effects of VEGF and cAng1.(A) Correlations between necrosis probability and regional perfusion rates were determined. (B) Differences in perfusion rates according to the time period are indicated for each group. ANOVA and Bonferroni post hoc test applied to the significant effect of groups on Δ (POD 3 - POD 7), (ANOVA F3,33 = 4.890, P = 0.006). ††, P = 0.004 vs. BSA control. Paired t-tests were performed for each intragroup comparison. (C) Representative examples of BSA control and combined treatment groups.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2626246&req=5

pone-0004275-g003: Synergistic proangiogenic effects of VEGF and cAng1.(A) Correlations between necrosis probability and regional perfusion rates were determined. (B) Differences in perfusion rates according to the time period are indicated for each group. ANOVA and Bonferroni post hoc test applied to the significant effect of groups on Δ (POD 3 - POD 7), (ANOVA F3,33 = 4.890, P = 0.006). ††, P = 0.004 vs. BSA control. Paired t-tests were performed for each intragroup comparison. (C) Representative examples of BSA control and combined treatment groups.
Mentions: For therapeutic angiogenesis studies, 70 mice were divided into four groups. The initial perfusion rates of the ischemic limbs were not significantly different among groups (ANOVA, F3,33 = 0.667, p = 0.578, Figure S4). After intramuscular injection of angiogenic factors in the ischemic limbs, follow-up ICG perfusion imaging was serially performed on POD 3 and 7. As expected, the probability of necrosis in regions with low perfusion rates (2–60%/min) was significantly improved by treatment with VEGF, cAng1, or both (Figure 3A). Intergroup comparisons of time-dependent increments in perfusion rates clearly demonstrated synergistic therapeutic effects of VEGF and cAng1, especially between POD 3 and 7 (Figure 3B and Figure S5); this was consistent with results from our previous study [25]. The representative comparison shows that combined treatment with VEGF and cAng1 improved perfusion and the subsequent prognosis of the ischemic hindlimbs (Figure 3C). In the control animals, the amount of necrotic tissue accurately matched the necrosis predicted by postoperative (post-op) perfusion measurements. Slightly diminished perfusion was initially observed in the combined treatment animal, which was predicted to have a poorer prognosis compared to the control; however, the final outcome was much better than that of the control, indicating a protective effect of combined treatment. Histogram analysis showed that the unimodal peak shifted to the right after surgery and was almost completely restored to the level of the normal hindlimb, suggesting a dominant effect of proangiogenic factors on the microvasculature.

Bottom Line: Because near infrared (NIR) radiation can penetrate relatively deep into tissue, significant attention has been given to intravital NIR fluorescence imaging.Time-series NIR fluorescence images were obtained after injecting ICG intravenously in a murine hindlimb ischemia model.We propose that this novel NIR-imaging-based strategy is a powerful tool for biomedical studies related to the evaluation of therapeutic interventions directed at stimulating angiogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Bio and Brain Engineering, KAIST, Daejeon, Korea.

ABSTRACT

Background: Accurate measurement of peripheral tissue perfusion is challenging but necessary to diagnose peripheral vascular insufficiency. Because near infrared (NIR) radiation can penetrate relatively deep into tissue, significant attention has been given to intravital NIR fluorescence imaging.

Methodology/principal findings: We developed a new optical imaging-based strategy for quantitative measurement of peripheral tissue perfusion by time-series analysis of local pharmacokinetics of the NIR fluorophore, indocyanine green (ICG). Time-series NIR fluorescence images were obtained after injecting ICG intravenously in a murine hindlimb ischemia model. Mathematical modeling and computational simulations were used for translating time-series ICG images into quantitative pixel perfusion rates and a perfusion map. We could successfully predict the prognosis of ischemic hindlimbs based on the perfusion profiles obtained immediately after surgery, which were dependent on the preexisting collaterals. This method also reflected increases in perfusion and improvements in prognosis of ischemic hindlimbs induced by treatment with vascular endothelial growth factor and COMP-angiopoietin-1.

Conclusions/significance: We propose that this novel NIR-imaging-based strategy is a powerful tool for biomedical studies related to the evaluation of therapeutic interventions directed at stimulating angiogenesis.

Show MeSH
Related in: MedlinePlus