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An athymic rat model of cutaneous radiation injury designed to study human tissue-based wound therapy.

Rifkin LH, Stojadinovic S, Stewart CH, Song KH, Maxted MC, Bell MH, Kashefi NS, Speiser MP, Saint-Cyr M, Story MD, Rohrich RJ, Brown SA, Solberg TD - Radiat Oncol (2012)

Bottom Line: With the highest dose excluded due to contraction-related distortions, correlation between dose and average ulceration showed a stronger relationship (r = 0.895).Eight additional wounds created using 41.5 Gy all reached peak ulceration above 50%, with all healing significantly but incompletely by the 65-day endpoint.Similar models may be widely applicable and useful the development of novel therapies which may improve radiotherapy management over a broad clinical spectrum.

View Article: PubMed Central - HTML - PubMed

Affiliation: 1Department of Plastic and Reconstructive Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA.

ABSTRACT

Purpose: To describe a pilot study for a novel preclinical model used to test human tissue-based therapies in the setting of cutaneous radiation injury.

Methods: A protocol was designed to irradiate the skin of athymic rats while sparing the body and internal organs by utilizing a non-occlusive skin clamp along with an x-ray image guided stereotactic irradiator. Each rat was irradiated both on the right and the left flank with a circular field at a 20 cm source-to-surface distance (SSD). Single fractions of 30.4 Gy, 41.5 Gy, 52.6 Gy, 65.5 Gy, and 76.5 Gy were applied in a dose-finding trial. Eight additional wounds were created using the 41.5 Gy dose level. Each wound was photographed and the percentage of the irradiated area ulcerated at given time points was analyzed using ImageJ software.

Results: No systemic or lethal sequelae occurred in any animals, and all irradiated skin areas in the multi-dose trial underwent ulceration. Greater than 60% of skin within each irradiated zone underwent ulceration within ten days, with peak ulceration ranging from 62.1% to 79.8%. Peak ulceration showed a weak correlation with radiation dose (r = 0.664). Mean ulceration rate over the study period is more closely correlated to dose (r = 0.753). With the highest dose excluded due to contraction-related distortions, correlation between dose and average ulceration showed a stronger relationship (r = 0.895). Eight additional wounds created using 41.5 Gy all reached peak ulceration above 50%, with all healing significantly but incompletely by the 65-day endpoint.

Conclusions: We developed a functional preclinical model which is currently used to evaluate human tissue-based therapies in the setting of cutaneous radiation injury. Similar models may be widely applicable and useful the development of novel therapies which may improve radiotherapy management over a broad clinical spectrum.

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Related in: MedlinePlus

Schematic of rat irradiation. Under anesthesia, skin was held outward in an acrylic clamp and exposed to x-ray radiation. The beam was centered on the skin edge, traversing a semicircular skin fold. As a result, a circular area of skin was irradiated.
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Figure 1: Schematic of rat irradiation. Under anesthesia, skin was held outward in an acrylic clamp and exposed to x-ray radiation. The beam was centered on the skin edge, traversing a semicircular skin fold. As a result, a circular area of skin was irradiated.

Mentions: A protocol was designed to irradiate the skin of athymic rats while sparing the body and internal organs from significant damage, the setup is shown in Figure 1. The loose lateral skin was gently pulled away from the body and held outward in a clamp. The clamp was constructed from two acrylic sheets with the gripping surface lightly abraded to increase friction. Acrylic spacers maintained the distance between the sheets to at least 1.8 mm to prevent vascular occlusion and crush injury. The clamp contained six holes of 1 mm diameter drilled through both sheets along the border of a 20 mm diameter semicircle. The six radiolucent holes were visible throughout the image guidance process and provided outline of the skin to be irradiated. As indicated in Figure 1, the three holes forming the diameter of the semicircle were aligned with the edge of folded skin. Next, the x-ray beam was made coincident with the radiolucent holes using the image guidance system. Due to geometric divergence, the beam diameter at treatment distance was slightly larger (26.6 mm) than the diameter of the collimator (20 mm).


An athymic rat model of cutaneous radiation injury designed to study human tissue-based wound therapy.

Rifkin LH, Stojadinovic S, Stewart CH, Song KH, Maxted MC, Bell MH, Kashefi NS, Speiser MP, Saint-Cyr M, Story MD, Rohrich RJ, Brown SA, Solberg TD - Radiat Oncol (2012)

Schematic of rat irradiation. Under anesthesia, skin was held outward in an acrylic clamp and exposed to x-ray radiation. The beam was centered on the skin edge, traversing a semicircular skin fold. As a result, a circular area of skin was irradiated.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3403853&req=5

Figure 1: Schematic of rat irradiation. Under anesthesia, skin was held outward in an acrylic clamp and exposed to x-ray radiation. The beam was centered on the skin edge, traversing a semicircular skin fold. As a result, a circular area of skin was irradiated.
Mentions: A protocol was designed to irradiate the skin of athymic rats while sparing the body and internal organs from significant damage, the setup is shown in Figure 1. The loose lateral skin was gently pulled away from the body and held outward in a clamp. The clamp was constructed from two acrylic sheets with the gripping surface lightly abraded to increase friction. Acrylic spacers maintained the distance between the sheets to at least 1.8 mm to prevent vascular occlusion and crush injury. The clamp contained six holes of 1 mm diameter drilled through both sheets along the border of a 20 mm diameter semicircle. The six radiolucent holes were visible throughout the image guidance process and provided outline of the skin to be irradiated. As indicated in Figure 1, the three holes forming the diameter of the semicircle were aligned with the edge of folded skin. Next, the x-ray beam was made coincident with the radiolucent holes using the image guidance system. Due to geometric divergence, the beam diameter at treatment distance was slightly larger (26.6 mm) than the diameter of the collimator (20 mm).

Bottom Line: With the highest dose excluded due to contraction-related distortions, correlation between dose and average ulceration showed a stronger relationship (r = 0.895).Eight additional wounds created using 41.5 Gy all reached peak ulceration above 50%, with all healing significantly but incompletely by the 65-day endpoint.Similar models may be widely applicable and useful the development of novel therapies which may improve radiotherapy management over a broad clinical spectrum.

View Article: PubMed Central - HTML - PubMed

Affiliation: 1Department of Plastic and Reconstructive Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA.

ABSTRACT

Purpose: To describe a pilot study for a novel preclinical model used to test human tissue-based therapies in the setting of cutaneous radiation injury.

Methods: A protocol was designed to irradiate the skin of athymic rats while sparing the body and internal organs by utilizing a non-occlusive skin clamp along with an x-ray image guided stereotactic irradiator. Each rat was irradiated both on the right and the left flank with a circular field at a 20 cm source-to-surface distance (SSD). Single fractions of 30.4 Gy, 41.5 Gy, 52.6 Gy, 65.5 Gy, and 76.5 Gy were applied in a dose-finding trial. Eight additional wounds were created using the 41.5 Gy dose level. Each wound was photographed and the percentage of the irradiated area ulcerated at given time points was analyzed using ImageJ software.

Results: No systemic or lethal sequelae occurred in any animals, and all irradiated skin areas in the multi-dose trial underwent ulceration. Greater than 60% of skin within each irradiated zone underwent ulceration within ten days, with peak ulceration ranging from 62.1% to 79.8%. Peak ulceration showed a weak correlation with radiation dose (r = 0.664). Mean ulceration rate over the study period is more closely correlated to dose (r = 0.753). With the highest dose excluded due to contraction-related distortions, correlation between dose and average ulceration showed a stronger relationship (r = 0.895). Eight additional wounds created using 41.5 Gy all reached peak ulceration above 50%, with all healing significantly but incompletely by the 65-day endpoint.

Conclusions: We developed a functional preclinical model which is currently used to evaluate human tissue-based therapies in the setting of cutaneous radiation injury. Similar models may be widely applicable and useful the development of novel therapies which may improve radiotherapy management over a broad clinical spectrum.

Show MeSH
Related in: MedlinePlus