Activation of hip prostheses in high energy radiotherapy and resultant dose to nearby tissue.

High energy radiotherapy can produce contaminant neutrons through the photonuclear effect. Patients receiving external beam radiation therapy to the pelvis may have high-density hip prostheses. Metallic materials such as those in hip prostheses, often have high cross-sections for neutron interaction. In this study, Thackray (UK) prosthetic hips have been irradiated by 18 MV radiotherapy beams to evaluate the additional dose to patients from the activation products. Hips were irradiated in- and out-of field at various distances from the beam isocenter to assess activation caused in-field by photo-activation, and neutron activation which occurs both in and out-of-field. NaI(Tl) scintillator detectors were used to measure the subsequent gamma-ray emissions and their half-lives. High sensitivity Mg, Cu, P doped LiF thermoluminescence dosimeter chips (TLD-100H) were used to measure the subsequent dose at the surface of a prosthesis over the 12 h following an in-field irradiation of 10,000 MU to a hip prosthesis located at the beam isocenter in a water phantom. 53 Fe, 56 Mn, and 52 V were identified within the hip following irradiation by radiotherapy beams. The dose measured at the surface of a prosthesis following irradiation in a water phantom was 0.20 mGy over 12 h. The dose at the surface of prostheses irradiated to 200 MU was below the limit of detection (0.05 mGy) of the TLD100H. Prosthetic hips are activated by incident photons and neutrons in high energy radiotherapy, however, the dose resulting from activation is very small.

The Importance of Quasi-4D Path-Integrated Dose Accumulation for More Accurate Risk Estimation in Stereotactic Liver Radiotherapy.

Intrafraction organ deformation may be accounted for by inclusion of temporal information in dose calculation models. In this article, we demonstrate a quasi-4-dimensional method for improved risk estimation. Conventional 3-dimensional and quasi-4-dimensional calculations employing dose warping for dose accumulation were undertaken for patients with liver metastases planned for 42 Gy in 6 fractions of stereotactic body radiotherapy. Normal tissue complication probabilities and stochastic risks for radiation-induced carcinogenesis and cardiac complications were evaluated for healthy peripheral structures. Hypothetical assessments of other commonly employed dose/fractionation schedules on normal tissue complication probability estimates were explored. Conventional 3-dimensional dose computation may result in significant under- or overestimation of doses to organ at risk. For instance, doses differ (on average) by 17% (σ = 14%) for the left kidney, by 14% (σ = 7%) for the right kidney, by 7% (σ = 9%) for the large bowel, and by 10% (σ = 14%) for the duodenum. Discrepancies in the excess relative risk range up to about 30%. The 3-dimensional approach was shown to result in cardiac complication risks underestimated by >20%. For liver stereotactic body radiotherapy, we have shown that conventional 3-dimensional dose calculation may significantly over-/underestimate dose to organ at risk (90%-120% of the 4-dimensional estimate for the mean dose and 20%-150% for D2%). Providing dose estimates that most closely represent the actual dose delivered will provide valuable information to improve our understanding of the dose response for partial volume irradiation using hypofractionated schedules. Excess relative risks of radiocarcinogenesis were shown to range up to approximately excess relative risk = 4 and the prediction thereof depends greatly on the use of either 3-dimensional or 4-dimensional methods (with corresponding results differing by tens of percent).

Evaluation of dosimetric misrepresentations from 3D conventional planning of liver SBRT using 4D deformable dose integration.

The purpose of this study is to evaluate dosimetric errors in 3D conventional plan- ning of stereotactic body radiotherapy (SBRT) by using a 4D deformable image registration (DIR)-based dose-warping and integration technique. Respiratory- correlated 4D CT image sets with 10 phases were acquired for four consecutive patients with five liver tumors. Average intensity projection (AIP) images were used to generate 3D conventional plans of SBRT. Quasi-4D path-integrated dose accumulation was performed over all 10 phases using dose-warping techniques based on DIR. This result was compared to the conventional plan in order to evalu- ate the appropriateness of 3D (static) dose calculations. In addition, we consider whether organ dose metrics derived from contours defined on the average intensity projection (AIP), or on a reference phase, provide the better approximation of the 4D values. The impact of using fewer (< 10) phases was also explored. The AIP- based 3D planning approach overestimated doses to targets by 1.4% to 8.7% (mean 4.2%) and underestimated dose to normal liver by up to 8% (mean -5.5%; range -2.3% to -8.0%), compared to the 4D methodology. The homogeneity of the dose distribution was overestimated when using conventional 3D calculations by up to 24%. OAR doses estimated by 3D planning were, on average, within 10% of the 4D calculations; however, differences of up to 100% were observed. Four-dimensional dose calculation using 3 phases gave a reasonable approximation of that calculated from the full 10 phases for all patients, which is potentially useful from a workload perspective. 4D evaluation showed that conventional 3D planning on an AIP can significantly overestimate target dose (ITV and GTV+5mm), underestimate normal liver dose, and overestimate dose homogeneity. Implementing nonadaptive quasi- 4D dose calculation can highlight the potential limitation of 3D conventional SBRT planning and the resultant misrepresentations of dose in some regions affected by motion and deformation. Where the 4D approach is unavailable, contouring on the full expiration phase may yield more accurate dose calculations, most relevant in the case of the healthy liver, but the absolute dose differences are in general small for the other healthy organs. The technique has the potential to quantify under- and over-dosage and improve treatment plan evaluation, retrospective plan analysis, and clinical outcome correlation. 

Consideration of the radiation dose delivered away from the treatment field to patients in radiotherapy.

Radiation delivery to cancer patients for radiotherapy is invariably accompanied by unwanted radiation to other parts of the patient's body. Traditionally, considerable effort has been made to calculate and measure the radiation dose to the target as well as to nearby critical structures. Only recently has attention been focused also on the relatively low doses that exist far from the primary radiation beams. In several clinical scenarios, such doses have been associated with cardiac toxicity as well as an increased risk of secondary cancer induction. Out-of-field dose is a result of leakage and scatter and generally difficult to predict accurately. The present review aims to present existing data, from measurements and calculations, and discuss its implications for radiotherapy.

A contemporary review of stereotactic radiotherapy: inherent dosimetric complexities and the potential for detriment.

OBJECTIVE: The advantages of highly localised, conformal treatments achievable with stereotactic radiotherapy (SRT) are increasingly being extended to extracranial sites as stereotactic body radiotherapy with advancements in imaging and beam collimation. One of the challenges in stereotactic treatment lies in the significant complexities associated with small field dosimetry and dose calculation. This review provides a comprehensive overview of the complexities associated with stereotactic radiotherapy and the potential for detriment. METHODS: This study is based on a comprehensive review of literature accessible via PubMed and other sources, covering stereotactic radiotherapy, small-field dosimetry and dose calculation. FINDINGS: Several key issues were identified in the literature. They pertain to dose prescription, dose measurement and dose calculation within and beyond the treatment field. Field-edge regions and penumbrae occupy a significant portion of the total field size. Spectral and dosimetric characteristics are difficult to determine and are compounded by effects of tissue inhomogeneity. Measurement of small-fields is made difficult by detector volume averaging and energy response. Available dosimeters are compared, and emphasis is given to gel dosimetry which offers the greatest potential for three-dimensional small-field dosimetry. The limitations of treatment planning system algorithms as applied to small-fields (particularly in the presence of heterogeneities) is explained, and a review of Monte Carlo dose calculation is provided, including simplified treatment planning implementations. Not incorporated into treatment planning, there is evidence that far from the primary field, doses to patients (and corresponding risks of radiocarcinogenesis) from leakage/scatter in SRT are similar to large fields. CONCLUSIONS: Improved knowledge of dosimetric issues is essential to the accurate measurement and calculation of dose as well as the interpretation and assessment of planned and delivered treatments. This review highlights such issues and the potential benefit that may be gained from Monte Carlo dose calculation and verification via three-dimensional dosimetric methods (such as gel dosimetry) being introduced into routine clinical practice.

Assessment of out-of-field doses in radiotherapy of brain lesions in children.

PURPOSE: To characterize the out-of-field doses in pediatric radiotherapy and to identify simple methods by which out-of-field dose might be minimized, with a view to reducing the risk of secondary cancers. METHODS AND MATERIALS: With the aim of characterizing the peripheral doses under different treatment conditions, the dose measurements in an anthropomorphic child phantom were taken in various organs and critical structures outside the primary field using thermoluminescent dosimetry. The doses from a Varian 600C and Varian Trilogy linear accelerator, both at 6 MV, were investigated. RESULTS: Larger field sizes have been shown to result in greater peripheral doses close to the primary beam, with the difference becoming less significant at large distances, indicating that most of out-of-field doses result from head leakage and collimator scatter>40 cm from the primary field. The use of lead shields has been shown to reduce the absorbed dose resulting from leakage. Aligning the craniocaudal axis of the patient with the x-plane of the collimator resulted in a dose reduction of 40%, for both machines. Out-of-field doses from the Varian Trilogy were shown to be approximately 40% greater than those from the 600C linear accelerator, despite being operated at the same energy. CONCLUSION: Out-of-field doses to pediatric patients can be minimized by using simple treatment options, such as using the single-energy mode linear accelerator rather than the multimode, orienting the couch and collimator such that the patient lies along the x-plane and avoiding fields directed along the trunk of the body.

An SIR epidemic model with partial temporary immunity modeled with delay.

The SIR epidemic model for disease dynamics considers recovered individuals to be permanently immune, while the SIS epidemic model considers recovered individuals to be immediately resusceptible. We study the case of temporary immunity in an SIR-based model with delayed coupling between the susceptible and removed classes, which results in a coupled set of delay differential equations. We find conditions for which the endemic steady state becomes unstable to periodic outbreaks. We then use analytical and numerical bifurcation analysis to describe how the severity and period of the outbreaks depend on the model parameters.

Inflammatory lipoproteins purified from a toxigenic and arthritogenic strain of Mycoplasma arthritidis are dependent on Toll-like receptor 2 and CD14.

Mycoplasma arthritidis is a naturally occurring murine pathogen, and the disease model has been used extensively to understand inflammatory mechanisms. Recently, Triton X-114 extracts of a virulent strain of M. arthritidis were found to be more potent in activating macrophages than were those from an avirulent strain, suggesting a role in disease. Here, octyl glucoside extraction of cells was used to identify four distinct bioactive moieties, with molecular masses of approximately 41, 37, 34, and 17 kDa. Their bioactivities were resistant to proteinase K but were destroyed by alkaline hydrolysis and oxidation. As for MALP-2, all were dependent upon Toll-like receptor 2, but unlike MALP-2, they were also dependent upon CD14. The M. arthritidis lipoproteins exhibited infrared absorbances at 2,900 cm(-1) and 1,662 cm(-1), similar to those seen in Pam(3)-Cys-Ser-(Lys)(4). Edman degradation failed to reveal N-terminal sequences, suggesting that they were blocked and therefore might be triacylated. However, mass spectrometry of fragments revealed that the 41-kDa moiety, which binds to serum apolipoprotein A-1, had similarity with the recently described MlpD lipoprotein of M. arthritidis.

Microscopy analysis of breast implant rupture caused by surgical instrument damage.

BACKGROUND: The mechanism of breast implant rupture has continued to be an important topic throughout the plastic surgery community and regulatory agencies, such as the US Food and Drug Administration. Retrieved ruptured implants returned to Allergan (Santa Barbara, CA; formerly Inamed Corporation) for analysis exhibit various modes of failure, which can include a small pinhole (approximately 1 to 2 mm in size) in the shell, a ruptured shell, or a severely fragmented shell. OBJECTIVE: The failure mechanisms and associated morphologic features for the modes of implant failure can be quite different. The objective of this study is to analyze and describe the rupture characteristics of silicone gel-filled implants that failed because of surgical instrument damage. METHODS: There are several types of diagnostic techniques available to analyze ruptured implants. Visual inspection, physical examination, and photographic analysis provided an overall description of the implant shape and gross features of the shell failure region. These techniques allowed categorization and documentation of the mode of failure and were quite useful as a supplemental tool in the diagnosis of implant failure mechanisms. Microscopy techniques provided details of the ruptured shell region and could be used to determine the cause of breast implant failure. This study involved the use of optical microscopy and scanning electron microscopy in the analysis of ruptured breast implants. RESULTS: Details of the geometry of ruptured shell regions are described. Illustrations are also presented in which 35-mm photography is used to assist in substantiating the cause of failure. Many of the ruptured regions exhibit striations across the thickness of the shell. Micrographs are presented that clearly show that the striations are due to lines in the cutting surface of the surgical instrument that were formed during the manufacturing process. CONCLUSIONS: This article demonstrates that, with the proper background and experience in analyzing ruptured breast implant shells, the features at the failure site can be correctly interpreted and the corresponding failure mechanisms can be diagnosed. Breast implants are subject to surgical instrument damage during implantation, and this damage can develop into a shell rupture, with the failure mode identifiable via microscopy analysis.

A microbial TLR2 agonist imparts macrophage-activating ability to apolipoprotein A-1.

There is increasing epidemiologic evidence implying a role for chronic infection in atherosclerosis and that microbial TLR agonists may contribute to this disease. Mycoplasma arthritidis is an agent of acute and chronic inflammatory disease in rodents, and has been used extensively as a model for defining the mechanisms involved in arthritis and other inflammatory diseases. We have purified a 28-kDa, apolipoprotein A-1 (apoA-1)-like TLR2-dependent macrophage-activating moiety from a culture of a virulent strain of M. arthritidis. ApoA-1 similarly isolated from uninoculated mycoplasma medium was without bioactivity. The activity of the mycoplasma-derived molecule was resistant to heat and to digestion with proteinase K, but was susceptible to alkaline hydrolysis and H(2)O(2) oxidation. Infrared profiles of normal apoA-1 and that derived from mycoplasma were distinct. Unlike the activity of other mycoplasmal TLR2 agonists such as macrophage-activating lipopeptide-2, activity of the M. arthritidis-derived 28-kDa component was dependent upon CD14, a coreceptor for LPS. Finally, we showed that bioactive lipopeptides prepared from M. arthritidis grown in serum-free medium and also from a 41-kDa known bioactive lipoprotein of M. arthritidis, avidly bound to purified apoA-1 that separated out by SDS-PAGE, induced TNF-alpha and IL-12p40 both in vitro and in vivo. ApoA-1 is a key functional component of the high-density lipoprotein cholesterol complex by scavenging and removing unwanted lipids. Our finding that this molecule can acquire macrophage-activating properties from microbial TLR2-dependent agonists suggests a novel mechanism whereby some microbial agents might reverse the protective role of apoA-1, thus contributing to the genesis of atherosclerosis.

Morphology of breast implant fold flaw failure.

The percent of modern silicone gel breast implants that fail due to shell rupture is quite low, amounting to less than 1% per year. Nonetheless, extensive retrieval and analysis studies are being conducted on failed devices returned to Allergan Medical (formerly Inamed Corporation) in order to determine the modes and causes of failure. With the modes and causes known, solutions can be implemented to eliminate the failure mechanisms. Analyses conducted thus far have demonstrated that there are several causes of breast implant failure. The focus of this paper is on one type of silicone gel breast implant failure, i.e., a failure associated with a fold or wrinkle, which is termed "fold flaw failure." Although fold flaw failure is not a dominant mode of failure for silicone gel breast implants, its failure characteristics must be understood in order for this type of shell rupture to be detected and eventually eliminated. In this study, optical microscopy and scanning electron microscopy are used to describe the morphology of fold flaw failure for explanted silicone gel breast implants with smooth shells. The microscopy analysis demonstrates that there are several different types of shell failure patterns that can be produced by a fold or wrinkle in a silicone gel breast implant.