Automatic Staging of Cancer Tumors Using AIM Image Annotations and Ontologies.

A second opinion about cancer stage is crucial when clinicians assess patient treatment progress. Staging is a process that takes into account description, location, characteristics, and possible metastasis of tumors in a patient. It should follow standards, such as the TNM Classification of Malignant Tumors. However, in clinical practice, the implementation of this process can be tedious and error prone. In order to alleviate these problems, we intend to assist radiologists by providing a second opinion in the evaluation of cancer stage. For doing this, we developed a TNM classifier based on semantic annotations, made by radiologists, using the ePAD tool. It transforms the annotations (stored using the AIM format), using axioms and rules, into AIM4-O ontology instances. From then, it automatically calculates the liver TNM cancer stage. The AIM4-O ontology was developed, as part of this work, to represent annotations in the Web Ontology Language (OWL). A dataset of 51 liver radiology reports with staging data, from NCI's Genomic Data Commons (GDC), were used to evaluate our classifier. When compared with the stages attributed by physicians, the classifier stages had a precision of 85.7% and recall of 81.0%. In addition, 3 radiologists from 2 different institutions manually reviewed a random sample of 4 of the 51 records and agreed with the tool staging. AIM4-O was also evaluated with good results. Our classifier can be integrated into AIM aware imaging tools, such as ePAD, to offer a second opinion about staging as part of the cancer treatment workflow.

Computational Identification of Tumor Anatomic Location Associated with Survival in 2 Large Cohorts of Human Primary Glioblastomas.

BACKGROUND AND PURPOSE: Tumor location has been shown to be a significant prognostic factor in patients with glioblastoma. The purpose of this study was to characterize glioblastoma lesions by identifying MR imaging voxel-based tumor location features that are associated with tumor molecular profiles, patient characteristics, and clinical outcomes. MATERIALS AND METHODS: Preoperative T1 anatomic MR images of 384 patients with glioblastomas were obtained from 2 independent cohorts (n = 253 from the Stanford University Medical Center for training and n = 131 from The Cancer Genome Atlas for validation). An automated computational image-analysis pipeline was developed to determine the anatomic locations of tumor in each patient. Voxel-based differences in tumor location between good (overall survival of >17 months) and poor (overall survival of <11 months) survival groups identified in the training cohort were used to classify patients in The Cancer Genome Atlas cohort into 2 brain-location groups, for which clinical features, messenger RNA expression, and copy number changes were compared to elucidate the biologic basis of tumors located in different brain regions. RESULTS: Tumors in the right occipitotemporal periventricular white matter were significantly associated with poor survival in both training and test cohorts (both, log-rank P < .05) and had larger tumor volume compared with tumors in other locations. Tumors in the right periatrial location were associated with hypoxia pathway enrichment and PDGFRA amplification, making them potential targets for subgroup-specific therapies. CONCLUSIONS: Voxel-based location in glioblastoma is associated with patient outcome and may have a potential role for guiding personalized treatment.

The harmful effects of aqueous contrast agents on the gastrointestinal tract: a study of mechanism and means of counteraction.

The effect of mildly and strongly hypertonic solutions on intestinal tone and motility was tested with aqueous contrast solutions and with mannitol as a control in 15 dogs. These experiments were repeated in animals premedicated with atropine sulfate and/or methysergide maleate. Intestinal motility was recorded on serial x-ray films. Tone and motility were estimated by variations of intestinal caliber and rate of transit of contrast solution, respectively. The results obtained contradict the currently accepted mechanism of action of iodinated contrast media on the intestinal tract, which assumes that the effect is osmotic like that of a saline laxative. Solutions of different osmolarity produce hyperperistalsis of the same magnitude. This effect begins rapidly after the onset of gastric emptying and much sooner than a significant osmotic fluid shift occurs. Atropine sulfate and methysergide maleate (serotonin blocker), when given individually, are incapable of completely inhibiting hyperperistalsis induced by hypertonic solutions. However, when these agents are given in combination, motility is completely inhibited. The evidence supports a serotonin role in the hyperperistalsis induced by hypertonic solutions, partly by direct action of serotonin on the smooth muscle cells and partly by indirect action on the intramural cholinergic ganglion cells. This concept offers a possible means of eliminating one of the adverse effects of aqueous contrast media on the gastrointestinal tract.

Magnetic susceptibility effects and their application in the development of new ferromagnetic catheters for magnetic resonance imaging.

Newly developed ferromagnetic catheters (Fe-Caths) are more conspicuous than conventional radiographic catheters (Rad-Caths) on magnetic resonance (MR) images because they produce recognizable ferromagnetic signal patterns (FSPs). To determine how MRI parameters influence these patterns, the imaging characteristics of nine Fe-Caths (ferromagnetic concentration 0.01 to 1.0 weight/weight %) were studied systematically and compared with three Rad-Caths. All catheters were studied in stationary and moving phantoms at mid-field (0.38 T) and high-field (1.5 T) strength using spin-echo and gradient-echo pulse sequences. Rad-Caths always produced a signal void. Fe-Caths produced FSPs, the size of which depended on the orientation of the catheter with respect to the main magnetic field, the concentration of ferromagnetic agent in the catheter, and the direction and strength of the frequency encoding gradient. When Fe-Caths were positioned perpendicular to the main magnetic field, they produced FSPs; however, when they were parallel to the main magnetic field, Fe-Caths produced no FSP, thus having a similar appearance to the Rad-Caths. Ferromagnetic catheters produce conspicuous patterns on MR images that depend on catheter orientation in the main magnetic field and vary predictably with the MRI parameters.

An experimental evaluation of central vs. peripheral injection for intravenous digital subtraction angiography (IV-DSA).

At a given radiation dosage and field of view, five variables are under meaningful control for intravenous digital subtraction angiography (IV-DSA): concentration and quantity of contrast media injected, volume of injectate, rate of injection, and site of injection. Some controversy exists regarding the selection of a central vs. a peripheral injection site for IV-DSA. This study determined the influence of the site of injection on the peak and width of the arterial time-concentration curve produced by contrast media. Using a noninvasive, in vivo, quantitative x-ray measurement method, 36 separate injections (10 ml of ioxaglate at 8 ml/sec) were administered into the cephalic vein, subclavian vein, and main pulmonary artery in dogs. Injection sites were varied using a Latin-square experimental design. Cardiac output, central blood volume and the peak and width of the contrast media time-concentration curves were measured. The average peak enhancement was greatest for the pulmonary artery injection site. Normalizing peak and width values to make the pulmonary artery values 100%, the average peak values for injections into the subclavian vein and cephalic vein were 93% and 56%, and the average widths were 141% and 163%, respectively. These data support the use of a more central injection site for optimizing IV-DSA examinations.

Optimization of an oral magnetic particle formulation as a gastrointestinal contrast agent for magnetic resonance imaging.

RATIONALE AND OBJECTIVES: Magnetically susceptible iron oxide (MSIO) contrast agents for magnetic resonance imaging (MRI) of the gastrointestinal (GI) tract are limited because they produce magnetic susceptibility artifacts. To determine whether oral magnetic particles (WIN 39996) can be an effective MRI contrast agent without producing induced image artifacts, we optimized a liquid formulation of WIN 39996. METHODS: A range of concentrations (25-250 micrograms iron/mL) and viscosities (1-600 cP) was imaged in a phantom at 1.5 T using conventional spin-echo and gradient-recalled echo pulse sequences. Some formulations also contained titanium. RESULTS: All concentrations of WIN 39996 at 1 cP produced susceptibility artifacts. For formulations in the 150 to 600 cP range, the 125 to 150 micrograms/mL concentrations produced signal blackening and magnetic susceptibility image distortion comparable to an air control. Concentrations greater than 150 micrograms/mL were unacceptable because they produced significant susceptibility artifacts, while concentrations less than 125 micrograms/mL were undesirable because they produced insufficient signal blackening. CONCLUSIONS: These preliminary in-vitro studies suggest that an optimized liquid formulation of WIN 39996 can be produced that yields excellent negative contrast without producing image artifacts.

Influence of viscosity on WIN 39996 as a contrast agent for gastrointestinal magnetic resonance imaging.

RATIONALE AND OBJECTIVES: The authors discuss the influence of viscosity on the imaging properties of WIN 39996 suspension. WIN 39996 suspension is a magnetically susceptible iron ferrite that provides negative (darkening) contrast enhancement in magnetic resonance imaging of the gastrointestinal tract. METHODS: The viscosity of WIN 39996 suspension was altered by various stress conditions (1 week to 4.5 months storage at temperatures of 5 degrees to 70 degrees C) or by various amounts of xanthan gum. Magnetic resonance imaging was performed in vitro on phantoms and in vivo on the gastrointestinal tract of anesthetized dogs. RESULTS: The results indicated that in vitro and in vivo imaging efficacies of WIN 39996 suspension depended on the viscosity, irrespective of the means by which the viscosity was altered. Specifically, the imaging quality was suitable at viscosities > or = 36.6 cp for in vitro imaging, and > 25 cp for in vivo imaging. The lower in vivo viscosity limit for magnetic resonance imaging compared with the in vitro limit may be due to gastrointestinal peristaltic activities continuously mixing the WIN 39996 suspension to prevent gravitational settling, and the enhancement of signal blackening by intraluminal WIN 39996 that was above and below the plane of image. CONCLUSIONS: It is speculated that the imaging quality of WIN 39996 suspension depends on the degree of dispersion of the magnetically susceptible iron ferrite in the WIN 39996 suspension, and that a minimum viscosity is needed to ensure such dispersion.

Magnetic resonance imaging in patients with central nervous system pathology: a comparison of OptiMARK (Gd-DTPA-BMEA) and Magnevist (Gd-DTPA).

RATIONALE AND OBJECTIVES: The objective of the two pivotal phase 3 studies was to evaluate the safety and efficacy of OptiMARK (Gd-DTPA-bis(methoxyethylamide) [Gd-DTPA-BMEA]) compared with Magnevist (Gd-DTPA) in magnetic resonance imaging of the central nervous system. METHODS: Two multicenter, randomized, double-blind, parallel group studies were conducted in 395 patients with known or suspected central nervous system pathology. Subjects were randomized to receive a single 0.1 mmol/kg intravenous injection of either Gd-DTPA-BMEA or Gd-DTPA. The safety of Gd-DTPA-BMEA and Gd-DTPA was monitored for up to 72 hours after study drug administration. Precontrast and postcontrast administration magnetic resonance scans were acquired using identical imaging planes and techniques. RESULTS: No deaths or unexpected adverse events were reported in either group. A comparison of adverse events by intensity and relation demonstrated no statistically significant differences between the two groups. Gd-DTPA-BMEA and Gd-DTPA were equivalent with respect to confidence in diagnosis, conspicuity, and border delineation. CONCLUSIONS: Gd-DTPA-BMEA and Gd-DTPA demonstrated comparable efficacy profiles, and the safety profiles were considered similar.

Methods for the systematic investigation of gastrointestinal contrast media for MRI: evaluation of intestinal distribution by radiographic monitoring.

Comparison of the effectiveness of various gastrointestinal (GI) contrast agents for magnetic resonance (MR) imaging is often complicated by varying amounts intraluminal filling with the orally administered agents. To achieve more uniform and reproducible imaging results with GI contrast agents for MR imaging (GICMR), we evaluated a radiographic method for monitoring intraluminal filling and distribution. Solutions of Mn-DPDP (2 mM), to which a small amount of barium sulfate (6 wt/vol%) was added, were administered orally to dogs. Gastric emptying and small bowel transit were monitored fluoroscopically. MR imaging was performed either 1) at a fixed time after administration of the contrast agent or 2) at a variable interval when the contrast agent was observed fluoroscopically to be in the terminal ileum. When initiation of MR imaging was guided by fluoroscopic monitoring of intestinal contrast distribution, uniform and reproducible intestinal contrast enhancement by GICMR was achieved. However, when MR imaging was performed at a fixed time interval after oral administration, non-uniform and variable GI visualization was obtained, and this corresponded to the variable intestinal distribution observed fluoroscopically. We conclude that reproducible intestinal filling with orally administered contrast agents can be accomplished with a radiographic monitoring technique, and this promotes more consistent GI visualization on MR images. Such standardized and reproducible methods are necessary for studies in which the effectiveness of GI contrast media for MR imaging is evaluated and compared.

Detection of hepatic malignancies using Mn-DPDP (manganese dipyridoxal diphosphate) hepatobiliary MRI contrast agent.

A new hepatobiliary contrast agent (Mn-DPDP) was used in the detection of liver metastases in six rabbits with seven hepatic V2 carcinomas. This contrast agent is derived from pyridoxyl-5-phosphate which is biomimetically designed to be secreted by the hepatocyte. After Mn-DPDP administration, a 105% increase in liver signal to noise was obtained using a 200/20 (TR/TE) pulsing sequence, and a 62% decrease in intensity was observed using a 1200/60 pulsing sequence. Liver V2 carcinoma contrast enhancement increased 427% using the 200/20 pulsing sequence and 176% using the 1200/60 pulsing sequence. Four of seven V2 carcinomas were not detectable prior to the administration of Mn-DPDP (50 mumol/kg). Two neoplasms were only detectable in retrospect (after Mn-DPDP) on the 1200/60 sequence. The smallest neoplasms detected in this study were 1-4 mm. Mn-DPDP appears to be a promising MRI contrast agent.

Interstitial MR and CT lymphography with Gd-dTPA-co-alpha, omega-diaminoPEG(1450) and Gd-dTPA-co-1,6-diaminohexane polymers: preliminary experience.

RATIONALE AND OBJECTIVES: The authors assessed the efficacy of two gadolinium-based polymers used as lymphotrophic contrast media for computed tomography (CT) and magnetic resonance (MR) imaging. MATERIALS AND METHODS: Two gadolinium-based polymers, gadolinium diethylenetriaminepentaacetic acid (DTPA)-co-1,6-diaminohexane (NC 22181) and Gd-DTPA-co-alpha, omega-diamino-polyethylene glycol(1450) (NC-66368), were formulated at a concentration of 80 mmol/L gadolinium. Doses of 0.1, 0.25, 1.0, or 2.0 mL per paw were administered subcutaneously into the hindpaws of normal rabbits. Spin-echo T1-weighted MR imaging (1.5 T) of rabbit popliteal and iliac nodes was performed before and immediately, 10 minutes, 2-3 hours, and 24 hours after injection. CT was performed 2-3 hours after injection of the high doses only. RESULTS: MR imaging revealed prompt enhancement of the popliteal nodes with both polymers at doses of 0.25 mL and above. For doses of 1.0 mL or less per paw, nodal percentage enhancement was maximal at 2 hours and then declined at 24 hours. At the highest doses, however, a reservoir of subcutaneous contrast material remained at the injection site and resulted in peak enhancement at 24 hours. At CT, popliteal node enhancement was faintly visible 2-3 hours after the administration of NC 22181. At lower doses, no enhancement was appreciable at CT. CONCLUSION: At 80 mmol/L formulations, the two gadolinium-based polymers provide excellent popliteal nodal enhancement on MR images. In addition, high doses of one polymer (NC 22181) were sufficiently concentrated in popliteal nodes to be visible on CT scans. Thus, this agent may be useful for both CT and MR lymphography.

Blood pool and liver enhancement in CT with liposomal lodixanol: comparison with lohexol.

RATIONALE AND OBJECTIVES: The authors compared the time course and blood pool and hepatic enhancement of three different doses of liposomal iodixanol with those of iohexol. MATERIALS AND METHODS: A liposomal iodixanol formulation was prepared with 200 mg of iodine per milliliter total and 80 mg of iodine per milliliter encapsulated. Twelve normal New Zealand white rabbits divided into four groups received 75-, 100-, or 150-mg encapsulated iodine per kilogram doses of liposomal iodixanol or 2 mL/kg iohexol with 300 mg of iodine per milliliter. A liver section was scanned with serial computed tomography (CT) before the injection, immediately afterward, and at 1-minute intervals for 10 minutes. Region-of-interest measurements of the aorta and liver were plotted at each time point, and contrast enhancement was plotted as a function of time and iodine dose. RESULTS: All liposomal iodixanol doses produced greater liver enhancement than iohexol. Results were significant (P < .05) for 100 mg and 150 mg iodine per kilogram dose groups at time points beyond 2 minutes. Peak hepatic enhancement (change in attenuation) was 54.9 HU +/- 7.6 with iohexol, compared with 59.6 HU +/- 6.1, 73.3 HU +/- 3.6, and 104.1 HU +/- 8.8 for 75, 100, and 150 mg encapsulated iodine per kilogram doses, respectively. Hepatic enhancement increased rapidly after injection of liposomal iodixanol, plateauing 2-3 minutes later. Blood pool enhancement decreased rapidly. Steady-state liver enhancement with liposomal iodixanol increased linearly with dose. Aortic enhancement was greater with iohexol. CONCLUSION: Liposomal iodixanol yielded greater hepatic enhancement at lower total iodine doses than iohexol. Although liver enhancement occurred rapidly after injection, blood pool enhancement was brief.

Terrorism. Part 1: Calibrating your risks and response.

Emergency service organizations are "in combat" every day. Yet with the experience and education we have amassed over the years, we remain ill-prepared to deal with the full effects of a terrorist attack. Terrorism has many definitions. For this article we choose this one: Terrorism: The use of violence, threats, intimidation or information manipulation for revenge, politics, support of a cause or the furthering of a criminal enterprise.

Terrorism. Part III--Response procedures for terrorist/tactical violence incidents.

A safe and effective response to a terrorist/tactical violence incident involves the following critical factors: Identify and train all potential convergent responders. 2-in/2-out--your partner is your life; have a plan to rescue the rescuers. Orient all responders to LACES. Search your command, staging and treatment areas for a secondary device. Restrict media coverage. Control the scene and relocate/evacuate if necessary. Alert medical receiving facilities early in the event chain to enable them to prepare for a patient onslaught.

Formative evaluation of ontology learning methods for entity discovery by using existing ontologies as reference standards.

OBJECTIVE: Developing a two-step method for formative evaluation of statistical Ontology Learning (OL) algorithms that leverages existing biomedical ontologies as reference standards. METHODS: In the first step optimum parameters are established. A 'gap list' of entities is generated by finding the set of entities present in a later version of the ontology that are not present in an earlier version of the ontology. A named entity recognition system is used to identify entities in a corpus of biomedical documents that are present in the 'gap list', generating a reference standard. The output of the algorithm (new entity candidates), produced by statistical methods, is subsequently compared against this reference standard. An OL method that performs perfectly will be able to learn all of the terms in this reference standard. Using evaluation metrics and precision-recall curves for different thresholds and parameters, we compute the optimum parameters for each method. In the second step, human judges with expertise in ontology development evaluate each candidate suggested by the algorithm configured with the optimum parameters previously established. These judgments are used to compute two performance metrics developed from our previous work: Entity Suggestion Rate (ESR) and Entity Acceptance Rate (EAR). RESULTS: Using this method, we evaluated two statistical OL methods for OL in two medical domains. For the pathology domain, we obtained 49% ESR, 28% EAR with the Lin method and 52% ESR, 39% EAR with the Church method. For the radiology domain, we obtain 87% ESA, 9% EAR using Lin method and 96% ESR, 16% EAR using Church method. CONCLUSION: This method is sufficiently general and flexible enough to permit comparison of any OL method for a specific corpus and ontology of interest.

Imaging informatics: toward capturing and processing semantic information in radiology images.

OBJECTIVES: To identify challenges and opportunities in imaging informatics that can lead to the use of images for discovery, and that can potentially improve the diagnostic accuracy of imaging professionals. METHODS: Recent articles on imaging informatics and related articles from PubMed were reviewed and analyzed. Some new developments and challenges that recent research in imaging informatics will meet are identified and discussed. RESULTS: While much literature continues to be devoted to traditional imaging informatics topics of image processing, visualization, and computerized detection, three new trends are emerging: (1) development of ontologies to describe radiology reports and images, (2) structured reporting and image annotation methods to make image semantics explicit and machine-accessible, and (3) applications that use semantic image information for decision support to improve radiologist interpretation performance. The informatics methods being developed have similarities and synergies with recent work in the biomedical informatics community that leverage large high-throughput data sets, and future research in imaging informatics will build on these advances to enable discovery by mining large image databases. CONCLUSIONS: Imaging informatics is beginning to develop and apply knowledge representation and analysis methods to image datasets. This type of work, already commonplace in biomedical research with large scale molecular and clinical datasets, will lead to new ways for computers to work with image data. The new advances hold promise for integrating imaging with the rest of the patient record as well as molecular data, for new data-driven discoveries in imaging analogous to that in bioinformatics, and for improved quality of radiology practice.