European Society of Pediatric Radiology survey of perioperative imaging in pediatric liver transplantation: (2) intraoperative imaging.

BACKGROUND: Liver transplantation is the state-of-the-art curative treatment for end-stage liver disease. Imaging is a key element in the detection of intraoperative and postoperative complications. So far, only limited data regarding the best radiological approach to monitor children during liver transplantation is available. OBJECTIVE: To harmonize the imaging of pediatric liver transplantation, the European Society of Pediatric Radiology Abdominal Taskforce initiated a survey addressing the current status of imaging including the pre-, intra- and postoperative phase. This paper reports the responses related to intraoperative imaging. MATERIALS AND METHODS: An online survey, initiated in 2021, asked European centers performing pediatric liver transplantation 48 questions about their imaging approach. In total, 26 centers were contacted, and 22 institutions from 11 countries returned the survey. RESULTS: Intraoperative ultrasound (US) is used by all sites to assess the quality of the vascular anastomosis in order to ensure optimal perfusion of the liver transplant. Vessel depiction is commonly achieved using color Doppler (95.3%). Additional US-based techniques are employed by fewer centers (power angio mode, 28.6%; B-flow, 19%; contrast-enhanced US, 14.3%). Most centers prefer a collaborative approach, with surgeons responsible for probe handling, while radiologists operate the US machine (47.6%). Less commonly, the intraoperative US is performed by the surgeon alone (28.6%) or by the radiologist alone (23.8%). Timing of US, imaging frequency, and documentation practices vary among centers. CONCLUSION: Intraoperative US is consistently utilized across all sites during pediatric liver transplantation. However, considerable variations were observed in terms of the US setup, technique preferences, timing of controls, and documentation practices. These differences provide valuable insights for future optimization and harmonization studies.

European Society of Pediatric Radiology survey of perioperative imaging in pediatric liver transplantation: (3) postoperative imaging.

BACKGROUND: Liver transplantation is the state-of-the-art curative treatment for end-stage liver disease. Imaging is a key element in the detection of postoperative complications. So far, limited data is available regarding the best radiologic approach to monitor children after liver transplantation. OBJECTIVE: To harmonize the imaging of pediatric liver transplantation, the European Society of Pediatric Radiology Abdominal Taskforce initiated a survey addressing the current status of imaging including the pre-, intra-, and postoperative phases. This paper reports the responses related to postoperative imaging. MATERIALS AND METHODS: An online survey, initiated in 2021, asked European centers performing pediatric liver transplantation 48 questions about their imaging approach. In total, 26 centers were contacted, and 22 institutions from 11 countries returned the survey. RESULTS: All sites commence ultrasound (US) monitoring within 24 h after liver transplantation. Monitoring frequency varies across sites, ranging from every 8 h to 72 h in early, and from daily to sporadic use in late postoperative phases. Predefined US protocols are used by 73% of sites. This commonly includes gray scale, color Doppler, and quantitative flow assessment. Alternative flow imaging techniques, contrast-enhanced US, and elastography are applied at 31.8%, 18.2%, and 63.6% of sites, respectively. Computed tomography is performed at 86.4% of sites when clarification is needed. Magnetic resonance imaging is used for selected cases at 36.4% of sites, mainly for assessment of biliary abnormalities or when blood tests are abnormal. CONCLUSION: Diagnostic imaging is extensively used for postoperative surveillance of children after liver transplantation. While US is generally prioritized, substantial differences were noted in US protocol, timing, and monitoring frequency. The study highlights potential areas for future optimization and standardization of imaging, essential for conducting multicenter studies.

Direct interhemispheric cortical communication via thalamic commissures: a new white matter pathway in the primate brain.

Cortical neurons of eutherian mammals project to the contralateral hemisphere, crossing the midline primarily via the corpus callosum and the anterior, posterior, and hippocampal commissures. We recently reported and named the thalamic commissures (TCs) as an additional interhemispheric axonal fiber pathway connecting the cortex to the contralateral thalamus in the rodent brain. Here, we demonstrate that TCs also exist in primates and characterize the connectivity of these pathways with high-resolution diffusion-weighted MRI, viral axonal tracing, and fMRI. We present evidence of TCs in both New World (Callithrix jacchus and Cebus apella) and Old World primates (Macaca mulatta). Further, like rodents, we show that the TCs in primates develop during the embryonic period, forming anatomical and functionally active connections of the cortex with the contralateral thalamus. We also searched for TCs in the human brain, showing their presence in humans with brain malformations, although we could not identify TCs in healthy subjects. These results pose the TCs as a vital fiber pathway in the primate brain, allowing for more robust interhemispheric connectivity and synchrony and serving as an alternative commissural route in developmental brain malformations.

European Society of Pediatric Radiology survey of perioperative imaging in pediatric liver transplantation: (1) pre-transplant evaluation.

BACKGROUND: Liver transplantation is the state-of-the-art curative treatment in end-stage liver disease. Imaging is a key element for successful organ-transplantation to assist surgical planning. So far, only limited data regarding the best radiological approach to prepare children for liver transplantation is available. OBJECTIVES: In an attempt to harmonize imaging surrounding pediatric liver transplantation, the European Society of Pediatric Radiology (ESPR) Abdominal Taskforce initiated a survey addressing the current status of imaging including the pre-, intra-, and postoperative phase. This paper reports the responses on preoperative imaging. MATERIAL AND METHODS: An online survey, initiated in 2021, asked European centers performing pediatric liver transplantation 48 questions about their imaging approach. In total, 26 centers were contacted and 22 institutions from 11 countries returned the survey. From 2018 to 2020, the participating centers collectively conducted 1,524 transplantations, with a median of 20 transplantations per center per annum (range, 8-60). RESULTS: Most sites (64%) consider ultrasound their preferred modality to define anatomy and to plan surgery in children before liver transplantation, and additional cross-sectional imaging is only used to answer specific questions (computed tomography [CT], 90.9%; magnetic resonance imaging [MRI], 54.5%). One-third of centers (31.8%) rely primarily on CT for pre-transplant evaluation. Imaging protocols differed substantially regarding applied CT scan ranges, number of contrast phases (range 1-4 phases), and applied MRI techniques. CONCLUSION: Diagnostic imaging is generally used in the work-up of children before liver transplantation. Substantial differences were noted regarding choice of modalities and protocols. We have identified starting points for future optimization and harmonization of the imaging approach to multicenter studies.

Evaluation of bone mineral density and bone turnover in children on anticoagulation.

Background: Childhood and adolescence are critical periods of bone mineral acquisition. Children on anticoagulation (AC) might have an increased risk for reduced bone mineral density (BMD). Risk factors for impaired bone accumulation include chronic diseases, immobility, and medication. Vitamin K (VK) deficiency reflected by undercarboxylated osteocalcin levels (ucOC) has been identified as a predictor of osteoporosis and fractures. Data on bone health in children under AC are sparse. Aims: To evaluate BMD in children on AC and characterize the risk factors of low BMD, including VK and Vitamin D (VD) status. Methods: Single-center cross-sectional study of clinical, biochemical, and densitometric parameters. Assessment of VK surrogate parameters included ucOC and matrix gla protein (MGP). Results: A total of 39 children (4-18 years; 12 females) receiving AC were included, 31 (79%) on VK antagonists and 8 (21%) on direct oral anticoagulants. Overall, BMD was decreased for both the lumbar spine (LS; -0.7SDS) and total body less head (TBLH; -1.32SDS) compared with pediatric reference data. Significant associations were found between early pubertal development and TBLH-BMD, and between BMI and LS-BMD. VK surrogate parameters were highly related to patients' age and pubertal development. Neither serum parameters nor AC-related factors predicted BMD. VD was detected in 10/39 patients with lower values during puberty. Conclusion: Our data indicate BMD reduction in pediatric patients on AC. Although AC-related factors did not predict reduced BMD, low BMI and pubertal stages represented important risk factors. Awareness of risk factors for low BMD and high prevalence of VD deficiency during puberty could contribute to the improvement of bone health in this vulnerable patient group.

Direct interhemispheric cortical communication via thalamic commissures: a new white-matter pathway in the primate brain.

Cortical neurons of eutherian mammals project to the contralateral hemisphere, crossing the midline primarily via the corpus callosum and the anterior, posterior, and hippocampal commissures. We recently reported an additional commissural pathway in rodents, termed the thalamic commissures (TCs), as another interhemispheric axonal fiber pathway that connects cortex to the contralateral thalamus. Here, we demonstrate that TCs also exist in primates and characterize the connectivity of these pathways with high-resolution diffusion-weighted magnetic resonance imaging, viral axonal tracing, and functional MRI. We present evidence of TCs in both New World (Callithrix jacchus and Cebus apella) and Old World primates (Macaca mulatta). Further, like rodents, we show that the TCs in primates develop during the embryonic period, forming anatomical and functionally active connections of the cortex with the contralateral thalamus. We also searched for TCs in the human brain, showing their presence in humans with brain malformations, although we could not identify TCs in healthy subjects. These results pose the TCs as an important fiber pathway in the primate brain, allowing for more robust interhemispheric connectivity and synchrony and serving as an alternative commissural route in developmental brain malformations.

Finding the most suitable puncture site for intraosseous access in term and preterm neonates: an ultrasound-based anatomical pilot study.

The purpose of this prospective ultrasound-based pilot study was to identify the most suitable tibial puncture site for intraosseous (IO) access in term and preterm neonates, describe tibial dimensions at this site, and provide anatomical landmarks for rapid localization. We measured the tibial dimensions and distances to anatomical landmarks at puncture sites A (proximal: 10 mm distal to the tibial tuberosity; distal: 10 mm proximal to the malleolus medialis) and B (chosen by palpation of the pediatrician), in 40 newborns in four weight groups (< 1000 g; 1000-2000 g, 2000-3000 g, and 3000-4000 g). Sites were rejected if they fell short of the assumed safety distance to the tibial growth plate of 10 mm. If both A and B were rejected, puncture site C was determined sonographically at the maximum tibial diameter while maintaining the safety distance. Puncture site A violated the safety distance in 53% and 85% (proximally and distally, respectively) and puncture site B in 38% and 33%. In newborns weighing 3000-4000 g, at median (IQR), the most suitable puncture site at the proximal tibia was 13.0 mm (12.0-15.8) distal to the tuberosity and 6.0 mm (4.0-8.0) medial to the anterior rim of the tibia. The median (IQR) diameters at this site were 8.3 mm (7.9-9.1) (transverse) and 9.2 mm (8.9-9.8) (anterior-posterior). The diameters increased significantly with increasing weight.  Conclusion: This study adds concise, practical information on the implementation of IO access in neonatal patients: the tibial dimensions in newborns in four different weight groups and initial data on anatomical landmarks to easily locate the IO puncture site. The results may help implement IO access in newborns more safely. What is Known: • Intraosseous access is a feasible option for emergency administration of vital drugs and fluids in newborns undergoing resuscitation when an umbilical venous catheter is impossible to place. • Severe complications of IO access due to malpositioned IO needles have been reported in neonates. What is New: • This study reports the most suitable tibial puncture sites for IO access and the tibial dimensions, in newborns of four weight groups. • The results can help to implement safe IO access in newborns.

Feasibility of aluminum phantom radiography for osteoporosis detection in postmenopausal women with a fragility fracture of the distal radius compared to DXA and HR-pQCT.

Recently, promising results have been reported for detection of osteoporosis with use of an aluminum phantom. Therefore, the aim of this study was to evaluate the feasibility of radiography-based bone mineral density (BMD) measurement using a graded aluminum phantom. This study included 27 postmenopausal women with a distal radius fracture. Aluminum phantom radiography of the healthy radius was conducted as well as high-resolution peripheral quantitative computed tomography (HR-pQCT) measurement of the ultradistal radius and dual energy X-ray absorptiometry (DXA) of the radius, spine, and hip. A strong correlation was observed between aluminum phantom radiography-based mean gray value (mGV) and DXA-derived BMD, especially for the ultradistal radius (ρ = 0.75; p < 0.001). A moderate correlation for the femoral neck (ρ = 0.61 and p < 0.001) between modalities was found. Radius mGV and HR-pQCT-derived BMD only showed a moderate correlation (ρ = 0.48; p < 0.09). Aluminum phantom radiography might serve as a cost efficient, highly available, low-radiation dose screening, and diagnostic method for osteoporosis additively to DXA measurements. Especially, an application in areas with constrained DXA availability and such as preoperative trauma settings would be beneficial. However, further investigation and assessment of specificity and sensitivity is needed.

Realistic 3D printed CT imaging tumor phantoms for validation of image processing algorithms.

Medical imaging phantoms are widely used for validation and verification of imaging systems and algorithms in surgical guidance and radiation oncology procedures. Especially, for the performance evaluation of new algorithms in the field of medical imaging, manufactured phantoms need to replicate specific properties of the human body, e.g., tissue morphology and radiological properties. Additive manufacturing (AM) technology provides an inexpensive opportunity for accurate anatomical replication with customization capabilities. In this study, we proposed a simple and cheap protocol using Fused Deposition Modeling (FDM) technology to manufacture realistic tumor phantoms based on the filament 3D printing technology. Tumor phantoms with both homogenous and heterogeneous radiodensity were fabricated. The radiodensity similarity between the printed tumor models and real tumor data from CT images of lung cancer patients was evaluated. Additionally, it was investigated whether a heterogeneity in the 3D printed tumor phantoms as observed in the tumor patient data had an influence on the validation of image registration algorithms. A radiodensity range between -217 to 226 HUs was achieved for 3D printed phantoms using different filament materials; this range of radiation attenuation is also observed in the human lung tumor tissue. The resulted HU range could serve as a lookup-table for researchers and phantom manufactures to create realistic CT tumor phantoms with the desired range of radiodensities. The 3D printed tumor phantoms also precisely replicated real lung tumor patient data regarding morphology and could also include life-like heterogeneity of the radiodensity inside the tumor models. An influence of the heterogeneity on accuracy and robustness of the image registration algorithms was not found.

Treatment of benign bone lesions with an injectable biphasic bone substitute.

BACKGROUND: Injectable biphasic ceramic bone substitutes (BCBSs) represent a modern alternative to conventional options for bone defect filling, as they further open the possibilities for percutaneous cavity reconstruction. Although recent studies have shown good surgical outcomes after treatment with BCBSs, mid-term follow-up data are still missing. PATIENTS AND METHODS: Between 2013 and 2017, 18 patients were [1] treated with BCBS [2] for benign bone lesions and [3] had a complete set of retrospective information, including surgical protocols, imaging, patient dismission letters and outpatient clinic protocols, [4] with a minimum follow-up time of one year. Eleven patients received percutaneous surgery, while 7 patients had open curettage and BCBS filling. The median follow-up time was 36.5 (range 12-80) months. RESULTS: Local recurrence was reported in four patients. A distinctive bone remodelling pattern was noted on follow-up X-ray and magnetic resonance imaging showing a double-line phenomenon and continuously increasing cortical thickness one year after treatment in nine of thirteen patients. Regarding surgical complications, one patient suffered from a septic complication that required BCBS removal and lavage. One patient experienced superficial surgical site inflammation with redness and swelling, while two other patients had prolonged wound secretion. CONCLUSION: In a limited case series, the studied BCBS demonstrated acceptable surgical outcomes. Initial wound leakage and recurrence seemed to be associated with percutaneous injection. Further studies are needed to compare recurrence and bone graft resorption after open and percutaneous bone cyst surgeries and to further evaluate postoperative surgical site inflammation, which appears self-limiting in most cases.

High-Resolution Transperineal Ultrasound in Anorectal Malformations-Can We Replace the Distal Colostogram?

Introduction Anorectal malformations (ARM) affect 1 in 5,000 newborns with a wide range of defects. In the absence of a visible fistula, the diagnosis and classification of ARM require an augmented pressure distal colostogram. This procedure can be done after a diverting colostomy has been performed and implies exposing the child to radiation. We hypothesized that high-resolution transperineal ultrasound could correctly diagnose the type of ARM, thus sparing radiation exposure. Case Description Four full-term male newborns with ARM and no visible anal opening were referred to our center for further management. A diverting descendostomy was performed in the first 48 hours of life in all cases. Prior to the reconstructive surgery, we performed a high-resolution transperineal ultrasound with 3D tomographic reconstruction of the perineal region to assess the urethra, the rectum, and a possible fistula. Findings were compared with a conventional augmented pressure distal colostogram. The image acquisition was fast and did not cause any additional distress to the children. Conclusion In all cases the results of the distal colostogram nicely correlated with the high-resolution transperineal ultrasound with 3D tomographic reconstruction. In the future, we envision a time when it can potentially replace the distal colostogram in preoperative assessment of ARM with no distress and exposure to radiation.

Low muscle volume of the anal sphincter complex: A novel prognostic factor in children with anorectal malformations?

BACKGROUND/PURPOSE: The anal sphincter complex (ASC) plays a key role in continence and is often dysfunctional in infants born with anorectal malformations (ARM). The ASC is well depicted by magnetic resonance (MR) imaging but volumetric reference data are lacking in infants. Thus, we tested the feasibility of MR based ASC volumetry, collected reference data, and compared them with cases of favorableprognosis and unfavorable prognosis (as defined by the type of ARM). METHODS: We determined ASC volume on T2 weighted MR images of seventy six infants (ARM n = 33; controls n = 43) by manual segmentation. Inter operator agreement was assessed by intraclass correlation coefficient. Linear regression was used to establish weight dependent reference data. Observed to expected ASC volumes of patients with unfavorable and favorable prognosis were compared (unpaired t test). RESULTS: ASC volumetry was feasible in all cases. Patients with ARM had low 'observed to expected' ASC volume ( 18.1%; p = 0.006). 'Observed to expected' ASC volume differed significantly between patients with favorableand unfavorable prognosis (p < 0.001). CONCLUSION: We confirmed the feasibility of MRI based ASC volumetry and provided initial reference data for infants. Although ASC volumes were lowest in infants with ARM of unfavorable prognosis for fecal continence, the value of ASC volume as prognostic parameter remains to be determined.

Expanding the Phenotype of the FAM149B1-Related Ciliopathy and Identification of Three Neurogenetic Disorders in a Single Family.

Biallelic truncating FAM149B1 variants result in cilia dysfunction and have been reported in four infants with Joubert syndrome and orofaciodigital syndrome type VI, respectively. We report here on three adult siblings, 18 to 40 years of age, homozygous for the known FAM149B1 c.354_357delinsCACTC (p.Gln118Hisfs*20) variant. Detailed clinical examinations were performed including ocular and gait analyses, skeletal- and neuroimaging. All three patients presented with neurological and oculomotor symptoms since birth and mild skeletal dysplasia in infancy resulting in characteristic gait abnormalities. We document mild skeletal dysplasia, abnormal gait with increased hip rotation and increased external foot rotation, ataxia, variable polydactyly, ocular Duane syndrome, progressive ophthalmoplegia, nystagmus, situs inversus of the retinal vessels, olfactory bulb aplasia, and corpus callosal dysgenesis as novel features in FAM149B1-ciliopathy. We show that intellectual disability is mild to moderate and retinal, renal and liver function is normal in these affected adults. Our study thus expands the FAM149B1-related Joubert syndrome to a mainly neurological and skeletal ciliopathy phenotype with predominant oculomotor dysfunction but otherwise stable outcome in adults. Diagnosis of FAM149B1-related disorder was impeded by segregation of multiple neurogenetic disorders in the same family, highlighting the importance of extended clinical and genetic studies in families with complex phenotypes.

Lethal Encephalopathy in an Infant with Hypophosphatasia despite Enzyme Replacement Therapy.

Hypophosphatasia (HPP) is an inborn error of metabolism caused by loss-of-function mutations in the biomineralization-associated alkaline phosphatase gene, encoding tissue-nonspecific alkaline phosphatase (TNSALP). Symptoms include skeletal hypomineralization and extra-skeletal manifestations such as pyridoxine (B6)-responsive seizures due to impaired cerebral B6 passage. Since the introduction of enzyme replacement therapy (ERT), skeletal manifestations and B6-responsive seizures were reported to improve significantly. Nevertheless, there is an increasing evidence of B6-independent neurological manifestation of HPP including HPP-associated encephalopathy. Here, we present for the first time the brain alterations of an infant with neonatal HPP who died of neurological complications at the age of 5 months despite early initiation of ERT. CSF analysis showed normal concentrations of biogenic amines reflecting sufficient intracellular B6 availability. Postmortem histopathology revealed severe, localized affection of the cerebral cortex including cortical lesions in layers 2 and 3 in direct proximity to TNSALP-expressing neurons and hippocampal sclerosis. Our findings confirm that TNSALP deficiency may lead to a severe encephalopathy. We hypothesize that HPP-associated encephalopathy resistant to currently available ERT may develop in addition and probably independently of typical B6-responsive seizures in some patients. Prospective, controlled studies with close neurological follow-up including brain imaging are needed to identify patients at risk for severe neurological symptoms despite ERT.

Is There an Association Between Bone Microarchitecture and Fracture in Patients who were Treated for High-grade Osteosarcoma? A Controlled Study at Long-term Follow-up Using High-resolution Peripheral Quantitative CT.

BACKGROUND: Neoadjuvant chemotherapy in patients with primary osteosarcoma improves survival rates, but it also causes side effects in various organs including bone. Low bone mineral density (BMD) can occur owing partly to chemotherapy or limited mobility. This can cause a higher risk of fractures compared with those who do not receive such treatment. Changes in BMD alone cannot explain the propensity of fractures. Studying microarchitectural changes of bone might help to understand the effect. QUESTIONS/PURPOSES: (1) Do patients who were treated for osteosarcoma (more than 20 years previously) have low BMD? (2) Do these patients experience more fractures than controls who do not have osteosarcoma? (3) What differences in bone microarchitecture are present between patients treated for high-grade osteosarcoma and individuals who have never had osteosarcoma? METHODS: We contacted 48 patients who were treated for osteosarcoma and who participated in an earlier study. These patients underwent multimodal treatment including chemotherapy more than 20 years ago. Of the original patient group, 60% (29 of 48) were missing, leaving 40% (19 of 48) available for inclusion in this study; all 19 agreed to participate. There were nine men and 10 women with a mean age of 46 ± 4 years and a mean time from surgery to examination of 28 ± 3 years. BMD was measured by dual-energy x-ray absorptiometry, and any fracture history was assessed using a questionnaire. Additionally, high-resolution peripheral quantitative CT was performed to compare the groups in terms of microarchitectural changes, such as cortical and trabecular area, cortical and trabecular thickness, cortical porosity, and endocortical perimeter. Participants in the control group were selected from a cohort consisting of a population-based random sample of 499 healthy adult women and men. Osteoporosis or low BMD was not an exclusion criterion for entering this study; however, the patients in the control group were selected based on a normal BMD (that is, T score > -1.0 at both the spine and hip). Also, the participants were matched based on age and sex. Differences between patients and controls were assessed using the Wilcoxon rank sum test for continuous variables and a chi-square test for categorical variables. A multiple regression analysis was performed. Model assumptions were checked using histograms and quantile-quantile plots of residuals. RESULTS: Twelve of 19 patients who were treated for osteosarcoma had either osteopenia (eight patients) or osteoporosis (four patients). More patients with osteosarcoma reported sustaining fractures (11 of 19 patients) than did control patients (2 of 19 controls; p < 0.001). Among all microarchitectural parameters, only the endocortical perimeter was increased in patients compared with the control group (75 ± 15 mm versus 62 ± 18 mm; p = 0.04); we found no differences between the groups in terms of cortical and trabecular area, cortical and trabecular thickness, or cortical porosity. CONCLUSION: Although patients who were treated for osteosarcoma had osteopenic or osteoporotic BMD and a higher proportion of patients experienced fractures than did patients in the control group, we could not confirm differences in microarchitectural parameters using high-resolution peripheral quantitative CT. Therefore, it seems that bone geometry and microstructural parameters are not likely the cause of the increased proportion of fractures observed in our patients who were treated for osteosarcoma. Until we learn more about the bone changes associated with chemotherapy in patients with osteosarcoma, we recommend that patients undergo regular BMD testing, and we recommend that physicians consider osteoporosis treatment in patients with low BMD. These data might provide the impetus for future multicenter prospective studies examining the association between chemotherapy and bone microarchitecture. LEVEL OF EVIDENCE: Level III, therapeutic study.

High Cardiovascular Risk in Older Men With Severe Peripheral Artery Calcification on High-Resolution Peripheral QCT Scans: The STRAMBO Study.

[Figure: see text].

Imaging of pediatric bone and growth disorders: Of diagnostic workhorses and new horizons.

Children and adolescents with bone and growth disorders require interdisciplinary care from various specialists including pediatric radiologists with a focus on musculoskeletal disorders. This article covers routine topics, differential diagnoses, and selected research imaging in children with osteogenesis imperfecta (OI), X­linked hypophosphatemic rickets (XLH), achondroplasia, and other bone and growth disorders from the standpoint of a tertiary referral center.