Calorimetric determination of kQ factors for NE 2561 and NE 2571 ionization chambers in 5 cm x 5 cm and 10 cm x 10 cm radiotherapy beams of 8 MV and 16 MV photons

The relative uncertainty of the ionometric determination of the absorbed dose to water, D(w), in the reference dosimetry of high-energy photon beams is in the order of 1.5% and is dominated by the uncertainty of the calculated chamber- and energy-dependent correction factors k(Q). In the present investigation, k(Q) values were determined experimentally in 5 cm x 5 cm and 10 cm x 10 cm radiotherapy beams of 8 MV and 16 MV bremsstrahlung by means of a water calorimeter operated at 4 degrees C. Ionization chambers of the types NE 2561 and NE 2571 were calibrated directly in the water phantom of the calorimeter. The measurements were carried out at the linear accelerator of the Physikalisch-Technische Bundesanstalt. It is shown that the k(Q) factor of a single ionization chamber can be measured with a standard uncertainty of less than 0.3%. No significant variations of k(Q) were found for the different lateral sizes of the radiation fields used in this investigation.     

Assessment of tissue ingrowth rates in polyurethane scaffolds for tissue engineering

The continuous development of new biomaterials for tissue engineering and the enhancement of tissue ingrowth into existing scaffolds, using growth factors, create the necessity for developing adequate tools to assess tissue ingrowth rates into porous biomaterials. Current histomorphometric techniques evaluating rates of tissue ingrowth tend either to measure the overall tissue content in an entire sample or to depend on the user to indicate a front of tissue ingrowth. Neither method is particularly suitable for the assessment of tissue ingrowth rates, as these methods either lack the sensitivity required or are problematic when there is a tissue ingrowth gradient rather than an obvious tissue ingrowth front. This study describes a histomorphometric method that requires little observer input, is sensitive, and renders detailed information for the assessment of tissue ingrowth rates into porous biomaterials. This is achieved by examining a number of computer-defined concentric zones, which are based on the distance of a pixel from the scaffold edge. Each zone is automatically analyzed for tissue content, eliminating the need for user definition of a tissue ingrowth front and thus reducing errors and observer dependence. Tissue ingrowth rates in two biodegradable polyurethane scaffolds (Estane and polycaprolactone-polyurethane [PCLPU]) specifically designed for tissue engineering of the knee meniscus were assessed. Samples were subcutaneously implanted in rats with follow-up until 6 months. Especially at the earlier follow-up points, PCLPU scaffolds showed significantly higher tissue ingrowth rates than Estane scaffolds, making the PCLPU scaffold a promising candidate for further studies investigating meniscus tissue engineering.     

Blisters on the anterior shin in 3 research subjects after a 1-MHz, 1.5-W/cm , continuous ultrasound treatment: a case series

CONTEXT: Clinicians should consider multiple factors when estimating tissue-heating rates. OBJECTIVE: To report 3 separate occurrences of blisters during an ultrasound treatment experiment. BACKGROUND: While we were conducting a research experiment comparing the measurement capabilities of 2 different intramuscular temperature devices, 3 female participants (age = 26.33 +/- 3.79 years, height = 169.34 +/- 3.89 cm, mass = 63.39 +/- 3.81 kg) out of 16 healthy volunteers (7 men: age = 22.83 +/- 1.17 years, height = 170.61 +/- 7.77 cm, mass = 74.62 +/- 19.24 kg; 9 women: age = 24.22 +/- 2.73 years, height = 171.88 +/- 6.35 cm, mass = 73.99 +/- 18.55 kg) developed blisters on the anterior shin after a 1-MHz, 1.5-W/cm (2) continuous ultrasound treatment delivered to the triceps surae muscle. DIFFERENTIAL DIAGNOSIS: Allergies; chemical reaction with cleaning agents; sunburn; negative interaction between the temperature measurement instruments and the ultrasound field; the ultrasound transducer not being calibrated properly, producing a nonuniform field and creating a hot spot or heating differently when compared with other ultrasound devices; the smaller anatomy of our female subjects; or a confounding interaction among these factors. TREATMENT: Participants were given standard minor burn care by a physician. UNIQUENESS: (1) The development of blisters on the anterior aspect of the shin as a result of an ultrasound treatment to the posterior aspect of the triceps surae muscle and (2) muscle tissue heating rates ranging from 0.19 degrees C to 1.1 degrees C/min, when ultrasound researchers have suggested tissue heating in the range of 0.3 degrees C/min with these settings. CONCLUSIONS: These adverse events raise important questions regarding treatment application and potential differences in heating and quality control among different ultrasound devices from different manufacturers.     

Performance of a 41 x 41 cm2 amorphous silicon flat panel x-ray detector designed for angiographic and R&F imaging applications

We measured the physical imaging performance of a 41 x 41 cm2 amorphous silicon flat panel detector designed for angiographic and R&F imaging applications using methods from the emerging IEC standard for the measurement of detective quantum efficiency (DQE) in digital radiographic detectors. Measurements on 12 production detectors demonstrate consistent performance. The mean DQE at the detector center is about 0.77 at zero frequency and 0.27 at the Nyquist frequency (2.5 cycles/mm) when measured with a 7 mm of Al HVL spectrum at about 3.6 microGy. The mean MTF at the center of the detector for this spectrum is 0.24 at the Nyquist frequency. For radiographic operation all 2048 x 2048 detector elements are read out individually. For fluoroscopy, the detector operates in two 30 frame per second modes: either the center 1024 x 1024 detector elements are read out or the entire detector is read out with 2 x 2 pixel binning. A model was developed to predict differences in performance between the modes, and measurements demonstrate agreement with the model. Lag was measured using a quasi-equilibrium exposure method and was found to be 0.044 in the first frame and less than 0.007 after 1 s. We demonstrated that it is possible to use the lag data to correct for temporal correlation in images when measuring DQE with a fluoroscopic imaging technique. Measurements as a function of position on the detector demonstrate a high degree of uniformity. We also characterized dependences on spectrum, exposure level, and direction. Finally, we measured the DQE of a current state of the art image intensifier/CCD system using the same method as for the flat panel. We found the image intensifier system to have lower DQE than the flat panel at high exposure levels and approximately equivalent DQE at fluoroscopic levels.     

Spectroscopic method for determination of the absorption coefficient in brain tissue

I use Monte Carlo simulations and phantom measurements to characterize a probe with adjacent optical fibres for diffuse reflectance spectroscopy during stereotactic surgery in the brain. Simulations and measurements have been fitted to a modified Beer-Lambert model for light transport in order to be able to quantify chromophore content based on clinically measured spectra in brain tissue. It was found that it is important to take the impact of the light absorption into account when calculating the apparent optical path length, lp, for the photons in order to get good estimates of the absorption coefficient, μa. The optical path length was found to be well fitted to the equation lp=a+b ln(Is)+c ln(μa)+d ln(Is)ln(μa), where Is is the reflected light intensity for scattering alone (i.e., zero absorption). Although coefficients a-d calculated in this study are specific to the probe used here, the general form of the equation should be applicable to similar probes.     

Computation of a finite element-conformal tetrahedral mesh approximation for simulated soft tissue deformation using a deformable surface model

In this article, we present a new method for the generation of surface meshes of biological soft tissue. The method is based on the deformable surface model technique and is extended to histological data sets. It relies on an iterative adjustment towards polygonal segments describing the histological structures of the soft tissue. The generated surface meshes allow for the construction of volumetric meshes through a standard constrained Delaunay approach and, thus, for the application in finite element methods. The geometric properties of volumetric meshes have an immediate influence on the numerical conditioning and, therewith, on the stability of the finite element method and the convergence of iterative solvers. In this article, the influence of the surface meshes on the quality of the volumetric meshes is analysed in terms of the spectral condition number of the stiffness matrices, which are assembled within Newton’s method. The non-linear material behavior of biological soft tissue is modeled by the Mooney–Rivlin material law. The subject is motivated by the requirements of virtual surgery.     

An anatomically realistic whole-body pregnant-woman model and specific absorption rates for pregnant-woman exposure to electromagnetic plane waves from 10 MHz to 2 GHz

The numerical dosimetry of pregnant women is an important issue in electromagnetic-field safety. However, an anatomically realistic whole-body pregnant-woman model for electromagnetic dosimetry has not been developed. Therefore, we have developed a high-resolution whole-body model of pregnant women. A new fetus model including inherent tissues of pregnant women was constructed on the basis of abdominal magnetic resonance imaging data of a 26-week-pregnant woman. The whole-body pregnant-woman model was developed by combining the fetus model and a nonpregnant-woman model that was developed previously. The developed model consists of about 7 million cubical voxels of 2 mm size and is segmented into 56 tissues and organs. This pregnant-woman model is the first completely anatomically realistic voxel model that includes a realistic fetus model and enables a numerical simulation of electromagnetic dosimetry up to the gigahertz band. In this paper, we also present the basic specific absorption rate characteristics of the pregnant-woman model exposed to vertically and horizontally polarized electromagnetic waves from 10 MHz to 2 GHz.     

A method for determination of the absorption and scattering properties interstitially in turbid media

We have developed a method to quickly determine tissue optical properties (absorption coefficient mu(a) and transport scattering coefficient mu'(s)) by measuring the ratio of light fluence rate to source power along a linear channel at a fixed distance (5 mm) from an isotropic point source. Diffuse light is collected by an isotropic detector whose position is determined by a computer-controlled step motor, with a positioning accuracy of better than 0.1 mm. The system automatically records and plots the light fluence rate per unit source power as a function of position. The result is fitted with a diffusion equation to determine mu(a) and mu'(s). We use an integrating sphere to calibrate each source-detector pair, thus reducing uncertainty of individual calibrations. To test the ability of this algorithm to accurately recover the optical properties of the tissue, we made measurements in tissue simulating phantoms consisting of Liposyn at concentrations of 0.23, 0.53 and 1.14% (mu'(s) = 1.7-9.1 cm(-1)) in the presence of Higgins black India ink at concentrations of 0.002, 0.012 and 0.023% (mu(a) = 0.1-1 cm(-1)). For comparison, the optical properties of each phantom are determined independently using broad-beam illumination. We find that mu(a) and mu'(s) can be determined by this method with a standard (maximum) deviation of 8% (15%) and 18% (32%) for mu(a) and mu'(s), respectively. The current method is effective for samples whose optical properties satisfy the requirement of the diffusion approximation. The error caused by the air cavity introduced by the catheter is small, except when mu(a) is large (mu(a) > 1 cm(-1)). We presented in vivo data measured in human prostate using this method.     

Positive and Negative Selection in Transgenic Mice Expressing a T-Cell Receptor Specific for Influenza Nucleoprotein and Endogenous Superantigen

A transgenic mouse was generated expressing on most (>80%) of thymocytes and peripheral T cells a T-cell receptor isolated from a cytotoxic T-cell clone (F5). This clone is CD8⁺ and recognizes αα366-374 of the nucleoprotein (NP 366-374) of influenza virus (A/NT/60/68), in the context of Class ,MHC D^b (Townsend et al., 1986). The receptor utilizes the Vβ11 and Vα4 gene segments for the β chain and α chain, respectively (Palmer et al., 1989). The usage of Vβ11 makes this TcR reactive to Class II IE molecules and an endogenous ligand recently identified as a product of the endogenous mammary tumour viruses (Mtv) 8, 9, and 11 (Dyson et al., 1991). Here we report the development of F5 transgenic T cells and their function in mice of the appropriate MHC (C57BL/10 H-2^b, IE^-) or in mice expressing Class II MHC IE (e.g., CBA/Ca H-2^k and BALB/c H-2^d) and the endogenous Mtv ligands. Positive selection of CD8⁺ T cells expressing the Vβ11 is seen in C57BL/10 transgenic mice (H-2^b). Peripheral T cells from these mice are capable of killing target cells in an antigen-dependent manner after a period of ^{in vitro} culture with IL-2. In the presence of Class II MHC IE molecules and the endogenous Mtv ligand, most of the single-positive cells carrying the transgenic T-cell receptor are absent in the thymus. Unexpectedly, CD8⁺ peripheral T-cells in these (H-2^k or H-2^d) F5 mice are predominantly Vβ11 positive and also have the capacity to kill targets in an antigen-dependent manner. This is true even following backcrossing of the F5 TcR transgene to H-2^d scid/scid mice, in which functional rearrangement of endogenous TcR alpha- and beta-chain genes is impaired.     

A Monte Carlo model for the absorption and flux distributions of light in tissue

A Monte Carlo computer model has been developed to study the propagation of light in tissues. Light attenuation is assumed to result from absorption and isotropic scattering. The model has been used to predict the distribution of absorbed dose in homogeneous tissues of different absorption/scattering ratios, for illumination both by external light beams and via implanted optical fibers. The photon flux into optical fibers placed in the tissue as detectors has also been investigated. The results are interpreted in relation to the use of visible light irradiation for photo radiation therapy.     

Relationship between %dd(10)x and stopping-power ratios for flattening filter free accelerators: a Monte Carlo study

The relationship between the photon beam quality specifier %dd(10)x and the Spencer-Attix water water to air restricted mass collision stopping-power ratio, (L/rho))air(water), is studied using Monte Carlo simulation with realistic beams in contrast to the previously used realistic but uniform spectra from an isotropic point source. The differences between accelerators with and without flattening filters are investigated since flattening filter free accelerators appear to be useful for IMRT. Our results show that the standard relationship between %dd(10)x and (L/rho)air(water), which is used in the TG-51 protocol to calculate the quality conversion factor kQ, is acceptable for beams with or without a flattening filter with a maximum error of 0.4%, although a fit to the new data would reduce the maximum error to 0.2%. Reasons for differences between the individual values of %dd(10)x and (L/ rho)air(water) with and without a flattening filter are studied. Specifically the differences due to the softening of the beam, the change in shape of the profile, and the inclusion of radial variations in the photon energy spectra, are investigated. It is shown that if TPR10(20) is used as a beam quality specifier, there are two different relationships between TPR10(20) and (L/rho)air(water) which differ by 0.4%-1%. When using TPR10(20) as a beam quality specifier in a beam without a flattening filter, one should subtract 0.5% from the value of kQ for a given value of TPR10(20).     

Analysis of specific absorption rate in biological tissue surrounding transcutaneous transformer for an artificial heart

 This paper reports on specific absorption rate (SAR) analysis of biological tissue surrounding a transcutaneous transformer for an artificial heart. An externally coupled type of transformer was used for transcutaneous energy transmission. The secondary (internal) coil of the transformer, which is covered with skin, protrudes from the body surface, forming a skin tunnel. A primary (external) coil closely wound around a toroidal ferrite core is inserted into the skin tunnel. In this transformer, most of the magnetic flux induced by the current of the primary coil is linked with the secondary coil, and the coupling factor between the primary and secondary coils is greater than 0.98, regardless of the skin thickness. The electromagnetic field in the biological tissue surrounding the transformer was analyzed by the transmission line modeling method, and the distributions of the electric field strength and the SAR as a function of output power, the number of coil loops, and the dimensions and output voltage of the transcutaneous transformer were estimated. We found that SARs near the transcutaneous transformer were larger than at other points, that is, the SARs far from the transformer were relatively small. It was also clear that by increasing the dimensions and number of coil loops, and reducing the output voltage, we could reduce the SAR in biological tissue surrounding the transcutaneous transformer. The SAR in the present study was within the limits recommended by the Ministry of Posts and Telecommunications of Japan. Received: March 21, 2001 / Accepted: December 27, 2001     

Calibration of near-infrared frequency-domain tissue spectroscopy for absolute absorption coefficient quantitation in neonatal head-simulating phantoms

Frequency-domain tissue spectroscopy is a method to measure the absolute absorption coefficient of bulk tissues, assuming that a representative model can be found to recover the optical properties from measurements. While reliable methods exist to calculate absorption coefficients from source-detector measurements less than a few centimeters apart along a flat tissue volume, it is less obvious what methods can be used for transmittance through the larger tissue volumes typically associated with neonatal cerebral monitoring. In this study we compare the use of multiple distance frequency-domain measurements processed with (i) a modified Beer-Lambert law method, (ii) an analytic infinite-medium diffusion theory expression, and (iii) a numerical finite element solution of the diffusion equation, with the goal of recovering the absolute absorption coefficient of the medium. Based upon our observations, the modified Beer-Lambert method provides accurate absolute changes in the absorption coefficient, while analytic infinite-medium diffusion theory solutions or finite element-based numerical solutions can be used to calculate the absolute absorption coefficient, assuming that the data can be measured at multiple source-detector distances. We recommend that the infinite-medium multi-distance method or the finite element method be used across large tissue regions for calculation of the absolute absorption coefficient using frequency-domain near-infrared measurements at multiple positions along the head.     

Otitis media in a mouse model for Down syndrome

The Ts65Dn mouse shares many phenotypic characteristics of human Down syndrome. Here, we report that otitis media, characterized by effusion in the middle ear and hearing loss, was prevalent in Ts65Dn mice. Of the 53 Ts65Dn mice tested, 81.1% had high auditory-evoked brainstem response (ABR) thresholds for at least one of the stimulus frequencies (click, 8 kHz, 16 kHz and 32 kHz), in at least one ear. The ABR thresholds were variable and showed no tendency toward increase with age, from 2 to 7 months of age. Observation of pathology in mice, aged 3–4 months, revealed middle ear effusion in 11 of 15 Ts65Dn mice examined, but only in two of 11 wild-type mice. The effusion in each mouse varied substantially in volume and inflammatory cell content. The middle ear mucosae were generally thickened and goblet cells were distributed with higher density in the epithelium of the middle ear cavity of Ts65Dn mice as compared with those of wild-type controls. Bacteria of pathogenic importance to humans also were identified in the Ts65Dn mice. This is the first report of otitis media in the Ts65Dn mouse as a model characteristic of human Down syndrome.     

Preparation of a biomimetic nanocomposite scaffold for bone tissue engineering via mineralization of gelatin hydrogel and study of mineral transformation in simulated body fluid

In this study, double diffusion method in a physiologically relevant environment was used to prepare a biomimetic gelatin-amorphous calcium phosphate nanocomposite scaffold. The precipitated calcium phosphate within gelatin as well as produced nanocomposite scaffolds were characterized by the commonly used bulk techniques. The results showed that nanocomposite scaffolds were porous with three-dimensionally interconnected microstructure, pore size ranging from 150 to 350 μm. Porosity was about 82% and nanocrystalline precipitated minerals were dispersed evenly among gelatin fibers. A mineral containing amorphous calcium phosphate and brushite precipitate was formed within the gelatin matrix at 4°C. After incubation in SBF solution at 37°C for 5 days, the mineral phase was transformed to nanocrystalline hydroxyapatite. It should be noted that precursor phases inside a scaffold implanted into the body can result in biomimetic conversion of precursors to hydroxyapatite that is very similar to the bone mineral and has a profound level of biocompatibility. Thus, our results highlight the potential use of engineered biomimetic bone tissue scaffolds in the bone tissue repair process.     

Heterotopic ossification: review of histologic findings and tissue distribution in a 10-year experience

Heterotopic ossification (HO) within tissues involved by a pathologic process is a well-recognized phenomenon. It is most frequently observed in atherosclerotic plaques, in soft tissue around joints, and in the central nervous system. Less frequently, carcinomas and some benign neoplasms will undergo heterotopic ossification. We performed a retrospective review of our experience with HO over a 10-year period to determine the frequency and tissue site distribution of heterotopic ossification. A computerized review of surgical pathology records of approximately 126,000 reports revealed 85 cases in which heterotopic ossification, ectopic bone or metaplastic bone was specifically mentioned in the surgical pathology diagnosis. Twenty-two cases were neoplasms of non-osseous tissues, and 63 cases were non-neoplastic lesions. Immunohistochemical staining for bone morphogenic proteins (BMP) 1, 4, and 6 was performed. Fourteen cases showed staining for BMP-1, 22 cases showed staining for BMP-4, and five cases showed weak staining for BMP-6. HO is a relatively infrequent finding and is more commonly seen in degenerative and reparative conditions than in neoplasms.