Jelle Overbosch

Coronary artery calcification score by multislice computed tomography predicts the outcome of dobutamine cardiovascular magnetic resonance imaging

The aim of this study was to determine whether a coronary artery calcium (CAC) score of less than 11 can reliably rule out myocardial ischemia detected by dobutamine cardiovascular magnetic resonance imaging (CMR) in patients suspected of having myocardial ischemia. In 114 of 136 consecutive patients clinically suspected of myocardial ischemia with an inconclusive diagnosis of myocardial ischemia, dobutamine CMR was performed and the CAC score was determined. The CAC score was obtained by 16-row multidetector compued tomography (MDCT) and was calculated according to the method of Agatston. The CAC score and the results of the dobutamine CMR were correlated and the positive predictive value (PPV) and the negative predictive value (NPV) of the CAC score for dobutamine CMR were calculated. A total of 114 (87%) of the patients were eligible for this study. There was a significant correlation between the CAC score and dobutamine CMR (p<0.001). Patients with a CAC score of less than 11 showed no signs of inducible ischemia during dobutamine CMR. For a CAC score of less than 101, the NPV and the PPV of the CAC score for the outcome of dobutamine CMR were, respectively, 0.96 and 0.29. In patients with an inconclusive diagnosis of myocardial ischemia a MDCT CAC score of less than 11 reliably rules out myocardial ischemia detected by dobutamine CMR.

Semi-automatic measurement of left ventricular function on dual source computed tomography using five different software tools in comparison with magnetic resonance imaging

PURPOSE To compare left ventricular (LV) function assessment using five different software tools on the same dual source computed tomography (DSCT) datasets with the results of MRI. MATERIALS AND METHODS Twenty-six patients, undergoing cardiac contrast-enhanced DSCT were included (20 men, mean age 59±12 years). Reconstructions were made at every 10% of the RR-interval. Function analysis was performed with five different, commercially available workstations. In all software tools, semi-automatic LV function measurements were performed, with manual corrections if necessary. Within 0-22 days, all 26 patients were scanned on a 1.5 T MRI-system. Bland-Altman analysis was performed to calculate limits of agreement between DSCT and MRI. Pearsons correlation coefficient was calculated to assess the correlation between the different DSCT software tools and MRI. Repeated measurements were performed to determine intraobserver and interobserver variability. RESULTS For all five DSCT workstations, mean LV functional parameters correlated well with measurements on MRI. Bland-Altman analysis of the comparison of DSCT and MRI showed acceptable limits of agreement. Best correlation and limits of agreement were obtained by DSCT software tools with software algorithms comparable to MRI software. CONCLUSION The five different DSCT software tools we examined have interchangeable results of LV functional parameters compared to regularly analysed results by MRI. The best correlation and the narrowest limits of agreement were found when the same software algorithm was used for both DSCT and MRI examinations, therefore our advice for clinical practice is to always evaluate images with the same type of post-processing tools in follow-up.

Assessment of global left ventricular functional parameters: analysis of every second short-axis Magnetic Resonance Imaging slices is as accurate as analysis of consecutive slices

The purpose of this study was to assess whether accurate global left-ventricular (LV) functional parameters can be obtained by analyzing every second short-axis magnetic resonance imaging cine series instead of consecutive slices, in order to reduce post-processing time. Forty patients, were scanned on a 1.5 T MRI-system (Magnetom Sonata, Siemens Medical Systems, Erlangen, Germany) using a steady-state free precession (SSFP) sequence. A stack of short-axis cine series from above the mitral valve through the apex was acquired. Post-processing was started at the most basal slice of the left ventricle, in which at least 50% of the circumference was myocardium. End-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF) and LV mass (LVM), were calculated. Data analysis was repeated, but now only every second slice was analyzed. Bland–Altman analysis showed slightly lower values for all LV parameters when only every second slice was analyzed, ranging from 1.7% difference for EF (limits of agreement −3.5 to 5.0) to 4.6% for SV (limits of agreement −7.2 to 15.0). Analysis of every second slice for quantification of global LV function is time-saving and as accurate as analysis of consecutive slices.

Evaluation of accuracy and precision of CT-guidance in Radiofrequency Ablation for osteoid osteoma in 86 patients

Background and purpose Osteoid osteoma is a benign skeletal tumour that accounts for 2–3% of all bone tumours. The male-to-female ratio is around 4:1 and it predominates in children and young adults. The most common symptom is pain, frequently at night-time. Historically the main form of treatment has been surgical excision. With the development of Radiofrequency Ablation (RFA) there is a percutaneus alternative. Success rates of RFA are lower but the main advantage is the minimal invasive character of the therapy and the low complication rate. As a result of the minimal invasiveness the hospitalization- and rehabilitation periods are relatively short. However, in current literature no values for accuracy and precision are known for the CT-guided positioning. Methods Accuracy and precision of the needle position are determined for 86 procedures. Furthermore the population is divided into groups based on tumour diameter, location and procedure outcome. Results The clinical success rate was 81.4%. In 79% of procedures complete ablation was achieved. Accuracy was 2.84 mm on average, precision was 2.94 mm. Accuracy was significantly lower in more profound lesions. Accuracy in tibia and fibula was significantly higher compared to the femur. No significant difference was found between different tumour diameters. Interpretation The accuracy and precision found are considered good. Needle position is of major importance for procedure outcomes. The question however rises how the results of this therapy will turn out in treatment of larger tumours.

Can FDG-PET/CT replace blind bone marrow biopsy of the posterior iliac crest in Ewing sarcoma?

ObjectiveTo determine and compare the value of 18F–fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) to blind bone marrow biopsy (BMB) of the posterior iliac crest in detecting metastatic bone marrow involvement in newly diagnosed Ewing sarcoma.Materials and methodsThis retrospective study included 20 patients with newly diagnosed Ewing sarcoma who underwent pretreatment FDG-PET/CT and a total of 38 blind BMBs (two unilateral and 18 bilateral) of the posterior iliac crest. FDG-PET/CT scans were evaluated for bone marrow involvement, both in the posterior iliac crest and other sites, and compared to blind BMB results.ResultsFDG-PET/CT was positive for bone marrow involvement in 7/38 posterior iliac crests, whereas BMB was positive in 5/38 posterior iliac crests. FDG-PET/CT and BMB results in the posterior iliac crest agreed in 36/38 cases (94.7%, 95% confidence interval [CI]: 82.7–98.5%). On a patient level, FDG-PET/CT was positive for bone marrow involvement in 4/20 patients, whereas BMB of the posterior iliac crest was positive in 3/20 patients. On a patient level, FDG-PET/CT and BMB results agreed in 19/20 patients (95.0%, 95% CI: 76.4–99.1%). The only discrepancies between FDG-PET/CT and BMB were observed in two BMBs of one patient. Both BMBs in this patient were negative, whereas FDG-PET/CT indicated bilateral posterior iliac crest involvement and also extensive bone marrow involvement elsewhere.ConclusionsFDG-PET/CT appears to be a valuable method for metastatic bone marrow assessment in newly diagnosed Ewing sarcoma. The routine use of blind BMB of the posterior iliac crest should be reconsidered when FDG-PET/CT is available.

A single digital droplet PCR assay to detect multiple KIT exon 11 mutations in tumor and plasma from patients with gastrointestinal stromal tumors

Background Gastrointestinal stromal tumors (GISTs) are characterized by oncogenic KIT mutations that cluster in two exon 11 hotspots. The aim of this study was to develop a single, sensitive, quantitative digital droplet PCR (ddPCR) assay for the detection of common exon 11 mutations in both GIST tumor tissue and in circulating tumor DNA (ctDNA) isolated from GIST patients’ plasma. Methods A ddPCR assay was designed using two probes that cover both hotspots. Available archival FFPE tumor tissue from 27 consecutive patients with known KIT exon 11 mutations and 9 randomly selected patients without exon 11 mutations were tested. Plasma samples were prospectively collected in a multicenter bio-databank from December 2014. ctDNA was analyzed of 22 patients with an exon 11 mutation and a baseline plasma sample. Results The ddPCR assay detected the exon 11 mutation in 21 of 22 tumors with exon 11 mutations covered by the assay. Mutations in ctDNA were detected at baseline in 13 of 14 metastasized patients, but in only 1 of 8 patients with localized disease. In serial plasma samples from 11 patients with metastasized GIST, a decrease in mutant droplets was detected during treatment. According to RECIST 1.1, 10 patients had radiological treatment response and one patient stable disease. Conclusion A single ddPCR assay for the detection of multiple exon 11 mutations in ctDNA is a feasible, promising tool for monitoring treatment response in patients with metastasized GIST and should be further evaluated in a larger cohort.

JOURNAL CLUB: CT-Guided Bone Biopsies With Indeterminate Results in Pediatric Patients

OBJECTIVE The objective of our study was to determine the frequency of indeterminate percutaneous CT-guided bone biopsy results in a pediatric population, the subsequent management of indeterminate biopsy results, and the factors associated with an indeterminate biopsy result. MATERIALS AND METHODS This retrospective study included 86 pediatric patients who underwent 89 CT-guided biopsies because of an unclear bone lesion in a tertiary referral center for bone tumors. RESULTS CT-guided bone biopsy results were indeterminate in 29 of 89 lesions (32.6%; 95% CI, 23.7-42.9%). Excluding two bone lesions with an uncertain diagnosis, all other 27 bone lesions proved to be benign on follow-up (0% malignancies; 95% CI, 0-12.5%). Compared with patients with diagnostic CT-guided bone biopsy results, patients with indeterminate biopsy results were significantly younger (median age, 14.0 vs 18.0 years; p = 0.0185), were female more frequently (72.4% vs 41.7%, p = 0.0007), and had bone lesion-related symptoms less frequently (62.1% vs 88.3%, p = 0.0094). Furthermore, bone lesions with indeterminate CT-guided bone biopsy results were significantly more frequently not visible at CT (24.1% vs 1.7%, p = 0.0021), more frequently had a sclerotic rim (40.9% vs 18.6%, p = 0.0477), less frequently showed cortical destruction (45.5% vs 72.9%, p = 0.0343), less frequently had an associated extraosseous soft-tissue mass (4.5% vs 32.2%, p = 0.0094), and were smaller (median diameter, 17.0 vs 31.0 mm; p = 0.0007) than bone lesions with diagnostic results; in addition, the maximum biopsy sample length was significantly shorter for bone lesions with indeterminate CT-guided bone biopsy results than for those with diagnostic results (mean length, 10.9 vs 17.8 mm; p = 0.0003). CONCLUSION A nondiagnostic CT-guided biopsy result in a child with an unclear bone lesion suggests benignity. Several clinical and CT features of bone lesions are associated with indeterminate CT-guided bone biopsy results.

Diagnostic value of MRI signs in differentiating Ewing sarcoma from osteomyelitis

Background The value of magnetic resonance imaging (MRI) signs in differentiating Ewing sarcoma from osteomyelitis has not be thoroughly investigated. Purpose To investigate the value of various MRI signs in differentiating Ewing sarcoma from osteomyelitis. Material and Methods Forty-one patients who underwent MRI because of a bone lesion of unknown nature with a differential diagnosis that included both Ewing sarcoma and osteomyelitis were included. Two observers assessed several MRI signs, including the transition zone of the bone lesion, the presence of a soft-tissue mass, intramedullary and extramedullary fat globules, and the penumbra sign. Results Diagnostic accuracies for discriminating Ewing sarcoma from osteomyelitis were 82.4% and 79.4% for the presence of a soft-tissue mass, and 64.7% and 58.8% for a sharp transition zone of the bone lesion, for readers 1 and 2 respectively. Inter-observer agreement with regard to the presence of a soft-tissue mass and the transition zone of the bone lesion were moderate (κ = 0.470) and fair (κ = 0.307), respectively. Areas under the receiver operating characteristic curve of the diameter of the soft-tissue mass (if present) were 0.829 and 0.833, for readers 1 and 2 respectively. Mean inter-observer difference in soft-tissue mass diameter measurement ± limits of agreement was 35.0 ± 75.0 mm. Diagnostic accuracies of all other MRI signs were all < 50%. Conclusion Presence and size of a soft-tissue mass, and sharpness of the transition zone, are useful MRI signs to differentiate Ewing sarcoma from osteomyelitis, but inter-observer agreement is relatively low. Other MRI signs are of no value in this setting.

Primary tumor volume measurements in Ewing sarcoma: MRI inter- and intraobserver variability and comparison with FDG-PET

Abstract Background: Primary tumor volume is as an important and independent prognostic factor in Ewing sarcoma. However, the observer variability of magnetic resonance imaging (MRI)-based primary tumor volume measurements in newly diagnosed Ewing sarcoma has never been investigated. Furthermore, it is unclear how MRI-based volume measurements compare to 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)-based volume measurements. This study aimed to determine the observer variability of simplified MRI-based primary tumor volume measurements in newly diagnosed treatment-naive Ewing sarcoma and to compare them to the actual primary tumor volume at MRI and the FDG-PET-based metabolically active tumor volume (MATV). Material and methods: Twenty-nine newly diagnosed Ewing sarcoma patients with pretreatment MRI (of whom 11 also underwent FDG-PET) were included. Both exact and dichotomized (according to the proposed threshold of 200 mL) primary tumor volume measurements were analyzed. Results: Mean inter- and intraobserver differences of MRI-based simplified tumor volume ± limits of agreement varied between 15–42 ± 155–204 mL and between 9–16 ± 64–250 mL, respectively. Inter- and intraobserver agreements of dichotomized MRI-based simplified tumor volume measurements was very good (κ = 0.827–1.000). Mean difference between simplified and actual tumor volumes at MRI ± limits of agreement was 60 ± 381 mL. Agreement between dichotomized simplified and actual tumor volumes at MRI was very good (κ = 0.839). Mean difference between MRI-based simplified tumor volume and MATV ± limits of agreement was 181 ± 549 mL and almost significantly different (p = .0581). Agreement between dichotomized MRI-based simplified tumor volume and MATV was moderate (κ = 0.560). Conclusions: Exact MRI-based simplified primary tumor volume measurements in Ewing sarcoma suffer from considerable observer variability, but observer agreement of dichotomized measurements (≤200 mL vs. >200 mL) is very good and generally matches MRI-based actual volume measurements. MRI-based primary tumor volume measurements poorly-moderately agree with and tend to be higher than the MATV.