Dosimetry of source stepping for intravascular brachytherapy

Purpose: Both β and γ sources of fixed length are currently used in the catheter-based intravascular brachytherapy (IVBT). Source stepping is often used to treat a lesion longer than the effective treatment length of the source. A major challenge for the stepping procedure is to attain a perfect dosimetric match (uniform dose) at the source junction. This work presents a quantitative and systematic dosimetric analysis for source stepping during an IVBT procedure. Materials and Methods: The three most commonly used β and γ sources (¹⁹²Ir by BEST, ⁹⁰Sr by NOVOSTE and ³²P by Guidant) were studied using the EGSnrc Monte Carlo code. Dose distributions were calculated for a perfect end-to-end match and for a range of end-to-end gaps and overlaps between consecutive steps. Results: It is found that a perfect end-to-end match during source stepping yields uniform dose distribution in the region of source junction. The doses in the case of a mismatch (in the presence of an end-to-end gap or overlap) were found to be significantly different from those with the perfect end-to-end match. The dose deviation depends on the size of the gap or overlap, radial distance and type of source. The dose deviation decreases with radial distance for a given gap/overlap. For example, for a gap/overlap of 2 mm, dose decreases/increases of 30%, 55% and 60% were found at the radial distance of 2 mm from source for ¹⁹²Ir, ⁹⁰Sr and ³²P, respectively. These dose deviations are reduced by approximately 10% when the radial distance increases from 2 to 3 mm. The dose deviations for gaps or overlaps in the range of 0–5 mm are presented. Conclusions: During an IVBT procedure involving source stepping, a perfect end-to-end match is always desired. Significant underdosing or overdosing can occur in the case of a source mismatch. A considerable caution should be exercised to ensure that sources are properly matched.     

A Monte Carlo approach to small-scale dosimetry of solid tumour microvasculature for nuclear medicine therapies with 223Ra-, 131I-, 177Lu- and 111In-labelled radiopharmaceuticals

The small-scale dosimetry of radionuclides in solid-tumours is directly related to the intra-tumoral distribution of the administered radiopharmaceutical, which is affected by its egress from the vasculature and dispersion within the tumour. The aim of the present study was to evaluate the combined dosimetric effects of radiopharmaceutical distribution and range of the emitted radiation in a model of tumour microvasculature.We developed a computational model of solid-tumour microenvironment around a blood capillary vessel, and we simulated the transport of radiation emitted by ²²³Ra, ¹¹¹In, ¹³¹I and ¹⁷⁷Lu using the GEANT4 Monte Carlo. For each nuclide, several models of radiopharmaceutical dispersion throughout the capillary vessel were considered.Radial dose profiles around the capillary vessel, the Initial Radioactivity (IR) necessary to deposit 100 Gy of dose at the edge of the viable tumour-cell region, the Endothelial Cell Mean Dose (ECMD) and the Tumour Edge Mean Dose (TEMD), i.e. the mean dose imparted at the 250-μm layer of tissue, were computed. The results for beta and Auger emitters demonstrate that the photon dose is about three to four orders of magnitude lower than that deposited by electrons. For ²²³Ra, the beta emissions of its progeny deliver a dose about three orders of magnitude lower than that delivered by the alpha emissions.Such results may help to characterize the dose inhomogeneities in solid tumour therapies with radiopharmaceuticals, taking into account the interplay between drug distribution from vasculature and range of ionizing radiations.     

On the need for massive additional shielding of a catheterization laboratory for the implementation of high dose rate 192Ir intravascular brachytherapy

Purpose: There is a widespread belief in the cardiology and radiation oncology community that high dose rate 192Ir intravascular brachytherapy cannot be implemented without massive additional shielding of the conventional catheterization labs. The purpose of this work is to show that this is a myth, which is not based on sound radiation protection principles.Methods: Exposure rates in air were calculated for a variety of point and line sources of 192Ir. Exposures per treatment at different distances from the source were calculated for a typical intravascular brachytherapy treatment of a 15-Gy dose at a radial distance of 2 mm from the source and for source lengths in the range of 0 to 10 cm. Additionally, exposure rates outside the catheterization lab were calculated for various lead shielding thicknesses typical of conventional X-ray facilities. These rates were used along with the NCRP recommendations on radiation facility design to assess shielding requirements.Results: For a treatment dose of 15 Gy at 2 mm, the occupational exposure per treatment at 2 m in air without any tissue attenuation or shielding was 7.8 mR for a lesion length of 3.0 cm. This exposure/treatment is independent of the dose rate or the activity of the source. However, it increases as lesion length is increased, increasing from 5.4 to 24.9 mR as lesion length increased from 2 to 10 cm. Exposures in unrestricted areas outside the catheterization lab using the NCRP shielding rationale can be kept below 2 mR per treatment and using appropriate workload, use, and occupancy factors below 2 mR per week.Conclusions: The feasibility of implementing a high dose rate 192Ir intravascular brachytherapy program in a catheterization laboratory is totally independent of the dose rate or the activity of the source. If it is feasible to implement 192Ir brachytherapy in a conventional catheterization lab using low activity 192Ir seeds, then it is also feasible to do so with a high activity 192Ir afterloader.     

Dosimetric parameters of the new design 103Pd brachytherapy source based on Monte Carlo study

In this study version 5 of the MCNP photon transport simulation was used to calculate the dosimetric parameters for new palladium brachytherapy source design following AAPM Task Group No. 43U1 report. The internal source components include four resin beads of 0.6 mm diameters with ¹⁰³Pd uniformly absorbed inside and one cylindrical copper marker with 1.5 mm length. The resin beads and marker are then encapsulated within 0.8 mm in diameter and 4.5 mm long cylindrical capsule of titanium. The dose rate constant, Λ, line and point-source radial dose function, g_L(r) and g_P(r), and the anisotropy function, F(r,θ) of the IR01-¹⁰³Pd seed have been calculated at distances from 0.25 to 5 cm. All the results are in good agreement with previously published thermoluminescence-dosimeter measured values [3] for the source. The dosimetric parameters calculated in this work showed that in dosimetry point of view, the IR01-¹⁰³Pd seed is suitable for use in brachytherapy of prostate cancer.     

Spatial distribution of beta extremity doses in nuclear medicine: A feasibility study with thin α-Al2O3:C TLDs

Exposures to the extremities have increased due to new therapeutic protocols involving beta sources. In this study, thermoluminescent dosimeters based on α-Al₂O₃:C were used to map the dose distribution to the extremities of physicians and paramedical personnel handling beta emitters. The results showed a strong inhomogeneous dose distribution between different phalanxes, fingers and hands of all the investigated subjects, without an indication of systematic trends in the dose patterns. Consequently, conventional dosimetric practices, based on the use of wrist or ring dosimeters, may be not suitable for providing reliable assessments of the inhomogeneous doses received at the fingertip.     

Measured TG-60 dosimetric parameters of the Novoste Beta-Cath 90Sr/Y source trains for intravascular brachytherapy

Measurements were performed on the 30, 40 and 60-mm 90Sr/Y beta-emitter source trains used in the Novoste Beta-Cath system to determine the dosimetric characteristics of the sources at millimeter distances and provide the necessary TG-60 dosimetry parameters for mapping the dose distributions. These measurements were carried out in a Solid Water phantom where MD-55-2 Gafchromic films were placed in direct contact with a 5 French (F) catheter used for the 30 and 60-mm source trains and a 3.5 F catheter used for a thinner 40-mm source train. The dosimetric analysis was performed according to the AAPM TG-60 formalism. For the 30-mm source train, data were collected with the source axis at distances of 0.41 and 1.19 mm from the film surface, respectively, in order to investigate possible dosimetric effects due to the intrinsic off centering of the source train lumen within the 5 F catheter. Absolute dose rates at 2 mm were determined by calibrating the radiochromic film in a high energy electron beam from a radiotherapy accelerator. The dose rates at a radial distance of 2 mm were found to be within 10% of the values provided by Novoste. Radial dose functions from this study were in good agreement (< or = 10%) with a 30-mm, 90Sr/Y source train dose data generated from C. G. Soares et al. 90Sr/Y single seed data. However, larger differences were observed at distances shorter than 1 mm when compared to radial dose functions from the Novoste Monte Carlo data.     

Intravascular brachytherapy to prevent restenosis: dosimetric considerations.

Acute myocardial infarction is often the result of occlusion of one or more coronary arteries. Occlusion and restenosis (re-closing of the vessel) are principal reasons that percutaneous transluminal coronary angioplasty (PTCA) may fail to provide long-term benefit. PTCA has been a popular treatment, which is less invasive than surgeries involving revascularization of the myocardium, promising a better quality of life for patients. Unfortunately, the rate of restenosis after balloon angioplasty is high (approximately 30-50% in the first year after treatment). Recent data suggest that intraluminal irradiation of coronary arteries in conjunction with balloon angioplasty and/or stent implantation reduces the proliferation of smooth muscle cells and neointima formation, thereby inhibiting restenosis. In order to study radiation dosimetry in the patient and for this therapy, dose distributions for electrons and photons, with discrete energies, were simulated for blood vessels of diameter 1.5, 3 and 4.5 mm irradiated with balloon and wire sources. Electron and photon transport was performed in a simple model representing the system used for irradiation using the MCNP 4B code (Monte Carlo N-Particles). Specific calculations for balloon and wire sources were also carried out for a few radionuclides. In this work, strengths and drawbacks conceming the use of each radionuclide simulated, as well as source geometries are discussed. The dosimetry performed in this study will improve understanding of the benefit-to-risk ratio in intracoronary brachytherapy.     

A Monte Carlo study on dose distribution evaluation of Flexisource 192Ir brachytherapy source

Aim

The aim of this study is to evaluate the dose distribution of the Flexisource ¹⁹²Ir source.

Background

Dosimetric evaluation of brachytherapy sources is recommended by task group number 43 (TG. 43) of American Association of Physicists in Medicine (AAPM).

Materials and methods

MCNPX code was used to simulate Flexisource ¹⁹²Ir source. Dose rate constant and radial dose function were obtained for water and soft tissue phantoms and compared with previous data on this source. Furthermore, dose rate along the transverse axis was obtained by simulation of the Flexisource and a point source and the obtained data were compared with those from Flexiplan treatment planning system (TPS).

Results

The values of dose rate constant obtained for water and soft tissue phantoms were equal to 1.108 and 1.106, respectively. The values of the radial dose function are listed in the form of tabulated data. The values of dose rate (cGy/s) obtained are shown in the form of tabulated data and figures. The maximum difference between TPS and Monte Carlo (MC) dose rate values was 11% in a water phantom at 6.0 cm from the source.

Conclusion

Based on dosimetric parameter comparisons with values previously published, the accuracy of our simulation of Flexisource ¹⁹²Ir was verified. The results of dose rate constant and radial dose function in water and soft tissue phantoms were the same for Flexisource and point sources. For Flexisource ¹⁹²Ir source, the results of TPS calculations in a water phantom were in agreement with the simulations within the calculation uncertainties. Furthermore, the results from the TPS calculation for Flexisource and MC calculation for a point source were practically equal within the calculation uncertainties.     

Nonstochastic effects of different energy beta emitters on pig skin

Circular areas of pig skin from 1- to 40-mm diameter were irradiated with beta emitters of high, medium, and low energies, 90Sr, 170Tm, and 147Pm, respectively. The study provides information for radiological protection problems of localized skin exposures. During the first 16 weeks after irradiation 90Sr produced a first reaction due to epithelial cell death followed by a second reaction attributable to damage to the dermal blood vessels. 170Tm and 147Pm produced the epithelial reaction only. The epithelial dose response varied as a function of beta energy. The doses required to produce moist desquamation in 50% of 15- to 22.5-mm fields (ED50) were 30-45 Gy from 90Sr, approximately 80 Gy from 170Tm, and approximately 500 Gy from 147Pm. A model involving different methods of epithelial repopulation is proposed to explain this finding. An area effect was observed in the epithelial response to 90Sr irradiation. The ED50 for moist desquamation ranged from approximately 25 Gy for a 40-mm source to approximately 450 Gy for a 1-mm source. The 5-, 9-, and 19-mm 170Tm sources all produced an ED50 of approximately 80 Gy, while the value for the 2-mm source was approximately 250 Gy. It is also suggested that the area effects could be explained by different modes of epithelial repopulation after irradiation. After high energy beta irradiation repopulation would be mainly from the field periphery, while after lower energy irradiation repopulation from hair follicle epithelium would predominate.     

Comparative study of chemiluminescence and resistance of serum and its components after radiation exposure

Kinetics of spontaneous chemiluminescence (CL) and electrochemiluminescence (ECL) and resistance of blood serum and its protein, lipid and carbohydrate components under the effect of X-rays (3 to 1622 Gy) and the indirect effect of radiation initiated by the addition of hydrogen peroxide (1.5 X 10(-5)-1.5%) was studied to estimate the contribution of each of the serum components to cumulative changes in the kinetics of free radical oxidation initiated by the effect of radiation. There was a parametric dependence between the absorbed dose, the rate of ECL and the resistance of blood serum and its components. As the absorbed dose or hydrogen peroxide concentration increased ECL contribution to the cumulative luminescence signal regularly decreased. Changes in CL and ECL of blood serum induced by ionizing radiation and H2O2 were qualitatively similar. The kinetics of free radical oxidation of blood serum initiated by irradiation was determined integrally (according to CL and ECL parameters) by a complex of changes in its components.     

Differential dose contributions on total dose distribution of 125I brachytherapy source

This work provides an improvement of the approach using Monte Carlo simulation for the Amersham Model 6711 ¹²⁵I brachytherapy seed source, which is well known by many theoretical and experimental studies. The source which has simple geometry was researched with respect to criteria of AAPM Tg-43 Report. The approach offered by this study involves determination of differential dose contributions that come from virtual partitions of a massive radioactive element of the studied source to a total dose at analytical calculation point. Some brachytherapy seeds contain multi-radioactive elements so the dose at any point is a total of separate doses from each element. It is momentous to know well the angular and radial dose distributions around the source that is located in cancerous tissue for clinical treatments. Interior geometry of a source is effective on dose characteristics of a distribution. Dose information of inner geometrical structure of a brachytherapy source cannot be acquired by experimental methods because of limits of physical material and geometry in the healthy tissue, so Monte Carlo simulation is a required approach of the study. EGSnrc Monte Carlo simulation software was used. In the design of a simulation, the radioactive source was divided into 10 rings, partitioned but not separate from each other. All differential sources were simulated for dose calculation, and the shape of dose distribution was determined comparatively distribution of a single-complete source. In this work anisotropy function was examined also mathematically.     

Novoste Beta-Cath integrity test with the active source train

Intravascular brachytherapy (IVB) to prevent restenosis is currently being performed using several different commercial delivery devices. The Novoste Beta-Cath system uses a source train of 90Sr/90Y pure beta emitters and two gold radiopaque markers. A nonactive transfer device with dummy sources is also supplied to test the delivery catheter. We have developed an alternate procedure using an acrylic shield to test both the active transfer device and delivery catheter prior to patient treatment.     

NASBA快速检测禽流感H5亚型病毒

采用建立的依赖核酸序列的扩增(Nucleicacidsequencebasedamplification,NASBA)对禽流感病毒3株H5亚型、1株H1、H3、H6亚型、3株禽流感H9亚型、5株不同宿主来源的新城疫病毒、鸭肝炎病毒、鸭瘟病毒、SPF鸡胚尿囊液及禽流感(H9)疫苗、新城疫疫苗、传染性法氏囊病疫苗、传染性支气管炎疫苗进行检测,结果NASBA(H5试剂)仅检测到禽流感病毒H5亚型,表明方法的特异性强。采用已知禽流感病毒A/Chicken/HK/1000/97(H5N1)的鸡胚尿囊液(ELD5010-7.5/mL),经10倍连续稀释,将经典的鸡胚病原分离法和NASBA进行比较,二种方法的灵敏度相当。用A/Chicken/HK/1000/97(H5N1)病毒人工感染SPF鸡、商品鸡,采用NASBA和病原分离法同时对人工感染鸡的粪拭子、血液进行了动态检测;采集感染死亡鸡的组织脏器,共检测了101个组织脏器,两种方法的符合率为90%(87/97)。     

Distribution of myocardial stress and its influence on coronary blood flow

The myocardial stress was analyzed by biomechanical modeling in correlation with experimental findings. The pressure-volume relationship follows the stress-strain relationship of muscle fibers. From the knowledge of fiber orientation and the distribution of sarcomere length, the myocardial stress components including fiber, longitudinal, circumferential and radial stresses were expressed as a function of fraction of wall thickness. The coronary blood flow is influenced by the myocardial radial stress. With the use of vascular waterfall theory, it is possible to correlate the theoretically defined stress distribution with experimentally obtained stress distribution. An elevation of radial stress in myocardium causes a reduction of vessel patency. During both systole and diastole, vessel patency remains constant at epicardium. At endocardium, however, vessel patency undergoes rhythmic changes following the systolic and diastolic influences of the radial stress. The physiological implication is that during systole, the endocardium suffers low blood flow and this transient ischemic state requires compensatory replenishment from diastolic perfusion. Such phenomena become less apparent toward the epicardium.     

Caffeine and length dependence of staircase potentiation in skeletal muscle

Skeletal muscle sensitivity to Ca2+ is greater at long lengths, and this results in an optimal length for twitch contractions that is longer than optimal length for tetanic contractions. Caffeine abolishes this length dependence of Ca2+ sensitivity. Muscle length (ML) also affects the degree of staircase potentiation. Since staircase potentiation is apparently caused by an increased Ca2+ sensitivity of the myofilaments, we tested the hypothesis that caffeine depresses the length dependence of staircase potentiation. In situ isometric twitch contractions of rat gastrocnemius muscle before and after 10 s of 10-Hz stimulation were analyzed at seven different lengths to evaluate the length dependence of staircase potentiation. In the absence of caffeine, length dependence of Ca2+ sensitivity was observed, and the degree of potentiation after 10-Hz stimulation showed a linear decrease with increased length (DT = 1.47 - 0.05 ML, r2 = 0.95, where DT is developed tension). Length dependence of Ca2+ sensitivity was decreased by caffeine when caffeine was administered in amounts estimated to result in 0.5 and 0.75 mM concentrations. Furthermore, the negative slope of the relationship between staircase potentiation and muscle length was diminished at the lower caffeine dose, and the slope was not different from zero after the higher dose (DT = 1.53 - 0.009 ML, r2 = 0.43). Our study shows that length dependence of Ca2+ sensitivity in intact skeletal muscle is diminished by caffeine. Caffeine also suppressed the length dependence of staircase potentiation, suggesting that the mechanism of this length dependence may be closely related to the mechanism for length dependence of Ca2+ sensitivity.     

Beta emitter systems and results from clinical trials. state of the art

Vascular brachytherapy has been established as the standard of care for the treatment of in-stent restenosis (ISR). Both beta and gamma emitters are currently in use for the prevention of ISR recurrence. The use of beta sources for vascular application is attractive from both the radiation exposure and safety points of view, and a wide variety of beta sources are available for this application. This review is intended to summarize the clinical trials utilizing beta emitter systems for the treatment of ISR and de novo lesions and their subsequent results.     

Radiation protection from external exposure to radionuclides: A Monte Carlo data handbook

The availability of a resource collecting dose factors for the evaluation of the absorbed doses from external exposure during the manipulation of radioactive substances is fundamental for radiological protection purposes. Monte Carlo simulations are useful for the accurate calculation of dose distributions in complex geometries, particularly in presence of extended spectra of multi-radiation sources. We considered, as possible irradiation scenarios, a point source, a uniform planar source resembling a contaminated surface, several source volumes contained in plastic or glass receptacles, and the direct skin contamination case, implementing the corresponding Monte Carlo simulations in GAMOS (GEANT4-based Architecture for Medicine-Oriented Simulations). A set of 50 radionuclides was studied, focusing the attention on those ones mainly used in nuclear medicine, both for diagnostic and therapeutic purposes, in nuclear physics laboratories and for instrument calibration. Skin dose equivalents at 70 μm of depth and deep dose equivalents at 10 mm of depth are reported for different configurations and organized in easy-to-read tables.     

Ontogeny of the fused tentacles in three species of ommastrephid squids (Cephalopoda, Ommastrephidae)

Abstract. The tentacles of ommastrephid squids fuse during embryonic development and remain fused as they grow through hatching, but eventually separate to become two fully functional adult tentacles. The external anatomy of individuals at several post‐hatching ontogenetic stages of three species of ommastrephid squids (Ommastrephes bartramii, Sthenoteuthis oualaniensis, and Hyaloteuthis pelagica) was examined using scanning electron microscopy and morphometrics. The fusion of the transverse muscle mass of the tentacles was examined using light microscopy. Five ontogenetic stages of tentacle separation were defined based on landmark features such as the extent of the fusion and the presence of suckers or sucker buds at the distal tip. The total tentacle length and fused tentacle length reached a maximum when the dorsal mantle length (ML) equaled 3–4 mm (H. pelagica) or 4–6 mm (O. bartramii, S. oualaniensis), and then decreased with increasing ML. The average split length (measured from the base of the tentacles to the point of tentacle fusion) increased gradually with increasing ML, and the separate tentacle diameter was roughly half the diameter of the fused portion at all sizes. In all three species, separation of the fused tentacles began earlier in development (2–3‐mm ML) and was more advanced at smaller sizes than previously reported. The sizes presented here are conservative because excess epithelium at the location of the split may disguise the actual site of separation. Post‐separation tentacles were much shorter than the arms, and the carpal region appeared torn in 2 of the 4 specimens of S. oualaniensis examined. Finally, none of the original distal tip suckers were retained on the post‐separation tentacles of S. oualaniensis. These observations are consistent with the hypothesis that the tentacles separate gradually then rupture at the “wrist” (presumptive carpus), and argue against the possibility of prey capture by the fused tentacles.