Water- and air-distributed conidia differ in sterol content and cytoplasmic microviscosity.

Airborne and waterborne fungal spores were compared with respect to cytoplasmic viscosity and the presence of ergosterol. These parameters differed markedly between the two spore types and correlated with spore survival. This suggests that the mode of spore dispersal has a bearing on cellular composition, which is relevant for the eradication of industrially relevant fungal propagules.

Hydrophilins in the filamentous fungus Neosartorya fischeri (Aspergillus fischeri) have protective activity against several types of microbial water stress.

Hydrophilins are proteins that occur in all domains of life and protect cells and organisms against drought and other stresses. They include most of the late embryogenesis abundant (LEA) proteins and the heat shock protein (HSP) Hsp12. Here, the role of a predicted LEA-like protein (LeamA) and two Hsp12 proteins (Hsp12A and Hsp12B) of Neosartorya fischeri was studied. This filamentous fungus forms ascospores that belong to the most stress-resistant eukaryotic cells described to date. Heterologous expression of LeamA, Hsp12A and Hsp12B resulted in increased tolerance against salt and osmotic stress in Escherichia coli. These proteins were also shown to protect lactate dehydrogenase against dry heat and freeze-thaw cycles in vitro. Deletion of leamA caused diminished viability of sexual ascospores after drought and heat. This is the first report on functionality of Hsp12 and putative LeamA proteins derived from filamentous fungi, and their possible role in N. fischeri ascospore resistance against desiccation, high temperature and osmotic stress is discussed.

Tumour resistance to cisplatin: a modelling approach.

Although chemotherapy has revolutionized the treatment of haematological tumours, in many common solid tumours the success has been limited. Some of the reasons for the limitations are: the timing of drug delivery, resistance to the drug, repopulation between cycles of chemotherapy and the lack of complete understanding of the pharmacokinetics and pharmacodynamics of a specific agent. Cisplatin is among the most effective cytotoxic agents used in head and neck cancer treatments. When modelling cisplatin as a single agent, the properties of cisplatin only have to be taken into account, reducing the number of assumptions that are considered in the generalized chemotherapy models. The aim of the present paper is to model the biological effect of cisplatin and to simulate the consequence of cisplatin resistance on tumour control. The 'treated' tumour is a squamous cell carcinoma of the head and neck, previously grown by computer-based Monte Carlo techniques. The model maintained the biological constitution of a tumour through the generation of stem cells, proliferating cells and non-proliferating cells. Cell kinetic parameters (mean cell cycle time, cell loss factor, thymidine labelling index) were also consistent with the literature. A sensitivity study on the contribution of various mechanisms leading to drug resistance is undertaken. To quantify the extent of drug resistance, the cisplatin resistance factor (CRF) is defined as the ratio between the number of surviving cells of the resistant population and the number of surviving cells of the sensitive population, determined after the same treatment time. It is shown that there is a supra-linear dependence of CRF on the percentage of cisplatin-DNA adducts formed, and a sigmoid-like dependence between CRF and the percentage of cells killed in resistant tumours. Drug resistance is shown to be a cumulative process which eventually can overcome tumour regression leading to treatment failure.

Laser-scanned agarose gel sections for radiation field mapping.

PURPOSE: A dedicated laser scanning system has been applied to the measurement of optical density change in ferrous sulphate-xylenol orange dye-agarose gel mixtures for applications in radiation field mapping. METHODS AND MATERIALS: The gels were poured, irradiated, and optically scanned in Lucite casts providing a uniform gel section thickness of 1 cm. The gel sections were optically scanned both pre- and postirradiation to determine the optical density change in the gel and consequently the absorbed dose. Irradiations of the gel sections were performed with an orthovoltage unit and a linear accelerator. RESULTS: For linear dose response up to 10 Gy, an appropriate gel mixture was found to be 0.4 mM Fe2+, 0.2mM xylenol orange dye, 25 mM sulphuric acid, and 1% by weight agarose gel with a mixing temperature of 60 degrees C. In dosimetry of a 20 x 10 cm 6 MV wedged x-ray field, good agreement in terms of relative dose was found between the gel values and ionization chamber readings. However, in repeated experiments with the gel dosimeter involving calculation of absolute dose at various points in the wedged field, variations in absolute dose measurements of up to +/- 5% were observed. CONCLUSION: The dosimetry technique involving laser scanning of agarose gel sections has potential for further applications in radiotherapy dosimetry.

Localization and treatment of familial malignant nonfunctional paraganglioma with iodine-131 MIBG: report of two cases.

Two cases of familial, malignant, nonfunctional paraganglioma are reported. Uptake of iodine-131 metaiodobenzylguanidine ([131I]MIBG) by the tumors and metastases was demonstrated. In the first case, with multicentric and locally invasive disease, [131I]MIBG correctly localized a right carotid body paraganglioma which had been missed arteriographically. In the second case, with widespread, symptomatic metastatic disease, a therapeutic dose of [131I]MIBG produced palliation of bone pain after the failure of radio- and chemotherapy. Uptake of [131I]MIBG by paragangliomas does not correlate with catecholamine secretory activity. Iodine-131 MIBG should be considered as a therapeutic option in unresectable, malignant paragangliomas which take up this radiopharmaceutical.

A design for a dual assembly multileaf collimator.

A multileaf collimator for radiation therapy has been designed that splits each leaf bank into two vertically displaced levels with each level consisting of alternate leaves and leaf spaces. The leaves in the upper level shield the spaces in the lower level. Each level can move laterally, in the direction perpendicular to leaf motion by one leaf width. Following lateral movement of one level, the leaves align with the other level and radiation is transmitted through the collimator as multiple slit fields in a grid pattern. This transmission can be used to form an image of the external anatomy and would enable double-exposure portal images to be acquired much more rapidly than at present. These could potentially be acquired during the treatment delivery. The radiation profiles transmitted for image formation through the collimator design were investigated. Individual and grid pattern slit field profiles formed by tungsten and lead alloy collimators were measured with varying slit width, source-collimator distance, collimator-detector distance, and collimation thickness. The slit width was found to have the major influence on the transmitted profiles. As the slit width decreases the profiles become broader than the geometric slit projection resulting in increasing overlap of adjacent profiles. The overlap results in a modulated image of the external anatomy for small slit widths, rather than a sampled or "grid" image for larger widths. The shielding of this design was found to be adequate provided the leaf faces of the adjacent vertically displaced leaves are at least aligned, therefore an overlap or tongue and groove is not required.

Evaluation of an algorithm for the assessment of the MTF using an edge method.

An algorithm to calculate the presampling modulation transfer function (MTF) of an imaging system from an angled edge image has its own inherent transfer function. Factors such as the angle of the sampling aperture to the edge, registration of edge function profiles using the determined edge angle, differentiation, smoothing, and folding all combine to produce the frequency response of the algorithm. In this work, the profile registration transfer function accounting for an error in the determined edge angle has been derived. This has been incorporated with other, previously reported, algorithm component transfer functions to fully characterize the MTF calculation algorithm. When registering profiles, small errors in the edge angle determination were found to result in large errors in the MTF, as the misalignment errors increase with the number of profiles. For example, registering 50 profiles a 0.07 degree error in a 7 degree edge angle (1% error) produces a 36% error in the MTF at the system cutoff frequency f=f(c) when profiles are oversampled at a frequency f(s)=8f(c)(f(c) is defined as the maximum frequency reproducible without aliasing when sampling at the limiting system Nyquist frequency f(s) = 2f(c)). These results highlight the importance of quantifying the transfer function of the algorithm used to determine an imaging system modulation transfer function. The MTF calculation algorithm and the transfer function analysis have been incorporated into a Windows-based software program to be made available for general use.

An indeterministic Monte Carlo technique for fast time of flight photon transport through optically thick turbid media.

A time-resolved indeterministic Monte Carlo (IMC) simulation technique is proposed for the efficient construction of the early part of the temporal point spread function (TPSF) of visible or near infrared photons transmitted through an optically thick scattering medium. By assuming a detected photon is a superposition of photon components, the photon is repropagated from a point in the original path where a significant delay in forward propagation occurred. A weight is then associated with each subsequently detected photon to compensate for shorter components. The technique is shown to reduce the computation time by a factor of at least 4 when simulating the sub-200 picosecond region of the TPSF and hence provides a useful tool for analysis of single photon detection in transillumination imaging.

Development of a CCD array imaging system for measurement of dose distributions in doped agarose gels.

An imaging system for agarose gel sections has been investigated for applications in rapid two-dimensional radiation dosimetry. The imaging system, with white light illumination and CCD camera detection, was designed for measurement of the radiation-induced optical density changes in iron- and xylenol orange dye-doped agarose gels. The performance of the imaging system was compared with that of a laser scanning system for the gels and with the accepted dosimetry standard, the ionization chamber. In measurement of beam profiles of two therapeutic radiation fields, relative dose values from the CCD camera imaging system were on average within 3% ranging from 0.005% to 7.5%) of values recorded with a parallel plate ionization chamber. In comparison with the laser scanner, the CCD camera imaging system provided comparable spatial resolution and an increased rate of data acquisition, although a consistently reduced signal to noise ratio was observed. Suggestions for improving the camera imaging technique include noise reduction through camera cooling and further frame averaging.

Modelling of post-irradiation accelerated repopulation in squamous cell carcinomas.

The mechanisms postulated to be responsible for the accelerated repopulation of squamous cell carcinomas during radiotherapy are the loss of asymmetry of stem cell division, acceleration of stem cell division, abortive division and/or recruitment of the non-cycling cell with proliferative capacity. Although accelerated repopulation was observed with recruitment and accelerated cell cycles, it was not sufficient to cause an observable change to the survival curve. However, modelling the loss of asymmetry in stem cell division has reshaped the curve with a 'growth' shoulder. Cell recruitment was not found to be a major contributor to accelerated tumour repopulation. A more significant contribution was provided through the multiplication of surviving tumour stem cells during radiotherapy, by reducing their cell cycle time, and due to loss of asymmetry of stem cell division.

First photon detection in time-resolved transillumination imaging: a theoretical evaluation.

First photon detection, as a special case of time-resolved transillumination imaging, is studied through the derivation of the temporal probability density function (pdf) for the first arriving photon. The pdf for different laser intensities, media and second and later arriving photons were generated. The arrival time of the first detected photon reduced as the laser power increased and also when the scattering and absorption coefficients decreased. The pdf for an imbedded totally absorbing 3 mm inhomogeneity may be distinguished from the pdf of a homogeneous turbid medium similar to that of human breast in dimensions and optical properties.

Spatial resolution in fast time-resolved transillumination imaging: an indeterministic Monte Carlo approach.

The spatial resolution achievable in time-resolved optical transillumination imaging through a turbid (scattering and absorbing) medium has been reassessed theoretically. The temporal point spread function was constructed assuming a delta function input pulse, a approximately 50 mm thick medium and a small detector with zero risetime. Temporal profiles were derived from an indeterministic Monte Carlo simulation for different time scales. From the temporal point spread function (TPSF), an analytic edge response function from which the spatial resolution was determined was derived. Previous analytical methods for determining the spatial resolution are approximations for very short flight times (sub-100 ps time region). The results show that a spatial resolution of about two millimetres is possible under ideal signal-to-noise ratio conditions and with detector gate times of the order of ten picoseconds. If this predicted spatial resolution can be achieved in an imaging system, it may be possible to improve the diagnosis of breast tumours.

Quality of life and metabolic control in patients with diabetes mellitus type 1 treated by continuous subcutaneous insulin infusion or multiple daily insulin injections.

OBJECTIVE: To assess the quality of life and metabolic control in patients with diabetes mellitus type 1 on continuous subcutaneous insulin infusion (CSII) in comparison with patients on multiple daily insulin injections (MDII). RESEARCH DESIGN AND METHODS: The study included 49 patients (13 males, 36 females), aged 41.4+/-11.3 years (mean+/-SD) on CSII for >1 year and 79 patients (43 males, 36 females), aged 43.1+/-14.8 years on MDII for >1 year, from three Dutch diabetic clinics. There were no statistically significant differences in duration of diabetes, social class, level of education, marital status, smoking or recent admissions to hospital. The questionnaires used were a Diabetes Quality of Life scale adapted from the DCCT, the Diabetes Satisfaction Questionnaire (DTSQ), and the WHO Well-Being Questionnaire. HbA1c was measured with an HPLC method (reference range 4.3 to 6.1 %). RESULTS: Using two-sided t-tests no statiscally significant differences were found between the patients on CSII and MDII with respect to quality of life (version A (<30 years) 4.32+/-0.22 vs 4.20+/-0.30; version B (> or =30 years) 4.18+/-0.25 vs 4.29+/-0.28), well-being (48.59+/-9.23 vs 50.99 +/-8.70), satisfaction with treatment (5.10+/-0.69 vs 5.15+/-0.71) and HbA1c (8.14+/-1.51 vs 8.47+/-1.40). Frequency of daily blood glucose monitoring was slightly higher in CSII than in MDII patients (4.52+/-1.19 vs 3.60+/-1.47; p<0.0001). CONCLUSION: The present data indicate that patients on CSII have similar QoL based on questionnaires when compared with patients on MDII. These data suggest that in patients with less optimal control on MDII, converting the treatment strategy to CSII is not associated with decreased quality of life.

Mass screening of Irish wolfhound puppies for portosystemic shunts by the dynamic bile acid test.

Five hundred and sixty-six Irish wolfhound puppies aged six to 15 weeks were tested for congenital portosystemic shunts by the dynamic bile acid method. Plasma ammonia concentration was also measured in 165 of the puppies both fasting and postprandially. Nineteen puppies (3.4 per cent), nine males and 10 females, had portosystemic shunts. Smaller litters appeared to be more likely to contain affected puppies. The postprandial bile acid concentration was a reliable predictor of the presence of a shunt, with the highest concentration in a normal puppy being 38 mumol/litre and the lowest in an affected puppy being 43 mumol/litre. In contrast, fasting bile acid concentrations were normal in the majority of the affected puppies. There was considerable overlap in fasting plasma ammonia concentrations between normal and affected puppies (26 puppies, 15.8 per cent of those tested). Postprandial ammonia concentration appeared to give better separation between the two groups, apart from two individuals which produced bizarre results. It was concluded that the postprandial or dynamic bile acid test is an appropriate test for the mass screening of Irish wolfhound puppies for portosystemic shunts, and guidelines are proposed for the interpretation and follow-up of the test.

Absorbance measurement with a helium-neon laser for chemical dosimetry.

A laser-based system for absorbance measurement has been developed for use in chemical dosimetry as an alternative to the spectrophotometer. The system incorporating a Helium-Neon laser operating at 543.5 nm is designed specifically for measurement of absorbed doses below 10 Gy with the ferrous sulphate-benzoic acid-xylenol orange (FBX) dosimeter. Absorbance measurement for the FBX dosimeter is normally carried out at 540 nm with a spectrophotometer. The performance of the laser-based system in measurement of absorbance is comparable to that of a standard spectrophotometer and it is concluded that the absorbance measurement technique is not the limiting factor in the sensitivity of the FBX dosimeter for absorbed doses below 1 Gy.

Radiographic measurement of bone mineral: reviewing dual energy x-ray absorptiometry.

Features of the three major brands of DEXA equipment available in Australasia have been summarised. Radiation hazard is small with patient effective doses of the order of a few microSieverts. In vivo measurement precision of the order of 1% is achievable for PA scans of the lumbar spine. Lateral scans can achieve measurement precision of the order of 4%. Recent technological developments using X-ray fan beams and multi element detector arrays on C-arm devices have resulted in faster scan times, higher resolution images, and an ability to perform PA and lateral scanning without the need to reposition the patient. Accuracy of DEXA is dependent upon specific instrumentation and data reduction algorithms, but results generally correlate well with ashed bone measurements. Major sources of inaccuracy include inhomogeneous distributions of fat, and machine specific factors such as edge detection algorithms. Lack of absolute inter unit comparability may cause difficulties in clinical practice.

The efficacy of K-edge filters in diagnostic radiology.

The application of K-edge filters in diagnostic radiology has been investigated by many workers for over twenty years. These investigations have analysed the effects of such filters on image quality and radiation dose as well as the practicalities of their application. This paper presents a synopsis of the published works and concludes that K-edge filters do not perceptibly improve image quality and make only limited reductions in patient dose. K-edge filters are also costly to purchase and potentially result in a reduction in the cost effectiveness of x-ray examinations by increasing the x-ray tube loading. Equivalent contrast enhancement and dose reductions can be achieved by the assiduous choice of non-selective filters.

Evaluation of the mechanical alignment of a linear accelerator with an electronic portal imaging device (EPID).

Mechanical misalignment of a medical linear accelerator can be caused by any combination of source position displacement relative to the collimator rotational axis, collimator jaw asymmetry, or when the rotational axes of the gantry and the collimator do not intersect. A test procedure sensitive to all of these problems has been developed using an Electronic Portal Imaging Device (EPID). Each marker is placed on top of the EPID housing and on the treatment couch, then two images are acquired for gantry positions 180 degrees apart. By comparing the positions of the markers and their distances to the beam centre, mechanical alignment of the linear accelerator can be assessed. By comparing the positions of the beam centre for another two images acquired at collimator angles 180 degrees apart, the three potential sources of misalignment can be distinguished. Results with Siemens' Beam View were presented and determination accuracy of better than 0.25 mm can be achieved.

The linear accelerator mechanical and radiation isocentre assessment with an electronic portal imaging device (EPID).

Regular checks on the performance of radiotherapy treatment units are essential and a variety of protocols has been published. These protocols identify that the determination of isocentre must be accurate and unambiguous since both the localization of a radiation field on a patient and positioning aids are referenced to it. An EPID (BIS 710) with a combined light and radiation scintillation detector screen was used to assess mechanical and radiation isocentres for different collimator and gantry angles. Crosshair positions within light field images were determined from fitted Gaussian intensity profiles and then used to calculate the displacement of the mechanical isocentre. For comparison, the position of the crosshair was also recorded on a graph paper. The radiation field centre was first calculated from the set up geometry for given gantry/collimator angles and then compared with measured values to assess the displacement of the radiation isocentre. The radiation isocentre was also checked by locating a marker, positioned on the couch, on the EPID radiation images for different treatment couch angles. The mechanical and radiation isocentres were determined from the EPID light field and radiation images respectively with an accuracy of 0.3 mm using simple PC based programs. The study has demonstrated the feasibility of using the EPID to assess mechanical and radiation isocentres of a linear accelerator in a quick and efficient way with a higher degree of accuracy achieved as compared to more conventional methods, e.g. the star shot.

Performance characteristics of a laser based planar imaging system.

With the advent of lasers and high sensitivity detectors, there has been a recent renewed interest in medical imaging at visible wavelengths. This paper reports on the investigation of the spatial resolution of a prototype laser based planar imaging system by examining the transmission of the laser beam through a phantom medium having similar absorption and scattering properties to that of soft tissue. The results of this work, whilst supporting the conclusions of other recent publications, have demonstrated a previously unreported phenomenon. With the experimental configuration described in this paper, opaque objects, in the form of thin wires, are equally well resolved at similar distances from both the input and exit boundaries of the scattering medium. The spatial resolution is a maximum nearest these boundaries.