Periostin and CCN2 Scaffolds Promote the Wound Healing Response in the Skin of Diabetic Mice.

IMPACT STATEMENT: Nonhealing skin wounds remain a significant burden on health care systems, with diabetic patients 20 times as likely to undergo a lower extremity amputation due to impaired healing. Novel treatments that suppress the proinflammatory signature and induce the proliferative and remodeling phases are needed clinically. We demonstrate that the addition of periostin and CCN2 in a scaffold form increases closure rates of full-thickness skin wounds in diabetic mice, concomitant with enhanced angiogenesis. Our results demonstrate the efficacy of periostin- and CCN2-containing biomaterials to stimulate wound closure, which could represent a novel method for the treatment of diabetic skin wounds.

Implementation and commissioning of an integrated micro-CT∕RT system with computerized independent jaw collimation.

PURPOSE: To design, construct, and commission a set of computer-controlled motorized jaws for a micro-CT∕RT system to perform conformal image-guided small animal radiotherapy. METHODS: The authors designed and evaluated a system of custom-built motorized orthogonal jaws, which allows the delivery of off-axis rectangular fields on a GE eXplore CT 120 preclinical imaging system. The jaws in the x direction are independently driven, while the y-direction jaws are symmetric. All motors have backup encoders, verifying jaw positions. Mechanical performance of the jaws was characterized. Square beam profiles ranging from 2×2 to 60×60 mm2 were measured using EBT2 film in the center of a 70×70×22 mm3 solid water block. Similarly, absolute depth dose was measured in a solid water and EBT2 film stack 50×50×50 mm3. A calibrated Farmer ion chamber in a 70×70×20 mm3 solid water block was used to measure the output of three field sizes: 50×50, 40×40, and 30×30 mm2. Elliptical target plans were delivered to films to assess overall system performance. Respiratory-gated treatment was implemented on the system and initially proved using a simple sinusoidal motion phantom. All films were scanned on a flatbed scanner (Epson 1000XL) and converted to dose using a fitted calibration curve. A Monte Carlo beam model of the micro-CT with the jaws has been created using BEAMnrc for comparison with the measurements. An example image-guided partial lung irradiation in a rat is demonstrated. RESULTS: The averaged random error of positioning each jaw is less than 0.1 mm. Relative output factors measured with the ion chamber agree with Monte Carlo simulations within 2%. Beam profiles and absolute depth dose curves measured from the films agree with simulations within measurement uncertainty. Respiratory-gated treatments applied to a phantom moving with a peak-to-peak amplitude of 5 mm showed improved beam penumbra (80%-20%) from 3.9 to 0.8 mm. CONCLUSIONS: A set of computer-controlled motorized jaws for a micro-CT∕RT system were constructed with position reliably better than a tenth of a millimeter. The hardware system is ready for image-guided conformal radiotherapy for small animals with capability of respiratory-gated delivery.

Contrast-enhanced microcomputed tomography using intraperitoneal contrast injection for the assessment of tumor-burden in liver metastasis models.

OBJECTIVES: To determine if intraperitoneally (IP) administered contrast (iohexol), used in conjunction with a liver-specific agent (Fenestra), can improve measurement precision and accuracy when quantifying tumor volume from micro-CT images of a liver metastasis model. MATERIALS AND METHODS: We compared images acquired with Fenestra alone to images acquired with the combination of Fenestra and IP iohexol. The variability in tumor volume and tumor-burden measurement was evaluated for both techniques. The tumor-burden measurement accuracy of both in vivo techniques was determined by comparison with tumor-burden quantified from ex vivo images. RESULTS: : The addition of IP iohexol decreased measurement variability for individual tumors and overall tumor-burden by 4-8 fold and 2-3 fold, respectively. IP iohexol significantly improved the accuracy of tumor-burden measurement for both low and high tumor-burdened animals. CONCLUSIONS: The combination of IP iohexol with Fenestra provides superior delineation of liver tumors, in comparison to Fenestra alone. The complete tumor delineation provided by this imaging strategy allows for noninvasive quantification of liver tumor-burden.

Assessment of intra- and interobserver variability of pulmonary vein measurements from CT angiography.

RATIONALE AND OBJECTIVES: Pulmonary vein (PV) stenosis is a common complication after radiofrequency ablation for atrial fibrillation. This study investigated the intra- and interobserver variability and precision of PV ostial measurements from three-dimensional computed tomography angiography. MATERIALS AND METHODS: Four observers measured the maximum and minimum diameters, as well as area, of the four PVs of seven patients who underwent a three-dimensional computed tomography scan before radiofrequency ablation. Each observer performed two sets of measurements. The intra- and interobserver variability of the measurements was calculated using analysis of variance. RESULTS: Intraobserver variability was approximately two times lower than interobserver variability in measurements of diameter and area. The standard error of the measurement (SEM), SEM(intra) and SEM(inter), were lower for the mean diameter than the maximum diameter. The minimum detectable changes in diameters, DeltaD(intra) and DeltaD(inter), and area, DeltaA(intra) and DeltaA(inter), demonstrated the same statistical trend as the corresponding SEM for each of the four veins. Both DeltaD(intra) and DeltaD(inter) and DeltaA(intra) and DeltaA(inter) were smaller than the corresponding lower bounds of the 95% confidence interval for 50% diameter reduction and 75% area reduction. The direct results of DeltaA(intra) and DeltaA(inter) for each of the four veins were consistently less than DeltaA's calculated from the corresponding DeltaD(intra) and DeltaD(inter). CONCLUSION: PV ostial measurements are less variable when made by a single observer than by multiple observers, and mean diameter measurements are more precise than a single, maximum diameter measurement. Both diameter and area measurements are capable of quantifying the mild PV stenosis. Furthermore, area can be measured with greater precision than mean diameter and should be used in PV ostium caliber determination.