Detection of Bone Marrow Edema in Patients with Osteoid Osteoma Using Three-Material Decomposition with Dual-Layer Spectral CT.

The aim of this study is to assess whether perifocal bone marrow edema (BME) in patients with osteoid osteoma (OO) can be accurately detected on dual-layer spectral CT (DLCT) with three-material decomposition. To that end, 18 patients with OO (25.33 ± 12.44 years; 7 females) were pairwise-matched with 18 patients (26.72 ± 9.65 years; 9 females) admitted for suspected pathologies other than OO in the same anatomic location but negative imaging findings. All patients were examined with DLCT and MRI. DLCT data was decomposed into hydroxyapatite and water- and fat-equivalent volume fraction maps. Two radiologists assessed DLCT-based volume fraction maps for the presence of perifocal BME, using a Likert scale (1 = no edema; 2 = likely no edema; 3 = likely edema; 4 = edema). Accuracy, sensitivity, and specificity for the detection of BME on DLCT were analyzed using MR findings as standard of reference. For the detection of BME in patients with OO, DLCT showed a sensitivity of 0.92, a specificity of 0.94, and an accuracy of 0.92 for both radiologists. Interreader agreement for the assessment of BME with DLCT was substantial (weighted κ = 0.78; 95% CI, 0.59, 0.94). DLCT with material-specific volume fraction maps allowed accurate detection of BME in patients with OO. This may spare patients additional examinations and facilitate the diagnosis of OO.

Opportunistic osteoporosis screening: contrast-enhanced dual-layer spectral CT provides accurate measurements of vertebral bone mineral density.

OBJECTIVES: Osteoporosis remains under-diagnosed, which may be improved by opportunistic bone mineral density (BMD) measurements on CT. However, correcting for the influence of intravenous iodine-based contrast agent is challenging. The purpose of this study was to assess the diagnostic accuracy of iodine-corrected vertebral BMD measurements derived from non-dedicated contrast-enhanced phantomless dual-layer spectral CT (DLCT) examinations. METHODS: Vertebral volumetric DLCT-BMD was measured in native, arterial, and portal-venous scans of 132 patients (63 ± 16 years; 32% women) using virtual monoenergetic images (50 and 200 keV). For comparison, conventional BMD was determined using an asynchronous QCT calibration. Additionally, iodine densities were measured in the abdominal aorta (AA), inferior vena cava, and vena portae (VP) on each CT phase to adjust for iodine-related measurement errors in multivariable linear regressions and a generalized estimated equation, and conversion equations were calculated. RESULTS: BMD values derived from contrast-enhanced phases using conversion equations adjusted for individual vessel iodine concentrations of VP and/or AA showed a high agreement with those from non-enhanced scans in Bland-Altman plots. Mean absolute errors (MAE) of DLCT-BMD were 3.57 mg/ml for the arterial (R2 = 0.989) and 3.69 mg/ml for the portal-venous phase (R2 = 0.987) (conventional BMD: 4.70 [R2 = 0.983] and 5.15 mg/ml [R2 = 0.981]). In the phase-independent analysis, MAE was 4.49 mg/ml for DLCT (R2 = 0.989) (conventional BMD: 4.82 mg/ml [R2 = 0.981]). CONCLUSIONS: Converted BMD derived from contrast-enhanced DLCT examinations and adjusted for individual vessel iodine concentrations showed a high agreement with non-enhanced DLCT-BMD, suggesting that opportunistic BMD measurements are feasible even in non-dedicated contrast-enhanced DLCT examinations. KEY POINTS: • Accurate BMD values can be converted from contrast-enhanced DLCT scans, independent from the used scan phase. • DLCT-BMD measurements from contrast-enhanced scans should be adjusted with iodine concentrations of portal vein and/or abdominal aorta, which significantly improves the goodness-of-fit of conversion models.

Bone mineral density measurements derived from dual-layer spectral CT enable opportunistic screening for osteoporosis.

OBJECTIVE: To investigate the in vivo applicability of non-contrast-enhanced hydroxyapatite (HA)-specific bone mineral density (BMD) measurements based on dual-layer CT (DLCT). METHODS: A spine phantom containing three artificial vertebral bodies with known HA densities was measured to obtain spectral data using DLCT and quantitative CT (QCT), simulating different patient positions and grades of obesity. BMD was calculated from virtual monoenergetic images at 50 and 200 keV. HA-specific BMD values of 174 vertebrae in 33 patients (66 ± 18 years; 33% women) were determined in non-contrast routine DLCT and compared with corresponding QCT-based BMD values. RESULTS: Examining the phantom, HA-specific BMD measurements were on a par with QCT measurements. In vivo measurements revealed strong correlations between DLCT and QCT (r = 0.987 [95% confidence interval, 0.963-1.000]; p < 0.001) and substantial agreement in a Bland-Altman plot. CONCLUSION: DLCT-based HA-specific BMD measurements were comparable with QCT measurements in in vivo analyses. This suggests that opportunistic DLCT-based BMD measurements are an alternative to QCT, without requiring phantoms and specific protocols. KEY POINTS: • DLCT-based hydroxyapatite-specific BMD measurements show a substantial agreement with QCT-based BMD measurements in vivo. • DLCT-based hydroxyapatite-specific measurements are on a par with QCT in spine phantom measurements. • Opportunistic DLCT-based BMD measurements may be a feasible alternative for QCT, without requiring dedicated examination protocols or a phantom.

Serum Levels of MicroRNA-371a-3p (M371 Test) as a New Biomarker of Testicular Germ Cell Tumors: Results of a Prospective Multicentric Study.

PURPOSE: Previous studies suggested that serum levels of microRNA (miR)-371a-3p (so-called M371 test) have a much higher sensitivity and specificity than the classic markers of testicular germ cell tumors (GCTs) and are applicable toward both seminoma and nonseminoma. We sought to confirm the usefulness of this test as a novel biomarker for GCT. PATIENTS AND METHODS: In a prospective, multicentric study, serum samples of 616 patients with testicular GCTs and 258 male controls were examined for serum levels of miRNA-371a-3p (miR levels) by quantitative polymerase chain reaction. The GCT population encompassed 359 patients with seminoma and 257 with nonseminoma; 371 had clinical stage I disease, 201 had systemic disease, and 46 had relapses. Paired measurements before and after orchiectomy were performed in 424 patients; 118 with systemic disease had serial measurements during treatment. miR levels were compared with those of ß-human chorionic gonadotropin, α-fetoprotein, and lactate dehydrogenase. RESULTS: For the primary diagnosis of GCT, the M371 test showed a sensitivity of 90.1%, a specificity of 94.0%, an area under the curve of 0.966 upon receiver operating characteristic analysis, and a positive predictive value of 97.2%. α-Fetoprotein, ß-human chorionic gonadotropin, and lactate dehydrogenase had sensitivities of less than 50% in seminoma and slightly higher sensitivities in nonseminomas. miR levels were significantly associated with clinical stage, primary tumor size, and response to treatment. Relapses had elevated miR levels that subsequently dropped to normal upon remission. Teratoma did not express miR-371a-3p. CONCLUSION: The M371 test outperforms the classic markers of GCT with both a sensitivity and a specificity greater than 90%. All histologic subgroups, except teratoma, express this marker. The test could be considered for clinical implementation after further validation.

Three-material decomposition with dual-layer spectral CT compared to MRI for the detection of bone marrow edema in patients with acute vertebral fractures.

OBJECTIVES: To assess whether bone marrow edema in patients with acute vertebral fractures can be accurately diagnosed based on three-material decomposition with dual-layer spectral CT (DLCT). MATERIALS AND METHODS: Acute (n = 41) and chronic (n = 18) osteoporotic thoracolumbar vertebral fractures as diagnosed by MRI (hyperintense signal in STIR sequences) in 27 subjects (72 ± 11 years; 17 women) were assessed with DLCT. Spectral data were decomposed into hydroxyapatite, edema-equivalent, and fat-equivalent density maps using an in-house-developed algorithm. Two radiologists, blinded to clinical and MR findings, assessed DLCT and conventional CT independently, using a Likert scale (1 = no edema; 2 = likely no edema; 3 = likely edema; 4 = edema). For DLCT and conventional CT, accuracy, sensitivity, and specificity for identifying acute fractures (Likert scale, 3 and 4) were analyzed separately using MRI as standard of reference. RESULTS: For the identification of acute fractures, conventional CT showed a sensitivity of 0.73-0.76 and specificity of 0.78-0.83, whereas the sensitivity (0.93-0.95) and specificity (0.89) of decomposed DLCT images were substantially higher. Accuracy increased from 0.76 for conventional CT to 0.92-0.93 using DLCT. Interreader agreement for fracture assessment was high in conventional CT (weighted κ [95% confidence interval]; 0.81 [0.70; 0.92]) and DLCT (0.96 [0.92; 1.00]). CONCLUSIONS: Material decomposition of DLCT data substantially improved accuracy for the diagnosis of acute vertebral fractures, with a high interreader agreement. This may spare patients additional examinations and facilitate the diagnosis of vertebral fractures.

The Novel Biomarker of Germ Cell Tumours, Micro-RNA-371a-3p, Has a Very Rapid Decay in Patients with Clinical Stage 1.

BACKGROUND: Accumulating evidence suggests serum levels of microRNA (miR)-371a-3p to be a novel tumour marker of testicular germ cell tumours (GCTs). Presently, there is only limited information regarding the velocity of decline of serum levels in response to treatment. PATIENTS AND METHODS: Twenty-four patients with testicular GCT (20 seminoma, 4 nonseminoma, median age 40 years) with clinical stage 1 had measurements of serum levels of miR-371a-3p preoperatively and repeatedly on the following 3 days. Three had additional tests done within 24 h after surgery. Measurement results were analysed using descriptive statistical methods. RESULTS: Serum levels dropped to 2.62, 1.27, and 0.47% of the preoperative level within 1, 2, and 3 days, respectively. The computed half-life amounts to 3.7-7 h. The velocity of decay is significantly associated with tumour size. CONCLUSIONS: Serum-levels of miR-371a-3p have a short half-life of less than 12 h. The rapid decay after treatment represents a valuable feature confirming the usefulness of miR-371a-3p as a valuable serum biomarker of GCT.

Serum Levels of MicroRNA miR-371a-3p: A Sensitive and Specific New Biomarker for Germ Cell Tumours.

BACKGROUND: Clinical management of germ cell tumours (GCTs) relies on monitoring of serum tumour markers. However, the markers α-fetoprotein (AFP), the ß-subunit of human chorionic gonadotropin (bHCG), and lactate dehydrogenase (LDH) are expressed in <60% of GCT cases. OBJECTIVE: To test the utility of the microRNAs (miRNAs) miR-371a-3p, miR-372-3p, miR-373-3p, and miR-367-3p as sensitive and specific GCT serum biomarkers. DESIGN, SETTING, AND PARTICIPANTS: Serum levels of miRNAs were measured in 166 consecutive patients with GCT before and after treatment and in 106 male controls. In the first 50 consecutive patients, all four miRNAs were measured. In the main study, only the most sensitive miRNA was further analysed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The specificity and sensitivity of the four miRNAs were studied using receiver operating characteristic curves. miRNA sensitivities were compared to those of classical markers. Statistical cross-comparisons of miRNA levels for GCT subgroups and controls were performed at various time points during treatment. RESULTS AND LIMITATIONS: Overall, miR-371a-3p performed best, with 88.7% sensitivity (95% confidence interval [CI] 82.5-93.3%) and 93.4% specificity (95% CI 86.9-97.3%) and an area under the curve of 0.94, outperforming AFP, bHCG, and LDH (combined sensitivity 50%). According to Kernel density estimation, the sensitivity and specificity were 86.3% and 92.5%, respectively. miR-371a-3p levels dropped to normal after completion of treatment. The miRNA levels correlated with treatment failure and relapse. Teratoma did not express miR-371a-3p. CONCLUSIONS: The miRNA miR-371a-3p is a specific and sensitive novel serum GCT biomarker that accurately correlates with disease activity. Validation of this test in a large-scale prospective study is needed. PATIENT SUMMARY: miR-371a-3p is a novel serum marker for germ cell tumours that is expressed by 88.7% of patients and thus is far more sensitive and specific than classical serum markers. It correlates with tumour burden and treatment results. Validation in a large patient cohort is needed.