Inter-reader Reproducibility Research Articles

Prostate Volume Estimation on MRI: Accuracy and Effects of Ellipsoid and Bullet-Shaped Measurements on PSA Density

PSA density (PSAd), an important decision-making parameter for patients with suspected prostate cancer (PCa), is dependent on magnetic resonance imaging prostate volume (PV) estimation. We aimed to compare the accuracy of the ellipsoid and bullet-shaped formulas with manual whole-gland segmentation as reference standard and to evaluate the corresponding PSAd diagnostic accuracy in predicting clinically significant PCa. We retrospectively analysed 195 patients with suspected PCa who underwent magnetic resonance imaging and prostate biopsy. Patients with PCa were categorized according to ISUP score. PV and corresponding PSAd were calculated with manual segmentation (mPV and mPSAd) as well as with ellipsoid (ePV and ePSAd) and bullet-shaped (bPV and bPSAd) formulas. Inter and intra-reader reproducibility were assessed with Lin's concordance correlation coefficient and the intraclass correlation coefficient (ICC). A 2-way analysis of variance with post-hoc Bonferroni test was used for assessing PV differences. Predictive values of PSAd calculated with different methods for detecting clinically significant PCa were evaluated by receiver operating characteristic curve analysis and Youden's index. Both intra (ρ = 0.99, ICC = 0.99) and inter-reader (ρ = 0.98, ICC = 0.98) reproducibility were excellent. No significant difference was found between ePV and reference standard (p = 1.00). bPV was significantly different from both (p = 0.00). PSAd (mPSAd/ePSAd cut-off ≥ 0.15, bPSAd cut-off ≥ 0.12) had sensitivity = 69-70%, specificity = 72-75%, areas under the curve = 0.757-0.760 (p = 0.70-0.88). Our work shows that when using bullet-shaped formula, a different PSAd cut-off must be considered to avoid PCa under-diagnosis and inaccurate risk-stratification.

Repeatability and Reproducibility of ADC Histogram Metrics from the ACRIN 6698 Breast Cancer Therapy Response Trial.

Mean tumor apparent diffusion coefficient (ADC) of breast cancer showed excellent repeatability but only moderate predictive power for breast cancer therapy response in the ACRIN 6698 multicenter imaging trial. Previous single-center studies have shown improved predictive performance for alternative ADC histogram metrics related to low ADC dense tumor volume. Using test/retest (TT/RT) 4 b-value diffusion-weighted imaging acquisitions from pretreatment or early-treatment time-points on 71 ACRIN 6698 patients, we evaluated repeatability for ADC histogram metrics to establish confidence intervals and inform predictive models for future therapy response analysis. Histograms were generated using regions of interest (ROIs) defined separately for TT and RT diffusion-weighted imaging. TT/RT repeatability and intra- and inter-reader reproducibility (on a 20-patient subset) were evaluated using wCV and Bland–Altman limits of agreement for histogram percentiles, low-ADC dense tumor volumes, and fractional volumes (normalized to total histogram volume). Pearson correlation was used to reveal connections between metrics and ROI variability across the sample cohort. Low percentiles (15th and 25th) were highly repeatable and reproducible, wCV < 8.1%, comparable to mean ADC values previously reported. Volumetric metrics had higher wCV values in all cases, with fractional volumes somewhat better but at least 3 times higher than percentile wCVs. These metrics appear most sensitive to ADC changes around a threshold of 1.2 μm2/ms. Volumetric results were moderately to strongly correlated with ROI size. In conclusion, Lower histogram percentiles have comparable repeatability to mean ADC, while ADC-thresholded volumetric measures currently have poor repeatability but may benefit from improvements in ROI techniques.

Right and left ventricle native T1 mapping in systolic phase in patients with congenital heart disease.

T1 mapping is emerging as a powerful tool in cardiac magnetic resonance (CMR) to evaluate diffuse fibrosis. However, right ventricular (RV) T1 mapping proves difficult due to the limited wall thickness in diastolic phase. Several studies focused on systolic T1 mapping, albeit only on the left ventricle (LV). To estimate intra- and inter-observer variability of native T1 (nT1) mapping of the RV, and its correlations with biventricular and pulmonary function in patients with congenital heart disease (CHD). In this retrospective, observational, cross-sectional study we evaluated 36 patients with CHD, having undergone CMR on a 1.5-T scanner. LV and RV functional evaluations were performed. A native modified look-locker inversion recovery short-axis sequence was acquired in the systolic phase. Intra- and inter-reader reproducibility were reported as complement to 100% of the ratio between coefficient of reproducibility and mean. Spearman ρ and Mann-Whitney U-test were used to compare distributions. Intra- and inter-reader reproducibility was 84% and 82%, respectively. Median nT1 was 1022 ms (interquartile range [IQR] 1108-972) for the RV and 947 ms (IQR 986-914) for the LV. Median RV-nT1 was 1016 ms (IQR 1090-1016) in patients with EDVI ≤100 mL/m2 and 1100 ms (IQR 1113-1100) in patients with EDVI >100 mL/m2 (P = 0.049). A significant negative correlation was found between RV ejection fraction and RV-nT1 (ρ = -0.284, P = 0.046). Systolic RV-nT1 showed a high reproducibility and a negative correlation with RV ejection fraction, potentially reflecting an adaptation of the RV myocardium to pulmonary valve/conduit (dys)-function.

Evaluation of an online training tool for scoring programmed cell death ligand-1 (PD-L1) diagnostic tests for lung cancer

BackgroundNumerous studies indicate that higher tumour programmed cell death ligand-1 (PD-L1) expression is associated with greater response to anti-programmed cell death-1 (PD-1)/PD-L1 immunotherapy in non-small cell lung cancer (NSCLC). In the era of precision medicine, there is a need to provide reliable, standardised training for pathologists to improve their accuracy of interpretation and scoring, as the results are used directly to inform clinical decisions. Here we present findings regarding reader reproducibility of PD-L1 tumour cell (TC) staining scoring for NSCLC using a PD-L1 e-trainer tool as part of a PD-L1 immunohistochemistry reader training course.MethodsThe PD-L1 training course was developed based on the use of VENTANA PD-L1 (SP263) and Dako PD-L1 IHC PharmDx 22C3 stained NSCLC samples in combination with a PD-L1 e-trainer tool. Five-hundred formalin-fixed, paraffin-embedded archival samples were obtained from commercial sources and stained for PD-L1. Slides were scored by two expert pathologists, then scanned to produce digital images and re-scored. Thirty-three cases were selected and sorted into three sets: a training set and two self-assessment tests (pre-test and ‘competence’ test). Participants (all selected board-certified pathologists) received face-to-face training including use of an e-trainer tool. Statistical analyses were performed using the competence test set. Overall percentage agreement (OPA) was assessed between the participant pathologists’ registered scores and the reference scores assigned by expert pathologists at clinically relevant PD-L1 cut-offs (≥1%, ≥25% and ≥ 50%).ResultsSeven sessions were held and 69 participant pathologists completed the training. Inter-reader concordance indicated high OPA (85–95%) for PD-L1 TC scoring at clinically relevant cut-offs, with Fleiss’ Kappa > 0.5.ConclusionsUse of this web-based training tool incorporated into classroom-style training was associated with an overall moderately good level of inter-reader reproducibility at key cut-offs for TC PD-L1 expression testing in NSCLC. Overall, the online training tool offers a means of standardised training for practising pathologists in a clinical setting.

The path to a better biomarker: application of a risk management framework for the implementation of PD-L1 and TILs as immuno-oncology biomarkers in breast cancer clinical trials and daily practice.

Immune checkpoint inhibitor therapies targeting PD-1/PD-L1 are now the standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). Patients with metastatic or locally advanced TNBC with PD-L1 expression on immune cells occupying ≥1% of tumor area demonstrated survival benefit with the addition of atezolizumab to nab-paclitaxel. However, concerns regarding variability between immunohistochemical PD-L1 assay performance and inter-reader reproducibility have been raised. High tumor-infiltrating lymphocytes (TILs) have also been associated with response to PD-1/PD-L1 inhibitors in patients with breast cancer (BC). TILs can be easily assessed on hematoxylin and eosin-stained slides and have shown reliable inter-reader reproducibility. As an established prognostic factor in early stage TNBC, TILs are soon anticipated to be reported in daily practice in many pathology laboratories worldwide. Because TILs and PD-L1 are parts of an immunological spectrum in BC, we propose the systematic implementation of combined PD-L1 and TIL analyses as a more comprehensive immuno-oncological biomarker for patient selection for PD-1/PD-L1 inhibition-based therapy in patients with BC. Although practical and regulatory considerations differ by jurisdiction, the pathology community has the responsibility to patients to implement assays that lead to optimal patient selection. We propose herewith a risk-management framework that may help mitigate the risks of suboptimal patient selection for immuno-therapeutic approaches in clinical trials and daily practice based on combined TILs/PD-L1 assessment in BC. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Accuracy and Reproducibility of Low-Dose Submillisievert Chest CT for the Diagnosis of COVID-19.

PurposeTo demonstrate the accuracy and reproducibility of low-dose submillisievert chest CT for the diagnosis of coronavirus disease 2019 (COVID-19) infection in patients in the emergency department.Materials and MethodsThis was a Health Insurance Portability and Accountability Act–compliant, institutional review board–approved retrospective study. From March 14 to 24, 2020, 192 patients in the emergency department with symptoms suggestive of COVID-19 infection were studied by using low-dose chest CT and real-time reverse transcription polymerase chain reaction (RT-PCR). Image analysis included the likelihood of COVID-19 infection and the semiquantitative extent of lung involvement. CT images were analyzed by two radiologists blinded to the RT-PCR results. Reproducibility was assessed using the McNemar test and intraclass correlation coefficient. Time between CT acquisition and report was measured.ResultsWhen compared with RT-PCR, low-dose submillisievert chest CT demonstrated excellent sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for diagnosis of COVID-19 (86.7%, 93.6%, 91.1%, 90.3%, and 90.2%, respectively), in particular in patients with clinical symptoms for more than 48 hours (95.6%, 93.2%, 91.5%, 96.5%, and 94.4%, respectively). In patients with a positive CT result, the likelihood of disease increased from 43.2% (pretest probability) to 91.1% or 91.4% (posttest probability), while in patients with a negative CT result, the likelihood of disease decreased to 9.6% or 3.7% for all patients or those with clinical symptoms for >48 hours. The prevalence of alternative diagnoses based on chest CT in patients without COVID-19 infection was 17.6%. The mean effective radiation dose was 0.56 mSv ± 0.25 (standard deviation). Median time between CT acquisition and report was 25 minutes (interquartile range: 13–49 minutes). Intra- and interreader reproducibility of CT was excellent (all intraclass correlation coefficients ≥ 0.95) without significant bias in the Bland-Altman analysis.ConclusionLow-dose submillisievert chest CT allows for rapid, accurate, and reproducible assessment of COVID-19 infection in patients in the emergency department, in particular in patients with symptoms lasting longer than 48 hours. Chest CT has the additional advantage of offering alternative diagnoses in a significant subset of patients.© RSNA, 2020

Real-time dynamic 3-T MRI assessment of spine kinematics: a feasibility study utilizing three different fast pulse sequences.

Half-Fourier acquisition single-shot turbo spin-echo (HASTE), continuous radial gradient-echo (GRE), and True FISP allow real-time dynamic assessment of the spine. To evaluate the feasibility of adding dynamic sequences to routine spine magnetic resonance imaging (MRI) for assessment of spondylolisthesis. Retrospective review was performed of patients referred for dynamic MRI of the cervical or lumbar spine between January 2017 and 2018 who had flexion-extension radiographs within two months of MRI. Exclusion criteria were: incomplete imaging; spinal hardware; and inability to tolerate dynamic examination. Blinded, independent review by two board-certified musculoskeletal radiologists was performed to assess for spondylolisthesis (>3 mm translation); consensus review of dynamic radiographs served as the gold standard. Cervical spinal cord effacement was assessed. Inter-reader agreement and radiographic concordance was calculated for each sequence. Twenty-one patients were included (8 men, 13 women; mean age 47.9 ± 16.5 years). Five had MRI of the cervical spine and 16 had MRI of the lumbar spine. Mean acquisition time was 18.4 ± 1.7 min with dynamic sequences in the range of 58-77 s. HASTE and True FISP had the highest inter-reader reproducibility (κ = 0.88). Reproducibility was better for the lumbar spine (κ = 0.94) than the cervical spine (κ = 0.28). Sensitivity of sequences for spondylolisthesis was in the range of 68.8%-78.6%. All three sequences had high accuracy levels: ≥90.5% averaged across the cervical and lumbar spine. Cervical cord effacement was observed during dynamic MRI in two cases (100% agreement). Real-time dynamic MRI sequences added to spine MRI protocols provide reliable and accurate assessment of cervical and lumbar spine spondylolisthesis during flexion and extension.

Repeatability and Reproducibility of Pancreas Volume Measurements Using MRI

Reduced pancreas volume, as measured by non-contrast magnetic resonance imaging (MRI), is observed in individuals with newly-diagnosed type 1 diabetes (T1D) and declines over the first year after diagnosis. In this study, we determined the repeatability and inter-reader reproducibility of pancreas volume measurements by MRI. Test-retest scans in individuals with or without T1D (n = 16) had an intraclass correlation coefficient (ICC) of 0.985 (95% CI 0.961 to 0.995) for pancreas volume. Independent pancreas outlines by two board-certified radiologists (n = 30) yielded an ICC of 0.945 (95% CI 0.889 to 0.973). The mean Dice coefficient, a measurement of the degree of overlap between pancreas regions of interest between the two readers, was 0.77. Prandial state did not influence pancreatic measurements, as stomach volume did not correlate with pancreas volume. These data demonstrate that MRI measurements of pancreas volume between two readers are repeatable and reproducible with ICCs that correspond to excellent clinical significance (ICC > 0.9), are not related to changes in stomach volume, and could be a useful tool for clinical investigation of diabetes and other pancreas pathologies.

Evaluation of 3D multi-contrast carotid vessel wall MRI: a comparative study.

Conventional reference multi-contrast black-blood (BB) MRI can be used for measuring luminal stenosis severity and plaque components, and its performance has been validated by intra- and inter-reader reproducibility test and histology. Recently, a set of 3D multi-contrast BB sequences have been developed, but its accuracy and reliability have not been well investigated. In this study, we evaluated the performance of 3D multi-contrast MRI (3D-MERGE, T2-VISTA, and SNAP) by comparing it with reference multi-contrast vessel wall MRI and assessing the inter-reader reproducibility. In total, 27 patients were recruited in this study. Twenty-six participants underwent reference and 3D multi-contrast imaging in a 3.0T MR scanner. One participant underwent carotid endarterectomy (CEA) after 3D MR imaging. Two trained reviewers interpreted reference and 3D datasets. Lumen area (LA), wall area (WA), normalized wall index (NWI), maximum wall thickness (MaxWT), and mean wall thickness (MWT) were measured, and the presence of lipid-rich necrotic core (LRNC), intra-plaque hemorrhage (IPH) and calcification (CA) were identified. Inter-reader reproducibility of 3D interpretation was assessed. 3D imaging provided comparable measurements with reference imaging in LA (43.81±25.74 vs. 43.35±24.66 mm2) and MaxWT (1.65±1.33 vs. 1.62±1.10 mm), with a lower NWI (0.40±0.15 vs. 0.43±0.11), WA (29.40±21.92 vs. 30.64±16.17 mm2) and MWT (1.09±0.69 vs. 1.14±0.47), and showed good agreement for identification of LRNC (κ=0.66, 95% CI: 0.30-1.00) and CA (κ=0.69, 95% CI: 0.42-0.97), and excellent agreement for IPH (κ=1.00, 95% CI: 1.00-1.00). Inter-reader agreement of 3D analysis was good (LRNC, κ=0.87, 95% CI: 0.61-1.00; CA, κ=0.66, 95% CI: 0.36-0.96; IPH, κ=1.00, 95% CI: 1.00-1.00). 3D multi-contrast vessel wall imaging provides comparable performance in morphological measurements and identification of carotid plaque components as reference multi-contrast MRI, with good inter-reader reproducibility.

P802 Delayed time to peak left ventricular outflow tract velocity is associated with symptomatic status in patients with hypertrophic obstructive cardiomyopathy

Abstract Funding Acknowledgements None. The presence and magnitude of left ventricular outflow tract (LVOT) obstruction in hypertrophic obstructive cardiomyopathy (HOCM) patients is weakly associated with presence of symptoms. The factors underlying this are not well understood. We hypothesize that time to peak velocity (TPV) of LVOT flow is associated with symptomatic status. We included 136 HOCM patients (58% men, mean age 55 ± 14 years) with peak gradients ≥30 mmHg at rest or during Valsalva without aortic valve stenosis. At rest and during Valsalva, continuous wave Doppler tracings from 3 consecutive beats were used to assess peak velocity (PV), left ventricular ejection time (LVET) and TPV, which was defined as the time interval between the onset of flow over the LVOT and the moment of PV. Differences were compared between asymptomatic and symptomatic patients (defined as New York Heart Association class I vs. II-IV). The relation between symptom status and TPV was investigated using logistic regression models. A random sample of 20 patients was examined by 2 observers and reproducibility was assessed using the intraclass correlation coefficient (ICC). Symptomatic patients were more often female (table) and had significantly higher mean TPV values (figure). In multivariable logistic regression models, TPV was an independent predictor of symptomatic status after correction for PV, LVOT diameter, heart rate and age (odds ratio 1.02 per 1 ms, p &amp;lt; 0.001). The ICC was 0.99 with a mean difference of 0.28 ± 8.5 ms. Delayed TPV is associated with symptomatic status in HOCM patients, after adjustment for heart rate, peak velocity, LVOT diameter and age, and is an easily measured echocardiographic variable with excellent inter-reader reproducibility. The clinical implications of delayed TPV, particularly in the context risk prediction and clinical decision making, remain to be determined. Characteristics per group Asymptomatic HOCM patients n = 47 Symptomatic HOCM patients n = 89 p value Age, y 55 ± 14 55 ± 14 0.99 Male gender 34 (72%) 45 (51%) 0.01 Body mass index, kg/m&amp;sup2; 27 ± 5 28 ± 5 0.08 Left atrial diameter, mm 46 ± 7 47 ± 7 0.64 Septal wall thickness, mm 18 ± 4 19 ± 5 0.58 LV outflow tract diameter, mm 22 ± 3 21 ± 3 0.001 Peak velocity, cm/s 403 ± 86 434 ± 79 0.03 LV ejection time, ms 316 ± 44 340 ± 42 0.002 Time to peak velocity, ms 157 ± 32 178 ± 32 &amp;lt;0.001 HOCM = hypertrophic obstructive cardiomyopathy, LV = left ventricular. Abstract P802 Figure. Time to peak velocity per NYHA class

DWI and PRECISE criteria in men on active surveillance for prostate cancer: A multicentre preliminary experience of different ADC calculations

PurposeThe PRECISE score estimates the likelihood of radiological progression in patients on active surveillance (AS) for prostate cancer (PCa) with serial multiparametric magnetic resonance imaging (mpMRI). A PRECISE score of 1 or 2 denotes radiological regression, PRECISE 3 indicates stability and PRECISE 4 or 5 implies progression.We evaluated the inter-reader reproducibility of different apparent diffusion coefficient (ADC) calculations and their relationship to the PRECISE score. Material and methodsBaseline and follow-up scans (on the same MR systems) of 30 patients with visible lesions from two different institutions (University College London and Sapienza University of Rome) were analysed by two radiologists (one from each site). The PRECISE score was initially assessed in consensus. At least six weeks later, to reduce the likelihood of being influenced by the consensus PRECISE reading, each radiologist independently calculated ADC for the following: lesion, non-cancerous tissue and urine in the bladder. Normalised ADC ratios were calculated with respect to normal prostatic tissue (npADC) and urine. Spearman's correlation (ρ), intraclass correlation coefficients (ICC), differences in ADC and ROC curves were computed. ResultsInterobserver reproducibility was very good (ρ > 0.8; ICC > 0.90). Lesion ADC (0.91 vs 0.73 × 10−3 mm2/s; p=0.025) and npADC ratio (0.68 vs 0.53; p=0.012) at follow-up mpMRI were different between patients with radiological regression or stability vs progression. Cut-offs of 0.77 × 10−3 mm2/s (lesion ADC) and 0.59 (npADC ratio) could differentiate the two groups (area under the curve: 0.74 and 0.77, respectively). ConclusionThe ADC, npADC ratio and the PRECISE score should be recorded for MRI-based AS.

Usefulness of the frontal lobe bottom and cerebellum tuber vermis line as an alternative clue to set the axial angle parallel to the AC-PC line in I-123 IMP SPECT imaging: a retrospective study.

We aimed to investigate whether the frontal lobe bottom and cerebellum tuber vermis (FLB-CTV) line on brain perfusion scintigraphy, using iodine-123 isopropyl iodoamphetamine single photon emission computed tomography (I-123 IMP SPECT) images, is useful to determine an axial angle parallel to the anterior commissure-posterior commissure (AC-PC) line. We measured the angular differences between the AC-PC line and the FLB-CTV line on midsagittal brain magnetic resonance imaging (MRI) scans of 100 patients. We also evaluated the angular differences of the FLB-CTV line between the IMP SPECT images and the computed tomography for attenuation correction (CTAC) images in the same 100 patients, using a reference line on the CTAC images. Furthermore, the inter-reader reproducibility of the FLB-CTV line measurements on IMP SPECT images of 50 patients between two readers was evaluated using the intra-class correlation coefficient (ICC) and 95% confidence interval (CI). The mean and standard deviation of the angular differences between the AC-PC and FLB-CTV lines on midsagittal brain MRI scans were - 1.24° and 1.14°, respectively. The mean and the standard deviation of the angular differences of the FLB-CTV line in the IMP SPECT and CTAC images were 0.87° and 0.48°, respectively. The ICC of the FLB-CTV line measurements on IMP SPECT images was 0.99 (95% CI 0.98-0.99). We demonstrated that the FLB-CTV line was almost parallel to the AC-PC line and could be reconstructed using IMP SPECT images. The FLB-CTV line can be used as additional evidence to set the axial angle parallel to the AC-PC line.

Breast Density Assessment in Young Women with Ultrasound based on Speed of Sound: Influence of the Menstrual Cycle.

To investigate changes in breast density (BD) during the menstrual cycle in young women in comparison to inter-breast and -segment changes as well as reproducibility of a novel Speed-of-Sound (SoS) Ultrasound (US) method.SoS-US uses a conventional US system with a reflector and a software add-on to quantify SoS in the retro-mammillary, inner and outer segments of both breasts. Twenty healthy women (18–40 years) with regular menstrual cycles were scanned twice with two weeks in-between. Three of these were additionally measured twice per week for 25 days. Average SoS (m/s) and ΔSoS (segment-variation SoS; m/s) were measured. Variations between follicular and luteal phases and changes over the four-week period were assessed. Inter-examiner and inter-reader agreements were also evaluated. Variances between cycle phases, examiners and readers were compared.No significant SoS difference was observed between follicular and luteal phases for the twenty women (P = .126), and between all different days for the three more frequently measured women (P = .892). Inter-reader (ICC = 0.999) and inter-examiner (ICC = 0.990) agreements were high. The SoS variance due to menstrual variations was not significantly larger than the inter-examiner uncertainty (P = .461). Inter-reader variations were significantly smaller than menstrual and examiner variations (P < .001).SoS-US showed high inter-examiner and inter-reader reproducibility. The alterations during the menstrual cycles were not significantly larger than the confidence interval of measurements.

Prognostic Value of CT Radiomic Features in Resectable Pancreatic Ductal Adenocarcinoma

In this work, we assess the reproducibility and prognostic value of CT-derived radiomic features for resectable pancreatic ductal adenocarcinoma (PDAC). Two radiologists contoured tumour regions on pre-operative CT of two cohorts from two institutions undergoing curative-intent surgical resection for PDAC. The first (n = 30) and second cohorts (n = 68) were used for training and validation of proposed prognostic model for overall survival (OS), respectively. Radiomic features were extracted using PyRadiomics library and those with weak inter-reader reproducibility were excluded. Through Cox regression models, significant features were identified in the training cohort and retested in the validation cohort. Significant features were then fused via Cox regression to build a single radiomic signature in the training cohort, which was validated across readers in the validation cohort. Two radiomic features derived from Sum Entropy and Cluster Tendency features were both robust to inter-reader reproducibility and prognostic of OS across cohorts and readers. The radiomic signature showed prognostic value for OS in the validation cohort with hazard ratios of 1.56 (P = 0.005) and 1.35 (P = 0.022), for the first and second reader, respectively. CT-based radiomic features were shown to be prognostic in patients with resectable PDAC. These features may help stratify patients for neoadjuvant or alternative therapies.

Assessment of 68Ga-PSMA-11 PET Accuracy in Localizing Recurrent Prostate Cancer

In retrospective studies, 68Ga-PSMA-11 positron emission tomographic (PET) imaging improves detection of biochemically recurrent prostate cancer compared with conventional imaging. To assess 68Ga-PSMA-11 PET accuracy in a prospective multicenter trial. In this single-arm prospective trial conducted at University of California, San Francisco and University of California, Los Angeles, 635 patients with biochemically recurrent prostate cancer after prostatectomy (n = 262, 41%), radiation therapy (n = 169, 27%), or both (n = 204, 32%) underwent 68Ga-PSMA-11 PET. Presence of prostate cancer was recorded by 3 blinded readers on a per-patient and per-region base. Lesions were validated by histopathologic analysis and a composite reference standard. Endpoints were positive predictive value (PPV), detection rate, interreader reproducibility, and safety. A total of 635 men were enrolled with a median age of 69 years (range, 44-95 years). On a per-patient basis, PPV was 0.84 (95% CI, 0.75-0.90) by histopathologic validation (primary endpoint, n = 87) and 0.92 (95% CI, 0.88-0.95) by the composite reference standard (n = 217). 68Ga-PSMA-11 PET localized recurrent prostate cancer in 475 of 635 (75%) patients; detection rates significantly increased with prostate-specific antigen (PSA): 38% for <0.5 ng/mL (n = 136), 57% for 0.5 to <1.0 ng/mL (n = 79), 84% for 1.0 to <2.0 ng/mL (n = 89), 86% for 2.0 to <5.0 ng/mL (n = 158), and 97% for ≥5.0 ng/mL (n = 173, P < .001). Interreader reproducibility was substantial (Fleiss κ, 0.65-0.78). There were no serious adverse events associated with 68Ga-PSMA-11 administration. PET-directed focal therapy alone led to a PSA drop of 50% or more in 31 of 39 (80%) patients. Using blinded reads and independent lesion validation, we establish high PPV for 68Ga-PSMA-11 PET, detection rate and interreader agreement for localization of recurrent prostate cancer. ClinicalTrials.gov identifiers: NCT02940262 and NCT03353740.

A Comparison Among Different Automatically Segmented Slabs to Assess Neovascular AMD using Swept Source OCT Angiography.

PurposeWe systematically compare the intermodality and interreader agreement in age-related macular degeneration(AMD)-associated neovascularization assessment for optical coherence tomography angiography (OCTA) images obtained using different slabs.MethodsWe collected data from 48 patients (50 eyes) with type 1 or 2 neovascularization (NV) and AMD. Subjects were imaged with a swept source (SS)-OCTA system. For each eye, three OCTA en face images generated from three different slabs were exported: (1) the outer retina to choriocapillaris (ORCC) image, (2) the choriocapillaris (CC) image, and (3) the retinal pigment epithelium (RPE)-RPE fit image. Each image was graded by two readers to assess interreader variability and a single image for each modality was used to assess the intermodality variability.ResultsIn the assessment of type 1 NV, mean absolute interreader difference between measured NV areas was 0.19, 0.30, and 0.16 mm2 for ORCC, CC, and RPE-RPE fit images, respectively. Similarly, the coefficient of repeatability (CR) and intraclass correlation coefficient (ICC) indicated that the RPE-RPE fit assessment was characterized by the highest interreader reproducibility. Type 1 NV size was 0.58 mm2 (0.30–1.60 mm2) on ORCC images, 0.00 mm2 (0.00–0.36 mm2) on CC images (P = 0.002 vs. ORCC), and 0.62 mm2 (0.31–2.03 mm2) on RPE-RPE fit images (P < 0.0001 vs. CC, P = 0.041 vs. ORCC).ConclusionsThe RPE-RPE fit OCTA images have the highest interreader agreement and deliver larger measurements in type 1 lesions.Translational RelevanceOCTA imaging may be used in ongoing trials of potential novel treatments for NV.

Surveillance of abdominal aortic aneurysm using accelerated 3D non-contrast black-blood cardiovascular magnetic resonance with compressed sensing (CS-DANTE-SPACE)

Background3D non-contrast high-resolution black-blood cardiovascular magnetic resonance (CMR) (DANTE-SPACE) has been used for surveillance of abdominal aortic aneurysm (AAA) and validated against computed tomography (CT) angiography. However, it requires a long scan time of more than 7 min. We sought to develop an accelerated sequence applying compressed sensing (CS-DANTE-SPACE) and validate it in AAA patients undergoing surveillance.MethodsThirty-eight AAA patients (all males, 73 ± 6 years) under clinical surveillance were recruited for this study. All patients were scanned with DANTE-SPACE (scan time 7:10 min) and CS-DANTE-SPACE (scan time 4:12 min, a reduction of 41.4%). Nine 9 patients were scanned more than 2 times. In total, 50 pairs of images were available for comparison. Two radiologists independently evaluated the image quality on a 1–4 scale, and measured the maximal diameter of AAA, the intra-luminal thrombus (ILT) and lumen area, ILT-to-muscle signal intensity ratio, and the ILT-to-lumen contrast ratio. The sharpness of the aneurysm inner/outer boundaries was quantified.ResultsCS-DANTE-SPACE achieved comparable image quality compared with DANTE-SPACE (3.15 ± 0.67 vs. 3.03 ± 0.64, p = 0.06). There was excellent agreement between results from the two sequences for diameter/area and ILT ratio measurements (ICCs> 0.85), and for quantifying growth rate (3.3 ± 3.1 vs. 3.3 ± 3.4 mm/year, ICC = 0.95.) CS-DANTE-SPACE showed a higher ILT-to-lumen contrast ratio (p = 0.01) and higher sharpness than DANTE-SPACE (p = 0.002). Both sequences had excellent inter-reader reproducibility for quantitative measurements (ICC > 0.88).ConclusionCS-DANTE-SPACE can reduce scan time while maintaining image quality for AAA imaging. It is a promising tool for the surveillance of patients with AAA disease in the clinical setting.

Intra- and interreader reproducibility of PI-RADSv2: A multireader study.

The Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) has been in use since 2015; while interreader reproducibility has been studied, there has been a paucity of studies investigating the intrareader reproducibility of PI-RADSv2. To evaluate both intra- and interreader reproducibility of PI-RADSv2 in the assessment of intraprostatic lesions using multiparametric magnetic resonance imaging (mpMRI). Retrospective. In all, 102 consecutive biopsy-naïve patients who underwent prostate MRI and subsequent MR/transrectal ultrasonography (MR/TRUS)-guided biopsy. Prostate mpMRI at 3T using endorectal with phased array surface coils (TW MRI, DW MRI with ADC maps and b2000 DW MRI, DCE MRI). Previously detected and biopsied lesions were scored by four readers from four different institutions using PI-RADSv2. Readers scored lesions during two readout rounds with a 4-week washout period. Kappa (κ) statistics and specific agreement (Po ) were calculated to quantify intra- and interreader reproducibility of PI-RADSv2 scoring. Lesion measurement agreement was calculated using the intraclass correlation coefficient (ICC). Overall intrareader reproducibility was moderate to substantial (κ = 0.43-0.67, Po = 0.60-0.77), while overall interreader reproducibility was poor to moderate (κ = 0.24, Po = 46). Readers with more experience showed greater interreader reproducibility than readers with intermediate experience in the whole prostate (P = 0.026) and peripheral zone (P = 0.002). Sequence-specific interreader agreement for all readers was similar to the overall PI-RADSv2 score, with κ = 0.24, 0.24, and 0.23 and Po = 0.47, 0.44, and 0.54 in T2 -weighted, diffusion-weighted imaging (DWI), and dynamic contrast-enhanced (DCE), respectively. Overall intrareader and interreader ICC for lesion measurement was 0.82 and 0.71, respectively. PI-RADSv2 provides moderate intrareader reproducibility, poor interreader reproducibility, and moderate interreader lesion measurement reproducibility. These findings suggest a need for more standardized reader training in prostate MRI. 2 Technical Efficacy: Stage 2.

FDG and FCH PET/CT of Multiple Myeloma at Various Clinical Situations: Lesion Detection, Proposal for a Patient-Based “Summ” Score and Reproducibility of Scoring

Introduction: In a previous pilot study, PET/CT performed for suspected relapsing or progressive multiple myeloma (MM) revealed more lesions with FCH than with FDG. We then launched a prospective comparison of FDG and FCH PET/CT in MM at initial staging, restaging and during therapeutic follow-up. The IMPeTUs scoring system was proposed in 2016 by Nanni et al. to summarize the results of FDG PET/CT. However, the IMPeTUs scoring system is not designed to reflect by one single patient-based score the extent of the disease, as determined on radiotracer uptake. To compare the performance of those two PET radiotracers, we set a single patient-based score, derived from the IMPeTUs approach, and we applied it to the comparison of FDG and FCH PET/CT at various clinical situations of MM.Aim: To compare (1) the reproducibility of reading and scoring of FDG and FCH PET/CT in initial staging, restaging and therapeutic follow-up of MM, (2) the correlation between the scores on FDG or on FCH PET/CT and serum concentration of M-protein, a quantitative criterion reflecting the secretory activity of MM, recommended at diagnosis and as a part of evaluation of therapeutic response.Patients and methods: FDG and FCH PET/CT were performed in 105 patients (20 at initial staging, 37 at relapse and 48 during follow-up).The FDG and FCH PET/CTs were read in a random order with a wash out period by two experienced readers blinded to any patient's clinical data. They scored according to IMPeTUs scoring system, evaluating the number and intensity of foci of radiotracer uptake in 5 sites (spine, skull, extraspinal, visceral and nodal), the presence of diffuse axial and/or appendicular bone marrow uptake, of PET-positive lytic lesions, or of fractures. According to the number of visible foci in each site, the site-score was: 1: 0 focus, 2: 1-3 foci, 3: 4-10 foci or 4: >10 lesions. In case of diffuse bone marrow uptake by the axial or appendicular skeleton, the site-score 4 was attributed to the corresponding site, to integrate this pattern in one single score per site. A “SUMM” score, theoretically ranging from 5 to 20, was obtained by summing up the site-scores of the 5 sites. The kappa coefficient was calculated to evaluate the inter-reader agreement in determining the SUMM score.A consensus reading was finally performed, to solve discordances in scoring between the two readers. The paired Wilcoxon test was used to compare the consensual SUMM scores of PET/CT with FDG and FCH; the correlation coefficient between the consensual SUMM scores and M-protein level was calculated.Results:Before final consensus, the inter-reader agreement in determining the SUMM score was better with FCH (Kappa=0.90; CI=0.85-0.95) than with FDG (Kappa=0.75; CI=0.64-0.86). The analysis was then continued on the data of consensus reading. FCH showed more foci in 28 patients (4 at initial staging, 13 at relapse, 11 during follow up) and FDG in 14 patients (3 at initial staging, 4 at relapse, 7 during follow up). The SUMM score was significantly greater with FCH than with FDG (p=0.0027).M-protein was present in the serum of 95/105 patients. The correlation with serum M-protein level was significantly >0 for both SUMM scores, but loose for FDG (r=0.3, p=0.0029) and stronger for FCH (r=0.7, p<0.001), the difference being significant (p=0.0001).Among 8 patients without M-protein detected in their serum, a negative PET/CT with FDG (SUMM FDG=5) but positive with FCH (SUMM FCH>5) was observed in 2 patients (1 referred for evaluation of relapsing MM and in one referred during therapeutic follow-up of MM).Conclusion: A patient-based “SUMM” score is proposed to characterize the extension and the number of foci on PET/CT imaging of MM. Using this SUMM score, a better inter-reader reproducibility, lesion detectability and correlation with serum M-protein was observed for FCH than for FDG, confirming FCH as a potential tracer in MM deserving further research. DisclosuresGarderet:Celgene: Consultancy; Amgen: Consultancy; Takeda: Consultancy.

Epicardial adipose tissue volume in patients with coronary artery disease or non-ischaemic dilated cardiomyopathy: evaluation with cardiac magnetic resonance imaging

To compare the amount of epicardial adipose tissue (EAT) in patients with coronary artery disease (CAD) or non-ischaemic dilated cardiomyopathy (NIDCM) with that in patients with negative cardiac magnetic resonance imaging (CMR). One hundred and fifty patients (median age 57 years, interquartile range [IQR] 46-66 years) who underwent CMR were evaluated retrospectively: 50 with CAD, 50 with NIDCM, and 50 with negative CMR. For each patient, the EAT mass index (EATMI) to body surface area, end-diastolic volume index (EDVI), end-systolic volume index (ESVI), stroke volume (SV), ejection fraction (EF) for both ventricles, and left ventricle (LV) mass index were estimated. Intra and inter-reader reproducibility was tested in a random subset of 30 patients, 10 for each group. Mann-Whitney U test, Kruskal-Wallis test, Spearman's correlation, and Bland-Altman statistics were used. The EATMI in CAD patients (median 15.7 g/m2, IQR 8.3-25.7) or in NIDCM patients (15.9 g/m2, 11.5-18.1) was significantly higher than that in negative CMR patients (9.1 g/m2, 6-12; p<0.001 both). No significant difference was found between CAD and NIDCM patients (p=1.000). A correlation between EATMI and LV mass index was found in NIDCM patients (r=0.455, p=0.002). Intra- and inter-reader reproducibility were up to 80% and 72%, respectively. Patients with NIDCM or CAD exhibited an increased EATMI in comparison to negative CMR patients. CMR can be used to estimate EAT with good reproducibility.