Using an artificial intelligence software improves emergency medicine physician intracranial haemorrhage detection to radiologist levels.

BACKGROUND: Tools to increase the turnaround speed and accuracy of imaging reports could positively influence ED logistics. The Caire ICH is an artificial intelligence (AI) software developed for ED physicians to recognise intracranial haemorrhages (ICHs) on non-contrast enhanced cranial CT scans to manage the clinical care of these patients in a timelier fashion. METHODS: A dataset of 532 non-contrast cranial CT scans was reviewed by five board-certified emergency physicians (EPs) with an average of 14.8 years of practice experience. The scans were labelled in random order for the presence or absence of an ICH. If an ICH was detected, the reader further labelled all subtypes present (ie, epidural, subdural, subarachnoid, intraparenchymal and/or intraventricular haemorrhage). After a washout period, the five EPs reviewed again the scans individually with the assistance of Caire ICH. The mean accuracy of the EP readings with AI assistance was compared with the mean accuracy of three general radiologists reading the films individually. The final diagnosis (ie, ground truth) was adjudicated by a consensus of the radiologists after their individual readings. RESULTS: Mean EP reader accuracy significantly increased by 6.20% (95% CI for the difference 5.10%-7.29%; p=0.0092) when using Caire ICH to detect an ICH. Mean accuracy of the EP cohort in detecting an ICH using Caire ICH was found to be more accurate than the radiologist cohort prior to discussion; this difference, however, was not statistically significant. CONCLUSION: The Caire ICH software significantly improved the accuracy and sensitivity of detecting an ICH by the EP to a level comparable to general radiologists. Further prospective research with larger numbers will be needed to understand the impact of Caire ICH on ED logistics and patient outcomes.

Simplifying Access to Targeted Protein Degraders via Nickel Electrocatalytic Cross-Coupling.

C-C linked glutarimide-containing structures with direct utility in the preparation of cereblon-based degraders (PROTACs, CELMoDs) can be assessed in a single step from inexpensive, commercial α-bromoglutarimide through a unique Brønsted-acid assisted Ni-electrocatalytic approach. The reaction tolerates a broad array of functional groups that are historically problematic and can be applied to the simplified synthesis of dozens of known compounds that have only been procured through laborious, wasteful, multi-step sequences. The reaction is scalable in both batch and flow and features a trivial procedure wherein the most time-consuming aspect of reaction setup is weighing out the starting materials.

Progression of Plaque Burden of Intracranial Atherosclerotic Plaque Predicts Recurrent Stroke/Transient Ischemic Attack: A Pilot Follow-Up Study Using Higher-Resolution MRI.

BACKGROUND: Patients with intracranial atherosclerotic disease (ICAD) have a high frequency of stroke recurrence. However, there has been little investigation into the prognostic value of higher-resolution magnetic resonance imaging (HR-MRI). PURPOSE: To investigate the use of intracranial atherosclerotic plaques features in predicting risk of recurrent cerebrovascular ischemic events using HR-MRI. STUDY TYPE: Prospective. POPULATION: Fifty-eight patients with acute/subacute stroke (N = 46) or transient ischemic attack (N = 12). FIELD STRENGTH/SEQUENCE: A 3.0 T, 3D time-of-flight gradient echo sequence and T1- and T2-weighted fast spin echo sequences with 0.31 x 0.39 mm2 in-plane resolution, twice (with >3 months between scans) following the initial event. ASSESSMENT: Patients were also followed clinically for recurrent ischemic events for up to 48 months or until a subsequent event occurred. The degree of stenosis, plaque burden (PB), minimal lumen area (MLA), and contrast enhancement ratio were assessed at each scanning session and the percentage change of each over time was calculated. STATISTICAL TESTS: Univariable and multivariable Cox regression analyses were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for predicting recurrent events. RESULTS: The mean time interval between baseline and follow-up MRI scans was 6.2 ± 4.1 months. After the second MRI scan, 20.7% of patients (N = 12) had experienced ipsilateral recurrent TIA/stroke within 10.9 ± 9.2 months. Univariable analyses showed that baseline triglyceride, percentage change of PB, and progression of PB were significantly associated with recurrent events (all P < 0.05). Multivariable Cox regression indicated that progression of PB (HR, 6.293; 95% CI, 1.620-24.444; P < 0.05) was a significant independent imaging feature for recurrent ischemic events. DATA CONCLUSION: Progression of PB was independently associated with recurrent ischemic cerebrovascular events. HR-MRI may help risk stratification of patients at risk of recurrent stroke. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 4.

Development of BET inhibitors as potential treatments for cancer: A search for structural diversity.

We describe our efforts to identify structurally diverse leads in the triazole-containing N1-carboline series of bromodomain and extra-terminal inhibitors. Replacement of the N5 "cap" phenyl moiety with various heteroaryls, coupled with additional modifications to the carboline core, provided analogs with similar potency, improved pharmacokinetic properties, and increased solubility compared to our backup lead, BMS-986225 (2). Rapid SAR exploration was enabled by a convergent, synthetic route. These efforts provided a potent BET inhibitor, 3-fluoropyridyl 12, that demonstrated robust efficacy in a multiple myeloma mouse tumor model at 1 mg/kg.

Development of BET inhibitors as potential treatments for cancer: A new carboline chemotype.

We describe our efforts to introduce structural diversity to a previously described triazole-containing N1-carboline series of bromodomain and extra-terminal (BET) inhibitors. N9 carbolines were designed to retain favorable binding interactions that the N1-carbolines possess. A convergent synthetic route enabled modifications to reduce clearance, enhance physicochemical properties, and improve the overall in vitro profile. This work led to the identification of a potent BET inhibitor, (S)-2-{8-fluoro-5-[(3-fluoropyridin-2-yl)(oxan-4-yl)methyl]-7-[4-(2H3)methyl-1-methyl-1H-1,2,3-triazol-5-yl]-5H-pyrido[3,2-b]indol-3-yl}propan-2-ol (10), a compound with enhanced oral exposure in mice. Subsequent evaluation in a mouse triple-negative breast cancer tumor model revealed efficacy at 4 mg/kg of N9-carboline 10.

Lipoblastoma: computed tomographic and magnetic resonance imaging features correlate with tumor behavior and pathology.

BACKGROUND: Lipoblastoma is a rare benign neoplasm of immature fat cells in children. Imaging appearances are frequently complex, sometimes simulating liposarcoma. OBJECTIVE: To characterize features of lipoblastoma on MRI and CT in comparison with recurrence risk. MATERIALS AND METHODS: We identified cases via retrospective review of histopathology-proven lipoblastoma cases in a large referral database and a pediatric medical center. Two radiologists scored CT and MRI on the basis of lesion features. RESULTS: We included a total of 56 children (32 boys and 24 girls) with a mean age of 2.6 years (range 0.1-13 years). Extremity lesions were most common (27%), followed by neck (19%), gluteal region (18%), chest (14%) and mesentery (14%). Children most commonly presented with painless masses (73%), followed by dyspnea (9%), distension (9%) and pain (7%). Non-adipose soft-tissue components were identified on CT and MRI in 78% of cases. Significant (moderate or marked) septations were noted in 59% and enhancement in 35%. Compartmental invasion was present in 43% of cases. Of paraspinal cases, 38% involved the neural foramina or central canal. Lesion complexity did not significantly correlate with age. Recurrence was observed in 9% of cases and was significantly correlated with compartmental invasion (correlation: 0.303, P=0.009) and septation complexity (correlation: 0.227, P=0.038) on initial imaging. CONCLUSION: Although lipoblastoma is a fat-containing entity, many lesions demonstrate marked complexity and local infiltration that resemble liposarcoma, which is exceedingly rare in younger children. Compartmental invasion and thicker septations appear to confer greater risk of recurrence following resection.

Establishing a magnetic resonance safety program.

Establishing a magnetic resonance (MR) safety program is crucial to ensuring the safe MR imaging of pediatric patients. The organizational structure includes a core safety council and broader safety committee comprising all key stakeholders. These groups work in synchrony to establish a strong culture of safety; create and maintain policies and procedures; implement device regulations for entry into the MR setting; construct MR safety zones; address intraoperative MR concerns; guarantee safe scanning parameters, including complying with specific absorption rate limitations; adhere to national regulatory body guidelines; and ensure appropriate communication among all parties in the MR environment. Perspectives on the duties of the safety council members provide important insight into the organization of program oversite. Ultimately, the collective dedication and vigilance of all MR staff are crucial to the success of a safety program.

Wall enhancement on black-blood MRI is independently associated with symptomatic status of unruptured intracranial saccular aneurysm.

OBJECTIVE: This study aims to investigate whether aneurysm wall enhancement (AWE) is independently associated with symptomatic status of unruptured intracranial aneurysms (UIAs). METHODS: One hundred thirty-nine consecutive patients (67 male, mean age 58 ± 11 years) with 79 symptomatic and 87 asymptomatic UIAs were imaged using black-blood MRI pre- and post-gadolinium contrast administration and 3D DSA. Symptoms related to aneurysms were identified including cranial nerve deficits and headache. AWE grade and area were characterized, and aneurysm size was measured on DSA. Multivariate binary logistic regression analysis was used to identify factors associated with symptoms. Further subgroup analysis was performed for aneurysms size < 10 mm. RESULTS: Symptomatic UIAs had significantly larger aneurysm size (11.2 ± 6.2 mm vs. 6.4 ± 3.3 mm), enhancement grade (1.3 ± 0.6 vs. 0.4 ± 0.6), enhancement area (2.0 ± 0.9 vs. 0.4 ± 0.7), and higher prevalence of thick enhancement (39% vs. 3%) compared with asymptomatic UIAs, all p < 0.001. In multivariate analysis, only AWE area (odds ratio [OR] 6.9, 95% confidence interval [4.0, 11.7]) was independently associated with symptoms. AWE area had an area under curve (AUC) value of 0.888, with 72.2% sensitivity and 92.0% specificity for symptoms, which was superior to aneurysm size (AUC of 0.771, with 75.9% sensitivity and 65.5% specificity). In the subgroup analysis of aneurysms smaller than 10 mm (n = 118), AWE area (OR, 7.0, p < 0.001) remained the only independent risk factor associated with symptoms. CONCLUSIONS: Larger AWE area is independently associated with symptomatic UIAs, which may provide additional value to guide UIA management and improve patient outcomes. KEY POINTS: • Symptomatic intracranial aneurysms are larger and more often demonstrate significant wall enhancement than asymptomatic aneurysms. • Larger wall enhancement area is independently associated with symptomatic intracranial aneurysm.

Evaluation of chronic carotid artery occlusion by non-contrast 3D-MERGE MR vessel wall imaging: comparison with 3D-TOF-MRA, contrast-enhanced MRA, and DSA.

OBJECTIVES: To analyze the accuracy of a non-contrast MR vessel wall imaging technique, three-dimensional motion-sensitized driven equilibrium prepared rapid gradient echo (3D-MERGE) for diagnosing chronic carotid artery occlusion (CCAO) characteristics compared with 3D time-of-flight (TOF) MRA, and contrast-enhanced MRA (CE-MRA), using digital subtraction angiography (DSA) as a reference standard. METHODS: Subjects diagnosed with possible CCAO by ultrasound were retrospectively analyzed. Patients underwent 3.0-T MR imaging with 3D-MERGE, 3D-TOF-MRA, and CE-MRA followed by DSA within 1 week. Diagnostic accuracy of occlusion, occlusion site, and proximal stump condition were assessed independently on 3 MRI sequences and DSA. Agreement of the above indicators was evaluated in reference to DSA. RESULTS: One hundred twenty-four patients with 129 suspected CCAO (5 with bilateral occlusions) met the inclusion criteria for our study. 3D-MERGE demonstrated a sensitivity, specificity, and accuracy of 97.0%, 86.7%, and 94.6%, respectively, with excellent agreement (Cohen's κ = 0.85; 95% CI, 0.71, 0.94) for diagnosing CCAO in reference to DSA. 3D-MERGE was superior in diagnosing CCAO compared with 3D-TOF-MRA (Cohen's κ = 0.61; 95% CI, 0.42, 0.77) and similar to CE-MRA (Cohen's κ = 0.93; 95% CI, 0.86, 1.00). 3D-MERGE also had excellent agreement compared with DSA for assessing occlusion sites (Cohen's κ = 0.85; 95% CI, 0.71, 0.97) and stump condition (Cohen's κ = 0.83; 95% CI, 0.71, 0.94). Moreover, 3D-MERGE provided additional information regarding the occluded segment, such as distal lumen collapse and vessel wall lesion components. CONCLUSION: 3D-MERGE can reliably assess chronic carotid occlusive characteristics and has the ability to identify other vessel wall features of the occluded segment. This non-contrast MR vessel wall imaging technique is promising for assessment of CCAO. KEY POINTS: • Excellent agreement was found between 3D-MERGE and DSA for assessing chronic carotid artery occlusion, occlusion site, and proximal stump condition. • 3D-MERGE was shown to be a more accurate and efficient tool than 3D-TOF-MRA to detect the characteristics of the occluded segment. • 3D-MERGE provides not only luminal images for characterizing the proximal characteristics of occlusion but also vessel wall images for assessing the distal lumen and morphology of occlusion segment, which might help clinicians to optimize the treatment strategy for patients with chronic carotid artery occlusion.

Solitary long-bone epiphyseal lesions in children: radiologic-pathological correlation and epidemiology.

BACKGROUND: Solitary epiphyseal lesions are rare and present with nonspecific imaging features. Knowledge regarding etiologies of pediatric epiphyseal lesions is limited to small studies. OBJECTIVE: The purpose of this study was to determine the relative incidence of pathologies affecting the pediatric epiphysis based on biopsy-proven cases with imaging. MATERIALS AND METHODS: We conducted a retrospective review of imaging studies including the terms "biopsy" or "resection" and entities known to affect the epiphysis and cross-referenced these with pathology reports, recording the relevant clinical data. Two radiologists performed comprehensive imaging review and recorded relevant features. RESULTS: Forty-nine children and adolescents met inclusion criteria. The long-bone epiphyseal lesion etiologies included chondroblastoma (n=22, 45%), nonspecific nonmalignant pathology (n=11, 22%), osteomyelitis (n=9, 18%), lymphoma (n=2, 4%) and 1 case of each of aneurysmal bone cyst, chondrosarcoma, enchondroma, hemangioendothelioma, and non-Langerhans cell histiocytosis. Median age was 13.1 years old (range 1.5-18.6 years). We performed comparative analysis of the two most common lesions in our series, chondroblastoma and osteomyelitis. Chondroblastoma was significantly more likely to be peripherally located (94% vs. 33%, P=0.002) and to demonstrate a discrete T1-weighted hypointense rim (94% vs. 33%, P=0.002); there were no significant differences in enhancement or intrinsic signal properties. Children with chondroblastoma were older (15.1 years vs. 7.3 years, P=0.001), and chondroblastoma lesions were significantly larger, with mean maximum lesion diameter of 25 mm (interquartile range [IQR] 20-30) vs. 12 mm (IQR 11-18) (P=0.001) and lesion volumes of 4.4 mL (IQR 2.4-7.9) vs. 0.4 mL (IQR 0.2-1.4) (P=0.01). CONCLUSION: This study reports the relative frequency of pathology of pediatric solitary epiphyseal lesions and describes several features that might assist in differentiating between chondroblastoma and osteomyelitis.

Osteochondritis Dissecans of the Elbow in Children: MRI Findings of Instability.

OBJECTIVE. The purpose of this study was to investigate the performance of MRI criteria for predicting instability of osteochondritis dissecans (OCD) lesions of the elbow in children. MATERIALS AND METHODS. This retrospective study included 41 children with 43 OCD lesions of the elbow who underwent an MRI examination between April 1, 2010, and May 31, 2018. Two radiologists blinded to clinical outcomes reviewed MRI studies to determine the presence or absence of joint effusion, osteochondral defect, intraarticular body, overlying cartilage changes, subchondral bone disruption, rim of high signal intensity on T2-weighted images, cysts, marginal sclerosis, and perilesional bone marrow edema. The stability of OCD lesions was determined with clinical follow-up and surgical findings as reference standards. Mann-Whitney U, chi-square, Fisher exact, and Cochran-Armitage tests were used to compare MRI findings between stable and unstable OCD lesions. RESULTS. There were 20 stable and 23 unstable OCD lesions. An osteochondral defect (p = 0.01), intraarticular body (p < 0.001), overlying cartilage changes (p = 0.001), subchondral bone plate disruption (p = 0.02), and hyperintense rim (p = 0.01) were significantly more common in unstable than stable OCD lesions. However, only osteochondral defect and intraarticular body were 100% specific for OCD instability. There was no significant difference between stable and unstable OCD lesions in the presence of joint effusion (p = 0.10), cysts (p = 0.45), marginal sclerosis (p = 0.70), or perilesional bone marrow edema (p = 1.00). CONCLUSION. MRI findings of OCD instability of the elbow include an osteochondral defect, intraarticular body, overlying cartilage changes, subchondral bone disruption, and rim of high signal intensity on T2-weighted MR images.

Proximal radius fractures in children: evaluation of associated elbow fractures.

BACKGROUND: Additional fractures occur in association with proximal radius fractures, but the extent of these secondary injuries has not been systematically assessed. OBJECTIVE: To ascertain the frequency and nature of additional fractures associated with proximal radius injuries in a large pediatric cohort. MATERIALS AND METHODS: Radiographs meeting search criteria for proximal radius fracture during a 5-year period were reviewed. Fracture characteristics and the coexistence of additional elbow fractures were recorded and analyzed. The retrospective review was compared with initial interpretation and a blinded review by two pediatric musculoskeletal radiologists. RESULTS: Four hundred ninety-four proximal radius fractures were included. The radial neck was the most common fracture site (89%). Neck fractures occurred in younger patients (mean: 7.3 years) than head fractures (mean: 13.3 years) (P<0.001). Additional elbow fractures occurred in 39%, most commonly at the olecranon (22%). Additional fractures occurred in younger patients (mean: 7.2 years) than isolated proximal radius fractures (mean: 8.5 years) (P<0.001). Elbow joint effusion and complete or displaced radius fractures were each associated with additional elbow fractures (P<0.001). When compared with initial interpretation, 25% of additional fractures were not identified on initial radiographs, of which 44% were occult retrospectively. Fracture identification demonstrated excellent inter-reader reliability (interclass correlation coefficient [ICC]: 0.88, 0.94), but joint effusion interobserver agreement was only fair (ICC: 0.52, 0.41). CONCLUSION: Proximal radius fractures in children often occur in association with other elbow fractures, most commonly involving the olecranon. Enhanced awareness of these fracture patterns, especially in the setting of joint effusion or complete and displaced radius fractures, may improve detection to guide appropriate management.

Whole-body magnetic resonance imaging of pediatric cancer predisposition syndromes: special considerations, challenges and perspective.

Cancer predisposition syndromes increase the incidence of tumors during childhood and are associated with significant morbidity and mortality. Imaging is paramount for ensuring early detection of neoplasms, impacting therapeutic interventions and potentially improving outcome. While conventional imaging techniques involve considerable exposure to ionizing radiation, whole-body MRI is a radiation-free modality that allows continuous imaging of the entire body and has increasingly gained relevance in the surveillance, diagnosis, staging and monitoring of pediatric patients with cancer predisposition syndromes. Nevertheless, widespread implementation of whole-body MRI faces several challenges as a screening tool. Some of these challenges include developing clinical indications, variability in protocol specifications, image interpretation as well as coding and billing practices. These factors impact disease management, patient and family experience and research collaborations. In this discussion we review the aforementioned special considerations and the potential direction that might help overcome these challenges and promote more widespread use of whole-body MRI in children with cancer predisposition syndromes.

Wall enhancement of intracranial unruptured aneurysm is associated with increased rupture risk and traditional risk factors.

OBJECTIVE: Aneurysm wall enhancement (AWE) on MRI has been considered an imaging marker to indicate active aneurysm inflammation, but no prospective studies have assessed the ability of AWE to predict rupture risk or growth. We aim to study the association of AWE with traditional risk factors and the estimated rupture risk. METHODS: Seventy-seven patients (mean age, 58.4 ± 10.8 years; 57% female) with 88 asymptomatic intracranial saccular aneurysms underwent both 3-T high-resolution MRI and three-dimensional (3D) rotational digital subtraction angiography (DSA). Geometric and morphologic parameters were measured on DSA, and the degree of AWE on MRI was graded. One- and 5-year rupture risks of aneurysms were estimated using the UCAS and PHASES calculator. Parameters associated with AWE were analyzed using uni- and multivariate logistic regression. RESULTS: Non-internal carotid artery location (OR 3.4, 95% CI 1.6-7.1) and aneurysm size (OR 1.9, 95% CI 1.3-2.7) were independently associated with AWE (p < 0.05). Aneurysms with AWE had significantly higher estimated rupture risk (1 and 5 year, 1.9% and 5.8%) than aneurysms without AWE (0.5% and 2.1%) (p < 0.001). Stronger and larger areas of AWE were correlated with the aneurysm size, size ratio and estimated rupture risk (R2 ≥ 0.30) (p < 0.01). CONCLUSIONS: Prospective assessment of asymptomatic intracranial aneurysms with MRI suggests that AWE is associated with traditional risk factors and estimated short- and medium-term rupture risk. KEY POINTS: • AWE independently associates with aneurysm location and size. • Aneurysms with AWE have higher rupture risk than aneurysms without AWE. • Stronger and larger areas of AWE correlated with the aneurysm size, size ratio and rupture risk.

Identification of high-risk plaque features in intracranial atherosclerosis: initial experience using a radiomic approach.

OBJECTIVES: To evaluate a quantitative radiomic approach based on high-resolution magnetic resonance imaging (HR-MRI) to differentiate acute/sub-acute symptomatic basilar artery plaque from asymptomatic plaque. METHODS: Ninety-six patients with basilar artery stenosis underwent HR-MRI between January 2014 and December 2016. Patients were scanned with T1- and T2-weighted imaging, as well as T1 imaging following gadolinium-contrast injection (CE-T1). The stenosis value, plaque area/burden, lumen area, minimal luminal area (MLA), intraplaque haemorrhage (IPH), contrast enhancement ratio and 94 quantitative radiomic features were extracted and compared between acute/sub-acute and asymptomatic patients. Multi-variate logistic analysis and a random forest model were used to evaluate the diagnostic performance. RESULTS: IPH, MLA and enhancement ratio were independently associated with acute/subacute symptoms. Radiomic features in T1 and CE-T1 images were associated with acute/subacute symptoms, but the features from T2 images were not. The combined IPH, MLA and enhancement ratio had an area under the curve (AUC) of 0.833 for identifying acute/sub-acute symptomatic plaques, and the combined T1 and CE-T1 radiomic approach had a significantly higher AUC of 0.936 (p = 0.01). Combining all features achieved an AUC of 0.974 and accuracy of 90.5%. CONCLUSIONS: Radiomic analysis of plaque texture on HR-MRI accurately distinguished between acutely symptomatic and asymptomatic basilar plaques. KEY POINTS: • High-resolution magnetic resonance imaging can assess basilar artery atherosclerotic plaque. • Radiomic features in T1 and CE-T1 images are associated with acute symptoms. • Radiomic analysis can accurately distinguish between acute symptomatic and asymptomatic plaque. • The highest accuracy may be achieved by combining radiomic and conventional features.

More Than Epiphyseal Osteochondromas: Updated Understanding of Imaging Findings in Dysplasia Epiphysealis Hemimelica (Trevor Disease).

OBJECTIVE: The purpose of this article is to discuss approaches to imaging dysplasia epiphysealis hemimelica in the context of recent advances in the understanding of the underlying pathophysiologic profile of this entity, which may result in pain, growth disturbance, and early development of osteoarthritis. CONCLUSION: Dysplasia epiphysealis hemimelica was first characterized as a skeletal disorder with osteochondromas characteristically involving epiphyses on one side of the same lower extremity. Upper extremity involvement was subsequently recognized. Previously conceptualized as epiphyseal osteochondromatosis, recent investigations have uncovered differences between these osteocartilaginous lesions and osteochondromas.

From imaging to reimbursement: what the pediatric radiologist needs to know about health care payers, documentation, coding and billing.

Medical coding and billing processes in the United States are complex, cumbersome and poorly understood by radiologists. Despite the direct implications of radiology documentation on reimbursement, trainees and practicing radiologists typically receive limited relevant training. This article summarizes the payer structure including the state-based Children's Health Insurance Programs, discusses the essential processes by which radiologists request and receive reimbursement, details the mechanisms of coding diagnoses using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes and imaging services using Current Procedural Terminology (CPT) and Healthcare Common Procedure Coding System (HCPCS) codes, and explores reimbursement and coding-related issues specific to pediatric radiology. Appropriate documentation, informed by knowledge of coding, billing and reimbursement fundamentals, facilitates appropriate payment for clinically relevant services provided by pediatric radiologists.

Pediatric neuroendocrine carcinoid tumors: Management, pathology, and imaging findings in a pediatric referral center.

BACKGROUND: While neuroendocrine (carcinoid) tumors are increasingly recognized in the adult population, they are often not suspected in children. PROCEDURE: Retrospective review of all well-differentiated neuroendocrine (carcinoid) tumors was performed based on pathology reports from a quaternary pediatric medical center between January 2003 and June 2016. Clinical presentations, treatment approaches, imaging findings, and outcomes were reviewed and analyzed. RESULTS: A total of 45 cases of pathology-proven carcinoid tumor were reported with an average age of 14.1 years (range: 7-21 years, SD: 2.8 years). Of these cases, 80% (36) were appendiceal, 11% (5) bronchial, 2% (1) colonic, 2% (1) gastric, 2% (1) enteric, and 2% (1) testicular. Metastases were observed in one (3%) appendiceal, one (100%) enteric, and two (40%) bronchial cases. No recurrence was demonstrated in any appendiceal carcinoid cases. Recurrence was seen in one of three extra-appendiceal gastrointestinal tumors. Tumor site and size significantly correlated with metastases and recurrence. CONCLUSIONS: Contrary to recent epidemiological investigations in adults, appendiceal carcinoid tumors remain the most common site for pediatric carcinoid tumors. Appendiceal carcinoid tumors exhibited benign clinical courses without recurrence during short-term follow-up. Extra-appendiceal gastrointestinal carcinoid tumors exhibited much more aggressive behavior with greater metastases and recurrence. Bronchial carcinoid tumors demonstrated good clinical response to resection even in cases with mediastinal lymph node involvement. While increased use of urine 5-HIAA levels and somatostatin receptor-specific imaging might improve detection and guide management of extra-appendiceal carcinoid tumors, longer-term follow-up is needed.

Pediatric Neuroendocrine Carcinoid Tumors: Review of Diagnostic Imaging Findings and Recent Advances.

OBJECTIVE: Although rare, pediatric neuroendocrine tumors including carcinoid tumor have increased in incidence over the past few decades. Despite increased recognition, survival rates have not significantly improved. Earlier detection of these tumors is necessary to improve clinical outcomes. This article discusses imaging approaches for detecting pediatric carcinoid tumors including anatomic imaging methods such as CT and MRI as well as functional imaging methods targeting the somatostatin receptor including 111In-labeled octreotide and newer 68Ga-based radiotracers that may hold promise in hybrid PET/CT or PET/MRI. CONCLUSION: Improvements in functional imaging with novel somatostatin receptor-specific radiotracers along with fused functional and anatomic imaging have substantially improved the clinical detection of carcinoid tumors. Although rare, these tumors are encountered in children, and an awareness of the appropriate use of various imaging methods is essential for pediatric specialists. Further research is needed to ascertain the diagnostic value of newer imaging methods and radiotracer-based treatment approaches, especially in the pediatric population.

Oxazolidinone-based allosteric modulators of mGluR5: Defining molecular switches to create a pharmacological tool box.

Herein we describe the structure activity relationships uncovered in the pursuit of an mGluR5 positive allosteric modulator (PAM) for the treatment of schizophrenia. It was discovered that certain modifications of an oxazolidinone-based chemotype afforded predictable changes in the pharmacological profile to give analogs with a wide range of functional activities. The discovery of potent silent allosteric modulators (SAMs) allowed interrogation of the mechanism-based liabilities associated with mGluR5 activation and drove our medicinal chemistry effort toward the discovery of low efficacy (fold shift) PAMs devoid of agonist activity. This work resulted in the identification of dipyridyl 22 (BMS-952048), a compound with a favorable free fraction, efficacy in a rodent-based cognition model, and low potential for convulsions in mouse.