How can the co-ordinate transformation method of beam matching be extended to include separately labelled collimators?

The problem of matching radiation beams was tackled by Siddon in 1980 using co-ordinate transformations. Since then, the need to distinguish between individual collimators in prescriptions of treatment set-up, brought about by the widespread use of 3-D treatment planning systems and asymmetric fields, as well as a reversal of the rotation sense in the turntable co-ordinate system proposed by the International Electrotechnical Commission, have made it necessary to revisit this particular problem. This paper builds upon Siddon's general equations for the particular case of matching beams, and derives expressions for calculating treatment-unit settings which may be used in a computer program without the need to perform matrix manipulation. The expression treat the individual collimator jaws separately.

Immunolocalization of endothelin in the traumatized spinal cord: relationship to blood-spinal cord barrier breakdown.

The purpose of this study was to determine the relationship between endothelin-1 (ET-1), a prominent vasoactive agent, and the breakdown of the blood-spinal cord barrier along the axis of the cord after a moderate spinal cord injury. In the first study rats (n = 10) were euthanized 24 h after spinal cord injury and compared to sham (n = 5) and unoperated (n = 10) controls. Endothelin and immunoglobulins (IgG) were immunolocalized in adjacent sections of spinal cord using semiquantitative immunocytochemical techniques. In the second study animals were pretreated with the endothelin antagonist Bosentan (n = 6) or vehicle (n = 6) prior to spinal cord injury. Animals were euthanized at 24 h postinjury. Ten minutes prior to euthanasia animals were given horseradish peroxidase (HRP) intravenously. After perfusion fixation sections of cord were prepared for quantitative HRP histochemistry. After spinal cord injury there was enhanced staining for endothelin along the axis of the cord that correlated with the anatomical pattern of barrier breakdown to IgG. In those animals that were pretreated with Bosentan, there was a significant reduction in barrier breakdown along the axis of the injured cord as compared to those animals that received vehicle only. Taken together, this data implicate involvement of endothelin in the axial pattern of barrier breakdown after spinal cord injury.

Intrathecal administration of endothelin-1 in the rat: impact on spinal cord blood flow and the blood-spinal cord barrier.

The purpose of this study was to examine the integrity of the blood-spinal cord barrier after intrathecal administration of endothelin-1 (ET-1) in the rat spinal cord. A laser Doppler probe was positioned in the exposed subarachnoid space at the T8 vertebral level. In the first experiment, horseradish peroxidase (HRP), a marker of barrier integrity, was given intravenously prior to the intrathecal application of ET-1. Blood flow was then recorded for 3 h, after which the anesthetized animals were euthanized. In the second experiment, animals exposed to endothelin were recovered after confirming a 50% reduction in blood flow. HRP was given 10 min prior to euthanasia at 24 h post infusion. The intensity of staining for HRP was quantified by optical density in fixed sections of spinal cord. There was a significant sustained reduction in spinal cord blood flow and significant barrier breakdown to HRP at both 3 and 24 h after administration of the peptide. Based upon these results we conclude that intrathecal infusion of ET-1 reduces spinal cord blood flow and results in prolonged breakdown of the blood-spinal cord barrier.

Preliminary report of a pilot study of photoradiation therapy for the treatment of superficial malignancies of the skin, head and neck.

Within the past few years photoradiation therapy has emerged as a promising new treatment for many forms of localized malignant disease and a number of clinical trials are now in progress. The pilot study described in this paper is the first clinical trial of photoradiation therapy to be carried out in Great Britain. Although it is not possible to draw significant conclusions from the results obtained, it has been shown that all the tumours responded to treatment and in four patients who had tumours which were suitable for photoradiation therapy, complete tumour regression was obtained. Further trials are in progress and others are planned in a number of centres.

Photodynamic therapy in the treatment of malignant tumours of the skin and head and neck.

Photodynamic therapy utilizes a tumour-localizing photosensitive substance which, when activated by light of an appropriate wavelength, releases cytotoxic substances causing destruction of the malignant tumour with preservation of surrounding normal tissues. In this technique the only drug/light combination which has been regularly used to date is that of haematoporphyrin derivative and red light at a wavelength of 630 nm usually produced by a dye or gold vapour laser. A pilot/feasibility study was set up in Southampton in 1983, with ethical permission, to treat tumours of the skin and head and neck which had failed all other treatment modalities or for which there was no practical alternative therapy. Thirty-eight patients were treated in this study and all tumours showed a response; significant palliation was achieved in a number of patients. Basal cell carcinomas and the multiple lesions of Bowen's disease were found to be particularly suitable for this form of therapy and prolonged local control was achieved in a number of patients.

A three-zone model of soft-tissue damage by a CO2 laser.

CO2 laser damage to soft tissue may be divided into three zones--an outer layer of carbonised material, a zone of vacuolation where cavities have been formed by the explosive conversion of water to steam and a coagulated zone which has been formed at temperatures below 100 degrees C. A model is proposed which predicts the maximum (i.e. dynamic equilibrium) depths of each of these layers. The maximum effective thickness of the vacuolated zone is shown to depend upon the absorption coefficient of the tissue for CO2 laser radiation, but not on the incident irradiance. The thickness of the carbonised zone is shown to decrease with increasing irradiance, and the depth of the sub-boiling coagulated zone also decreases with increasing irradiance, but depends to some extent on the penetration of laser radiation through the soft tissue. Redistribution of heat within these zones after extinction of the laser radiation is considered, as is the effect of pulsed laser radiation. The predictions of the model could be tested by suitable experiments.

An extension of the three-zone model to predict depth of tissue damage beneath Er:YAG and Ho:YAG laser excisions.

Pulsed lasers such as Er:YAG and Ho:YAG with outputs at mid-infrared wavelengths emit radiation which may be transmitted by fibre to a treatment site. The thickness of soft-tissue damage beneath excisions made by these lasers is predicted using an extension to a model previously devised for CO2 laser radiation. The minimum achievable thickness occurs at a water absorption peak and at such high irradiance that heat cannot diffuse significantly compared with the radiation penetration depth. This minimum thickness is estimated to be in the order of 10 microns for the Er:YAG laser.

How far does thermal damage extend beneath the surface of CO2 laser incisions?

One of the principal advantages of the CO2 surgical laser over other types available is that there is little evidence of thermal injury extending very far beyond the surface of the laser wound. The degree of such damage is of interest because it affects tissue healing and the likelihood of post-operative infection. This paper presents a simple physical model of tissue irradiated by a CO2 laser beam. The depth of damage is predicted for the case where the ablation front and the damage wave ahead of it advance together at the same speed. The depth of damage is also calculated for the case of laser pulses of short duration where there has not been time to establish dynamic equilibrium. The results are plotted against local laser power density and show a trend of narrower damage depths with short laser pulses and high power densities. As a consequence, care should be taken not to ablate tissue at low power densities, as occurs when the laser beam is defocussed. The predicted damage depths are in broad agreement with histopathological experience.

What is the explanation for the changes to cobalt-60 tissue-air ratios in BJR Supplement 25?

Values of tissue-air ratio (TAR) in the recent British Journal of Radiology (BJR) Supplement 25 have been increased by nearly 2% over the values which have been accepted for the past 30 years. The need for this was shown by analysis of previous data using scaling laws, together with Monte Carlo calculations and careful re-measurement. However, it was not clear why previous determinations of TAR were in error: it was not, as some workers argued, because scattered radiation had been included in the absorbed dose in the miniphantom, because TAR data in BJR Supplement 17 had been derived from peak scatter factor (PSF), which is not based on the miniphantom concept. The purpose of this paper is to find the real explanation of why the PSF and, therefore, TAR were underestimated for so long. Two definitions of PSF are considered: one based on kerma and one based on dose. This paper relates PSF of either definition to measurements of air kerma by including in the derivation the scatter in the plug which replaces the chamber when it has been removed from the surface of the water phantom. The kerma-based PSF is found to be 2% higher than the simple ratio of chamber readings in phantom and in air. The value of the dose-based definition agrees with that of the kerma-based definition to within 0.2%. It is the scatter in the replacement plug in the surface of the water phantom which was effectively ignored by previous workers, and which explains the underestimates of around 2% in PSF and TAR. The value of the dose-based PSF differs slightly from that of the kerma-based PSF because of the different distributions of primary and scatter photon fluence.

Air-gap correction in electron treatment planning.

In electron treatment planning involving irregular surface contours the technique of shifting standard isodose curves to compensate for air gaps is unsatisfactory for oblique angles of incidence. For electron beams at normal incidence on a flat surface, earlier workers reported that the broad electron beam may be considered as the sum of many narrow beams, and that the standard isodose curves may be reproduced using the data for a narrow beam derived from a collimation experiment. This paper describes a simple alternative experiment to derive the necessary data, which include electrons scattered from the applicator walls. Computed plans using these data for electrons incident at 45 degrees on a flat surface and for incidence on an irregular surface agree with experiment. The method is compatible with, and was designed for, a very limited computing facility.

A simple method for matching electron beams in radiotherapy.

Many solutions have been proposed to solve the problem of 'hot' and 'cold' spots in the junction between abutting electron fields. Although some of these methods have proved satisfactory, the designs of the modifications to the applicators are generally applicator dependent and involve measuring data for individual fields. An idea which was originally proposed as a solution to a different problem is resurrected here because it happens to solve the beam-matching problem and because it is very simple to apply. The idea is to cover the end of the electron applicator completely with a slab of plastic, called a 'spoiler'. Formulae are proposed and tested for estimating the penumbra broadening and the extent of over- or underdosing at field junctions. The technique is applicator independent, and no extra beam-data measurements need be made for computer treatment planning of matching fields. The price paid for such simplicity is that consideration needs to be given to leading-off the other borders of the treatment fields because of the increased penumbra widths.

Can photography be used to measure isodose distributions of space irradiance for laser photodynamic therapy?

The space irradiance isodose distribution of light delivered in tissue by an interstitial optical fibre may be determined by photographing the light diffusing out of the tissue. Provided that a plane of symmetry is photographed, it is shown that there is no significant distortion of the isodose distribution measured in this way. Two series of photographs were taken to test the method. In one set, a partially reflecting film was used to simulate the presence of the missing tissue. Isodose distributions obtained were in agreement with the predictions of diffusion theory. The isodoses were "scaled' by measuring the space irradiance at one point with a bulb-tipped optical fibre. Optical parameters are deduced from the measurements. The method, which is simple and fast in use, should be of wide applicability.

Twenty-five years of MTPR--a theoretical and experimental analysis.

The system of modified tissue phantom ratio (called tissue standard factor, or TSF, in this paper) was introduced to facilitate the calculation of monitor units in isocentric configurations. Twenty-five years later, TSFS have been measured at 6 MV on different linear accelerators, and are in agreement with the original values, highlighting the property of machine independence. The utility of TSF is shown by the simplicity of the equation for calculating dose per monitor unit at any depth, field size and distance from source. New equations are given for relating isocentric systems to fixed-SSD systems, and the table of TSFS is extended to include a symbolic zero-area column, which is shown to be the primary-dose component of TSF in electronic equilibrium.

Intercomparison of whole-body counters using a multinuclide calibration phantom.

Whole-body counters in the UK have been compared using a multinuclide anthropomorphic phantom. A standard Bush phantom was modified by inserting channels into the long axis of each section. Radionuclide sources sealed in a urea-formaldehyde polymer were then inserted into the channels to simulate distributions of radioactivity in a human. The phantom was taken to 10 whole-body counters in the UK and estimates of 134Cs, 137Cs and 40K were obtained both separately and as mixtures. Results showed close agreement between the median estimates and the known activities. The technique also allowed diagnosis of particular problems in calibration for several of the counters.

The width of margins in radiotherapy treatment plans.

Publication of ICRU Reports 50 and 62 has highlighted the need to devise protocols for the process of drawing the planning target volume (PTV) around the clinical target volume (CTV). The margin surrounding the CTV should be wide enough to account for all geometric errors so that no part of the CTV accumulates a dose less than, for instance, 95% of that prescribed. One approach to the problem has been to draw a margin around the CTV delineated at the treatment preparation stage which is sufficiently wide that the mean position of the CTV will be encompassed in a specific percentage of cases, for example 90%. This accounts for the systematic errors. A further margin is then drawn to account for random set-up and organ-motion uncertainties during treatment. The width of this second margin has previously been shown to be 1.64(sigma - sigmap). Here sigma, a vector quantity, is the standard deviation which results from convolving the penumbra spread function of standard deviation sigmap with the Gaussian distributions of the daily positional uncertainties of organ motion and set-up error. However, it is shown in this paper that the calculation should take into account the beam configuration of the treatment plan. In a typical coplanar multibeam plan, usually in the transverse plane, any given edge of the target volume is normally defined by a single beam or two parallel and opposed beams. However, because of the presence of the other beams, the effect of the blurring of the edge-defining beam(s) is reduced, which changes the value of the required margin to beta (sigma - sigmap) where, for example, beta can be as low as 1.04 in the transverse plane of a three-beam plan. The width of the required margins is calculated for up to six beams and presented in a table. It is shown that, while the table was derived using an idealized plan of equally weighted plane beams irradiating a spherical target, it is also valid for non-uniform beam weightings, wedged-beam plans, target volumes of general shape and intensity-modulated radiotherapy (IMRT).

How should breathing motion be combined with other errors when drawing margins around clinical target volumes?

Geometric uncertainties in radiotherapy treatment may be accommodated by drawing an adequate margin around the clinical target volume (CTV). The width of the margin is commonly based upon the quadrature sum of the standard deviations of the contributory errors. This approach is satisfactory when the probability distributions of the component errors are Gaussian, but breathing-induced motion of the CTV is generally not Gaussian. This paper shows that the blurred dose distribution D(z) arising from a step function beam edge that is moving cyclically along the z-axis is given by D(z) = 2t/tau, where t(z) relates time to position and tau is the cycle duration. Applying this relation to realistic breathing models results in a dose distribution in which the sharp edge of the step function is still evident even after blurring caused by the motion. This suggests that breathing-induced motion should be accounted for separately, with the breathing margin added linearly to the quadrature sum of the other contributing errors.

Assessment of effective dose from concomitant exposures required in verification of the target volume in radiotherapy.

The requirement of the Ionising Radiation (Medical Exposure) Regulation 2000 [IR(ME)R] of justifying all exposures to ionizing radiation includes those from radiotherapy double exposure portal images resulting in exposure to normal tissues outside the treatment volume. Typical effective doses were calculated for a range of common sites using CT data to outline those parts of specific organs subject to concomitant radiation and generate dose-volume histograms. The product of the mean dose and the relative probability of inducing a fatal cancer in specific organs was used to determine a representative total effective dose in mSv per monitor unit for each site. A table of representative effective doses, ranging from 0.32 mSv to 2.56 mSv per monitor unit, was produced, which may be used to monitor cumulative effective doses of individual patients from double exposure portal images, in addition to those received from localization procedures.

Pulsed microamperage stimulation: a controlled study of healing of surgically induced wounds in Yucatan pigs.

BACKGROUND AND PURPOSE: Microamperage direct current and microamperage electromagnetic stimulation are used to accelerate healing in bone. Although many clinicians are using microamperage stimulation to relieve pain and facilitate wound healing, there is significant question regarding whether this low-intensity direct current significantly accelerates soft tissue wound repair. The purpose of this study was to determine whether low-voltage pulsed microamperage current (100 microA, 60 V, 0.1 Hz) enhances the healing of superficial, full-thickness, or incisional wounds created to simulate acute abrasions, ulcers, and lacerations. SUBJECTS: Ten adult Yucatan mini pigs served as the subjects for this study. METHODS: Variables associated with healing were measured in 60 matched pairs of surgically induced partial-thickness, full-thickness, and incisional wounds after either sham or anodal (positive-polarity) stimulation with pulsed microamperage current (100 microA) was administered for 1 hour per day for 5 days. Sterile, disposable electrodes (2 x 4 cm) were placed over each wound, which was kept wrapped and protected throughout the study. RESULTS: At 7 days postinjury, all wounds were healing well with no signs of infection. There were no differences in tensile strength, collagen density, maturity, or deposition (hydroxyproline), wound size, or visual appearance between the sham treatment and treatment lesions. No changes in local subcutaneous oxygen or temperature were found in the swine during or after microamperage stimulation. CONCLUSION AND DISCUSSION: This study did not provide any evidence to support the use of microamperage stimulation to accelerate wound healing. No negative effects, however, were found. Further research is needed to determine whether there is a critical interaction between the size of the electrode relative to the wound, the density of the current, the duration of the treatment, the polarity of the treatment electrode, and the acuity or chronicity of wounding and the effectiveness of microcurrent stimulation for wound healing.

Safety with surgical lasers.

As the sales of surgical lasers continue to grow, the problem of laser safety in hospitals becomes increasingly more urgent. This article considers both the principles and the practice of laser safety, and indicates how safety codes should be organized within a hospital. Eye safety is of paramount importance, and the effects of different wavelengths of laser radiation on the eye are described, both for intrabeam and extended-source exposure. An account is given of the concept of Maximum Permissible Exposure (MPE) and how it depends upon wavelength and exposure duration. The standard laser classification is developed in relation to MPE. The use of laser protective eyewear is discussed for the surgeon, other theatre staff and the patient. Finally, the role of the Laser Protection Supervisor and of the Laser Protection Adviser are explained in the context of establishing a local laser safety code.

Interpreting common hydration biomarkers on the basis of solute and water excretion.

BACKGROUND/OBJECTIVES: This investigation evaluated 12 hydration biomarkers, to determine which represent 24-h whole-body water balance (that is, measured as water retention or clearance (WR-C) by the kidneys). SUBJECTS/METHODS: Healthy males (n=59; body mass, 75.1±7.9 kg; height, 178±6 cm; age, 22±3 years; body mass index, 23.9±2.4 kg/m(2)) met with a registered dietitian each morning (days 1-11) to optimize completeness and accuracy of food and fluid records, then went about ordinary daily activities. These men visited the laboratory for blood samples and collected all urine produced on days 1, 3, 6, 9 and 12. The reference standard (WR-C) was calculated using 24-h urine volume, 24-h urine osmolality, and serum osmolality (single morning venous sample). RESULTS: Statistical regression analyses indicated that, among the 12 hydration biomarkers, only 24-h urine osmolality (r(2)=0.60, P<0.0001) and 24-h urine specific gravity (r(2)=0.52, P<0.0001) strongly predicted WR-C. The 24-h fluid intake, 24-h body mass change, 24-h urine color and 24-h urine volume were weak (P>0.05) predictors of WR-C, similar to serum osmolality and other single measurements (range of r(2) values, 0.19-0.0001). CONCLUSIONS: These observations of healthy, active young men demonstrate that WR-C is strongly related to the 24-h concentration of urine, which in turn reflects the excretion of total solids in the diet. Although morning urine assessments provided information about a single time point, 24-h urine osmolality and 24-h urine specific gravity were the best predictors of 24-h body water balance.