Multi-vendor multi-site quantitative MRI analysis of cartilage degeneration 10 Years after anterior cruciate ligament reconstruction: MOON-MRI protocol and preliminary results.

OBJECTIVE: To describe the protocol of a multi-vendor, multi-site quantitative MRI study for knee post-traumatic osteoarthritis (PTOA), and to present preliminary results of cartilage degeneration using MR T1ρ and T2 imaging 10 years after anterior cruciate ligament reconstruction (ACLR). DESIGN: This study involves three sites and two MR platforms. The patients are from a nested cohort (termed as Onsite cohort) within the Multicenter Orthopaedic Outcomes Network (MOON) cohort 10 years after ACLR. Phantoms and controls were scanned for evaluating reproducibility. Cartilage was automatically segmented, and T1ρ and T2 were compared between operated, contralateral, and control knees. RESULTS: Sixty-eight ACL-reconstructed patients and 20 healthy controls were included. In phantoms, the intra-site coefficients of variation (CVs) of repeated scans ranged 1.8-2.1% for T1ρ and 1.3-1.7% for T2. The inter-site CVs ranged 1.6-2.1% for T1ρ and 1.1-1.4% for T2. In human subjects, the intra-site scan/rescan CVs ranged 2.2-3.5% for T1ρ and 2.6-4.9% for T2 for the six major compartments. In patients, operated knees showed significantly higher T1ρ and T2 values mainly in medial femoral condyle, medial tibia and trochlear cartilage compared with contralateral knees, and showed significantly higer T1ρ and T2 values in all six compartments compared to healthy control knees. The patient contralateral knees showed higher T1ρ and T2 values mainly in the lateral femoral condyle, lateral tibia, trochlear, and patellar cartilage compared to healthy control knees. CONCLUSION: A platform and workflow with rigorous quality control has been established for a multi-vendor multi-site quantitative MRI study in evaluating PTOA 10 years after ACLR. Our preliminary report suggests significant cartilage matrix changes in both operated and contralateral knees compared with healthy control knees.

Donor-matched comparison of chondrogenic progenitors resident in human infrapatellar fat pad, synovium, and periosteum - implications for cartilage repair.

Purpose: There is a clinical need to better characterize tissue sources being used for stem cell therapies. This study focuses on comparison of cells and connective tissue progenitors (CTPs) derived from native human infrapatellar fatpad (IPFP), synovium (SYN), and periosteum (PERI). Materials and Methods: IPFP, SYN, PERI were harvested from twenty-eight patients undergoing arthroplasty. CTPs were quantitatively characterized using automated colony-forming-unit assay to compare total nucleated cell concentration-[Cell], cells/mg; prevalence-(PCTP), CTPs/million nucleated cells; CTP concentration-[CTP], CTPs/mg; proliferation and differentiation potential; and correlate outcomes with patient's age and gender. Results: [Cell] did not differ between IPFP, SYN, and PERI. PCTP was influenced by age and gender: patients >60 years, IPFP and SYN had higher PCTP than PERI (p < 0.001) and females had higher PCTP in IPFP (p < 0.001) and SYN (p = 0.001) than PERI. [CTP] was influenced by age: patients <50 years, SYN (p = 0.0165) and PERI (p < 0.001) had higher [CTP] than IPFP; patients between 60 and 69 years, SYN (p < 0.001) had higher [CTP] than PERI; patients >70 years, IPFP (p = 0.006) had higher [CTP] than PERI. In patients >60 years, proliferation potential of CTPs differed significantly (SYN>IPFP>PERI); however, differentiation potentials were comparable between all three tissue sources. Conclusion: SYN and IPFP may serve as a preferred tissue source for patients >60 years, and PERI along with SYN and IPFP may serve as a preferred tissue source for patients <60 years for cartilage repair. However, the heterogeneity among the CTPs in any given tissue source suggests performance-based selection might be useful to optimize cell-sourcing strategies to improve efficacy of cellular therapies for cartilage repair.

Meniscus treatment and age associated with narrower radiographic joint space width 2-3 years after ACL reconstruction: data from the MOON onsite cohort.

OBJECTIVE: To identify risk factors for radiographic signs of post-traumatic osteoarthritis (OA) 2-3 years after anterior cruciate ligament (ACL) reconstruction through multivariable analysis of minimum joint space width (mJSW) differences in a specially designed nested cohort. METHODS: A nested cohort within the Multicenter Orthopaedic Outcomes Network (MOON) cohort included 262 patients (148 females, average age 20) injured in sport who underwent ACL reconstruction in a previously uninjured knee, were 35 or younger, and did not have ACL revision or contralateral knee surgery. mJSW on semi-flexed radiographs was measured in the medial compartment using a validated computerized method. A multivariable generalized linear model was constructed to assess mJSW difference between the ACL reconstructed and contralateral control knees while adjusting for potential confounding factors. RESULTS: Unexpectedly, we found the mean mJSW was 0.35 mm wider in ACL reconstructed than in control knees (5.06 mm (95% CI 4.96-5.15 mm) vs 4.71 mm (95% CI 4.62-4.80 mm), P < 0.001). However, ACL reconstructed knees with meniscectomy had narrower mJSW compared to contralateral normal knees by 0.64 mm (95% C.I. 0.38-0.90 mm) (P < 0.001). Age (P < 0.001) and meniscus repair (P = 0.001) were also significantly associated with mJSW difference. CONCLUSION: Semi-flexed radiographs can detect differences in mJSW between ACL reconstructed and contralateral normal knees 2-3 years following ACL reconstruction, and the unexpected wider mJSW in ACL reconstructed knees may represent the earliest manifestation of post-traumatic osteoarthritis and warrants further study.

Comparison of radiation dose and image quality from single-energy and dual-energy CT examinations in the same patients screened for hepatocellular carcinoma.

AIM: To compare radiation dose surrogates [volume CT dose index (CTDIvol), dose-length product (DLP), size-specific dose estimate (SSDE), and effective dose] and image noise in a cohort of patients undergoing hepatocellular carcinoma screening who underwent both single-energy CT (SECT) and dual-energy CT (DECT). MATERIALS AND METHODS: In this institutional review board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study, 74 adults (mean age 59.5 years) underwent 64 section SECT (120 kVp and weight-based reference mAs) and 128 section dual-source DECT (100/Sn 140 kVp and CTDIvol, adjusted to match the CDTIvol of the SECT protocol) on different occasions. Noise levels were measured in the liver, inferior vena cava (IVC), retroperitoneal (RP) fat, and aorta. Generalized linear models were constructed to compare dose and noise, adjusting for effective diameter. RESULTS: The total DLP (1371.11 mGy-cm, SD = 527.91) and effective dose (20.57 mSv, SD = 7.92) with SECT were significantly higher than the DLP (864.84 mGy-cm, SD = 322.10) and effective dose (12.97 mSv, SD = 4.83) with DECT (p < 0.001). The differences between SECT and DECT increased as the patient's effective diameter increased (p < 0.001). Noise levels in the liver (22.4 versus 21.9 HU), IVC (22.3 versus 23.4 HU), and RP fat (23.5 versus 23 HU) were similar for DECT and SECT (p > 0.05) but were significantly lower in the aorta for DECT (25.3 versus 26.4 HU; p = 0.006). CONCLUSION: DECT imaging of the abdomen can achieve noise levels comparable to those seen with SECT imaging without a dose penalty to patients.

Primary Cells Isolated from Human Knee Cartilage Reveal Decreased Prevalence of Progenitor Cells but Comparable Biological Potential During Osteoarthritic Disease Progression.

BACKGROUND: Current decisions on cellular therapies for osteoarthritis are based primarily on clinical experience or on assumptions about preferred cell sourcing. They have not been informed by rigorous standardized measurements of the chondrogenic connective-tissue progenitors (CTP-Cs) or their intrinsic diversity of chondrogenic potential. The goal of this study was to quantitatively define the CTP-Cs resident in cartilage of different grades of osteoarthritis and to compare their concentration, prevalence, and biological potential. METHODS: Twenty-three patients who had varus malalignment of the knee and were scheduled to undergo elective total knee arthroplasty for idiopathic osteoarthritis and who had grade 1-2 osteoarthritis on the lateral femoral condyle and grade 3-4 osteoarthritis on the medial femoral condyle were recruited for study of the cartilage removed during surgery. CTP-Cs were assayed by a standardized colony-forming-unit assay using automated image-analysis software based on ASTM standard test method F2944-12. RESULTS: Cell concentration was significantly greater (p < 0.001) in grade 3-4 cartilage than in grade 1-2 cartilage. The prevalence of CTP-Cs varied widely, but it trended lower in grade 3-4 cartilage than in grade 1-2 samples (p = 0.078). The biological performance of CTP-Cs from grade 1-2 and grade 3-4 cartilage was comparable. Increased cell concentration was a significant predictor of decreased CTP-C prevalence (p = 0.002). CONCLUSIONS: Although grade 3-4 cartilage showed fewer CTP-Cs than grade 1-2 cartilage, the range of biological performance was comparable, which suggests that either may be used as a source for potent CTP-Cs. However, the biological reason for the heterogeneity of CTP-Cs in cartilage and the biological implications of that heterogeneity are not well understood and require further study. CLINICAL RELEVANCE: In order to improve the efficacy of cartilage cell therapy procedures, it is key to characterize the quality and quantity of the cells and progenitors being administered. Additionally, understanding the heterogeneity in order to select appropriate subsets of populations will improve the rigor of decisions concerning cell sourcing and targeting for pharmacological and cellular therapies.

Histopathological assessment of primary osteoarthritic knees in large patient cohort reveal the possibility of several potential patterns of osteoarthritis initiation.

OBJECTIVE: The two main objectives of the study include (1) Test the hypothesis that the lateral femoral condyle (LFC) in patients with primary OA and varus knees undergoing total knee arthroplasty (TKA) can be used as a model to better characterize varying histological features of human OA, (2) Correlate characteristic OA features using the established histopathological scoring systems (HHGS and OARSI) to understand potential histopathological patterns of OA initiation. DESIGN: Two osteochondral specimens (4×4×8mm) were collected from fifty patient's LFC at the time of TKA (total 100 specimens), who presented preserved lateral knee compartment with joint space width>2mm. Three independent readers graded the sections on three different occasions using HHGS and OARSI systems. The correlation between individual parameters of the two scoring systems and their inter- and intra-reader variability, reliability and reproducibility were estimated. RESULTS: All samples in this cohort showed abnormal histopathological features. Total histopathological scores of the LFC ranged from HHGS median=4.6 (range=0 to 11), and OARSI median=5.2 (range=0 to 19.5). The four individual sub-items of HHGS scoring system (structure, cells, safraninO staining, tidemark) were weakly correlated, with the correlation between structure and cellularity being the strongest (r=0.40). Both the scoring systems had similar repeatability and reproducibility coefficients of<21%. CONCLUSIONS: OA changes in the LFC are not confined to any one region, and maybe seen in different regions of cartilage, tidemark, subchondral bone, and/or the marrow space vascularity. These variations may point to the possibility of several potential patterns of initiation in OA.

Comparison of FDG-PET and sestamibi-SPECT in primary hyperparathyroidism.

UNLABELLED: Preoperative localization of hyperfunctioning parathyroid tissue in patients with primary hyperparathyroidism has been a longstanding diagnostic challenge. This study directly compared FDG-PET and sestamibi-SPECT for preoperative detection of abnormal parathyroid tissue. METHODS: Twenty-one consecutive patients with primary hyperparathyroidism were studied prospectively before surgical neck exploration. SPECT of the neck and chest was performed at 15 min and 2 hr after intravenous 99mTc-sestamibi. Regional body PET was performed 45 min after intravenous FDG. RESULTS: Surgery revealed 19 solitary parathyroid adenomas, 2 parathyroid adenomas in one patient; and 3 hyperplastic parathyroid glands in one patient, and 51 normal parathyroid glands. The diagnostic sensitivities for detection of parathyroid adenomas of 43% (9 of 21) for dual-phase sestamibi-SPECT and 86% (18 of 21) for FDG-PET were significantly different (p < 0.001). The difference in diagnostic specificities of 78% (40 of 51) for FDG-PET and 90% (46 of 51) for dual-phase sestamibi-SPECT approached statistical significance (p = 0.063). CONCLUSION: This study demonstrates that FDG-PET is more sensitive than sestamibi-SPECT in the preoperative localization of parathyroid adenomas in patients with primary hyperparathyroidism.

Postoperative portable chest radiographs: optimum use in thoracic surgery.

PURPOSE: Daily portable chest radiographs are routinely ordered in many institutions after thoracic surgery. Our purpose was to assess the efficacy and cost of this practice and to determine the optimum use of postoperative x-ray studies. METHODS: A prospective review of all portable chest x-ray films after 100 consecutive elective thoracotomies (DRG 75) was conducted. Each x-ray study initiated a three-part survey. First, the surgeon listed whether the x-ray study was routine and the anticipated management had it not been available. The radiologist then interpreted and scored the x-ray study as follows: negative, expected findings; A, minor findings necessitating no intervention; B, minor findings necessitating intervention; or C, major findings necessitating intervention. Finally, the x-ray film and the interpretation were returned to the surgeon. Any interventions necessitated by the x-ray study were recorded. RESULTS: In 6 months, 99 patients underwent 82 pulmonary resections and 18 other major procedures. In the postoperative period, 769 portable chest x-ray studies were ordered, median five per patient (range 2 to 49). Of these, 731 (95%) were routine and 38 (5%), nonroutine. Severity scores were as follows: negative in 106 (13.8%), A in 558 (72.5%), B in 59 (7.7%), and C in 46 (6.0%). X-ray findings altered management in 43 of 769 studies (5.6%): in 33 routine (4.5%), in 10 nonroutine (26.3%), in 13 A (2.3%), in 22 B (37.3%), and in 8 C (17.4%). CONCLUSIONS: These results demonstrate that routine daily portable chest x-ray studies have a minimal impact on management. It is, in fact, nonroutine x-ray studies that more often alter management. Had routine portable chest x-ray studies, which cost $114 each in our institution, been limited to one immediately after the operation, only 133 such studies (100 routine and 33 nonroutine) would have been needed in the care of these patients. Elimination of 636 (82.7%) x-ray studies reduces the cost of care by $725 per patient ($286,000 annually). For major thoracic procedures, it is safe, efficacious, and cost effective to eliminate routine postoperative portable chest x-ray studies and order nonroutine portable studies only when clinically indicated.

Computing sample size for receiver operating characteristic studies.

RATIONALE AND OBJECTIVES: Hanley and McNeil (1982) proposed a nonparametric method for computing the standard error of the area under the receiver operating characteristic (ROC) curve. The method has been important in planning the minimum sample size for ROC studies. However, the validity of this method for rating data with various standard deviation ratios has not been investigated. METHODS: A simulation study was conducted to compare the empirical standard error of the area under the curve with Hanley and McNeil's estimate over a range of parameters. An alternative method of computing the standard error based on a binormal distribution is proposed. RESULTS: The method of Hanley and McNeil can lead to underestimation of the minimum sample size. The proposed method provides more appropriate estimates of sample size. CONCLUSIONS: When determining sample size for a study of the area under the ROC curve where rating data are used, the standard error estimator based on the binormal distribution should be used.

Nonparametric estimation of degenerate ROC data sets used for comparison of imaging systems.

Maximum likelihood estimation, assuming a binormal model, has been used extensively to estimate the area under receiver operating characteristic (ROC) curves and thus provide an index of diagnostic accuracy for the comparison of two imaging systems. However, in some instances, a degenerate data set results in a fitted ROC curve of inappropriate shape. In those instances, a nonparametric Wilcoxon statistic may be used to compare the areas under two ROC curves. Simulation of this approach indicates that the procedure has relatively high statistical power and its use in specific degenerate data sets shows its applications potential.

Effect of two rating formats in multi-disease ROC study of chest images.

ROC methodology has been expanded in recent years to include multi-disease experiments. To accommodate these changes, different rating formats, general or disease specific, can be used. No experimental data are available concerning the possible effects of the rating format on the results of these studies. We performed a multi-observer, multi-disease study in which 196 chest images were rated using a format where each disease was evaluated individually and one in which the cases were evaluated without scoring a specific disease. The results indicate that for our data set, the overall assessment of accuracy was not significantly affected by the study format used. Thus, in spite of the difficulties in selecting appropriate controls and the necessity of reassessing sample size considerations, the disease-specific format appears to produce an assessment of accuracy equivalent to that produced by the general format. This equivalence permits the use of the disease-specific approach since it more closely simulates the readers' true environment and is more appropriate for comparing imaging systems that may have a relative accuracy that is disease specific.

Effect of observer instruction on ROC study of chest images.

Receiver-operating characteristic (ROC) analysis has been used in many medical imaging applications during the past decade. In order to ensure that reader-confidence ratings are analyzable (well distributed to meet convergence requirements of curve-fitting algorithms) and meaningful (limit extrapolation of the data), many investigators train readers specifically for this purpose. No experimental data are available concerning the possible effects of such training on the results of ROC studies. We performed a multi-observer, multi-disease study in which 300 chest images were rated by four radiologists before and after they were trained to provide well-distributed confidence ratings. The results indicate that for our data set, reader and disease-specific accuracy was not significantly affected by the training process for interstitial disease and pneumothoraces. However, the accuracy of two readers was significantly affected for the detection of nodules (P less than 0.05), and the overall accuracy of one reader was significantly affected for the classification of normal versus abnormal images (P less than 0.01). Thus, in spite of the difficulties associated with the performance of ROC studies in a free-reading environment, one should carefully consider the possible effects of any intervention on the results prior to conducting ROC studies.

Segmented three-dimensional echo-planar flow imaging of the cervical carotid arteries.

PURPOSE: To implement and assess the application of segmented three-dimensional echo-planar MR imaging time-of-flight flow sequences for studying the anatomy of the cervical carotid arteries at 1.5 T. METHODS: The 3-D echo-planar sequences were segmented along the in-plane phase-encoding direction. Echo train lengths (ETLs) of 3 and 5 and signal bandwidths of +/-25, +/-33, and +/-50 KHz were tested along with a conventional (ETL = 1) 3-D MR flow study in six healthy volunteers and in five patients with known arteriosclerotic disease involving the carotid bifurcation as confirmed by conventional angiography. The volunteer data were used to rank the techniques with respect to vessel dimension, vessel/background contrast, and quality by four trained neuroradiologists. For the patient studies, the percentage of stenoses was measured for all MR studies and compared against the conventional angiographic data using the criteria of the North American Symptomatic Carotid Endarterectomy Trial. RESULTS: Using Wilcoxon's test statistic and a significance level of .05, we found that the conventional MR flow examination was better than the segmented techniques and that the segmented techniques with ETL of 3 were superior to their counterparts with ETL of 5. For the ETL of 3 techniques, the high-bandwidth studies were inferior to their lower bandwidth counterparts; however, there was no significant difference between the performance of the medium- and low-bandwidth sequences. The patient data revealed that the segmented techniques consistently overestimated the severity of stenosis; however, in no instance did any of the segmented examinations erroneously indicate the presence of disease. CONCLUSIONS: The reduction in acquisition time and the zero false-positive rate we obtained suggest that segmented 3-D echo-planar MR flow techniques may be used as a screening/locating study for cervical carotid artery disease.

Efficacy of endovascular treatment of meningiomas: evaluation with matched samples.

PURPOSE: To evaluate the clinical efficacy, cost-effectiveness, and safety of presurgical devascularization of meningiomas. METHODS: Matched samples of embolized and nonembolized groups of meningiomas were compared. The study variables for clinical efficacy were estimated blood loss, number of transfusions, surgical resection time, and length of hospitalization. The cost-effectiveness was evaluated by adjusting all hospital costs to 1991 dollar amounts, and adding additional embolization costs and fees to the hospital cost totals for the embolized group. A qualitative comparison of complications was made. RESULTS: All dependent variables evaluating the clinical efficacy of the procedure (estimate blood loss, 533 cc versus 836 cc; number of transfusions, 0.39 units versus 1.56 units; surgical resection time, 305.8 minutes versus 337.5 minutes; and length of hospitalization, 10.6 days versus 15.0 days) displayed trends of higher means in the nonembolized group; however, only the estimated blood loss and number of transfusions variables were significant. The cost-effectiveness of the procedure was not statistically significant. The mean cost was $29,605 for the embolized group and $38,449 for the nonembolized group. There were three major and nine minor complications in the nonembolized group and zero major and six minor complications in the embolized group. There were four additional minor complications caused by the embolization procedure. CONCLUSION: Endovascular devascularization of meningiomas is beneficial for large meningiomas because it diminishes the necessity of intraoperative transfusions and decreases blood loss. The additional day of hospitalization, emolization costs, and costs of complications do not conversely increase treatment costs. There were no major complications or adverse long-term effects caused by the embolization procedure.

Fast spin-echo imaging of the neck: comparison with conventional spin-echo, utility of fat suppression, and evaluation of tissue contrast characteristics.

PURPOSE: To determine whether fast spin-echo sequences could replace conventional spin-echo methods in the evaluation of head and neck neoplasms and associated adenopathy and to evaluate differences in tissue contrast characteristics between conventional spin-echo and fast spin-echo examinations of head and neck disease. METHODS: Twenty-seven patients with squamous cell carcinoma were imaged on a 1.5-T imager with both conventional spin-echo and fast spin-echo sequences with identical section thickness and position. Twenty-one of the 27 fast spin-echo studies were performed with frequency-selective fat suppression. Three radiologists independently evaluated the images using a five-point scale to compare primary lesion margin definition and conspicuity, lymph node margin definition and conspicuity, gross motion artifact, and flow artifact. Quantitative percent contrast and contrast-to-noise ratios were calculated and compared in 7 cases with fat-suppressed fast spin-echo. RESULTS: Fast spin-echo was preferred by all three readers for lesion margin conspicuity and lymph node conspicuity. Gross motion and flow artifact demonstrated trends toward reader preference for fast spin-echo. Quantitative contrast values for fast spin-echo were significantly greater than those for conventional spin-echo. CONCLUSIONS: Fast spin-echo with fat suppression can replace conventional spin-echo at a time savings of more than 50% and improves tissue contrast and the conspicuity and definition of margins for primary lesions and lymph nodes. Fat-suppression heterogeneity remains the major limitation of this technique. Thus, careful attention to fat-suppression failure and unwanted water saturation is essential.

Quantitative classification of breast tumors in digitized mammograms.

The goal of this study was to develop a technique to distinguish benign and malignant breast lesions in secondarily digitized mammograms. A set of 51 mammograms (two views/patient) containing lesions of known pathology were evaluated using six different morphological descriptors: circularity, mu R/sigma R (where mu R = mean radial distance of tumor boundary, sigma R = standard deviation); compactness, P2/A (where P = perimeter length of tumor boundary and A = area of the tumor); normalized moment classifier; fractal dimension; and a tumor boundary roughness (TBR) measurement (the number of angles in the tumor boundary with more than one boundary point divided by the total number of angles in the boundary). The lesion was segmented from the surrounding background using an adaptive region growing technique. Ninety-seven percent of the lesions were segmented using this approach. An ROC analysis was performed for each parameter and the results of this analysis were compared to each other and to those obtained from a subjective review by two board-certified radiologists who specialize in mammography. The results of the analysis indicate that all six parameters are diagnostic for malignancy with areas under their ROC curves ranging from 0.759 to 0.928. We observed a trend towards increased specificity at low false-negative rates (0.01 and 0.001) with the TBR measurement. Additionally, the diagnostic accuracy of a classification model based on this parameter was similar to that of the subjective reviewers.

The safety and effectiveness of brain arteriovenous malformation embolization using acrylic and particles: the experiences of a single institution.

The purpose of this article is to report on the safety and effectiveness of brain arteriovenous malformation (AVM) embolization for two series of patients, of which one was treated with particulate embolization and the other with acrylic embolization. Sixty-five consecutive patients from embolization logs and patient records from 1988 to 1993 were reviewed. AVMs were routinely treated with particulate embolization early in the review (1988-1991), and after a transition period, the technique was changed to acrylic embolization for the remainder of the study period (1992-1993). All patients were treated with the ultimate goal of complete AVM obliteration. AVMs were embolized and resected, if possible, and if unresectable, they were reduced in size with embolization and radiated. The course of treatment for each patient was reviewed. The effectiveness at the end of treatment was analyzed for the ability to resect the AVM and, if unresectable, the ability to reduce the AVM to radiation size. Additionally, the safety of each embolization technique was evaluated in the context of comprehensive care, in terms of the safety of the procedure itself, the surgical resection after embolization, and the outcome at the end of comprehensive treatment. This article outlines the safety and effectiveness of acrylic and particulate embolization at a single institution. The ability to surgically resect an AVM after embolization and to reduce nidus size with acrylic was at least comparable with that with particulate embolization. Comprehensive complication rates were lower after acrylic embolization and were heavily influenced by a decreased number of surgical complications in the acrylic series. These data support the need to conduct a randomized prospective clinical trial to compare the relative safety and effectiveness of the two methods of embolization.

Current implications for the efficacy of noninvasive screening for occult intracranial aneurysms in patients with a family history of aneurysms.

Although the technology exists for accurate noninvasive screening for intracranial aneurysms, the efficacy of screening depends on several key parameters of the natural history of aneurysms. Recent studies suggest that the prevalence of intracranial aneurysms may reach 20% in the subpopulation of patients with a family history of these lesions; other key parameters are less certain. The authors investigated factors that impact the efficacy of screening to establish interim guidelines. Three plausible models for the natural history of aneurysms were constructed. For each model the monetary cost of screening and the average gain in life expectancy were computed for a range of screening ages and prevalence rates. It is shown that the efficacy of screening depends on the pattern of aneurysm rupture. If aneurysms develop and rupture rapidly, then screening has no benefit. On the other hand, if aneurysms remain at risk for some time after formation, then screening may improve average life expectancy depending on when it occurs. The authors recommend that patients with a positive family history of aneurysms who are 30 years of age or younger be screened. This recommendation is based on the belief that the gains attributable to screening, assuming a constant rupture rate, outweigh the losses attributable to screening using a decreasing rupture rate model.

Correlation of valve closing to visualization of single-leg separation in radiographic images of Björk-Shiley convexo-concave heart valves.

BACKGROUND AND AIM OF THE STUDY: The study goal was to determine whether the visualization of single-leg separation (SLS) in cineangiographic sequences of Björk-Shiley convexo-concave heart valves could be correlated to the position of the occluder disk within the cardiac cycle. METHODS: Images from ten patient cases with SLS valves were reviewed by three experts, who identified the image frames within a cine sequence that appeared suspicious for SLS. The position of the occluder disk, the frame rate, and the length of the cardiac cycle were noted relative to these image frames. RESULTS: The probability of detecting a SLS was not significantly correlated to any of these factors. CONCLUSIONS: Visualization of SLS in cineangiographic images is limited to a few frames within an imaging sequence. It appears that other features within the image play a larger role in a clinician's ability to detect a fracture than do the cardiac dynamics of the system.

Sample size calculations in studies of test accuracy.

Methods for determining sample size for studies of the accuracy of diagnostic tests are reviewed. Several accuracy indices are considered, including sensitivity and specificity, the full and partial area under the receiver operating characteristic curve, the sensitivity at a fixed false positive rate, and the likelihood ratio. Sample size formulae are presented for studies evaluating a single test and studies comparing the accuracy of tests. Four real examples illustrate the concepts involved in sample size determination. Lastly, various study design issues are discussed, such as sampling methods, choices in format for the test results, and the issue of replicated readings.