Real-time ultrasound-derived fat fraction in pediatric population: feasibility validation with MR-PDFF.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children. To avoid limitations of liver biopsy and MRI, quantitative ultrasound has become a research focus. Ultrasound-derived fat fraction (UDFF) is based on a combination of backscatter coefficient and attenuation parameter. OBJECTIVE: The objectives of the study were to determine (1) agreement between UDFF/MRI proton density fat fraction (MR-PDFF) and (2) whether BMI and age are predictive for UDFF. MATERIALS AND METHODS: This cross-sectional prospective study included a convenience sample of 46 children referred for clinically indicated abdominal MRI. MR-PDFF and five acquisitions of UDFF were collected. Intraclass correlation coefficient (ICC) and Bland-Altman analysis were used to assess agreement between MR-PDFF and UDFF. Receiver operating characteristic curves were calculated for UDFF prediction of liver steatosis (MR-PDFF ≥ 6%). Multivariable regression was performed to assess BMI and age as predictors for UDFF. RESULTS: Twenty-two participants were male, 24 were female, and the mean age was 14 ± 3 (range: 7-18) years. Thirty-six out of 46 participants had normal liver fat fraction <6%, and 10/46 had liver steatosis. UDFF was positively associated with MR-PDFF (ICC 0.92 (95% CI, 0.89-0.96). The mean bias between UDFF and MR-PDFF was 0.64% (95% LOA, -5.3-6.6%). AUROC of UDFF for steatosis was of 0.95 (95% CI, 0.89-0.99). UDFF cutoff of 6% had a sensitivity of 90% (95% CI, 55-99%) and a specificity of 94% (95% CI, 81-0.99%). BMI was an independent predictor of UDFF (correlation: 0.55 (95% CI, 0.35-0.95)). CONCLUSIONS: UDFF shows strong agreement with MR-PDFF in children. A UDFF cutoff of 6% provides good sensitivity and specificity for detection of MR-PDFF of ≥ 6%.

Use of Artificial Intelligence in Radiology: Impact on Pediatric Patients, a White Paper From the ACR Pediatric AI Workgroup.

In this white paper, the ACR Pediatric AI Workgroup of the Commission on Informatics educates the radiology community about the health equity issue of the lack of pediatric artificial intelligence (AI), improves the understanding of relevant pediatric AI issues, and offers solutions to address the inadequacies in pediatric AI development. In short, the design, training, validation, and safe implementation of AI in children require careful and specific approaches that can be distinct from those used for adults. On the eve of widespread use of AI in imaging practice, the group invites the radiology community to align and join Image IntelliGently (www.imageintelligently.org) to ensure that the use of AI is safe, reliable, and effective for children.

Perspective: Mandatory Radiology Education for Medical Students.

Radiology education of medical students is increasingly important given the intersection of radiology with virtually all medical specialties and integral role of imaging in modern patient care. Yet radiology education requirements in US medical schools are variable with only a minority of schools requiring a clerkship in radiology. When required, the radiology curriculum is often limited to anatomy courses in the preclinical years or partially incorporated into required core clerkships and often taught by nonradiologists. Given the growing mandate for value-based care and emphasis on patient outcomes, medical students require better imaging education, both interpretive and non-interpretative skills. They should be taught how to apply appropriateness criteria for exam ordering and the relative costs of different imaging modalities given the economic implications of imaging overutilization. Medical students should also be educated regarding imaging safety considerations. In addition, they must learn the radiologist's role as consultant to assure appropriate ordering of imaging studies, oversight for performance of diagnostic exams and image-guided procedures, interpretation of studies, and communication of results. Increasing radiologist teaching and engagement with medical students also has the potential to improve diversity and inclusivity in radiology by increasing interest in the specialty as physicians who identify as underrepresented minorities (URMs) are more likely to practice in underserved areas and with underserved populations thus addressing healthcare disparities and improving access to healthcare for those patient populations. Medical schools should support preclinical and clinical curricula that is designed and taught by radiologists.

Contrast-enhanced ultrasound of blunt abdominal trauma in children.

Trauma is the leading cause of morbidity and mortality in children, and rapid identification of organ injury is essential for successful treatment. Contrast-enhanced ultrasound (CEUS) is an appealing alternative to contrast-enhanced CT in the evaluation of children with blunt abdominal trauma, mainly with respect to the potential reduction of population-level exposure to ionizing radiation. This is particularly important in children, who are more vulnerable to the hazards of ionizing radiation than adults. CEUS is useful in hemodynamically stable children with isolated blunt low- to moderate-energy abdominal trauma to rule out solid organ injuries. It can also be used to further evaluate uncertain contrast-enhanced CT findings, as well as in the follow-up of conservatively managed traumatic injuries. CEUS can be used to detect abnormalities that are not apparent by conventional US, including infarcts, pseudoaneurysms and active bleeding. In this article we present the current experience from the use of CEUS for the evaluation of pediatric blunt abdominal trauma, emphasizing the examination technique and interpretation of major abnormalities associated with injuries in the liver, spleen, kidneys, adrenal glands, pancreas and testes. We also discuss the limitations of the technique and offer a review of the major literature on this topic in children, including an extrapolation of experience from adults.

Starting a pediatric contrast ultrasound service: made simple!

The addition of contrast US to an existing pediatric US service requires several preparatory steps. This overview provides a guide to simplify the process. Initially, it is important to communicate to all stakeholders the justifications for pediatric contrast US, including (1) its comparable or better diagnostic results relative to other modalities; (2) its reduction in procedural sedation or anesthesia by avoiding MRI or CT; (3) its reduction or elimination of radiation exposure by not having to perform fluoroscopy or CT; (4) the higher safety profile of US contrast agents (UCA) compared to other contrast agents; (5) the improved exam comfort and ease inherent to US, leading to better patient and family experience, including bedside US exams for children who cannot be transported; (6) the need for another diagnostic option in light of increasing demand by parents and providers; and (7) its status as an approved and reimbursable exam. It is necessary to have an UCA incorporated into the pharmacy formulary noting that only SonoVue/Lumason is currently approved for pediatric use. In the United States this UCA is approved for intravenous administration for cardiac and liver imaging and for vesicoureteric reflux detection with intravesical application. In Europe and China it is only approved for the intravesical use in children. All other applications are off-label. The US scanner needs to be equipped with contrast-specific software. The UCA has to be prepared just before the exam and it is important to strictly follow the steps as outlined in the packaging inserts in order to prevent premature destruction of the microbubbles. The initial training in contrast US is best focused on the frontline staff actually performing the US studies; these might be sonographers, pediatric or interventional radiologists, or trainees. It is important from the outset to educate the referring physicians about contrast US. It is helpful to participate in existing contrast US courses, particularly those with hands-on components.

Ultrasound shear wave elastography: does it add value to gray-scale ultrasound imaging in differentiating biliary atresia from other causes of neonatal jaundice?

BACKGROUND: Neonatal/infantile jaundice is relatively common, and most cases resolve spontaneously. However, in the setting of unresolved neonatal cholestasis, a prompt and accurate assessment for biliary atresia is vital to prevent poor outcomes. OBJECTIVE: To determine whether shear wave elastography (SWE) alone or combined with gray-scale imaging improves the diagnostic performance of US in discriminating biliary atresia from other causes of neonatal jaundice over that of gray-scale imaging alone. MATERIALS AND METHODS: Infants referred for cholestatic jaundice were assessed with SWE and gray-scale US. On gray-scale US, two radiology readers assessed liver heterogeneity, presence of the triangular cord sign, hepatic artery size, presence/absence of common bile duct and gallbladder, and gallbladder shape; associated interobserver correlation coefficients (ICC) were calculated. SWE speeds were performed on a Siemens S3000 using 6C2 and 9 L4 transducers with both point and two-dimensional (2-D) SWE US. Both univariable and multivariable analyses were performed, as were receiver operating characteristic curves (ROC) and statistical significance tests (chi-squared, analysis of variance, t-test and Wilcoxon rank sum) when appropriate. RESULTS: There were 212 infants with biliary atresia and 106 without biliary atresia. The median shear wave speed (SWS) for biliary atresia cases was significantly higher (P<0.001) than for non-biliary-atresia cases for all acquisition modes. For reference, the median L9 point SWS was 2.1 m/s (interquartile range [IQR] 1.7-2.4 m/s) in infants with biliary atresia and 1.5 m/s (IQR 1.3-1.9 m/s) in infants without biliary atresia (P<0.001). All gray-scale US findings were significantly different between biliary-atresia and non-biliary-atresia cohorts (P<0.001), intraclass correlation coefficient (ICC) range 0.7-1.0. Triangular cord sign was most predictive of biliary atresia independent of other gray-scale findings or SWS - 96% specific and 88% sensitive. Multistep univariable/multivariable analysis of both gray-scale findings and SWE resulted in three groups being predictive of biliary atresia likelihood. Abnormal common bile duct/gallbladder and enlarged hepatic artery were highly predictive of biliary atresia independent of SWS (100% for girls and 95-100% for boys). Presence of both the common bile duct and the gallbladder along with a normal hepatic artery usually excluded biliary atresia independent of SWS. Other gray-scale combinations were equivocal, and including SWE improved discrimination between biliary-atresia and non-biliary-atresia cases. CONCLUSION: Shear wave elastography independent of gray-scale US significantly differentiated biliary-atresia from non-biliary-atresia cases. However, gray-scale findings were more predictive of biliary atresia than elastography. SWE was useful for differentiating biliary-atresia from non-biliary-atresia cases in the setting of equivocal gray-scale findings.

Clinical use of shear-wave elastography for detecting liver fibrosis in children and adolescents with cystic fibrosis.

BACKGROUND: Complications from liver cirrhosis are a leading cause of death in children with cystic fibrosis. Identifying children at risk for developing liver cirrhosis and halting its progression are critical to reducing liver-associated mortality. OBJECTIVE: Quantitative US imaging, such as shear-wave elastography (SWE), might improve the detection of liver fibrosis in children with cystic fibrosis (CF) over gray-scale US alone. We incorporated SWE in our pediatric CF liver disease screening program and evaluated its performance using magnetic resonance (MR) elastography. MATERIALS AND METHODS: Ninety-four children and adolescents with CF underwent 178 SWE exams, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT) and platelet measurements. Of these, 27 children underwent 34 MR elastography exams. We evaluated SWE performance using 6-MHz and 9-MHZ point SWE, and 9-MHz two-dimensional (2-D) SWE. RESULTS: The 6-MHz point SWE was the only method that correlated with MR elastography (r=0.52; 95% confidence interval [CI] 0.20-0.74; P=0.003). SWE of 1.45 m/s distinguished normal from abnormal MR elastography (79% sensitivity, 100% specificity, 100% positive predictive value [PPV], 55% negative predictive value [NPV], area under the receiver operating characteristic [AUROC] curve 0.94). SWE of 1.84 m/s separated mild-moderate (3.00-4.77 kPa) from severe (>4.77 kPa) MR elastography (88% sensitivity, 86% specificity, 78% PPV, 93% NPV, AUROC 0.79). Elevations of AST, ALT, GGT and thrombocytopenia were associated with higher SWE. AST-to-platelet ratio index of 0.42, fibrosis-4 of 0.29, and GGT-to-platelet ratio of 1.43 all had >95% NPV for SWE >1.84 m/s. CONCLUSION: Given its correlation with MR elastography, SWE might be a clinically useful predictor of liver fibrosis. We identified imaging criteria delineating the use of SWE to identify increased liver stiffness in children with CF. With multicenter validation, these data might be used to improve the detection and monitoring of liver fibrosis in children with CF.

Liver Fat Quantification by Ultrasound in Children: A Prospective Study.

BACKGROUND. Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children in certain regions and is rising in prevalence with increasing obesity. Accurate noninvasive imaging methods for diagnosing and quantifying liver fat are needed to guide NAFLD management. OBJECTIVE. The purpose of this article is to evaluate four ultrasound technologies for quantitative assessment of liver fat content in children using MRI proton density fat fraction (PDFF) as a reference standard. METHODS. This prospective study enrolled children who underwent clinical abdominal MRI without general anesthesia between November 2018 and July 2019. Patients underwent investigational liver ultrasound within a day of 1.5-T or 3-T MRI. Acquired ultrasound radiofrequency data were processed offline to compute the acoustic attenuation coefficient, hepatorenal index (HRI), Nakagami parameter, and shear-wave elastography (SWE) parameters (elasticity, viscosity, and dispersion). Ultrasound parameters were compared with MRI PDFF obtained using a multiecho sequence. A second observer independently performed offline attenuation coefficient and HRI measurements in all patients. RESULTS. A total of 48 patients were enrolled: 22 girls, 26 boys; mean age of 13 years (range, 7-17 years); mean body mass index (weight in kilograms divided by the square of height in meters) of 22.25 (range, 14.5-48.1). A total of 21% (10/48) had steatosis (PDFF ≥ 5%). PDFF was correlated with attenuation coefficient (r = 0.76; 95% CI, 0.60-0.86; p < .001), HRI (r = 0.84; 95% CI, 0.74-0.91; p < .001), and Nakagami parameter (r = 0.55, 95% CI, 0.32-0.72, p < .001), but not SWE parameters (r = 0.05-0.25; p > .05). In patients with no, mild, moderate, and severe steatosis according to PDFF, the mean (± SD) attenuation coefficient was 0.48 ± 0.08, 0.54 ± 0.03, 0.57 ± 0.04, and 0.86 ± 0.07 dB/cm/MHz, respectively, and the mean HRI was 1.28 ± 0.30, 1.59 ± 0.23, 2.25 ± 0.04, and 3.06 ± 0.49, respectively. For the attenuation coefficient, the threshold of 0.54 dB/cm/MHz achieved a sensitivity of 80% and a specificity of 82% for steatosis, and 0.60 dB/cm/MHz achieved a sensitivity of 80% and a specificity of 98% for moderate steatosis. For HRI, the threshold of 1.48 achieved sensitivity of 90% and specificity of 76% for steatosis, and 2.11 achieved sensitivity of 100% and specificity of 100% for moderate steatosis. The interobserver concordance coefficient was 0.92 for attenuation coefficient and 0.91 for HRI. CONCLUSION. Attenuation coefficient and HRI accurately detected and quantified liver fat in this small sample of children. CLINICAL IMPACT. Quantitative ultrasound parameters may guide NAFLD diagnosis and management in children.

Obstetric and neonatal outcomes in pregnancies complicated by fetal lung masses: does final histology matter?

PURPOSE: Fetal lung masses complicate approximately 1 in 2000 live births. Our aim was to determine whether obstetric and neonatal outcomes differ by final fetal lung mass histology. MATERIALS AND METHODS: A review of all pregnancies complicated by a prenatally diagnosed fetal lung mass between 2009 and 2017 at a single academic center was conducted. All cases included in the final analysis underwent surgical resection and histology diagnosis was determined by a trained pathologist. Clinical data were obtained from review of stored electronic medical records which contained linked maternal and neonatal records. Imaging records included both prenatal ultrasound and magnetic resonance imaging. Fisher's exact test was used for categorical variables and the Kruskal-Wallis test was used for continuous variables. The level of significance was p<.05. RESULTS: Of 61 pregnancies complicated by fetal lung mass during the study period, 45 cases underwent both prenatal care and postnatal resection. Final histology revealed 10 cases of congenital pulmonary airway malformation (CPAM) type 1, nine cases of CPAM type 2, and 16 cases of bronchopulmonary sequestration. There was no difference in initial, maximal, or final CPAM volume ratio between groups, with median final CPAM volume ratio of 0.6 for CPAM type 1, 0.7 for CPAM type 2, and 0.3 for bronchopulmonary sequestration (p = .12). There were no differences in any of the maternal or obstetric outcomes including gestational age at delivery and mode of delivery between the groups. The primary outcome of neonatal respiratory distress was not statistically different between groups (p = .66). Median neonatal length of stay following delivery ranged from 3 to 4 days, and time to postnatal resection was similar as well, with a median of 126 days for CPAM type 1, 122 days for CPAM type 2, and 132 days for bronchopulmonary sequestration (p = .76). CONCLUSIONS: In our cohort, there was no significant association between histologic lung mass subtypes and any obstetric or neonatal morbidity including respiratory distress.

Prospective Assessment of Ultrasound Shear Wave Elastography for Discriminating Biliary Atresia from other Causes of Neonatal Cholestasis.

OBJECTIVE: To prospectively assess the diagnostic performance of ultrasound shear wave elastography (SWE) and hepatobiliary laboratory biomarkers for discriminating biliary atresia from other causes of neonatal cholestasis. STUDY DESIGN: Forty-one patients <3 months of age with neonatal cholestasis (direct bilirubin >2 mg/dL) and possible biliary atresia were prospectively enrolled. Both 2-dimensional (2D) and point ultrasound SWE were performed prior to knowing the final diagnosis. Median 2D (8) and point (10) shear wave speed measurements were calculated for each subject and used for analyses. The Mann-Whitney U test was used to compare shear wave speed and laboratory measurements between patients with and without biliary atresia. Receiver operating characteristic curve analyses and multivariable logistic regression were used to evaluate diagnostic performance. RESULTS: Thirteen subjects (31.7%) were diagnosed with biliary atresia, and 28 subjects (68.3%) were diagnosed with other causes of neonatal cholestasis. Median age at the time of ultrasound SWE was 37 days. Median 2D (2.08 vs 1.49 m/s, P = .0001) and point (1.95 vs 1.21 m/s, P = .0014) ultrasound SWE measurements were significantly different between subjects with and without biliary atresia. Using a cut-off value of >1.84 m/s, 2D ultrasound SWE had a sensitivity = 92.3%, specificity = 78.6%, and area under the receiver operating characteristic curve (AuROC) of 0.89 (P < .0001). Using a cut-off value of >320 (U/L), gamma-glutamyl transferase (GGT) had a sensitivity = 100.0%, specificity = 77.8%, and AuROC of 0.85 (P < .0001). Multivariable logistic regression demonstrated an AuROC of 0.93 (P < .0001), with 2 significant covariates (2D ultrasound SWE [OR = 23.06, P = .01]; GGT [OR = 1.003, P = .036]). CONCLUSIONS: Ultrasound SWE and GGT can help discriminate biliary atresia from other causes of neonatal cholestasis.

New Algorithm for the Integration of Ultrasound Into Cystic Fibrosis Liver Disease Screening.

OBJECTIVES: Liver nodularity occurs across the spectrum of cystic fibrosis liver disease (CFLD), from regenerative nodules to cirrhosis, and can occur without liver enzyme abnormalities. Our aims were to determine if incorporating abdominal ultrasound (US) with annual laboratory testing improves the detection of CFLD and establish CF-specific thresholds for liver screening labs. METHODS: CF patients at least 6 years old who were exocrine pancreatic-insufficient had an US with Doppler and shear wave elastography. Patients were divided into Normal, Echogenic, or Nodular groups, based on US findings. Results were compared with aspartate aminotransferase (AST), alanine aminotransferase (ALT), platelets, AST to platelet ratio index (APRI), Fibrosis 4 (FIB-4), and gamma-glutamyl transferase (GGT) to platelet ratio (GPR). Receiver operator curve, sensitivity, specificity, positive predictive value, negative predictive value, and optimal cut-off with Youden Index were calculated. RESULTS: From 82 patients, incorporation of US identified more nodular livers than using labs alone. The Nodular group had significantly greater median AST (44), ALT (48), GGT (46), APRI (0.619), FIB-4 (0.286), GPR (1.431). Optimal cut-offs to detect liver nodularity in CF were AST >33, ALT >45, GGT >21, Platelets <230, APRI >0.367, FIB-4 >0.222, GPR >0.682. Using GGT, APRI, and GPR, we generated an algorithm to direct the use of US in CFLD screening. CONCLUSIONS: Using modified serum lab thresholds, addition of liver fibrosis indices, and/or abdominal US can increase detection of liver nodularity in CF. A combination of GGT, GPR, and APRI can help direct which CF children should undergo US evaluation. These tools may improve earlier identification of fibrosis and/or cirrhosis in CF patients.

Normal values of the resistivity index of the pericallosal artery with and without compression of the anterior fontanelle.

BACKGROUND: Resistivity index (RI) of the pericallosal artery as is commonly measured during head ultrasound (US) examination in neonates. Some studies have shown that RI measured with gentle compression of the fontanelle provides additional information in cases of neonatal brain anomalies. OBJECTIVE: The purpose of this study was to establish normal RI values with and without compression in a large population of neonates with normal cranial ultrasound as a function of gestational age. MATERIALS AND METHODS: The authors of this retrospective study reviewed the RI of 323 infants with normal gray-scale cranial US and with a gestational age ranging 26-42 weeks. We conducted the exams both with and without compression of the anterior fontanelle and we studied changes in RI depending on gestational age, gender and type of delivery. RESULTS: Infants with a gestational age of more than 35 weeks tended to have a lower RI (P=0.011). The compression of the anterior fontanelle emphasized the change in RI with increasing gestational age, with higher gestational ages having a lower RI (P<0.001). The results concerning the percentage change between baseline RI and RI with compression showed that infants with higher gestational ages have a smaller percentage change in RI (P=0.002). CONCLUSION: We established the normal values for RI from 26 weeks to 42 weeks of gestation. The results of the study show the importance of taking the gestational age into consideration when evaluating the RI.

Predicting Pathology From Imaging in Children Undergoing Resection of Congenital Lung Lesions.

BACKGROUND: Prenatal magnetic resonance imaging (MRI) is increasingly obtained to define congenital lung lesions (CLL) for surgical management. Postnatal, preoperative computed tomography (CT) provides further clarity at the cost of radiation. Depending on the lesion identified, the indication for resection remains controversial. We investigated the differences in detail found on prenatal MRI and postnatal CT compared with final pathology to determine their utility in preoperative decision-making. MATERIALS AND METHODS: All children undergoing resection of CLLs at a single institution between July 2009 and February 2018 were retrospectively identified. Their imaging, operative, and pathology reports were compared. All imaging studies were examined by pediatric radiologists with experience in prenatal CLL diagnosis. RESULTS: Fifty-five patients underwent CLL resection during the study period with 31 undergoing prenatal MRI, 45 postnatal CT, and 22 both. Resection was performed before 6 mo of age in 62% of patients. In the cohort undergoing both imaging studies, pathologic CLL diagnosis correlated with prenatal MRI and CT in 82% and 100% of patients, respectively (P = 0.13). Eight patients had systemic feeding vessels, of which 38% were identified on MRI, and 88% on CT (P = 0.13). Both studies had a specificity of 100% for detecting systemic feeding vessels. CONCLUSIONS: For children where prenatal MRI detected a systemic feeding vessel, CT was redundant for preoperative planning but had greater sensitivity. Ultimately, the CLL type predicted from postnatal CT was not significantly different from that predicted by prenatal MRI; however, both imaging modalities had some level of discrepancy with pathology.

Utility of prenatal MRI in the evaluation and management of fetal ventriculomegaly.

OBJECTIVE: Fetal ventriculomegaly may occur in isolation or as part of a broader syndrome. We aimed to determine the added value of magnetic resonance imaging (MRI) for informing the pre-natal and postnatal care of pregnancies complicated by ventriculomegaly (VM). STUDY DESIGN: Retrospective analysis of all cases of prenatally diagnosed VM referred to the fetal center at Lucile Packard Children's Hospital Stanford 1/1/2009-6/1/2014 were reviewed. Ultrasound (US) and MRI findings were reviewed, and the added yield of MRI evaluated. RESULTS: A total of 91 cases of fetal VM were identified and 74 (81%) underwent MRI. In 62/74 (84%) cases, additional CNS or non-CNS findings, not seen on US, were discovered on MRI, of which 58 were CNS-related. Forty-six (62%) of the additional findings were considered clinically relevant, of which 45 were CNS-related. CONCLUSION: Fetal MRI identifies additional, clinically relevant CNS and non-CNS findings in a majority of cases of VM following initial US.