Functional characterization of variants found in Japanese patients with hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant form of vascular dysplasia. Genetic diagnosis is made by identifying loss-of-function variants in genes, such as ENG and ACVRL1. However, the causal mechanisms of various variants of unknown significance remains unclear. In this study, we analyzed 12 Japanese patients from 11 families who were clinically diagnosed with HHT. Sequencing analysis identified 11 distinct variants in ACVRL1 and ENG. Three of the 11 were truncating variants, leading to a definitive diagnosis, whereas the remaining eight were splice-site and missense variants that required functional analyses. In silico splicing analyses demonstrated that three variants, c.526-3C > G and c.598C > G in ACVRL1, and c.690-1G > A in ENG, caused aberrant splicing, as confirmed by a minigene assay. The five remaining missense variants were p.Arg67Gln, p.Ile256Asn, p.Leu285Pro, and p.Pro424Leu in ACVRL and p.Pro165His in ENG. Nanoluciferase-based bioluminescence analyses demonstrated that these ACVRL1 variants impaired cell membrane trafficking, resulting in the loss of bone morphogenetic protein 9 (BMP9) signal transduction. In contrast, the ENG mutation impaired BMP9 signaling despite normal cell membrane expression. The updated functional analysis methods performed in this study will facilitate effective genetic testing and appropriate medical care for patients with HHT.

Cerebellar peduncle damage in Langerhans cell histiocytosis-associated neurodegenerative disease revealed by diffusion tensor imaging.

PURPOSE: To confirm the hypothesis that brain white matter damage is involved in the pathogenesis and disease progression of Langerhans cell histiocytosis (LCH)-associated neurodegenerative disease (ND), we aimed to analyze pediatric patients with LCH using diffusion tensor imaging (DTI). METHODS: We enrolled 33 patients with LCH and obtained 33 DTI datasets. Using DTI-based tractography, fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD) were measured in the cerebral and cerebellar white matter tracts. The participants were divided into three groups-non-ND, ND without clinical symptoms (r-ND), and ND with clinical symptoms (c-ND)-according to their clinical status during the examination with DTI. We compared the DTI parameters in white matter tracts were compared among the three groups. RESULTS: In the order of non-ND, r-ND, and c-ND groups, the FA in superior cerebellar peduncle (SCP) and middle cerebellar peduncle (MCP) significantly decreased, the ADC, AD, and RD of MCP, and the RD of SCP were significantly elevated (FA-SCP; p < 0.001, FA-MCP; p = 0.026, ADC-MCP; p < 0.001, AD-MCP; p = 0.002, RD-MCP; p = 0.003, and RD-SCP; p = 0.018). Furthermore, in the simple linear regression analysis, the FA, ADC, AD, and RD values in the MCP and the FA value in the SCP were significantly influenced by the presence of neurological symptoms and ND findings on MRI (all p < 0.001). CONCLUSION: In LCH-ND, we identified microstructural damage in the SCP and MCP. DTI parameters in these tracts may help monitor LCH-ND; therefore, future studies are required to validate these results in a large cohort.

Assessment of mediastinal shift angles in congenital pulmonary airway malformation: a new fetal magnetic resonance imaging indicator of congenital lung disease.

BACKGROUND: The mediastinal shift angle is a new fetal magnetic resonance imaging (MRI) index that is reportedly correlated with postnatal survival in fetuses with congenital diaphragmatic hernia. However, its correlation in patients with congenital pulmonary airway malformation (CPAM) has not been assessed. OBJECTIVE: This study aimed to establish a normal range for the right/left mediastinal shift angles, to evaluate the mediastinal shift angle in fetuses with CPAM, to compare the mediastinal shift angle with the CPAM volume ratio, and to evaluate the predictive value of the mediastinal shift angle measurements. MATERIALS AND METHODS: To establish the normal range, we measured the mediastinal shift angle bilaterally in 124 fetuses without any lung abnormality (the control group). Subsequently, the mediastinal shift angle was measured in 32 fetuses pathologically diagnosed with CPAM. Moreover, the mediastinal shift angle and CPAM volume ratio were compared using fetal MRI. RESULTS: The mean values for the right/left mediastinal shift angles were 18.6°/26.3° and 39.2°/35.9° for control fetuses and fetuses with CPAM, respectively. The mediastinal shift angle and the CPAM volume ratio showed a positive statistical correlation. The area under the curve demonstrated high discriminatory accuracy for the mediastinal shift angle (0.76). CONCLUSION: The mediastinal shift angle has potential to replace the CPAM volume ratio for evaluating the severity of CPAM in fetal MRI.

Osteoid osteoma appearing after bony fracture in a girl with osteogenesis imperfecta.

Osteoid osteoma (OO) is a common, benign bone tumor. However, there are no case reports of OO associated with osteogenesis imperfecta (OI), or pathological fractures in OO. A 3-year-old girl with OI sustained a complete right tibial diaphyseal fracture. Bony fusion was completed after 4 months of conservative therapy; nevertheless, 18 months later spontaneous pain appeared at the fracture site, without any cause. Plain radiographs showed a newly apparent, rounded area of translucency 1 cm in diameter, just overlapping the previous fracture. Images obtained using three-dimensional time-resolved contrast-enhanced magnetic resonance angiography showed strong central enhancement in the early phase, with an apparent nidus, suggesting the diagnosis of OO. Nineteen months after the first fracture, while skipping, the patient refractured her tibial diaphysis at the site of the previous fracture. This is a very rare case of OO, apparently co-existing with OI and leading to a bony fracture. In our case, the combination of bone fragility in OI and a recent fracture at the site of the OO may have caused the re-fracture.

Value of parametric indexes to identify tracheal atresia with or without fistula on fetal magnetic resonance imaging.

BACKGROUND: Tracheal atresia causes some secondary changes (dilated trachea, flattened/inverted diaphragm, hyperintense and hyperinflated lungs). They can be reduced if a high airway fistula is present. OBJECTIVE: This study evaluated fetal MR images of tracheal atresia and the secondary changes, focusing on the presence of a fistula. MATERIALS AND METHODS: We assessed fetal MR images of tracheal atresia without fistula (n=4, median 26 weeks), tracheal atresia with fistula (n=4, median 33 weeks) and controls (n=30, median 32 weeks). We evaluated airway obstruction using true-positive rate in tracheal atresia and false-positive rate in controls indicating they are likely normal variants. Tracheal diameter, craniocaudal-anteroposterior ratio of the right hemidiaphragm, lung-to-liver signal intensity ratio, and cardiothoracic ratio were compared among the three groups using the Kruskal-Wallis test followed by pairwise comparison using the Mann-Whitney U test. RESULTS: True-positive rate was 100% in tracheal atresia, while false-positive rate was 20% in controls. The Kruskal-Wallis test showed differences among groups in craniocaudal-anteroposterior ratio and cardiothoracic ratio (P<0.001) but not in tracheal diameter (P=0.256) or lung-to-liver signal intensity ratio (P=0.082). The pairwise comparison in craniocaudal-anteroposterior ratio and cardiothoracic ratio showed differences between controls and tracheal atresia without fistula (P<0.01) and with fistula (P<0.05). CONCLUSION: Fetal MRI is useful for the diagnosis of tracheal atresia, and detection of airway obstruction is essential. Lower craniocaudal-anteroposterior ratio and cardiothoracic ratio might be reliable measures even if a fistula is present.

Acute hematogenous pelvic osteomyelitis: appropriate timing for magnetic resonance imaging.

BACKGROUND: The precise time of appearance of bone marrow edema in acute hematogenous pelvic osteomyelitis (AHPO) is unknown. The purpose of the present research is to clarify the time of appearance of bone marrow edema on magnetic resonance imaging (MRI) in AHPO. Our hypothesis was that onset is slower than in long-bone osteomyelitis. METHODS: We selected 12 patients (mean, 11.8 years) with MRI findings and clinical diagnosis of AHPO. The signal ratios of bone marrow (BM) and gluteus maximus muscle (M, BM/M ratio) in fat-suppressed T2- and T1-weighted images (T2WI, T1WI) were calculated to evaluate changes in bone-marrow signals. The correlation between BM/M ratios and days from onset was evaluated statistically and compared with lower extremity osteomyelitis. RESULTS: Bone marrow/M ratio of T2WI increased over time after the onset of the primary symptom in all patients and showed a statistically positive correlation (r = 0.36). In seven patients in whom an MRI scan was conducted twice, all showed higher values for the second MRI, and changes were more pronounced over time. The mean BM/M ratio of T2WI was 4.1 when 7 days or less had elapsed from the primary symptom, and 6.4 when more than 7 days had elapsed. The BM/M ratios in the sacroiliac joint group were lower than in the non-sacroiliac joint group. CONCLUSIONS: Unlike long-bone osteomyelitis, it took 1 week before findings for AHPO became fully evident. A definitive diagnosis can be made in patients with suspected sacroiliitis by performing a further MRI scan at 7 days or later.

Mediastinal and hilar soft tissue mass-like lesions in congenital unilateral pulmonary vein atresia: A retrospective review of seven pediatric patients.

BACKGROUND: Congenital unilateral pulmonary vein atresia (CUPVA) is known to lead to the formation of an abnormal confluent mediastinal and hilar soft tissue mass, thoracic hypoplasia, and interlobular septal thickening on the affected side. The purpose of the present study is to investigate the frequency and severity of mediastinal soft tissue mass-like lesions and examine other abnormal findings associated with CUPVA. METHODS: We retrospectively reviewed seven children with CUPVA who underwent contrast-enhanced CT scans and measured the soft tissue mass volume in the bilateral mediastinum (affected and normal side). The location of abnormal soft tissue was divided into three anatomical sections (paratracheal, peribronchial, and the dorsal aspect of the left atrium). The relationships among soft tissue volume and anatomical section were statistically evaluated. Also, the presence of thoracic hypoplasia, small ipsilateral pulmonary arteries, interlobular septal thickening, and ground-glass opacities were investigated. RESULTS: In all cases, CT scans confirmed the presence of confluent soft tissue mass-like lesions in the affected mediastinum. The soft tissue volume on the affected side was 5.5-fold greater than the volume on the normal side (average: 18.0 cm3 and 4.25 cm3 respectively, P < 0.01). Thoracic hypoplasia and interlobular septal thickening were found in all patients. Small pulmonary arteries and ground-glass opacities were present in six of the seven patients. CONCLUSION: Abnormal mediastinal and hilar soft tissue is commonly found in patients with CUPVA. So, if we encounter the mediastinal soft tissue mass in patients with CUPVA, no further test will be indicated.

Osteomyelitis of a sacral neurocentral synchondrosis: a case report of another metaphyseal equivalent.

Pelvic osteomyelitis may occur in a metaphyseal equivalent, defined as a portion of flat or irregular bone that is adjacent to cartilage. The pelvic bone is known to have several metaphyseal equivalents and of these, the sacroiliac joint is the most frequent site of involvement. However, a sacral neurocentral synchondrosis has not been recognized as a metaphyseal equivalent, and there have been no previous reports describing this as the site of origin of sacral osteomyelitis. We here report two cases of sacral osteomyelitis originating in a neurocentral synchondrosis, another metaphyseal equivalent. We, as pediatric radiologists, should recognize a sacral neurocentral synchondrosis as another metaphyseal equivalent, especially in infants and younger patients.

Apparent diffusion coefficient of intracranial germ cell tumors.

The role of diffusion weighted imaging and apparent diffusion coefficient in intracranial germ cell tumors has not been fully elucidated. The aim of this study was to evaluate whether the ADC correlates with the histologic subtypes of germ cell tumors. We also aimed to investigate whether the ADC values can predict treatment response. The authors retrospectively analyzed the ADC values of the enhancing and solid regions of germ cell tumors. The absolute ADC values and the normalized ADC values were compared among different histologic diagnoses. The ADC values before and after the first course of chemotherapy were also compared between the different prognostic groups. Ten patients were included in the study. The median age at diagnosis was 9.3 years (range 5.3-13.8 years). There were four patients with germinoma and six patients with nongerminomatous germ cell tumor (NGGCT) including five mixed germ cell tumors and one immature teratoma. The mean absolute and normalized ADC values (×10(-3) mm(2)/s) were significantly lower in germinomas [0.835 ± 0.065 (standard deviation) and 1.11 ± 0.096, respectively] than in NGGCTs (1.271 ± 0.145 and 1.703 ± 0.223, respectively) (p = 0.01). The ADC values before and after the first course of chemotherapy were available in four patients. The ADC value after the first chemotherapy had a tendency to increase more in patients who eventually demonstrated complete response with chemotherapy than in patients who required second-look surgery. Assessment of the ADC values of germ cell tumors is considered to facilitate differentiation of histological subtypes of germ cell tumors. Evaluation of the ADC may also be useful for predicting treatment response.

Nanofibrillar chitin aerogels as renewable base catalysts.

We demonstrate the fabrication of chitin nanofibril aerogels and their successful application as base catalysts for the production of useful chemicals. Squid-pen chitin nanofibrils (ChNF) with primary C2-amine groups on their crystalline surfaces were fabricated into highly porous aerogels with high specific surface areas up to 289 m(2) g(-1) using freeze-drying or a supercritical drying process. The prepared ChNF aerogel was used in the aqueous Knoevenagel-condensation reaction and acted as a highly efficient base catalyst, suggesting that the combination of the nanofibrous aerogel structure and primary C2-amines exposed on the crystalline ChNF surface was effective for continuous flow catalysis. Because the ChNF aerogel can be easily prepared from abundant and renewable chitin present in nature, this strategy is a gateway to promoting and conducting green and sustainable chemistry.

Outcomes of five cases of retinoblastoma with optic nerve invasion on imaging.

PURPOSE: To investigate the timing of enucleation, treatment course, and outcome for retinoblastoma (RB) with optic nerve (ON) invasion on imaging. STUDY DESIGN: Retrospective clinical study. METHODS: Of the 160 patients with RB who presented to the National Center for Child Health and Development in Japan between 2005 and 2022, ON invasion on imaging at the initial presentation was seen in five patients. The clinical, computed tomography (CT), and magnetic resonance imaging (MRI) findings, and treatment courses were reviewed retrospectively. RESULTS: MRI showed ON invasion in all five patients (three with unilateral RB, 2 with bilateral RB); in two patients CT detected no invasion. Enucleation was performed in four patients, three of whom underwent neoadjuvant therapy and one had a positive ON resection margin following the enucleation as initial treatment. One patient did not undergo enucleation due to cerebrospinal fluid dissemination. All enucleated patients underwent adjuvant chemotherapy. Four patients underwent radiotherapy. During follow-up (mean, 89.4 months), four patients survived and one died. CONCLUSION: MRI is recommended to evaluate ON invasion and determine the timing of enucleation for RB. The appropriate choice of neoadjuvant or adjuvant therapy would be helpful to avoid radiotherapy for RB with ON invasion on imaging.

Syndromes associated with vascular tumors and malformations: a pictorial review.

Use of the International Society for the Study of Vascular Anomalies (ISSVA) classification system has been strongly recommended in recent years because of the need for separate therapeutic measures for patients with vascular tumors and malformations. In the ISSVA classification system, vascular tumors, which are neoplastic, are distinguished from vascular malformations, which are caused by vascular structural anomalies and are not neoplastic, on the basis of the presence or absence of neoplastic proliferation of vascular endothelial cells. It is important that radiologists be familiar with the development, diagnosis, and treatment of vascular tumors and malformations, especially the imaging features of low- and high-flow vascular malformations. Some vascular tumors and malformations develop in isolation, whereas others develop within the phenotype of a syndrome. Syndromes that are associated with vascular tumors include PHACE syndrome. Syndromes that are associated with vascular malformations include Sturge-Weber, Klippel-Trénaunay, Proteus, blue rubber bleb nevus, Maffucci, and Gorham-Stout syndromes, all of which demonstrate low flow, and Rendu-Osler-Weber, Cobb, Wyburn-Mason, and Parkes Weber syndromes, all of which demonstrate high flow. Because imaging findings may help identify such syndromes as systemic, it is important that radiologists familiarize themselves with these conditions.

"Another inchworm sign" on dynamic contrast-enhanced magnetic resonance imaging in pediatric patients with cystitis cystica and glandularis: Radiologic-pathologic correlation.

Cystitis cystica and glandularis is a hyperproliferative disease of the urothelium, and may form a papillary or polypoid mass. Clinically, these mass lesions are often difficult to distinguish from malignant tumors. We present a pediatric patient of cystitis cystica and glandularis with a bladder mass and discuss dynamic contrast-enhanced magnetic resonance imaging (MRI) findings and histopathological profiles, which have not been previously explored in the literature. Dynamic contrast-enhanced MRI showed unique, superficial, strong enhancement that resembles an inchworm in appearance. The term "inchworm sign" is a characteristic finding on diffusion-weighted MRI, proposed as a criterion for T-staging in non-muscle-invasive bladder cancer. We would like to propose another "inchworm sign" on dynamic contrast-enhanced MRI as a new hallmark of cystitis cystica and glandularis, which may differentiate it from a malignant tumor.

Evaluation of radiation dose reduction in head CT using the half-dose method.

PURPOSE: The present study introduced the half-dose method (HDM), which halves the radiation dose for conventional head computed tomography (CT), for postoperative hydrocephalus and follow-up for craniosynostosis at a children's hospital. This study aimed to evaluate the contribution of selective head CT scanning optimization towards the overall reduction of radiation exposure. MATERIALS AND METHODS: We retrospectively assessed 1227 and 1352 head CT examinations acquired before and after the introduction of the HDM, respectively, in children aged 0-15 years. The radiation exposure was evaluated using the CT dose index volume (CTDI-vol), dose-length product (DLP), rate of HDM introduction, and effect of reducing in-hospital radiation dose before and after the introduction of the HDM. For an objective evaluation of the image quality, head CT scans acquired with HDM and full-dose method (FDM) were randomly selected, and the image noise standard deviation (SD) was measured for each scan. In addition, some HDM images were randomly selected and independently reviewed by two radiologists. RESULTS: The HDM was introduced in 27.9% of all head CTs. The mean CTDI-vol of all head CTs was 21.5 ± 6.9 mGy after the introduction, a 14.9% reduction. The mean DLP was 418.4 ± 152.9 mGy.cm after the introduction, a 17.2% reduction. Compared to the FDM images, the noise SD of the HDM ones worsened by almost 0.9; however, none of the images were difficult or impossible to evaluate. CONCLUSION: The HDM yielded diagnostically acceptable images. In addition, a change in protocol for only two diseases successfully reduced the patients' overall radiation exposure by approximately 15%. Introducing and optimizing the HDM for frequently performed target diseases will be useful in reducing the exposure dose for the hospital's patient population.

Central-variant posterior reversible encephalopathy syndrome in an infant with mid-aortic syndrome: A rare case of symmetric basal ganglia lesions.

Central-variant posterior reversible encephalopathy syndrome is an atypical subtype of posterior reversible encephalopathy syndrome that occurs during rapid fluctuations in blood pressure, leading to cerebrovascular autoregulatory failure and endothelial dysfunction. Few reports have described posterior reversible encephalopathy syndrome in infants. A 4-month-old girl, who was diagnosed a month before with hypoxic ischemic encephalopathy due to sudden cardiac arrest, showed persistent renovascular hypertension with a systolic blood pressure of 200 mmHg. Computed tomography of the head revealed a new-onset low-attenuation area in the bilateral basal ganglia, and computed tomography of the trunk revealed severe long-segment narrowing of the abdominal aorta encompassing the bilateral renal arteries. She was treated with antihypertensive drugs and peritoneal dialysis. Follow-up imaging after blood pressure stabilization showed resolution of the low-attenuation area in the bilateral basal ganglia. We diagnosed her basal ganglia lesions as central-variant posterior reversible encephalopathy syndrome. She suffered from neurological sequelae attributable to hypoxic ischemic encephalopathy but showed no evidence of basal ganglia dysfunction. Here, we report a case of infantile central-variant posterior reversible encephalopathy syndrome involving bilateral basal ganglia lesions with mid-aortic syndrome. The differential diagnosis of infantile symmetric bilateral basal ganglia lesions is broad and includes genetic, acquired metabolic or toxic, infectious, inflammatory, vascular, and neoplastic pathologies. Among them, central-variant posterior reversible encephalopathy syndrome is rare but important because neurological prognosis may be favorable, and specific treatment, such as administration of antihypertensive drugs or discontinuation of drugs that induce posterior reversible encephalopathy syndrome, is possible.

Predisposing conditions for bacterial meningitis in children: what radiologists need to know.

A variety of underlying diseases can predispose infants and children to bacterial meningitis (BM). For the diagnosis, treatment, and prevention of its recurrence, radiologists should be familiar with its predisposing conditions so that they can suggest the appropriate imaging approach. Predisposing conditions of BM can be broadly classified into two categories: infection spread from the adjacent tissue to the cerebrospinal fluid (CSF) space and immunodeficiency. Diseases in the former category are further divided according to regardless of whether there is a structural defect between the CSF space and the adjacent tissue. When a structural defect is suspected in a patient with BM, computed tomography (CT) of the head and magnetic resonance (MR) imaging are first-line imaging examinations. Radionuclide cisternography should be implemented as a second-line step to identify the CSF leak site. In patients with suspected parameningeal infection without any structural defect, such as sinusitis or otitis media/mastoiditis, CT or MR images can identify not only the disease itself but also the associated intracranial complications. The purpose of this article is to discuss the diagnostic approach and imaging findings associated with the variety of conditions predisposing patients to recurrent BM, focusing on the role of radiology in their management.