A homozygous AP3D1 missense variant in patients with sensorineural hearing loss as the leading manifestation.

Loss-of-function variants in AP3D1 have been linked to Hermansky-Pudlak syndrome (HPS) 10, a severe multisystem disorder characterized by oculocutaneous albinism, immunodeficiency, neurodevelopmental delay, hearing loss (HL), and neurological abnormalities, fatal in early childhood. Here, we report a consanguineous family who presented with presumably isolated autosomal recessive (AR) HL. Whole-exome sequencing was performed on all core family members, and selected patients were screened using array-based copy-number analysis and karyotyping. Candidate variants were validated by Sanger sequencing and assessed in silico. A homozygous, likely pathogenic p.V711I missense variant in AP3D1 segregated with the HL. The family was characterized by thorough medical and laboratory examination. The HL was consistent across patients and accompanied by neurological manifestations in two brothers. The sole female patient was diagnosed with premature ovarian failure. Further findings, including mild neutropenia and reduced NK-cell cytotoxicity in some as well as brain alterations in all homozygous patients, were reminiscent of HPS10, though milder and lacking the characteristic albinism. Previously unrecognized, milder, isolated HL was identified in all heterozygous carriers. A protein model indicates that the variant interferes with protein-protein interactions. These results suggest that a missense variant alters inner-ear-specific functions leading to HL with mild HPS10-like symptoms of variable penetrance. Milder HL in heterozygous carriers may point towards semi-dominant inheritance of this trait. Since all previously reported HPS10 cases were pediatric, it is unknown whether the observed primary ovarian insufficiency recapitulates the subfertility in Ap3d1-deficient mice.

Chest computed tomography findings of adult patients with antimelanoma differentiation-associated protein 5 antibody-positive interstitial lung disease.

OBJECTIVES: Interstitial lung disease (ILD) associated with the antimelanoma differentiation-associated protein 5 (anti-MDA5) antibody is a rapidly progressive disease that requires timely, aggressive treatment. However, prompt diagnosis is difficult due to the longer time required for antibody detection. This study described the computed tomography (CT) findings of anti-MDA5 antibody-positive ILD (anti-MDA5-ILD). METHODS: CT findings of 20 patients (7 men, 13 women; mean age, 53.6 ± 13.5 years) with anti-MDA5-ILD were retrospectively reviewed. All patients had clinical diagnoses of dermatomyositis, and 14 patients presented with amyopathic findings. RESULTS: Bilateral ground-glass attenuation, air-space consolidation, and reticular shadows were observed in 20 (100%), 15 (75%), and 3 (15%) patients, respectively. The spread of air-space consolidation was 6.0 ± 5.6% (mean ± standard deviation). Univariate analysis revealed that high Krebs von den Lungen-6, high spread of consolidation, low partial pressure of oxygen, and low forced vital capacity were significant predictors for poor survival. The final radiological diagnoses were nonspecific interstitial pneumonia and organising pneumonia (OP) in 2 (10%) and 16 (80%) patients, respectively. Further, 30% of OP patients showed fibrosis. CONCLUSION: The characteristic CT findings of patients with anti-MDA5-ILD were ground-glass attenuation, air-space consolidation, and less reticulation. These CT findings were compatible with those of OP.

Midfacial Advancement Line-A Comparative Evaluation of a New Measurement Method in Orthognathic Surgery.

PURPOSE: In planning intraoral quadrangular Le Fort II osteotomy (IQLFIIO), simulation of hard and soft tissue changes will be important at the infraorbital, Le Fort I, and incisor level. The aim of our study was to evaluate a new method for visualization and quantification. MATERIALS AND METHODS: Three different methods of quantification were compared: the point-to-point (PTP) measurement, which has been viewed as the reference standard; part comparison analysis (PCA); and a new method, the midfacial advancement line (MFAL) measurement. We performed a measurement comparison study using the Bland-Altman method to measure agreement and enrolled patients with midfacial deficiency and Class III malocclusion who had undergone IQLFIIO. The primary predictor variable was the method of measurement. The primary outcome variable was the amount of midfacial advancement. We also investigated the time required, visualization quality, and interobserver agreement. RESULTS: The sample included 12 subjects with a mean age of 21.6 years; 7 patients were male. The PTP and MFAL showed no significant observer dependence. The advancement measured with PTP and MFAL showed no significant differences. However, the advancement measured using MFAL and PCA showed a significant difference. The highest rating of visualization was found for MFAL. The time requirements were similar for all 3 methods. CONCLUSIONS: Our results have shown that the MFAL is a suitable method for visualization and quantification of soft and hard tissue changes at all 3 face levels in 1 image. It could be a valuable tool for virtual planning of midfacial advancement surgery.

Computed tomography accelerates staging in patients with Merkel cell carcinoma.

PURPOSE: No imaging algorithms for diagnostic imaging in patients suffering from Merkel cell carcinoma (MCC) have been established so far and thus staging work-up is challenging. Long presentation-to-treatment intervals determine further treatment course and, consequently, have an impact on clinical outcome in patients with MCC. METHODS: In this retrospective study, diagnostic imaging of 37 MCC patients was analyzed. CT, ultrasound, and PET/PET-CT imaging for primary staging work-up with time frames from patients´ initial presentation and imaging until completion of tumor staging were analyzed. RESULTS: Tumor staging could be completed earlier when (1) less examinations (35 vs. 42 days) were carried out or (2) computed tomography was used as the initial imaging modality (28 vs. 35 days). Furthermore, CT imaging, when used as the initial imaging study, was linked to less follow-up imaging (3 vs. 6). CONCLUSION: Computed tomography as the first-staging imaging technique in MCC patients leads to less follow-up studies and fastest completion of tumor staging.

Normal spectrum of pulmonary parametric response map to differentiate lung collapsibility: distribution of densitometric classifications in healthy adult volunteers.

OBJECTIVES: Pulmonary parametric response map (PRM) was proposed for quantitative densitometric phenotypization of chronic obstructive pulmonary disease. However, little is known about this technique in healthy subjects. The purpose of this study was to describe the normal spectrum of densitometric classification of pulmonary PRM in a group of healthy adults. METHODS: 15 healthy volunteers underwent spirometrically monitored chest CT at total lung capacity (TLC) and functional residual capacity (FRC). The paired CT scans were analyzed by PRM for voxel-by-voxel characterization of lung parenchyma according to 4 densitometric classifications: normal lung (TLC ≥ -950 HU, FRC ≥ -856 HU); expiratory low attenuation area (LAA) (TLC ≥ -950 HU, FRC < -856 HU); dual LAA (TLC<-950 HU, FRC < -856 HU); uncharacterized (TLC < -950 HU, FRC ≥ -856 HU). RESULTS: PRM spectrum was 78 % ± 10 % normal lung, 20 % ± 8 % expiratory LAA, and 1 % ± 1 % dual LAA. PRM was similar between genders, there was moderate correlation between dual LAA and spirometrically assessed TLC (R = 0.531; p = 0.042), and between expiratory LAA and VolExp/Insp ratio (R = -0.572; p = 0.026). CONCLUSIONS: PRM reflects the predominance of normal lung parenchyma in a group of healthy volunteers. However, PRM also confirms the presence of physiological expiratory LAA seemingly related to air trapping and a minimal amount of dual LAA likely reflecting emphysema. KEY POINTS: • Co-registration of inspiratory and expiratory computed tomography allows dual-phase densitometry. • Dual-phase co-registered densitometry reflects heterogeneous regional changes in lung function. • Quantification of lung in healthy subjects is needed to set reference values. • Expiratory low attenuation areas <30 % could be considered within normal range.

Clinical Management of Impacted and Transmigrated Lower Canines.

PURPOSE: Impacted, in particular transmigrated, lower canines are rare. If they transmigrate, then the most common treatment is extraction. Alternatively, the native tooth can be preserved; however, management is complex. This report describes a decision-making flowchart (DMFC) with surgical strategies for the management of impacted lower canines. MATERIALS AND METHODS: Fifty-six patients had impacted lower canines, of which 16 were transmigrated. A preliminary version of the DMFC was used for the development of treatment plans to decide which strategy to apply to these complex cases. After removal of associated pathologies (for experimental tooth-preserving therapies), miniscrews were used as transient skeletal anchorage devices (TADs). The TADs allowed a closed surgical approach for impacted and transmigrated lower canine eruption. For autotransplantation, a dummy tooth was used for socket preparation to minimize the period of no blood supply to the graft. RESULTS: After surgical exposure and TAD insertion, orthodontic treatment was performed in 4 patients. One patient was selected for successful autotransplantation. Nine patients had the transmigrated canines surgically removed. The remaining patients opted for "leave and observe." Based on the satisfactory long-term results with orthodontic treatment and autotransplantation and on published reports, the resulting DMFC presents key aspects of the treatment plan, namely 1) associated pathology, 2) patient age, 3) compliance, and 4) root tip position. CONCLUSIONS: TAD-assisted orthodontic treatment and autotransplantation of impacted lower canines are tooth-preserving alternatives to extraction. The developed DMFC assists the complex treatment planning of impacted and transmigrated lower canines.

Comparison of four software packages for CT lung volumetry in healthy individuals.

OBJECTIVES: To compare CT lung volumetry (CTLV) measurements provided by different software packages, and to provide normative data for lung densitometric measurements in healthy individuals. METHODS: This retrospective study included 51 chest CTs of 17 volunteers (eight men and nine women; mean age, 30 ± 6 years), who underwent spirometrically monitored CT at total lung capacity (TLC), functional residual capacity (FRC), and mean inspiratory capacity (MIC). Volumetric differences assessed by four commercial software packages were compared with analysis of variance (ANOVA) for repeated measurements and benchmarked against the threshold for acceptable variability between spirometric measurements. Mean lung density (MLD) and parenchymal heterogeneity (MLD-SD) were also compared with ANOVA. RESULTS: Volumetric differences ranged from 12 to 213 ml (0.20 % to 6.45 %). Although 16/18 comparisons (among four software packages at TLC, MIC, and FRC) were statistically significant (P < 0.001 to P = 0.004), only 3/18 comparisons, one at MIC and two at FRC, exceeded the spirometry variability threshold. MLD and MLD-SD significantly increased with decreasing volumes, and were significantly larger in lower compared to upper lobes (P < 0.001). CONCLUSIONS: Lung volumetric differences provided by different software packages are small. These differences should not be interpreted based on statistical significance alone, but together with absolute volumetric differences. KEY POINTS: • Volumetric differences, assessed by different CTLV software, are small but statistically significant. • Volumetric differences are smaller at TLC than at MIC and FRC. • Volumetric differences rarely exceed spirometric repeatability thresholds at MIC and FRC. • Differences between CTLV measurements should be interpreted based on comparison of absolute differences. • MLD increases with decreasing volumes, and is larger in lower compared to upper lobes.

MR neurography of ulnar nerve entrapment at the cubital tunnel: a diffusion tensor imaging study.

OBJECTIVES: MR neurography, diffusion tensor imaging (DTI) and tractography at 3 Tesla were evaluated for the assessment of patients with ulnar neuropathy at the elbow (UNE). METHODS: Axial T2-weighted and single-shot DTI sequences (16 gradient encoding directions) were acquired, covering the cubital tunnel of 46 patients with clinically and electrodiagnostically confirmed UNE and 20 healthy controls. Cross-sectional area (CSA) was measured at the retrocondylar sulcus and FA and ADC values on each section along the ulnar nerve. Three-dimensional nerve tractography and T2-weighted neurography results were independently assessed by two raters. RESULTS: Patients showed a significant reduction of ulnar nerve FA values at the retrocondylar sulcus (p = 0.002) and the deep flexor fascia (p = 0.005). At tractography, a complete or partial discontinuity of the ulnar nerve was found in 26/40 (65%) of patients. Assessment of T2 neurography was most sensitive in detecting UNE (sensitivity, 91%; specificity, 79%), followed by tractography (88%/69%). CSA and FA measurements were less effective in detecting UNE. CONCLUSION: T2-weighted neurography remains the most sensitive MR technique in the imaging evaluation of clinically manifest UNE. DTI-based neurography at 3 Tesla supports the MR imaging assessment of UNE patients by adding quantitative and 3D imaging data. KEY POINTS: • DTI and tractography support conventional MR neurography in the detection of UNE • Regionally reduced FA values and discontinuous tractography patterns indicate UNE • T2-weighted MR neurography remains the imaging gold standard in cases of UNE • DTI-based ulnar nerve tractography offers additional topographic information in 3D.

Use of diagnostic dynamic contrast-enhanced (DCE)-MRI for targeting of soft tissue tumour biopsies at 3T: preliminary results.

OBJECTIVES: To test the feasibility and accuracy of MR-guided soft tissue tumour biopsy at 3T, using the dynamic contrast-enhanced (DCE) information from staging MRI for intralesional targeting. METHODS: After obtaining written informed consent for this institutional review board-approved study, 53 patients with suspected soft tissue tumours prospectively underwent preoperative staging MRI at 3T, including DCE, and subsequent MR-guided core needle biopsy. In 44/53 cases, DCE was heterogeneous and was used for intralesional biopsy targeting. Surgical, whole-specimen histology was used as the gold standard in 43/44 patients and revealed 42 soft tissue tumours (24 men; 18 women; mean age, 52 years; range, 19 - 84). RESULTS: Final surgical histology revealed eight benign lesions, six tumours of intermediate dignity, and 28 malignancies. All malignancies had shown heterogeneous DCE. The diagnostic yield of the biopsies was 100% (42/42). Histological accuracy rates of biopsy were 100% in predicting the dignity (42/42; 95% CI [0.916 - 1.000]), 95.2% for the tissue-specific entity (40/42; 95% CI [0.847 - 0.987]), and 90.5% for the tumour grade (38/42; 95% CI [0.779 - 0.962]). CONCLUSIONS: Our preliminary study indicates that biopsy of soft tissue tumours can be performed accurately and safely with DCE targeted MR-guidance at 3T, using a combined staging/biopsy MRI protocol. KEY POINTS: • MR-guided soft tissue tumour biopsy using DCE for intralesional targeting is feasible. • Targeting by staging-MRI allows reliable planning of the biopsy approach. • The method seems accurate and safe as a combined staging/biopsy procedure in outpatients. • DCE-targeted biopsy seems useful in challenging large and heterogeneous tumours.

Normal mandibular growth and diagnosis of micrognathia at prenatal MRI.

OBJECTIVE: The aim of this article is to present reference data for fetal mandibular growth on magnetic resonance imaging, enabling the diagnosis of micrognathia. METHODS: Retrospectively, on 355 magnetic resonance scans of apparently facially normal fetuses [gestational age (GA), 20-36 weeks], mandibular anterior-posterior diameter (APD = mandibular size), inferior facial angle (IFA = mandibular position), and jaw index (APD normalized to biparietal diameter) were correlated with GA by Pearson correlation. APD-age relationship was modeled. A receding chin was subjectively determined. Ten fetuses with mandibular anomalies were compared with normal fetuses. RESULTS: For GA, APD showed high correlation (r = 0.850; P < 0.001), IFA (r = 0.086; P = 0.119) no correlation, and jaw index (r = -0.139; P = 0.018) weak correlation. APD-age relationship was expressed by the following: APD = 0.281 + 0.989 * GA (r(2) = 0.723). A receding chin was identified in 7/10 abnormal fetuses. APD, IFA, and jaw index of abnormal and normal fetuses were significantly different (P < 0.001). In 10/10 abnormal fetuses, IFA was <50.0°; in 7/10, jaw index was less than the fifth percentile (micrognathia); in 3/10, jaw index was at low normal range (retrognathia). CONCLUSIONS: Subjective identification of micrognathia may be limited. Reference data provide quantitative evaluation of mandibular size and position. An IFA <50° reflects micrognathia or retrognathia; a jaw index less than the fifth percentile suggests micrognathia.

Radiological follow-up of cemento-osseous dysplasia on cone-beam computed tomography.

This study investigated the natural course of cemento-osseous dysplasia (COD) on cone-beam computed tomography (CBCT). Retrospectively, 104 CBCT scans from 36 patients (mean age, 44.5 years; 33 female and three male) with mandibular COD (10 florid, seven focal, 19 periapical) were included, based upon clinico-radiological features, without complications such as infection and related surgery. Changes in maximum diameter and morphology (lytic, mixed lytic-sclerotic, sclerotic) were evaluated in 83 lesions, with a mean follow-up of 28.3 months. The occurrence of a diameter increase was assessed by time-to-event analysis; interreader agreement for diameter and morphological evaluation by intraclass correlation coefficient and weighted κ statistics, respectively. Fifteen of 83 (18.1%) lesions (eight florid, one focal, six periapical) in 10 patients increased in diameter; 12 of 83 (14.5%) lesions (five florid, seven periapical) in 11 patients changed morphologically. The median period until a diameter increase was longest (120 months) for periapical COD, and shortest (66 months) for florid COD (p = 0.023). There was high reader agreement (ICC = 0.891; weighted κ = 0.901). In conclusion, CBCT is an effective tool with which to follow-up COD. If any, the natural progress in uncomplicated COD is prolonged, which underlines its non-surgical character and aids in its long-term management.

Human long bone development in vivo: analysis of the distal femoral epimetaphysis on MR images of fetuses.

PURPOSE: To investigate human long bone development in vivo by analyzing distal femoral epimetaphyseal structures and bone morphometrics on magnetic resonance (MR) images of fetuses. MATERIALS AND METHODS: An institutional review board approved this retrospective study, and informed consent was waived. Included were 272 MR imaging examinations (April 2004-July 2011) in 253 fetuses with a mean gestational age (GA) of 26 weeks 6 days (range, 19 weeks 2 days to 35 weeks 6 days) without known musculoskeletal abnormalities. Two independent readers qualitatively analyzed epiphyseal and metaphyseal shape, secondary ossification, and the perichondrium on 1.5-T echo-planar MR images and correlated the results with the GA that was derived from previous fetal ultrasonography (US). Diaphyseal and epiphyseal morphometric measurements were correlated with GA by means of the Pearson correlation and linear regression. MR imaging measurements of diaphyseal length and US normative values were compared graphically. Interreader agreement analysis was performed with weighted κ statistics and the intraclass correlation coefficient. RESULTS: With advancing GA, the epiphyseal shape changed from spherical (r(2) = 0.664) to hemispherical with a notch (r(2) = 0.804), and the metaphyseal shape changed from flat (r(2) = 0.766) to clearly undulated (r(2) = 0.669). Secondary ossification (r(2) = 0.777) was not observed until 25 weeks 3 days. The perichondrium decreased (r(2) = 0.684) from 20 weeks onward. Correlation coefficients were 0.897 for diaphyseal length, 0.738 for epiphyseal length, and 0.801 for epiphyseal width with respect to GA. The range of measurements of diaphyseal length was larger than that of the reported US normative values. Interreader agreement was good for bone morphometrics (intraclass correlation coefficient, 0.906-0.976), and moderate for bone characteristics (weighted κ, 0.448-0.848). CONCLUSION: Prenatal MR imaging allows visualization of human bone development in vivo by means of epimetaphyseal characteristics and bone morphometrics. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13112441/-/DC1.

Texture-based and diffusion-weighted discrimination of parotid gland lesions on MR images at 3.0 Tesla.

The purpose of this study was to evaluate whether texture-based analysis of standard MRI sequences and diffusion-weighted imaging can help in the discrimination of parotid gland masses. The MR images of 38 patients with a biopsy- or surgery-proven parotid gland mass were retrospectively analyzed. All patients were examined on the same 3.0 Tesla MR unit, with one standard protocol. The ADC (apparent diffusion coefficient) values of the tumors were measured with three regions of interest (ROIs) covering the entire tumor. Texture-based analysis was performed with the texture analysis software MaZda (version 4.7), with ROI measurements covering the entire tumor in three slices. COC (co-occurrence matrix), RUN (run-length matrix), GRA (gradient), ARM (auto-regressive model), and WAV (wavelet transform) features were calculated for all ROIs. Three subsets of 10 texture features each were used for a linear discriminant analysis (LDA) in combination with k nearest neighbor classification (k-NN). Using histology as a standard of reference, benign tumors, including subtypes, and malignant tumors were compared with regard to ADC and texture-based values, with a one-way analysis of variance with post-hoc t-tests. Significant differences were found in the mean ADC values between Warthin tumors and pleomorphic adenomas, as well as between Warthin tumors and benign lesions. Contrast-enhanced T1-weighted images contained the most relevant textural information for the discrimination between benign and malignant parotid masses, and also for the discrimination between pleomorphic adenomas and Warthin tumors. STIR images contained the least relevant texture features, particularly for the discrimination between pleomorphic adenomas and Warthin tumors. Texture analysis proved to differentiate benign from malignant lesions, as well as pleomorphic adenomas from Warthin tumors, based on standard T(1w) sequences (without and with contrast). Of all benign parotid masses, Warthin tumors had significantly lower ADC values than the other entities.

Noninfectious inflammatory lung disease: imaging considerations and clues to differential diagnosis.

OBJECTIVE: Noninfectious inflammatory lung diseases represent a spectrum of idiopathic and secondary conditions that may involve the airspaces, vasculature, or interstitium. The most important clinical and pathologic characteristics are reviewed, emphasizing CT findings and potential clues to differential diagnosis. CONCLUSION: Noninfectious inflammatory lung diseases translate into various CT appearances that are important in making the correct diagnosis.

Fetal magnetic resonance imaging of lymphangiomas.

OBJECTIVES: To evaluate the fetal magnetic resonance imaging findings of lymphangiomas. METHODS: The magnetic resonance scans of eight fetuses with lymphangiomas were evaluated. Magnetic resonance evaluation included: number; size; signal intensities of the lesions; thickness of the septae; configuration of the margins; presence of blood breakdown products; change in size or signal intensity (in four patients with multiple examinations); exact expansion of the lesions to the adjacent anatomical structures; and concomitant pathological findings. Results were compared with postpartum clinical assessment and imaging in seven patients and with autopsy in one patient. RESULTS: Two retroperitoneal, three thoracic, and three cervical lymphangiomas (diameters between 3.3 and 15.6 cm) were included. All lesions consisted of macrocysts, and additional microcystic parts were found in three lymphangiomas. Blood breakdown products were found in one lesion. Agreement with postpartum imaging was excellent. One patient received intrauterine drainage for chylothorax, and one pregnancy was terminated. CONCLUSIONS: Fetal lymphangiomas display the same magnetic resonance imaging features as postnatal lymphangiomas. Intrauterine magnetic resonance characterization of lymphangiomas provides the exact delineation, detection of associated and/or concomitant pathologies, and differential diagnosis among other cystic pathologies. Patient management may be altered with respect to the type and/or time of treatment, and with regard to the continuation or termination of pregnancy.

Real-world Data of Palliative First-line Checkpoint Inhibitor Therapy for Head and Neck Cancer.

BACKGROUND/AIM: Pembrolizumab alone or combined with chemotherapy is now approved in PD-L1-positive patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Since real-world data are pending, our goal was to evaluate the efficacy and safety of immune checkpoint inhibitor (CPI) therapy in an unselected cohort of patients with SCCHN. PATIENTS AND METHODS: We analyzed 78 patients with recurrent or metastatic SCCHN from three Austrian cancer centers that received CPI therapy alone or with chemotherapy as palliative first-line systemic treatment for this retrospective study. Patient characteristics, details on treatment, and survival were analyzed by a chart-based review. RESULTS: Of the 78 patients analyzed, 55 patients were treated with CPI alone (45 with Pembrolizumab, 10 with Nivolumab) and 23 patients received chemotherapy with a platinum and 5-FU in addition to CPI. With a median follow-up of twelve months, the median PFS of all patients was 4 months [95% confidence interval (CI)=2.2-5.8] and the median OS was 11 months (95% CI=7.1-14.9). The overall response and disease control rates were 20.5% and 46.1%, respectively. There was no statistically significant difference in clinical outcome between patient groups with a different combined positive score (CPS). The rate of reported immune related adverse events was comparable to existing data. CONCLUSION: Our findings confirm the results of the KEYNOTE-048 trial that CPI therapy alone or together with chemotherapy is an effective treatment for patients with recurrent or metastatic CPS-positive SCCHN.

Quantitative evaluation of contrast-enhanced ultrasound after intravenous administration of a microbubble contrast agent for differentiation of benign and malignant thyroid nodules: assessment of diagnostic accuracy.

OBJECTIVES: To investigate the diagnostic accuracy, through quantitative analysis, of contrast-enhanced ultrasound (CEUS), using a microbubble contrast agent, in the differentiation of thyroid nodules. METHODS: This prospective study enrolled 46 patients with solitary, scintigraphically non-functional thyroid nodules. These patients were scheduled for surgery and underwent preoperative CEUS with pulse-inversion harmonic imaging after intravenous microbubble contrast medium administration. Using histology as a standard of reference, time-intensity curves of benign and malignant nodules were compared by means of peak enhancement and wash-out enhancement relative to the baseline intensity using a mixed model ANOVA. ROC analysis was performed to assess the diagnostic accuracy in the differentiation of benign and malignant nodules on CEUS. RESULTS: The complete CEUS data of 42 patients (31/42 [73.8%] benign and 11/42 [26.2%] malignant nodules) revealed a significant difference (P < 0.001) in enhancement between benign and malignant nodules. Furthermore, based on ROC analysis, CEUS demonstrated sensitivity of 76.9%, specificity of 84.8% and accuracy of 82.6%. CONCLUSIONS: Quantitative analysis of CEUS using a microbubble contrast agent allows the differentiation of benign and malignant thyroid nodules and may potentially serve, in addition to grey-scale and Doppler ultrasound, as an adjunctive tool in the assessment of patients with thyroid nodules. KEY POINTS: • Contrast-enhanced ultrasound (CEUS) helps differentiate between benign and malignant thyroid nodules. • Quantitative CEUS analysis yields sensitivity of 76.9% and specificity of 84.8%. • CEUS may be a potentially useful adjunct in assessing thyroid nodules.

MR imaging of the fetal musculoskeletal system.

Magnetic resonance imaging (MRI) appears to be increasingly used, in addition to standard ultrasonography for the diagnosis of abnormalities in utero. Previous studies have recently drawn attention to the technical refinement of MRI to visualize the fetal bones and muscles. Beyond commonly used T2-weighted MRI, echoplanar, thick-slab T2-weighted and dynamic sequences, and three-dimensional MRI techniques, are about to provide new imaging insights into the normal and the pathological musculoskeletal system of the fetus. This review emphasizes the potential significance of MRI in the visualization of the fetal musculoskeletal system.