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Magnetic Resonance Imaging Allows the Evaluation of Tissue Damage and Regeneration in a Mouse Model of Critical Limb Ischemia.

Zaccagnini G, Palmisano A, Canu T, Maimone B, Lo Russo FM, Ambrogi F, Gaetano C, De Cobelli F, Del Maschio A, Esposito A, Martelli F - PLoS ONE (2015)

Bottom Line: Interestingly, K-trans positively correlated with capillary density.Overall, Gastrocnemius and Tibialis anterior muscles displayed similar patterns of MRI parameters dynamic, with more marked responses and less variability in Tibialis anterior.We conclude that MRI provides quantitative information about both tissue damage after ischemia and the subsequent vascular and muscle regeneration, accounting for the differences between subjects and, within the same individual, between different muscles.

View Article: PubMed Central - PubMed

Affiliation: Molecular Cardiology Laboratory, IRCCS-Policlinico San Donato, San Donato Milanese, Milan, Italy.

ABSTRACT
Magnetic resonance imaging (MRI) provides non-invasive, repetitive measures in the same individual, allowing the study of a physio-pathological event over time. In this study, we tested the performance of 7 Tesla multi-parametric MRI to monitor the dynamic changes of mouse skeletal muscle injury and regeneration upon acute ischemia induced by femoral artery dissection. T2-mapping (T2 relaxation time), diffusion-tensor imaging (Fractional Anisotropy) and perfusion by Dynamic Contrast-Enhanced MRI (K-trans) were measured and imaging results were correlated with histological morphometric analysis in both Gastrocnemius and Tibialis anterior muscles. We found that tissue damage positively correlated with T2-relaxation time, while myofiber regeneration and capillary density positively correlated with Fractional Anisotropy. Interestingly, K-trans positively correlated with capillary density. Accordingly, repeated MRI measurements between day 1 and day 28 after surgery in ischemic muscles showed that: 1) T2-relaxation time rapidly increased upon ischemia and then gradually declined, returning almost to basal level in the last phases of the regeneration process; 2) Fractional Anisotropy dropped upon ischemic damage induction and then recovered along with muscle regeneration and neoangiogenesis; 3) K-trans reached a minimum upon ischemia, then progressively recovered. Overall, Gastrocnemius and Tibialis anterior muscles displayed similar patterns of MRI parameters dynamic, with more marked responses and less variability in Tibialis anterior. We conclude that MRI provides quantitative information about both tissue damage after ischemia and the subsequent vascular and muscle regeneration, accounting for the differences between subjects and, within the same individual, between different muscles.

No MeSH data available.


Related in: MedlinePlus

Longitudinal profiles of MRI measurements through time.Time trend analysis of T2-rt, FA and K-trans levels for Gastrocnemius and Tibialis anterior muscles. All values were normalized to values measured in non-ischemic limbs. Mean observed (circle: Gastrocnemius; triangle: Tibialis anterior) and model estimates (continuous line: Gastrocnemius; broken line: Tibialis anterior) are reported. Vertical bars represents 95% confidence intervals according to the mixed regression model. Evidence of a different time trend between the two muscles was found for all MRI measurements (interaction with time T2-rt: p = 0.03; FA: p<0.001; K-trans: p = 0.03). Evidence of a non-linear trend was found for both FA and K-trans. The recovery rate of Tibialis anterior appeared always greater than that of Gastrocnemius. A) T2-rt (ischemic/contralateral*100); B) FA (ischemic/contralateral*100); C) K-trans [(Ischemic-controlateral)/controlateral*100].
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pone.0142111.g005: Longitudinal profiles of MRI measurements through time.Time trend analysis of T2-rt, FA and K-trans levels for Gastrocnemius and Tibialis anterior muscles. All values were normalized to values measured in non-ischemic limbs. Mean observed (circle: Gastrocnemius; triangle: Tibialis anterior) and model estimates (continuous line: Gastrocnemius; broken line: Tibialis anterior) are reported. Vertical bars represents 95% confidence intervals according to the mixed regression model. Evidence of a different time trend between the two muscles was found for all MRI measurements (interaction with time T2-rt: p = 0.03; FA: p<0.001; K-trans: p = 0.03). Evidence of a non-linear trend was found for both FA and K-trans. The recovery rate of Tibialis anterior appeared always greater than that of Gastrocnemius. A) T2-rt (ischemic/contralateral*100); B) FA (ischemic/contralateral*100); C) K-trans [(Ischemic-controlateral)/controlateral*100].

Mentions: To highlight these differences, the temporal trend of Tibialis anterior and Gastrocnemius muscles were normalized and directly compared (Fig 5). The longitudinal analysis of ischemic/contralateral T2-rt ratios provided evidence for a different temporal trend between Gastrocnemius and Tibialis anterior. T2-rt levels at day 1 were significantly different and then started to decrease, but at a rate about double for Tibialis anterior compared to Gastrocnemius muscle (Fig 5A). Likewise, a different temporal trend between Gastrocnemius and Tibialis anterior was found also for FA. The difference of the drop at day 1 of FA between Gastrocnemius and TA was statistically significant. When FA started to recover, the recovery rate of Tibialis anterior was always greater than that of Gastrocnemius and both rates attenuated after day 7 (Fig 5B). The longitudinal analysis of K-trans levels also provided evidence for a different temporal trend between Gastrocnemius and Tibialis anterior (Fig 5C).


Magnetic Resonance Imaging Allows the Evaluation of Tissue Damage and Regeneration in a Mouse Model of Critical Limb Ischemia.

Zaccagnini G, Palmisano A, Canu T, Maimone B, Lo Russo FM, Ambrogi F, Gaetano C, De Cobelli F, Del Maschio A, Esposito A, Martelli F - PLoS ONE (2015)

Longitudinal profiles of MRI measurements through time.Time trend analysis of T2-rt, FA and K-trans levels for Gastrocnemius and Tibialis anterior muscles. All values were normalized to values measured in non-ischemic limbs. Mean observed (circle: Gastrocnemius; triangle: Tibialis anterior) and model estimates (continuous line: Gastrocnemius; broken line: Tibialis anterior) are reported. Vertical bars represents 95% confidence intervals according to the mixed regression model. Evidence of a different time trend between the two muscles was found for all MRI measurements (interaction with time T2-rt: p = 0.03; FA: p<0.001; K-trans: p = 0.03). Evidence of a non-linear trend was found for both FA and K-trans. The recovery rate of Tibialis anterior appeared always greater than that of Gastrocnemius. A) T2-rt (ischemic/contralateral*100); B) FA (ischemic/contralateral*100); C) K-trans [(Ischemic-controlateral)/controlateral*100].
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4640853&req=5

pone.0142111.g005: Longitudinal profiles of MRI measurements through time.Time trend analysis of T2-rt, FA and K-trans levels for Gastrocnemius and Tibialis anterior muscles. All values were normalized to values measured in non-ischemic limbs. Mean observed (circle: Gastrocnemius; triangle: Tibialis anterior) and model estimates (continuous line: Gastrocnemius; broken line: Tibialis anterior) are reported. Vertical bars represents 95% confidence intervals according to the mixed regression model. Evidence of a different time trend between the two muscles was found for all MRI measurements (interaction with time T2-rt: p = 0.03; FA: p<0.001; K-trans: p = 0.03). Evidence of a non-linear trend was found for both FA and K-trans. The recovery rate of Tibialis anterior appeared always greater than that of Gastrocnemius. A) T2-rt (ischemic/contralateral*100); B) FA (ischemic/contralateral*100); C) K-trans [(Ischemic-controlateral)/controlateral*100].
Mentions: To highlight these differences, the temporal trend of Tibialis anterior and Gastrocnemius muscles were normalized and directly compared (Fig 5). The longitudinal analysis of ischemic/contralateral T2-rt ratios provided evidence for a different temporal trend between Gastrocnemius and Tibialis anterior. T2-rt levels at day 1 were significantly different and then started to decrease, but at a rate about double for Tibialis anterior compared to Gastrocnemius muscle (Fig 5A). Likewise, a different temporal trend between Gastrocnemius and Tibialis anterior was found also for FA. The difference of the drop at day 1 of FA between Gastrocnemius and TA was statistically significant. When FA started to recover, the recovery rate of Tibialis anterior was always greater than that of Gastrocnemius and both rates attenuated after day 7 (Fig 5B). The longitudinal analysis of K-trans levels also provided evidence for a different temporal trend between Gastrocnemius and Tibialis anterior (Fig 5C).

Bottom Line: Interestingly, K-trans positively correlated with capillary density.Overall, Gastrocnemius and Tibialis anterior muscles displayed similar patterns of MRI parameters dynamic, with more marked responses and less variability in Tibialis anterior.We conclude that MRI provides quantitative information about both tissue damage after ischemia and the subsequent vascular and muscle regeneration, accounting for the differences between subjects and, within the same individual, between different muscles.

View Article: PubMed Central - PubMed

Affiliation: Molecular Cardiology Laboratory, IRCCS-Policlinico San Donato, San Donato Milanese, Milan, Italy.

ABSTRACT
Magnetic resonance imaging (MRI) provides non-invasive, repetitive measures in the same individual, allowing the study of a physio-pathological event over time. In this study, we tested the performance of 7 Tesla multi-parametric MRI to monitor the dynamic changes of mouse skeletal muscle injury and regeneration upon acute ischemia induced by femoral artery dissection. T2-mapping (T2 relaxation time), diffusion-tensor imaging (Fractional Anisotropy) and perfusion by Dynamic Contrast-Enhanced MRI (K-trans) were measured and imaging results were correlated with histological morphometric analysis in both Gastrocnemius and Tibialis anterior muscles. We found that tissue damage positively correlated with T2-relaxation time, while myofiber regeneration and capillary density positively correlated with Fractional Anisotropy. Interestingly, K-trans positively correlated with capillary density. Accordingly, repeated MRI measurements between day 1 and day 28 after surgery in ischemic muscles showed that: 1) T2-relaxation time rapidly increased upon ischemia and then gradually declined, returning almost to basal level in the last phases of the regeneration process; 2) Fractional Anisotropy dropped upon ischemic damage induction and then recovered along with muscle regeneration and neoangiogenesis; 3) K-trans reached a minimum upon ischemia, then progressively recovered. Overall, Gastrocnemius and Tibialis anterior muscles displayed similar patterns of MRI parameters dynamic, with more marked responses and less variability in Tibialis anterior. We conclude that MRI provides quantitative information about both tissue damage after ischemia and the subsequent vascular and muscle regeneration, accounting for the differences between subjects and, within the same individual, between different muscles.

No MeSH data available.


Related in: MedlinePlus