The combined effects of diabetes and ionising radiation on the rat retina: an ultrastructural study

The combined effect of STZ-diabetes and ionising radiation on the rat retina was investigated. Wistar rats, which had been diabetic for 6 months, were irradiated with a single dose of x-rays (1500 cGy) and the ultrastructural effects evaluated at 4-10 mths post-irradiation. At 4 months post-irradiation, the outer nuclear layer of the retina was greatly reduced in thickness and the photoreceptor outer segments were disorganised and reduced in length. In addition, the nerve fibre layer contained many cytoid bodies and there were many redundant basement membrane tubes throughout the inner retina. By 6 months post-irradiation, the photoreceptor cells were virtually absent, bringing the external limiting membrane into close apposition to the RPE. Throughout large areas of the outer retina, RPE cells were hypertrophic and some had proliferated into the inner retina. In many regions, proliferating retinal capillaries were observed within the RPE layer, and at 8 months post-irradiation, some vessels extended into the inner retina accompanied by RPE cells. At 10 months post-irradiation, the RPE was atrophic and degenerative with retinal glial cells coming into contact with Bruch's membrane. In some areas, the glia which had breached Bruch's membrane had invaded the underlying choroid. Where glial cells contacted the choriocapillaries, the vessels assumed the appearance of retinal vessels with plump endothelia and no fenestrations. This study has described a progressive inner retinal ischemia, with cytoid bodies, capillary non-perfusion and general atrophy of the inner retina intensifying markedly with increasing post-irradiation time.(ABSTRACT TRUNCATED AT 250 WORDS)

The combined effect of diabetes and ionising radiation on the retinal vasculature of the rat

The clinical impression that pre-existing diabetes exacerbates radiation injury to the retinal vasculature was studied in STZ diabetic rats. Half of 2 groups of streptozotocin (STZ)-induced diabetic rats and 1 group of normal animals had their right eyes irradiated with 1000 cGy of 90 KVP x-rays. The prevalence of acellular capillaries in trypsin digests of the retinal vasculature was quantified for each of the 6 groups of animals at 6.5 months post-irradiation. The prevalence of acellular capillaries in both non-irradiated diabetic groups was significantly higher than in controls while the irradiated animals in each of the three main categories showed a statistically significant increase compared to their non-irradiated equivalents. However, the net increase in acellular capillaries following irradiation was much greater in rats with an 8 month term of pre-existing diabetes (180%) than in those which had only been diabetic for 3 months (36%). The results of this study suggest a synergistic relationship between pre-existing diabetes and ionising radiation in the development of retinal vasculopathy, and that the potentiation of the vascular damage is dependent on the duration of diabetes prior to radiation exposure.

Late ultrastructural changes in the retina of the rat following low-dose X-irradiation

This study describes ultrastructural changes in the pigmented hooded Lister rat retina, 3-12 months following X-irradiation with single doses of between 200 and 2000 cGy. The extreme radiosensitivity of the photoreceptor cells was underlined by the continued manifestation of fine structural changes and cell death up to 6 months post-radiation in animals receiving doses above 500 cGy. The retinal pigment epithelial (RPE) cells were more radioresistant than photoreceptors and RPE cell loss was only observed at doses of more than 1500 cGy. One year after irradiation with 1500 cGy the retinal vasculature showed capillary occlusion with some evidence of recanalisation. Telangiectasia was observed in the large retinal veins. Although the inner retinal neurones and glial cells showed no evidence of direct radiation damage, the nerve fibre layer adjacent to occluded retinal vessels demonstrated ultrastructural evidence of ischaemic neuropathy and retinal oedema. At doses above 1500 cGy the choriocapillaris showed platelet aggregation and capillary loss.

Ionizing radiation and the retina

This review considers the effects of ionizing radiation on the retina and examines the relationship between the natural course of radiation retinopathy and the radiobiology of the retinal vascular endothelial cell (RVEC). Radiation retinopathy presents clinically as a progressive pattern of degenerative and proliferative vascular changes, chiefly affecting the macula, and ranging from capillary occlusion, dilation, and microaneurysm formation, to telangiectasia, intraretinal microvascular abnormalities, and neovascularization. The total-radiation dose and fractionation schedule are the major determinants for the time of onset, rate of progression, and severity of retinopathy, although other factors such as concomitant chemotherapy and preexisting diabetes may exaggerate the vasculopathy by intensifying the oxygen-derived free-radical assault on the vascular cells. The differential radiosensitivity of RVECs is attributed to their nuclear chromatin conformation, their antioxidant status, and their environment. We propose pathogenetic mechanisms for radiation retinopathy and suggest that the peculiar latency and unique clinical pattern is related to the life cycle of the RVEC. A rationale is also proposed for the use of radiotherapy in the treatment of subneovascularization and age-related macular degeneration.

IMRT for image-guided single vocal cord irradiation

PURPOSE: We have been developing an image-guided single vocal cord irradiation technique to treat patients with stage T1a glottic carcinoma. In the present study, we compared the dose coverage to the affected vocal cord and the dose delivered to the organs at risk using conventional, intensity-modulated radiotherapy (IMRT) coplanar, and IMRT non-coplanar techniques.

METHODS AND MATERIALS: For 10 patients, conventional treatment plans using two laterally opposed wedged 6-MV photon beams were calculated in XiO (Elekta-CMS treatment planning system). An in-house IMRT/beam angle optimization algorithm was used to obtain the coplanar and non-coplanar optimized beam angles. Using these angles, the IMRT plans were generated in Monaco (IMRT treatment planning system, Elekta-CMS) with the implemented Monte Carlo dose calculation algorithm. The organs at risk included the contralateral vocal cord, arytenoids, swallowing muscles, carotid arteries, and spinal cord. The prescription dose was 66 Gy in 33 fractions.

RESULTS: For the conventional plans and coplanar and non-coplanar IMRT plans, the population-averaged mean dose ± standard deviation to the planning target volume was 67 ± 1 Gy. The contralateral vocal cord dose was reduced from 66 ± 1 Gy in the conventional plans to 39 ± 8 Gy and 36 ± 6 Gy in the coplanar and non-coplanar IMRT plans, respectively. IMRT consistently reduced the doses to the other organs at risk.

CONCLUSIONS: Single vocal cord irradiation with IMRT resulted in good target coverage and provided significant sparing of the critical structures. This has the potential to improve the quality-of-life outcomes after RT and maintain the same local control rates.

Control of leaky-mode propagation and radiation properties in hybrid dielectric-waveguide printed-circuit technology: Experimental results

Experimental results are presented to show how a planar circuit, printed on a laterally shielded dielectric waveguide, can induce and control the radiation from a leaky-mode. By studying the leaky-mode complex propagation constant, a desired radiation pattern can be synthesized, controlling the main radiation characteristics (pointing direction, beamwidth, sidelobes level) for a given frequency, This technique leads to very flexible and original leaky-wave antenna designs. The experiments show to be in very good agreement with the leaky-mode theory.

Radiation retinopathy--clinical, histopathological, ultrastructural and experimental correlations

Clinical, pathological and experimental studies of radiation retinopathy confirm that the primary vascular event is endothelial cell loss and capillary closure. Pericytes are less susceptible, but typically atrophy as the capillaries become non-functional. The immediate effects of radiation reflect interphase and early mitotic death of injured endothelial cells, whereas later changes may be attributed to delayed mitotic death of compromised endothelial cells as they attempt division in the ordinary course of repair and replacement. Capillary occlusion leads to the formation of dilated capillary collaterals which may remain serviceable and competent for years. Microaneurysms develop in acellular and poorly supported capillaries, predominantly on the arterial side of the circulation and adjacent to regions of poorly perfused retina. Alterations in haemodynamics produce large telangiectatic-like channels which, typically develop a thick collagenous adventitia and may become fenestrated. Limited capillary regeneration occurs, usually evident as recanalisation of arterioles or venules by new capillaries. Vitreo-retinal neovascularisation may occur where retinal ischaemia is widespread. Radiation produces an exaggerated vasculopathy in patients with diabetes mellitus, and five month streptozotocin-induced diabetic rats develop a severe ischaemic retinopathy with vitreoretinal neovascularisation when exposed to 1500 cGy of radiation. Later photocoagulation is useful in containing or reversing microvascular incompetence and vasoproliferation in some patients with advanced radiation retinopathy.

Localised gamma irradiation and experimental intraocular proliferation

A controlled study was undertaken to assess the effect of gamma irradiation on post-traumatic intraocular cellular proliferation. A standard perforating injury in the posterior segment of the rabbit eye was used to induce intraocular cellular proliferation and vitreo-retinal membrane formation. The site of injury was irradiated with an ophthalmic Cobalt60 applicator which provided a continuous source of gamma rays. Non-irradiated eyes developed traction retinal detachments associated with post-traumatic vitreo-retinal membranes. Irradiated eyes developed attenuated membranes or atrophic retinal scars, with the retina remaining attached. The membranes in non-irradiated eyes were highly cellular with abundant collagen, while irradiated membranes had fewer cells within a sparse collagen matrix. The episcleral fibroblasts, on autoradiographic studies appeared to be the main source of the cells that formed the proliferating tissue in both non-irradiated and irradiated eyes. In irradiated eyes both the inflammatory response and division of fibroblasts were delayed and reduced.

A novel experimental approach to investigate radiolysis processes in liquid samples using collimated radiation sources

Here is detailed a novel and low-cost experimental method for high-throughput automated fluid sample irradiation. The sample is delivered via syringe pump to a nozzle, where it is expressed in the form of a hanging droplet into the path of a beam of ionising radiation. The dose delivery is controlled by an upstream lead shutter, which allows the beam to reach the droplet for a user defined period of time. The droplet is then further expressed after irradiation until it falls into one well of a standard microplate. The entire system is automated and can be operated remotely using software designed in-house, allowing for use in environments deemed unsafe for the user (synchrotron beamlines, for example). Depending on the number of wells in the microplate, several droplets can be irradiated before any human interaction is necessary, and the user may choose up to 10 samples per microplate using an array of identical syringe pumps, the design of which is described here. The nozzles consistently produce droplets of 25.1 ± 0.5 μl.

Experimental measurements of the collisional absorption of XUV radiation in warm dense aluminium

The collisional (or free-free) absorption of soft x rays in warm dense aluminium remains an unsolved problem. Competing descriptions of the process exist, two of which we compare to our experimental data here. One of these is based on a weak scattering model, another uses a corrected classical approach. These two models show distinctly different behaviors with temperature. Here we describe experimental evidence for the absorption of 26-eV photons in solid density warm aluminium (Te≈1 eV). Radiative x-ray heating from palladium-coated CH foils was used to create the warm dense aluminium samples and a laser-driven high-harmonic beam from an argon gas jet provided the probe. The results indicate little or no change in absorption upon heating. This behavior is in agreement with the prediction of the corrected classical approach, although there is not agreement in absolute absorption value. Verifying the correct absorption mechanism is decisive in providing a better understanding of the complex behavior of the warm dense state.

Experimental and Modelling Studies of the Thermodynamics and Kinetics of Phase and Structural Transformations in a Gamma TiAl-based Alloy

This work combines microscopy, synchrotron radiation X-ray diffraction, differential scanning calorimetry and thermodynamic calculations in the characterisation of phase transformation behaviour of a Ti–46Al–1.9Cr–3Nb alloy upon continuous heating at constant rates. It has been found that the Ti–46Al–1.9Cr–3Nb alloy after being forged at 1200 °C without further treatment has a duplex microstructure consisting of fine equiaxed and lamellar ? grains with a small amount of a2 plates and particles and about 1 wt.% B2 phase. Differential scanning calorimetry revealed reproducibly several thermal effects upon heating of the as-forged alloy. These thermal effects are related to the equilibration and homogenisation of the sample, change of phase ratios between a2, ? and B2 phases in particular the increase of B2 in respect to a2 and ?, and the following five phase transformations: a2 + ? + B2 a + ? + B2, a + ? + B2 a + ?, ? + a a, a a + ß, a + ß a + ß + L. The observation of these transformations by differential scanning calorimetry is largely in agreement with literature phase diagrams and thermodynamic calculations, though care is needed to consider the different alloy compositions. Kinetics of the ? + a a phase transformation in the Ti–46Al–1.9Cr–3Nb alloy has been quantitatively derived from the calorimetry data, giving phase compositions at any point during the transformation upon continuous heating.

Experimental characterization of the nonlinear optical and magneto-optical properties of interfaces

An effective ellipsometric technique to determine parameters that characterize second-harmonic optical and magneto-optical effects in centrosymmetric media within the electric-dipole approximation is proposed and outlined in detail. The parameters, which are ratios of components of the nonlinear-surface-susceptibility tensors, are obtained from experimental data related to the state of polarization of the second-harmonic-generated radiation as a function of the angle between the plane of incidence and the polarization plane of the incident, linearly polarized, fundamental radiation. Experimental details of the technique are described. A corresponding theoretical model is given as an example for a single isotropic surface assuming polycrystalline samples. The surfaces of air-Au and air-Ni (in magnetized and demagnetized states) have been investigated ex situ in ambient air, and the results are presented. A nonlinear, least-squares-minimization fitting procedure between experimental data and theoretical formulas has been shown to yield realistic, unambiguous results for the ratios corresponding to each of the above materials. Independent methods for verifying the validity of the fitting parameters are also presented. The influence of temporal variations at the surfaces on the state of polarization (due to adsorption, contamination, or oxidation) is also illustrated for the demagnetized air-Ni surface. (C) 2005 Optical Society of America

New advances in radiation biology.

Current understanding of risk associated with low-dose radiation exposure has for many years been embedded in the linear-no-threshold (LNT) approach, based on simple extrapolation from the Japanese atomic bomb survivors. Radiation biology research has supported the LNT approach although much of this has been limited to relatively high-dose studies. Recently, with new advances for studying effects of low-dose exposure in experimental models and advances in molecular and cellular biology, a range of new effects of biological responses to radiation has been observed. These include genomic instability, adaptive responses and bystander effects. Most have one feature in common in that they are observed at low doses and suggest significant non-linear responses. These new observations pose a significant challenge to our understanding of low-dose exposure and require further study to elucidate mechanisms and determine their relevance.