Inter- and intraobserver agreement for CT measurement of mandibular and medial retropharyngeal lymph nodes is excellent in dogs with histologically confirmed oral melanoma.

Mandibular and medial retropharyngeal lymph nodes are routinely evaluated with CT when staging dogs with oral melanomas. While size alone is considered inadequate for detecting nodal metastasis, it is critical in evaluating treatment response, as clinical decisions are based on changes in size. It is common for different radiologists to measure the size of pre- and posttreatment lymph nodes in the same patient. The objective of this retrospective, observer agreement study was to evaluate the inter- and intraobserver agreement in measuring canine mandibular and medial retropharyngeal lymph nodes by a diverse population of veterinary radiologists and trainees. Fourteen dogs with documented oral melanoma and head CT studies identified from records of a single institution were included in this study. North American veterinary radiologists and trainees were recruited to measure the mandibular and medial retropharyngeal lymph nodes; in triplicate. Prior to performing the study measurements, participants completed a training tool demonstrating the lymph node measurements. Overall, interobserver intraclass correlation coefficient (ICC) was 0.961 (95% confidence interval [CI]: 0.946, 0.972) and intraobserver ICC was 0.977 (95% CI: 0.968, 0.983), indicating excellent agreement (ICC > 0.9 considered excellent). Similar findings were noted following sub-analysis for most variables (experience, size, laterality, axis of measurement). These results suggest that follow-up measurement of the long and short axis of the mandibular lymph nodes and short axis of the medial retropharyngeal lymph nodes in the transverse plane, performed by different veterinary radiologists using the same method of measure, should have minimal impact on clinical decision making.

Canadian Association of Radiologists Recommendations for the Safe Use of MRI During Pregnancy.

The use of magnetic resonance imaging (MRI) during pregnancy is associated with concerns among patients and health professionals with regards to fetal safety. In this work, the Canadian Association of Radiologists (CAR) Working Group on MRI in Pregnancy presents recommendations for the use of MRI in pregnancy, derived from literature review as well as expert panel opinions and discussions. The working group, which consists of academic subspecialty radiologists and obstetrician-gynaecologists, aimed to provide updated, evidence-based recommendations addressing safety domains related to energy deposition, acoustic noise, and gadolinium-based contrast agent use based on magnetic field strength (1.5T and 3T) and trimester scanned, in addition to the effects of sedative use and occupational exposure.

Two children with extra-nodal Mycobacterium avium complex infection.

Mycobacterium avium complex (MAC) is usually considered an opportunistic organism, which infects immunocompromised children or those with structural airway abnormalities. We present two cases of MAC infection affecting immune competent children, likely from hot tubs with primary involvement of pulmonary and urinary systems. These cases highlight the importance of asking about hot tub use in immune competent children with suspected or confirmed MAC infections.

Integrated genome and transcriptome sequencing identifies a noncoding mutation in the genome replication factor DONSON as the cause of microcephaly-micromelia syndrome.

While next-generation sequencing has accelerated the discovery of human disease genes, progress has been largely limited to the "low hanging fruit" of mutations with obvious exonic coding or canonical splice site impact. In contrast, the lack of high-throughput, unbiased approaches for functional assessment of most noncoding variants has bottlenecked gene discovery. We report the integration of transcriptome sequencing (RNA-seq), which surveys all mRNAs to reveal functional impacts of variants at the transcription level, into the gene discovery framework for a unique human disease, microcephaly-micromelia syndrome (MMS). MMS is an autosomal recessive condition described thus far in only a single First Nations population and causes intrauterine growth restriction, severe microcephaly, craniofacial anomalies, skeletal dysplasia, and neonatal lethality. Linkage analysis of affected families, including a very large pedigree, identified a single locus on Chromosome 21 linked to the disease (LOD > 9). Comprehensive genome sequencing did not reveal any pathogenic coding or canonical splicing mutations within the linkage region but identified several nonconserved noncoding variants. RNA-seq analysis detected aberrant splicing in DONSON due to one of these noncoding variants, showing a causative role for DONSON disruption in MMS. We show that DONSON is expressed in progenitor cells of embryonic human brain and other proliferating tissues, is co-expressed with components of the DNA replication machinery, and that Donson is essential for early embryonic development in mice as well, suggesting an essential conserved role for DONSON in the cell cycle. Our results demonstrate the utility of integrating transcriptomics into the study of human genetic disease when DNA sequencing alone is not sufficient to reveal the underlying pathogenic mutation.

Antenatal diagnosis of bronchopulmonary sequestration: A case report and review of the literature.

Congenital lung malformations are a constellation of pathologies that can be diagnosed antenatally by ultrasound and fetal MRI. Ultrasound is considered the modality of choice for a routine assessment of second-trimester scans worldwide. Bronchopulmonary sequestration (BPS) and congenital pulmonary airway malformation (CPAM) are the 2 most common echogenic chest masses discovered incidentally during routine ultrasound scans in the second trimester. This paper describes BPS and differentiates it from CPAM sonographically in utero. An extensive literature search involving antenatal ultrasound is undertaken to review the most up-to-date understanding of the BPS. Furthermore, a case study at our institution and the literature review will help better describe the salient features of BPS. A 41-year-old female G3P1 visits our department for a routine second-trimester ultrasound. An echogenic lesion with a cystic component is visualized in this scan. Based on the grayscale and color imaging, this complex echogenic lesion was reported as CPAM and was referred to fetal assessment for confirmation. The fetal assessment diagnosed the lesion as BPS because of the pathognomonic feeding vessel from the thoracic aorta. Regardless of the congenital lung mass, any large mass compromising fetal well-being is an indication for intervention. The prognosis of BPS in the absence of fetal hydrops is excellent. A robust collaboration among radiologists, obstetricians, and pediatricians is required for the best outcome for the pregnancy and the neonate.

Blood and Hand Surface Lead in Veterinary Workers Using Lead Shielding During Diagnostic Radiography.

OBJECTIVES: The objectives are to compare lead blood concentrations in veterinary workers using lead shielding with concentrations in a control population, to measure hand surface lead before and after use of shielding, and to compare hand surface lead with and without the use of disposable gloves worn under hand shielding. METHODS: Blood and hand wipe samples were analyzed for lead using inductively coupled plasma mass spectrometry. RESULTS: There was no difference in blood lead between exposed and control groups. After lead glove use, 69% (18/26) of hand surface lead samples from workers not using disposable gloves were greater than 500 µg, 42% (11/26) were greater than 1000 µg, and 12% (3/26) were greater than 2000 µg. CONCLUSIONS: If lead shielding use is unavoidable, disposable gloves should be worn, and skin should be decontaminated after use.

MRI overestimates articular cartilage thickness and volume compared to synchrotron radiation phase-contrast imaging.

Accurate evaluation of morphological changes in articular cartilage are necessary for early detection of osteoarthritis (OA). 3T magnetic resonance imaging (MRI) has highly sensitive contrast resolution and is widely used clinically to detect OA. However, synchrotron radiation phase-contrast imaging computed tomography (SR-PCI) can also provide contrast to tissue interfaces that do not have sufficient absorption differences, with the added benefit of very high spatial resolution. Here, MRI was compared with SR-PCI for quantitative evaluation of human articular cartilage. Medial tibial condyles were harvested from non-OA donors and from OA patients receiving knee replacement surgery. Both imaging methods revealed that average cartilage thickness and cartilage volume were significantly reduced in the OA group, compared to the non-OA group. When comparing modalities, the superior resolution of SR-PCI enabled more precise mapping of the cartilage surface relative to MRI. As a result, MRI showed significantly higher average cartilage thickness and cartilage volume, compared to SR-PCI. These data highlight the potential for high-resolution imaging of articular cartilage using SR-PCI as a solution for early OA diagnosis. Recognizing current limitations of using a synchrotron for clinical imaging, we discuss its nascent utility for preclinical models, particularly longitudinal studies of live animal models of OA.

Indirect magnetic resonance lymphography of the head and neck of dogs using Gadofluorine M and a conventional gadolinium contrast agent: a pilot study.

The purpose of this pilot study was to evaluate lymph node enhancement with an indirect magnetic resonance (MR) lymphography technique using 2 different contrast agents in the head and neck region of healthy dogs. Five dogs were imaged at various times after intradermal injection of gadoversetamide and Gadofluorine M (minimum of 1 week apart) in the right and left mandibular, temporal, and lateral neck regions. We observed consistent progressive enhancement with time in the mandibular, retropharyngeal, and superficial cervical lymph nodes. The node enhancement was comparable for both contrast agents. Contrast enhancement of the parotid lymph nodes was not seen. We conclude that this technique of indirect MR lymphography using either agent could be used to identify those lymph nodes at highest risk of metastatic disease in dogs with cancer, and to guide staging and treatment.

Lymphographie par résonance magnétique indirecte de la tête et du cou des chiens en utilisant Gadofluorine M et un agent de contraste conventionnel au gadolinium : étude pilote. Le but de cette étude pilote était d'évaluer le contraste des ganglions lymphatiques à l'aide d'une technique de lymphographie par résonance magnétique (RM) indirecte en utilisant 2 agents de contraste différents dans la région de la tête et du cou des chiens en santé. L'imagerie de 5 chiens a été réalisée à divers moments après l'injection intradermique de gadoversétamide et de Gadofluorine M (avec un intervalle minimum de 1 semaine) dans les régions mandibulaires droite et gauche, temporale et du cou. Nous avons observé une augmentation progressive constante dans le temps dans les ganglions mandibulaires, rétropharyngiens et cervicaux superficiels. Le contraste des ganglions était comparable pour les deux agents. L'augmentation de contraste des ganglions lymphatiques parotidiens n'a pas été vue. Nous concluons que cette technique de lymphographie par RM indirecte, en utilisant l'un ou l'autre des agents, pourrait être utilisée pour identifier les ganglions lymphatiques les plus à risque de maladie métastasique chez les chiens atteints de cancer et pour guider la détermination des stades et le traitement.(Traduit par Isabelle Vallières).

Developing a Microbubble-Based Contrast Agent for Synchrotron Multiple-Image Radiography.

PURPOSE: Multiple-image radiography (MIR) is an analyzer-based synchrotron X-ray imaging approach capable of dissociating absorption, refraction, and scattering components of X-ray interaction with the material. It generates additional image contrast mechanisms (besides absorption), especially in the case of soft tissues, while minimizing absorbed radiation dose. Our goal is to develop a contrast agent for MIR using ultrasound microbubbles by carrying out a systematic assessment of size, shell material, and concentration. PROCEDURES: Microbubbles were synthesized with two different shell materials: phospholipid and polyvinyl-alcohol. Polydisperse perfluorobutane-filled lipid microbubbles were divided into five size groups using centrifugation. Two distributions of air-filled polymer microbubbles were generated: 2-3 µm and 3-4 µm. A subset of polymer microbubbles 3-4 µm had iron oxide nanoparticles incorporated into their shell or coated on their surface. Microbubbles were immobilized in agar with different concentrations: 5 × 107, 5 × 106, and 5 × 105 MBs/ml. MIR was conducted on the BioMedical Imaging and Therapy beamline at the Canadian Light Source. Three images were generated: Gaussian amplitude, refraction, and ultra-small-angle X-ray scattering (USAXS). The contrast signal was quantified by measuring mean pixel values and comparing them with agar. RESULTS: No difference was detected in absorption or refraction images of all tested microbubbles. Using USAXS, a significant signal increase was observed with lipid microbubbles 6-10 µm at the highest concentration (p = 0.02), but no signal was observed at lower concentrations. CONCLUSIONS: These data indicate that lipid microbubbles 6-10 µm are candidates as contrast agents for MIR, specifically for USAXS. A minimum concentration of 5 × 107 microbubbles (lipid-shell 6-10 µm) per milliliter was needed to generate a detectable signal.

Idiopathic infantile arterial calcification in a 12-year-old girl presenting as chronic mesenteric ischemia: imaging findings and angioplasty results.

We report an unusual case of chronic mesenteric ischemia presenting in a 12-year-old girl with idiopathic infantile arterial calcinosis (IIAC). This is the first reported case in the literature of chronic mesenteric ischemia in the setting of IIAC. The girl presented with a classical history of postprandial abdominal pain. Imaging demonstrated significant stenoses of the celiac axis, superior mesenteric artery (SMA) and inferior mesenteric artery (IMA). Angioplasty of the celiac axis and SMA was attempted, with successful dilation of the SMA only. At 3-, 6- and 12-month follow-ups, the child's symptoms had almost resolved. This case report has three important ramifications: chronic mesenteric ischemia is a possible clinical presentation in children with IACC, pre-angioplasty imaging is important in guiding treatment approach, and angioplasty was effective in this case of chronic mesenteric ischemia and offers hope for other similarly affected children.

Developing a Microbubble-Based Contrast Agent for Synchrotron In-Line Phase Contrast Imaging.

OBJECTIVE: X-ray phase contrast imaging generates contrast from refraction of X-rays, enhancing soft tissue contrast compared to conventional absorption-based imaging. Our goal is to develop a contrast agent for X-ray in-line phase contrast imaging (PCI) based on ultrasound microbubbles (MBs), by assessing size, shell material, and concentration. METHODS: Polydisperse perfluorobutane-core lipid-shelled MBs were synthesized and size separated into five groups between 1 and 10 µm. We generated two size populations of polyvinyl-alcohol (PVA)-MBs, 2-3 µm and 3-4 µm, whose shells were either coated or integrated with iron oxide nanoparticles (SPIONs). Microbubbles were then embedded in agar at three concentrations: 5 × 107, 5 × 106 and 5 × 105 MBs/ml. In-line phase contrast imaging was performed at the Canadian Light Source with filtered white beam micro-computed tomography. Phase contrast intensity was measured by both counting detectable MBs, and comparing mean pixel values (MPV) in minimum and maximum intensity projections of the overall samples. RESULTS: Individual lipid-MBs 6-10 µm, lipid-MBs 4-6 µm and PVA-MBs coated with SPIONs were detectable at each concentration. At the highest concentration, lipid-MBs 6-10 µm and 4-6 µm showed an overall increase in positive contrast, whereas at a moderate concentration, only lipid-MBs 6-10 µm displayed an increase. Negative contrast was also observed from two largest lipid-MBs at high concentration. CONCLUSION: These data indicate that lipid-MBs larger than 4 µm are candidates for PCI, and 5 × 106 MBs/ml may be the lowest concentration suitable for generating visible phase contrast in vivo. SIGNIFICANCE: Identifying a suitable MB for PCI may facilitate future clinical translation.

Clinical and radiologic findings in an adult male with dysosteosclerosis.

Dysosteosclerosis is a rare autosomal recessive skeletal dysplasia characterized by osteosclerosis and platyspondyly. A case of dysosteosclerosis in a 17-year-old male from our institution was first published by Houston et al. 1978. This patient has survived into adulthood and to our knowledge, is the only reported adult with dysosteosclerosis. We will review the clinical and radiographic features in our patient.

Data of low-dose phase-based X-ray imaging for in situ soft tissue engineering assessments.

This article presents the data of using three phase-based X-ray imaging techniques to characterize biomaterial scaffold and soft tissues in situ, as reported in our study "Low-dose phase-based X-ray imaging techniques for in situ soft tissue engineering assessments" [1]. The examined parameters include the radiation dose, scan time, and image quality, which are all critical to longitudinal in situ live animal assessments. The data presented were obtained from three dimensional imaging of scaffolds in situ cartilage by means of synchrotron-based computed tomography-diffraction enhanced imaging (CT-DEI), analyzer based imaging (CT-ABI), and in-line phase contrast imaging (CT-PCI) at standard and low dose imaging modalities.

Low-dose phase-based X-ray imaging techniques for in situ soft tissue engineering assessments.

In tissue engineering, non-invasive imaging of biomaterial scaffolds and tissues in living systems is essential to longitudinal animal studies for assessments without interrupting the repair process. Conventional X-ray imaging is inadequate for use in soft tissue engineering due to the limited absorption difference between the soft tissue and biomaterial scaffolds. X-ray phase-based imaging techniques that derive contrast from refraction or phase effects rather than absorption can provide the necessary contrast to see low-density biomaterial scaffolds and tissues in large living systems. This paper explores and compares three synchrotron phase-based X-ray imaging techniques-computed tomography (CT)-diffraction enhanced imaging (DEI), -analyzer based imaging (ABI), and -phase contrast imaging (PCI)-for visualization and characterization of low-density biomaterial scaffolds and tissues in situ for non-invasive soft tissue engineering assessments. Intact pig joints implanted with polycaprolactone scaffolds were used as the model to assess and compare the imaging techniques in terms of different qualitative and quantitative criteria. For long-term in vivo live animal imaging, different strategies for reducing the imaging radiation dose and scan time-reduced number of CT projections, region of interest, and low resolution imaging-were examined with the presented phase-based imaging techniques. The results demonstrated promising capabilities of the phase-based techniques for visualization of biomaterial scaffolds and soft tissues in situ. The low-dose imaging strategies were illustrated effective for reducing the radiation dose to levels appropriate for live animal imaging. The comparison among the imaging techniques suggested that CT-DEI has the highest efficiency in retaining image contrast at considerably low radiation doses.

Diffraction-Enhanced Computed Tomographic Imaging of Growing Piglet Joints by Using a Synchrotron Light Source.

The objective of this project was to develop and test a new technology for imaging growing joints by means of diffraction-enhanced imaging (DEI) combined with CT and using a synchrotron radiation source. DEI-CT images of an explanted 4-wk-old piglet stifle joint were acquired by using a 40-keV beam. The series of scanned slices was later 'stitched' together, forming a 3D dataset. High-resolution DEI-CT images demonstrated fine detail within all joint structures and tissues. Striking detail of vasculature traversing between bone and cartilage, a characteristic of growing but not mature joints, was demonstrated. This report documents for the first time that DEI combined with CT and a synchrotron radiation source can generate more detailed images of intact, growing joints than can currently available conventional imaging modalities.

Cystic fibrosis: an unusual neonatal presentation.

In mechanically ventilated neonates it is not uncommon to observe obstructive atelectasis from various causes. However it is extremely rare to see mucous plugging and massive pulmonary atelectasis in the absence of infection, aspiration, and respiratory distress syndrome in the first couple of days of life. In this report we describe a neonate born with cystic fibrosis (CF) who presented to us with hypoxic respiratory failure, pulmonary hypertension, and hypercarbia without lactic acedemia from sticky mucous plugging and massive lung collapse. Neonatal respiratory distress and wide spread pulmonary atelectasis has not been reported in infants born with CF.

A median-Gaussian filtering framework for Moiré pattern noise removal from X-ray microscopy image.

Moiré pattern noise in Scanning Transmission X-ray Microscopy (STXM) imaging introduces significant errors in qualitative and quantitative image analysis. Due to the complex origin of the noise, it is difficult to avoid Moiré pattern noise during the image data acquisition stage. In this paper, we introduce a post-processing method for filtering Moiré pattern noise from STXM images. This method includes a semi-automatic detection of the spectral peaks in the Fourier amplitude spectrum by using a local median filter, and elimination of the spectral noise peaks using a Gaussian notch filter. The proposed median-Gaussian filtering framework shows good results for STXM images with the size of power of two, if such parameters as threshold, sizes of the median and Gaussian filters, and size of the low frequency window, have been properly selected.

Diffraction enhanced imaging of a rat model of gastric acid aspiration pneumonitis.

RATIONALE AND OBJECTIVES: Diffraction-enhanced imaging (DEI) is a type of phase contrast x-ray imaging that has improved image contrast at a lower dose than conventional radiography for many imaging applications, but no studies have been done to determine if DEI might be useful for diagnosing lung injury. The goals of this study were to determine if DEI could differentiate between healthy and injured lungs for a rat model of gastric aspiration and to compare diffraction-enhanced images with chest radiographs. MATERIALS AND METHODS: Radiographs and diffraction-enhanced chest images of adult Sprague Dawley rats were obtained before and 4 hours after the aspiration of 0.4 mL/kg of 0.1 mol/L hydrochloric acid. Lung damage was confirmed with histopathology. RESULTS: The radiographs and diffraction-enhanced peak images revealed regions of atelectasis in the injured rat lung. The diffraction-enhanced peak images revealed the full extent of the lung with improved clarity relative to the chest radiographs, especially in the portion of the lower lobe that extended behind the diaphragm on the anteroposterior projection. CONCLUSIONS: For a rat model of gastric acid aspiration, DEI is capable of distinguishing between a healthy and an injured lung and more clearly than radiography reveals the full extent of the lung and the lung damage.

Biomolecular diagnosis of human glioblastoma multiforme using Synchrotron mid-infrared spectromicroscopy.

Glioblastoma multiforme (GBM) is one of the most malignant human tumors, with a uniformly poor outcome. One obstacle in curing malignant brain tumors is the limitation of conventional light microscopy in detecting microscopic residual tumor in biopsy samples from the perimeter of the surgically resected tumor. We further refined the identification of GBM tumor tissue at the sub-cellular level, utilising the technique of Synchrotron, sourced mid-infrared (mid-IR) spectromicroscopy. Paired, thin (5 microm) cryosections of snap-frozen human GBM tumor samples removed at elective surgery were mounted on glass slides (hematoxylin and eosin-stained tissue section) and calcium fluoride (CaF2) windows (unstained tissue section for transmission spectromicroscopy), respectively. Concordance of tumor bearing areas identified in the stained section with the unstained IR tissue section was confirmed by the pathologist of the study. Compared with molecular signatures obtained from normal control brain tissue, unique spectroscopic patterns were detected in GBM tumor samples from 6 patients. The identifying features of GBM were: i) high protein-to-lipid ratios (amide I+II/CH2 symmetric stretch; amide I+II/CH2+CH3 symmetric and asymmetric stretch), and ii) considerable enhancement of the intensities of characteristic peaks at 2,957 and 2,871 cm(-1) representing CH3 asymmetric and symmetric stretch, respectively. Spectral data sets were subjected to Ward's algorithm for assignment to similar groups, and then subjected to hierarchical cluster analysis (HCA) by means of false color digital maps. False color images of 5 clusters obtained by HCA identified dominant clusters corresponding to tumor tissue. Corroboration of these findings in a larger number of GBM may allow for more precise identification of these and other types of brain tumors.