Independent Reference Standard Research Articles

Comparing Semiquantitative and Qualitative Methods of Vascular 18F-FDG PET Activity Measurement in Large-Vessel Vasculitis.

The study rationale was to assess the performance of qualitative and semiquantitative scoring methods for 18F-FDG PET assessment in large-vessel vasculitis. Methods: Patients with giant cell arteritis or Takayasu arteritis underwent independent clinical and imaging assessments within a prospective observational cohort. 18F-FDG PET/CT scans were interpreted for active vasculitis by central reader assessment. Arterial 18F-FDG uptake was scored by qualitative visual assessment using the PET vascular activity score (PETVAS) and by semiquantitative assessment using SUVs and target-to-background ratios (TBRs) relative to liver or blood activity. The performance of each scoring method was assessed by intrarater reliability using the intraclass correlation coefficient (ICC) and areas under the receiver-operating-characteristic curve, applying physician assessment of clinical disease activity and reader interpretation of vascular PET activity as independent reference standards. The Wilcoxon signed-rank test was used to analyze change in arterial 18F-FDG uptake over time. Results: Ninety-five patients (giant cell arteritis, 52; Takayasu arteritis, 43) contributed 212 18F-FDG PET studies. The ICC for semiquantitative evaluation (0.99 [range, 0.98-1.00]) was greater than the ICC for qualitative evaluation (0.82 [range, 0.56-0.93]). PETVAS and target-to-background ratio metrics were more strongly associated with reader interpretation of PET activity than SUV metrics. All assessment methods were significantly associated with physician assessment of clinical disease activity, but the semiquantitative metric liver tissue-to-background ratio (TBRLiver) achieved the highest area under the receiver-operating-characteristic curve (0.66). Significant but weak correlations with C-reactive protein were observed for SUV metrics (r = 0.19, P < 0.01) and TBRLiver (r = 0.20, P < 0.01) but not for PETVAS. In response to increased treatment in 56 patients, arterial 18F-FDG uptake was significantly reduced when measured by semiquantitative (TBRLiver, 1.31-1.23; 6.1% change; P < 0.0001) or qualitative (PETVAS, 22-18; P < 0.0001) methods. Semiquantitative metrics provided information complementary to qualitative evaluation in cases of severe vascular inflammation. Conclusion: Both qualitative and semiquantitative methods of measuring arterial 18F-FDG uptake are useful in assessing and monitoring vascular inflammation in large-vessel vasculitis. Compared with qualitative metrics, semiquantitative methods have superior reliability and better discriminate treatment response in cases of severe inflammation.

A case control study examining the feasibility of using eye tracking perimetry to differentiate patients with glaucoma from healthy controls

To explore the feasibility of using Saccadic Vector Optokinetic Perimetry (SVOP) to differentiate glaucomatous and healthy eyes. A prospective case–control study was performed using a convenience sample recruited from a single university glaucoma clinic and a group of healthy controls. SVOP and standard automated perimetry (SAP) was performed with testing order randomised. The reference standard was a diagnosis of glaucoma based a comprehensive ophthalmic examination and abnormality on standard automated perimetry (SAP). The index test was SVOP. 31 patients with glaucoma and 24 healthy subjects were included. Mean SAP mean deviation (MD) in those with glaucoma was − 8.7 ± 7.4 dB, with mean SAP and SVOP sensitivities of 23.3 ± 0.9 dB and 22.1 ± 4.3 dB respectively. Participants with glaucoma were significantly older. On average, SAP sensitivity was 1.2 ± 1.4 dB higher than SVOP (95% limits of agreement = − 1.6 to 4.0 dB). SVOP sensitivity had good ability to differentiate healthy and glaucomatous eyes with a 95% CI for area under the curve (AUC) of 0.84 to 0.96, similar to the performance of SAP sensitivity (95% CI 0.86 to 0.97, P = 0.60). For 80% specificity, SVOP had a 95% CI sensitivity of 75.7% to 94.8% compared to 77.8% to 96.0% for SAP. SVOP took considerably longer to perform (514 ± 54 s compared to 267 ± 76 s for SAP). Eye tracking perimetry may be useful for detection of glaucoma but further studies are needed to evaluate SVOP within its intended sphere of use, using an appropriate design and independent reference standard.

The Effect of Clinical History on Diagnostic Imaging Interpretation – A Systematic Review

To provide updated information on the effect of clinical history on diagnostic image interpretation and to provide study methodology and design recommendations for future studies assessing the effect of clinical history on diagnostic image performance. A literature search of Medline, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases was conducted from database inception to July 21, 2020. Studies comparing diagnostic imaging performance with and without clinical history, using observers reading images under both conditions that used an independent reference standard were included. Twenty-two studies met the inclusion criteria, with 15 showing clinical history improved diagnostic performance. One study reported a decrease in diagnostic performance with clinical history and the remaining six studies found no significant change in performance. Two studies used the free response paradigm with both reporting clinical history increased location sensitivity, decreased specificity and had no overall change in diagnostic performance. The disease spectrum of included cases was largely unreported and a balanced reading design was not used in 19 studies. Most published studies found that clinical history improved diagnostic performance. More recent studies accounting for abnormality location and multiple abnormalities showed an increase in false positives and no significant change in overall diagnostic performance with clinical history.

Predictive value of indicators for identifying child maltreatment and intimate partner violence in coded electronic health records: a systematic review and meta-analysis

ObjectiveElectronic health records (EHRs) are routinely used to identify family violence, yet reliable evidence of their validity remains limited. We conducted a systematic review and meta-analysis to evaluate the positive...

Testing COVID-19 tests faces methodological challenges

In battling the COVID-19 pandemic, testing is essential. The detection of viral RNA allows the identification of infected persons, whereas the detection of antibodies may reveal a response to a previous infection. Tests for coronavirus should be rigorously evaluated in terms of their analytical and clinical performance. This poses not only logistic challenges, but also methodological ones. Some of these are generic for the diagnostic accuracy paradigm, whereas others are more specific for tests for viruses. Problematic for evaluations of the clinical performance of tests for viral RNA is the absence of an independent reference standard. Many studies lack rigor in terms of the recruitment of study participants. Study reports are often insufficiently informative, which makes it difficult to assess the applicability of study findings. Attempts to summarize the performance of these tests in terms of a single estimate of the clinical sensitivity fail to do justice to the identifiable sources of the large heterogeneity in mechanisms for generating false negative results.

Olonkho Comparisons: Stability and Transformations (based on the Texts from the Northern Epic Tradition of the Yakuts)

The results of a comparative analysis of options for staible comparisons characteristic of the northern epic tradition of the Yakuts are presented. The relevance of the study is due to insufficient research of comparisons on the material of epic texts of the northern regions matching the established traditions of the olonkho of the central and Vilyuy regions of Yakutia to identify their commonality and specificity. Particular attention is paid to the structure of comparative constructions, their parallelization and the content of comparison images. A detailed analysis of the components of the five stable comparisons operating in all four texts is provided. As a result of the study, increased stability of comparisons was established in the Verkhoyansk, Mom and Oymyakon texts of the olonkho, in which only the peripheral part varies (epithets, additional terms of parallelism). The author’s notable introduction of the narrator in the Middle Kolyma text is considered, where peculiar objects and images of comparison are revealed. A comparison image was found that is characteristic only of the northern epic tradition when describing the heroic table. The definitions of individual obsolete words and their interpretation with the aim of establishing the original images of olonkho are given. A definition of the word kunnyalyk , missing in the dictionaries of the Yakut language, used as an epithet, included in the comparison construction and as a designation of an independent reference standard is proposed.

A 3D deep convolutional neural network approach for the automated measurement of cerebellum tracer uptake in FDG PET-CT scans.

The purpose of this work was to assess the potential of deep convolutional neural networks in automated measurement of cerebellum tracer uptake in F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) scans. Three different three-dimensional (3D) convolutional neural network architectures (U-Net, V-Net, and modified U-Net) were implemented and compared regarding their performance in 3D cerebellum segmentation in FDG PET scans. For network training and testing, 134 PET scans with corresponding manual volumetric segmentations were utilized. For segmentation performance assessment, a fivefold cross-validation was used, and the Dice coefficient as well as signed and unsigned distance errors were calculated. In addition, standardized uptake value (SUV) uptake measurement performance was assessed by means of a statistical comparison to an independent reference standard. Furthermore, a comparison to a previously reported active-shape-model-based approach was performed. Out of the three convolutional neural networks investigated, the modified U-Net showed significantly better segmentation performance. It achieved a Dice coefficient of 0.911±0.026, a signed distance error of 0.220±0.103mm, and an unsigned distance error of 1.048±0.340mm. When compared to the independent reference standard, SUV uptake measurements produced with the modified U-Net showed no significant error in slope and intercept. The estimated reduction in total SUV measurement error was 95.1%. The presented work demonstrates the potential of deep convolutional neural networks in automated SUV measurement of reference regions. While it focuses on the cerebellum, utilized methods can be generalized to other reference regions like the liver or aortic arch. Future work will focus on combining lesion and reference region analysis into one approach.

Abstract 1381: Technical validation of Roche AVENIO sequencing platform for liquid biopsies

Abstract Purpose Circulating cell-free tumor DNA (ctDNA) is rapidly gaining attention as a valuable biosource for the detection and diagnosis of multiple types of cancer. ctDNA can be easily obtained through a minimally invasive liquid biopsy. Multiple NGS-based methods have been developed specifically for application in liquid biopsies. Before such methods can be implemented in clinical care, they need to be technically validated through measurement of independent reference standards. In the current project we technically validated the Roche AVENIO ctDNA Assay, which is based on the CAPP-seq technology [Newman AM, et al. Nat Biotechnol. 2016;34:547-55]. Its Targeted Kit interrogates 17 genes for Single Nucleotide Variants (SNVs), Insertions and Deletions (InDels), Copy Number Variations (CNVs) and gene fusions in a single workflow. Methods The detection of SNVs, CNVs, Indels and gene fusions was evaluated as follows: - SeraCare Seraseq ctDNA Complete was analyzed in four replicates at 2.5%, 0.5% and 0.1% mutant allele frequency (AF), and at 50ng and 10ng input. This material contains SNVs, InDels, CNVs and gene fusions. - An in-house characterized reference pool of patient plasma, containing SNVs and InDels at various AF (0.07% - 5.51%), was analyzed in four replicates at 50ng and 10ng input. - Plasma and serum samples obtained from patients with tissue confirmed presence of CNV were used to validate the robustness of CNV detection. Twelve samples were selected to represent a range of background DNA (serum had 2-4 times higher wildtype DNA levels compared to plasma), amplification levels (CNV levels 1.4-fold to 4.2-fold by ddPCR) and total input (10-50ng cfDNA input). - Plasma obtained from five patients with EML4-ALK gene fusion confirmed on tissue was used to further validate fusion detection. Sequencing was performed on an Illumina NextSeq on High Output mode with sixteen samples per run (20-33M read pairs per sample). Results Sensitivity for detection of SNVs and InDels was 100% for all variants down to 0.18% AF when using 50ng input, and 50% for variants at 0.10% AF. For 10ng input the variants were detected down to 0.60% AF with sensitivity of 92%. For variants with AF between 0.07% and 0.53%, sensitivity was 67%. Results from twelve plasma and serum samples obtained from patients with EGFR CNV were 100% concordant with ddPCR results. These results were confirmed in SeraCare samples at 10ng and 50ng input. Sensitivity of fusion detection in SeraCare material was 100% for AF of 0.5% and 50ng input, and 38% for input of 10ng. No fusions were detected at 50ng or 10ng input for AF of 0.1%. We furthermore confirmed 3 out of the 5 fusions found in tissue. Conclusions We have determined the lower limits of detection for SNVs, CNVs and gene fusions. Sensitivity was dependent on DNA input with performance optimized at 50ng. Our results confirm the feasibility of in-house use of the AVENIO ctDNA Targeted Kit for broad molecular profiling in liquid biopsies. Citation Format: Daan C. Vessies, Theodora C. Linders, Kalpana L. Ramkisoensing, Petra M. Nederlof, Gerrit A. Meijer, Kim Monkhorst, Daan van den Broek. Technical validation of Roche AVENIO sequencing platform for liquid biopsies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1381.

Diagnostic Performance of the Instantaneous Wave-Free Ratio: Comparison With Fractional Flow Reserve.

Aim of the present study was to perform a meta-analysis of all available studies comparing the instantaneous wave-free ratio (iFR) with fractional flow reserve (FFR). Published trials comparing the iFR with FFR were searched for in PubMed, Google Scholar, and Scopus electronic databases. A total of 23 studies were available for the analysis, including 6381 stenoses. First, a meta-analysis of all studies was performed exploring the correlation between FFR and iFR. Interestingly, we found good correlation (0.798 [0.78-0.82]) between the 2 indices (P<0.001). In addition, to evaluate the diagnostic performance of iFR to identify FFR-positive coronary stenoses, we performed an additional meta-analysis, summarizing the results of receiver operating characteristics analyses from individual studies reporting the area under the curve. Summing the results of these studies, we found that iFR has a good diagnostic performance for the identification of FFR-positive stenoses (area under the curve=0.88 [0.86-0.90]; P<0.001). Furthermore, our search results included 5 studies that compared iFR and FFR to a third independent reference standard. Interestingly, no significant differences between iFR and FFR were reported in those studies. The present meta-analysis shows that iFR significantly correlates with standard FFR and shows a good diagnostic performance in identifying FFR-positive coronary stenoses. Finally, iFR and FFR have similar diagnostic efficiency for detection of ischemia-inducing stenoses when tested against a third comparator.

Automated model-based quantitative analysis of phantoms with spherical inserts in FDG PET scans.

Quality control plays an increasingly important role in quantitative PET imaging and is typically performed using phantoms. The purpose of this work was to develop and validate a fully automated analysis method for two common PET/CT quality assurance phantoms: the NEMA NU-2 IQ and SNMMI/CTN oncology phantom. The algorithm was designed to only utilize the PET scan to enable the analysis of phantoms with thin-walled inserts. We introduce a model-based method for automated analysis of phantoms with spherical inserts. Models are first constructed for each type of phantom to be analyzed. A robust insert detection algorithm uses the model to locate all inserts inside the phantom. First, candidates for inserts are detected using a scale-space detection approach. Second, candidates are given an initial label using a score-based optimization algorithm. Third, a robust model fitting step aligns the phantom model to the initial labeling and fixes incorrect labels. Finally, the detected insert locations are refined and measurements are taken for each insert and several background regions. In addition, an approach for automated selection of NEMA and CTN phantom models is presented. The method was evaluated on a diverse set of 15 NEMA and 20 CTN phantom PET/CT scans. NEMA phantoms were filled with radioactive tracer solution at 9.7:1 activity ratio over background, and CTN phantoms were filled with 4:1 and 2:1 activity ratio over background. For quantitative evaluation, an independent reference standard was generated by two experts using PET/CT scans of the phantoms. In addition, the automated approach was compared against manual analysis, which represents the current clinical standard approach, of the PET phantom scans by four experts. The automated analysis method successfully detected and measured all inserts in all test phantom scans. It is a deterministic algorithm (zero variability), and the insert detection RMS error (i.e., bias) was 0.97, 1.12, and 1.48 mm for phantom activity ratios 9.7:1, 4:1, and 2:1, respectively. For all phantoms and at all contrast ratios, the average RMS error was found to be significantly lower for the proposed automated method compared to the manual analysis of the phantom scans. The uptake measurements produced by the automated method showed high correlation with the independent reference standard (R2 ≥ 0.9987). In addition, the average computing time for the automated method was 30.6 s and was found to be significantly lower (P ≪ 0.001) compared to manual analysis (mean: 247.8 s). The proposed automated approach was found to have less error when measured against the independent reference than the manual approach. It can be easily adapted to other phantoms with spherical inserts. In addition, it eliminates inter- and intraoperator variability in PET phantom analysis and is significantly more time efficient, and therefore, represents a promising approach to facilitate and simplify PET standardization and harmonization efforts.

Multiplex tests to identify gastrointestinal bacteria, viruses and parasites in people with suspected infectious gastroenteritis: a systematic review and economic analysis.

Gastroenteritis is a common, transient disorder usually caused by infection and characterised by the acute onset of diarrhoea. Multiplex gastrointestinal pathogen panel (GPP) tests simultaneously identify common bacterial, viral and parasitic pathogens using molecular testing. By providing test results more rapidly than conventional testing methods, GPP tests might positively influence the treatment and management of patients presenting in hospital or in the community. To systematically review the evidence for GPP tests [xTAG® (Luminex, Toronto, ON, Canada), FilmArray (BioFire Diagnostics, Salt Lake City, UT, USA) and Faecal Pathogens B (AusDiagnostics, Beaconsfield, NSW, Australia)] and to develop a de novo economic model to compare the cost-effectiveness of GPP tests with conventional testing in England and Wales. Multiple electronic databases including MEDLINE, EMBASE, Web of Science and the Cochrane Database were searched from inception to January 2016 (with supplementary searches of other online resources). Eligible studies included patients with acute diarrhoea; comparing GPP tests with standard microbiology techniques; and patient, management, test accuracy or cost-effectiveness outcomes. Quality assessment of eligible studies used tailored Quality Assessment of Diagnostic Accuracy Studies-2, Consolidated Health Economic Evaluation Reporting Standards and Philips checklists. The meta-analysis included positive and negative agreement estimated for each pathogen. A de novo decision tree model compared patients managed with GPP testing or comparable coverage with patients managed using conventional tests, within the Public Health England pathway. Economic models included hospital and community management of patients with suspected gastroenteritis. The model estimated costs (in 2014/15 prices) and quality-adjusted life-year losses from a NHS and Personal Social Services perspective. Twenty-three studies informed the review of clinical evidence (17 xTAG, four FilmArray, two xTAG and FilmArray, 0 Faecal Pathogens B). No study provided an adequate reference standard with which to compare the test accuracy of GPP with conventional tests. A meta-analysis (of 10 studies) found considerable heterogeneity; however, GPP testing produces a greater number of pathogen-positive findings than conventional testing. It is unclear whether or not these additional 'positives' are clinically important. The review identified no robust evidence to inform consequent clinical management of patients. There is considerable uncertainty about the cost-effectiveness of GPP panels used to test for suspected infectious gastroenteritis in hospital and community settings. Uncertainties in the model include length of stay, assumptions about false-positive findings and the costs of tests. Although there is potential for cost-effectiveness in both settings, key modelling assumptions need to be verified and model findings remain tentative. No test-treat trials were retrieved. The economic model reflects one pattern of care, which will vary across the NHS. The systematic review and cost-effectiveness model identify uncertainties about the adoption of GPP tests within the NHS. GPP testing will generally correctly identify pathogens identified by conventional testing; however, these tests also generate considerable additional positive results of uncertain clinical importance. An independent reference standard may not exist to evaluate alternative approaches to testing. A test-treat trial might ascertain whether or not additional GPP 'positives' are clinically important or result in overdiagnoses, whether or not earlier diagnosis leads to earlier discharge in patients and what the health consequences of earlier intervention are. Future work might also consider the public health impact of different testing treatments, as test results form the basis for public health surveillance. This study is registered as PROSPERO CRD2016033320. The National Institute for Health Research Health Technology Assessment programme.

Initial experience of SPECT/CT in the diagnosis of occult scaphoid fracture.

Background *Equal contributors.Planar bone scintigraphy (PBS) is often advocated for diagnosing occult scaphoid fractures. PBS is a sensitive diagnostic modality, but lacks specificity, which may result in over-diagnosis.PurposeTo examine, in a pilot study, the potential additional value of single photon emission computed tomography (SPECT) combined with low dose computed tomography (CT) for the diagnosis of an occult scaphoid fracture.Material and MethodsTen patients that underwent combined PBS and SPECT/CT for a clinically suspected scaphoid fracture, where radiographs could not detect a fracture, were included in this pilot study. The PBS and SPECT/CT results were independently and separately evaluated by a nuclear physician for scaphoid fractures and other injuries.ResultsPBS was positive for a scaphoid fracture in four patients and diagnosed three other fractures. SPECT/CT showed five scaphoid fractures and one other fracture. SPECT/CT – PBS had discrepant results in three patients. In two patients PBS diagnosed a trapezoid fracture where SPECT/CT showed a scaphoid fracture. The other patient was diagnosed with a scaphoid fracture on PBS, whereas SPECT/CT showed bone bruise of other carpal bones.ConclusionSPECT/CT has the potential to be more accurate than PBS as it uses anatomical information of the CT to discriminate between the scaphoid, other carpal bones, and bone bruises. Larger studies with an independent reference standard are needed for confirmation of these preliminary data.

Quantitative magnetic resonance imaging of hepatic steatosis: Validation in ex vivo human livers.

Emerging magnetic resonance imaging (MRI) biomarkers of hepatic steatosis have demonstrated tremendous promise for accurate quantification of hepatic triglyceride concentration. These methods quantify the proton density fat-fraction (PDFF), which reflects the concentration of triglycerides in tissue. Previous in vivo studies have compared MRI-PDFF with histologic steatosis grading for assessment of hepatic steatosis. However, the correlation of MRI-PDFF with the underlying hepatic triglyceride content remained unknown. The aim of this ex vivo study was to validate the accuracy of MRI-PDFF as an imaging biomarker of hepatic steatosis. Using ex vivo human livers, we compared MRI-PDFF with magnetic resonance spectroscopy-PDFF (MRS-PDFF), biochemical triglyceride extraction, and histology as three independent reference standards. A secondary aim was to compare the precision of MRI-PDFF relative to biopsy for the quantification of hepatic steatosis. MRI-PDFF was prospectively performed at 1.5 Tesla in 13 explanted human livers. We performed colocalized paired evaluation of liver fat content in all nine Couinaud segments using single-voxel MRS-PDFF (n=117) and tissue wedges for biochemical triglyceride extraction (n=117), and five core biopsies performed in each segment for histologic grading (n=585). Accuracy of MRI-PDFF was assessed through linear regression with MRS-PDFF, triglyceride extraction, and histology. Intraobserver agreement, interobserver agreement, and repeatability of MRI-PDFF and histologic grading were assessed through Bland-Altman analyses. MRI-PDFF showed an excellent correlation with MRS-PDFF (r=0.984, confidence interval 0.978-0.989) and strong correlation with histology (r=0.850, confidence interval 0.791-0.894) and triglyceride extraction (r=0.871, confidence interval 0.818-0.909). Intraobserver agreement, interobserver agreement, and repeatability showed a significantly smaller variance for MRI-PDFF than for histologic steatosis grading (all P<0.001). MRI-PDFF is an accurate, precise, and reader-independent noninvasive imaging biomarker of liver triglyceride content, capable of steatosis quantification over the entire liver.

Temporal and spatial characteristics of the area at risk investigated using computed tomography and T1-weighted magnetic resonance imaging.

AimsCardiovascular magnetic resonance (CMR) imaging can measure the myocardial area at risk (AAR), but the technique has received criticism for inadequate validation. CMR commonly depicts an AAR that is wider than the infarct, which in turn would require a lateral perfusion gradient within the AAR. We investigated the presence of a lateral perfusion gradient within the AAR and validated CMR measures of AAR against three independent reference standards of high quality.Methods and resultsComputed tomography (CT) perfusion imaging, microsphere blood flow analysis, T1-weighted 3T CMR and fluorescent microparticle pathology were used to investigate the AAR in a canine model (n = 10) of ischaemia and reperfusion. AAR size by CMR correlated well with CT (R2 = 0.80), microsphere blood flow (R2 = 0.80), and pathology (R2 = 0.74) with good limits of agreement [−0.79 ± 4.02% of the left ventricular mass (LVM) vs. CT; −1.49 ± 4.04% LVM vs. blood flow and −1.01 ± 4.18% LVM vs. pathology]. The lateral portion of the AAR had higher perfusion than the core of the AAR by CT perfusion imaging (40.7 ± 11.8 vs. 25.2 ± 17.7 Hounsfield units, P = 0.0008) and microsphere blood flow (0.11 ± 0.04 vs. 0.05 ± 0.02 mL/g/min, lateral vs. core, P = 0.001). The transmural extent of MI was lower in the lateral portion of the AAR than the core (28.2 ± 10.2 vs. 17.4 ± 8.4% of the wall, P = 0.001).ConclusionT1-weighted CMR accurately quantifies size of the AAR with excellent agreement compared with three independent reference standards. A lateral perfusion gradient results in lower transmural extent of infarction at the edges of the AAR compared with the core.

Temporal and spatial characteristics of the area at risk investigated using computed tomography and T1-weighted magnetic resonance imaging

Background Cardiovascular magnetic resonance (CMR) imaging can measure the myocardial area at risk (AAR), but the technique has received criticism for inadequate validation. CMR commonly depicts an AAR that is wider than the infarct, which in turn would require al ateral perfusion gradient within the AAR. We investigated the presence of a lateral perfusion gradient within the AAR and validated CMR measures of AAR against 3 independent reference standards of high quality. Methods Computed tomography (CT) perfusion imaging, microsphere blood flow analysis, T1-weighted 3T CMR, and fluorescent microparticle pathology were used to investigate the AAR in a canine model (n=10) of ischemia and reperfusion.

Feasibility and Validity of the Self-administered Computerized Assessment of Mild Cognitive Impairment With Older Primary Care Patients

We investigated whether a validated computerized cognitive test, the Computerized Assessment of Mild Cognitive Impairment (CAMCI), could be independently completed by older primary care patients. We also determined the optimal cut-off for the CAMCI global risk score for mild cognitive impairment against an independent neuropsychological reference standard. All eligible patients aged 65 years and older, seen consecutively over 2 months by 1 family practice of 13 primary care physicians, were invited to participate. Patients with a diagnosis or previous work-up for dementia were excluded. Primary care physicians indicated whether they, the patient, or family had concerns about each patient's cognition. A total of 130 patients with cognitive concerns and a matched sample of 133 without cognitive concerns were enrolled. The CAMCI was individually administered after instructions to work independently. Comments were recorded verbatim. A total of 259 (98.5%) completed the entire CAMCI. Two hundred and forty-one (91.6%) completed it without any questions or after simple acknowledgment of their question. Lack of computer experience was the only patient characteristic that decreased the odds of independent CAMCI completion. These results support the feasibility of using self-administered computerized cognitive tests with older primary care patients, given the increasing reliance on computers by people of all ages. The optimal cut-off score had a sensitivity of 80% and specificity of 74%.

Critical review of SPECT imaging in pulmonary embolism

Outcome studies have shown that pulmonary embolism can be safely excluded in patients with negative ventilation/perfusion (V/Q) single-photon emission computed tomography (SPECT). The effective radiation dose of V/Q SPECT is much less than with computed tomographic (CT) pulmonary angiography, which would make it preferable to CT angiography in many young female patients. The accuracy of V/Q SPECT, however, is difficult to assess, because most published investigations are limited by incorporation bias or partial verification bias, as well as other limitations in study design and reporting. Consequently, the accuracy of V/Q SPECT relative to planar V/Q scintigraphy or CT angiography has not been definitively determined. There is need for a prospective investigation of the accuracy of V/Q SPECT with consecutive patients, blinded interpretations, and an independent reference standard, or independent composite reference standard.

Robust Initialization of Active Shape Models for Lung Segmentation in CT Scans: A Feature-Based Atlas Approach.

Model-based segmentation methods have the advantage of incorporating a priori shape information into the segmentation process but suffer from the drawback that the model must be initialized sufficiently close to the target. We propose a novel approach for initializing an active shape model (ASM) and apply it to 3D lung segmentation in CT scans. Our method constructs an atlas consisting of a set of representative lung features and an average lung shape. The ASM pose parameters are found by transforming the average lung shape based on an affine transform computed from matching features between the new image and representative lung features. Our evaluation on a diverse set of 190 images showed an average dice coefficient of 0.746 ± 0.068 for initialization and 0.974 ± 0.017 for subsequent segmentation, based on an independent reference standard. The mean absolute surface distance error was 0.948 ± 1.537 mm. The initialization as well as segmentation results showed a statistically significant improvement compared to four other approaches. The proposed initialization method can be generalized to other applications employing ASM-based segmentation.

A Systematic Review of Head-to-Head Comparison Studies of the Roland-Morris and Oswestry Measures' Abilities to Assess Change

To determine if the sensitivity to change of Roland-Morris Questionnaire (RMQ) and Oswestry Disability Index (ODI) scores differ when applied to patients with low back pain (LBP). A secondary purpose was to critique the methodological rigour of the identified head-to-head comparison studies. A systematic review of five online databases was performed to locate head-to-head comparison studies of the RMQ and the ODI that assessed the sensitivity to change of the two measures. Studies were eligible if they met a pre-determined set of inclusion criteria. A newly developed quality criteria form was used to evaluate the methodological rigour of head-to-head comparison studies. Nine articles met the inclusion criteria. Although there was a statistically significant difference in favour of the RMQ for two studies, there was no apparent consistent advantage of one measure over the other. Frequent methodological deficiencies included no formal sample size calculation, no formal between-measure comparison, and no independent reference standard. There was no consistent evidence supporting one measure over the other. Many studies displayed methodological deficiencies.

Quantifying the margin sharpness of lesions on radiological images for content‐based image retrieval

To develop a method to quantify the margin sharpness of lesions on CT and to evaluate it in simulations and CT scans of liver and lung lesions. The authors computed two attributes of margin sharpness: the intensity difference between a lesion and its surroundings, and the sharpness of the intensity transition across the lesion boundary. These two attributes were extracted from sigmoid curves fitted along lines automatically drawn orthogonal to the lesion margin. The authors then represented the margin characteristics for each lesion by a feature vector containing histograms of these parameters. The authors created 100 simulated CT scans of lesions over a range of intensity difference and margin sharpness, and used the concordance correlation between the known parameter and the corresponding computed feature as a measure of performance. The authors also evaluated their method in 79 liver lesions (44 patients: 23 M, 21 F, mean age 61) and 58 lung nodules (57 patients: 24 M, 33 F, mean age 66). The methodology presented takes into consideration the boundary of the liver and lung during feature extraction in clinical images to ensure that the margin feature do not get contaminated by anatomy other than the normal organ surrounding the lesions. For evaluation in these clinical images, the authors created subjective independent reference standards for pairwise margin sharpness similarity in the liver and lung cohorts, and compared rank orderings of similarity used using our sharpness feature to that expected from the reference standards using mean normalized discounted cumulative gain (NDCG) over all query images. In addition, the authors compared their proposed feature with two existing techniques for lesion margin characterization using the simulated and clinical datasets. The authors also evaluated the robustness of their features against variations in delineation of the lesion margin by simulating five types of deformations of the lesion margin. Equivalence across deformations was assessed using Schuirmann's paired two one-sided tests. In simulated images, the concordance correlation between measured gradient and actual gradient was 0.994. The mean (s.d.) and standard deviation NDCG score for the retrieval of K images, K = 5, 10, and 15, were 84% (8%), 85% (7%), and 85% (7%) for CT images containing liver lesions, and 82% (7%), 84% (6%), and 85% (4%) for CT images containing lung nodules, respectively. The authors' proposed method outperformed the two existing margin characterization methods in average NDCG scores over all K, by 1.5% and 3% in datasets containing liver lesion, and 4.5% and 5% in datasets containing lung nodules. Equivalence testing showed that the authors' feature is more robust across all margin deformations (p < 0.05) than the two existing methods for margin sharpness characterization in both simulated and clinical datasets. The authors have described a new image feature to quantify the margin sharpness of lesions. It has strong correlation with known margin sharpness in simulated images and in clinical CT images containing liver lesions and lung nodules. This image feature has excellent performance for retrieving images with similar margin characteristics, suggesting potential utility, in conjunction with other lesion features, for content-based image retrieval applications.