Validation of genomic and transcriptomic models of homologous recombination deficiency in a real-world pan-cancer cohort.

BACKGROUND: With the introduction of DNA-damaging therapies into standard of care cancer treatment, there is a growing need for predictive diagnostics assessing homologous recombination deficiency (HRD) status across tumor types. Following the strong clinical evidence for the utility of DNA-sequencing-based HRD testing in ovarian cancer, and growing evidence in breast cancer, we present analytical validation of the Tempus HRD-DNA test. We further developed, validated, and explored the Tempus HRD-RNA model, which uses gene expression data from 16,750 RNA-seq samples to predict HRD status from formalin-fixed paraffin-embedded tumor samples across numerous cancer types. METHODS: Genomic and transcriptomic profiling was performed using next-generation sequencing from Tempus xT, Tempus xO, Tempus xE, Tempus RS, and Tempus RS.v2 assays on 48,843 samples. Samples were labeled based on their BRCA1, BRCA2 and selected Homologous Recombination Repair pathway gene (CDK12, PALB2, RAD51B, RAD51C, RAD51D) mutational status to train and validate HRD-DNA, a genome-wide loss-of-heterozygosity biomarker, and HRD-RNA, a logistic regression model trained on gene expression. RESULTS: In a sample of 2058 breast and 1216 ovarian tumors, BRCA status was predicted by HRD-DNA with F1-scores of 0.98 and 0.96, respectively. Across an independent set of 1363 samples across solid tumor types, the HRD-RNA model was predictive of BRCA status in prostate, pancreatic, and non-small cell lung cancer, with F1-scores of 0.88, 0.69, and 0.62, respectively. CONCLUSIONS: We predict HRD-positive patients across many cancer types and believe both HRD models may generalize to other mechanisms of HRD outside of BRCA loss. HRD-RNA complements DNA-based HRD detection methods, especially for indications with low prevalence of BRCA alterations.

Traumatic injury to the unfused anterior arch of C1 in the setting of bipartite atlas.

We present a case of a pediatric patient with congenital unfused anterior and posterior arches of the atlas (C1), also known as bipartite atlas, who sustained a traumatic injury during gymnastics. A computed tomography (CT) scan of the cervical spine raised concern for abnormal separation of the midline cleft of the anterior arch of C1. Subsequent magnetic resonance imaging (MRI) showed focal, edema-like signal in the midline cleft of C1. She was advised by neurosurgery to remain in a hard cervical collar for 6 weeks. She recovered after conservative treatment and returned to gymnastics. This case shows that a congenital unfused anterior arch of the atlas identified on CT after cervical trauma should not always be interpreted as an incidental finding. If a superimposed injury is suspected, MRI helps evaluate for traumatic injury, particularly if it is associated with upper cervical pain and tenderness or pain with neck movements. An additional case reiterates our findings.

Optimization of Pediatric Body CT Angiography: What Radiologists Need to Know.

OBJECTIVE. Pediatric CT angiography (CTA) presents unique challenges compared with adult CTA. Because of the ionizing radiation exposure, CTA should be used judiciously in children. The pearls offered here are observations gleaned from the authors' experience in the use of pediatric CTA. We also present some potential follies to be avoided. CONCLUSION. Understanding the underlying principles and paying meticulous attention to detail can substantially optimize dose and improve the diagnostic quality of pediatric CTA.

Applications of Pediatric Body CT Angiography: What Radiologists Need to Know.

OBJECTIVE. Pediatric CT angiography (CTA) can be useful for assessing numerous congenital and acquired disorders. This article discusses common pediatric applications of thoracoabdominal CTA, including for congenital pulmonary airway malformation, sequestration, vascular rings, aortic coarctation, pulmonary embolism, nontraumatic hemorrhage, abdominal transplant evaluation, and several vascular disorders, and highlights key clinical and imaging features. CONCLUSION. With appropriate use, CTA can play a fundamental role in diagnostic and preprocedural assessment in a variety of pediatric conditions.

Pediatric fibrocartilaginous embolism inducing paralysis.

BACKGROUND: Fibrocartilaginous embolism (FCE) is a rare cause of pediatric ischemic myelopathy. The pathology is thought to result from fragmentation with embolization into the microvasculature of the radicular artery often secondary to high axial force. While most cases arise in the setting of vigorous activity, our case reveals that FCE can also occur during relative physical inactivity. Additionally, while a majority of cases are associated with neck or back pain, our case also reveals that FCE can present without concurrent pain episodes. We describe a rare case of spinal cord infarction (SCI) likely due to FCE in a 14 year old male. Our patient was sitting with his feet elevated, playing a video game, when he developed sudden difficulty moving his arms. Initially presenting with a negative MRI scan and la belle indifference, our patient was suspected to exhibit functional quadraparesis secondary to psychosomatization/adjustment disorder. Repeat MR imaging 7 days later revealed typical findings for FCE with SCI (irregular, pencil-like T2 hyperintensity in the ventral cervical/upper thoracic cord and owl's eye pattern on axial images). Six months later, the diagnosis of FCE remains predominant. Our patient continues to improve with occupational and physical therapy. Ambulatory efforts and bladder function continue to progress. To improve functional gains, the patient is being considered for a chemodenervation procedure. CONCLUSION: Our case reveals that FCE can occur during physical inactivity and present without concurrent pain. Outcome regarding pediatric fibrocartilaginous embolism is highly variant; however, the two largest outcomes reported were either patient death or discharge.

A primer for pediatric radiologists on infection control in an era of COVID-19.

Pediatric radiology departments across the globe face unique challenges in the midst of the current COVID-19 pandemic that have not been addressed in professional guidelines. Providing a safe environment for personnel while continuing to deliver optimal care to patients is feasible when abiding by fundamental recommendations. In this article, we review current infection control practices across the multiple pediatric institutions represented on the Society for Pediatric Radiology (SPR) Quality and Safety committee. We discuss the routes of infectious transmission and appropriate transmission-based precautions, in addition to exploring strategies to optimize personal protective equipment (PPE) supplies. This work serves as a summary of current evidence-based recommendations for infection control, and current best practices specific to pediatric radiologists.

Practical considerations for establishing and maintaining a magnetic resonance imaging safety program in a pediatric practice.

Magnetic resonance imaging is a multipurpose imaging modality that is largely safe, given the lack of ionizing radiation. However there are electromagnetic and biological effects on human tissue when exposed to magnetic environments, and hence there is a risk of adverse events occurring with these exams. It is imperative to understand these risks and develop methods to minimize them and prevent consequent adverse events. Implementing these safety practices in pediatric MR imaging has been somewhat limited because of gaps in information and knowledge among the personnel who are closely involved in the MR environment. The American College of Radiology has provided guidelines on MR safety practices that are helpful in minimizing such adverse events. This article provides an overview of the issues related to MR safety and practical ways to implement them across different health care facilities.

Survey of peer review programs among pediatric radiologists: report from the SPR Quality and Safety Committee.

During the last 15 years, peer review has been widely incorporated into radiology quality improvement programs. However, current implementations are variable and carry concerns, including subjectivity of numerical scores and a sense of merely satisfying regulatory requirements. The Society for Pediatric Radiology (SPR) Quality and Safety Committee sought to evaluate the state of peer review programs in pediatric radiology practices, including implementation methods, perceived functions, strengths and weaknesses, and opportunities for improvement. We distributed an online 16-question survey to SPR members. Questions pertained to the type of peer review system, the use of numerical scores and comments, how feedback on discordances is given and received, and the use of peer learning conferences. We collected 219 responses (15% of survey invitations), 80% of which were from children's hospitals. Fifty percent of respondents said they use a picture archiving and communication system (PACS)-integrated peer review system. Comment-enhanced feedback for interpretive discordances was either very important or somewhat important to performance improvement in 86% of responses, compared to 48% with a similar perception of numerical scores. Sixty-eight percent of respondents said they either rarely or never check their numerical scores, and 82% either strongly or somewhat agreed that comments are more effective feedback than numerical scores. Ninety-three percent either strongly or somewhat agreed that peer learning conferences would be beneficial to their practice. Forty-eight percent thought that their current peer review system should be modified. Survey results demonstrate that peer review systems in pediatric radiology practices are implemented variably, and nearly half of respondents believe their systems should be modified. Most respondents prefer feedback in the form of comments and peer learning conferences, which are thought to be more beneficial for performance improvement than numerical scores.

Non-Catheter-related Venous Thromboembolism in Children: Imaging Review from Head to Toe.

Non-catheter-related venous thromboembolism (VTE) is less common in children than in adults. Although the presence of a central venous catheter is the most common cause of venous thrombosis in children, infection and inflammation, malignancy, hypercoagulability, dehydration, and certain sites of normal variant and pathologic anatomic narrowing all predispose to VTE in children. The mortality and morbidity of VTE vary according to the underlying cause, including whether malignancy is present. Various modalities including ultrasonography (US), computed tomography, and magnetic resonance imaging can be used to image VTE, with some modalities better suited to particular parts of the body and clinical scenarios than others. When feasible, US is the initial test of choice for the diagnosis of VTE. US findings of acute VTE include a dilated noncompressible vein, intraluminal echoes, lack of color flow, and abnormal spectral venous waveforms. Serial US examinations are useful for monitoring patient response to therapy; a normal compressible vein will be seen after complete resolution of thrombus, and chronic venous changes including wall thickening, intraluminal webs, and phleboliths, which are readily apparent at US. Accurate and timely diagnosis of VTE must take into account the various advantages and disadvantages of each modality including speed, accuracy, availability, exposure to ionizing radiation, and need for sedation, as well as the clinical stability and transportability of the child. This article reviews some of the more common causes of VTE in children (other than those related to a central venous catheter) according to body part and discusses the associated imaging findings. ©RSNA, 2017.

Sonographic spinal imaging of normal anatomy, pathology and magnetic growing rods in children.

The wide availability of ultrasound, along with its lack of ionizing radiation burden and need for sedation for most exams, often make sonography the first line in the imaging evaluation of children. The developing osseous anatomy of the spine in young infants provides a distinct window allowing for a detailed depiction of the spinal canal and its contents, which is not present in older children or adults. Here we review the clinical indications, sonographic technique, normal anatomy and pathology for imaging the lumbosacral spine in neonates and young infants. Additionally, we review the procedure for ultrasound assessment of the lengthening of magnetically controlled growing spinal rods, which allows orthopedists and radiologists to evaluate the effectiveness of distraction procedures of this hardware without the use of ionizing radiation.

Imaging correlates of neural control of ocular movements.

The purpose of oculomotor movements is maintenance of clear images on the retina. Beyond this oversimplification, it requires several different types of ocular movements and reflexes to focus objects of interest to the fovea-the only portion of retina capable of sharp and clear vision. The different movements and reflexes that execute this task are the saccades, smooth pursuit movements, fixation, accommodation, and the optokinetic and vestibulo-ocular reflexes. Many different centres in the cerebrum, cerebellum, brainstem and thalami, control these movements via different pathways. At the outset, these mechanisms appear dauntingly complex to a radiologist. However, only a little effort could make it possible to understand these neural controls and empower the reading session. The following review on ocular movements and their neural control will enable radiologists and clinicians to correlate lesions with clinical deficits effectively without being swamped by exhaustive detail. Key Points • Knowledge of cortical and subcortical areas controlling ocular movements is important. • Understanding of neural control of ocular movements makes a good foundation. • Awareness of anatomic areas controlling ocular movements helps in clinico-radiologic correlation.

Early Detection by Ultrasound of Partial Hydatidiform Mole With a Coexistent Live Fetus.

INTRODUCTION: Twin pregnancy with hydatidiform mole and coexistent live fetus is a rare condition with severe maternal and fetal complications such as preeclampsia, vaginal bleeding, persistent gestational trophoblastic tumor, and fetal death. CASE PRESENTATION: We report a case of a twin pregnancy with histopathologically proven hydatidiform mole and a coexistent live fetus in a 30-year-old Indian woman diagnosed by first trimester ultrasound. DISCUSSION: Our case emphasizes the role of ultrasound in diagnosing this condition in early pregnancy. A succinct overview of etiological mechanisms, possible complications, and clinical management is provided. CONCLUSION: Ultrasound is an effective diagnostic tool to diagnose hydatidiform mole with coexistent live fetus. Early diagnosis of this condition is important for risk stratification and facilitates an informed decision by the patient whether to terminate the pregnancy or to continue until full term with close monitoring after delivery.

ACR Appropriateness Criteria® Urinary Tract Infection-Child: 2023 Update.

Urinary tract infection (UTI) is a frequent infection in childhood. The diagnosis is usually made by history and physical examination and confirmed by urine analysis. Cystitis is infection or inflammation confined to the bladder, whereas pyelonephritis is infection or inflammation of kidneys. Pyelonephritis can cause renal scarring, which is the most severe long-term sequela of UTI and can lead to accelerated nephrosclerosis, leading to hypertension and chronic renal failure. The role of imaging is to guide treatment by identifying patients who are at high risk to develop recurrent UTIs or renal scarring. This document provides initial imaging guidelines for children presenting with first febrile UTI with appropriate response to medical management, atypical or recurrent febrile UTI, and follow-up imaging for children with established vesicoureteral reflux. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Bronchogenic cyst in the intradiaphragmatic location.

Bronchogenic cysts are congenital foregut malformations thought to develop due to abnormal budding of tracheal diverticulumand proximal bronchial structures during embryologic development. The cyst is lined by ciliated pseudostratified columnar epithelium and the wall contains cartilage and layers of smooth muscle. These lesions most commonly are seen in the mediastinum, lung, or pleural spaces. The intradiaphragmatic location of the bronchogenic cyst rarely has been reported in the literature. We report the clinical presentation and computed tomography and magnetic resonance imaging findings in a pediatric patient who presented with left-sided chest pain and was found to have a mass in the region of the diaphragm.

Giant Mesenchymal Hepatic Hamartomas With Adrenal Involvement Precipitating Respiratory Failure: A Myxomatous Mystery in a Three-Month-Old.

The combination of placental mesenchymal dysplasia and hepatic mesenchymal hamartomas is an extremely rare finding. We present the case of a three-month-old female born at 35 weeks gestation with a history of placental mesenchymal dysplasia who presented with non-bilious, non-bloody emesis, and episodes of respiratory distress due to multiple enlarging abdominal cystic lesions. The patient's presentation was unique due to both liver and adrenal solid and cystic lesions. After extensive imaging and multiple biopsies, expert interpretation of biopsy tissue revealed hepatic mesenchymal hamartoma within the liver and the adrenal gland. To our knowledge, this is one of the few documented cases of unresectable hepatic mesenchymal hamartomas with adrenal involvement successfully undergoing a whole liver transplant.

Tethered Cord Syndrome: Role of Imaging Findings in Surgical Decision-Making.

For infants presenting with urinary problems or lower extremity weakness, imaging is ordered to investigate spinal pathology. Tethered cord syndrome (TCS) often manifests without conclusive anatomic evidence. In our case, a premature infant presented with urosepsis and was found to have an asymmetric gluteal crease and a sacral dimple. Renal ultrasound showed mild hydronephrosis, and a cystourethrogram revealed bilateral high-grade vesicoureteral reflux. Ultrasound and magnetic resonance imaging demonstrated a borderline low-lying spinal cord at the mid-L3 vertebral level. Urodynamic testing to confirm neurogenic bladder could not be completed on the first attempt due to urinary tract infection and on the second attempt due to instrument intolerance. Despite the lack of conclusive imaging evidence of a tethered cord, enough supportive clinical data was present to proceed with surgical intervention with the goal of preventing the progression of neurological dysfunction. Because TCS is ultimately a clinical diagnosis, appropriate management should not be discouraged by inconclusive or borderline imaging findings.

Developmental Abnormalities of the Pediatric Spine: A Review of the Correlation Between Ultrasound and MRI Findings.

A broad spectrum of spinal pathologies can affect the pediatric population. Ultrasound (US) is the primary modality for pediatric spine assessment due to its widespread availability, non-requirement of sedation, and absence of ionizing radiation. Supplementing this, MRI offers an in-depth exploration of these conditions, aiding in preoperative strategizing. In this review, we examine the clinical indications, methodologies, and protocols for US and MRI scans of the pediatric spine. Additionally, we illustrate normal pediatric spinal anatomy, highlighting several examples of normal variants that are often misinterpreted. Through a series of case-based illustrations, we offer a comprehensive overview of various pathological conditions such as tethered cord, spinal dysraphism, spinal lipoma, diastematomyelia, and dermal sinus tract, among others. Furthermore, we explore the correlation between US and MRI findings for these lesions, employing real-world cases to enhance our understanding of this topic.

Pearls and Pitfalls of Imaging in Pediatric Brain Tumors.

The central nervous system (CNS) tumors constitute the most common type of solid tumors in the pediatric population. The cerebral and cerebellar parenchyma are the most common site of pediatric CNS neoplasms. Imaging plays an important role in detection, characterization, staging and prognostication of brain tumors. The focus of the current article is pediatric brain tumor imaging with emphasis on pearls and pitfalls of conventional and advanced imaging in various pediatric brain tumor subtypes. The article also elucidates changes in brain tumor terms and entities as applicable to pediatric patients, updated as per World Health Organization (WHO) 2016 classification of primary CNS tumors. This classification introduced the genetic and/or molecular information of primary CNS neoplasms as part of comprehensive tumor pathology report in the routine clinical workflow. The concepts from 2016 classification have been further refined based on current research, by the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) group and published in the form of updates. The updates serve as guidelines in the time interval between WHO updates and expect to be broadly adopted in the subsequent WHO classification. The current review covers most pediatric brain tumors except pituitary tumors, meningeal origin tumors, nerve sheath tumors and CNS lymphoma/leukemia.

Rhabdomyosarcoma With Diffuse Bone Marrow Metastases.

Rhabdomyosarcoma is a highly aggressive cancer that is generally considered a disease of childhood. A vast majority of cases occur in those below the age of 20. Rhabdomyosarcoma can occur in any soft tissue in the body but is primarily found in the head, neck, orbit, genitourinary tract, genitals, and extremities. Prognosis is closely tied to the location of the primary tumor and the extent of metastatic spread. As with most sarcomas, rhabdomyosarcoma has a pattern of hematogenous spread which favors metastasis to the lungs. Other common areas include bone marrows, liver, breasts, and brain. One unusual pattern is the presence of diffuse bone marrow metastases in absence of significant soft tissue disease other than primary (no distant nodal disease, absence of visceral disease in chest and abdomen). Frequently in such cases, patients may have initial presentation similar to hematologic malignancy especially when the primary tumor is not evident. This pattern has been rarely described in the radiology literature. This pattern appears to be well documented in pathology literature. Even more rarely, in some cases, the primary tumor site may not be found after imaging and may remain undetermined even postmortem - only diagnosed by bone marrow aspiration. Awareness of this unique pattern is clearly important for radiologists, especially pediatric radiologists, as misdiagnosis can lead to delay in appropriate treatment that ultimately results in increased mortality. We present a case of rhabdomyosarcoma with this unique pattern of bone marrow metastases in which initial differential diagnosis favored a leukemic picture. This paper will go over the diagnostic techniques utilized throughout our patient's disease course as well as treatment.

Pulmonary Metastases of Chondroblastoma in a Pediatric Patient: A Case Report and Review of Literature.

Chondroblastoma is a locally destructive, cartilaginous bone tumor that accounts for a small percentage of cases of primary bone tumors. Although considered a benign tumor, chondroblastoma can locally recur and can rarely metastasize. Here, we report a rare presentation of a locally recurrent chondroblastoma with pulmonary metastases. A 13-year-old female presented with palpitations, dry cough, difficulty breathing, and chest tightness four years after her original surgical resection of tibial chondroblastoma. On chest CT, multiple pulmonary soft tissue nodules with confluent punctate areas of calcification were seen. The patient underwent robotic-assisted bilateral pulmonary wedge resections. She is now undergoing denosumab therapy. This case underlined the importance of suspecting metastatic disease in patients with a history of chondroblastoma when pulmonary nodules are detected on imaging.