Development of a dosimetry inter-comparison for IMRT as part of site credentialing for a TROG multi-centre clinical trial for prostate cancer.

A methodology has been developed for a dosimetry inter-comparison of intensity modulated radiation therapy (IMRT) delivery in Australasia. The inter-comparison is part of site credentialing for those sites participating in the prostate fractionated irradiation trial (PROFIT) for intermediate-risk prostate patients developed by the Ontario Clinical Oncology Group and coordinated in Australasia by the Trans Tasman Radiation Oncology Group. Features of the dosimetry inter-comparison design included the use of a dedicated pelvic anthropomorphic phantom, the use of a single CT data set of the phantom including contours and the use of radiochromic film as a dosimeter. Action levels for agreement between measured dose and treatment planning system dose have been proposed based on measurement uncertainty and international experience. A trial run of the dosimetry procedure at the reference centre gave results within the predefined action levels.

Theoretical evidence for a c60 "window" mechanism.

On the basis of semiempirical and high-level ab initio calculations, theoretical evidence is presented of a "window" mechanism operable on the surface of C(60) and other fullerenes. Through this mechanism, large holes may be formed in fullerenes excited to their triplet state, openings through which atoms and small molecules can pass. This work provides a theoretical foundation for experiments that have prepared endohedral noble gas compounds of C(60) under thermal excitation. A method is proposed that could increase the efficiency of the process of noble gas insertion into C(60) and provide a more general means to create endohedral fullerene compounds.

Spline modelling electron insert factors using routine measurements.

There are many methods available to predict electron output factors; however, many centres still measure the factors for each irregular electron field. Creating an electron output factor prediction model that approaches measurement accuracy--but uses already available data and is simple to implement--would be advantageous in the clinical setting. This work presents an empirical spline model for output factor prediction that requires only the measured factors for arbitrary insert shapes. Equivalent ellipses of the insert shapes are determined and then parameterised by width and ratio of perimeter to area. This takes into account changes in lateral scatter, bremsstrahlung produced in the insert material, and scatter from the edge of the insert. Agreement between prediction and measurement for the 12 MeV validation data had an uncertainty of 0.4% (1SD). The maximum recorded deviation between measurement and prediction over the range of energies was 1.0%. The validation methodology showed that one may expect an approximate uncertainty of 0.5% (1SD) when as little as eight data points are used. The level of accuracy combined with the ease with which this model can be generated demonstrates its suitability for clinical use. Implementation of this method is freely available for download at https://github.com/SimonBiggs/electronfactors.

Output factor measurements for a kilovoltage X-ray therapy unit.

Output factors at the surface for treatment cones and lead cut-outs have been measured for a Pantak Therapax SXT 150 superficial therapy unit with x-ray beam qualities from 1 to 13 mm A1 HVL. A variety of phantom materials and two ionisation chambers were tested for their suitability in output factor and percentage depth dose measurement. Solid water proved a useful water-equivalent phantom material with discrepancies between measurements in water and solid water less than 2.3% for percentage depth dose and less than 0.6% for output factors. Larger measurement discrepancies were found for Plastic Water and Perspex. A PTW Markus chamber was found to compare well with a NE 2532/3 low energy chamber in percentage depth dose measurement, but discrepancies arose between the chambers in output factor measurements, up to 5% for small field sizes. Measurements indicated that the Markus chamber had an energy dependent response in the kilovoltage range, which could account for the discrepancy in output factor measurement.

Measurement of mechanical properties of bone material in vitro by ultrasound reflection: methodology and comparison with ultrasound transmission.

An ultrasound reflection technique was designed and implemented to study the mechanical properties of bone material. The technique uses the fact that an ultrasound beam produced in water undergoes total internal reflection off a bone sample at a critical angle formally related to the velocity of a pressure wave in bone. When the plane of scattering is rotated around the normal to the sample surface, the critical angle varies with a periodic dependence dictated by the intrinsic symmetry of the bone structure at the point being examined. Most current measurements of sound velocity are made using transmission techniques. A double-blind intercomparison between this technique and a transmission technique, which was previously validated against tensile mechanical testing, was performed for samples of isotropic materials and of human cortical bone. Strong correlations were found for both sets of samples. For the isotropic materials the velocities were approximately equal, but for bone they were on average 11% higher in reflection than in transmission. This was the result both of the higher frequency employed in reflection (3.5 rather than 2.25 MHz) and of the different effects of sample imperfections on the two measurements. In particular, the reflection technique used in this work studied the surface of the sample, but the ultrasound beam in the transmission method propagated through its interior. In assessing the mechanical properties of bone specimens by ultrasound, the reflection technique samples a discrete bone surface element and the transmission method analyzes the entire volume of the specimen. Thus the reflection technique may yield a measure of the mechanical property of bone trabeculae that is largely unaffected by the mass of the entire specimen, but mass and the structural density of the specimen affect the transmission method.

Amino acid signatures in the detached cat retina.

PURPOSE: Expressions of certain macromolecules are altered by experimental retinal detachment in the cat. Related alterations in micromolecular signatures of neurons, Müller cells, and the retinal pigment epithelium (RPE) were investigated. METHODS: High-performance immunochemical mapping, image registration, and quantitative pattern recognition were combined to analyze the amino acid contents of virtually all retinal cell types after 3 to 84 days of detachment. RESULTS: Retinal micromolecular signatures showed a spectrum of alterations. The glutamate contents of Müller cells increased and remained elevated for weeks after detachment. Multispectral signatures of Müller cells showed massive metabolic instability in early detachment stages that ultimately resolved as a homogeneous profile significantly depleted in glutamine. Retinal pigment epithelial cell signals also changed dramatically, displaying an initial glutamate spike and then a prolonged decline, even as taurine levels followed an opposite pattern of initial loss and slow restoration. Neurotransmitter signatures of surviving neurons showed extensive precursor-level variation, and, in one case, GABAergic horizontal cells displayed anomalous sprouting. CONCLUSIONS: Dramatic changes in Müller cell amino acid signatures triggered by retinal detachment are partially consistent with losses in glutamine synthetase activity. Taurine signal variations suggest that orthotopic RPE cells attempt to regulate abnormal taurine concentrations in the enlarged subretinal space. Surviving neurons possess characteristic neurotransmitter signals, but their metabolite regulation seems abnormal. On balance, microchemical and structural anomalies develop in the detached cat retina that represent serious barriers to recovery of normal visual function.

Amino acid signatures in the normal cat retina.

PURPOSE: To establish a nomogram of amino acid signatures in normal neurons, glia, and retinal pigment epithelium (RPE) of the cat retina, guided by the premise that micromolecular signatures reflect cellular identity and metabolic integrity. The long-range objective was to provide techniques to detect subtle aberrations in cellular metabolism engendered by model interventions such as focal retinal detachment. METHODS: High-performance immunochemical mapping, image registration, and quantitative pattern recognition were combined to analyze the amino acid contents of virtually all cell types in serial 200-nm sections of normal cat retina. RESULTS: The cellular cohorts of the cat retina formed 14 separable biochemical theme classes. The photoreceptor --> bipolar cell --> ganglion cell pathway was composed of six classes, each possessing a characteristic glutamate signature. Amacrine cells could be grouped into two glycine- and three gamma-aminobutyric acid (GABA)-dominated populations. Horizontal cells possessed a distinctive GABA-rich signature completely separate from that of amacrine cells. A stable taurine-glutamine signature defined Müller cells, and a broad-spectrum aspartate-glutamate-taurine-glutamine signature was present in the normal RPE. CONCLUSIONS: In this study, basic micromolecular signatures were established for cat retina, and multiple metabolic subtypes were identified for each neurochemical class. It was shown that virtually all neuronal space can be accounted for by cells bearing characteristic glutamate, GABA, or glycine signatures. The resultant signature matrix constitutes a nomogram for assessing cellular responses to experimental challenges in disease models.

Initial roentgenographic manifestations of pulmonary Mycobacterium tuberculosis, M kansasii, and M intracellularis infections.

The initial radiographic features of 188 patients with pulmonary infections due to Mycobacterium tuberculosis were compared to 184 patients with M kansasii and 100 patients with M intracellularis infections. The patients were all from the University of Texas Health Center at Tyler, all had at least two positive sputum cultures and no other potential pathogen, and none had a past medical history of any type of tuberculosis. The comparison showed that all three organisms have a strong tendency to produce cavitary infiltrates in the posterior portions of the upper lobes. No distinctive or pathognomonic feature could be found. The atypical organisms were more likely to produce thin-walled cavities and far advanced unilateral disease, but both of these patterns also occurred with M tuberculosis. Endobronchial spread and volume loss were common in all three diseases. The only definite difference seems to be the absence of a primary or juvenile form of atypical tuberculosis and a much greater incidence of empyema and postprimary pleural effusions with M tuberculosis. In an individual case, the roentgenographic manifestations of the three diseases are indistinguishable.

Grid versus non-grid techniques for the detection of pulmonary nodules in a chest phantom.

A partial chest phantom was constructed to compare two commonly employed radiographic techniques, 70 kVp without a grid and 120 kVp with a grid, for the detection of pulmonary nodules. The phantom consisted of human ribs embedded in paraffin, the lungs of a dog injected with silicone rubber, a tissue equivalent wax heart and beeswax nodules. The nodules ranged in size from 3-7 mm. A series of 120 films was exposed, half with each technique, and the films were interpreted by three senior residents and seven staff radiologists. More nodules of all sizes except 3 mm were detected with the 120 kVp technique. The 3 mm nodules were rarely detected with either technique. The disadvantages of the 120 kVp technique were an approximate 50 percent increase in patient exposures and almost twice as many false-positive nodule detections.

Effects of ORG 2766, a neurotrophic ACTH4-9 analogue, in neuroblastoma cells.

Treatment of Neuro2a cells with drugs known to affect the integrity of microfilaments and microtubules, as well as with a calcium ionophore produced damage to the cellular membrane that was quantifiable by measuring the release of LDH into the culture medium. Concurrent exposure of the cells to ORG 2766 was found to modulate the release of LDH in a dose- and time-dependent fashion. ORG 2766 treatment was also able to reduce the basal release of LDH into the culture medium. [table: see text] The ORG 2766-induced reduction in LDH release was not due to down-regulation of protein synthesis. The peptide produced significant increases in protein synthesis relative to control conditions at concentrations of 10(-11) to 10(-6) M with 10(-8) M being an optimal dose. SDS-PAGE and 2-D PAGE analysis showed that de novo synthesis of most polypeptides was increased by about 40%. Additionally, a family of polypeptides tentatively identified as actins appear to undergo ORG 2766-dependent post translational charge modifications. These data are consistent with the hypothesis that regulation of transcription and/or translation are mechanisms important to the neurotrophic actions of ORG 2766.

Clinical application of digital tomosynthesis: a preliminary report.

Digital tomosynthesis represents a new technique for digital manipulation of data acquired during a single tomographic sweep. With the aid of a computer, data can be processed to yield images in any parallel plane of the body. This technique allows rapid tomographic studies requiring a much lower radiation dose to the patient. Dynamic studies such as angiotomography are feasible, and application to digital subtraction intravenous angiography is also possible with this technique. Early experience with clinical application in patient studies is presented.

Results from a multicenter prostate IMRT dosimetry intercomparison for an OCOG-TROG clinical trial.

PURPOSE: A multi-institution dosimetry intercomparison has been undertaken of prostate intensity modulated radiation therapy (IMRT) delivery. The dosimetry intercomparison was incorporated into the quality assurance for site credentialing for the Trans-Tasman Radiation Oncology Group Prostate Fractionated Irradiation Trial 08.01 clinical trial. METHODS: An anthropomorphic pelvic phantom with realistic anatomy was used along with multiplanar dosimetry tools for the assessment. Nineteen centers across Australia and New Zealand participated in the study. RESULTS: In comparing planned versus measured dose to the target at the isocenter within the phantom, all centers were able to achieve a total delivered dose within 3% of planned dose. In multiplanar analysis with radiochromic film using the gamma analysis method to compare delivered and planned dose, pass rates for a 5%/3 mm criterion were better than 90% for a coronal slice through the isocenter. Pass rates for an off-axis coronal slice were also better than 90% except for one instance with 84% pass rate. CONCLUSIONS: Strengths of the dosimetry assessment procedure included the true anthropomorphic nature of the phantom used, the involvement of an expert from the reference center in carrying out the assessment at every site, and the ability of the assessment to detect and resolve dosimetry discrepancies.

Testing of a treatment planning system with beam data from IAEA TECDOC 1540.

Quality assurance of external-beam treatment-planning systems is recommended, and this can be partly achieved with predefined type tests. The beam data and test geometries of IAEA TECDOC 1540 have been used to test the analytical anisotropic algorithm (AAA) and pencil-beam convolution (PBC) algorithm of the Varian Eclipse treatment planning system. Beam models were created in Eclipse for 6 MV, 10 MV and 18 MV from the available beam data. Twelve test geometries were re-created in Eclipse, and the differences between Eclipse dose calculations and dose measurements were recorded. The AAA algorithm generally performed better than the PBC algorithm for the 12 tests, but both algorithms did not meet predefined tolerances for asymmetric wedge fields. An in-house monitor unit check program based on collimator and phantom scatter factors with tissue-phantom ratios was also tested and its calculations were found to agree with measurements to within 3.2% for on-axis points.

Amino acid signatures in the primate retina.

Pattern recognition of amino acid signals partitions virtually all of the macaque retina into 16 separable biochemical theme classes, some further divisible by additional criteria. The photoreceptor-->bipolar cell-->ganglion cell pathway is composed of six separable theme classes, each possessing a characteristic glutamate signature. Neuronal aspartate and glutamine levels are always positively correlated with glutamate signals, implying that they largely represent glutamate precursor pools. Amacrine cells may be parsed into four glycine-dominated (including one glycine/GABA immunoreactive population) and four GABA-dominated populations. Horizontal cells in central retina possess a distinctive GABA signature, although their GABA content is constitutively lower than that of amacrine cells and shows both regional and sample variability. Finally, a taurine-glutamine signature defines Müller's cells. We thus have established the fundamental biochemical signatures of the primate retina along with multiple metabolic subtypes for each neurochemical class and demonstrated that virtually all neuronal space can be accounted for by cells bearing characteristic glutamate, GABA, or glycine signatures.

Pattern recognition of amino acid signatures in retinal neurons.

Pattern recognition of amino acid signals partitions the cells of the goldfish retina into nine statistically unique biochemical theme classes and permits a first-order chemical mapping of virtually all cellular space. Photoreceptors, bipolar cells, and ganglion cells display a set of unique, nominally glutamatergic type E1, E1+E2, and E4 signatures, respectively. All horizontal cells are assignable to a GABAergic gamma 2 class or a non-GABAergic class with a glutamate-rich E3 signature. The amacrine cell layer is largely a mixture of (1) a taurine-dominated T1 Müller's cell signature and (2) GABAergic gamma 1, glycinergic G1, and dual glycinergic/GABAergic G gamma 1 amacrine cell signatures. Several major conclusions emerge from this work. (1) Glutamatergic, GABAergic, and glycinergic neural signatures and glial signatures account for over 99% of the cellular space in the retina. (2) All known neurons in the goldfish retina are associated with a set of conventional nonpeptide neurotransmitters. (3) Multiple forms of metabolic profiles are associated with a single nominal neurotransmitter category. (4) Glutamate and aspartate contents exhibit overlapping distributions and are not adequate univariate probes for identifying cell classes. (5) Signatures can serve as quantitative measures of cell state.

Effect of collimator motion on image quality in nuclear medicine.

To investigate the quality of gamma camera images obtained with moving collimators, a group of collimators was constructed which could be rotated or sinusoidally oscillated in two dimensions. The date indicate a broadening effect on images in the direction of collimator motion. Moving the collimator during imaging will reduce septal aberrations but will not increase resolution.

Digital tomosynthesis: technique for electronic reconstructive tomography.

A technique is described for obtaining tomographic images through retrospective reconstruction of digital data. The apparatus used for this technique, called digital tomosynthesis consists of a linear tomographic x-ray machine that has been modified by the addition of a fluoroscope and TV system, a video disk recorder, an analog-to-digital converter, and a small computer for data processing and manipulation. Video frames are collected and stored during a single tomographic sweep. The stored data are then digitized and retrospectively processed in the computer for reconstruction of any desired tomographic plane within the body. The major advantages of DTS include short patient study time, low radiation dose compared with conventional tomography, the ability to enhance the digitized image through manipulation of window and level display, and the applicability of this technique to dynamic studies such as angiotomography. Phantom studies show good diagnostic quality of the resulting images, and preliminary vascular studies in dogs indicate the clinical potential of this technique for use in digital subtraction angiotomography.