A novel automated platform for quantifying the extent of skeletal tumour involvement in prostate cancer patients using the Bone Scan Index.

BACKGROUND: There is little consensus on a standard approach to analysing bone scan images. The Bone Scan Index (BSI) is predictive of survival in patients with progressive prostate cancer (PCa), but the popularity of this metric is hampered by the tedium of the manual calculation. OBJECTIVE: Develop a fully automated method of quantifying the BSI and determining the clinical value of automated BSI measurements beyond conventional clinical and pathologic features. DESIGN, SETTING, AND PARTICIPANTS: We conditioned a computer-assisted diagnosis system identifying metastatic lesions on a bone scan to automatically compute BSI measurements. A training group of 795 bone scans was used in the conditioning process. Independent validation of the method used bone scans obtained ≤3 mo from diagnosis of 384 PCa cases in two large population-based cohorts. An experienced analyser (blinded to case identity, prior BSI, and outcome) scored the BSI measurements twice. We measured prediction of outcome using pretreatment Gleason score, clinical stage, and prostate-specific antigen with models that also incorporated either manual or automated BSI measurements. MEASUREMENTS: The agreement between methods was evaluated using Pearson's correlation coefficient. Discrimination between prognostic models was assessed using the concordance index (C-index). RESULTS AND LIMITATIONS: Manual and automated BSI measurements were strongly correlated (ρ=0.80), correlated more closely (ρ=0.93) when excluding cases with BSI scores≥10 (1.8%), and were independently associated with PCa death (p<0.0001 for each) when added to the prediction model. Predictive accuracy of the base model (C-index: 0.768; 95% confidence interval [CI], 0.702-0.837) increased to 0.794 (95% CI, 0.727-0.860) by adding manual BSI scoring, and increased to 0.825 (95% CI, 0.754-0.881) by adding automated BSI scoring to the base model. CONCLUSIONS: Automated BSI scoring, with its 100% reproducibility, reduces turnaround time, eliminates operator-dependent subjectivity, and provides important clinical information comparable to that of manual BSI scoring.

Whole-body diffusion-weighted imaging compared with FDG-PET/CT in staging of lymphoma patients.

BACKGROUND: Diffusion-weighted imaging (DWI) has become increasingly valuable in lymph node imaging, yet the clinical utility of this technique in the staging of lymphoma has not been established. PURPOSE: To compare whole-body DWI with FDG-PET/CT in the staging of lymphoma patients. MATERIAL AND METHODS: Thirty-one patients, eight with Hodgkin lymphoma (HL) and 23 with non-Hodgkin's lymphoma (18 aggressive and five indolent) underwent both whole-body DWI, whole-body MRI (T1W and T2W-STIR) and FDG-PET/CT. Lesions on whole-body DWI were only considered positive if they correlated with lesions on T1W and T2W-STIR images. The staging given by each technique was compared, according to the Ann Arbor staging system. Differences in staging were solved using biopsy results, and clinical and CT follow-ups as standard of reference. RESULTS: The staging was the same for DWI and FDG-PET/CT in 28 (90.3%) patients and different in three (9.7%). Of the 28 patients with the same staging, 11 had stage IV in both techniques and 17 had stages 0-III. No HL or aggressive non-Hodgkin's lymphoma patients had different staging. Three indolent small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) lymphoma had higher staging with DWI when compared with FDG-PET/CT. One small subcutaneous breast lymphoma was not seen but all other extranodal sites were detected by both techniques. CONCLUSION: Whole-body DWI is a promising technique for staging of both (aggressive and indolent) non-Hodgkin's lymphoma and HL.

Evaluation of sorafenib treatment in metastatic renal cell carcinoma with 2-fluoro-2-deoxyglucose positron emission tomography and computed tomography.

OBJECTIVE: New potent tyrosine kinase inhibitors such as sorafenib are the most effective treatment for metastatic renal cell carcinoma (MRCC) today. In this study, we used [18F]-2-fluoro-2-deoxyglucose (FDG) with positron emission tomography (PET) combined with computed tomography (CT) to evaluate early effects of sorafenib in patients with MRCC. METHODS: Ten patients, eight males and two females, with a mean age of 61 years (49-72 years), with MRCC were enrolled. A total of 52 lesions, two to nine lesions/patient, out of which 39 were soft lesions, were evaluated. The [18F]FDG-PET/CT was performed before treatment and after 1-2 months. A region of interest (ROI) was identified including the lesions where the glucose uptake was measured, calculating the average value within the ROI and using the cerebellum as the reference. The same ROI was measured in the subsequent FDG-PET. The sum of the diameters was measured in CT according to the Response Evaluation Criteria in Solid Tumors (RECIST). Sorafenib was given 400 mg twice daily orally. RESULTS: After 1-2 months, the mean glucose uptake in all lesions decreased to 75% (32-105%) of initial values of ROI as measured by FDG-PET. The mean glucose uptake in soft lesions decreased to 71% (32-108%) and in skeletal lesions to 82% (53-101%). The sum of the diameters measured by CT decreased to 80% (57-94%) of the initial value in soft lesions according to the RECIST. CONCLUSION: An early decrease in the mean glucose uptake was found in both soft and skeletal lesions after treatment with sorafenib. FDG-PET thus seems to be advantageous, compared with RECIST evaluation, which is limited to soft lesions.

Improved classifications of planar whole-body bone scans using a computer-assisted diagnosis system: a multicenter, multiple-reader, multiple-case study.

UNLABELLED: The aim of this multicenter study was to investigate whether a computer-assisted diagnosis (CAD) system could improve performance and reduce interobserver variation in bone-scan interpretations of the presence or absence of bone metastases. METHODS: The whole-body bone scans (anterior and posterior views) of 59 patients with breast or prostate cancer who had undergone scintigraphy for suspected bone metastatic disease were studied. The patients were selected to reflect the spectrum of pathology found in everyday clinical work. Thirty-five physicians working at 18 of the 30 nuclear medicine departments in Sweden agreed to participate. The physicians were asked to classify each case for the presence or absence of bone metastasis, without (baseline) and with the aid of the CAD system (1 y later), using a 4-point scale. The final clinical assessments, based on follow-up scans and other clinical data including the results of laboratory tests and available diagnostic images (such as MRI, CT, and radiographs from a mean follow-up period of 4.8 y), were used as the gold standard. Each physician's classification was pairwise compared with the classifications made by all the other physicians, resulting in 595 pairs of comparisons, both at baseline and after using the CAD system. RESULTS: The physicians increased their sensitivity from 78% without to 88% with the aid of the CAD system (P < 0.001). The specificity did not change significantly with CAD. Percentage agreement and kappa-values between paired physicians on average increased from 64% to 70% and from 0.48 to 0.55, respectively, with the CAD system. CONCLUSION: A CAD system improved physicians' sensitivity in detecting metastases and reduced interobserver variation in planar whole-body bone scans. The CAD system appears to have significant potential in assisting physicians in their clinical routine.

Computer-assisted interpretation of planar whole-body bone scans.

UNLABELLED: The purpose of this study was to develop a computer-assisted diagnosis (CAD) system based on image-processing techniques and artificial neural networks for the interpretation of bone scans performed to determine the presence or absence of metastases. METHODS: A training group of 810 consecutive patients who had undergone bone scintigraphy due to suspected metastatic disease were included in the study. Whole-body images, anterior and posterior views, were obtained after an injection of (99m)Tc-methylene diphosphonate. The image-processing techniques included algorithms for automatic segmentation of the skeleton and automatic detection and feature extraction of hot spots. Two sets of artificial neural networks were used to classify the images, 1 classifying each hot spot separately and the other classifying the whole bone scan. A test group of 59 patients with breast or prostate cancer was used to evaluate the CAD system. The patients in the test group were selected to reflect the spectrum of pathology found in everyday clinical work. As the gold standard for the test group, we used the final clinical assessment of each case. This assessment was based on follow-up scans and other clinical data, including the results of laboratory tests, and available diagnostic images, such as from MRI, CT, and radiography, from a mean follow-up period of 4.8 y. RESULTS: The CAD system correctly identified 19 of the 21 patients with metastases in the test group, showing a sensitivity of 90%. False-positive classification of metastases was made in 4 of the 38 patients not classified as having metastases by the gold standard, resulting in a specificity of 89%. CONCLUSION: A completely automated CAD system can be used to detect metastases in bone scans. Application of the method as a clinical decision support tool appears to have significant potential.

Quality of planar whole-body bone scan interpretations--a nationwide survey.

PURPOSE: The purpose of this study was to investigate, in a nationwide study, the inter-observer variation and performance in interpretations of bone scans regarding the presence or absence of bone metastases. METHODS: Bone scan images from 59 patients with breast or prostate cancer, who had undergone scintigraphy due to suspected bone metastatic disease, were studied. The patients were selected to reflect the spectrum of pathology found in everyday clinical work. Whole body images, anterior and posterior views, were sent to all 30 hospitals in Sweden that perform bone scans. Thirty-seven observers from 18 hospitals agreed to participate in the study. They were asked to classify each of the patient studies regarding the presence of bone metastasis, using a four-point scale. Each observer's classifications were pairwise compared with the classifications made by all the other observers, resulting in 666 pairs of comparisons. The interpretations of the 37 observers were also compared with the final clinical assessment, which was based on follow-up scans and other clinical data. RESULTS: On average, two observers agreed on 64% of the bone scan classifications. Kappa values ranged between 0.16 and 0.82, with a mean of 0.48. Sensitivity and specificity for the observers compared with the final clinical assessment were 77% and 96%, respectively, for detecting bone metastases in planar whole-body bone scanning. CONCLUSION: Moderate inter-observer agreement was found when observers were compared pairwise. False-negative errors seem to be the major problem in the interpretations of bone scan images, whilst the specificities for the observers were high.

A new computer-based decision-support system for the interpretation of bone scans.

OBJECTIVE: To develop a completely automated method, based on image processing techniques and artificial neural networks, for the interpretation of bone scans regarding the presence or absence of metastases. METHODS: A total of 200 patients, all of whom had the diagnosis of breast or prostate cancer and had undergone bone scintigraphy, were studied retrospectively. Whole-body images, anterior and posterior, were obtained after injection of 99mTc-methylene diphosphonate. The study material was randomly divided into a training group and a test group, with 100 patients in each group. The training group was used in the process of developing the image analysis techniques and to train the artificial neural networks. The test group was used to evaluate the automated method. The image processing techniques included algorithms for segmentation of the head, chest, spine, pelvis and bladder, automatic thresholding and detection of hot spots. Fourteen features from each examination were used as input to artificial neural networks trained to classify the images. The interpretations by an experienced physician were used as the 'gold standard'. RESULTS: The automated method correctly identified 28 of the 31 patients with metastases in the test group, i.e., a sensitivity of 90%. A false positive classification of metastases was made in 18 of the 69 patients not classified as having metastases by the experienced physician, resulting in a specificity of 74%. CONCLUSION: A completely automated method can be used to detect metastases in bone scans. Future developments in this field may lead to clinically valuable decision-support tools.

Indium-111-octreotide scintigraphy, intraoperative gamma-detector localisation and somatostatin receptor expression in primary human breast cancer.

12 women with primary breast cancer underwent somatostatin receptor scintigraphy (SRS) with 111In-DTPA-D-Phe1-octreotide. The tumour sizes varied between 2 and 5 cm and were all, except one, palpable at clinical examination. Tumour biopsies were taken with additional sampling from normal breast tissue, fat, muscle, axillary lymph nodes and peripheral blood. Ratios between the 111In activity concentration in the tissue biopsies (Ti) and in peripheral blood (B) as well as in normal breast tissue (Br) were calculated. In 8/12 patients the scintillation detector was used intraoperatively for radioactivity measurements of the biopsies in situ and ex vivo. The sstr-subtype profiles were determined by northern blot analysis and the relative expression of sstr2 by ribonuclease protection assay (RPA) and immunocytochemistry. Preoperative SRS visualised all primary breast cancer tumours. The scintigraphic image showed no correlation with the histopathological type of the tumour or with the abundance of oestrogen/progesterone receptors on the tumour. Two patients with a massive tumour infiltration of the lymph nodes had a distinct positive SRS of the ipsilateral axilla. In one patient with three nodal metastases the scintigraphic image of the axilla was weak but visible. Four other patients with a negative axillary scintigraphy had 1-2 lymph node metastases. The Ti/B ratios for the breast tumours varied between four and 33 and were not different from Ti/Br ratios. In lymph node metastases the Ti/B ratios were higher (10-41). Intraoperative detector measurements showed a significant difference between the breast tumour and normal tissue in 2/8 patients in situ. Similar measurements on excised tissues (ex vivo) showed a significant difference in 6/8 patients. Two patients with lymph node metastases exhibited a significantly increased uptake ex vivo by detector measurements, but in only one of them in situ. All tumour biopsies expressed the presence of sstrl, 3, 4 and 5, but not of sstr2 at northern analysis. On the other hand, sstr2 was detected in all tumours by RPA and immunocytochemistry. Preoperative SRS visualised primary breast cancer lesions in all 12 patients. SRS could also demonstrate extensive axillary tumour infiltration. Intraoperative use of the scintillation detector could not exclude axillary metastases in situ. The low Ti/B values of both primary tumours and metastases indicate limitations of the radiopharmaceutical used.

Red cell mass, spleen size and plasma erythropoietin in polycythaemia vera and apparent polycythaemia.

Most frequently, an elevated packed cell volume (PCV) value arouses the suspicion of a polycythaemic state. The aim of the present work was to assess a few readily available variables which could help the clinician to differentiate between polycythaemia vera (PV) and apparent polycythaemia (AP). During a 5-year period, 31 consecutive newly diagnosed patients with PV were identified, and during a 4-year period 38 consecutive subjects were considered to be afflicted with AP. In each subject: (i) the red cell mass (RCM) and plasma volume were measured, (ii) the spleen size was assessed using gamma-camera imaging, and (iii) the plasma erythropoietin (EPO) concentration was determined. The diagnosis of PV was based upon recently proposed criteria. By definition, all PV patients had absolute erythrocytosis, i.e. the RCM was greater than 25% above the mean normal predicted value for the individual. There was no statistical difference between the plasma volumes for PV and AP patients. However, the mean measured/predicted plasma volume for subjects with AP was significantly lower than the mean for PV. The means for spleen scan areas (posterior and left lateral projections) for AP patients were identical to the mean reference values for our laboratory. As compared to AP, in PV the spleen scan areas were significantly increased, and the lateral spleen scan area was significantly larger than the posterior area. It was also shown that, in contrast to AP, both spleen scan areas were significantly larger in male than in female PV patients. All PV patients had plasma EPO concentrations below the lower reference limit, and in 68% of the patients undetectable EPO concentrations were present. Most AP patients (84%) had EPO values within the reference range; 8% had slightly subnormal, but not undetectable, plasma EPO levels.