In vivo dosimetry for external photon treatments of head and neck cancers by diodes and TLDS

In vivo dosimetry was implemented for treatments of head and neck cancers in the large fields. Diode and thermoluminescence dosemeter (TLD) measurements were carried out for the linear accelerators of 6 MV photon beams. ESTRO in vivo dosimetry protocols were followed in the determination of midline doses from measurements of entrance and exit doses. Of the fields monitored by diodes, the maximum absolute deviation of measured midline doses from planned target doses was 8%, with the mean value and the standard deviation of -1.0 and 2.7%. If planned target doses were calculated using radiological water equivalent thicknesses rather than patient geometric thicknesses, the maximum absolute deviation dropped to 4%, with the mean and the standard deviation of 0.7 and 1.8%. For in vivo dosimetry monitored by TLDs, the shift in mean dose remained small but the statistical precision became poor.     

In vivo thermoluminescence dosimetry for total body irradiation

An improvement in the clinical results obtained using total body irradiation (TBI) with photon beams requires precise TBI treatment planning, reproducible irradiation, precise in vivo dosimetry, accurate documentation and careful evaluation. In vivo dosimetry using LiF Harshaw TLD-100 chips was used during the TBI treatments performed in our department. The results of in vivo thermoluminescence dosimetry (TLD) show that using TLD measurements and interactive adjustment of some treatment parameters based on these measurements, like monitor unit calculations, lung shielding thickness and patient positioning, it is possible to achieve high precision in absorbed dose delivery (less than 0.5%) as well as in homogeneity of irradiation (less than 6%).     

Energy and angular anisotropy optimisation of a p-type diode for in vivo dosimetry in photon-beam radiotherapy

We present simulation work using the Monte Carlo code MCNPX that shows that there is a possibility of improving the silicon p-type diode as a radiation dosemeter, by altering the construction of the diode. Altering the diode die thickness can reduce the inherent angular anisotropy of the diode, with little effect on its energy response. Conversely, the contact material and geometry have a large impact on the energy response with little effect on the inherent angular anisotropy. By correct choice of contact material, the typical over-response -100 keV relative to the response at 60Co energy can be reduced from approximately 20 to 4. It is expected that further enhancements may be made with different geometries and materials.     

Miniature thermoluminescent detectors for dosimetry in radiotherapy

At the Institute of Nuclear Physics in Kraków (INP), in collaboration with the Centre of Oncology in Kraków, several types of miniature thermoluminescent LiF:Mg,Ti and LiF:Mg,Cu,P detectors specially designed for clinical dosimetry in radiotherapy have been developed. The detectors are manufactured in the form of solid pellets of diameter down to 1 mm and typical thickness 0.5 mm, in the form of rods with a diameter of 0.5 mm and a length of a few mm, and as two-layer detectors with a thin (in the range of 0.065 mm) active layer of high-sensitive LiF:Mg,Cu,P. All three types of newly developed detectors have already been applied in proton beam dosimetry, surface dosimetry of eye-plaque brachytherapy applicators, phantom dosimetry for vascular brachytherapy and in vivo dosimetry in interstitial brachytherapy. These detectors were found to be very useful for dose measurements in high dose gradients, where spatial resolution better than 1 mm is required.     

Improvements in CVD diamond properties for radiotherapy dosimetry

The goal of this work was to compare the behaviour of a chemical vapour deposited (CVD) diamond sample, grown at the University of Florence using a local procedure, with that of a commercial CVD diamond. The comparison was performed exposing both systems to 25 MV photons and measuring the current response during irradiation. Properties of dosimetric interest such as stability of response, dose rate dependence and rise time were investigated. After a preliminary study, which evidenced better performances of the commercial device with respect to the local CVD diamond, the latter was irradiated with a high fluence of fast neutrons. As a result of the neutron treatment, the quality of the CVD home-made diamond has been improved to match with that of the commercial dosemeter.     

Miniature semiconductor detectors for in vivo dosimetry

Silicon mini-semiconductor detectors are found in wide applications for in vivo personal dosimetry and dosimetry and microdosimetry of different radiation oncology modalities. These applications are based on integral and spectroscopy modes of metal oxide semiconductor field effect transistor and silicon p-n junction detectors. The advantages and limitations of each are discussed.     

In vivo EPR dosimetry to quantify exposures to clinically significant doses of ionising radiation

As a result of terrorism, accident or war, populations potentially can be exposed to doses of ionising radiation that could cause direct clinical effects within days or weeks. There is a critical need to determine the magnitude of the exposure to individuals so that those with significant risk can have appropriate procedures initiated immediately, while those without a significant probability of acute effects can be reassured and removed from the need for further consideration in the medical/emergency system. It is extremely unlikely that adequate dosemeters will be worn by the potential victims, and it also will be unlikely that prompt and accurate dose reconstruction at the level of individuals will be possible. Therefore, there is a critical need for a method to measure the dose from radiation-induced effects that occur within the individual. In vivo EPR measurements of radiation-induced changes in the enamel of teeth is a method, perhaps the only such method, which can differentiate among doses sufficiently to classify individuals into categories for treatment with sufficient accuracy to facilitate decisions on medical treatment. In its current state, the in vivo EPR dosemeter can provide estimates of absorbed dose of +/- 0.5 Gy in the range from 1 to >10 Gy. The lower limit and the precision are expected to improve, with improvements in the resonator and the algorithm for acquiring and calculating the dose. In its current state of development, the method is already sufficient for decision-making action for individuals with regard to acute effects from exposure to ionising radiation for most applications related to terrorism, accidents or nuclear warfare.     

State of the art of in vivo dosimetry

The complexity of modern radiotherapy requires a comprehensive quality assurance programme, including in vivo dosimetry. In this paper, the use of the detector systems most often used for in vivo dosimetry [diodes, thermoluminescence detectors, metal oxide field effect transistors and electronic portal imaging devices (EPIDs)] will be summarised. Although point detectors are useful for the verification of conventional 3-D conformal radiotherapy, the use of 2-D detector systems, such as EPIDs, is required for the verification of more complicated techniques, including intensity-modulated radiotherapy.     

Patient and personnel dosimetry in endovascular radiotherapy with 90Sr/90Y sources

Endovascular brachytherapy (EVBT) is an established treatment to reduce the probability of restenosis after a percutaneous coronary intervention. The purpose of this study was to assess (1) the manufacturer's stated dosimetric data for (90)Sr/(90)Y source trains to be used in EVBT and (2) the procedure-related radiation burden. The radiation fields in water around six (90)Sr/(90)Y source trains were studied using phantoms made of 'solid water' and MD55-2 radiochromic films. The water equivalence of the phantom material was tested by applying quantitative computed tomography. Thermoluminescence dosemeters were used to assess personal radiation burden and crosscheck the dose distribution along the source trains. Technical failure was observed in one source train and this train was excluded from analysis. The measured dose rate in water at 2 mm radial distance was on average 8% higher than the manufacture's stated value (range of measured to stated values 1.05--1.15). The dose rate decreased exponentially with radial distance between 2 and 6 mm. The dose rate in contact with the source viewing window of the delivery devices ranged between 0.5 and 7.5 mGy h(-1). Low-energy photons were the main contributors to personal dose.     

Gated fiber-optic-coupled detector for in vivo real-time radiation dosimetry

Gated detection of the output of a fiber-optic-coupled radiation dosimeter effectively eliminated the direct contribution of Cerenkov radiation to the signal. The radiation source was an external beam radiotherapy machine that provided pulses of 6-MeV x rays. Gated detection was used to discriminate the signal collected during the radiation pulses, including Cerenkov interference, from the signal collected between the radiation pulses due only to phosphorescence from the Cu(1+)-doped glass detector. Gated detection of the long-lived phosphorescence of the Cu(1+)-doped glass provided real-time dose measurements that were linear with the absorbed dose and that were accurate for all field sizes studied.     

In vivo port-wine stain depth determination with a photoacoustic probe

We have designed a photoacoustic probe for port-wine stain (PWS) depth measurements consisting of optical fibers for laser light delivery and a piezoelectric element for acoustic detection. We characterized the capabilities and limitations of the probe for profiling PWS skin. The probe induced and measured photoacoustic waves in acrylamide tissue phantoms and PWS skin in vivo. The optical properties of the phantoms were chosen to mimic those of PWS skin. We denoised acoustic waves using spline wavelet transforms, then deconvolved with the impulse response of the probe to yield initial subsurface pressure distributions in phantoms and PWS skin. Using the phantoms, we determined that the limit in resolving epidermal and PWS layers was less than 70 microm. In addition, we used the phantoms to determine that the maximum epidermal melanin concentration that allowed detection of PWS was between 13 and 20%. In vivo measurements of PWS skin with different epidermal melanin concentrations correlated with the phantoms. Thus the photoacoustic probe can be used to determine PWS depth for most patients receiving laser therapy.     

Monte Carlo based voxel phantoms for in vivo internal dosimetry

The purpose of this communication is to describe briefly the computer programs developed to generate the MCNP input file corresponding to any segmented tomographic data and its application to the calibration procedures for in vivo internal dosimetry. The method has been applied to the determination of 241Am in bone by measurement in skull and knee using MCNP voxel models of a real human head and knee based on the tomographic Voxelman and Arms Down phantoms developed by Zubal et al. at Yale University.     

Development of physical and numerical techniques of Alanine/EPR dosimetry in radiotherapy

In this work, a set of 50 alanine dosimeters has been used in a radiotherapy context, simulating a two-dimensional treatment in a non-overlapping dosimeter configuration. The dose is reconstructed from physical and numerical simulation of the electron paramagnetic resonance signal, calculating the spin density. Thus, it can be used to better adjust the error in the calibration curve to give a final accuracy of <0.03 Gy. A complete set of experimental test parameters have been used with a standard dosimeter in order to obtain the best analysis configuration. These results indicate that for a conventional treatment of some hundreds of mGy, this method can be useful with a correct signal validation. A numerical test and fitting software has been developed. The general use of alanine/electron paramagnetic resonance dosimetry in radiotherapy context is discussed.     

In vivo/ex vivo cellular interactions with titanium and copper

Machined, commercially pure titanium (Ti) disks were coated with approximately 400 nm copper (Cu) by physical vapor deposition or left uncoated. The kinetics of inflammatory cell recruitment, distribution and viability was evaluated around Ti, Cu, and in sham sites after 1, 3, 12, 18, 24, and 48 h in a rat subcutaneous (s.c.) model. Further analysis of the cells on implant surfaces was performed by ex vivo incubation of the disks. Ti and Cu stimulated an increased recruitment of inflammatory cells in comparison with sham sites. A markedly higher amount of cells, predominantly polymorpho-nuclear granulocytes (PMN), was detected around Cu after 18 h and onwards. More cells were found at the implant surfaces than in the surrounding exudates after 18 h. The total amount of lactate dehydrogenase (LDH), an indicator of plasma membrane injury, was higher in Cu exudates after 18 h in comparison with Ti and sham. In contrast, no differences in the proportion of dead cells (trypan blue dye uptake) were detected in the exudates. Further, LDH levels were higher around Ti than Cu during the initial 18 h of ex vivo incubation. The results of this study indicate that the early inflammatory process associated with a cytotoxic material in soft tissues is largely attributed to the induction of a markedly strong and prolonged chemotactic response. In contrast, this process is characterized by a higher amount of inflammatory cells around a biocompatible material than in sham sites, but with a transient course and total LDH similar to sham sites.     

In vivo validation of a blood vector velocity estimator with MR angiography

Conventional Doppler methods for blood velocity estimation only estimate the velocity component along the ultrasound beam direction. This implies that a Doppler angle under examination close to 90° results in unreliable information about the true blood direction and blood velocity. The novel method transverse oscillation (TO), which combines estimates of the axial and the transverse velocity components in the scan plane, makes it possible to estimate the vector velocity of the blood regardless of the Doppler angle. The present study evaluates the TO method with magnetic resonance phase contrast angiography (MRA) by comparing in vivo measurements of stroke volume. Eleven healthy volunteers were included in this prospective study. From the obtained data sets recorded with the 2 modalities, vector velocity sequences were constructed and stroke volume calculated. Angle of insonation was approximately 90° for TO measurements. The correlation between the stroke volume estimated by TO and MRA was 0.91 (p < 0.01) with the equation for the line of regression: MRA = 1.1?TO-0.4. A Bland-Altman plot was additionally constructed where the mean difference was 0.2 ml with limits of agreement at ?1.4 ml and 1.9 ml. The results indicate that reliable vector velocity estimates can be obtained in vivo using the presented angle-independent 2-D vector velocity method. The TO method can be a useful alternative to conventional Doppler systems by avoiding the angle artifact, thus giving quantitative velocity information.     

In vitro and in vivo evaluation of a desonide gel-cream photostabilized with benzophenone-3

Context: Our group previously reported the photoinstability of some desonide topical commercial formulations under direct exposure to UVA radiation.

Objective: This study aimed to prepare and characterize a gel-cream containing desonide, with greater photostability than the commercial gel-cream (C-GC). Benzophenone-3 (BP-3) was used as a photostabilizing agent.

Methods: The gel-cream developed (D-GC) containing BP-3 at 0.1% was prepared and characterized regarding its pH, drug content, spreadability, viscosity, in vitro drug release and in vitro permeation. The in vivo anti-inflammatory effect was assessed by ear edema measurement, croton oil-induced acute skin inflammation and myeloperoxidase assay.

Results and Discussion: D-GC presented characteristics compatible with topical application, appropriate drug content and good spreadability, and non-Newtonian behavior with pseudoplastic flow. D-GC showed a good photostability profile, presenting a desonide content of 95.70% after 48?h of exposure to UVA radiation, and stability under room conditions during 60 days. The amount of desonide released from D-GC and C-GC was 57.8 and 51.7?µg/cm², respectively, measured using the vertical Franz cell. The in vitro skin permeation showed that desonide reached the site of action of the topical corticosteroids, from both formulations; however, the desonide amount retained in the dermis was lower with D-GC. The in vivo evaluation of topical anti-inflammatory activity indicated that D-GC presented the same biological effect as C-GC.

Conclusion: D-GC represents a promising approach to treat dermatological disorders, since it presented satisfactory physicochemical characteristics, the same biological activity as C-GC and superior photostability, conferred by the addition of BP-3 at 0.1%.     

Differential dosimetry in a neutron-proton mixed field with low-pressure proportional counters

For a mixed radiation field of neutrons and protons, radiation events were discriminated between photons, neutrons, and protons using a thin plastic scintillator. Distributions of lineal energy were measured with low-pressure proportional counters (LPPCs). To estimate the distribution of lineal energy for ICRU muscle, measurements were carried out using A-150-walled, graphite-walled, ZrO2-walled, and Zr-walled counters. Data were corrected for different atomic compositions between the A-150 plastic and ICRU muscle.     

In vivo andin vitro evaluation of a biomachinable glassceramic

In this paper we describe the toxicological tests done on a machinable glassceramic, prepared at the Defence Metallurgical Research Laboratory. Tests show no toxicity and biocompatibility is inferred.     

In vivo imaging of hydrogen peroxide with chemiluminescent nanoparticles

The overproduction of hydrogen peroxide is implicated in the development of numerous diseases and there is currently great interest in developing contrast agents that can image hydrogen peroxide in vivo. In this report, we demonstrate that nanoparticles formulated from peroxalate esters and fluorescent dyes can image hydrogen peroxide in vivo with high specificity and sensitivity. The peroxalate nanoparticles image hydrogen peroxide by undergoing a three-component chemiluminescent reaction between hydrogen peroxide, peroxalate esters and fluorescent dyes. The peroxalate nanoparticles have several attractive properties for in vivo imaging, such as tunable wavelength emission (460-630 nm), nanomolar sensitivity for hydrogen peroxide and excellent specificity for hydrogen peroxide over other reactive oxygen species. The peroxalate nanoparticles were capable of imaging hydrogen peroxide in the peritoneal cavity of mice during a lipopolysaccharide-induced inflammatory response. We anticipate numerous applications of peroxalate nanoparticles for in vivo imaging of hydrogen peroxide, given their high specificity and sensitivity and deep-tissue-imaging capability.     

In vitro and in vivo anti-tumor effects of gemcitabine loaded with a new drug delivery system

In recent years, much attention has been given to liposomal formulation as an efficient drug loading system (DDS) in chemotherapy of cancer. In this study, the advantages of magnetic nanoparticles and Polyethylene Glyco (PEG) materials were considered to synthesize magnetic gemcitabine long-circulating liposomes (MGLL) and the potential of MGLL as a brand new delivery system was evaluated. MGLL was prepared using the reverse-phase evaporation method. In the optimized preparation, MGLL had an average diameter of 201 nm with a narrow size distribution measured by dynamic light scattering (DLS), which could be easily dispersed in ultrapure water under a stable state for 90 days. The encapsulation efficiency of gemcitabine in MGLL reached 87.2% as determined by HPLC. In vitro MTT assay showed that MGLL had significant cytotoxicity to MCF-7 cells compared with the conventional modalities. In vivo, the inhibition of tumor growth in MGLL group was more remarkable than that of other groups (P < 0.05). In conclusion, MGLL under optimized condition could be used as an effective carrier for tumor-targeted therapy.