The distribution of fibronectin in developing zebrafish (Danio rerio) cartilage

The extracellular matrix (ECM) plays a complex and vital role throughout the process of cartilage formation. Fibronectin is a large ECM glycoprotein with an important role in various developmental processes, including skeletogenesis. Taking advantage of the known sequence of cartilage development in zebrafish and using an immunohistochemical stain for collagen type II to identify differentiation phase cartilage, we evaluate the distribution of fibronectin in various cartilaginous elements of the zebrafish (elements of the splanchnocranium, and of the dorsal, caudal, pelvic and pectoral fins). Contrary to what is observed in tetrapods, our data on zebrafish indicate the apparent lack of fibronectin during the condensation phase of cartilage development. This lack is possibly linked to the high developmental rate of the zebrafish and the small size of the condensations, which brings different needs for the extracellular environment to ensure cell survival. Furthermore, the fin disk cartilage of the pectoral fin develops an ECM with a strong fibronectin signal, whereas other cartilage elements show only a weak fibronectin signal in early differentiation, which gradually disappears. Thus, the pectoral fin disk cartilage is unique not only because of its specific way of development (subdivision of a continuous plate into four elements, the proximal radials), but also because of its strong fibronectin-positive ECM

Predicting and implications of target volume changes of brain metastases during fractionated stereotactic radiosurgery

a b s t r a c t: Objective: To study the impact of target volume changes in brain metastases during fractionated stereotactic radiosurgery (fSRS) and identify patients that benefit from MRI guidance. Material and methods: For 15 patients (18 lesions) receiving fSRS only (fSRSonly) and 19 patients (20 lesions) receiving fSRS postoperatively (fSRSpostop), a treatment planning MRI (MR0) and repeated MRI during treatment (MR1) were acquired. The impact of target volume changes on the target coverage was analyzed by evaluating the planned dose distribution (based on MR0) on the planning target volume (PTV) during treatment as defined on MR1. The predictive value of target volume changes before treatment (using the diagnostic MRI (MRD)) was studied to identify patients that experienced the largest changes during treatment. Results: Target volume changes during fSRS did result in large declines of the PTV dose coverage up to 34.8% (median = 3.2%) for fSRSonly patients. For fSRSpostop the variation and declines were smaller (median PTV dose coverage change = 0.5% ( 4.5% to 1.9%)). Target volumes changes did also impact the minimum dose in the PTV (fSRSonly; 2.7 Gy ( 16.5 to 2.3 Gy), fSRSpostop; 0.4 Gy ( 4.2 to 2.5 Gy)). Changes in target volume before treatment (i.e. seen between the MRD and MR0) predicted which patients experienced the largest dose coverage declines during treatment. Conclusion: Target volume changes in brain metastases during fSRS can result in worsening of the target dose coverage. Patients benefiting the most from a repeated MRI during treatment could be identified before treatment

Significant tumor shift in patients treated with stereotactic radiosurgery for brain metastasis

Introduction: Linac-based stereotactic radiosurgery (SRS) for brain metastases may be influenced by the time interval between treatment preparation and delivery, related to risk of anatomical changes. We studied tumor position shifts and its relations to peritumoral volume edema changes over time, as seen on MRI. Methods: Twenty-six patients who underwent SRS for brain metastases in our institution were included. We evaluated the occurrence of a tumor shift between the diagnostic MRI and radiotherapy planning MRI. For 42 brain metastases the tumor and peritumoral edema were delineated on the contrast enhanced T1weighted and FLAIR images of both the diagnostic MRI and planning MRI examinations. Centre of Mass (CoM) shifts and tumor borders were evaluated. We evaluated the influence of steroids on peritumoral edema and tumor volume and the correlation with CoM and tumor border changes. Results: The median values of the CoM shifts and of the maximum distances between the tumor borders obtained from the diagnostic MRI and radiotherapy planning MRI were 1.3 mm (maximum shift of 5.0 mm) and 1.9 mm (maximum distance of 7.4 mm), respectively. We found significant correlations between the absolute change in edema volume and the tumor shift of the CoM (p < 0.001) and tumor border (p = 0.040). Patients who received steroids did not only had a decrease in peritumoral edema, but also had a median decrease in tumor volume of 0.02 cc while patients who did not receive steroids had a median increase of 0.06 cc in tumor volume (p = 0.035). Conclusion: Our results show that large tumor shifts of brain metastases can occur over time. Because shifts may have a significant impact on the local dose coverage, we recommend minimizing the time between treatment preparation and delivery for Linac based SRS