Nonaneurysmal perimesencephalic subarachnoid hemorrhage on noncontrast head CT: An accuracy, inter-rater, and intra-rater reliability study.

BACKGROUND AND PURPOSE: To evaluate the reliability and accuracy of nonaneurysmal perimesencephalic subarachnoid hemorrhage (NAPSAH) on Noncontrast Head CT (NCCT) between numerous raters. MATERIALS AND METHODS: 45 NCCT of adult patients with SAH who also had a catheter angiography (CA) were independently evaluated by 48 diverse raters; 45 raters performed a second assessment one month later. For each case, raters were asked: 1) whether they judged the bleeding pattern to be perimesencephalic; 2) whether there was blood anterior to brainstem; 3) complete filling of the anterior interhemispheric fissure (AIF); 4) extension to the lateral part of the sylvian fissure (LSF); 5) frank intraventricular hemorrhage; 6) whether in the hypothetical presence of a negative CT angiogram they would still recommend CA. An automatic NAPSAH diagnosis was also generated by combining responses to questions 2-5. Reliability was estimated using Gwet's AC1 (κG), and the relationship between the NCCT diagnosis of NAPSAH and the recommendation to perform CA using Cramer's V test. Multi-rater accuracy of NCCT in predicting negative CA was explored. RESULTS: Inter-rater reliability for the presence of NAPSAH was moderate (κG = 0.58; 95%CI: 0.47, 0.69), but improved to substantial when automatically generated (κG = 0.70; 95%CI: 0.59, 0.81). The most reliable criteria were the absence of AIF filling (κG = 0.79) and extension to LSF (κG = 0.79). Mean intra-rater reliability was substantial (κG = 0.65). NAPSAH weakly correlated with CA decision (V = 0.50). Mean sensitivity and specificity were 58% (95%CI: 44%, 71%) and 83 % (95%CI: 72 %, 94%), respectively. CONCLUSION: NAPSAH remains a diagnosis of exclusion. The NCCT diagnosis was moderately reliable and its impact on clinical decisions modest.

Assessment of Radiology Artificial Intelligence Software: A Validation and Evaluation Framework.

Artificial intelligence (AI) software in radiology is becoming increasingly prevalent and performance is improving rapidly with new applications for given use cases being developed continuously, oftentimes with development and validation occurring in parallel. Several guidelines have provided reporting standards for publications of AI-based research in medicine and radiology. Yet, there is an unmet need for recommendations on the assessment of AI software before adoption and after commercialization. As the radiology AI ecosystem continues to grow and mature, a formalization of system assessment and evaluation is paramount to ensure patient safety, relevance and support to clinical workflows, and optimal allocation of limited AI development and validation resources before broader implementation into clinical practice. To fulfil these needs, we provide a glossary for AI software types, use cases and roles within the clinical workflow; list healthcare needs, key performance indicators and required information about software prior to assessment; and lay out examples of software performance metrics per software category. This conceptual framework is intended to streamline communication with the AI software industry and provide healthcare decision makers and radiologists with tools to assess the potential use of these software. The proposed software evaluation framework lays the foundation for a radiologist-led prospective validation network of radiology AI software. Learning Points: The rapid expansion of AI applications in radiology requires standardization of AI software specification, classification, and evaluation. The Canadian Association of Radiologists' AI Tech & Apps Working Group Proposes an AI Specification document format and supports the implementation of a clinical expert evaluation process for Radiology AI software.

Non-contrast CT markers of intracerebral hematoma expansion: a reliability study.

OBJECTIVES: We evaluated whether clinicians agree in the detection of non-contrast CT markers of intracerebral hemorrhage (ICH) expansion. METHODS: From our local dataset, we randomly sampled 60 patients diagnosed with spontaneous ICH. Fifteen physicians and trainees (Stroke Neurology, Interventional and Diagnostic Neuroradiology) were trained to identify six density (Barras density, black hole, blend, hypodensity, fluid level, swirl) and three shape (Barras shape, island, satellite) expansion markers, using standardized definitions. Thirteen raters performed a second assessment. Inter- and intra-rater agreement were measured using Gwet's AC1, with a coefficient > 0.60 indicating substantial to almost perfect agreement. RESULTS: Almost perfect inter-rater agreement was observed for the swirl (0.85, 95% CI: 0.78-0.90) and fluid level (0.84, 95% CI: 0.76-0.90) markers, while the hypodensity (0.67, 95% CI: 0.56-0.76) and blend (0.62, 95% CI: 0.51-0.71) markers showed substantial agreement. Inter-rater agreement was otherwise moderate, and comparable between density and shape markers. Inter-rater agreement was lower for the three markers that require the rater to identify one specific axial slice (Barras density, Barras shape, island: 0.46, 95% CI: 0.40-0.52 versus others: 0.60, 95% CI: 0.56-0.63). Inter-observer agreement did not differ when stratified for raters' experience, hematoma location, volume, or anticoagulation status. Intra-rater agreement was substantial to almost perfect for all but the black hole marker. CONCLUSION: In a large sample of raters with different backgrounds and expertise levels, only four of nine non-contrast CT markers of ICH expansion showed substantial to almost perfect inter-rater agreement. KEY POINTS: • In a sample of 15 raters and 60 patients, only four of nine non-contrast CT markers of ICH expansion showed substantial to almost perfect inter-rater agreement (Gwet's AC1> 0.60). • Intra-rater agreement was substantial to almost perfect for eight of nine hematoma expansion markers. • Only the blend, fluid level, and swirl markers achieved substantial to almost perfect agreement across all three measures of reliability (inter-rater agreement, intra-rater agreement, agreement with the results of a reference reading).

Numerical modeling and observations of seismo-acoustic waves propagating as modes in a fluid-solid waveguide.

This paper discusses the nature of the low-frequency seismo-acoustic waves generated by submarine earthquakes in the ocean. In a finite-depth homogeneous ocean over a semi-infinite solid crust, the derivation of the acoustic equations shows that waves propagate as modes. The waves propagating with the speed of sound in water (T waves) are preceded by waves with frequencies below the Airy phase. Furthermore, the group speeds of these modes are sensitive to the environmental setting. As a test, we applied the spectral finite-element code SPECFEM2D in a simplified configuration with an ocean layer overlaying a solid crust, and a seismic source below a Gaussian seamount surrounded by a flat seafloor. The simulations confirm that the generated T waves and their precursors follow the theoretical dispersion curves. A more realistic environment with a seismically-layered crust and a sound-speed profile in the ocean is then used to predict the expected acoustic modes. Although noisy, recordings by ocean bottom seismometers from the southwest Indian Ocean show T waves preceded by ultra-low frequency waves, which display two modes comparable to the theoretical ones. They are in good agreement for mode 1, whereas, for mode 0, a slight offset in frequency has yet to be explained.

Papilledema: A Review of the Pathophysiology, Imaging Findings, and Mimics.

Increased intracranial pressure is the most common cause of papilledema. Multiple etiologies such as cerebral edema, hydrocephalus, space occupying lesions, infection, and idiopathic intracranial hypertension among others should be considered. Imaging plays a critical role in the detection of pathologies that can cause papilledema. MRI with contrast and CE-MRV, in particular, are key for the diagnosis of idiopathic intracranial hypertension. This review will focus in common and infrequent causes of papilledema, the role of imaging in patients with papilledema as well as its potential mimickers.

Angiographic results of surgical or endovascular treatment of intracranial aneurysms: a systematic review and inter-observer reliability study.

PURPOSE: Results of surgical or endovascular treatment of intracranial aneurysms are often assessed using angiography. A reliable method to report results irrespective of treatment modality is needed to enable comparisons. Our goals were to systematically review existing classification systems, and to propose a 3-point classification applicable to both treatments and assess its reliability. METHODS: We conducted two systematic reviews on classification systems of angiographic results after clipping or coiling to select a simple 3-category scale that could apply to both treatments. We then circulated an electronic portfolio of angiograms of clipped (n=30) or coiled (n=30) aneurysms, and asked raters to evaluate the degree of occlusion using this scale. Raters were also asked to choose an appropriate follow-up management for each patient based on the degree of occlusion. Agreement was assessed using Krippendorff's α statistics (αK), and relationship between occlusion grade and clinical management was analyzed using Fisher's exact and Cramer's V tests. RESULTS: The systematic reviews found 70 different grading scales with heterogeneous reliability (kappa values from 0.12 to 1.00). The 60-patient portfolio was independently evaluated by 19 raters of diverse backgrounds (neurosurgery, radiology, and neurology) and experience. There was substantial agreement (αK=0.76, 95%CI, 0.67-0.83) between raters, regardless of background, experience, or treatment used. Intra-rater agreement ranged from moderate to almost perfect. A strong relationship was found between angiographic grades and management decisions (Cramer's V: 0.80±0.12). CONCLUSION: A simple 3-point scale demonstrated sufficient reliability to be used in reporting aneurysm treatments or in evaluating treatment results in comparative randomized trials.

Corticotroph tumor progression during long-term therapy with osilodrostat in a patient with persistent Cushing's disease.

PURPOSE: Corticotroph tumor progression (CTP) or Nelson's syndrome (NS) can occur in patients with Cushing's disease (CD) following bilateral adrenalectomy. It has rarely been observed in patients treated with long-term medical therapy for persistent CD. Osilodrostat (LCI699) is a new steroidogenesis inhibitor of 11ß-hydroxylase (CYP11ß1) that induced remission of hypercortisolism in 86% of patients with refractory CD in the randomized placebo-controlled trial LINC-3 (NCT02180217). METHODS: A 40-year-old woman with persistent CD following transsphenoidal surgery was treated with osilodrostat in the LINC-3 trial and was followed with regular hormonal assessments and imaging of residual corticotroph tumor. RESULTS: Under oral therapy with osilodrostat 10 mg twice daily, urinary free cortisol (UFC) normalized and clinical signs of CD regressed during therapy. However after 4 years of treatment, ACTH levels increased from 73 to 500 pmol/L and corticotroph tumor size increased rapidly from 3 to 14 mm, while UFCs remained well controlled. Surgical resection of an atypical tumor with weak ACTH expression and increased proliferative index (Ki-67 ≥ 8%) resulted in current remission but will require close follow-up. CONCLUSION: This case highlights the importance of monitoring ACTH and corticotroph tumor size in patients with persistent CD, either under effective treatment with steroidogenesis inhibitors or after bilateral adrenalectomy.

Three-dimensional modeling of earthquake generated acoustic waves in the ocean in simplified configurations.

The low-frequency (4-40 Hz) acoustic waves generated by undersea earthquakes are of great importance to monitor the low-level seismic activity associated with seafloor spreading ridges. To better understand the near-source interaction of seismic waves with the seafloor and the resulting generation of low-frequency acoustic waves, the wave propagation in a solid medium (the Earth's crust) and in the overlaying fluid medium (the ocean) were jointly simulated using a three-dimensional (3D) spectral finite-element code (SPECFEM3D). Due to numerical limitations of 3D simulations, the focus was on simple model configurations with a 1 Hz source located below a Gaussian seamount or ridge. The simulated acoustic waves (0-2.5 Hz) propagate as Rayleigh modes and are affected by modal dispersion; their horizontal speed increases away from the source and reaches the sound speed about 140 km away. The amplitude of the generated acoustic waves is affected by the shape of the seafloor topography above the seismic source, as well as their travel times to hydrophones. Consequently, localization of the acoustic sources by trilateration from arrival times may be biased by 3D-effects, and thus the seismic/acoustic conversion zone may not match the epicenter.

Effects of SYN1Q555X mutation on cortical gray matter microstructure.

A new Q555X mutation on the SYN1 gene was recently found in several members of a family segregating dyslexia, epilepsy, and autism spectrum disorder. To describe the effects of this mutation on cortical gray matter microstructure, we performed a surface-based group study using novel diffusion and quantitative multiparametric imaging on 13 SYN1Q555X mutation carriers and 13 age- and sex-matched controls. Specifically, diffusion kurtosis imaging (DKI) and neurite orientation and dispersion and density imaging (NODDI) were used to analyze multi-shell diffusion data and obtain parametric maps sensitive to tissue structure, while quantitative metrics sensitive to tissue composition (T1, T2* and relative proton density [PD]) were obtained from a multi-echo variable flip angle FLASH acquisition. Results showed significant microstructural alterations in several regions usually involved in oral and written language as well as dyslexia. The most significant changes in these regions were lowered mean diffusivity and increased fractional anisotropy. This study is, to our knowledge, the first to successfully use diffusion imaging and multiparametric mapping to detect cortical anomalies in a group of subjects with a well-defined genotype linked to language impairments, epilepsy and autism spectrum disorder (ASD).

Low-Energy Virtual Monochromatic Dual-Energy Computed Tomography Images for the Evaluation of Head and Neck Squamous Cell Carcinoma: A Study of Tumor Visibility Compared With Single-Energy Computed Tomography and User Acceptance.

OBJECTIVE: Dual-energy computed tomography (CT) 40-keV virtual monochromatic images (VMIs) have been reported to improve visualization of head and neck squamous cell carcinoma, but a direct comparison to single-energy CT (SECT) is lacking, and there is debate regarding subjective user preference. We compared 40-keV VMIs with SECT and performed a subjective evaluation of their utility and acceptability for clinical use. METHODS: A total of 60 dual-energy CT and 60 SECT scans from 2 different institutions were evaluated. Tumor conspicuity was evaluated objectively using absolute and relative attenuation and subjectively by 3 head and neck specialists and 3 general radiologists. RESULTS: Tumors had significantly higher absolute and relative attenuation on 40-keV VMIs (P < 0.0001). Subjectively, the 40-keV VMIs improved visualization, with substantial (κ, 0.61-0.80) to almost perfect (κ, 0.81-1) interrater agreements. CONCLUSIONS: The 40-keV VMIs improve tumor visibility objectively and subjectively both by head and neck specialists and general radiologists.

Cell-cell contacts confine public goods diffusion inside Pseudomonas aeruginosa clonal microcolonies.

The maintenance of cooperation in populations where public goods are equally accessible to all but inflict a fitness cost on individual producers is a long-standing puzzle of evolutionary biology. An example of such a scenario is the secretion of siderophores by bacteria into their environment to fetch soluble iron. In a planktonic culture, these molecules diffuse rapidly, such that the same concentration is experienced by all bacteria. However, on solid substrates, bacteria form dense and packed colonies that may alter the diffusion dynamics through cell-cell contact interactions. In Pseudomonas aeruginosa microcolonies growing on solid substrate, we found that the concentration of pyoverdine, a secreted iron chelator, is heterogeneous, with a maximum at the center of the colony. We quantitatively explain the formation of this gradient by local exchange between contacting cells rather than by global diffusion of pyoverdine. In addition, we show that this local trafficking modulates the growth rate of individual cells. Taken together, these data provide a physical basis that explains the stability of public goods production in packed colonies.

Spherical wave reflection in layered media with rough interfaces: Three-dimensional modeling.

In the context of sediment characterization, layer interface roughnesses may be responsible for sound-speed profile measurement uncertainties. To study the roughness influence, a three-dimensional (3D) modeling of a layered seafloor with rough interfaces is necessary. Although roughness scattering has an abundant literature, 3D modeling of spherical wave reflection on rough interfaces is generally limited to a single interface (using Kirchhoff-Helmholtz integral) or computationally expensive techniques (finite difference or finite element method). In this work, it is demonstrated that the wave reflection over a layered medium with irregular interfaces can be modeled as a sum of integrals over each interface. The main approximations of the method are the tangent-plane approximation, the Born approximation (multiple reflection between interfaces are neglected) and flat-interface approximation for the transmitted waves into the sediment. The integration over layer interfaces results in a method with reasonable computation cost.

A cell biological view of the siderophore pyochelin iron uptake pathway in Pseudomonas aeruginosa.

Pyochelin (PCH) is a siderophore produced and secreted by Pseudomonas aeruginosa for iron capture. Using (55) Fe uptake and binding assays, we showed that PCH-Fe uptake in P. aeruginosa involves, in addition to the highly studied outer membrane transporter FptA, the inner membrane permease FptX, which recognizes PCH-(55) Fe with an affinity of 0.6 ± 0.2 nM and transports the ferri-siderophore complex from the periplasm into the cytoplasm: fptX deletion inhibited (55) Fe accumulation in the bacterial cytoplasm. Chromosomal replacement was used to generate P. aeruginosa strains producing fluorescent fusions with FptX, PchR (an AraC regulator), PchA (the first enzyme involved in the PCH biosynthesis) and PchE (a non-ribosomic peptide-synthetase involved in a further step). Fluorescence imaging and cellular fractionation showed a uniform repartition of FptX in the inner membrane. PchA and PchE were found in the cytoplasm, associated to the inner membrane all over the bacteria and also concentrated at the bacterial poles. PchE clustering at the bacterial poles was dependent on PchA expression, but on the opposite PchA clustering and membrane association was PchE-independent. PchA and PchE cellular organization suggests the existence of a siderosome for PCH biosynthesis as previously proposed for pyoverdine biosynthesis (another siderophore produced by P. aeruginosa).

Canadian Expert Panel Recommendations for MRI Use in MS Diagnosis and Monitoring.

BACKGROUND: A definitive diagnosis of multiple sclerosis (MS), as distinct from a clinically isolated syndrome, requires one of two conditions: a second clinical attack or particular magnetic resonance imaging (MRI) findings as defined by the McDonald criteria. MRI is also important after a diagnosis is made as a means of monitoring subclinical disease activity. While a standardized protocol for diagnostic and follow-up MRI has been developed by the Consortium of Multiple Sclerosis Centres, acceptance and implementation in Canada have been suboptimal. METHODS: To improve diagnosis, monitoring, and management of a clinically isolated syndrome and MS, a Canadian expert panel created consensus recommendations about the appropriate application of the 2010 McDonald criteria in routine practice, strategies to improve adherence to the standardized Consortium of Multiple Sclerosis Centres MRI protocol, and methods for ensuring effective communication among health care practitioners, in particular referring physicians, neurologists, and radiologists. RESULTS: This article presents eight consensus statements developed by the expert panel, along with the rationale underlying the recommendations and commentaries on how to prioritize resource use within the Canadian healthcare system. CONCLUSIONS: The expert panel calls on neurologists and radiologists in Canada to incorporate the McDonald criteria, the Consortium of Multiple Sclerosis Centres MRI protocol, and other guidance given in this consensus presentation into their practices. By improving communication and general awareness of best practices for MRI use in MS diagnosis and monitoring, we can improve patient care across Canada by providing timely diagnosis, informed management decisions, and better continuity of care.