Development and reliability of a multi-modality scoring system for evaluation of disease progression in pre-clinical models of osteoarthritis: celecoxib may possess disease-modifying properties

SummaryObjectiveWe sought to develop a comprehensive scoring system for evaluation of pre-clinical models of osteoarthritis (OA) progression, and use this to evaluate two different classes of drugs for management of OA.MethodsPost-traumatic OA (PTOA) was surgically induced in skeletally mature rats. Rats were randomly divided in three groups receiving either glucosamine (high dose of 192 mg/kg) or celecoxib (clinical dose) or no treatment. Disease progression was monitored utilizing micro-magnetic resonance imaging (MRI), micro-computed tomography (CT) and histology. Pertinent features such as osteophytes, subchondral sclerosis, joint effusion, bone marrow lesion (BML), cysts, loose bodies and cartilage abnormalities were included in designing a sensitive multi-modality based scoring system, termed the rat arthritis knee scoring system (RAKSS).ResultsOverall, an inter-observer correlation coefficient (ICC) of greater than 0.750 was achieved for each scored feature. None of the treatments prevented cartilage loss, synovitis, joint effusion, or sclerosis. However, celecoxib significantly reduced osteophyte development compared to placebo. Although signs of inflammation such as synovitis and joint effusion were readily identified at 4 weeks post-operation, we did not detect any BML.ConclusionWe report the development of a sensitive and reliable multi-modality scoring system, the RAKSS, for evaluation of OA severity in pre-clinical animal models. Using this scoring system, we found that celecoxib prevented enlargement of osteophytes in this animal model of PTOA, and thus it may be useful in preventing OA progression. However, it did not show any chondroprotective effect using the recommended dose. In contrast, high dose glucosamine had no measurable effects

A Monte Carlo derived TG-51 equivalent calibration for helical tomotherapy

Helical tomotherapy (HT) requires a method of accurately determining the absorbed dose under reference conditions. In the AAPM's TG-51 external beam dosimetry protocol, the quality conversion factor, k Q, is presented as a function of the photon component of the percentage depth-dose at 10 cm depth, %dd(10) x, measured under the reference conditions of a 10 × 10 cm 2 field size and a source-to-surface distance (SSD) of 100 cm. The value of %dd(10) x from HT cannot be used for the determination of k Q because the design of the HT does not meet the following TG-51 reference conditions: (i) the field size and the practical SSD required by TG-51 are not obtainable and (ii) the absence of the flattening filter changes the beam quality thus affecting some components of k Q. The stopping power ratio is not affected because of its direct relationship to %dd(10) x. We derive a relationship for the Exradin A1SL ion chamber converting the %dd(10) x measured under HT "reference conditions" of SSD=85 cm and a 5 × 10 cm 2 field-size [%dd(10) x[HT Ref]], to the dosimetric equivalent value under for TG-51 reference conditions [%dd(10) x[HT TG-51]] for HT. This allows the determination of k Q under the HT reference conditions. The conversion results in changes of 0.1% in the value of k Q for our particular unit. The conversion relationship should also apply to other ion chambers with possible errors on the order of 0.1%

Evaluation of dose-volume metrics for microbeam radiation therapy dose distributions in head phantoms of various sizes using Monte Carlo simulations

International audiencehis work evaluates four dose-volume metrics applied to microbeam radiation therapy (MRT) using simulated dosimetric data as input. We seek to improve upon the most frequently used MRT metric, the peak-to-valley dose ratio (PVDR), by analyzing MRT dose distributions from a more volumetric perspective. Monte Carlo simulations were used to calculate dose distributions in three cubic head phantoms: a 2 cm mouse head, an 8 cm cat head and a 16 cm dog head. The dose distribution was calculated for a 4 × 4 mm2 microbeam array in each phantom, as well as a 16 × 16 mm2 array in the 8 cm cat head, and a 32 × 32 mm2 array in the 16 cm dog head. Microbeam widths of 25, 50 and 75 µm and center-to-center spacings of 100, 200 and 400 µm were considered. The metrics calculated for each simulation were the conventional PVDR, the peak-to-mean valley dose ratio (PMVDR), the mean dose and the percentage volume below a threshold dose. The PVDR ranged between 3 and 230 for the 2 cm mouse phantom, and between 2 and 186 for the 16 cm dog phantom depending on geometry. The corresponding ranges for the PMVDR were much smaller, being 2-49 (mouse) and 2-46 (dog), and showed a slightly weaker dependence on phantom size and array size. The ratio of the PMVDR to the PVDR varied from 0.21 to 0.79 for the different collimation configurations, indicating a difference between the geometric dependence on outcome that would be predicted by these two metrics. For unidirectional irradiation, the mean lesion dose was 102%, 79% and 42% of the mean skin dose for the 2 cm mouse, 8 cm cat and 16 cm dog head phantoms, respectively. However, the mean lesion dose recovered to 83% of the mean skin dose in the 16 cm dog phantom in intersecting cross-firing regions. The percentage volume below a 10% dose threshold was highly dependent on geometry, with ranges for the different collimation configurations of 2-87% and 33-96% for the 2 cm mouse and 16 cm dog heads, respectively. The results of this study illustrate that different dose-volume metrics exhibit different functional dependences on MRT geometry parameters, and suggest that reliance on the PVDR as a predictor of therapeutic outcome may be insufficient