March 2015Representing and Extracting Lung Cancer Study Metadata: Study Objective and Study Design.
This paper describes the information retrieval step in Casama (Contextualized Semantic Maps), a project that summarizes and contextualizes current research papers on driver mutations in non-small cell lung cancer. Casama's representation of lung cancer studies aims to capture elements that will assist an end-user in retrieving studies and, importantly, judging their strength. This paper focuses on two types of study metadata: study objective and study design. 430 abstracts on EGFR and ALK mutations in lung cancer were annotated manually. Casama's support vector machine (SVM) automatically classified the abstracts by study objective with as much as 129% higher F-scores compared to PubMed's built-in filters. A second SVM classified the abstracts by epidemiological study design, suggesting strength of evidence at a more granular level than in previous work. The classification results and the top features determined by the classifiers suggest that this scheme would be generalizable to other mutations in lung cancer, as well as studies on driver mutations in other cancer domains.
March 2015Multifocality and Prostate Cancer Detection by Multiparametric Magnetic Resonance
BACKGROUND: Multiparametric magnetic resonance imaging (mp-MRI) is increasingly used in prostate cancer (CaP). Understanding the limitations of tumor detection, particularly in multifocal disease, is important in its clinical application. OBJECTIVE: To determine predictors of CaP detection by mp-MRI as confirmed by whole-mount histopathology. DESIGN, SETTING, AND PARTICIPANTS: A retrospective study was performed of 122 consecutive men who underwent mp-MRI before radical prostatectomy at a single referral academic center. A genitourinary radiologist and pathologist collectively determined concordance. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The odds of tumor detection were calculated for clinical, MRI, and histopathologic variables using a multivariate logistic regression model.
March 2015Emerging Potential of Natural Products for Targeting Mucins for Therapy Against Inflammation and Cancer.
Deregulated mucin expression is a hallmark of several inflammatory and malignant pathologies. Emerging evidence suggests that, apart from biomarkers, these deregulated mucins are functional contributors to the pathogenesis in inflammation and cancer. Both overexpression and downregulation of mucins in various organ systems is associated with pathobiology of inflammation and cancer. Restoration of mucin homeostasis has become an important goal for therapy and management of such disorders has fueled the quest for selective mucomodulators. With improved understanding of mucin regulation and mechanistic insights into their pathobiological roles, there is optimism to find selective non-toxic agents capable of modulating mucin expression and function. Recently, natural compounds derived from dietary sources have drawn attention due to their anti-inflammatory and anti-oxidant properties and low toxicity. Considerable efforts have been directed towards evaluating dietary natural products as chemopreventive and therapeutic agents; identification, characterization and synthesis of their active compounds; and improving their delivery and bioavailability. We describe the current understanding of mucin regulation, rationale for targeting mucins with natural products and discuss some natural products that modulate mucin expression and functions. We further discuss the approaches and parameters that should guide future research to identify and evaluate selective natural mucomodulators for therapy.
March 2015Catheter Ablation of Accessory Pathways Near the Coronary Sinus: Value of Defining Coronary Arterial Anatomy.
BACKGROUND: Accessory pathways can lie near or within the coronary sinus (CS). Radiofrequency catheter ablation of accessory pathways is a well-established treatment option, but this procedure can cause damage to adjacent coronary arteries. OBJECTIVE: The purpose of this study was to evaluate the anatomic relationship between the coronary arteries and the CS. METHODS: Retrospective data of patients who underwent catheter ablation of supraventricular tachycardia between June 2011 and August 2013 was reviewed. In addition, detailed analysis of coronary computed tomographic angiography (CTA) data from 50 patients was performed.
March 2015High-resolution, Whole-body Vascular Imaging with Ferumoxytol as an Alternative to Gadolinium Agents in a Pediatric Chronic Kidney Disease Cohort.
BACKGROUND: Exposure to gadolinium-based contrast agents (GBCA) in patients with chronic kidney disease (CKD) has been associated with the development of a potentially fatal disorder, nephrogenic systemic fibrosis (NSF). Although contrast-enhanced computed tomography (CT) is an alternative to magnetic resonance imaging (MRI), it carries the risk of radiation exposure and further reduction of residual renal function. Therefore we sought to assess the feasibility of ferumoxytol as an alternative to GBCA for contrast-enhanced MR angiography (MRA) in a pediatric cohort with CKD. Ferumoxytol is a parenteral iron supplement that contains ultrasmall superparamagnetic iron oxide (USPIO) and is a potent relaxivity agent for MRI. METHODS: We describe the MRI findings in ten pediatric patients who needed detailed vascular mapping. Ferumoxytol (4 mg/kg) was administered intravenously for contrast-enhanced MRA. The patients tolerated the procedure without complications.
March 2015Novel Technique for Characterizing Prostate Cancer Utilizing MRI Restriction Spectrum Emaging: Proof of Principle and Initial Clinical Experience with Extraprostatic Extension.
BACKGROUND: Standard magnetic resonance imaging (MRI) of the prostate lacks sensitivity in the diagnosis and staging of prostate cancer (PCa). To improve the operating characteristics of prostate MRI in the detection and characterization of PCa, we developed a novel, enhanced MRI diffusion technique using restriction spectrum imaging (RSI-MRI). METHODS: We compared the efficacy of our novel RSI-MRI technique with standard MRI for detecting extraprostatic extension (EPE) among 28 PCa patients who underwent MRI and RSI-MRI prior to radical prostatectomy, 10 with histologically proven pT3 disease. RSI cellularity maps isolating the restricted isotropic water fraction were reconstructed based on all b-values and then standardized across the sample with z-score maps. Distortion correction of the RSI maps was performed using the alternating phase-encode technique.
March 2015Optimal Flip Angle for High Contrast Balanced SSFP Cardiac Cine Imaging.
PURPOSE: To determine the optimal flip angle (FA) for cardiac cine imaging that maximizes myocardial signal and blood-myocardium contrast. METHODS: Bloch equation simulations of stationary myocardium and flowing blood with an imperfect slice profile were compared to in vivo measurements of blood and myocardium signal-to-noise ratio (SNR) and blood-myocardium contrast-to-noise ratio (CNR) in healthy subjects (N = 10) in the short-axis and four-chamber views and in patients (N = 7) in the three-chamber imaging plane.
February 2015Alvarado Score: Can it Reduce Unnecessary CT Scans for Evaluation of Acute Appendicitis?
OBJECTIVE: The objective of the study is to assess the utility of Alvarado score in the diagnosis of acute appendicitis and the utility of computed tomographic (CT) scan for evaluation of acute appendicitis when stratified by Alvarado scores. MATERIALS AND METHODS: Retrospective cohort study comprised adult patients who underwent abdominal CT for suspected acute appendicitis between January 2006 and December 2009. Two abdominal radiologists independently reviewed the CT scans; any discrepancies were resolved by a consensus review. Alvarado scores were calculated and categorized as low (0-3), equivocal (4-6), or high (7-10) probability for appendicitis. The diagnostic utility of CT scans and Alvarado score for acute appendicitis were compared with the criterion standard of combined medical chart review and pathology findings.
February 2015Correlation of Clot Imaging with Endovascular Recanalization in Internal Carotid Artery Terminus Occlusion.
BACKGROUND AND PURPOSE: In a swine stroke model we have previously demonstrated a high-intensity fluid attenuated inversion recovery (FLAIR) signal representing the erythrocyte component of the clot. We hypothesized that the intensity of the FLAIR clot signal in patients with acute stroke may predict the efficacy of recanalization by thrombectomy devices. In this study we compared the pretreatment FLAIR signal intensity of the clots in the distal internal carotid artery (ICA) and the degree of angiographic recanalization rate after mechanical thrombectomy. METHODS: 25 consecutive acute stroke patients with ICA terminus (ICA-T) occlusion diagnosed with MRI at the UCLA Medical Center between 2002 and 2013 were retrospectively reviewed. The intensity of the FLAIR clot signal at the distal ICA was blindly compared with the angiographic recanalization status (successful recanalization defined as Thrombolysis In Cerebral Infarction (TICI) score of 2b-3) and non-successful recanalization as TICI score 0-2a) after endovascular treatment. Multivariate logistic regression analysis for successful recanalization was performed.
February 2015A Novel Bicompartmental Mathematical Model of Glioblastoma Multiforme.
Glioblastoma multiforme (GBM) is the most common primary CNS neoplasm, and continues to have a dismal prognosis. A widely-used approach to the mathematical modeling of GBM involves utilizing a reaction-diffusion model of cell density as a function of space and time, which accounts for both the infiltrative nature of the tumor using a diffusion term, and the proliferation of tumor cells using a proliferation term. The current paper extends the standard models by incorporating an advection term to account for the so-called 'cell streaming' which is often seen with GBM, where some of the tumor cells seem to stream widely along the white matter pathways. The current paper introduces a bicompartmental GBM model in the form of coupled partial differential equations with a component of dispersive cells. The parameters needed for this model are explored. It is shown that this model can account for the rapid distant dispersal of GBM cells in the CNS, as well as such phenomena as multifocal gliomas with tumor foci distant from the core tumor site. The model suggests a higher percentage of tumor cells below the threshold of MRI images in comparison to the standard model. By incorporating an advection component, the proposed model is able to account for phenomena such as multicentric gliomas and rapid distant dispersion of a small fraction of tumor cells throughout the CNS, features important to the prognosis of GBM, but not easily accounted for by current models.
February 2015Native Renal Biopsy: the Perfect Storm.
We would like to thank Kriegshauser and coworkers (1) for a well written and interesting article. Even though the conclusion was somewhat expected, that higher preprocedure blood pressures increase the complication risk of native renal biopsy, what we found surprising was the magnitude of the relative risk increase that they encountered. They found that the risk of a major complication was 23 times higher for a patient with a systolic blood pressure greater than 170 mm Hg, and seven times higher for a patient with systolic blood pressure of 141–170 mm Hg, compared with normotensive patients. Previous studies have shown a range of odds ratios for systolic hypertension in native renal biopsy, ranging from no increased risk (2) to a fourfold increased risk (3), but never an odds ratio of this magnitude.
February 2015Frequency of Nonthromboembolic Imaging Abnormalities in Pregnant Women Referred for Computed Tomography Pulmonary Arteriography.
PURPOSE: The study sought to determine the frequency of nonthromboembolic imaging abnormalities in pregnant women referred for computed tomography pulmonary arteriography (CTPA). MATERIALS AND METHODS: CTPA studies on 100 consecutive pregnant women performed over a 5-year period were reviewed independently by 2 radiologists, with conflicts resolved by consensus. Age range was 18-43 years (mean 28 years). The presence or absence of pulmonary embolism and of nonthromboembolic imaging abnormalities was recorded. These were graded as A if the abnormalities were thought to provide potential alternative explanations for acute symptoms, B if findings were incidental that required clinical or radiologic follow-up, and C if the findings did not require further action.
February 2015White Matter Ischemic Changes in Hyperacute Ischemic Stroke: Voxel-Based Analysis Using Diffusion Tensor Imaging and MR Perfusion.
BACKGROUND AND PURPOSE: The purpose of this study was to evaluate changes in fractional anisotropy (FA), as measured by diffusion tensor imaging, of white matter (WM) infarction and hypoperfusion in patients with acute ischemic stroke using a quantitative voxel-based analysis. METHODS: In this prospective study, diffusion tensor imaging and dynamic susceptibility contrast perfusion sequences were acquired in 21 patients with acute ischemic stroke who presented within 6 hours of symptom onset. The coregistered FA, apparent diffusion coefficient, and dynamic susceptibility contrast time to maximum (Tmax) maps were used for voxel-based quantification using a region of interest approach in the ipsilateral affected side and in the homologous contralateral WM. The regions of WM infarction versus hypoperfusion were segmented using a threshold method. Data were analyzed by regression and ANOVA.
February 2015Genomics of Brain Tumor Imaging.
Imaging genomics combines imaging-defined phenotypes with molecular determinants of disease. Recent studies have examined the relationship between MRI-derived feature sets and gene expression in gliomas, including glioblastoma (GBM). Several groups have identified correlations between the expression of particular molecularly defined oncogenic pathways in GBM and malignant phenotypes on MRI. The combination of clinical, genetic, and imaging data has improved prognostic modeling and has identified potential therapeutic targets. Many challenges remain in fully leveraging the associations between such large datasets, but even current methodology shows promise in helping to craft individually tailored treatments to patients with brain tumors and other diseases.
February 2015Neuroimaging Abnormalities, Neurocognitive Function, and Fatigue in Patients with Hepatitis C.
OBJECTIVE: This study examined neurologic abnormalities (as measured by proton magnetic resonance spectroscopy imaging and diffusion tensor imaging), neurocognitive performance, and fatigue among a sample of adults with hepatitis C virus (HCV). We hypothesized that HCV+ individuals would demonstrate structural brain abnormalities and neurocognitive compromise consistent with frontostriatal dysfunction as well as increased fatigue compared to controls. METHOD: Participants were 76 individuals diagnosed with HCV and 20 controls who underwent a comprehensive neurocognitive evaluation and clinical assessments. A subset of the HCV+ participants (n = 29) and all controls underwent MRI.
February 2015Phase Contrast MRI with Flow Compensation View Sharing.
PURPOSE: To develop and evaluate a technique for accelerating phase contrast MRI (PC-MRI) acquisitions without significant compromise in flow quantification accuracy. METHODS: PC-MRI is commonly acquired using interleaved flow-compensated (FC) and flow-encoded (FE) echoes. We hypothesized that FC data, which represent background phase, do not change significantly over time. Therefore, we proposed to undersample the FC data and use an FC view sharing (FCVS) approach to synthesize a composite FC frame for each corresponding FE frame. FCVS was evaluated in a flow phantom and healthy volunteers and compared with a standard FC/FE PC-MRI.
January 2015The Hangman Technique: a Modified Loop Snare Technique for the Retrieval of Inferior Vena Cava Filters with Embedded Hooks.
The loop snare technique is a method for inferior vena cava (IVC) filter retrieval that creates a wire loop between the filter legs; this technique may fail in cases with an embedded hook. This report describes the hangman technique, a modified loop snare technique for filter retrieval that creates a wire loop between the filter neck and IVC wall for release of embedded filter hooks. The hangman technique was attempted in 11 cases complicated by tilt (mean tilt, 13.3 degrees ± 3.9) and an embedded hook (mean dwell time, 194.5 d) with a retrieval success rate of 81.8% (9 of 11 cases) and no associated complications.
January 2015Radiogenomics and Imaging Phenotypes in Glioblastoma: Novel Observations and Correlation with Molecular Characteristics.
Radiogenomics is a provocative new area of research based on decades of previous work examining the association between radiological and histological features. Many generalized associations have been established linking anatomical imaging traits with underlying histopathology, including associations between contrast-enhancing tumor and vascular and tumor cell proliferation, hypointensity on pre-contrast T1-weighted images and necrotic tissue, and associations between hyperintensity on T2-weighted images and edema or nonenhancing tumor. Additionally, tumor location, tumor size, composition, and descriptive features tend to show significant associations with molecular and genomic factors, likely related to the cell of origin and growth characteristics. Additionally, physiologic MRI techniques also show interesting correlations with underlying histology and genomic programs, including associations with gene expression signatures and histological subtypes. Future studies extending beyond simple radiology-histology associations are warranted in order to establish radiogenomic analyses as tools for prospectively identifying patient subtypes that may benefit from specific therapies.
January 2015Impact of 68Ga-DOTATATE PET/CT on the Management of Neuroendocrine Tumors: The Referring Physician's Perspective.
Somatostatin receptor imaging with 68Ga-DOTATATE PET/CT (DOTATATE) is increasingly used for managing patients with neuroendocrine tumors. The objective of this study was to determine referring physicians' perspectives on the impact of DOTATATE on the management of neuroendocrine tumors. METHODS: A set of 2 questionnaires (pre-PET and post-PET) was sent to the referring physicians of 100 consecutive patients with known or suspected neuroendocrine tumors, who were evaluated with DOTATATE. Questionnaires on 88 patients were returned (response rate, 88%). Referring physicians categorized the DOTATATE findings on the basis of the written PET reports as negative, positive, or equivocal for disease. The likelihood for metastatic disease was scored as low, moderate, or high. The intended management before and changes as a consequence of the PET study were indicated.
January 2015Comparison of the Quantitative CT Imaging Biomarkers of Idiopathic Pulmonary Fibrosis at Baseline and Early Change with an Interval of 7 Months.
RATIONALE AND OBJECTIVES: Median survival of patients with idiopathic pulmonary fibrosis (IPF) is 2-5 years. Sensitive imaging metrics can play a role in detecting early changes in therapeutic development. The aim of the present study was to compare known computed tomography (CT) histogram kurtosis and a classifier-based quantitative score to assess baseline severity and change over time in patients with IPF. MATERIALS AND METHODS: A total of 57 patients with at least baseline and paired follow-up scans were selected from an imaging database of standardized CT scans obtained from patients with IPF. CT histogram measurement of kurtosis and quantitative lung fibrosis (QLF) and quantitative interstitial lung disease (QILD) scores from a classification algorithm were calculated. Spearman rank correlations were used to assess associations between baseline severity and changes for all CT-derived measures compared to forced vital capacity (FVC) and carbon monoxide diffusion capacity (DLCO) (percent predicted).
January 2015Nitroxoline Induces Apoptosis and Slows Glioma Growth in vivo.
BACKGROUND: Nitroxoline is an FDA-approved antibiotic with potential antitumor activity. Here we evaluated whether nitroxoline has antiproliferative properties on glioma cell growth in vitro and in vivo using glioma cell lines and a genetically engineered PTEN/KRAS mouse glioma model. METHODS: The effect of nitroxoline treatment on U87 and/or U251 glioma cell proliferation, cell-cycle arrest, invasion, and ability to induce an apoptotic cascade was determined in vitro. Magnetic resonance imaging was used to measure glioma volumes in genetically engineered PTEN/KRAS mice prior to and after nitroxoline therapy. Induction of apoptosis by nitroxoline was evaluated at the end of treatment using terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick end labeling (TUNEL).
January 2015Y90 Selective Internal Radiation Therapy.
Primary liver malignancies and liver metastases are affecting millions of individuals worldwide. Because of their late and advanced stage presentation, only 10% of patients can receive curative surgical treatment, including transplant or resection. Alternative treatments, such as systemic chemotherapy, ablative therapy, and chemoembolization, have been used with marginal survival benefits. Selective internal radiation therapy (SIRT), also known as radioembolization, is a compelling alternative treatment option for primary and metastatic liver malignancies with a growing body of evidence. In this article, an introduction to SIRT including background, techniques, clinical outcomes, and complications is reviewed.
January 2015Biomimetic Scaffolds Facilitate Healing of Critical-sized Segmental Mandibular Defects.
OBJECTIVE: To investigate the efficacy of biomimetic PLGA scaffolds, alone and in combination with bone morphogenic protein (BMP-2) and adipose-derived stem cells (ASCs), to heal a critical-sized segmental mandibular defect in a rat model. STUDY DESIGN: Prospective animal study. METHODS: ASCs were isolated and cultured from the inguinal fat of Lewis rat pups. Using three-dimensional printing, PLGA scaffolds were fabricated and impregnated with BMP-2 and/or ASCs. Critical-sized 5-mm segmental mandibular defects were created in adult Lewis rats and implanted with (1) blank PLGA scaffolds, (2) PLGA scaffolds with ASCs, (3) PLGA scaffolds with BMP, or (4) PLGA scaffolds with BMP and ASCs. Animals were sacrificed at 12weeks. Bone regeneration was assessed using microCT, and graded on a semi-quantitative bone formation and bone union scale.
January 2015High-field MR Imaging in Pediatric Congenital Heart Disease: Initial Results.
BACKGROUND: Comprehensive assessment of pediatric congenital heart disease (CHD) at any field strength mandates evaluation of both vascular and dynamic cardiac anatomy for which diagnostic quality contrast-enhanced magnetic resonance angiography (CEMRA) and cardiac cine are crucial. OBJECTIVE: To determine whether high-resolution (HR) CEMRA and steady-state free precession (SSFP) cine can be performed reliably at 3.0 T in children with CHD and to compare the image quality to similar techniques performed at 1.5 T. MATERIALS AND METHODS: Twenty-eight patients with a median age of 5 months and average weight 9.0 ± 7.8 kg with suspected or known CHD were evaluated at 3.0 T. SSFP cine (n = 86 series) and HR-CEMRA (n = 414 named vascular segments) were performed and images were scored for image quality and artifacts. The findings were compared to those of 28 patients with CHD of similar weight who were evaluated at 1.5 T.
January 2015Delayed Intravenous Contrast-enhanced 3D FLAIR MRI in Meniere's Disease: Correlation of Quantitative Measures of Endolymphatic Hydrops with Hearing.
OBJECTIVE: Using three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging (3D-FLAIR MRI), our goal was to correlate quantifiable measures of endolymphatic hydrops (EH) with auditory function in the setting of Meniere's disease (MD). MATERIALS AND METHODS: Forty-one ears were analyzed in 21 subjects (12 ears with MD, 29 without MD). Vestibular endolymphatic space size measurements obtained with two different techniques were referenced against clinical data.
January 2015Fine Needle Elastography (FNE) Device for Biomechanically Determining Local Variations of Tissue Mechanical Properties.
Diseased tissues exhibit changes in mechanical properties and thus possess clinical diagnostic significance. We report the design and development of a Fine Needle Elastography (FNE) prototype device integrated with Fine Needle Aspiration Cytology (FNAC) needle that allows for quantitative and sensitive assessment of tissues and materials based on local variations in elastic, friction, and cutting forces on needle insertion. A piezoelectric force-sensor at the base of FNA needle measures the forces opposing needle penetration with micrometer scale resolution. Measurement precision (±5µm) and axial resolution (~20µm) of FNE device was tested using control mm size gelatin matrices and unripe pear in assessing needle penetration resistance, force heterogeneity and optimization of needle penetration velocity. Further, we demonstrated the usefulness of FNE in quantitative, biomechanical differentiation of simulated thyroid tumor nodules in an ultrasound neck phantom. Fluid or solid nodules were probed in the phantom study coupled with ultrasound guidance. Our data shows significantly higher force variations (1-D force heterogeneity; HF,a=6.5mN, HF,q=8.25mN and stiffness heterogeneity; HS,a=0.0274kN/m, HS,q=0.0395kN/m) in solid nodules compared either to fluid nodules or to regions corresponding to healthy thyroid tissue within the ultrasound phantom. The results suggest future applications of in vivo FNE biopsies based on force heterogeneity to diagnose thyroid tumors in areas where ultrasound instrumentation or access to a qualified pathologist for FNAC are unavailable, as well as an ancillary diagnostic tool in thyroid cancer management.