RESUMO
Structural changes of soft tissues on the cellular level can be characterized by histopathology, but not longitudinally in the same tissue. Alterations of cellular structures and tissue matrix are associated with changes in biophysical properties which can be monitored longitudinally by quantitative diffusion-weighted imaging (DWI) and magnetic resonance elastography (MRE). In this work, DWI and MRE examinations were performed in a 0.5-Tesla compact scanner to investigate longitudinal changes in water diffusivity, stiffness and viscosity of ex-vivo rat livers for up to 20 h post-mortem (pm). The effect of blood on biophysical parameters was examined in 13 non-perfused livers (containing blood, NPLs) and 14 perfused livers (blood washed out, PLs). Changes in cell shape, cell packing and cell wall integrity were characterized histologically. In all acquisitions, NPLs presented with higher shear-wave speed (c), higher shear-wave penetration rate (a) and smaller apparent-diffusion-coefficients (ADCs) than PL. Time-resolved analysis revealed three distinct phases: (i) an initial phase (up to 2 h pm) with markedly increased c and a and reduced ADCs; (ii) an extended phase with relatively stable values; and (iii) a degradation phase characterized by significant increases in a (10 h pm in NPLs and PLs) and ADCs (10 h pm in NPLs, 13 h pm in PLs). Histology revealed changes in cell shape and packing along with decreased cell wall integrity, indicating tissue degradation in NPLs and PLs 10 h pm. Taken together, our results demonstrate that the biophysical properties of fresh liver tissue rapidly change within 2 h pm, which seems to be an effect of both cytotoxic edema and vascular blood content. Several hours later, disruption of cell walls resulted in higher water diffusivity and wave penetration. These results reveal the individual contributions of vascular components and cellular integrity to liver elastography and provide a biophysical, imaging-based fingerprint of liver tissue degradation.
RESUMO
During pregnancy, the body's hyperestrogenic state alters hepatic metabolism and synthesis. While biochemical changes related to liver function during normal pregnancy are well understood, pregnancy-associated alterations in biophysical properties of the liver remain elusive. In this study, we investigated 26 ex vivo fresh liver specimens harvested from pregnant and non-pregnant rats by diffusion-weighted imaging (DWI) and magnetic resonance elastography (MRE) in a 0.5-Tesla compact magnetic resonance imaging (MRI) scanner. Water diffusivity and viscoelastic parameters were compared with histological data and blood markers. We found livers from pregnant rats to have (i) significantly enlarged hepatocytes (26 ± 15%, p < 0.001), (ii) increased liver stiffness (12 ± 15%, p = 0.012), (iii) decreased viscosity (-23 ± 14%, p < 0.001), and (iv) increased water diffusivity (12 ± 11%, p < 0.001). In conclusion, increased stiffness and reduced viscosity of the liver during pregnancy are mainly attributable to hepatocyte enlargement. Hypertrophy of liver cells imposes fewer restrictions on intracellular water mobility, resulting in a higher hepatic water diffusion coefficient. Collectively, MRE and DWI have the potential to inform on structural liver changes associated with pregnancy in a clinical context.
RESUMO
PURPOSE: To experimentally investigate a new homogenously paclitaxel/resveratrol-coated balloon catheter in terms of transport of the coating to the treated tissue and local effects including histology and functional tests. METHODS: Adherence of the coating to the balloon was explored by in vitro simulation of its passage to the lesion. Paclitaxel and resveratrol transfer to the vessel wall was investigated in porcine coronary and peripheral arteries. Matrix-assisted laser desorption/ionization (MALDI) was used for direct microscopic visualization of paclitaxel in arterial tissue. Inhibition of neointimal proliferation and tolerance of complete coating and resveratrol-only coating was investigated in pigs 4 weeks after treatment, and the effect of resveratrol on inflammation and healing after 3 and 7 days. RESULTS: Drug loss on the way to the lesion was < 10% of dose, while 65 ± 13% was detected at the site of balloon inflation. After treatment similar proportions of drug were detected in coronary and peripheral arteries, i.e., 7.4 ± 4.6% of dose or 125 ± 74 ng/mg tissue. MALDI showed circumferential deposition. Inhibition of neointimal proliferation by paclitaxel/resveratrol coating was significant (p = 0.001) whereas resveratrol-only coating did not inhibit neointimal proliferation. During the first week after treatment of peripheral arteries with resveratrol-only balloons, we observed nominally less inflammation and fibrin deposition along with a significant macrophage reduction and more pronounced re-endothelialization. No safety issues emerged including left ventricular ejection fraction for detection of potential distal embolization after high-dose treatment of coronary arteries. CONCLUSIONS: Paclitaxel/resveratrol-coated balloons were effective and safe in animal studies. Beyond acting as excipient resveratrol may contribute to vascular healing.