Whole-body MRI versus an [18F]FDG-PET/CT-based reference standard for early response assessment and restaging of paediatric Hodgkin's lymphoma: a prospective multicentre study.

OBJECTIVES: To compare WB-MRI with an [18F]FDG-PET/CT-based reference for early response assessment and restaging in children with Hodgkin's lymphoma (HL). METHODS: Fifty-one children (ages 10-17) with HL were included in this prospective, multicentre study. All participants underwent WB-MRI and [18F]FDG-PET/CT at early response assessment. Thirteen of the 51 patients also underwent both WB-MRI and [18F]FDG-PET/CT at restaging. Two radiologists independently evaluated all WB-MR images in two separate readings: without and with DWI. The [18F]FDG-PET/CT examinations were evaluated by a nuclear medicine physician. An expert panel assessed all discrepancies between WB-MRI and [18F]FDG-PET/CT to derive the [18F]FDG-PET/CT-based reference standard. Inter-observer agreement for WB-MRI was calculated using kappa statistics. Concordance, PPV, NPV, sensitivity and specificity for a correct assessment of the response between WB-MRI and the reference standard were calculated for both nodal and extra-nodal disease presence and total response evaluation. RESULTS: Inter-observer agreement of WB-MRI including DWI between both readers was moderate (κ 0.46-0.60). For early response assessment, WB-MRI DWI agreed with the reference standard in 33/51 patients (65%, 95% CI 51-77%) versus 15/51 (29%, 95% CI 19-43%) for WB-MRI without DWI. For restaging, WB-MRI including DWI agreed with the reference standard in 9/13 patients (69%, 95% CI 42-87%) versus 5/13 patients (38%, 95% CI 18-64%) for WB-MRI without DWI. CONCLUSIONS: The addition of DWI to the WB-MRI protocol in early response assessment and restaging of paediatric HL improved agreement with the [18F]FDG-PET/CT-based reference standard. However, WB-MRI remained discordant in 30% of the patients compared to standard imaging for assessing residual disease presence. KEY POINTS: • Inter-observer agreement of WB-MRI including DWI between both readers was moderate for (early) response assessment of paediatric Hodgkin's lymphoma. • The addition of DWI to the WB-MRI protocol in early response assessment and restaging of paediatric Hodgkin's lymphoma improved agreement with the [18F]FDG-PET/CT-based reference standard. • WB-MRI including DWI agreed with the reference standard in respectively 65% and 69% of the patients for early response assessment and restaging.

Whole-body MRI versus an FDG-PET/CT-based reference standard for staging of paediatric Hodgkin lymphoma: a prospective multicentre study.

OBJECTIVES: To assess the concordance of whole-body MRI (WB-MRI) and an FDG-PET/CT-based reference standard for the initial staging in children with Hodgkin lymphoma (HL) METHODS: Children with newly diagnosed HL were included in this prospective, multicentre, international study and underwent WB-MRI and FDG-PET/CT at staging. Two radiologists and a nuclear medicine physician independently evaluated all images. Discrepancies between WB-MRI and FDG-PET/CT were assessed by an expert panel. All FDG-PET/CT errors were corrected to derive the FDG-PET/CT-based reference standard. The expert panel corrected all reader errors in the WB-MRI DWI dataset to form the intrinsic MRI data. Inter-observer agreement for WB-MRI DWI was calculated using overall agreement, specific agreements and kappa statistics. Concordance for correct classification of all disease sites and disease stage between WB-MRI (without DWI, with DWI and intrinsic WB-MRI DWI) and the reference standard was calculated as primary outcome. Secondary outcomes included positive predictive value, negative predictive value and kappa statistics. Clustering within patients was accounted for using a mixed-effect logistic regression model with random intercepts and a multilevel kappa analysis. RESULTS: Sixty-eight children were included. Inter-observer agreement between WB-MRI DWI readers was good for disease stage (κ = 0.74). WB-MRI DWI agreed with the FDG-PET/CT-based reference standard for determining disease stage in 96% of the patients versus 88% for WB-MRI without DWI. Agreement between WB-MRI DWI and the reference standard was excellent for both nodal (98%) and extra-nodal (100%) staging. CONCLUSIONS: WB-MRI DWI showed excellent agreement with the FDG-PET/CT-based reference standard. The addition of DWI to the WB-MRI protocol improved the staging agreement. KEY POINTS: • This study showed excellent agreement between WB-MRI DWI and an FDG-PET/CT-based reference standard for staging paediatric HL. • Diffusion-weighted imaging is a useful addition to WB-MRI in staging paediatric HL. • Inter-observer agreement for WB-MRI DWI was good for both nodal and extra-nodal staging and determining disease stage.

Whole-body MRI reveals high incidence of osteonecrosis in children treated for Hodgkin lymphoma.

Osteonecrosis is a well-recognized complication in patients treated with corticosteroids. The incidence of osteonecrosis in children treated for Hodgkin lymphoma is unknown because prospective whole-body magnetic resonance imaging (MRI) studies are lacking in this patient population. Paediatric patients with newly diagnosed Hodgkin lymphoma who were treated according to a uniform paediatric Hodgkin protocol were eligible for inclusion in this prospective study. Whole-body MRI was performed in all 24 included patients (mean age 15·1 years, 12 girls) both before treatment and after 2 cycles of chemotherapy, and in 16 patients after completion of chemotherapy. Osteonecrosis was identified in 10 patients (41·7%, 95% confidence interval: 22·0-61·4%), with a total of 56 osteonecrotic sites. Osteonecrosis was detected in 8 patients after 2 cycles of OEPA (vincristine, etoposide, prednisone, doxorubicin), and in 2 additional patients after completion of chemotherapy. Epiphyseal involvement of long bones was seen in 4 of 10 children. None of the patients with osteonecrosis had any signs of bone collapse at the times of scanning. Whole-body MRI demonstrates osteonecrosis to be a common finding occurring during therapy response assessment of paediatric Hodgkin lymphoma. Detection of early epiphyseal osteonecrosis could allow for treatment before bone collapse and joint damage may occur.

Whole-body MRI for initial staging of paediatric lymphoma: prospective comparison to an FDG-PET/CT-based reference standard.

OBJECTIVE: To compare whole-body MRI, including diffusion-weighted imaging (whole-body MRI-DWI), with FDG-PET/CT for staging newly diagnosed paediatric lymphoma. METHODS: A total of 36 children with newly diagnosed lymphoma prospectively underwent both whole-body MRI-DWI and FDG-PET/CT. Whole-body MRI-DWI was successfully performed in 33 patients (mean age 13.9 years). Whole-body MRI-DWI was independently evaluated by two blinded observers. After consensus reading, an unblinded expert panel evaluated the discrepant findings between whole-body MRI-DWI and FDG-PET/CT and used bone marrow biopsy, other imaging data and clinical information to derive an FDG-PET/CT-based reference standard. RESULTS: Interobserver agreement of whole-body MRI-DWI was good [all nodal sites together (κ = 0.79); all extranodal sites together (κ = 0.69)]. There was very good agreement between the consensus whole-body MRI-DWI- and FDG-PET/CT-based reference standard for nodal (κ = 0.91) and extranodal (κ = 0.94) staging. The sensitivity and specificity of consensus whole-body MRI-DWI were 93 % and 98 % for nodal staging and 89 % and 100 % for extranodal staging, respectively. Following removal of MRI reader errors, the disease stage according to whole-body MRI-DWI agreed with the reference standard in 28 of 33 patients. CONCLUSIONS: Our results indicate that whole-body MRI-DWI is feasible for staging paediatric lymphoma and could potentially serve as a good radiation-free alternative to FDG-PET/CT. KEYPOINTS: • Accurate staging is important for treatment planning and assessing prognosis • Whole-body MRI-DWI could be a good radiation-free alternative to FDG-PET/CT • Interobserver agreement of whole-body MRI-DWI is good • Agreement between whole-body MRI and the FDG-PET/CT reference standard is good • Most discrepancies were caused by suboptimal accuracy of size measurements on MRI.

Congenital lung malformations: radiological findings and clues for differential diagnosis.

Congenital lung malformations encompass a wide spectrum of conditions with a broadly varying clinical presentation. They are often a source of morbidity in infants and children. Their management depends on the type of malformation and its clinical presentation. Usually, the diagnosis requires an imaging evaluation. Classifications of bronchopulmonary malformations have undergone significant revision in recent years and several theories have attempted to explain their confusing pathogenesis. There are considerable degrees of overlapping and hybrid conditions are common, with interrelated malformations showing various radiologic and pathologic features. Attending to the pathophysiological mechanisms and structures involved, lung malformations can be divided into three categories: bronchopulmonary anomalies, combined lung and vascular abnormalities, and vascular anomalies. The purpose of this article is to review the current imaging techniques for evaluating lung malformations in pediatric patients and their characteristic imaging findings. Moreover, this review discusses a useful classification and offers some clues to facilitate the differential diagnosis.

Tracheobronchomegaly following intrauterine tracheal occlusion for congenital diaphragmatic hernia.

BACKGROUND: Fetuses with severe congenital diaphragmatic hernia (CDH) and pulmonary hypoplasia may benefit from fetal endoluminal tracheal occlusion (FETO). Enlargement of the main bronchi and trachea appears to be a common complication of FETO. OBJECTIVE: To retrospectively evaluate the trachea and main bronchi of infants who underwent FETO for CDH and compare diameters with age-matched references. MATERIAL AND METHODS: Postnatal and follow-up chest radiographs were performed in seven children with unilateral CDH treated by FETO. Additional CT was performed in six of these (one neonate died before CT could be performed). Images were acquired from 3 days to 23 months of age. For each child, radiographs and CT images with optimal visualisation of the airways were selected for retrospective analysis. Tracheal and bronchial morphology was assessed by two experienced paediatric radiologists, and the diameters of these structures measured and compared with age-matched references. RESULTS: Mean diameters of the trachea and main bronchi were above the age-matched normal range in all patients, regardless of the side of the hernia or the degree of lung hypoplasia. CONCLUSION: Enlargement of the trachea and main bronchi appears following FETO and persists at least to the age of 5 years.

Thoracic findings of systemic diseases at high-resolution CT in children.

Pulmonary involvement in systemic diseases is common, but the radiographic appearance of early-stage pulmonary changes is often subtle. Computed tomography (CT) has higher sensitivity and specificity than radiography, and high-resolution CT is the method of choice for accurate assessment of diffuse parenchymal lung disease. Even with reductions in the peak voltage and tube charge to minimize the exposure of pediatric patients to radiation, CT performed with a meticulous acquisition technique can provide detailed information. In some cases, high-resolution CT may depict clinically silent lung lesions. The information provided by CT is invaluable for planning therapy in pediatric patients with pulmonary involvement in connective tissue disease (eg, juvenile rheumatoid arthritis, dermatomyositis, systemic sclerosis, systemic lupus erythematosus, or mixed connective tissue disease), vasculitis, a primary or acquired immune deficiency disorder, immotile cilia syndrome, cystic fibrosis, or Langerhans cell histiocytosis.

Side effects of oncologic therapies in the pediatric central nervous system: update on neuroimaging findings.

The need for early, accurate diagnosis of central nervous system (CNS) complications occurring during and after pediatric cancer treatment is growing because of the improvement in overall survival rates related to innovative and aggressive oncologic therapies. An elevated degree of suspicion is needed to recognize the radiologic features of these CNS complications. Radiologists need familiarity with the early and late side effects of cancer therapy in the pediatric CNS (eg, toxic effects, infection, endocrine or sensory dysfunction, neuropsychologic impairment, second malignancies), in order to accelerate the imaging diagnosis and minimize as much as possible the associated morbidity. Acquisition of knowledge about these complications will enable the development of more appropriate therapeutic trials and more effective patient surveillance and will lead to an improved quality of life by decreasing the long-term sequelae in survivors.

White hemithorax in children.

The aim of this pictorial review is to introduce the radiologist to the differential diagnosis of a white hemithorax in children, to provide significant information on the diagnostic work-up, and to promote radiation-free techniques whenever possible. There are many causes of white hemithorax in children and it can be due to a variety of chest disorders. In most cases, plain chest radiographs and ultrasound will suffice. However, additional information provided by, e.g., CT or MRI is sometimes required.

Correlation between US and MRI for prenatal lung volumetry in diaphragmatic hernia, and use of Doppler to identify the ipsilateral lung cap.

BACKGROUND: Pulmonary hypoplasia is a common cause of neonatal death. OBJECTIVE: To describe the correlation between relative fetal lung volume (RFLV) and lung-to-head ratio (LHR) in fetuses with unilateral diaphragmatic hernia. Additionally, to describe identification of the ipsilateral lung cap by power Doppler. MATERIALS AND METHODS: Single-institution study of consecutive fetuses with diaphragmatic hernia. LHR (by US) and RFLV (by MRI) were correlated in fetuses with and without an ipsilateral lung cap seen at MRI. In four, color/power Doppler was used to follow the pulmonary artery of the ipsilateral lung to identify the compressed cap. RESULTS: The study included 48 fetuses of 20-38 weeks' gestational age (mean, 26 weeks). Mean LHR was 1.52 (range, 0.6-3) in fetuses with a lung cap and 1.15 (range, 0.6-2.58) in fetuses without (P = 0.043). Mean RFLV was 47.4% (range, 18-80%) in fetuses with and 32.9% (range, 14-57%) in fetuses without a lung cap (P = 0.005). RFLV and LHR correlated (r = 0.41, P = 0.01 in those with a cap; r = 0.50, P = 0.05 in those without). Power Doppler identified the ipsilateral lung cap and pulsed Doppler confirmed pulmonary vascularization in four of four fetuses. CONCLUSION: LHR underestimates lung volume in fetuses with an ipsilateral lung cap. Power Doppler may be useful for identifying the cap.

Low-dose pioglitazone, flutamide, metformin plus an estro-progestagen for non-obese young women with polycystic ovary syndrome: increasing efficacy and persistent safety over 30 months.

CONTEXT: Therapy of androgen excess should not only confer cosmetic benefit, but also improve long-term markers of endocrine-metabolic and cardiovascular health. Here we report on our pilot experience with a low-dose polytherapy for 30 months. DESIGN, PATIENTS, INTERVENTION: Unblinded extension (24-30 months) of a double-placebo study exploring low-dose polytherapy over 24 months. Between 24 and 30 months, women with hyperinsulinemic androgen excess (N = 36; mean age: 19.4 year; BMI: 23.7 kg/m(2)) received metformin (850 mg/day), flutamide (62.5 mg/day), pioglitazone (7.5 mg/day), ethinylestradiol (20 µg/day) plus drospirenone (3 mg/day) for 24/28 days. MAIN OUTCOMES: Carotid IMT, body composition (by absorptiometry), abdominal fat (by magnetic resonance), hirsutism score, fasting glycaemia, insulin, androgens, HDL cholesterol, C-reactive protein and hepatic safety indices. RESULTS: Low-dose polytherapy for 30 months was not accompanied by a change in body weight or bone mineral density, but it was associated with a marked rise of insulin sensitivity (p < 0.00001), with a loss of visceral fat (mean: -27%; p < 0.00001) and with a lowering of IMT (-0.16 mm; p < 0.00001). Aspartate aminotransferase, gamma-glutamyl transferase and lactate dehydrogenase levels decreased slightly over 30 months. CONCLUSION: Low-dose polytherapy (24/28 day) with pioglitazone, flutamide, metformin and estro-progestagen was found to improve, without changing weight, a spectrum of long-term health markers in young women with hyperinsulinemic androgen excess.

Long-term skeletal findings in Menkes disease.

Skeletal findings in infants with Menkes disease, the most characteristic of which are metaphyseal spurs, long-bone fractures and wormian bones, have been widely reported. However, the changes in skeletal features over time are not well known. The long-term findings differ completely from those initially observed and consist of undertubulation and metaphyseal flaring, similar to the findings seen in some types of bone dysplasia. The initial and long-term radiological features in an 8-year-old boy with Menkes disease are illustrated.

Solitary osteochondroma: spontaneous regression.

Osteochondromas are the most common benign bone tumours. Nevertheless, their origin and biological behaviour are poorly understood. Rarely, spontaneous regression of osteochondromas may occur. We report the case of a 9-year-old girl with a solitary osteochondroma of the femur that regressed almost completely within 4 years, a fact that should be taken into account when deciding the management of these lesions, especially in young children.

Low-dose pioglitazone and low-dose flutamide added to metformin and oestro-progestagens for hyperinsulinaemic women with androgen excess: add-on benefits disclosed by a randomized double-placebo study over 24 months.

CONTEXT AND AIM: Metformin plus oestro-progestagen is a combination treatment for non-obese women with hyperinsulinaemic androgen excess. We explored whether low-dose pioglitazone (Pio) and flutamide (Flu) has readily detectable add-on effects. DESIGN PATIENTS, INTERVENTION: Randomized, double-placebo pilot study over 24 months; 38 women with hyperinsulinaemic androgen excess (mean age 20 years; BMI 23.7 kg/m(2)); all women received metformin and an oestro-progestagen for 24 months, and add-on Flu (62.5 mg/day; 21/28 days) for 18 months. A first randomization was performed at start of the study, for Pio (7.5 mg/day; 21/28 days) vs. Pio-placebo, with a cross-over of Pio subgroups at 18 month. A second randomization was performed at 18 months, for Flu vs. Flu-placebo until 24 months. MAIN OUTCOMES: Intima media thickness (IMT); body composition by absorptiometry; abdominal fat partitioning by magnetic resonance; circulating glucose, insulin, IGF-I, androgens, LDL : HDL ratio, RBP4, vaspin. RESULTS: Add-on effects of Pio included a gain of lean mass (mirrored by a loss of fat) and an accelerated lowering of IMT (P

Congenital tumours involving the head, neck and central nervous system.

Congenital intracranial tumours are uncommon and differ from those occurring in older children in clinical presentation, imaging characteristics and prognosis. These tumours are often detected incidentally on routine prenatal US and/or fetal MRI. Hence, the paediatric radiologist should be familiar with the features of those lesions that should be included in the differential diagnosis. In general, the prognosis of these conditions is poor owing to large tumour size and the limitations of adjuvant therapy at such a young age. Congenital lesions involving the head and neck region require a meticulous imaging approach using both US and MRI techniques to better guide prenatal planning and fetal or neonatal surgical procedures.

Pioglitazone (7.5 mg/day) added to flutamide-metformin in women with androgen excess: additional increments of visfatin and high molecular weight adiponectin.

BACKGROUND AND AIM: Low-dose pioglitazone (Pio), flutamide (Flu), metformin (Met) plus an oestro-progestagen is a novel polytherapy lowering total and visceral adiposity, and reducing carotid intima media thickness (IMT) in hyperinsulinaemic women with androgen excess, without changing their body mass index (BMI). In a search for mediators of PioFluMet's actions, we measured serum levels of visfatin and high molecular weight (HMW) adiponectin. DESIGN AND PATIENTS: In a double-blind study, we enrolled 38 young women with hyperinsulinaemic androgen excess [mean BMI: 23.7 kg/m(2)], all of whom started on Flu (62.5 mg/day), Met (850 mg/day) and a transdermal oestro-progestagen, each for 21/28 days over 1 year. Patients were randomly assigned to receive, in addition, placebo (n = 19) or Pio (7.5 mg/day; n = 19) on the same 21/28 days. MEASUREMENTS: Serum concentrations of visfatin and HMW adiponectin, visceral fat by magnetic resonance imaging, carotid IMT by ultrasound, all carried out during study start and after 1 year. RESULTS: PioFluMet raised visfatin by a mean 84% and HMW adiponectin by 157% (P < 0.001), and reduced visceral fat and IMT by a mean 22% and 31% (both P < 0.001). Low-dose Pio accounted for about half of the PioFluMet effects on IMT, visfatin and HMW adiponectin. CONCLUSION: In hyperinsulinaemic women with androgen excess, low-dose polytherapy with PioFluMet evoked striking rises in both circulating visfatin and HMW adiponectin, while lowering IMT and reducing visceral adiposity within 1 year.

Combined low-dose pioglitazone, flutamide, and metformin for women with androgen excess.

CONTEXT AND OBJECTIVE: One of the treatments for hyperinsulinemic hyperandrogenism in nonobese women is combined androgen receptor blockade (with flutamide; Flu), insulin sensitization (with metformin; Met) plus an estroprogestagen contraceptive. We tested whether adding low-dose pioglitazone (Pio; 7.5 mg/d) confers more benefit. SETTING: The study was conducted at a university hospital. STUDY POPULATION AND DESIGN: This double-blind study enrolled 38 young women with hyperinsulinemic hyperandrogenism [mean body mass index (BMI) 24 kg/m(2)], all of whom started on Flu (62.5 mg/d) and Met (850 mg/d) plus a transdermal estroprogestagen, each for 21 of 28 d over 6 months. Patients were randomly assigned to receive, in addition, placebo (n=19) or Pio (n=19; 7.5 mg/d) for the same 21 of 28 d over 6 months. MAIN OUTCOMES: BMI, waist to hip ratio, hirsutism score, fasting endocrine-metabolic markers, body composition, abdominal fat (visceral vs. sc), and carotid intima-media thickness were measured at study start and after 6 months. RESULTS: PioFluMet reduced intima-media thickness more than FluMet and lowered glucose, IGF-I, and C-reactive protein more as well as the ratio of low-density lipoprotein to high-density lipoprotein cholesterol and the ratio of neutrophils to lymphocytes. PioFluMet treatment was followed by a leaner body composition and a loss of visceral fat (both P < 0.001). In the total group, the changes included not only decreases in waist to hip ratio, hirsutism score, and testosterone (all P < 0.001) but also minor drops in alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, and lactate dehydrogenase (all P < 0.005), indicating absence of hepatotoxicity; BMI remained unchanged. Clinical side effects were not detected. CONCLUSION: In this proof-of-concept study, addition of Pio to FluMet plus an estroprogestagen led to improvements in the endocrine-metabolic condition, in low-grade inflammation, in total and visceral adiposity, and in markers of cardiovascular health.

Gray-scale and color Doppler sonography of scrotal disorders in children: an update.

Ultrasonography (US) is well suited to the study of pathologic conditions of the scrotum in children. US provides excellent anatomic detail; when color Doppler and power Doppler imaging are added, testicular perfusion can be assessed. Gray-scale, color Doppler, and power Doppler US were used to study a spectrum of scrotal disorders in 750 boys aged 1 day to 17 years. The entities studied included processus vaginalis-related disorders (cryptorchidism, inguinal-scrotal hernia, and hydrocele); varicocele; acute scrotum (epididymo-orchitis, torsion of the testicular appendages, and testicular torsion); scrotal tumors; testicular microlithiasis; scrotal trauma; and systemic diseases with scrotal involvement. When combined with the results of clinical and physical examination, the information obtained with US is sufficient to enable diagnosis in most cases of scrotal disease. Moreover, color Doppler imaging is essential for differentiation between processes such as epididymo-orchitis or torsion of the testicular appendages and testicular torsion, which have similar clinical manifestations (pain, swelling, and redness) but are managed differently.

Posterior fontanelle sonography: an acoustic window into the neonatal brain.

BACKGROUND AND PURPOSE: Sonographic brain studies are classically performed through the anterior fontanelle, but visualization of posterior supratentorial and infratentorial structures is poor with this approach. Posterior fontanelle sonography is recommended for better assessment of these structures. Our purpose was 1) to determine whether sonography of the brain through the posterior fontanelle (PF) improves visualization of brain lesions when added to the routine anterior fontanelle (AF) approach and 2) to describe standardized PF coronal and sagittal sections. METHODS: In this prospective study (conducted from February 1999 to January 2001), PF sonography was added to AF sonography in 165 consecutive premature neonates with a birth weight of < 2000 g. Sonograms were recorded in digital format for re-evaluation at the end of the study. Lesions were grouped as congenital, infectious, hemorrhagic, or hypoxic-ischemic. The chi2 test for paired data and the kappa coefficient were used to compare diagnoses with AF alone and diagnoses with AF plus PF. RESULTS: PF sonography was performed in 164 of 165 patients. Results were normal in 86 and abnormal in 78. The single posterior fossa malformation detected in this series was best delineated with the PF approach. PF sonography increased the diagnostic rate of grade II hemorrhage by 32%. Cerebellar hemorrhage (two patients) and cerebellar abscesses (one patient) were diagnosed by using the PF approach. PF sonography did not contribute to the diagnosis of periventricular leukomalacia. CONCLUSION: Study of the neonatal brain with the addition of PF sonography afforded greater accuracy in detecting intraventricular hemorrhage compared with AF sonography alone, especially when the ventricle was not dilated. The PF approach better defines posterior fossa malformations.