Diabet. Med. 29, 776783 (2012) Abstract Aims To develop and evaluate an image grading external quality assurance system for the Scottish Diabetic Retinopathy Screening Programme. Method A web-based image grading system was developed which closely matches the current Scottish national screening software. Two rounds of external quality assurance were run in autumn 2008 and spring 2010, each time using the same 100 images. Graders were compared with a consensus standard derived from the top-level graders results. After the first round, the centre lead clinicians and top-level graders reviewed the results and drew up guidance notes for the second round. Results Grader sensitivities ranged from 60.0 to 100% (median 92.5%) in 2008, and from 62.5 to 100% (median 92.5%) in 2010. Specificities ranged from 34.0 to 98.0% (median 86%) in 2008, and 54.0 to 100% (median 88%) in 2010. There was no difference in sensitivity between grader levels, but first-level graders had a significantly lower specificity than level-two and level-three graders. In 2008, one centre had a lower sensitivity but higher specificity than the majority of centres. Following the feedback from the first round, overall agreement improved in 2010 and there were no longer any significant differences between centres. Conclusions A useful educational tool has been developed for image grading external quality assurance.

Results Results show that as the dose was decreased below D ref , both the clarity and detectability of lesions in the lung images worsened when there was no facility to manipulate the image. The onset of a significant difference in image clarity in the lung area occurred at 0.06 mGy while significant detectability changes were observed at 0.04 mGy. Similar changes in image quality were observed with the use of image manipulation. However, dose reduction produced statistically significant differences ( p < 0.05) in both image clarity and detectability at 0.10 mGy. Image clarity and detectability in the mediastinal area showed no statistical difference at all doses ( p > 0.05) with and without image manipulation. Conclusion The clarity and detectability of lesion images as a function of patient doses in computed radiography may be dependent on whether or not contrast enhancement techniques are employed. There is also evidence to suggest that low dose images of the high density mediastinum can be enhanced with post processing, making exposure at high doses unnecessary. Further work and clinical trials would be needed to confirm the generalizablity of these findings. Keywords Computed radiography Chest Clarity Detectability Manipulation Contrast Introduction Digital imaging techniques are increasingly used in diagnostic radiology. Computerised radiography (CR), which has several advantages over film screen radiography (FSR), is at the moment the most common digital imaging modality used in diagnostic radiology departments. 1,2 The high level of growth makes it necessary to study and review resulting patient doses during the imaging process. A number of workers have investigated optimising techniques in CR imaging. 3–5 Unlike film screen radiography (FSR), the CR image is not directly dependent on radiation exposure, 6 and while it offers the benefit of separate acquisition and processing tasks, 7,8 practise has shown, there are several exposure related issues that require regular assessment and review. One of these is dose – image quality optimisation. To evaluate medical X-ray doses and image quality, “phantoms” that mimic particular aspects of the patient have been used. To facilitate widespread use, such phantoms need to be simple, affordable and easy to use. We have described such a phantom previously for film screen chest radiography (FSR). 9 It is based on a design by the Centre for Devices and Radiological Health (CDRH), USA, with a modification first proposed by Vassileva. 10 The wide dynamic range in CR imaging suggests the potential for dose reduction, especially with the benefit of the availability of image manipulation. Given the differences between FSR and CR media, and as reported in the literature, 11,12 there is need to assess the applicability of the phantom in assessing the performance of CR images at low doses (with and without image manipulation) using current dose levels as the baseline for dose reduction. This study uses the phantom to assess the effects of dose reduction on image quality in CR with a view to investigating the influence of dose reduction on observer perceptibility in chest radiography. Methodology The chest phantom is based on a design by the Centre for Devices in Radiological Health (CDRH) with a quasi anatomical insert first proposed by Vassileva. 10 It has previously been used by Egbe et al. 9 for both dose and image quality studies in film screen radiography (FSR). Lesion simulation and positioning on the phantom were as reported in this earlier study. The lesions were made of gelatine, a known tissue substitute, 13 and were half spherical in shape with a diameter of 5 mm. The choice of 5 mm diameter for the size of lesions was thought appropriate against the homogeneous phantom background, although a clinical study has cited lung nodules of between 0.7 and 6.5 cm diameter. 14 Exposure of phantoms Exposure factors were set with a Siemens Multix Pro P x-ray generator, to obtain the current mean ESD. Total tube filtration was equivalent to 3.5 mm of aluminium. Reproducibility of the tube for kVp, mA and time were less than ±5% for the range of exposures used in diagnostic radiology. The mean ESD obtained was taken as the reference dose (D ref ) for each examination. Initial tests were carried out with chest doses reduced by increasing the kVp from 102 to 150 with unchanged AEC settings, to determine dose points with significant perceptible differences in image quality from D ref . From these, three dose points 0.10, 0.06 and 0.04 mGy, were selected for the study. The selected doses and D ref , with the corresponding kVps and the percent dose reduction at which they were obtained are shown in Table 1 . Four exposures were made at each dose point. The positions of lesions within the phantom were randomly altered to reduce the tendency for observer familiarity during viewing. A total of 40 and 24 lesion images in the lung and the mediastinum, respectively, were obtained. Images were obtained with Kodak Direct View cassettes with GP-25 storage phosphor screens and a Kodak Direct View CR 800 system reader. All exposures were made within the same day using a single plate for each projection to eliminate variations that could occur from the use of multiple cassettes. Irradiated plates were processed within the first half hour of exposure to rule out variation due to scan delay. 15 Assessment of image quality A team of four observers made up of Medical Physicists with wide ranging experiences in image interpretation and quality studies assessed the images. Each observer reviewed 40 (lung) and 24 (mediastinum) lesion images per dose over three sessions lasting between 24 h to one week. There were no restrictions on reading distance although the average measured reading distance was 33 ± 3.5 cm. Observers were not aware of the doses used in the irradiation process, but were instructed on the shape of the lesions to be studied. An explanation of the ranking system was also given. The method of ranked scoring, 16 allows for quantification of the degree of perceptibility 17 and has been widely used in image quality studies. 18–20 Quality was measured in terms of both lesion clarity and detectability; observer scores provided a measure of clarity while the number of lesions seen represented detectability. 9 Images were scored according to a pre-selected scale which defined the degree of certainty with which a conclusion was made. Trial assessments were necessary to ensure compliance with the requirements of the process. Scores ranked from 0 to 3 and were interpreted as 0 (not seen); 1 (barely seen); 2 (seen but not clear); and 3 (clearly seen). Image viewing Images were stored as lossless JPEG to facilitate viewing outside the hospital network. JPEG images have the same image reconstruction as the original. 21 Soft copy viewing was done with a 21 inch Iiyama ® Vision Master Pro 454 CRT monitor, with a maximum resolution of 3 megapixels and a refresh rate of 85 Hz. The choice of this monitor was based on availability. Monitor luminance and ambient lighting were determined with an UNFORS Xi meter to ensure that viewing conditions were acceptable. The monitor had undergone (DICOM) greyscale calibration 22 prior to its installation. A warm up time of at least 30 min was observed prior to all reading sessions in order to optimise the monitor’s performance. 8 The CRT monitor luminance was in the range 381–428 cd m −2 . This was in agreement with the 50 foot-lamberts (∼170 cd m −2 ) minimum luminance recommended by the American College of Radiologists (ACR) for primary image interpretation. 8 Illuminance, measured at 30 cm from the monitor screen was 8.9 ± 2.5 lux and was in line with the value of 10 lux recommended for ambient lighting levels by the American Association of Physicists in Medicine. 22 Images were presented using the Microsoft Windows and Fax Viewer (MWFV) software. Images were viewed both with and without the facility for the observer to do simple image enhancement. The image enhancement software, known as the Viewer (TV), was developed locally and allowed the user to alter the image contrast as required, to improve their perception of lesions (contrast enhancement). Results were compared for images, with and without manipulation, to assess the effects of dose reduction on image quality under both conditions. Intra-reader uniformity over the three reading sessions was evaluated using the reliability analysis from the SPSS statistical software. Values of Cronbach alpha were accepted at 0.6 or greater. The intraclass correlation coefficient (ICC) was used to assess inter-reader consistency. The SPSS software version 14 (SPSS inc. Chicago, Illinois, USA) indicates threshold values of statistical significance for the calculated ICC values. ICC values of 0 implied agreement due to chance, while 1 showed perfect agreement. 23 Following this, observer agreement deduced from ICC values obtained in this study was interpreted as poor to fair (0–0.4), moderate (0.41–0.6), excellent (0.61–0.8) and almost perfect (0.81–1). 24 Results Average within reader consistency was good at 0.76 (0.27–0.95) for assessment of images without image manipulation and 0.84 (0.11–0.97) for those with image manipulation. Agreement between observers measured by the ICC showed a wide degree of variation, ranging from poor to excellent ( Table 2 ). Observers agreed better on clarity than they did on detectability. ICC values were statistically significant ( p < 0.05) for clarity in images assessed by both methods. It was observed from the calculations that the ICC values for detectability were not significant in the chest images with no manipulation ( p = 0.2), but were statistically significant in 50% of the manipulated chest images ( p = 0.03). Figs. 1 and 2 show how, as the dose is decreased below D ref , both the clarity and detectability of lesions in the chest phantom images worsen when there was no facility to manipulate the image. The onset of a significant difference in image clarity in the lung area occurred at 0.06 mGy while significant detectability changes were observed at 0.04 mGy. This implies that the clarity of images was affected by dose reduction earlier than any change in detectability could be observed. Both clarity and detectability in the mediastinal region did not follow the trend observed in the lung area, showing no statistically significant difference at all doses ( p > 0.05). The use of image manipulation did not change the trend of decreasing image quality with dose reduction for both clarity and detectability ( Figs. 3 and 4 ). Dose reduction produced statistically significant differences ( p < 0.05) in both image clarity and detectability at 0.10 mGy, respectively. Both clarity and detectability in the mediastinal area showed no statistical difference at all doses ( p > 0.05). Figs. 5 and 6 compare the perceptibility results with and without image manipulation. Image manipulation improved image quality in the mediastinum; clarity improved by an average of 56.7% (range 49–65%) and detectability by an average of 55.5% (range 48.4–66%). In contrast, when manipulation was used both image clarity and detectability in the lung area decreased by an average of 31.2% (range 30–34% and 28–34.8%, respectively) over the range of doses. The use of contrast enhancement has a statistically significant effect at all doses in chest radiography ( p < 0.05). Discussion Assessment of the clarity and detectability of images of phantom objects simulating chest lung and mediastinal lesions radiography is reported. A tendency for reduced lesion perception with lower doses in the lung area of the phantom is observed, while the denser mediastinal area showed no change. However this is probably accounted for by the fact that mediastinal image quality was poor even at the reference dose level. The detectability of low contrast objects in medical images is dependent on their sizes, contrast characteristics, the superimposed noise in the surroundings, 22 and exposure. Differences due to visual processing mechanisms and inherent unsharpness in the case of small diameter lesions are usual. 25 This study has shown that the clarity and detectability of low contrast 5 mm diameter lesions worsen with dose reduction. Dose reduction in this study was achieved by kVp increase (and mAs decrease using AEC). In CR, tube potential (kVp) determines the subject contrast while the mAs accounts for the number of absorbed photons, and therefore the noise. The processing algorithm affects the image density (output signal). CR images in the current study were the product of low mAs and high kVp values. High average photon energies arising from the increase in kVp reduce the sensitivity of the phosphor plate, introduce reduced beam attenuation and therefore increased penetration of objects, as well as increased scatter in the forward direction. The work of Fetterley and Hangiandreou 26 has shown a decrease in the detective quantum efficiency (DQE) of a CR system when tube voltages were increased from 70 to 120 kVp. Values of kVp used in the chest study were in the range of 102–150 for mAs in the range of 2.5–0.72. The accompanying lower values of mAs as a result of automatic exposure timing (AEC) effectively reduce the number of x-ray photons reaching the imaging plate and therefore increase quantum noise. The observed decrease in lesion perception with dose reduction in the lung area of the chest phantom ( Figs. 1 and 2 ) may be partially explained by the increased noise (or decrease SNR) in addition to the possible over penetration of the lesions as a result of high tube potentials, which switches the interaction process from photoelectric to predominantly Compton effect. It follows that exposure factors employing low mAs values may not be suitable for CR imaging in the lung area of the chest; this agrees with the work of Weatherburn and Davies. 27 It has been shown that signal to noise ratios has strong correlation to visual grading of images. 5 Images of the mediastinal lesions assessed without manipulation showed no statistical difference in both clarity and detectability over the range of doses used ( Figs. 1 and 2 ). The high kVp used could produce excessive penetration of the lesions and therefore degrade subject (lesion) contrast. Decreased beam attenuation as well as the production and effect of secondary radiation on the image, could also contribute to the poor visibility of objects in the mediastinum. In addition, the sensitivity of the phosphor in the PSP plate is lower at high photon energies. 28,29 The PSP phosphor has also been shown to be very sensitive to scatter radiation because of its low absorption edge. 30 The use of simple image manipulation, windowing and contrast enhancement, had different effects for lung and mediastinal lesions. Although the trend of reduced image quality with reduced doses was sustained in the lung, both clarity and detectability worsened when image manipulation was available. In contrast, the quality of mediastinal images improved with manipulation. Thus, where image quality was poor in the relatively more dense parts of the image, with a narrow range of grey levels, manipulation had the ability to effect an improvement. However where quality was already reasonable, and there was a wide range of image grey levels, simple manipulation actually worsened quality. Baring any limitations due to the software used, the results suggest that the method of image assessment may be a major factor in determining dose reduction levels applicable to CR. Without observer image manipulation there is the possibility of further dose reduction in chest radiography up to 0.06 mGy, especially when the lung area is the region of interest. Further dose reduction in chest radiography when image manipulation is employed may not yield satisfactory results in the lungs, but it may be crucial for improving clarity and detectability in the mediastinum. Dose reduction from D ref to 0.10 mGy, which agrees with a dose of 0.11 mGy obtained in a clinical study by Compagnone and colleagues, 31 may possible for imaging lesions in the lungs. The results suggest that much lower doses may be achievable in the mediastinum with image manipulation. The homogeneity of the phantom and limitations of spatial and temporal noise from the CRT 22 are limitations in the study. The locally made software used for image manipulation may also have introduced some limitations, being originally designed for studying retinal images. Notwithstanding, the foregoing confirms that using low doses achieved with high kVp technique in CR may produce visually acceptable images, which may however be lacking in detail. 21 It is possible that these results could be improved upon by using a higher resolution monitor 32,33 and a standard or reference image for each grade of the ranked scores used. Conclusion Using a simple chest phantom, the effects of extending dose reduction below current values on the clarity and detectability (image quality) of CR images have been assessed. It was found that observer perceptibility decreased with dose reduction in lung lesion images, indicating that the characteristics of the photo-stimulable plate may have limited application for radiographic procedures that employ high kVp and low mAs to achieve low doses, due to an increased SNR. However, chest radiography doses can be further reduced, the extent depending on whether or not contrast enhancement techniques are employed. There is also evidence to suggest that low dose images of the high density mediastinum can be enhanced with post processing, making exposure at high doses unnecessary. Further work and clinical trials would be needed to confirm the generalizablity of these findings. Acknowledgments The authors are grateful to staff of the Radiology department of Aberdeen Royal Infirmary, Aberdeen, UK; the Biomedical Physics workshop staff for assistance with construction of phantoms, the University of Calabar, Nigeria , and the Commonwealth Scholarships Commission for funding this work. Parts of the results in this study have been presented at the UKRC 2008 References 1 N.D. Lamontagne Will digital edge out film? Biophotonics International 10 4 2003 48 53 2 O. Rampado P. Isoardi R. 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Sharp Quantifying image quality Clinical Physics and Physiological Measurements 11 Suppl. A 1990 21 26 8 ACR practice guidelines for digital radiography 2007 American College of Radiologists 9 N.O. Egbe B. Heaton P.F. Sharp Application of a simple phantom in assessing the effects of dose reduction on image quality in chest radiography Radiography 16 2010 108 114 10.1016/j.radi.2009.09.007 10 J. Vassileva A phantom for dose-image quality optimization in chest radiography The British Journal of Radiology 75 2002 837 842 11 K. Al Khalifah A. Brindhaban Comparison between conventional radiography and digital radiography for various kVp and mAs settings using a pelvic phantom Radiography 10 2004 119 125 12 J.A. Rowlands The physics of computed radiography Physics in Medicine and Biology 47 2002 R123 R166 13 D.R. White Tissue substitutes in experimental radiation physics Physics in Medicine and Biology 5 6 1978 467 479 14 E.A. Kazerooni M. Bhalla J.O. Shepard T.C. McLoud Adenosquamous carcinoma of the lung: radiologic appearance American Journal of Roentgenology 163 1994 301 306 15 B. Akdeniz H. Grondahl Degradation of storage phosphor images due to scanning delay Dentomaxillofacial Radiology 35 2 2006 74 77 16 ICRU ICRU Report No. 54: medical imaging. The assessment of image quality 1996 International Commission for Radiation Units and Measurements 17 C.J. Martin P.F. Sharp D.G. Sutton Measurement of image quality in diagnostic radiology Applied Radiation and Isotopes 50 1 1999 21 38 18 P.C. Brennan S. McDonnell D. O’Leary Increasing film-focus distance (FFD) reduces radiation dose for x-ray examinations Radiation Protection Dosimetry 108 3 2004 263 268 19 L.J.M. Kroft W.J.H. Veldkamp B.J.A. Mertens J.-A. Van Delft J. Geleijns Dose reduction in digital chest radiography and perceived image quality The British Journal of Radiology 80 960 2007 984 988 20 W. Huda K.M. Ogden E. Samei E.M. Scalzetti R.L. Lavallee M.L. Roskopf Inter-reader variability in alternate forced choice studies Proceedings of SPIE 6917 2008 10.1117/12.770618 691711-691711 21 J. Oakley Digital imaging: a primer for radiographers, radiologists and health care professionals 2006 Cambridge University Press Cambridge, UK 22 AAPM assessment of display performance for medical imaging systems 2005 American Association of Physicists in Medicine Maryland, USA 23 M. Ovsenik F. Farcnik I. Verdenik Intra- and inter-examination reliability of intraoral malocclusion assessment European Journal of Orthodontics 29 2007 88 94 24 J.R. Landis G.G. Koch The measurement of observer agreement for categorical data Biometrics 33 1977 159 174 25 A. Workman A.R. Cowen Signal, noise and SNR transfer properties of computed radiography Physics in Medicine and Biology 38 1993 1789 1808 26 K.A. Fetterley N.J. Hangiandreou Effects of the x-ray spectra on the DQE of a computed radiography system Medical Physics 28 2001 241 248 27 G.C. Weatherburn J.G. Davies Comparison of film, hard copy computed radiography (CR) and soft copy picture archiving and communication (PACS) systems using a contrast detail test object The British Journal of Radiology 72 1999 856 863 28 D.J. Dowsett P.A. Kenny R.E. Johnston The physics of diagnostic imaging 2nd ed. 2006 Hodder Arnold London 29 A. Cowen A. Workman J. Price Physical aspects of photostimulable phosphor computed radiography The British Journal of Radiology 66 784 1993 332 345 30 C.J. Martin Optimisation in general radiography Biomedical Imaging and Intervention Journal 3 2 2007 http://www.biij.org/2007/2/e18 Available from 31 G. Compagnone M.C. Baleni L. Pagan F.L. Calzolaio L. Barozzi C. Bergamini Comparison of radiation doses to patients undergoing standard radiographic examinations with conventional screen-film radiography, computed radiography and direct digital radiography The British Journal of Radiology 79 947 2006 899 904 32 M. Scharitzer M. Prokop M. Weber M. Fuchsjager E. Oschatz C. Schaefer-Prokop Detectability of catheters on bedside chest radiographs: comparison between liquid crystal display and high resolution cathode ray tube monitors Radiology 234 2 2005 611 616 33 C.M. Park H.J. Lee J.M. Goo D.H. Han J.H. Kim K.Y. Lim Comparison of observer performance on soft-copy reading of digital chest radiographs: high resolution liquid-crystal display monitors versus cathode-ray tube monitors European Journal of Radiology 66 1 2008 13 18

Aims To assess the cost-effectiveness of an improved automated grading algorithm for diabetic retinopathy against a previously described algorithm, and in comparison with manual grading.Methods Efficacy of the alternative algorithms was assessed using a reference graded set of images from three screening centres in Scotland (1253 cases with observable/referable retinopathy and 6333 individuals with mild or no retinopathy). Screening outcomes and grading and diagnosis costs were modelled for a cohort of 180 000 people, with prevalence of referable retinopathy at 4%. Algorithm (b), which combines image quality assessment with detection algorithms for microaneurysms (MA), blot haemorrhages and exudates, was compared with a simpler algorithm (a) (using image quality assessment and MA/dot haemorrhage (DH) detection), and the current practice of manual grading.Results Compared with algorithm (a), algorithm (b) would identify an additional 113 cases of referable retinopathy for an incremental cost of 68 pound per additional case. Compared with manual grading, automated grading would be expected to identify between 54 and 123 fewer referable cases, for a grading cost saving between 3834 pound and 1727 pound per case missed. Extrapolation modelling over a 20-year time horizon suggests manual grading would cost between 25 pound 676 and 267 pound 115 per additional quality adjusted life year gained.Conclusions Algorithm (b) is more cost-effective than the algorithm based on quality assessment and MA/DH detection. With respect to the value of introducing automated detection systems into screening programmes, automated grading operates within the recommended national standards in Scotland and is likely to be considered a cost-effective alternative to manual disease/no disease grading.

Purpose: Firstly, to evaluate a commercial chest phantom incorporating a quasi anthropomorphic insert by comparing exposure measurements on the phantom with those of actual patients and, secondly, to assess the value of the phantom for image quality and dose optimisation.Methods: In the first part of the study entrance surface doses (ESD), Beam transmission (BT), and optical density (OD) were obtained for 77 chest radiography patients and compared with measurements made from exposures of the phantom using the respective patient exposure factors from chest examination. Differences were assessed with a student t-test, while the Pearson's linear correlation coefficient was used to test for any linear relationship. The second part assessed the applicability of the phantom to image quality studies by investigating the effect, on the clarity and detectability of lung lesions made from gelatine, of reducing patient dose below current dose levels. Clarity of linear objects of different dimensions was also studied. Lesion detectability and clarity was assessed by four observers. The possibility of extending dose reduction below current dose levels (D-ref) was assessed from comparison of doses that produced statistically significant differences in image quality from D-ref .Results: Results show that, with the exception of entrance doses and beam transmission through the diaphragm (P > 0.05), differences in OD and beam transmission between patients and phantom were statistically significant (P < 0.05). A Pearson's correlation test showed good positive correlation in ESD (r = 0.9) and beam transmission (r = 0.8) for all regions and a weaker positive correlation (r = 0.3) for OD in all areas. In both cases the correlation was statistically significant (P < 0.05). Extending dose reduction by between 41 and 65% below D-ref produced significant changes in both clarity and detectability.Conclusion: Within limits posed by the observed differences, the phantom can be applied to image quality studies in diagnostic radiology. (C) 2009 The College of Radiographers. Published by Elsevier Ltd. All rights reserved..

One of the main aims of the European Federation of Organisations for Medical Physics is to propose guidelines for education, training and accreditation programmes. This is achieved through the publication of Policy Statements and the organisation of education and training courses, seminars and conferences. It represents a long-term work-programme aimed at harmonising the education and training of the Medical Physicist across Europe. This paper presents these efforts together with the challenges EFOMP needs to overcome in order to achieve these aims.

The EFOMP (European Federation of Organisations for Medical Physics) Council at its September 2008 meeting in Krakow set in motion the 'Tuning Educational Structures in Europe' process for Masters' programmes in Medical Physics in Europe. For the medical physics profession a fundamental component of Tuning would be the setting up of an inventory of agreed pan-European learning outcome competences for such programs. This would represent the minimum set of competences that a student should acquire at the exit point of the program. An initial form of this inventory is presented. The inventory was set up on the basis of a thorough analysis of Tuning documentation, lists of medical physics competences used by universities in the various EU states and other competence inventories such as those of ESTRO (European Society for Therapeutic Radiology and Oncology) for radiotherapy physicists. Best-practice elements of these inventories were identified and used as inputs for the inventory. The final form of the inventory must be acceptable for the medical physics profession and associated stakeholders on a European scale. It is important to ensure that this inventory dovetails seamlessly with any EFOMP policy statements regarding the competences of the Qualified Medical Physicist (QMP) and Specialized Medical Physicist (SMP). It is also suggested that in future EFOMP would use the inventory to propose a system of accreditation for programs in Europe similar to that used by CAMPEP (Commission on Accreditation of Medical Physics Educational Programs) in the US.

Aims: National screening programmes for diabetic retinopathy using digital photography and multi-level manual grading systems are currently being implemented in the UK. Here, we assess the cost-effectiveness of replacing first level manual grading in the National Screening Programme in Scotland with an automated system developed to assess image quality and detect the presence of any retinopathy.Methods: A decision tree model was developed and populated using sensitivity/specificity and cost data based on a study of 6722 patients in the Grampian region. Costs to the NHS, and the number of appropriate screening outcomes and true referable cases detected in 1 year were assessed.Results: For the diabetic population of Scotland (approximately 160 000), with prevalence of referable retinopathy at 4% (6400 true cases), the automated strategy would be expected to identify 5560 cases (86.9%) and the manual strategy 5610 cases (87.7%). However, the automated system led to savings in grading and quality assurance costs to the NHS of 201 pound 600 per year. The additional cost per additional referable case detected (manual vs automated) totalled 4088 pound and the additional cost per additional appropriate screening outcome (manual vs automated) was 1990 pound.Conclusions: Given that automated grading is less costly and of similar effectiveness, it is likely to be considered a cost-effective alternative to manual grading.

Aim:To assess the efficacy of automated “disease/no disease” grading for diabetic retinopathy within a systematic screening programme.Methods:Anonymised images were obtained from consecutive patients attending a regional primary care based diabetic retinopathy screening programme. A training set of 1067 images was used to develop automated grading algorithms. The final software was tested using a separate set of 14 406 images from 6722 patients. The sensitivity and specificity of manual and automated systems operating as “disease/no disease” graders (detecting poor quality images and any diabetic retinopathy) were determined relative to a clinical reference standard.Results:The reference standard classified 8.2% of the patients as having ungradeable images (technical failures) and 62.5% as having no retinopathy. Detection of technical failures or any retinopathy was achieved by manual grading with 86.5% sensitivity (95% confidence interval 85.1 to 87.8) and 95.3% specificity (94.6 to 95.9) and by automated grading with 90.5% sensitivity (89.3 to 91.6) and 67.4% specificity (66.0 to 68.8). Manual and automated grading detected 99.1% and 97.9%, respectively, of patients with referable or observable retinopathy/maculopathy. Manual and automated grading detected 95.7% and 99.8%, respectively, of technical failures.Conclusion:Automated “disease/no disease” grading of diabetic retinopathy could safely reduce the burden of grading in diabetic retinopathy screening programmes.

One of the main aims of the European Federation for Organisations of Medical Physics is to propose guidelines for education, training and accreditation programmes. This is achieved through the publication of Policy Statements and the organisation of education and training course, seminars and conferences. This is a continuous effort in an attempt to harmonise the education and training of the Medical Physicist across Europe. This paper presents an overview of the past, present and future efforts of EFOMP to achieve this aim.

PURPOSE: To evaluate the clinical applicability of a novel scanning laser ophthalmoscopy imaging system for ultra-wide-field fluorescein angiography.DESIGN: Observational case report.METHODS: Wide-field fluorescein angiography images were captured in normal volunteers and in patients with a variety of clinical disorders with a newly developed scanning laser ophthalmoscope (Optomap; Optos PLC., Dunfermline, Scotland, United Kingdom) that produces high-resolution images of the fundus up to a 200-degree field. Fluorescein angiograms were performed using standard sequence times.RESULTS: Peripheral vascular perfusion of all four quadrants of a normal fundus was observed with good detail of the capillary architecture. Patients with diabetes and ocular inflammatory eye disease showed evidence of peripheral retinal nonperfusion. The relative degrees of retinal perfusion and nonperfusion could be compared in single images.CONCLUSIONS: Ultra-wide,field fundus fluorescein an, giography offers the possibility of evaluating and quanti, tating peripheral retinal perfusion and vascular pathology in fundus disease. (Am J Ophthalmol 2005;140: 525-527. (c) 2005 by Elsevier Inc. All rights reserved).

The scanning laser ophthalmoscope (SLO) offers the potential for retinal imaging that is complementary both to that of the fundus camera and also the newly developing technique of optical coherence tomography (OCT). It has the ability to produce rapid images at low light levels using light of specific wavelengths. This permits temporal studies of fluorescent-labelled cells which offer a unique insight into inflammatory processes in the eye. The facility to image with several different wavelengths simultaneously offers the potential for spectral imaging of retinal tissue with the aim of revealing those early changes in tissue perfusion that indicate the onset of retinal disease, so increasing the probability of successful therapy.

Although activated T lymphocytes can migrate through unstimulated neural endothelium to perform immune surveillance or initiate inflammation, the precise mechanism by which this occurs is not clear. In this study, we have used intravital scanning laser ophthalmoscopy to show that circulating, activated T cells induce early changes in the retinal venules that enable T cell diapedesis in the absence of cell rolling, and without any reduction in shear stress within the venules. Concanavalin A (Con A)-activated T cells, but not naı̈ve T cells, were able to penetrate the normal blood–retinal barrier (BRB) 8–16 h after adoptive transfer. A minimum number (≥1×105 cells/mouse) of Con A-activated T cells needed to be transferred before lymphocytes crossed the normal BRB. Cell rolling and reduction of shear stress did not occur in normal retinal venules and post-capillary venules. In contrast, in mice with experimental autoimmune uveoretinitis (EAU), in which the BRB has broken down, 45% of blast cells were rolling in retinal venules. Cell rolling correlated with significantly reduced shear stress. Both naı̈ve and Con A-activated T cells could cross the disabled barrier, with Con A-activated T cells migrating faster and in greater numbers than naive cells. Adoptive transfer of Con A-activated cells into normal recipient mice induced limited and transient breakdown of the BRB and up-regulation of ICAM-1 but not P-selectin. Pretreatment of Con A-activated cells with anti-LFA-1 significantly suppressed T cell infiltration in normal recipient mice. Our data indicate that critical to immune surveillance in the central nervous system (CNS) is the ability of activated T cells to interact with the endothelium, up-regulating ICAM-1 and inducing transient breakdown of the barrier.

OBJECTIVES:To assess the performance of digital imaging, compared with other modalities, in screening for and monitoring the development of diabetic retinopathy.DESIGN:All imaging was acquired at a hospital assessment clinic. Subsequently, study optometrists examined the patients in their own premises. A subset of patients also had fluorescein angiography performed every 6 months.SETTING:Research clinic at the hospital eye clinic and optometrists' own premises.PARTICIPANTS:Study comprised 103 patients who had type 1 diabetes mellitus, 481 had type 2 diabetes mellitus and two had secondary diabetes mellitus; 157 (26.8%) had some form of retinopathy ('any') and 58 (9.9%) had referable retinopathy.INTERVENTIONS:A repeat assessment was carried out of all patients 1 year after their initial assessment. Patients who had more severe forms of retinopathy were monitored more frequently for evidence of progression.MAIN OUTCOME MEASURES:Detection of retinopathy, progression of retinopathy and determination of when treatment is required.RESULTS:Manual grading of 35-mm colour slides produced the highest sensitivity and specificity figures, with optometrist examination recording most false negatives. Manual and automated analysis of digital images had intermediate sensitivity. Both manual grading of 35-mm colour slides and digital images gave sensitivities of over 90% with few false positives. Digital imaging produced 50% fewer ungradable images than colour slides. This part of the study was limited as patients with the more severe levels of retinopathy opted for treatment. There was an increase in the number of microaneurysms in those patients who developed from mild to moderate. There was no difference between the turnover rate of either new or regressed microaneurysms for patients with mild or with sight-threatening retinopathy. It was not possible in this study to ascertain whether digital imaging systems determine when treatment is warranted.CONCLUSIONS:In the context of a national screening programme for referable retinopathy, digital imaging is an effective method. In addition, technical failure rates are lower with digital imaging than conventional photography. Digital imaging is also a more sensitive technique than slit-lamp examination by optometrists. Automated grading can improve efficiency by correctly identifying just under half the population as having no retinopathy. Recommendations for future research include: investigating whether the nasal field is required for grading; a large screening programme is required to ascertain if automated grading can safely perform as a first-level grader; if colour improves the performance of grading digital images; investigating methods to ensure effective uptake in a diabetic retinopathy screening programme.

AIMS:To compare the respective performances of digital retinal imaging, fundus photography and slit-lamp biomicroscopy performed by trained optometrists, in screening for diabetic retinopathy. To assess the potential contribution of automated digital image analysis to a screening programme.METHODS:A group of 586 patients recruited from a diabetic clinic underwent three or four mydriatic screening methods for retinal examination. The respective performances of digital imaging (n=586; graded manually), colour slides (n=586; graded manually), and slit-lamp examination by specially trained optometrists (n=485), were evaluated against a reference standard of slit-lamp biomicroscopy by ophthalmologists with a special interest in medical retina. The performance of automated grading of the digital images by computer was also assessed.RESULTS:Slit-lamp examination by optometrists for referable diabetic retinopathy achieved a sensitivity of 73% (52-88) and a specificity of 90% (87-93). Using two-field imaging, manual grading of red-free digital images achieved a sensitivity of 93% (82-98) and a specificity of 87% (84-90), and for colour slides, a sensitivity of 96% (87-100) and a specificity of 89% (86-91). Almost identical results were achieved for both methods with single macular field imaging. Digital imaging had a lower technical failure rate (4.4% of patients) than colour slide photography (11.9%). Applying an automated grading protocol to the digital images detected any retinopathy, with a sensitivity of 83% (77-89) and a specificity of 71% (66-75) and diabetic macular oedema with a sensitivity of 76% (53-92) and a specificity of 85% (82-88).CONCLUSIONS:Both manual grading methods produced similar results whether using a one- or two-field protocol. Technical failures rates, and hence need for recall, were lower with digital imaging. One-field grading of fundus photographs appeared to be as effective as two-field. The optometrists achieved the lowest sensitivities but reported no technical failures. Automated grading of retinal images can improve efficiency of resource utilization in diabetic retinopathy screening.

PURPOSE. An automated system for the measurement of microaneurysm (MA) turnover was developed and compared with manual measurement. The system analyses serial fluorescein angiogram (FA) or red-free (RF) fundus images; fluorescein angiography was used in this study because it is the more sensitive test for MAs. Previous studies have shown that the absolute number of MAs observed does not reflect the dynamic temporal nature of the MA population. In this study, almost half of the MAs present at baseline had regressed after a year and been replaced by new lesions elsewhere.METHODS. Two clinical datasets were used to evaluate the performance of the automated turnover measurement system. The first consisted of 10 patients who had two fluorescein angiograms acquired a year apart. These data were analyzed, both manually and using the automated system, to investigate the inter- and intraobserver variations associated with manual measurement and to assess the performance of the automated system. The second dataset contained FAs from a further 25 patients. This dataset was analyzed only with the automated system to investigate some properties of microaneurysm turnover, in particular the differing detection sensitivities of new, static and regressed microaneurysms.RESULTS. Manual measurements exhibited large inter- and intraobserver variation. The sensitivity and specificity of the automated system were similar to those of the human observers. However, the automated measurements were more consistent-an important condition for accurate turnover quantification. Regressed MAs were more difficult to detect reliably than new MAs, which were themselves more difficult to detect reliably than static MAs.CONCLUSIONS. The automated system was shown to be fast, reliable, and repeatable, making it suitable for processing large numbers of images. Performance was similar to that of trained manual observers.

This study has enabled us to identify the influence of the chemokine, macrophage inflammatory protein-1alpha (MIP-1alpha), on leukocyte behavior at the blood-retina barrier in vivo and its link with the inflammatory process and disease pathogenesis. MIP-1alpha has not previously been thought to be effective under conditions of physiological shear flow. However, short-term anti-MIP-1alpha treatment inhibited leukocyte slowing and accumulation and subsequent extravasation of leukocytes at the blood-retina barrier in animals with experimental autoimmune uveoretinitis. This was effective predominantly in the post-capillary venules which have been shown to be the main site of passage of leukocytes across the blood-retina barrier. Long-term anti-MIP-1alpha treatment also prevented decreased leukocyte velocity and reduced disease severity as measured clinically, histologically and in terms of blood-retina barrier breakdown.

In the present study, we investigated the involvement of CD44 in leukocyte trafficking in vivo at the blood-retinal barrier using experimental autoimmune uveoretinitis (EAU) as a model system. Leukocyte trafficking was evaluated using adoptive transfer of calcein-AM (C-AM)-labeled spleen cells harvested from syngeneic mice at prepeak severity of EAU to mice at a similar stage of disease. CD44 and its ligand hyaluronan were up-regulated in the eye during EAU. CD44-positive leukocytes were found sticking in the retinal venules and postcapillary venules but not in the retinal arterioles nor in mesenteric vessels. Preincubation of in vitro C-AM-labeled leukocytes with anti-CD44 monoclonal antibodies (mAb; IM7) or high molecular weight hyaluronic acid (HA) before transfer significantly suppressed leukocyte rolling but not sticking in retinal venules and also reduced cell infiltration in the retinal parenchyma. Administration of the HA-specific enzyme hyaluronidase to mice before cell transfer also reduced leukocyte infiltration, suggesting that CD44-HA interactions are involved in leukocyte recruitment in EAU. This was further supported by the observation that disease severity was reduced by administration of anti-CD44 mAb (IM7) at the early leukocyte-infiltration stage. Further studies also indicated that CD44 activation was associated with increased levels of apoptosis, and this may also be in part responsible for the reduction in disease severity. These findings demonstrate that CD44 is directly involved in leukocyte-endothelial interaction in vivo and influence the trafficking of primed leukocytes to the retina and their overall survival.

The purpose of this study is to develop a new method with which to visualize leukocyte dynamics in murine choroidal and retinal circulation. Both pigmented (B10.RIII) and non-pigmented (BALB/c) mice were used in this study. One hundredμl of 0·05% sodium fluorescein was injected via the mice tail vein to outline the vessel, followed by 150μl (107 cells) C-AM labelled leukocytes. Fundus images were obtained with a confocal scanning laser ophthalmoscope. The dynamic image sequences were recorded simultaneously on videotape (S-VHS) and digitally at 25 frames per sec. The digital images were later analysed with a custom-made personal computer-based image analysis system. Both the choroidal and retinal circulation can be visualized in non-pigmented mice in the first few seconds of fluorescein angiography. However, the view of the choroidal and the retinal capillary circulation is soon blurred due to the rapid fluorescein leakage in the choroid. In contrast, in pigmented mice, retinal circulation is clear against the dark background of the choroid, while choroidal circulation is masked behind the pigment epithelial layer and cannot be seen at all. C-AM labelled leukocytes were clearly seen in the retinal circulation of all experimental mice and in the choroidal circulation of non-pigmented mice for as long as 30min. The number of labelled circulating cells decreased as time clasped. Cells moved rapidly in the retinal arteries, slowing down or even stopping for a few seconds in the capillary system, and then moved slightly faster again through the postcapillary venules and veins. In non-pigmented mice, significant number of cells were seen to have arrested in the choroidal circulation. There was no difference between B10.RIII mice and BALB/c mice in vessel diameters, leukocyte velocities and shear stresses. This method allows the visualization of leukocytes and provides data on their behavior as they move through the choroidal and retinal circulation of non-pigmented mice, and in the retinal circulation of pigmented mice. It provides a valuable new tool for the investigation of real time leukocyte dynamics in murine retinal and choroidal microcirculations both under physiological conditions and during the development of ocular disease.