Evaluating tumors in transcatheter arterial chemoembolization (TACE) using dual-phase cone-beam CT.

C-arm cone-beam computed tomography (CBCT) can be used to visualize tumor-feeding vessels and parenchymal staining during transcatheter arterial chemoembolization (TACE). To capture these two phases, all current commercially available CBCT systems necessitate two separate contrast-enhanced scans. In this feasibility study, we report initial results of novel software that enhanced our current CBCT system to capture these two phases using only one contrast injection. Novelty of this work is the addition of software that enabled the acquisition of two sequential, back-to-back CBCT scans (dual-phase CBCT, DPCBCT) so both tumor feeding vessels and parenchyma are captured using only one contrast injection. To illustrate our initial experience, DPCBCT was used for TACE treatments involving lipiodol, drug-eluting beads, and Yttrium-90 radioembolizing microspheres. For each case, the DPCBCT images were compared to pre-intervention contrast-enhanced MR/CT. DPCBCT is feasible for TACE treatments and the preliminary results show positive correlation with pre-intervention conventional CT and MR. In addition, the degree of embolization can be monitored. DPCBCT is a promising technology that provides comprehensive visualization of tumor-feeding vessels and parenchymal staining using a single injection of contrast. DPCBCT could potentially be used during TACE to verify catheter position and monitor the embolization effect.

Percutaneous radiofrequency ablation of osteoid osteomas with use of real-time needle guidance for accurate needle placement: a pilot study.

PURPOSE: To evaluate the accuracy and technical success of positioning a radiofrequency ablation (RFA) electrode in osteoid osteomas by use of a new real-time needle guidance technology combining cone-beam computed tomography (CT) and fluoroscopy. MATERIALS AND METHODS: Percutaneous RFA of osteoid osteomas was performed in five patients (median age 18 years), under general anesthesia, with the use of cone-beam CT and fluoroscopic guidance for electrode positioning. The outcome parameters were technical success, meaning correct needle placement in the nidus; accuracy defined as the deviation (in mm) from the center of the nidus; and clinical outcome at follow-up. RESULTS: In all five cases, positioning was possible within 3 mm of the determined target location (median nidus size 6.8 mm; range 5-10.2 mm). All procedures were technically successful. All patients were free of pain at clinical follow-up. No complications were observed. CONCLUSION: Real-time fluoroscopy needle guidance based on cone-beam CT is a useful tool to accurately position radiofrequency needles for minimally invasive treatment of osteoid osteomas.

Hypoxia induces near-native mechanical properties in engineered heart valve tissue.

BACKGROUND: Previous attempts in heart valve tissue engineering (TE) failed to produce autologous valve replacements with native-like mechanical behavior to allow for systemic pressure applications. Because hypoxia and insulin are known to promote protein synthesis by adaptive cellular responses, a physiologically relevant oxygen tension and insulin supplements were applied to the growing heart valve tissues to enhance their mechanical properties. METHODS AND RESULTS: Scaffolds of rapid-degrading polyglycolic acid meshes coated with poly-4-hydroxybutyrate were seeded with human saphenous vein myofibroblasts. The tissue-engineered constructs were cultured under normal oxygen tension (normoxia) or hypoxia (7% O(2)) and incubated with or without insulin. Glycosaminoglycan production in the constructs approached that of native values under the influence of hypoxia and under the influence of insulin. Both insulin and hypoxia were associated with enhanced matrix production and improved mechanical properties; however, a synergistic effect was not observed. Although the amount of collagen and cross-links in the engineered tissues was still lower than that in native adult human aortic valves, constructs cultured under hypoxic conditions reached native human aortic valve levels of tissue strength and stiffness after 4 weeks of culturing. CONCLUSIONS: These results indicate that oxygen tension may be a key parameter for the achievement of sufficient tissue quality and mechanical integrity in tissue-engineered heart valves. Engineered tissues of such strength, based on rapid-degrading polymers, have not been achieved to date. These findings bring the potential use of tissue-engineered heart valves for systemic applications a step closer and represent an important improvement in heart valve tissue engineering.

Tailoring fiber diameter in electrospun poly(epsilon-caprolactone) scaffolds for optimal cellular infiltration in cardiovascular tissue engineering.

Despite the attractive features of nanofibrous scaffolds for cell attachment in tissue-engineering (TE) applications, impeded cell ingrowth has been reported in electrospun scaffolds. Previous findings have shown that the scaffold can function as a sieve, keeping cells on the scaffold surface, and that cell migration into the scaffold does not occur in time. Because fiber diameter is directly related to the pore size of an electrospun scaffold, the objective of this study was to systematically evaluate how cell delivery can be optimized by tailoring the fiber diameter of electrospun poly(epsilon-caprolactone) (PCL) scaffolds. Five groups of electrospun PCL scaffolds with increasing average fiber diameters (3.4-12.1 microm) were seeded with human venous myofibroblasts. Cell distribution was analyzed after 3 days of culture. Cell penetration increased proportionally with increasing fiber diameter. Unobstructed delivery of cells was observed exclusively in the scaffold with the largest fiber diameter (12.1 microm). This scaffold was subsequently evaluated in a 4-week TE experiment and compared with a poly(glycolic acid)-poly(4-hydroxybutyrate) scaffold, a standard scaffold used successfully in cardiovascular tissue engineering applications. The PCL constructs showed homogeneous tissue formation and sufficient matrix deposition. In conclusion, fiber diameter is a crucial parameter to allow for homogeneous cell delivery in electrospun scaffolds. The optimal electrospun scaffold geometry, however, is not generic and should be adjusted to cell size.

Stress related collagen ultrastructure in human aortic valves--implications for tissue engineering.

Understanding the response of tissue structures to mechanical stress is crucial for optimization of mechanical conditioning protocols in the field of heart valve tissue engineering. In heart valve tissue, it is unclear to what extent mechanical loading affects the collagen fibril morphology. To determine if local stress affects the collagen fibril morphology, in terms of fibril diameter, its distribution, and the fibril density, this was investigated in adult native human aortic valve leaflets. Transmission electron microscopy images of collagen fibrils were analyzed at three locations: the commissures, the belly, and the fixed edge of the leaflets. Subsequently, the mechanical behavior of human aortic valves was used in a computational model to predict the stress distribution in the valve leaflet during the diastolic phase of the cardiac cycle. The local stresses at the three locations were related to the collagen fibril morphology. The fibril diameter and density varied significantly between the measured locations, and appeared inversely related. The average fibril diameter increased from the fixed edge, to the belly, and to the commissures of the leaflets, while fibril density decreased. Interestingly, these differences corresponded well with the level of stress at the locations. The presented data showed that large tissue stress is associated with greater average fibril diameter, lower fibril density, and wider fibril size distribution compared with low stress locations in the leaflets. The findings here provide insight in the effect of mechanical loading on the collagen ultrastructure, and are valuable to improve conditioning protocols for tissue engineering.

The role of collagen cross-links in biomechanical behavior of human aortic heart valve leaflets--relevance for tissue engineering.

A major challenge in tissue engineering of functional heart valves is to determine and mimic the dominant tissue structures that regulate heart valve function and in vivo survival. In native heart valves, the anisotropic matrix architecture assures sustained and adequate functioning under high-pressure conditions. Collagen, being the main load-bearing matrix component, contributes significantly to the biomechanical strength of the tissue. This study investigates the relationship between collagen content, collagen cross-links, and biomechanical behavior in human aortic heart valve leaflets and in tissue-engineered constructs. In the main loading direction (circumferential) of native valve leaflets, a significant positive linear correlation between modulus of elasticity and collagen cross-link concentration was found, whereas no correlation between modulus of elasticity and collagen content was found. Similar findings were observed in tissue-engineered constructs, where cross-link concentration was higher for dynamically strained constructs then for statically cultured controls. These findings suggest a dominant role for collagen cross-links over collagen content with respect to biomechanical tissue behavior in human heart valve leaflets. They further suggest that dynamic tissue straining in tissue engineering protocols can enhance cross-link concentration and biomechanical function.