OARSI Clinical Trials Recommendations: Knee imaging in clinical trials in osteoarthritis.

Significant advances have occurred in our understanding of the pathogenesis of knee osteoarthritis (OA) and some recent trials have demonstrated the potential for modification of the disease course. The purpose of this expert opinion, consensus driven exercise is to provide detail on how one might use and apply knee imaging in knee OA trials. It includes information on acquisition methods/techniques (including guidance on positioning for radiography, sequence/protocol recommendations/hardware for magnetic resonance imaging (MRI)); commonly encountered problems (including positioning, hardware and coil failures, sequences artifacts); quality assurance (QA)/control procedures; measurement methods; measurement performance (reliability, responsiveness, validity); recommendations for trials; and research recommendations.

The effect of anterior cruciate ligament injury on bone curvature: exploratory analysis in the KANON trial.

OBJECTIVE: Investigate the 5-year longitudinal changes in bone curvature after acute anterior cruciate ligament (ACL) injury, and identify predictors of such changes. METHODS: In the KANON-trial (ISRCTN 84752559), 111/121 young active adults with an acute ACL tear to a previously un-injured knee had serial 1.5 T MR images from baseline (within 5 weeks from injury) to 5 years after injury. Of these, 86 had ACL reconstruction (ACLR) performed early or delayed, 25 were treated with rehabilitation alone. Measures of articulating bone curvature were obtained from computer-assisted segmentation of MR images. Curvature (mm(-1)) was determined for femur, tibia, medial/lateral femur, trochlea, medial/lateral tibia. Age, sex, treatment, BMI, meniscal injury, osteochondral fracture on baseline MR images were tested for association. RESULTS: Over 5 years, curvature decreased in each region (P < 0.001) suggesting flattening of convex shapes and increased concavity of concave shapes. A higher BMI was associated with flattening of the femur (P = 0.03), trochlea (P = 0.007) and increasing concavity of the lateral tibia (LT) (P = 0.011). ACLR, compared to rehabilitation alone, was associated with flatter curvature in the femur (P < 0.001), medial femoral condyle (P = 0.006) and trochlea (P = 0.003). Any meniscal injury at baseline was associated with a more flattened curvature in the femur (P = 0.038), trochlea (P = 0.039), lateral femoral condyle (P = 0.034) and increasing concavity of the LT (P = 0.048). CONCLUSION: ACL injury is associated with significant changes in articulating bone curvature over a 5 year period. Higher BMI, baseline meniscal injury and undergoing ACL reconstruction (as distinct from undergoing rehabilitation alone) are all associated with flattening of the articulating bone.

Quantitative 3D MRI reveals limited intra-lesional bony overgrowth at 1 year after microfracture-based cartilage repair.

OBJECTIVE: Intra-lesional bony overgrowth (BO) identified during or following cartilage repair treatment is being frequently described through subjective reports focusing primarily on incidence. Our objective was to quantify the exact volume of intra-lesional BO at 12 months post-cartilage repair treatment, to determine if a correlation exists between the extent of BO and clinical outcomes, and to visualize and characterize the BO. DESIGN: MRI scans were systematically obtained during a randomized clinical trial for cartilage repair (Stanish et al., 2013) that compared two microfracture-based treatments in 78 patients. Semi-automated morphological segmentation of pre-treatment, 1 and 12 months post-treatment scans utilizing a programmed anatomical atlas for all knee bone and cartilage structures permitted three-dimensional reconstruction, quantitative analysis, as well as qualitative characterization and artistic visualization of BO. RESULTS: Limited intra-lesional BO representing only 5.8 ± 5.7% of the original debrided cartilage lesion volume was found in 78 patients with available MRIs at 12 months. The majority (80%) of patients had very little BO (<10%). Most occurrences of BO carried either spotty (56.4%) or planar (6.4%) morphological features, and the remaining balance (37.2%) was qualitatively unobservable by eye. Pre-existing BO recurred at 12 months in the same intra-lesional location in 36% of patients. No statistical correlations were found between BO and clinical outcomes. CONCLUSIONS: Intra-lesional BO following microfracture-based treatments may not be as severe as previously believed, its incidence is partly explained by pre-existing conditions, and no relationship to clinical outcomes exists at 12 months. Morphologically, observable BO was categorized as comprising either spotty or planar bone.

Region of interest analysis: by selecting regions with denuded areas can we detect greater amounts of change?

INTRODUCTION: Based on recent analyses, the measures of short-term responsiveness of magnetic resonance imaging (MRI) derived cartilage morphometry may not be as large as earlier studies had suggested. We examined if by selecting regions of interest with denuded cartilage, the remaining cartilage within this region of interest was susceptible to greater rates of cartilage loss. METHODS: Subjects included for this analysis are a subset of the approximately 4700 participants in the Osteoarthritis Initiative (OAI) Study. Bilateral radiographs and 3T MRI (Siemens Trio) of the knees and clinical data are obtained at baseline and annually in all participants. Hundred and fifty subjects from the OAI progression subcohort all of whom had both frequent symptoms and, in the same knee, radiographic osteoarthritis (ROA defined as definite tibio-femoral osteophytes on X-ray) based on a screening reading done at the OAI clinics. One knee from each subject was selected for analysis. Using sagittal 3D DESSwe MR images from the baseline and 12-month follow-up visit, a segmentation algorithm was applied to the cartilage plates of the index knee to compute the cartilage volume, normalized cartilage volume (volume normalized to bone surface interface area), and percent denuded area (Total Cartilage Bone Interface area denuded of cartilage). Summary statistics of the changes (absolute and percentage) from baseline at 1 year and the standardized response mean (SRM), i.e., mean change divided by the standard deviation (SD) of that change were calculated. Analyses are stratified into three groups according to baseline assessment of denuded area: those with no denuded area in the region of interest at baseline, and then two groups (intermediate denuded area (or=median) denuded area) of equal sample size. RESULTS: On average the subjects were 60.9 years of age and obese with a mean body mass index (BMI) of 30.3 kg/m(2). For the combined central medial femur and tibia the mean volume change for the whole sample was -48.2 (SD 159.8) mm(3), which gives an SRM of -0.30. In the subsample of knees with no denuded area the SRM was -0.25, in the knees with intermediate denuded area the SRM was -0.30, and in knees with severe denuded area the SRM was -1.00. For normalized volume of the central medial femur in the subsample of knees with no denuded area the SRM was -0.22, in the knees with intermediate denuded area the SRM was -0.26, and in knees with severe denuded area (n=23) the SRM was -0.71. The magnitude of the SRMs was generally smaller in participants with no denuded area. In contrast, the SRMs in participants with denuded area were larger. CONCLUSION: By selecting participants with the presence of cartilage regions with denuded area the ability to demonstrate change in cartilage loss in that specific location is markedly improved compared to persons without a full thickness lesion in that cartilage plate. This option for screening during recruitment in clinical trials could facilitate the detection of participants at greater risk of subsequent cartilage loss.

Change in cartilage morphometry: a sample of the progression cohort of the Osteoarthritis Initiative.

OBJECTIVE: The performance characteristics of hyaline articular cartilage measurement on magnetic resonance imaging (MRI) need to be accurately delineated before widespread application of this technology. Our objective was to assess the rate of natural disease progression of cartilage morphometry measures from baseline to 1 year in knees with osteoarthritis (OA) from a subset of participants from the Osteoarthritis Initiative (OAI). METHODS: Subjects included for this exploratory analysis are a subset of the approximately 4700 participants in the OAI Study. Bilateral radiographs and 3T MRI (Siemans Trio) of the knees and clinical data were obtained at baseline and annually in all participants. 160 subjects from the OAI Progression subcohort all of whom had both frequent symptoms and, in the same knee, radiographic OA based on a screening reading done at the OAI clinics were eligible for this exploratory analysis. One knee from each subject was selected for analysis. 150 participants were included. Using sagittal 3D DESSwe (double echo, steady-state sequence with water excitation) MR images from the baseline and 12 follow-up month visit, a segmentation algorithm was applied to the cartilage plates of the index knee to compute the cartilage volume, normalised cartilage volume (volume normalised to bone surface interface area), and percentage denuded area (total cartilage bone interface area denuded of cartilage). RESULTS: Summary statistics of the changes (absolute and percentage) from baseline at 1 year and the standardised response mean (SRM), ie, mean change divided by the SD change were calculated. On average the subjects were 60.9 years of age and obese, with a mean body mass index of 30.3 kg/m2. The SRMs for cartilage volume of various locations are: central medial tibia -0.096; central medial femur -0.394; and patella -0.198. The SRMs for normalised cartilage volume of the various locations are central medial tibia -0.044, central medial femur -0.338 and patella -0.193. The majority of participants had a denuded area at baseline in the central medial femur (62%) and central medial tibia (60%). In general, the SRMs were small. CONCLUSIONS: These descriptive results of cartilage morphometry and its change at the 1-year time point from the first substantive MRI data release from the OAI Progression subcohort indicate that the annualised rates of change are small with the central medial femur showing the greatest consistent change.

The acutely ACL injured knee assessed by MRI: changes in joint fluid, bone marrow lesions, and cartilage during the first year.

OBJECTIVES: To investigate changes in the knee during the first year after acute rupture of the anterior cruciate ligament (ACL) of volumes of joint fluid (JF), bone marrow lesions (BMLs), and cartilage volume (VC), and cartilage thickness (ThCcAB) and cartilage surface area (AC). To identify factors associated with these changes. METHODS: Fifty-eight subjects (mean age 26 years, 16 women) with an ACL rupture to a previously un-injured knee were followed prospectively using a 1.5T MR imager at baseline (within 5 weeks from injury), 3 months, 6 months, and 1 year. Thirty-four subjects were treated with ACL reconstruction followed by a structured rehabilitation program and 24 subjects were treated with structured rehabilitation only. Morphometric data were acquired from computer-assisted segmentation of MR images. Morphometric cartilage change was reported as mean change divided by the standard deviation of change (standard response mean, SRM). RESULTS: JF and BML volumes gradually decreased over the first year, although BML persisted in 62% of the knees after 1 year. One year after the ACL injury, a reduction of VC, AC and ThCcAB (SRM -0.440 or greater) was found in the trochlea femur (TrF), while an increase of VC and ThCcAB was found in the central medial femur (cMF) (SRM greater than 0.477). ACL reconstruction was directly and significantly related to increased JF volume at 3 and 6 months (P<0.001), BML volume at 6 months (P=0.031), VC and ThCcAB in cMF (P<0.002) and decreased cartilage area in TrF (P=0.010) at 12 months. CONCLUSION: Following an acute ACL tear, cMF and TrF showed the greatest consistent changes of cartilage morphometry. An ACL reconstruction performed within a mean of 6 weeks from injury was associated with increased ThCcAB and VC in cMF and decreased AC in TrF, compared to knees treated without reconstruction. This may suggest a delayed structural restitution in ACL reconstructed knees.

The acutely ACL injured knee assessed by MRI: are large volume traumatic bone marrow lesions a sign of severe compression injury?

OBJECTIVES: To map by magnetic resonance imaging (MRI) and quantitative MRI (qMRI) concomitant fractures and meniscal injuries, and location and volume of traumatic bone marrow lesions (BMLs) in the acutely anterior cruciate ligament (ACL) injured knee. To relate BML location and volume to cortical depression fractures, meniscal injuries and patient characteristics. METHODS: One hundred and twenty-one subjects (26% women, mean age 26 years) with an ACL rupture to a previously un-injured knee were studied using a 1.5T MR imager within 3 weeks from trauma. Meniscal injuries and fractures were classified by type, size and location. BML location and volume were quantified using a multi-spectral image data set analyzed by computer software, edited by an expert radiologist. RESULTS: Fractures were found in 73 (60%) knees. In 67 (92%) of these knees at least one cortical depression fracture was found. Uni-compartmental meniscal tears were found in 44 (36%) subjects and bi-compartmental in 24 (20%). One hundred and nineteen (98%) knees had at least one BML, all but four (97%) located in the lateral compartment. Knees with a cortical depression fracture had larger BML volumes (P<0.001) than knees without a cortical depression fracture, but no associations were found between meniscal tears and BML volume or fractures. Older age at injury was associated with smaller BML volumes (P<0.01). CONCLUSION: A majority of the ACL injured knees had a cortical depression fracture, which was associated with larger BML volumes. This indicates strong compressive forces to the articular surface and cartilage at the time of injury, which may constitute an additional risk factor for later knee osteoarthritis development.

The effect of etanercept on osteoclast precursor frequency and enhancing bone marrow oedema in patients with psoriatic arthritis.

OBJECTIVE: The frequency of osteoclast precursors (OCPF) and the presence of bone marrow oedema (BMO) are potential response biomarkers in psoriatic arthritis (PsA). Previous studies suggest a central role for tumour necrosis factor (TNF) in the formation of osteoclast precursors. To better understand this association, the effect of etanercept on OCPF and BMO was analysed in PsA patients with erosive arthritis. METHODS: A total of 20 PsA patients with active erosive PsA were enrolled. Etanercept was administered twice weekly for 24 weeks. OCPF was measured and clinical assessments were performed at baseline, 2, 12 and 24 weeks. Gadolinium enhanced MR images were obtained at baseline and 24 weeks. RESULTS: Significant improvements in joint score (p<0.001), HAQ scores (p<0.001) and SF-36 parameters were observed after 6 months of therapy with etanercept compared to baseline. The median OCPF decreased from 24.5 to 9 (p = 0.04) and to 7 (p = 0.006) after 3 months and 6 months of treatment, respectively. MR images were available for 13 patients. The BMO volume decreased in 47 and increased in 31 sites at 6 months. No correlation was noted between OCPF, BMO and clinical parameters. CONCLUSION: The rapid decline in OCPF and overall improvement in BMO after anti-TNFalpha therapy provides one mechanism to explain the anti-erosive effects of TNF blockade in PsA. Persistence of BMO after etanercept treatment, despite a marked clinical response, was unexpected, and suggests ongoing subchondral inflammation or altered remodelling in PsA bone.

MRI and non-cartilaginous structures in knee osteoarthritis.

Magnetic resonance imaging (MRI) provides a sensitive tool for examining all the structures involved in the osteoarthritis (OA) process. While much of the MRI literature previously focussed on cartilage, there is increasing research on whole-organ evaluation and including features such as synovitis, bone marrow edema, and meniscal and ligamentous pathology. The aim of this session at the Outcome Measures in Rheumatology Clinical Trials (OMERACT)-Osteoarthritis Research Society International (OARSI) Workshop for Consensus in Osteoarthritis Imaging was to describe the current MRI methods for identifying and quantifying non-cartilaginous structures and review their associations with both OA symptoms and structural progression. Although there is much experience in measuring synovitis (derived from the rheumatoid arthritis literature), only one study has reported an association of MRI-detected synovitis and effusions with OA pain. Bone marrow edema lesions, which may represent areas of trabecular remodelling, have been associated with pain and compartment-specific structural deterioration. MRI studies have confirmed the frequency and importance of meniscal damage in progressive cartilage loss, but not related such damage to symptoms. Osteophytes have been associated with cartilage loss and malalignment to the side of the osteophyte. Ligament damage, including anterior cruciate ligament tears, has been found more commonly than expected in painful OA knees. Improvements in quantitative and semi-quantitative assessments of non-cartilage features will greatly assist understanding of the OA process and its response to therapy.

Proposal for a nomenclature for magnetic resonance imaging based measures of articular cartilage in osteoarthritis.

OBJECTIVE: Magnetic resonance imaging (MRI) of articular cartilage has evolved to be an important tool in research on cartilage (patho)physiology and osteoarthritis (OA). MRI provides a wealth of novel and quantitative information, but there exists no commonly accepted terminology for reporting these metrics. The objective of this initiative was to propose a nomenclature for definitions and names to be used in scientific communications and to give recommendations as to which minimal methodological information should be provided when reporting MRI-based measures of articular cartilage in OA. METHODS: An international group of experts with direct experience in MRI measurement of cartilage morphology or composition reviewed the existing literature. Through an iterative process that included a meeting with a larger group of scientists and clinicians (December 2nd, 2004, Chicago, IL, USA), they discussed, refined, and proposed a nomenclature for MRI-based measures of articular cartilage in OA. RESULTS: The group proposes a nomenclature that describes: (1) the anatomical location and (2) the structural feature being measured, each name consisting of a metric variable combined with a tissue label. In addition, the group recommends minimal methodological information that should be described. CONCLUSIONS: Utilization of this nomenclature should facilitate communication within the scientific community. Further, the uniform adoption of comprehensive nomenclature to describe quantitative MRI- features of articular cartilage should strengthen epidemiological, clinical, and pharmacological studies in OA.

MRI findings of scapholunate instabilities in coronal images: a short communication.

The plain radiographic findings of scapholunate instabilities are very well described in the literature. However, even though the same phenomena that are seen in plain radiographs are also seen in magnetic resonance (MR) images, there are very few reports in the literature regarding MRI findings in scapholunate instabilities. This short communication describes the findings seen in coronal MR images in advanced scapholunate instabilities.

Three-dimensional registration and fusion of ultrasound and MRI using major vessels as fiducial markers.

This paper describes fusion of three-dimensional (3-D) ultrasound (US) and magnetic resonance imaging (MRI) data sets, without the assistance of external fiducial markers or external position sensors. Fusion of these two modalities combines real-time 3-D ultrasound scans of soft tissue with the larger anatomical framework from MRI. The complementary information available from multiple imaging modalities warrants the development of robust fusion capabilities. We describe the data acquisition, specialized algorithms, and results for 3-D fused data from phantom studies and in vivo studies of the normal human vasculature and musculoskeletal systems.

The association of bone marrow lesions with pain in knee osteoarthritis.

BACKGROUND: The cause of pain in osteoarthritis is unknown. Bone has pain fibers, and marrow lesions, which are thought to represent edema, have been noted in osteoarthritis. OBJECTIVE: To determine whether bone marrow lesions on magnetic resonance imaging (MRI) are associated with pain in knee osteoarthritis. DESIGN: Cross-sectional observational study. SETTING: Veterans Affairs Medical Center. PATIENTS: 401 persons (mean age, 66.8 years) with knee osteoarthritis on radiography who were drawn from clinics in the Veterans Administration health care system and from the community. Of these persons, 351 had knee pain and 50 had no knee pain. MEASUREMENTS: Knee radiography and MRI of one knee were performed in all participants. Those with knee pain quantified the severity of their pain. On MRI, coronal T(2)-weighted fat-saturated images were used to score the size of bone marrow lesions, and each knee was characterized as having any lesion or any large lesion. The prevalence of lesions and large lesions in persons with and without knee pain was compared; in participants with knee pain, the presence of lesions was correlated with severity of pain. RESULTS: Bone marrow lesions were found in 272 of 351 (77.5%) persons with painful knees compared with 15 of 50 (30%) persons with no knee pain (P < 0.001). Large lesions were present almost exclusively in persons with knee pain (35.9% vs. 2%; P < 0.001). After adjustment for severity of radiographic disease, effusion, age, and sex, lesions and large lesions remained associated with the occurrence of knee pain. Among persons with knee pain, bone marrow lesions were not associated with pain severity. CONCLUSIONS: Bone marrow lesions on MRI are strongly associated with the presence of pain in knee osteoarthritis.

Interleaved water and fat dual-echo spin echo imaging with intrinsic chemical-shift elimination.

A new technique was developed to simultaneously acquire water and fat dual-echo spin echo images in a single acquisition period. Chemical shifts between water and fat images are intrinsically eliminated, and the images are combined to form water-plus-fat image. In vivo water-only images show fat suppression superior to that of conventional spin echo images. This technique may be clinically useful for musculoskeletal imaging.

3D interleaved water and fat image acquisition with chemical-shift correction.

A new technique, 3D interleaved water and fat image acquisition with chemical-shift correction (3-DIWFAC), was developed to acquire 3D water and fat images in a single acquisition time and to combine the water and fat images to produce chemical-shift-free images. A 3D gradient-recalled-echo (GRE) sequence was implemented with a 1-3-3-1 binomial Shinnar-Le Roux spatial-spectral excitation, and with interleaved phase-encoding lines that alternate between water and fat excitations separated by half TR. Water-only and fat-only images were then realigned to remove chemical shift artifacts. Results from phantoms and human subjects demonstrated that the image contrast was the same as in the regular GRE sequence. With the chemical shift corrected, the shadow artifacts often seen at water and fat boundaries were removed. Since this sequence simultaneously provides water-only images showing cartilage and bone lesions, and water-fat images that depict soft tissue anatomy, it may be clinically useful in musculoskeletal imaging. Magn Reson Med 44:322-330, 2000.

Radiologic measurement of the scapholunate joint: implications of biologic variation in scapholunate joint morphology.

To determine the optimal location for measurement of the scapholunate (SL) joint intercortical width, normal biologic variation in SL joint morphology was evaluated in 40 normal, skeletally mature wrists (16 volunteers, 24 cadavers) using thin-section 1.5T magnetic resonance imaging performed in the axial and coronal planes. The integrity of the SL ligaments was confirmed by magnetic resonance imaging and verified with anatomic dissection of the cadaver wrists. Patterns of SL articular morphology were qualitatively determined using similarity grouping. Scapholunate interval measurements were made at 3 locations each on the mid-SL joint image from both the axial and coronal planes: the articular margins (dorsal-palmar and proximal-distal) and midjoint. Three patterns of midjoint space cortical conformation were observed: parallel congruent (78%), inverted Y (15%), and point-like (8%). The most consistent and narrowest distance between the scaphoid and lunate was found at midjoint: coronal 1.45 mm (44% coefficient of variation) and axial 1.00 mm (22% coefficient of variation). This study demonstrated that measurement of the apparent SL joint interval in an inappropriate site, as with extended or flexed clenched fist views, may provide inaccurate SL joint interval distance assessments. Regardless of SL joint configuration, the midportion of the SL joint shows only moderate biologic variation and the least absolute measurement variance in width and should be the most precise part of the joint to measure. On magnetic resonance imaging, the normal SL joint interval measures less than 2 mm.

A volume adjustable four-coil phased array for high resolution MR imaging of the hip.

A four-coil phased array was specifically designed and built for MR imaging of the hip at 1.5 T. Its RF and imaging properties were evaluated using phantom and in-vivo studies and the results were compared to those of three different commercial coils commonly used for hip imaging. Our coil gave a significantly higher S/N at anatomic locations commonly evaluated for hip diagnosis. The increased S/N supports higher image spatial resolution and improves the visualization of fractures and lateral injuries.

Meniscal subluxation: association with osteoarthritis and joint space narrowing.

OBJECTIVE: Since complete meniscectomy leads to knee OA, we investigated the potential links among meniscal subluxation, joint space narrowing and symptomatic OA. MATERIALS AND METHODS: 233 cases with symptomatic knee OA and 58 asymptomatic controls underwent radiography and MR imaging of the knee. Joint space narrowing was measured on weight-bearing PA fluoroscopy-positioned radiographs. The amount of medial or lateral meniscal subluxation was measured on coronal MR images. The prevalence and severity of meniscal subluxation was compared in cases and controls. We evaluated the correlation of the degree of meniscal subluxation with joint space narrowing, Kellgren and Lawrence grade, and two major risk factors for the development of OA, age and weight. RESULTS: Cases had more medial and lateral subluxation than controls. Mean medial meniscal subluxation was 5.1 mm in cases and 2.8 mm in controls (P=0.001). Modest degrees of meniscal subluxation were common in both cases and controls: 81% of cases and 64% of controls had >/=3 mm of subluxation; age and gender adjusted (P=0.006). Severe degrees of subluxation were almost unique to OA cases (e.g. prevalence of >/=7 mm, 35% cases vs. 7% controls, P< 0.001). Among controls, severe degrees of subluxation were present only in those with radiographic joint space narrowing (defined as >/=grade 1 narrowing on a 0-3 scale). In cases, there was a strong correlation between the degree of medial meniscal subluxation and the severity of medial joint space narrowing (r=0.56, P=0.0001). Similar results were present in the lateral compartment. Meniscal subluxation did not correlate with age or weight. CONCLUSION: Meniscal subluxation is highly associated with symptomatic knee OA. In subjects with osteoarthritis, increasing meniscal subluxation on MR correlates with the severity of joint space narrowing.

Ovarian cancer: comparison of observer performance for four methods of interpreting CT scans.

PURPOSE: To assess the effects of four interpretative methods on observers' mean sensitivity and specificity by using computed tomography (CT) of ovarian carcinoma as a model. MATERIALS AND METHODS: CT scans in 98 patients with ovarian carcinoma and 49 women who were disease free were retrospectively reviewed by four experienced blinded radiologists to compare single-observer reading, single-observer reading with an anatomic checklist, paired-observer reading (simultaneous double reading), and replicated reading (combination of two independent readings). Confidence level scoring was used to identify three possible disease forms in each patient: extranodal tumor, lymphadenopathy, and ascites. Patient conditions were then categorized as abnormal or normal. RESULTS: There were no significant improvements in sensitivity or specificity for classification of patient conditions as abnormal or normal when comparing single-observer interpretation with single-observer interpretation with a checklist or paired-observer interpretation. Although there was no significant improvement in the mean sensitivity (93% vs 94%) by using the replicated reading method, there was a statistically significant improvement in mean specificity (85% vs 79%) for the replicated readings compared with single-observer interpretations (P < .05). CONCLUSION: Diagnostic aids such as checklists and paired simultaneous readings did not lead to an improved mean observer performance for experienced readers. However, an increase in the mean specificity occurred with replicated readings.