Imaging the Cerebral Veins in Pediatric Patients: Beyond Dural Venous Sinus Thrombosis.

The range of intracranial venous anomalies in children differs from that in adults. As a commonly encountered highly morbid disease, sinovenous thrombosis has been discussed extensively in the literature, and the associated imaging considerations are similar in pediatric and adult patients. The authors shift the focus to less frequently discussed cerebral venous diseases in pediatric patients. First, the practical embryology pertinent to malformations, syndromes, and variants such as vein of Galen aneurysmal malformation, Sturge-Weber syndrome, and developmental venous anomalies are discussed. Second, anatomic considerations that are applicable to neuroimaging in pediatric patients with cerebral venous anomalies are reviewed. In the discussion of anatomy, special attention is given to the medullary venous system that serves the cerebral white matter, superficial cortical veins (tributaries of the dural venous sinuses), and bridging veins, which carry blood from the superficial cortical veins through the potential subdural space into the dural venous sinuses. Third, the selection of imaging modalities (US, CT and CT venography, and MRI) is addressed, and various MR venographic pulse sequences (time-of-flight, phase-contrast, and contrast-enhanced sequences) are compared. Finally, a broad variety of congenital and acquired superficial and deep venous diseases in children are reviewed, with emphasis on less frequently discussed entities involving the medullary (eg, deep medullary venous engorgement and thrombosis, periventricular hemorrhagic venous infarction due to germinal matrix hemorrhage), cortical (eg, cortical venous thrombosis), and bridging (eg, acute and chronic manifestations of injury in abusive head trauma) veins, as well as the deep veins and dural venous sinuses (eg, varix). © RSNA, 2023 Quiz questions for this article are available through the Online Learning Center. Online supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article.

Imaging of Vertebral Artery Dissection in Children: An Underrecognized Condition with High Risk of Recurrent Stroke.

Vertebral artery dissection (VAD) is a common cause of a rare condition, pediatric posterior circulation arterial ischemic stroke (PCAIS). VAD is clinically important due to the risk of multifocal and continuing infarcts from artery-to-artery thromboembolism, with the potential for occlusion of arteries that perfuse the brainstem. Early diagnosis is important, as recurrent stroke is a common effect of VAD in children. Although the relative efficacies of different treatment regimens for VAD in children remain unsettled, early initiation of treatment can mitigate the risk of delayed stroke. Clinical diagnosis of PCAIS may be delayed due to multiple factors, including nonspecific symptoms and the inability of younger patients to express symptoms. In fact, subacute or chronic infarcts are often present at initial imaging. Although the most common cause of isolated PCAIS is VAD, imaging of the cervical arteries has been historically underused in this setting. Cervical vascular imaging (MR angiography, CT angiography, and digital subtraction angiography) for VAD must be optimized to detect the sometimes subtle findings, which may be identified at initial or follow-up imaging. Osseous variants of the craniocervical junction and upper cervical spine and other extrinsic lesions that may directly injure the vertebral arteries or lead to altered biomechanics have been implicated in some cases. The authors review characteristic imaging features and optimized imaging of VAD and associated PCAIS and related clinical considerations. Identification of VAD has important implications for evaluation, treatment, and imaging follow-up, as this condition may result in progressive arteriopathy and recurrent stroke. © RSNA, 2023 Supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.

ToxCast Chemical Landscape: Paving the Road to 21st Century Toxicology.

The U.S. Environmental Protection Agency's (EPA) ToxCast program is testing a large library of Agency-relevant chemicals using in vitro high-throughput screening (HTS) approaches to support the development of improved toxicity prediction models. Launched in 2007, Phase I of the program screened 310 chemicals, mostly pesticides, across hundreds of ToxCast assay end points. In Phase II, the ToxCast library was expanded to 1878 chemicals, culminating in the public release of screening data at the end of 2013. Subsequent expansion in Phase III has resulted in more than 3800 chemicals actively undergoing ToxCast screening, 96% of which are also being screened in the multi-Agency Tox21 project. The chemical library unpinning these efforts plays a central role in defining the scope and potential application of ToxCast HTS results. The history of the phased construction of EPA's ToxCast library is reviewed, followed by a survey of the library contents from several different vantage points. CAS Registry Numbers are used to assess ToxCast library coverage of important toxicity, regulatory, and exposure inventories. Structure-based representations of ToxCast chemicals are then used to compute physicochemical properties, substructural features, and structural alerts for toxicity and biotransformation. Cheminformatics approaches using these varied representations are applied to defining the boundaries of HTS testability, evaluating chemical diversity, and comparing the ToxCast library to potential target application inventories, such as used in EPA's Endocrine Disruption Screening Program (EDSP). Through several examples, the ToxCast chemical library is demonstrated to provide comprehensive coverage of the knowledge domains and target inventories of potential interest to EPA. Furthermore, the varied representations and approaches presented here define local chemistry domains potentially worthy of further investigation (e.g., not currently covered in the testing library or defined by toxicity "alerts") to strategically support data mining and predictive toxicology modeling moving forward.

Mandibular condyle erosion and sclerosis in pediatric patients treated with radiotherapy to the head and neck region.

Head and neck radiotherapy in children is associated with significant acute and late morbidities. Temporomandibular joint dysfunction and trismus has been widely reported in patients receiving radiotherapy for sarcomas and nasopharyngeal carcinoma; however, erosion of the mandibular condyle is a rare sequela of modern radiotherapy techniques. In this report, we present three cases of erosion of the temporomandibular joint amongst pediatric patients treated with radiotherapy for distinct head, neck and brain malignancies.

Contrasting pediatric specialty provider opinion between contextualized and structured radiology reports.

BACKGROUND: Structured reporting (SR) replaced narrative (free text) reporting and utilizes templated headings and subheadings with findings typically based on the anatomy included in the examination. Its use has been widely advocated by radiology and non-radiology organizations as the new reporting standard. There are, however, shortcomings to SR, such as templated text not addressing a specific clinical indication. Contextual reporting (CR) fills this gap. CR is a type of SR which is tailored to a narrow clinical indication by including pertinent positive and negative findings for that specific clinical entity. OBJECTIVE: This study assesses provider preferences for CR as compared to SR in the pediatric practice environment using a survey methodology. METHODS & MATERIALS: Surveys with examples of SR and CR reports were sent electronically to two groups. One group was focused on neurological diseases and included pediatric specialists in neurosurgery, neurology, ENT, ED, and ophthalmology (190 people), referred to as the pediatric neuroimaging group. The pediatric neuroimaging group survey contained examples of CR and SR reports of an orbital CT for orbital cellulitis and a head CT for stroke. The other group was focused on gastrointestinal diseases, and included pediatric specialists in gastroenterology, general surgery, and the ED (159 people), referred to as the pediatric gastrointestinal (GI) imaging group. The pediatric GI imaging group survey contained example reports of an abdominal CT for appendicitis and an MRI enterography for Crohn's disease. Surveys utilizing a 5-point Likert scale were analyzed via Fischer's exact test with a p-value deemed statistically significant at less than 0.05. RESULTS: 349 individuals were contacted to participate in the survey. There were 81 (23 %, 81/349) survey respondents; 41 (22 %, 41/190) from the neuro group, and 40 (25 %, 40/159) from the GI group. 56 % (45/81) of all respondents preferred CR reports over traditional SR reports, while 29 % (23/81) did not. Most respondents (59 %, 48/81) indicated that CR reports are easier to interpret than traditional SR reports. Respondents from the pediatric neuroimaging group favored CR reports to a lesser degree (44 %, 36/81) compared to respondents from the pediatric GI imaging group (68 %, 55/81). CONCLUSIONS: We learned from this survey that it would be beneficial to be very intentional about selecting clinical indications where CR would be most valued rather than trying to develop CR for any specific clinical indication. The study results indicate it is reasonable to continue further efforts at exploring the utility of contextualized reports.

Antimicrobial stewardship in Australia: the role of qualitative research in programme development.

Antimicrobial stewardship (AMS) in Australia is supported by a number of factors, including enabling national policies, sectoral clinical governance frameworks and surveillance programmes, clinician-led educational initiatives and health services research. A One Health research programme undertaken by the National Centre for Antimicrobial Stewardship (NCAS) in Australia has combined antimicrobial prescribing surveillance with qualitative research focused on developing antimicrobial use-related situational analyses and scoping AMS implementation options across healthcare settings, including metropolitan hospitals, regional and rural hospitals, aged care homes, general practice clinics and companion animal and agricultural veterinary practices. Qualitative research involving clinicians across these diverse settings in Australia has contributed to improved understanding of contextual factors that influence antimicrobial prescribing, and barriers and facilitators of AMS implementation. This body of research has been underpinned by a commitment to supplementing 'big data' on antimicrobial prescribing practices, where available, with knowledge of the sociocultural, technical, environmental and other factors that shape prescribing behaviours. NCAS provided a unique opportunity for exchange and cross-pollination across the human and animal health programme domains. It has facilitated synergistic approaches to AMS research and education, and implementation of resources and stewardship activities. The NCAS programme aimed to synergistically combine quantitative and qualitative approaches to AMS research. In this article, we describe the qualitative findings of the first 5 years.

Molecular modeling for screening environmental chemicals for estrogenicity: use of the toxicant-target approach.

There is a paucity of relevant experimental information available for the evaluation of the potential health and environmental effects of many man made chemicals. Knowledge of the potential pathways for activity provides a rational basis for the extrapolations inherent in the preliminary evaluation of risk and the establishment of priorities for obtaining missing data for environmental chemicals. The differential step in many mechanisms of toxicity may be generalized as the interaction between a small molecule (a potential toxicant) and one or more macromolecular targets. An approach based on computation of the interaction between a potential molecular toxicant and a library of macromolecular targets of toxicity has been proposed for preliminary chemical screening. In the current study, the interaction between a series of environmentally relevant chemicals and models of the rat estrogen receptors (ER) was computed and the results compared to an experimental data set of their relative binding affinities. The experimental data set consists of 281 chemicals, selected from the U.S. EPA's Toxic Substances Control Act (TSCA) inventory, that were initially screened using the rat uterine cytosolic ER-competitive binding assay. Secondary analysis, using Lineweaver-Burk plots and slope replots, was applied to confirm that only 15 of these test chemicals were true competitive inhibitors of ER binding with experimental inhibition constants (K(i)) less than 100 microM. Two different rapid computational docking methods have been applied. Each provides a score that is a surrogate for the strength of the interaction between each ligand-receptor pair. Using the score that indicates the strongest interaction for each pair, without consideration of the geometry of binding between the toxicant and the target, all of the active molecules were discovered in the first 16% of the chemicals. When a filter is applied on the basis of the geometry of a simplified pharmacophore for binding to the ER, the results are improved, and all of the active molecules were discovered in the first 8% of the chemicals. In order to obtain no false negatives in the model that includes the pharmacophore filter, only 8 molecules are false positives. These results indicate that molecular docking algorithms that were designed to find the chemicals that act most strongly at a receptor (and therefore are potential pharmaceuticals) can efficiently separate weakly active chemicals from a library of primarily inactive chemicals. The advantage of using a pharmacophore filter suggests that the development of filters of this type for other receptors will prove valuable.

Computational molecular modeling for evaluating the toxicity of environmental chemicals: prioritizing bioassay requirements.

BACKGROUND: The human health risk from exposure to environmental chemicals often must be evaluated when relevant elements of the preferred data are unavailable. Therefore, strategies are needed that can predict this information and prioritize the outstanding data requirements for the risk evaluation. Many modes of molecular toxicity require the chemical or one of its biotransformation products to interact with specific biologic macromolecules (i.e., proteins and DNA). Molecular modeling approaches may be adapted to study the interactions of environmental chemicals with biomolecular targets. OBJECTIVE: In this commentary we provide an overview of the challenges that arise from applying molecular modeling tools developed and commonly used for pharmaceutical discovery to the problem of predicting the potential toxicities of environmental chemicals. DISCUSSION: The use of molecular modeling tools to predict the unintended health and environmental consequences of environmental chemicals differs strategically from the use of the same tools in the pharmaceutical discovery process in terms of the goals and potential applications. It also requires consideration of the greater diversity of chemical space and binding affinity domains than is covered by pharmaceuticals. CONCLUSION: Molecular modeling methods offer one of several complementary approaches to evaluate the risk to human health and the environment as a result of exposure to environmental chemicals. These tools can streamline the hazard assessment process by simulating possible modes of action and providing virtual screening tools that can help prioritize bioassay requirements. Tailoring these strategies to the particular challenges presented by environmental chemical interactions make them even more effective.

Magnetic resonance urography for diagnosis of pediatric ureteral stricture.

PURPOSE: Ureteral stricture is a rare cause of hydronephrosis in children and is often misdiagnosed on ultrasound (US) and diuretic renal scintigraphy (DRS), requiring intraoperative diagnosis. We evaluated ureteral strictures diagnosed by magnetic resonance urography (MRU) at our institution. MATERIALS AND METHODS: Children with ureteral stricture who underwent MRU were identified. Patient demographics, prior imaging, MRU findings, and management were assessed. The efficacy of MRU in diagnosis of stricture was compared with US and DRS. Patients with ureteropelvic or ureterovesical junction obstruction were excluded. RESULTS: Twenty-eight ureteral strictures diagnosed by MRU between 2003 and 2013 were identified; 22% of strictures were diagnosed by DRS ± US. The mean age at MRU diagnosis was 2.4 years (range 4 weeks-15 years). Hydronephrosis was the most common presentation, accounting for 20 (71%) cases. Other etiologies included pain (3), incontinence (2), and urinary tract infection, cystic kidney, and absent kidney, present in one case each. A mean of 2.7 imaging studies was obtained prior to MRU diagnosis. Twenty-one (75%) ureteral strictures required surgical intervention, with the approach dependent upon location. CONCLUSIONS: MRU provides excellent anatomic and functional detail of the collecting system, leading to accurate diagnosis and management of ureteral stricture in children.

Evaluation of UPJ obstruction before and after pyeloplasty using MR urography.

This article builds on the previous article in this symposium and shows how MR urography contributes to the postoperative evaluation of children with UPJ obstruction. By analyzing the postoperative results, we derived new insights into their preoperative evaluation. With MR urography we combine simultaneous physiological and anatomic evaluation that enables us to identify changes in renal pathophysiology that occur in association with impaired drainage and obstruction. We studied 35 children before and after pyeloplasty. The pyeloplasty was considered successful in 30 and unsuccessful in 5. Both anatomic and functional criteria were used. The anatomic parameters included the degree of hydronephrosis, the appearance of the renal parenchyma, the quality of the nephrogram and the presence of crossing vessels. The functional criteria included the renal transit time, the calyceal transit time, the volumetric differential function, the Patlak differential function, the difference between the volumetric and Patlak differential function and the Patlak number per milliliter of renal tissue. No single parameter was sufficient to fully characterize UPJ obstruction, but by synthesizing all the information we were able to subdivide UPJ obstruction into compensated, decompensated and uropathic kidneys. Decompensated systems had the most significant improvement following successful pyeloplasty. Compensated systems showed little improvement in renal function, and uropathic kidneys were associated with a poor prognosis. It is clear that not all UPJ obstructions are the same, and it seems logical that treatment should be individually tailored rather than using a standard approach for all cases. Because MR urography can identify pathophysiological differences in children with UPJ obstruction that are occult to renal scintigraphy, it has an important potential role in identifying those who will benefit most from pyeloplasty and those who are probably best observed.

MR urography evaluation of obstructive uropathy.

Hydronephrosis and the evaluation of obstructive uropathy are the most common indications for MR urography in our practice. Typically our patients fall into one of two groups: infants with antenatal hydronephrosis and older children who present with abdominal pain, hematuria or urinary tract infection. Obstruction in children is usually chronic and partial. Intermittent episodes of increased pressure occur when the urine production exceeds the capacity for drainage. MR urography uses a fluid and diuretic challenge to assess the hydronephrotic kidney. High-quality anatomic images provide a morphologic assessment of the hydronephrotic system. Although it is relatively straightforward to determine if a system is not obstructed on the basis of the renal transit time (RTT), no single parameter is adequate to fully characterize obstruction. By evaluating the changes in signal intensity in the renal parenchyma following contrast administration, the hydronephrotic systems are classified as compensated or decompensated. Delayed RTT and the presence of urine-contrast levels indicate stasis. Calyceal transit time and the difference between the volumetric and the Patlak differential renal function (vDRF-pDRF) are measures of the physiologic changes within the kidney. Additionally, MR urography provides prognostic information by assessing the quality of the renal parenchyma and identifying uropathy preoperatively. MR urography combines both anatomic and functional information in a single test and is capable of providing a comprehensive evaluation of obstructive uropathy that could ultimately help select those patients most likely to benefit from surgical intervention.

Evaluation of reflux nephropathy, pyelonephritis and renal dysplasia.

MR urography has the potential to significantly improve our understanding of the relationship between reflux nephropathy, pyelonephritis, vesicoureteric reflux and renal dysplasia. MR urography utilizes multiple parameters to assess both renal anatomy and function and provides a more complete characterization of acquired and congenital disease. Pyelonephritis and renal scarring can be distinguished by assessing the parenchymal contours and signal intensity. Characteristic imaging features of renal dysplasia include small size, subcortical cysts, disorganized architecture, decreased and patchy contrast enhancement as well as a dysmorphic pelvicalyceal system. Because of its ability to subdivide and categorize this heterogeneous group of disorders, it seems inevitable that MR urography will replace DMSA renal scintigraphy as the gold standard for assessment of pyelonephritis and renal scarring. MR urography will contribute to our understanding of renal dysplasia and its relationship to reflux nephropathy.

MR urography in children: how we do it.

In this article we introduce the topic of MR urography in children, focusing on the details required to obtain consistently high-quality scans. Much of the information presented is based on our experience during the last 7 years. We have performed almost 1,000 MR urograms in children, and the technique has evolved considerably during this time. We have learned through trial and error and have improved our protocols to the point that our approach is now standardized and reliably generates high-quality studies. From this standardized protocol, further refinements in technique can be readily implemented. It is important to remember that this clinical application is in its infancy and will improve significantly with further technical development. This paper provides an overview of the practical issues associated with obtaining high-quality scans as well as an introduction into the interpretation of MR urograms.

MRU post-processing.

Dynamic magnetic resonance urography (MRU) scans acquired in conjunction with an injection of a contrast agent can be used to estimate a number of parameters that reflect renal function. This article discusses the methodologies and assumptions used in the estimation of these parameters, with special attention to the problem of deriving the concentration of the contrast agent from the change in the MR signal. The estimates of split renal function derived from MRU are in good agreement with those obtained using nuclear medicine studies. The time-intensity curves show subtle differences from those measured using nuclear medicine but still allow the transit of the contrast agent through the kidney to be assessed. Quantitative estimates of renal function (GFR) can be derived from MRU but have yet to be validated in a pediatric population.

Dynamic contrast-enhanced MR urography in the evaluation of pediatric hydronephrosis: Part 1, functional assessment.

OBJECTIVE: The purpose of our study was to derive time-intensity curves for the renal cortex and medulla from 3D dynamic MR urography and to assess whether these curves are predictive of obstruction. MATERIALS AND METHODS: Fifty-nine examinations were performed in 53 pediatric patients and the degree of obstruction assessed using the renal transit time. The cortex and medulla were segmented using a semiautomatic method, and mean time-intensity curves were derived for the segmented volumes. The basic parameters of the curves (amplitude, washout) were assessed, as was the presence of certain characteristic features of the curves. RESULTS: The images allowed clear visualization of three phases of the uptake of contrast material in the cortex, the medulla, and the collecting system. Both the amplitude of the curves and the washout of the contrast material were predictive of obstruction. The distal tubular peak was reliably detected in the cortex of nonobstructed kidneys. CONCLUSION: Combining signal-intensity-versus-time-curve analysis with the other parameters that can be derived from the same MR urography data set provides a powerful tool for the diagnosis of obstruction.

Dynamic contrast-enhanced MR urography in the evaluation of pediatric hydronephrosis: Part 2, anatomic and functional assessment of ureteropelvic junction obstruction [corrected].

OBJECTIVE: The purpose of our study was to retrospectively review our experience using MR urography in the diagnosis of ureteropelvic junction (UPJ) obstruction in children. MATERIALS AND METHODS: Sixty-one studies were performed in 50 children with hydronephrosis but without hydroureter. Anatomic criteria assessed included degree of hydronephrosis, morphology of the renal pelvis, atrophy of medulla, swirling contrast material, fluid levels, and the presence of fetal folds and crossing vessels. Functional criteria included renal transit time, differential renal function, and time-intensity curves when available. RESULTS: Thirty-one kidneys were classified as obstructed, 15 as equivocal, and 15 as nonobstructed. Obstructed systems had more marked hydronephrosis, more extensive medullary atrophy, more fluid levels, and more swirling contrast material. Fetal folds were seen in only the equivocal and nonobstructed groups. Crossing vessels were seen in all groups. Obstructed systems also showed greater functional derangement, decreased split renal function, and abnormal time-intensity curves. CONCLUSION: MR urography provides both excellent anatomic and functional information in children with UPJ obstruction in a single test that does not use ionizing radiation. MR urography may lead to greater understanding of the pathophysiology of UPJ obstruction.

Benzo[a]pyrene and benz[c]phenanthrene: the effect of structure on the binding of water molecules to the diol epoxides.

The interactions with water of the diol epoxides (DEs) of both a planar and a nonplanar PAH have been examined using molecular dynamics. To determine probable water locations around the DE for later use in the study of DE protonation, molecular dynamics simulations using the OPLS force field were carried out on diol epoxides surrounded by a 22 A box of explicit water molecules. Results for 30 ps simulations indicate that 10-60% of the time, depending strongly on the conformation and type of the DE, there is a water molecule forming a hydrogen bond with the epoxide oxygen. The patterns seen in the frequency at which a DE binds a water molecule reflect patterns seen in the relationship between the type of PAH DE and amount of DNA adduct formation. Examination of the orientations and arrangements of the water and DEs during the simulations showed that the bound waters existed in several preferred configurations which are also dependent upon the PAH DE geometry.