Peter F. Sharp

Positron Emission Tomography Using [18F]-Fluorodeoxy-d-Glucose to Predict the Pathologic Response of Breast Cancer to Primary Chemotherapy

PURPOSE To determine whether [(18)F]-fluorodeoxy-D-glucose ([(18)F]-FDG) positron emission tomography (PET) can predict the pathologic response of primary and metastatic breast cancer to chemotherapy. PATIENTS AND METHODS Thirty patients with noninflammatory, large (> 3 cm), or locally advanced breast cancers received eight doses of primary chemotherapy. Dynamic PET imaging was performed immediately before the first, second, and fifth doses and after the last dose of treatment. Primary tumors and involved axillary lymph nodes were identified, and the [(18)F]-FDG uptake values were calculated (expressed as semiquantitative dose uptake ratio [DUR] and influx constant [K]). Pathologic response was determined after chemotherapy by evaluation of surgical resection specimens. RESULTS Thirty-one primary breast lesions were identified. The mean pretreatment DUR values of the eight lesions that achieved a complete microscopic pathologic response were significantly (P =.037) higher than those from less responsive lesions. The mean reduction in DUR after the first pulse of chemotherapy was significantly greater in lesions that achieved a partial (P =.013), complete macroscopic (P =.003), or complete microscopic (P =.001) pathologic response. PET after a single pulse of chemotherapy was able to predict complete pathologic response with a sensitivity of 90% and a specificity of 74%. Eleven patients had pathologic evidence of lymph node metastases. Mean pretreatment DUR values in the metastatic lesions that responded did not differ significantly from those that failed to respond (P =.076). However, mean pretreatment K values were significantly higher in ultimately responsive cancers (P =.037). The mean change in DUR and K after the first pulse of chemotherapy was significantly greater in responding lesions (DUR, P =.038; K, P =.012). CONCLUSION [(18)F]-FDG PET imaging of primary and metastatic breast cancer after a single pulse of chemotherapy may be of value in the prediction of pathologic treatment response.

Automated microaneurysm detection using local contrast normalization and local vessel detection

Screening programs using retinal photography for the detection of diabetic eye disease are being introduced in the U.K. and elsewhere. Automatic grading of the images is being considered by health boards so that the human grading task is reduced. Microaneurysms (MAs) are the earliest sign of this disease and so are very important for classifying whether images show signs of retinopathy. This paper describes automatic methods for MA detection and shows how image contrast normalization can improve the ability to distinguish between MAs and other dots that occur on the retina. Various methods for contrast normalization are compared. Best results were obtained with a method that uses the watershed transform to derive a region that contains no vessels or other lesions. Dots within vessels are handled successfully using a local vessel detection technique. Results are presented for detection of individual MAs and for detection of images containing MAs. Images containing MAs are detected with sensitivity 85.4% and specificity 83.1%

Staging of the axilla in breast cancer: accurate in vivo assessment using positron emission tomography with 2-(fluorine-18)-fluoro-2-deoxy-D-glucose.

OBJECTIVE To evaluate the ability of positron emission tomography (PET) with 18F-fluoro-2-deoxy-D-glucose (18F-FDG) to determine noninvasively axillary lymph node status in patients with breast cancer. BACKGROUND The presence of axillary lymph node metastasis is the most important prognostic factor in women with breast cancer. It signifies the presence of occult metastatic disease and indicates the need for adjuvant therapy. The only reliable way in which this important prognostic information may be obtained is by performing axillary dissection, which may be associated with significant complications and delay in discharge from the hospital. PET with 18F-FDG can visualize primary cancers in the breast and metastatic tumor deposits. METHODS Fifty patients with untreated breast cancer had clinical examination of their axilla performed (graded as positive or negative), followed by PET of the axilla and midthorax. PET data were analyzed blindly and graded as positive or negative, depending on the presence or absence of axillary nodal metastases. Cytopathologic assessment of the axillary nodes was carried out within 1 week of PET, by fine-needle aspiration cytology in 5 patients and axillary dissection in 45; the excised specimens were examined by a single pathologist. RESULTS The overall sensitivity of PET in 50 patients was 90% and the specificity was 97%. Clinical examination of the same patients had an overall sensitivity of 57% and a specificity of 90%. In the 24 patients with locally advanced breast cancer (T3, T4, TxN2), PET had a sensitivity of 93% and a specificity of 100%. In T1 tumors (seven patients), the sensitivity and specificity were 100%. PET had a high predictive value (>90%) and accuracy (94%) in staging the axilla. CONCLUSIONS PET is a sensitive and specific method of staging the axilla in patients with breast cancer. It may obviate the need for axillary surgery in women with small primary tumors, define the women likely to benefit from axillary dissection, or allow radiotherapy to be substituted for surgery, particularly in post-menopausal women.

A fully automated comparative microaneurysm digital detection system

A fully automated digital image processing system, which provides an objective and repeatable way to quantify microaneurysms in digitised fluorescein angiograms, has been developed. The automated computer processing includes registration of same-eye retinal images for serial studies, cutting of regions-of-interest centred on the fovea, the detection of microaneurysms and the comparison of serial images for microaneurysm turnover. The microaneurysm detector was trained against a database of 68 images of patients with diabetes containing 394 true microaneurysms, as identified by an ophthalmologist. The microaneurysm detector achieved 82% sensitivity with 2.0 false-positives per image. An independent test set, comprising 20 images containing 297 true microaneurysms, was used to compare the microaneurysm detector with clinicians. The microaneurysm detector achieved a sensitivity of 82% for 5.7 false-positives per image, whereas the clinician receiver-operator-characteristic (ROC) curve gives 3.2 false-positives per image at a sensitivity of 82%. It is concluded that the computer system can reliably detect microaneurysms. The advantages of the computer system include objectivity, repeatability, speed and full automation.

A comparative evaluation of digital imaging, retinal photography and optometrist examination in screening for diabetic retinopathy

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.

Automatic detection of retinal anatomy to assist diabetic retinopathy screening

Screening programmes for diabetic retinopathy are being introduced in the United Kingdom and elsewhere. These require large numbers of retinal images to be manually graded for the presence of disease. Automation of image grading would have a number of benefits. However, an important prerequisite for automation is the accurate location of the main anatomical features in the image, notably the optic disc and the fovea. The locations of these features are necessary so that lesion significance, image field of view and image clarity can be assessed. This paper describes methods for the robust location of the optic disc and fovea. The elliptical form of the major retinal blood vessels is used to obtain approximate locations, which are refined based on the circular edge of the optic disc and the local darkening at the fovea. The methods have been tested on 1056 sequential images from a retinal screening programme. Positional accuracy was better than 0.5 of a disc diameter in 98.4% of cases for optic disc location, and in 96.5% of cases for fovea location. The methods are sufficiently accurate to form an important and effective component of an automated image grading system for diabetic retinopathy screening.

Automated detection of microaneurysms in digital red‐free photographs: a diabetic retinopathy screening tool

SUMMARY

The efficacy of automated "disease/no disease" grading for diabetic retinopathy in a systematic screening programme

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.

Automated detection and quantification of retinal exudates

Retinal exudates are a common manifestation of vascular damage in a variety of retinal diseases. We have used computerized image analysis to detect and measure the area of exudates from digitized colour fundus slides of patients with diabetic retionpathy and have assessed the repeatability, reproducibility, and accuracy of the technique. The analysis was entirely independent of the operator apart from choice of the region to be analysed. The coefficient of variation for repeatability was between 3% for large areas of exudate and 17% for small areas of exudate. The reproducibility was also within this range. Sensitivity was between 61 and 100% o (mean 87%). False-positives were observed in 5 of 30 regions analysed, and these could have been eliminated by using more stringent criteria for selection of images for analysis. Time taken for the analysis was approximately 3 min.

Differential diagnosis in dementia using the cerebral blood flow agent 99mTc HM-PAO: a SPECT study.

One of the potential clinical uses of the new cerebral blood flow agent 99mTc-hexamethylpropyleneamineoxime (HM-PAO) is the investigation of dementia, in particular to differentiate between dementia of the Alzheimer type (DAT) and multiinfarct dementia (MID). In this study 27 patients, 17 with DAT and 10 with MID, and three normal volunteers were imaged both with single photon emission CT and magnetic resonance. The HM-PAO perfusion deficits were much more common in the DAT group than in the MID group, especially in the temporoparietooccipital (TPO) regions. The two groups of patients were found to be significantly different (p less than 0.02), as regards the frequency of occurrence of bilateral TPO perfusion deficits. Four of the 17 DAT patients did not have bilateral TPO deficits but these included the three least impaired patients as assessed by psychometric testing.