Susan C. Shelmerdine

Stresses and strains on the human fetal skeleton during development

Mechanical forces generated by fetal kicks and movements result in stimulation of the fetal skeleton in the form of stress and strain. This stimulation is known to be critical for prenatal musculoskeletal development; indeed, abnormal or absent movements have been implicated in multiple congenital disorders. However, the mechanical stress and strain experienced by the developing human skeleton in utero have never before been characterized. Here, we quantify the biomechanics of fetal movements during the second half of gestation by modelling fetal movements captured using novel cine-magnetic resonance imaging technology. By tracking these movements, quantifying fetal kick and muscle forces, and applying them to three-dimensional geometries of the fetal skeleton, we test the hypothesis that stress and strain change over ontogeny. We find that fetal kick force increases significantly from 20 to 30 weeks gestation, before decreasing towards term. However, stress and strain in the fetal skeleton rises significantly over the latter half of gestation. This increasing trend with gestational age is important because changes in fetal movement patterns in late pregnancy have been linked to poor fetal outcomes and musculoskeletal malformations. This research represents the first quantification of kick force and mechanical stress and strain due to fetal movements in the human skeleton in utero, thus advancing our understanding of the biomechanical environment of the uterus. Further, by revealing a potential link between fetal biomechanics and skeletal malformations, our work will stimulate future research in tissue engineering and mechanobiology.

MRI of paediatric liver tumours: How we review and report

Liver tumours are fortunately rare in children. Benign tumours such as haemangiomas and cystic mesenchymal hamartomas are typically seen in infancy, often before 6xa0months of age. After that age, malignant hepatic tumours increase in frequency. The differentiation of a malignant from benign lesion on imaging can often negate the need for biopsy. Ultrasound is currently the main screening tool for suspected liver pathology, and is ideally suited for evaluation of hepatic lesions in children due to their generally small size. With increasing research, public awareness and parental anxiety regarding radiation dosage from CT imaging, MRI is now unquestionably the modality of choice for further characterisation of hepatic mass lesions.Nevertheless the cost, length of imaging time and perceived complexity of a paediatric liver MR study can be intimidating to the general radiologist and referring clinician. This article outlines standard MR sequences utilised, reasons for their utilisation, types of mixed hepatocyte specific/extracellular contrast agents employed and imaging features that aid the interpretation of paediatric liver lesions. The two commonest paediatric liver malignancies, namely hepatoblastoma and hepatocellular carcinoma are described. Differentiation of primary hepatic malignancies with metastatic disease and mimickers of malignancy such as focal nodular hyperplasia (FNH) and hepatic adenomas are also featured in this review..Imaging should aim to clarify the presence of a lesion, the likelihood of malignancy and potential for complete surgical resection. Reviewing and reporting the studies should address these issues in a systematic fashion whilst also commenting upon background liver parenchymal appearances. Clinical information and adequate patient preparation prior to MR imaging studies help enhance the diagnostic yield.

Presentation to publication: proportion of abstracts published for ESPR, SPR and IPR.

BackgroundAdvancement of knowledge requires presentation and publication of high-quality scientific research. Studies submitted for presentation undergo initial peer review before acceptance and the rate of subsequent publication may be taken as an indicator of access to publication for pediatric radiology studies.ObjectivesEvaluate the proportion of abstracts also published in journals for pediatric radiology conferences and identify factors associated with publication success.Materials and methodsAll Medline articles that originated from oral presentations at the European Society for Paediatric Radiology (ESPR), the Society for Pediatric Radiology (SPR) or the International Pediatric Radiology (IPR) conferences between 2010 – 2012 were evaluated. Descriptive statistics to evaluate published and unpublished groups were calculated overall and split by characteristics of the abstracts such as number of authors.ResultsOverall number of abstracts published was 300/715 (41.9%), with most articles published in radiology specific journals (181/300; 60.3%), with median impact factor 2.31 (interquartile range [IQR]: 1.65-3.14, range: 0-18.03). Those published after the conference (262/300, 87.6%) had a median time to publication of 18 months and for those published before, the median time was -11 months. Median sample size in published articles was 52 (IQR: 33-105, range: 1-6,351).ConclusionOf pediatric radiology oral abstracts, 41.9% achieve publication after a period of at least 3 years from presentation. Studies originating from certain countries and on certain subspecialty topics were more likely to get published.

Who are we missing? Too few skeletal surveys for children with humeral and femoral fractures

AIMnTo determine the potential shortfall in skeletal survey referral for children presenting with an acute non-supracondylar humeral or femoral fracture.nnnMATERIALS AND METHODSnPlain radiograph reports were reviewed retrospectively using the radiology information system database over a 5 year study period (May 2008-2013) in children under 18 months of age who presented with an acute fracture. Subsequent skeletal survey referral was used as a surrogate marker for further investigation of child abuse. Application of robust meta-analysis derived probability data regarding likelihood of child abuse as a cause of non-supracondylar humeral or femoral fracture was applied. An estimation of the expected number of cases of abuse, with shortfall in skeletal survey referrals, was then calculated.nnnRESULTSnThere were 288 fractures in 281 children. Three children presented with multiple fractures and were considered separately in the present data. The mean patient age was 10.5 months. Nine (3%) non-supracondylar humeral fractures were identified of which four cases may have been due to non-accidental injury (NAI). One (11%) of these patients was referred for a skeletal survey indicating a potential shortfall of three referrals. Twenty-five (9%) femoral fractures were identified of which 13 cases may have been due to NAI, with six (24%) referrals for skeletal surveys generated. This indicates a potential shortfall of seven referrals.nnnCONCLUSIONnThe present study serves as a current analysis of practice within a tertiary paediatric referral centre. There appeared to be local under-investigation of NAI. Improved child protection education and awareness programmes have now been introduced.

Early clinical applications for imaging at microscopic detail: microfocus computed tomography (micro-CT)

Microfocus CT (micro-CT) has traditionally been used in industry and preclinical studies, although it may find new applicability in the routine clinical setting. It can provide high-resolution three-dimensional digital imaging data sets to the same level of detail as microscopic examination without the need for tissue dissection. Micro-CT is already enabling non-invasive detailed internal assessment of various tissue specimens, particularly in breast imaging and early gestational fetal autopsy, not previously possible from more conventional modalities such as MRI or CT. In this review, we discuss the technical aspects behind micro-CT image acquisition, how early work with small animal studies have informed our knowledge of human disease and the imaging performed so far on human tissue specimens. We conclude with potential future clinical applications of this novel and emerging technique.

Achondroplasia: Really rhizomelic?

Achondroplasia is the most common form of short limb dwarfism in humans. The shortening of the limb lengths in achondroplasia is widely described as “rhizomelic.” While this appearance may be convincing clinically, the description is not necessarily true or helpful radiologically. The aims of this study, were therefore, to determine whether rhizomelic shortening is a true feature of achondroplasia at diagnosis in infancy. Humeral, radial, femoral, and tibial diaphyseal lengths were recorded by two independent observers from 22 skeletal surveys of infants with achondroplasia and compared with 150 normal age‐matched control subjects. Upper and lower limb bone length ratios (radial/humeral and tibial/femoral lengths, respectively) in both groups were compared using an unpaired t‐test. Mean upper limb length ratios were statistically higher within the achondroplasia group at 0.87u2009±u20090.04 (nu2009=u200922, mean age 70u2009±u200994 days) compared to normal controls at 0.79u2009±u20090.02 (nu2009=u2009150, mean age 113 daysu2009±u200988 days; Pu2009<u20090.0001). Lower limb length ratios were not significantly different between groups (0.84u2009±u20090.04 vs. 0.83u2009±u20090.02, Pu2009=u20090.46). There was good inter‐observer agreement of limb length measurements, with an average measurement difference of 0.1u2009±u20091.4u2009mm. In conclusion, infants with achondroplasia demonstrate statistically significant rhizomelic shortening within the upper limbs, but not lower limbs at diagnosis, compared to normal controls. The term “rhizomelic shortening” in relation to achondroplasia should be reserved when describing upper limb proportions.

Postmortem image‐guided biopsy for less‐invasive diagnosis of congenital intracranial teratoma

In certain cases, postmortem magnetic resonance imaging (PM-MRI) can obviate the need for formal autopsy and dissection by providing high-quality imaging which can guide tissue sampling. Percutaneous needle organ biopsy to obtain tissue samples for microscopic examination, as part of the less-invasive perinatal autopsy, has been described previously1 and endoscopicor laparoscopic-guided sampling has also been piloted2. We present a case of congenital malformation in

Postmortem microfocus computed tomography for early gestation fetuses: a validation study against conventional autopsy

BACKGROUND: Perinatal autopsy provides useful clinical information in up to 40% of cases. However, there is a substantial unmet clinical need with regards to postmortem investigation of early gestation fetal loss for parents for whom standard autopsy is either not available or not acceptable. Parents dislike the invasive nature of autopsy, but current clinical imaging techniques do not provide high‐enough imaging resolution in small fetuses. We hypothesized that microfocus computed tomography, which is a rapid high‐resolution imaging technique, could give accurate diagnostic imaging after early gestation fetal loss. OBJECTIVE: The objective of the study was to evaluate the diagnostic accuracy of microfocus computed tomography for noninvasive human fetal autopsy for early gestation fetuses, with the use of conventional autopsy as the reference standard. STUDY DESIGN: We compared iodinated whole body microfocus computed tomography in 20 prospectively recruited fetuses (11–21 weeks gestation from 2 centers) with conventional autopsy in a double‐blinded manner for a main diagnosis and findings in specific body organs. Fetuses were prepared with 10% formalin/potassium tri‐iodide. Images were acquired with a microfocus computed tomography scanner with size‐appropriate parameters. Images were evaluated independently by 2 pediatric radiologists, who were blinded to formal perinatal autopsy results, across 40 individual indices to reach consensus. The primary outcome was agreement between microfocus computed tomography and conventional autopsy for overall diagnosis. RESULTS: Postmortem whole body fetal microfocus computed tomography gave noninvasive autopsy in minutes, at a mean resolution of 27&mgr;m, with high diagnostic accuracy in fetuses at <22 weeks gestation. Autopsy demonstrated that 13 of 20 fetuses had structural abnormalities, 12 of which were also identified by microfocus computed tomography (92.3%). Overall, microfocus computed tomography agreed with overall autopsy findings in 35 of 38 diagnoses (15 true positive, 18 true negative; sensitivity 93.8% [95% confidence interval, 71.7–98.9%], specificity 100% [95% confidence interval, 82.4–100%]), with 100% agreement for body imaging diagnoses. Furthermore, after removal of nondiagnostic indices, there was agreement for 700 of 718 individual body organ indices that were assessed on microfocus computed tomography and autopsy (agreement, 97.5%; 95% confidence interval, 96.1–98.4%), with no overall differences between fetuses at ≤14 or >14 weeks gestation (agreement, 97.2% and 97.9%, respectively). Within first‐trimester fetal loss cases (<14 weeks gestation), microfocus computed tomography analysis yielded significantly fewer nondiagnostic indices than autopsy examination (22/440 vs 48/348, respectively; P<.001). CONCLUSION: Postmortem whole‐body fetal microfocus computed tomography gives noninvasive, detailed anatomic examinations that are achieved in minutes at high resolution. Microfocus computed tomography may be preferable to magnetic resonance imaging in early gestation fetuses and may offer an acceptable method of examination after fetal loss for parents who decline invasive autopsy. This will facilitate autopsy and subsequent discussions between medical professionals who are involved in patient care and counselling for future pregnancies.

Filamin A (FLNA) mutation—A newcomer to the childhood interstitial lung disease (ChILD) classification

Interstitial lung disease (ILD) in infants represents a rare and heterogenous group of disorders, distinct from those occurring in adults. In recent years a new entity within this category is being recognized, namely filamin A (FLNA) mutation related lung disease. Our aims are to describe the clinical and radiological course of patients with this disease entity to aid clinicians in the prognostic counseling and management of similar patients they may encounter.

Rib Fractures in Osteogenesis Imperfecta: Have we Learnt Anything About Child Abuse?

We read with interest the recent paper by Greeley et al1 entitled “Fractures at diagnosis in infants and children with osteogenesis imperfecta” and the recent accompanying commentary by Paterson. We believe the research question presented by Greeley and colleagues raises important issues especially for the subgroup of patients suffering from milder types of osteogenesis imperfecta (OI), where the radiographic findings may be difficult to differentiate from child physical abuse (CPA) (or nonaccidental injury). Greeley et al1 hypothesized that fracture patterns seen in children with OI at time of diagnosis differ from those seen in CPA; however, we are concerned that their methodology did not allow them to address this question for several reasons. They did not robustly define their study group relying on a loose definition of OI. They did not study a control group, against which to compare their group of suspected OI cases. There were insufficient details presented regarding the radiographic protocols and fracture identification methodology. The number of radiologic images obtained were not documented, and may have varied between patients. Analysis of the radiographs was not conducted, instead relying on documentation within the patient notes. The lack of details of the fractures, including fracture location or bone mineral density underplays the role these features might play in differentiating bone fragility states from CPA or alternative diagnoses. Finally, it should be recognized that bone fragility states and CPA are not mutually exclusive. Unless genetic testing and confessionals are taken in every case, whether a fracture was caused accidentally or not cannot be based on a single radiograph. Paterson argues that Greeley’s study is flawed because they did not find rib fractures in OI although “rib fractures do occur in known cases.” He illustrates his point with a chest radiograph of OI type III as an “infant with rib fracturesy present on the day of birth.” Few practitioners would suggest CPA in the presence of multiple healing rib and humeral fractures in a severely osteopenic infant on the day of birth, implying antenatal in utero fractures. Although Greeley and colleagues do not give details of the exact ages of their cases, they did identify rib fractures in 15 (22%), of which 13 were diagnosed prenatally or immediately after birth, 12 had blue sclera, 10 had osteopenia, and 5 had a family history of OI, largely consistent with our own clinical experience. Paterson also suggests that “spontaneous rib fracturesy are found in a wide range of metabolic disorders.” While rib fractures are a well-recognized feature of osteopathy of prematurity, there is no systematic evidence that rib fractures occur in vitamin D deficiency in the absence of rickets, and even in the presence of rickets, rib fractures are rare in a nonmobile infant.3 Low-trauma rib fractures have not been reported in copper deficiency in term infants.4 When they occur in preterm infants, copper deficiency is likely to be only one of several factors leading to severe bony fragility. There are few publications to support this.5 Overall, it is difficult to draw any strong conclusions from the data, and we are surprised that Greeley and colleagues were able to justify their statement that “infants with multiple rib fractures are unlikely to be suffering from undiagnosed OI.” We are especially concerned by how these data may be adapted and used in the medicolegal setting where such “evidence” may be upheld by a prosecuting team to refute an alternative diagnosis in a child with multiple rib injuries. Improvements in study methodology may have produced more meaningful results, which could have allowed stronger conclusions to help the medicolegal system.