scholarly journals Elastin-specific MRI of extracellular matrix-remodelling following hepatic radiofrequency-ablation in a VX2 liver tumor model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Federico Collettini ◽  
Carolin Reimann ◽  
Julia Brangsch ◽  
Julius Chapiro ◽  
Lynn Jeanette Savic ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Radiofrequency Ablation ◽  
Mr Imaging ◽  
Liver Tumor ◽  
Tumor Model ◽  
Elastic Fibers ◽  
Specific Probe ◽  
Left Liver Lobe ◽  
Ecm Remodeling ◽  
Icp Ms

AbstractHepatic radiofrequency ablation (RFA) induces a drastic alteration of the biomechanical environment in the peritumoral liver tissue. The resulting increase in matrix stiffness has been shown to significantly influence carcinogenesis and cancer progression after focal RF ablation. To investigate the potential of an elastin-specific MR agent (ESMA) for the assessment of extracellular matrix (ECM) remodeling in the periablational rim following RFA in a VX2 rabbit liver tumor-model, twelve New-Zealand-White-rabbits were implanted in the left liver lobe with VX2 tumor chunks from donor animals. RFA of tumors was performed using a perfused RF needle-applicator with a mean tip temperature of 70 °C. Animals were randomized into four groups for MR imaging and scanned at four different time points following RFA (week 0 [baseline], week 1, week 2 and week 3 after RFA), followed by sacrifice and histopathological analysis. ESMA-enhanced MR imaging was used to assess ECM remodeling. Gadobutrol was used as a third-space control agent. Molecular MR imaging using an elastin-specific probe demonstrated a progressive increase in contrast-to-noise ratio (CNR) (week 3: ESMA: 28.1 ± 6.0; gadobutrol: 3.5 ± 2.0), enabling non-invasive imaging of the peritumoral zone with high spatial-resolution, and accurate assessment of elastin deposition in the periablational rim. In vivo CNR correlated with ex vivo histomorphometry (ElasticaVanGiesson-stain, y = 1.2x − 1.8, R2 = 0.89, p < 0.05) and gadolinium concentrations at inductively coupled mass spectroscopy (ICP-MS, y = 0.04x + 1.2, R2 = 0.95, p < 0.05). Laser-ICP-MS confirmed colocalization of elastin-specific probe with elastic fibers. Following thermal ablation, molecular imaging using an elastin-specific MR probe is feasible and provides a quantifiable biomarker for the assessment of the ablation-induced remodeling of the ECM in the periablational rim.

scholarly journals Assessment of the hepatic tumor extracellular matrix using elastin-specific molecular magnetic resonance imaging in an experimental rabbit cancer model

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Sarah Keller ◽  
Tabea Borde ◽  
Julia Brangsch ◽  
Carolin Reimann ◽  
Avan Kader ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Extracellular Matrix ◽  
Magnetic Resonance ◽  
Mixed Model ◽  
Ex Vivo ◽  
Elastic Fibers ◽  
Specific Probe ◽  
Cancer Model ◽  
Resonance Imaging ◽  
Icp Ms

AbstractTo investigate the imaging performance of an elastin-specific molecular magnetic resonance imaging (MRI) probe with respect to the extracellular matrix (ECM) in an experimental hepatic cancer model. Twelve rabbits with hepatic VX2 tumors were examined using 3 T MRI 14, 21, and 28 days after tumor implantation for two subsequent days (gadobutrol, day 1; elastin-specific probe, day 2). The relative enhancement (RE) of segmented tumor regions (central and margin) and the peritumoral matrix was calculated using pre-contrast and delayed-phase T1w sequences. MRI measurements were correlated to histopathology and element-specific and spatially resolved mass spectrometry (MS). Mixed-model analysis was performed to assess the performance of the elastin-specific probe. In comparison to gadobutrol, the elastin probe showed significantly stronger RE, which was pronounced in the tumor margin (day 14–28: P ≤ 0.007). In addition, the elastin probe was superior in discriminating between tumor regions (χ2(4) = 65.87; P < 0.001). MRI-based measurements of the elastin probe significantly correlated with the ex vivo elastinstain (R = .84; P <0 .001) and absolute gadolinium concentrations (ICP-MS: R = .73, P <0 .01). LA-ICP-MS imaging confirmed the colocalization of the elastin-specific probe with elastic fibers. Elastin-specific molecular MRI is superior to non-specific gadolinium-based contrast agents in imaging the ECM of hepatic tumors and the peritumoral tissue.

Liver Tumor Model with Implanted Rhabdomyosarcoma in Rats: MR Imaging, Microangiography, and Histopathologic Analysis

Radiology ◽  
2006 ◽  
Vol 239 (2) ◽  
pp. 554-562 ◽  
Author(s):  
Feng Chen ◽  
Xihe Sun ◽  
Frederik De Keyzer ◽  
Jie Yu ◽  
Ronald Peeters ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Liver Tumor ◽  
Tumor Model ◽  
Histopathologic Analysis

Design of a Novel Electrode of Radiofrequency Ablation for Large Tumors: In Vitro Validation and Evaluation

2019 ◽  
Vol 141 (3) ◽  
Author(s):  
Zheng Fang ◽  
Micheal A. J. Moser ◽  
Edwin Zhang ◽  
Wenjun Zhang ◽  
Bing Zhang
Keyword(s):  
Computer Simulation ◽  
Radiofrequency Ablation ◽  
Liver Tumor ◽  
Tumor Model ◽  
Egg White ◽  
Large Tumor ◽  
Ablation Volume ◽  
Conventional Electrode

In a prior study, we proposed a novel monopolar expandable electrode (MEE) for use in radiofrequency ablation (RFA). The purpose of our work was to now validate and evaluate this electrode using on in vitro experimental model and computer simulation. Two commercially available RF electrodes (conventional electrode (CE) and umbrella electrode (UE)) were used to compare the ablation results with the novel MEE using an in vitro egg white model and in vivo liver tumor model to verify the efficacy of MEE in the large tumor ablation, respectively. The sharp increase in impedance during RFA procedures was taken as the termination of RFA protocols. In the in vitro egg white experiment, the ablation volume of MEE, CE, and UE was 75.3 ± 1.6 cm3, 2.7 ± 0.4 cm3, and 12.4±1.8 cm3 (P < 0.001), respectively. Correspondingly, the sphericity was 88.1±0.9%, 12.9±1.3%, and 62.0 ± 3.0% (P < 0.001), respectively. A similar result was obtained in the in vitro egg white computer simulation. In the liver tumor computer simulation, the volume and sphericity of ablation zone generated by MEE, CE, and UE were 36.6 cm3 and 93.6%, 3.82 cm3 and 16.9%, and 13.5 cm3 and 56.7%, respectively. In summary, MEE has the potential to achieve complete ablation in the treatment of large tumors (>3 cm in diameter) compared to CE and UE due to the larger electrode–tissue interface and more round shape of hooks.

scholarly journals Structural Remodeling of the Extracellular Matrix in Arteriogenesis: A Review

2021 ◽  
Vol 8 ◽  
Author(s):  
Rohan Kulkarni ◽  
Elizabeth Andraska ◽  
Ryan McEnaney
Keyword(s):  
Extracellular Matrix ◽  
Mesenteric Artery ◽  
Arterial Occlusion ◽  
Elastic Fibers ◽  
Pressure Gradients ◽  
Internal Elastic Lamina ◽  
Ecm Remodeling ◽  
Vessel Stenosis ◽  
Flow Through ◽  
Collateral Formation

Lower extremity arterial occlusive disease (AOD) results in significant morbidity and mortality for the population, with up to 10% of patients ultimately requiring amputation. An alternative method for non-surgical revascularization which is yet to be fully understood is the optimization of the body's own natural collateral arterial network in a process known as arteriogenesis. Under conditions of conductance vessel stenosis or occlusion resulting in increased flow, shear forces, and pressure gradients within collaterals, positive remodeling occurs to increase the diameter and capacity of these vessels. The creation of a distal arteriovenous fistula (AVF) will drive increased arteriogenesis as compared to collateral formation with the occlusion of a conductance vessel alone by further increasing flow through these arterioles, demonstrating the capacity for arteriogenesis to form larger, more efficient collaterals beyond what is spontaneously achieved after arterial occlusion. Arteries rely on an extracellular matrix (ECM) composed of elastic fibers and collagens that provide stability under hemodynamic stress, and ECM remodeling is necessary to allow for increased diameter and flow conductance in mature arterial structures. When positive remodeling occurs, digestion of lamella and the internal elastic lamina (IEL) by matrix metalloproteinases (MMPs) and other elastases results in the rearrangement and thinning of elastic structures and may be replaced with disordered elastin synthesis without recovery of elastic function. This results in transmission of wall strain to collagen and potential for aneurysmal degeneration along collateral networks, as is seen in the pancreaticoduodenal artery (PDA) after celiac occlusion and inferior mesenteric artery (IMA) with concurrent celiac and superior mesenteric artery (SMA) occlusions. Further understanding into the development of collaterals is required to both better understand aneurysmal degeneration and optimize collateral formation in AOD.

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