Martin Stenzel

Chronic nonbacterial osteomyelitis in childhood: prospective follow-up during the first year of anti-inflammatory treatment

IntroductionChronic nonbacterial osteomyelitis (CNO) is an inflammatory disorder of unknown etiology. In children and adolescents CNO predominantly affects the metaphyses of the long bones, but lesions can occur at any site of the skeleton. Prospectively followed cohorts using a standardized protocol in diagnosis and treatment have rarely been reported.MethodsThirty-seven children diagnosed with CNO were treated with naproxen continuously for the first 6 months. If assessment at that time revealed progressive disease or no further improvement, sulfasalazine and short-term corticosteroids were added. The aims of our short-term follow-up study were to describe treatment response in detail and to identify potential risk factors for an unfavorable outcome.ResultsNaproxen treatment was highly effective in general, inducing a symptom-free status in 43% of our patients after 6 months. However, four nonsteroidal anti-inflammatory drug (NSAID) partial-responders were additionally treated with sulfasalazine and short-term corticosteroids. The total number of clinical detectable lesions was significantly reduced. Mean disease activity estimated by the patient/physician and the physical aspect of health-related quality of life including functional ability (global assessment/childhood health assessment questionnaire and childhood health assessment questionnaire) and pain improved significantly. Forty-one percent of our patients showed radiological relapses, but 67% of them were clinically silent.ConclusionsMost children show a favorable clinical course in the first year of anti-inflammatory treatment with NSAIDs. Relapses and new radiological lesions can occur at any time and at any site in the skeleton but may not be clinically symptomatic. Whole-body magnetic resonance imaging proved to be very sensitive for initial and follow-up diagnostics.

Benign liver tumors in pediatric patients - Review with emphasis on imaging features

Benign hepatic tumors are commonly observed in adults, but rarely reported in children. The reasons for this remain speculative and the exact data concerning the incidence of these lesions are lacking. Benign hepatic tumors represent a diverse group of epithelial and mesenchymal tumors. In pediatric patients, most benign focal liver lesions are inborn and may grow like the rest of the body. Knowledge of pediatric liver diseases and their imaging appearances is essential in order to make an appropriate differential diagnosis. Selection of the appropriate imaging test is challenging, since it depends on a number of age-related factors. This paper will discuss the most frequently encountered benign liver tumors in children (infantile hepatic hemangioendothelioma, mesenchymal hamartoma, focal nodular hyperplasia, nodular regenerative hyperplasia, and hepatocellular adenoma), as well as a comparison to the current knowledge regarding such tumors in adult patients. The current emphasis is on imaging features, which are helpful not only for the initial diagnosis, but also for pre- and post-treatment evaluation and follow-up. In addition, future perspectives of contrast-enhanced ultrasound (CEUS) in pediatric patients are highlighted, with descriptions of enhancement patterns for each lesion being discussed. The role of advanced imaging tests such as CEUS and magnetic resonance imaging, which allow for non-invasive assessment of liver tumors, is of utmost importance in pediatric patients, especially when repeated imaging tests are needed and radiation exposure should be avoided.

Atlas-Guided Cluster Analysis of Large Tractography Datasets

Diffusion Tensor Imaging (DTI) and fiber tractography are important tools to map the cerebral white matter microstructure in vivo and to model the underlying axonal pathways in the brain with three-dimensional fiber tracts. As the fast and consistent extraction of anatomically correct fiber bundles for multiple datasets is still challenging, we present a novel atlas-guided clustering framework for exploratory data analysis of large tractography datasets. The framework uses an hierarchical cluster analysis approach that exploits the inherent redundancy in large datasets to time-efficiently group fiber tracts. Structural information of a white matter atlas can be incorporated into the clustering to achieve an anatomically correct and reproducible grouping of fiber tracts. This approach facilitates not only the identification of the bundles corresponding to the classes of the atlas; it also enables the extraction of bundles that are not present in the atlas. The new technique was applied to cluster datasets of 46 healthy subjects. Prospects of automatic and anatomically correct as well as reproducible clustering are explored. Reconstructed clusters were well separated and showed good correspondence to anatomical bundles. Using the atlas-guided cluster approach, we observed consistent results across subjects with high reproducibility. In order to investigate the outlier elimination performance of the clustering algorithm, scenarios with varying amounts of noise were simulated and clustered with three different outlier elimination strategies. By exploiting the multithreading capabilities of modern multiprocessor systems in combination with novel algorithms, our toolkit clusters large datasets in a couple of minutes. Experiments were conducted to investigate the achievable speedup and to demonstrate the high performance of the clustering framework in a multiprocessing environment.

Ultrasound elastography and contrast-enhanced ultrasound in infants, children and adolescents

OBJECTIVE To describe prerequisites, use, and safety of ultrasound elastography and contrast-enhanced ultrasound in infants, children, and adolescents. METHOD This review deals with two latest developments in ultrasonography in children. The principle of strain elastography, transient elastography, and acoustic radiation force imaging is discussed, including limitations, and advantages of the different techniques in diagnosing focal and diffuse organ disease. The intravesical (contrast-enhanced voiding ultrasonography) and intravascular use of contrast-media to outline blood, and urinary flow is described, with special emphasis on indications, off-label use, and diagnostic gain. Examples of indications for performing the advanced ultrasound techniques are presented. SUMMARY AND CONCLUSION Latest developments in ultrasound machine engineering, and the availability of contrast-media that interact with ultrasound waves allow for assessment of tissue stiffness/elasticity properties, blood, and urinary flow. Thereby ultrasound is capable not only to depict morphology, but gives the additional information on organ, and focal lesion perfusion, and urinary flow dynamics. The information gap to other cross-sectional techniques such as magnetic resonance imaging, that make potential harmful sedation, and anaesthesia in the youngest children necessary, thereby gets closer.

[Whole-body MR imaging in children with suspected osteonecrosis after intensive chemotherapy: preliminary results].

PURPOSE Use of multidrug chemotherapy poses the risk of avascular osseous necroses in children. Depiction of the whole body, including clinically non-apparent sites is mandatory for starting early and proper treatment, including surgical approaches in lesions near the joints. We analyzed the value of whole-body MRI in the detection of osteonecrosis, (1) in relation to conventional X-ray imaging and clinical symptoms, (2) using different MRI sequences, (3) with follow-up examinations. MATERIALS AND METHODS 5 patients suffering from an oncological disease, 13 to 16 years old (3 x ALL, 1 x medulloblastoma, 1 x CML), and recently developing bone pain were examined with X-ray imaging of the particular region and a whole-body MRI (T2w TIRM, T 1w TSE sequences, pre- and post-contrast GD-DTPA, including fat suppression techniques). Neck/thorax/abdomen/pelvis, and upper and lower extremities were acquired in the coronal plane, and the feet in sagittal orientation. 4 of 5 patients had at least one follow-up examination (in the mean after 10 +/- 4 months). RESULTS None of the initial X-ray images revealed an abnormal finding. The whole-body MRI showed in 4 of 5 children bone marrow lesions compatible with osteonecrosis. The locations were around the knee joints (n = 3) and the tibiae/ankle joints (n = 4). In addition to the symptomatic sites, MRI revealed additional lesions at the following sites: humerus (n = 5), hip joints (n = 4), knee joints (n = 6), ankle joints (n = 4). The size varied from small focal lesions to lesions measuring 90 % of the whole transverse diameter of the bone. The lesions were able to be detected most easily with heavily T 2-weighted (TIRM) sequences, and the diagnosis was most easily established using the non-enhanced TSE T 1-weighted sequences. As a consequence of the results of the whole-body MRI, all patients with lesions compatible with osteonecrosis received symptomatic (n = 2) or specific (n = 2) therapy. In the follow-up examinations, a higher number of patients showed no changes in the lesions as to size and distribution. 2 patients showed partial resolution of the osteonecroses. CONCLUSION Whole-body MR imaging allows early diagnosis of symptomatic as well as clinically non-apparent osteonecroses. It can be used in planning and monitoring surgical and pharmacological therapies.

Magnetic resonance imaging in children and adolescents with chronic inflammatory bowel disease.

Inflammatory bowel diseases (IBD) represent challenges, both from a diagnostic, and therapeutic point of view. Deep-seated anatomic structures are difficult to assess by ultrasound technique alone. As radiation-free alternative cross-sectional imaging method, magnetic resonance imaging of the intestinal structures is costly and time-consuming. Examination of pediatric patients imply additional considerations: reduction of body motions in younger children and consideration of the most appropriate preparation, and examination technique. The demanding Sellink technique is the only means for appropriately distending the lesser intestine in order to detect small bowel strictures. Oral intake of contrast medium (CM) alone shows its limitations regarding distensibility. The need for intravenous contrast media application needs to be considered, too. Active inflammation of both intestinal wall, and mesentery can be demonstrated accurately. Nevertheless, viable alternatives to CM application is desirable, considering non-negligible adverse reactions. Recent data suggest diffusion weighted imaging might fill this diagnostic gap. Irrespective of sequence technique chosen, bowel movement remains a major obstacle. Antispasmolytics in their function as smooth muscle relaxants help in improving image quality, however, their use in children might be off-label. Optimal preparation for the examination and appropriate imaging technique allow for diagnosing typical patterns of changes in IBD, such as bowel wall thickening, ulcers, mural stratification, strictures, creeping fat, and comb sign, and lymphadenopathy. The article gives a detailed overview of current significance of magnetic resonance imaging pediatric patients suffering from IBD, considering indications, limitations, and safety aspects.

Pharmacokinetics and Safety of Macrocyclic Gadobutrol in Children Aged Younger Than 2 Years Including Term Newborns in Comparison to Older Populations.

ObjectivesThis clinical study evaluated the pharmacokinetics (PK) and safety data of macrocyclic extracellular contrast agent gadobutrol in pediatric subjects aged younger than 2 years. Materials and MethodsPediatric subjects (term newborns to those aged younger than 2 years) with normal renal function undergoing magnetic resonance imaging with gadobutrol (0.1 mmol/kg body weight [BW]) were prospectively enrolled in this open-label, multicenter clinical trial to evaluate PK as a primary end point. Plasma PK was analyzed using a population-based PK approach. Safety and qualitative efficacy (evaluation of images) were secondary end points. Safety and tolerability were assessed throughout study participation (approximately 7 days). Imaging efficacy variables were assessed by investigators. ResultsForty-four subjects were evaluated for safety and efficacy; 43 subjects were eligible for PK evaluation including 9 term newborns and infants aged younger than 2 months. Gadobutrol PK in pediatric subjects aged younger than 2 years were adequately described by a linear 2-compartmental model with elimination from the central compartment. Total median systemic exposure (area under the curve) of gadobutrol was estimated at 776 &mgr;mol · h/L (range, 544–1470 &mgr;mol · h/L). Simulated median concentration at 20 minutes after injection of gadobutrol (C20) was 339 &mgr;mol/L (range, 230–456 &mgr;mol/L). Safety and tolerability profile were similar to older populations. In 1 subject (2.3%), vomiting was reported as a mild adverse event related to gadobutrol, and there were no reported serious adverse events. The evaluation of gadobutrol-enhanced images provided improved diagnosis, increased confidence in diagnosis, and contributed to subject clinical management. ConclusionsThe PK profile of gadobutrol in children aged younger than 2 years including newborns is similar to that in older children and adults. At the dose of 0.1 mmol/kg BW, gadobutrol had a favorable safety profile and was well tolerated with similar profile across the age range 0 to younger than 2 years and compared with older children and adults. Extrapolation of efficacy data from adults to the younger pediatric population, including term newborns, is justified. The recommended standard dose of gadobutrol (0.1 mmol/kg BW), as used in the population aged 2 years and older, is also appropriate in children aged younger than 2 years.

Bisphosphonate treatment for patients with chronic nonbacterial osteomyelitis

Chronic recurrent multifocal osteomyelitis (CRMO) is a severe form of chronic nonbacterial osteomyelitis (CNO) that affects the long bones as well as other skeletal sites, such as the spine. Gleeson et al. recently described seven patients affected by CRMO who were treated with intravenous pamidronate, and concluded that pamidronate therapy should be considered early in the treatment of CRMO affecting the spine. No nonvertebral effects of pamidronate were noted, indicating that additional anti-inflammatory medication should be used in patients who have vertebral and nonvertebral CNO lesions. Although adverse effects of bisphosphonate therapy on bone have been noted previously, Gleeson et al. only reported undesirable effects such as generalized aches and pains, fever and injection-site reaction. As with previous studies of bisphosphonate treatment of patients with CNO, however, the number of patients included in this study was small (n = 7) and the follow-up was limited; therefore, bisphosphonate treatment of children and adolescents should only be considered as a last resort until controlled trials with long-term follow-up are performed.

Intravenous contrast-enhanced sonography in children and adolescents - a single center experience.

Compared to adult patients, ultrasonography in children and adolescents is much more common, due to lack of ionizing radiation, and its wide availability. With the introduction of contrast-media for use in ultrasonography, one major drawback of the method could be overcome. In Europe, SonoVue® is the only widely available agent, which due to improved stability makes it possible to image normal and diseased tissue perfusion and vascularization with high accuracy. Inability to hold the breath and voluntary body movement of the patient is less of an obstacle compared to color Doppler techniques and makes the method very attractive for use in children, which, depending on age, may not be very cooperative. Use of intravenous contrast-medium in minors is currently very limited for several reasons: availability, lack of recommendation in national and international guidelines, and lack of official licensing. The article will touch medical indications, technique, safety considerations, and perspective of intravenous use of contrast-media in children and adolescents, including data from a 6-year period in 37 patients. Purpose The purpose of the study was to collect data on ultrasonographic examinations, expanded by intravenous administration of the contrast agent SonoVue® in children and adolescents. Besides assessing diagnostic yield, data on adverse medication effects was collected. Materials and methods The study includes contrast-enhanced ultrasound examinations in 37 children at a single institution. Indications for the examinations were tumor lesions, infections, traumatic organ injuries, and parenchymal organ ischemia. Parents of the patients and adolescent patients were informed about the off-label use of the contrast agent. Thirty-nine examinations were performed, the average age of the patient was 11.1 years (range 1 to 17 years). Results All of the examinations yielded additional diagnostic value, always expanding results from B mode and color coded sonography. Overall, most examinations were done to assess the liver (n=16), followed by the kidney in 10 cases. The different etiologies were encountered in the following order: tumor (n=22), infection (n=9), trauma (n=5), ischemia (n=4). Most examinations were performed to evaluate a hepatic lesion (n=12). There was one incident recorded that fit the criteria of a possible adverse effect. In an 8-year-old girl nausea was noted, that started 15 minutes after the end of the examination and resolved spontaneously. In none of the patients medical treatment for adverse effects was necessary. Conclusion Ultrasonography in children, enhanced by intravenous use of contrast medium is feasible and allows for further evaluating cystic and solid tumors, and organ perfusion. Given that proper medical equipment and correct ultrasound machine settings are used, it is a robust method without diagnostic failures. In this small-sized case series there were no severe adverse effects, however, off-label use in children needs to be addressed.

ESPR postmortem imaging task force: where we begin.

A new task force on postmortem imaging was established at the annual meeting of the European Society of Paediatric Radiology (ESPR) in Graz, Austria, in 2015. The postmortem task force is separate from the child abuse task force as it covers all aspects of fetal, neonatal and non-forensic postmortem imaging. The main focus of the task force is the guidance and standardization of non-radiographic postmortem imaging, particularly postmortem CT and postmortem MRI. This manuscript outlines the starting point of the task force, with a mission statement, outline of current experience, and short- and long-term goals.