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Research Publications


June 2015

AngioVac Aspiration for Paradoxical Emboli Protection Through a Fenestrated Fontan During Central Venous Thrombus Manipulation.

Al-Hakim R, Patel K, Moriarty JM.

This case reports describes a 39-year-old female with a history of surgically repaired hypoplastic left heart syndrome who presented with a left peripherally inserted central catheter (PICC) with associated large volume subclavian and brachiocephalic vein thrombus. Due to the presence of a right-to-left shunt via a fenestrated Fontan, there was clinical concern for a paradoxical embolism during removal of the PICC. The AngioVac aspiration system was successfully utilized to aspirate thromboemboli from the level of the proximal Glenn shunt during manipulation and removal of the PICC. This is the first reported case to demonstrate the safe and effective use of the AngioVac aspiration system for protection of paradoxical emboli through a cardiac right-to-left shunt during a procedure at high risk for thromboembolism.


June 2015

Response Assessment and Magnetic Resonance Imaging Issues for Clinical Trials Involving High-Grade Gliomas.

Boxerman JL, Ellingson BM.

There exist multiple challenges associated with the current response assessment criteria for high-grade gliomas, including the uncertain role of changes in nonenhancing T2 hyperintensity, and the phenomena of pseudoresponse and pseudoprogression in the setting of antiangiogenic and chemoradiation therapies, respectively. Advanced physiological magnetic resonance imaging (MRI), including diffusion and perfusion (dynamic susceptibility contrast MRI and dynamic contrast-enhanced MRI) sensitive techniques for overcoming response assessment challenges, has been proposed, with their own potential advantages and inherent shortcomings. Measurement variability exists for conventional and advanced MRI techniques, necessitating the standardization of image acquisition parameters in order to establish the utility of these imaging methods in multicenter trials for high-grade gliomas. This review chapter highlights the important features of MRI in clinical brain tumor trials, focusing on the current state of response assessment in brain tumors, advanced imaging techniques that may provide additional value for determining response, and imaging issues to be considered for multicenter trials.


June 2015

Investigation of DNA Damage Dose-Response Kinetics After Ionizing Radiation Schemes Similar to CT Protocols.

Elgart SR, Bostani M, Mok KC, Adibi A, Ruehm S, Enzmann D, McNitt-Gray M, Iwamoto KS.

Although there has been extensive research done on the biological response to doses of ionizing radiation relevant to radiodiagnostic procedures, very few studies have examined radiation schemes similar to those frequently utilized in CT exams. Instead of a single exposure, CT exams are often made up of a series of scans separated on the order of minutes. DNA damage dose-response kinetics after radiation doses and schemes similar to CT protocols were established in both cultured (ESW-WT3) and whole blood lymphocytes and compared to higher dose exposures. Both the kinetics and extent of H2AX phosphorylation were found to be dose dependent. Damage induction and detection showed a clear dose response, albeit different, at all time points and differences in the DNA repair kinetics of ESW-WT3 and whole blood lymphocytes were characterized. Moreover, using a modified split-dose in vitro experiment, we show that phosphorylation of H2AX is significantly reduced after exposure to CT doses fractionated over a few minutes compared to the same total dose delivered as a single exposure. Because the split-dose exposures investigated here are more similar to those experienced during a CT examination, it is essential to understand why and how these differences occur. This work provides compelling evidence supporting differential biological responses not only between high and low doses, but also between single and multiple exposures to low doses of ionizing radiation.


June 2015

Intraductal Cooling via a Nasobiliary Tube During Radiofrequency Ablation of Central Liver Tumors Reduces Biliary Injuries.

Felker ER, Lee-Felker SA, Ajwichai K, Tan N, Lu DS, Durazo FA, Raman SS.

OBJECTIVE: The objective of our study was to determine the safety and efficacy of intraductal perfusion of chilled 5% dextrose in water (D5W) via an endoscopic nasobiliary tube (NBT) for the prevention of thermal bile duct injury in patients undergoing percutaneous radiofrequency ablation (RFA) of central liver tumors. MATERIALS AND METHODS: We performed a retrospective study comparing outcomes of 32 consecutive patients who underwent percutaneous RFA of central liver tumors without intraductal perfusion of chilled D5W (control cohort) and 14 consecutive patients who underwent temporary intraductal perfusion of chilled D5W at 2 mL/s via endoscopic NBT placement before RFA (endoscopic NBT cohort). The primary and secondary outcomes were the rate of biliary complications and local tumor progression, respectively.


June 2015

CT Staging and Monitoring of Fibrotic Interstitial Lung Diseases in Clinical Practice and Treatment Trials: a Position Paper from the Fleischner Society.

Hansell DM, Goldin JG, King TE Jr, Lynch DA, Richeldi L, Wells AU.

CT is increasingly being used to stage and quantify the extent of diffuse lung diseases both in clinical practice and in treatment trials. The role of CT in the assessment of patients entering treatment trials has greatly expanded as clinical researchers and pharmaceutical companies have focused their efforts on developing safe and effective drugs for interstitial lung diseases, particularly for idiopathic pulmonary fibrosis. These efforts have culminated in the simultaneous approval by the US Food and Drug Administration of two new drugs for the treatment of idiopathic pulmonary fibrosis. CT features are a key part of the inclusion criteria in many drug trials and CT is now being used to refine the type of patients enrolled. Interest in the potential use of serial CT as an effectiveness endpoint is increasing. For chronic progressive diseases, mortality may not be a feasible endpoint and many surrogate markers have been explored, ranging from pulmonary function decline to biomarkers. However, these surrogate markers are not entirely reliable and combinations of endpoints, including change in disease extent on CT, are being investigated. Methods to assess disease severity with CT range from simple visual estimates to sophisticated quantification by use of software. In this Position Paper, which cannot be regarded as a comprehensive set of guidelines in view of present knowledge, we examine the uses of serial CT in clinical practice and in drug trials and draw attention to uncertainties and challenges for future research.


June 2015

Patient-specific Characterization of the Invasiveness and Proliferation of Low-grade Gliomas Using Serial MR Imaging and a Mathematical Model of Tumor Growth.

Hathout L, Ellingson BM, Cloughesy TF, Pope WB.

Low-grade gliomas (LGGs) represent a significant proportion of hemispheric gliomas in adults. Although less aggressive than glioblastomas (GBMs), they have a broad range of biologic behavior, and often a limited prognosis. The aim of the present study was to explore LGG growth kinetics through a combination of routine MRI imaging and a novel adaptation of a mathematical tumor model. MRI imaging in 14 retrospectively identified grade II LGGs that showed some tumor enhancement was used to assess tumor radii at two separate time-points. This information was combined with a reaction-diffusion partial-differential equation model of tumor growth to calculate diffusion (D) and proliferation (ρ) coefficients for each tumor, representing measures of tumor invasiveness and cellular multiplication, respectively. The results were compared to previously published data on GBMs. The average value of D was 0.034 mm2/day and ρ was 0.0056/day. Grade II LGGs had a broad range of D and ρ. On average, the proliferation coefficient ρ was significantly lower than previously published values for GBM, by about an order of magnitude. The diffusion coefficient, modeling invasiveness, however, was only slightly lower but without statistical significance. It was possible to calculate detailed growth kinetic parameters for some LGGs, potentially providing a new way to assess tumor aggressiveness and possibly gauge prognosis. Even within a single-grade (WHO II), LGGs were found to have broad range of D and ρ, possibly correlating to their variable biologic behavior. Overall, the model parameters suggest that LGG is less aggressive than GBM based primarily on a lower index of tumor proliferation rather than on lesser invasiveness.


June 2015

An Integrated, Ontology-driven Approach to Constructing Observational Databases for Research.

Hsu W, Gonzalez NR, Chien A, Pablo Villablanca J, Pajukanta P, Viñuela F, Bui AA.

The electronic health record (EHR) contains a diverse set of clinical observations that are captured as part of routine care, but the incomplete, inconsistent, and sometimes incorrect nature of clinical data poses significant impediments for its secondary use in retrospective studies or comparative effectiveness research. In this work, we describe an ontology-driven approach for extracting and analyzing data from the patient record in a longitudinal and continuous manner. We demonstrate how the ontology helps enforce consistent data representation, integrates phenotypes generated through analyses of available clinical data sources, and facilitates subsequent studies to identify clinical predictors for an outcome of interest. Development and evaluation of our approach are described in the context of studying factors that influence intracranial aneurysm (ICA) growth and rupture. We report our experiences in capturing information on 78 individuals with a total of 120 aneurysms. Two example applications related to assessing the relationship between aneurysm size, growth, gene expression modules, and rupture are described. Our work highlights the challenges with respect to data quality, workflow, and analysis of data and its implications toward a learning health system paradigm.


June 2015

Relationship Between [(18)F]FDOPA PET Uptake, Apparent Diffusion Coefficient (ADC), and Proliferation Rate in Recurrent Malignant Gliomas.

Karavaeva E, Harris RJ, Leu K, Shabihkhani M, Yong WH, Pope WB, Lai A, Nghiemphu PL, Liau LM, Chen W, Czernin J, Cloughesy TF, Ellingson BM.

PURPOSE: Diffusion magnetic resonance imaging (MRI) and 6-[(18)F]fluoro-L-dopa ([(18)F]FDOPA) positron emission tomography (PET) are used to interrogate malignant tumor microenvironment. It remains unclear whether there is a relationship between [(18)F]FDOPA uptake, diffusion MRI estimates of apparent diffusion coefficient (ADC), and mitotic activity in the context of recurrent malignant gliomas, where the tumor may be confounded by the effects of therapy. The purpose of the current study is to determine whether there is a correlation between these imaging techniques and mitotic activity in malignant gliomas. PROCEDURES: We retrospectively examined 29 patients with recurrent malignant gliomas who underwent structural MRI, diffusion MRI, and [(18)F]FDOPA PET prior to surgical resection. Qualitative associations were noted, and quantitative voxel-wise and median measurement correlations between [(18)F]FDOPA PET, ADC, and mitotic index were performed.


June 2015

Balloon-Occluded Retrograde Transvenous Obliteration (BRTO) for Treatment of Gastric Varices: Review and Meta-Analysis.

Park JK, Saab S, Kee ST, Busuttil RW, Kim HJ, Durazo F, Cho SK, Lee EW.

AIM: To perform a systematic review and meta-analysis of the effectiveness and complications of BRTO for gastric varices. MATERIALS AND METHODS: A systematic review was performed to identify relevant articles. Inclusion criteria were applied to select studies with at least ten patients with acute bleeding or at-risk gastric varices treated with BRTO. Meta-analysis with random effects model was performed to calculate data for immediate technical success, clinical success, and complications.


June 2015

Successful Management of Chronic Gastrointestinal Hemorrhage Using Bevacizumab in the Setting of Hereditary Hemorrhagic Telangiectasia.

Sehl ME, M Gruber T, McWilliams JP, Marder VJ.

A 74-year-old gentleman was referred to our clinic because of a 6-month history of recurrent gastrointestinal bleeding. He had developed black stools prompting an endoscopic evaluation that revealed multiple AVMs. His chronic bleeding was so severe that he required regular blood transfusions, approximately one per week. His hemoglobin had dropped to 8.3 g dL-1. He was treated initially with amicar 500 mg every 6 hr without reduction in bleeding. He was later treated with cryoprecipitate transfusions with a regimen of 2 packs (10 U) three times a week with subsequent stability in hemoglobin at a level around 10 g dL-1. However, his hemoglobin subsequently decreased and he continued to require blood transfusions.


June 2015

Alternative Aortic Access: Translumbar, Transapical, Subclavian, Conduit, and Transvenous Access to the Aorta.

Steinberger JD, McWilliams JP, Moriarty JM.

Large-caliber access to the arterial system is more frequently required in the age of thoracic endovascular aneurysm repair, endovascular aneurysm repair, and transaortic valve implantation. Frequently either anatomical or vessel size constraints preclude use of common access points such as the common femoral, radial, and brachial arteries. Alternative approaches include percutaneous access at alternate sites (subclavian, axillary, and carotid), open surgical access to the heart (left ventricular apex), open surgical access to large-caliber vessels (ascending aorta, subclavian, and axillary arteries, retroperitoneal access to the iliac artery or distal aorta), and novel percutaneous approaches (transvenous). Such approaches require additional skill sets, equipment, and, frequently, multidisciplinary teams to ensure safety and success. The techniques and approaches outlined in this article may allow expansion of endovascular treatments to greater patient populations and disease states than previously thought feasible.


June 2015

Prevalence of Incidental Findings on Abdominal Computed Tomography Angiograms on Prospective Renal Donors.

Tan N, Charoensak A, Ajwichai K, Gritsch HA, Danovitch G, Schulam P, Lu DS, Margolis DJ, Raman SS.

OBJECTIVE: To evaluate the prevalence of incidental findings on preoperative abdominal computed tomography angiography-computed tomography urography in asymptomatic prospective renal donors. METHODS: A Health Insurance Portability and Accountability Act (HIPAA)-compliant, Institutional Review Board (IRB)-approved retrospective study of 1,597 subjects undergoing renal transplant evaluation from June 1, 2006, to March 31, 2011, was performed. Candidates underwent multiphasic multidetector computed tomography angiography-computed tomography urography for presurgical evaluation of renal vascular and parenchymal anatomy. All scans were reviewed by one of three fellowship-trained abdominal radiologists. The diagnoses were made on the basis of computed tomography characteristics of each lesion, and pathology confirmation was available for seven patients. We calculated the prevalence of each incidental finding, performed Fisher exact test or chi-square test for categorical variables between the cohort that did and did not undergo donor nephrectomy, and performed simple linear logistic regression analysis of incidental findings which predicted renal donation.


May 2015

Percutaneous Cryoablation for the Treatment of Recurrent Thymoma: Preliminary Safety and Efficacy.

Abtin F, Suh RD, Nasehi L, Han SX, Hsu W, Quirk M, Genshaft S, Gutierrez AJ, Cameron RB.

Thymoma is the most common primary tumor of the anterior mediastinum and often recurs after initial surgical resection. In this case series, percutaneous cryoablation, a locally ablative technique, was used to treat 25 mediastinal and pleural recurrent thymoma lesions in five patients. Safety and short-term efficacy data were collected. In 23 percutaneous cryoablations (92%), there were no or minimal complications. One serious complication, myasthenia gravis flare, occurred. Over the duration of follow-up (median, 331 d), 18 of 20 ablated lesions (90%) showed no evidence of local recurrence. Percutaneous cryoablation shows promise as a safe and effective treatment modality for recurrent thymoma.


May 2015

Diffusion MRI Quality Control and Functional Diffusion Map Results in ACRIN 6677/RTOG 0625: A Multicenter, Randomized, Phase II Trial of Bevacizumab and Chemotherapy in Recurrent Glioblastoma.

Ellingson BM, Kim E, Woodworth DC, Marques H, Boxerman JL, Safriel Y, McKinstry RC, Bokstein F, Jain R, Chi TL, Sorensen AG, Gilbert MR, Barboriak DP.

Functional diffusion mapping (fDM) is a cancer imaging technique that quantifies voxelwise changes in apparent diffusion coefficient (ADC). Previous studies have shown value of fDMs in bevacizumab therapy for recurrent glioblastoma multiforme (GBM). The aim of the present study was to implement explicit criteria for diffusion MRI quality control and independently evaluate fDM performance in a multicenter clinical trial (RTOG 0625/ACRIN 6677). A total of 123 patients were enrolled in the current multicenter trial and signed institutional review board-approved informed consent at their respective institutions. MRI was acquired prior to and 8 weeks following therapy. A 5-point QC scoring system was used to evaluate DWI quality. fDM performance was evaluated according to the correlation of these metrics with PFS and OS at the first follow-up time-point. Results showed ADC variability of 7.3% in NAWM and 10.5% in CSF. A total of 68% of patients had usable DWI data and 47% of patients had high quality DWI data when also excluding patients that progressed before the first follow-up. fDM performance was improved by using only the highest quality DWI. High pre-treatment contrast enhancing tumor volume was associated with shorter PFS and OS. A high volume fraction of increasing ADC after therapy was associated with shorter PFS, while a high volume fraction of decreasing ADC was associated with shorter OS. In summary, DWI in multicenter trials are currently of limited value due to image quality. Improvements in consistency of image quality in multicenter trials are necessary for further advancement of DWI biomarkers.


May 2015

MRI Perfusion Measurements Calculated Using Advanced Deconvolution Techniques Predict Survival in Recurrent Glioblastoma Treated with Bevacizumab.

Harris RJ, Cloughesy TF, Hardy AJ, Liau LM, Pope WB, Nghiemphu PL, Lai A, Ellingson BM.

Bevacizumab is a therapeutic drug used in treatment of recurrent glioblastoma to inhibit angiogenesis. Treatment response is often monitored through the use of perfusion MRI measures of cerebral blood volume, flow, and other pharmacokinetic parameters; however, most methods for deriving these perfusion parameters can produce errors depending on bolus kinetics. Recently, a number of new methods have been developed to overcome these challenges. In the current study we examine cerebral blood volume and blood flow characteristics in 45 recurrent glioblastoma patients before and after treatment with bevacizumab. Perfusion MRI data was processed using a standard single value decomposition (SVD) technique, two block-circulant SVD techniques, and a Bayesian estimation technique. A proportional hazards model showed that patients with a large decrease in relative blood volume (RBV) after treatment had extended overall survival (P = 0.0048). Patients with large pre-treatment relative blood flow (RBF) showed extended progression-free survival (P = 0.0216) and overall survival (P = 0.0112), and patients with a large decrease in RBF following treatment showed extended overall survival (P = 0.0049). These results provide evidence that blood volume and blood flow measurements can be used as biomarkers in patients treated with bevacizumab.


May 2015

Endovascular Treatment of Acute Ischemic Stroke.

Kidwell CS, Jahan R.

Endovascular therapy for acute stroke has evolved with the use of intra-arterial thrombolytics, intravenous/intra-arterial bridging strategies, and mechanical thrombectomy/aspiration devices. Despite widespread use in clinical practice, randomized trials of first-generation devices failed to demonstrate improved outcomes compared with standard care. New-generation stent retriever devices demonstrate higher rates of revascularization and clinical outcomes compared with first-generation devices. Additional randomized trials are underway and have the potential to confirm clinical efficacy of new-generation devices compared with standard care. The role of additional advanced imaging for patient selection remains unclear, and further trials are needed to demonstrate the role of these techniques for patient selection.


May 2015

ACR Appropriateness Criteria Imaging in the Diagnosis of Thoracic Outlet Syndrome.

Moriarty JM, Bandyk DF, Broderick DF, Cornelius RS, Dill KE, Francois CJ, Gerhard-Herman MD, Ginsburg ME, Hanley M, Kalva SP, Kanne JP, Ketai LH, Majdalany BS, Ravenel JG, Roth CJ, Saleh AG, Schenker MP, Mohammed TL, Rybicki FJ.

Thoracic outlet syndrome is a clinical entity characterized by compression of the neurovascular bundle, and may be associated with additional findings such as venous thrombosis, arterial stenosis, or neurologic symptoms. The goal of imaging is to localize the site of compression, the compressing structure, and the compressed organ or vessel, while excluding common mimics. A literature review is provided of current indications for diagnostic imaging, with discussion of potential limitations and benefits of the respective modalities. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. In this document, we provided guidelines for use of various imaging modalities for assessment of thoracic outlet syndrome.


May 2015

Isolated Common Iliac Aneurysm and Spontaneous Ilioiliac Arteriovenous Fistula in a Patient with Subsequent Type II Endoleak and Successful Endovascular Management.

Park JK, Lee M, So A, Lee HY.

Common iliac artery aneurysms (CIAAs) complicated by spontaneous ilioiliac arteriovenous (AV) fistulae (IIAVFs) are rare (1). The present report describes a patient with CIAA and IIAVF managed with endovascular techniques to solve this complex clinical problem, and a subsequent complication in the form of a type II endoleak. Institutional review board approval was not required for this case report.


May 2015

Vitamin D Deficiency in Children with Intestinal Failure Receiving Home Parenteral Nutrition.

Wozniak LJ, Bechtold HM, Reyen LE, Hall TR, Vargas JH.

BACKGROUND: Vitamin D plays important roles in both skeletal and nonskeletal health. Limited data suggest that patients with intestinal failure (IF) receiving home parenteral nutrition (PN) are at risk for vitamin D deficiency due to inadequate oral intake, poor absorption, and chronic illness. The purpose of this study was to document vitamin D status in pediatric patients with IF receiving home PN. MATERIALS AND METHODS: We performed a 2-year retrospective review of children with IF followed at our center who had been on home PN for ≥6 months and had ≥1 serum 25-hydroxyvitamin D (25-OHD) level checked as part of routine clinical care. Patients were then categorized as deficient (<20 ng/mL), insufficient (20-29 ng/mL), or normal (≥30 ng/mL) based on their lowest vitamin D level. Demographic data and clinical characteristics were also assessed.


May 2015

Breast Cancer: Radiogenomic Biomarker Reveals Associations among Dynamic Contrast-enhanced MR Imaging, Long Noncoding RNA, and Metastasis.

Yamamoto S, Han W, Kim Y, Du L, Jamshidi N, Huang D, Kim JH, Kuo MD.

Purpose To perform a radiogenomic analysis of women with breast cancer to study the multiscale relationships among quantitative computer vision-extracted dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging phenotypes, early metastasis, and long noncoding RNA (lncRNA) expression determined by means of high-resolution next-generation RNA sequencing. Materials and Methods In this institutional review board-approved study, an automated image analysis platform extracted 47 computational quantitative features from DCE MR imaging data in a training set (n = 19) to screen for MR imaging biomarkers indicative of poor metastasis-free survival (MFS). The lncRNA molecular landscape of the candidate feature was defined by using an RNA sequencing-specific negative binomial distribution differential expression analysis. Then, this radiogenomic biomarker was applied prospectively to a validation set (n = 42) to allow prediction of MFS and lncRNA expression by using quantitative polymerase chain reaction analysis. Results The quantitative MR imaging feature, enhancing rim fraction score, was predictive of MFS in the training set (P = .007). RNA sequencing analysis yielded an average of 55.7 x 10(6) reads per sample and identified 14 880 lncRNAs from a background of 189 883 transcripts per sample. Radiogenomic analysis allowed identification of three previously uncharacterized and five named lncRNAs significantly associated with high enhancing rim fraction, including Homeobox transcript antisense intergenic RNA (HOTAIR) (P < .05), a known predictor of poor MFS in patients with breast cancer. Independent validation confirmed the association of the enhancing rim fraction phenotype with both MFS (P = .002) and expression of four of the top five differentially expressed lncRNAs (P < .05), including HOTAIR. Conclusion The enhancing rim fraction score, a quantitative DCE MR imaging lncRNA radiogenomic biomarker, is associated with early metastasis and expression of the known predictor of metastatic progression, HOTAIR.


April 2015

Advances in MR Imaging for Cervical Spondylotic Myelopathy.

Ellingson BM, Salamon N, Holly LT.

PURPOSE: To outline the pathogenesis of cervical spondylotic myelopathy (CSM), the correlative abnormalities observed on standard magnetic resonance imaging (MRI), the biological implications and current status of diffusion tensor imaging (DTI), and MR spectroscopy (MRS) as clinical tools, and future directions of MR technology in the management of CSM patients. METHODS: A systematic review of the pathogenesis and current state-of-the-art in MR imaging technology for CSM was performed.


April 2015

The Risks of Innovation in Health Care.

Enzmann DR.

Innovation in health care creates risks that are unevenly distributed. An evolutionary analogy using species to represent business models helps categorize innovation experiments and their risks. This classification reveals two qualitative categories: early and late diversification experiments. Early diversification has prolific innovations with high risk because they encounter a "decimation" stage, during which most experiments disappear. Participants face high risk. The few decimation survivors can be sustaining or disruptive according to Christensen's criteria. Survivors enter late diversification, during which they again expand, but within a design range limited to variations of the previous surviving designs. Late diversifications carry lower risk. The exception is when disruptive survivors "diversify," which amplifies their disruption. Health care and radiology will experience both early and late diversifications, often simultaneously. Although oversimplifying Christensen's concepts, early diversifications are likely to deliver disruptive innovation, whereas late diversifications tend to produce sustaining innovations. Current health care consolidation is a manifestation of late diversification. Early diversifications will appear outside traditional care models and physical health care sites, as well as with new science such as molecular diagnostics. They warrant attention because decimation survivors will present both disruptive and sustaining opportunities to radiology. Radiology must participate in late diversification by incorporating sustaining innovations to its value chain. Given the likelihood of disruptive survivors, radiology should seriously consider disrupting itself rather than waiting for others to do so. Disruption entails significant modifications of its value chain, hence, its business model, for which lessons may become available from the pharmaceutical industry's current simultaneous experience with early and late diversifications.


April 2015

ACR Appropriateness Criteria Indeterminate Renal Mass.

Heilbrun ME, Remer EM, Casalino DD, Beland MD, Bishoff JT, Blaufox MD, Coursey CA, Goldfarb S, Harvin HJ, Nikolaidis P, Preminger GM, Raman SS, Sahni A, Vikram R, Weinfeld RM.

Renal masses are increasingly detected in asymptomatic individuals as incidental findings. An indeterminate renal mass is one that cannot be diagnosed confidently as benign or malignant at the time it is discovered. CT, ultrasonography, and MRI of renal masses with fast-scan techniques and intravenous (IV) contrast are the mainstays of evaluation. Dual-energy CT, contrast-enhanced ultrasonography, PET/CT, and percutaneous biopsy are all technologies that are gaining traction in the characterization of the indeterminate renal mass. In cases in which IV contrast cannot be used, whether because of IV contrast allergy or renal insufficiency, renal mass classification with CT is markedly limited. In the absence of IV contrast, ultrasonography, MRI, and biopsy have some advantages. Owing to the low malignant and metastatic potential of small renal cell carcinomas (≤4 cm in diameter), active surveillance is additionally emerging as a diagnostic strategy for patients who have high surgical risk or limited life expectancy. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and application by the panel of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.


April 2015

Meniere's Disease: Histopathology, Cytochemistry, and Imaging.

Ishiyama G, Lopez IA, Sepahdari AR, Ishiyama A.

Meniere's disease is a poorly understood, disabling syndrome causing spells of vertigo, hearing fluctuation, tinnitus, and aural fullness. In this paper, we present a review of the histopathology, cytochemistry, and imaging of Meniere's disease. Histopathology is significant for neuroepithelial damage with hair cell loss, basement membrane thickening, and perivascular microvascular damage. Cytochemical alterations are significant for altered AQP4 and AQP6 expression in the supporting cell, and altered cochlin and mitochondrial protein expression. Current developments include imaging techniques to determine the degree and presence of endolymphatic hydrops, and future studies will endeavor to correlate the observance of hydrops with clinical findings.


April 2015

Brain Biopsy in Neurologic Decline of Unknown Etiology.

Magaki S, Gardner T, Khanlou N, Yong WH, Salamon N, Vinters HV.

Brain biopsies have an uncertain role in the diagnosis of patients with dementia or neurologic decline of unknown etiology. They are often performed only after an exhaustive panel of less invasive tests and procedures have failed to provide a definitive diagnosis. The objective of this study was to evaluate the sensitivity of brain biopsies in this patient group through the retrospective analysis of 53 brain biopsies performed for neurologic disease of unknown etiology at a single tertiary care institution between December 2001 and December 2011. Patients with known nonlymphomatous neoplasms thought to be associated with the neurologic symptoms or with immunodeficiency were excluded from the study. Furthermore, the clinical presentation, imaging and laboratory tests were compared between diagnostic groups to identify factors more likely to yield a diagnosis. Sixty percent of the biopsies were diagnostic (32 of 53), with the most common histologic diagnosis of central nervous system lymphoma in 14 of 53 patients (26% of total) followed by infarct in four subjects (7.5%). A few patients were found to have rare and unsuspected diseases such as lymphomatosis cerebri, neurosarcoidosis and neuroaxonal leukodystrophy. Complications from biopsy were uncommon and included hemorrhage and infection with abscess formation at the biopsy site. These results suggest that brain biopsies may be useful in difficult cases in which less invasive measures have been unable to yield a definitive diagnosis.


April 2015

Criteria for Identifying Radiologists with Acceptable Screening Mammography Interpretive Performance on Basis of Multiple Performance Measures.

Miglioretti DL, Ichikawa L, Smith RA, Bassett LW, Feig SA, Monsees B, Parikh JR, Rosenberg RD, Sickles EA, Carney PA.

OBJECTIVE: Using a combination of performance measures, we updated previously proposed criteria for identifying physicians whose performance interpreting screening mammography may indicate suboptimal interpretation skills. MATERIALS AND METHODS: In this study, six expert breast imagers used a method based on the Angoff approach to update criteria for acceptable mammography performance on the basis of two sets of combined performance measures: set 1, sensitivity and specificity for facilities with complete capture of false-negative cancers; and set 2, cancer detection rate (CDR), recall rate, and positive predictive value of a recall (PPV1) for facilities that cannot capture false-negative cancers but have reliable cancer follow-up information for positive mammography results. Decisions were informed by normative data from the Breast Cancer Surveillance Consortium (BCSC).


April 2015

Prevalence of Coronary Artery Disease Evaluated by Coronary CT Angiography in Women with Mammographically Detected Breast Arterial Calcifications.

Mostafavi L, Marfori W, Arellano C, Tognolini A, Speier W, Adibi A, Ruehm SG.

To assess the correlation between breast arterial calcifications (BAC) on digital mammography and the extent of coronary artery disease (CAD) diagnosed with dual source coronary computed tomography angiography (CTA) in a population of women both symptomatic and asymptomatic for coronary artery disease. 100 consecutive women (aged 34 - 86 years) who underwent both coronary CTA and digital mammography were included in the study. Health records were reviewed to determine the presence of cardiovascular risk factors such as hypertension, hyperlipidemia, diabetes mellitus, and smoking. Digital mammograms were reviewed for the presence and degree of BAC, graded in terms of severity and extent. Coronary CTAs were reviewed for CAD, graded based on the extent of calcified and non-calcified plaque, and the degree of major vessel stenosis. A four point grading scale was used for both coronary CTA and mammography. The overall prevalence of positive BAC and CAD in the studied population were 12% and 29%, respectively. Ten of the 12 patients with moderate or advanced BAC on mammography demonstrated moderate to severe CAD as determined by coronary CTA. For all women, the positive predictive value of BAC for CAD was 0.83 and the negative predictive value was 0.78. The presence of BAC on mammography appears to correlate with CAD as determined by coronary CTA (Spearman's rank correlation coefficient = 0.48, p<.000001). Using logistic regression, the inclusion of BAC as a feature in CAD predication significantly increased classification results (p=0.04).


April 2015

Role of the Quantitative Imaging Biomarker Alliance in Optimizing CT for the Evaluation of Lung Cancer Screen-Detected Nodules.

Mulshine JL, Gierada DS, Armato SG 3rd, Avila RS, Yankelevitz DF, Kazerooni EA, McNitt-Gray MF, Buckler AJ, Sullivan DC.

The Quantitative Imaging Biomarker Alliance (QIBA) is a multidisciplinary consortium sponsored by the RSNA to define processes that enable the implementation and advancement of quantitative imaging methods described in a QIBA profile document that outlines the process to reliably and accurately measure imaging features. A QIBA profile includes factors such as technical (product-specific) standards, user activities, and relationship to a clinically meaningful metric, such as with nodule measurement in the course of CT screening for lung cancer. In this report, the authors describe how the QIBA approach is being applied to the measurement of small pulmonary nodules such as those found during low-dose CT-based lung cancer screening. All sources of variance with imaging measurement were defined for this process. Through a process of experimentation, literature review, and assembly of expert opinion, the strongest evidence was used to define how to best implement each step in the imaging acquisition and evaluation process. This systematic approach to implementing a quantitative imaging biomarker with standardized specifications for image acquisition and postprocessing for a specific quantitative measurement of a pulmonary nodule results in consistent performance characteristics of the measurement (eg, bias and variance). Implementation of the QIBA small nodule profile may allow more efficient and effective clinical management of the diagnostic workup of individuals found to have suspicious pulmonary nodules in the course of lung cancer screening evaluation.


April 2015

Imaging-histologic Discordance at Percutaneous Biopsy of the Lung.

Oh AS, Arnold CW, Vangala S, Wallace WD, Genshaft SJ, Sarma K, Aberle DR.

RATIONALE AND OBJECTIVES: The purpose of this study was to quantify the degree of imaging-histologic discordance in a cohort of patients undergoing computed tomography (CT)-guided lung biopsy for focal lung disease. MATERIALS AND METHODS: A retrospective review was performed of 186 patients who underwent percutaneous lung biopsy of a parenchymal lesion at our institution between January and December 2009. Diagnostic radiology reports of CT or positron emission tomography-CTs performed before biopsy were used to classify the lesion as malignant or benign by five readers. Pathology reports of the biopsied lesions were classified by three readers. Inter-reader agreement and imaging-histologic concordance were quantified using kappa statistics. Discordant benign cases were then revisited to determine downstream effects.


April 2015

Arterial Spin-labeling Perfusion MRI Stratifies Progression-free Survival and Correlates with Epidermal Growth Factor Receptor Status in Glioblastoma.

Qiao XJ, Ellingson BM, Kim HJ, Wang DJ, Salamon N, Linetsky M, Sepahdari AR, Jiang B, Tian JJ, Esswein SR, Cloughesy TF, Lai A, Nghiemphu L, Pope WB.

BACKGROUND AND PURPOSE: Glioblastoma is a common primary brain tumor with a poor but variable prognosis. Our aim was to investigate the feasibility of MR perfusion imaging by using arterial spin-labeling for determining the prognosis of patients with glioblastoma. MATERIALS AND METHODS: Pseudocontinuous arterial spin-labeling with 3D background-suppressed gradient and spin-echo was acquired before surgery on 53 patients subsequently diagnosed with glioblastoma. The calculated CBF color maps were visually evaluated by 3 independent readers blinded to patient history. Pathologic and survival data were correlated with CBF map findings. Arterial spin-labeling values in tumor tissue were also quantified by using manual fixed-size ROIs.


April 2015

Incremental Value of Secretin-enhanced Magnetic Resonance Cholangiopancreatography in Detecting Ductal Communication in a Population with High Prevalence of Small Pancreatic Cysts.

Rastegar N, Matteoni-Athayde LG, Eng J, Takahashi N, Tamm EP, Mortele KJ, Syngal S, Margolis D, Lennon AM, Wolfgang CL, Fishman EK, Hruban RH, Goggins M, Canto MI, Kamel IR.

PURPOSE: We investigated the incremental diagnostic yield of S-MRCP in a population with high prevalence of small pancreatic cysts. METHODS: Standard MRCP protocol was performed with and without secretin using 1.5 T units in subjects undergoing pancreatic screening because of a strong family history of pancreatic cancer as part of the multicenter Cancer of the Pancreas Screening-3 trial (CAPS 3). All studies were reviewed prospectively by two independent readers who recorded the presence and number of pancreatic cysts, the presence of visualized ductal communication before and after secretin, and the degree of confidence in the diagnoses.


April 2015

SolitaireTM with the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) Trial: Protocol for a Randomized, Controlled, Multicenter Study Comparing the Solitaire Revascularization Device with IV tPA with IV tPA Alone in Acute Ischemic Stroke.

Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, Albers GW, Cognard C, Cohen DJ, Hacke W, Jansen O, Jovin TG, Mattle HP, Nogueira RG, Siddiqui AH, Yavagal DR, Devlin TG, Lopes DK, Reddy V, du Mesnil de Rochemont R, Jahan R; SWIFT PRIME Investigators.

RATIONALE: Early reperfusion in patients experiencing acute ischemic stroke is critical, especially for patients with large vessel occlusion who have poor prognosis without revascularization. Solitaire™ stent retriever devices have been shown to immediately restore vascular perfusion safely, rapidly, and effectively in acute ischemic stroke patients with large vessel occlusions. AIM: The aim of the study was to demonstrate that, among patients with large vessel, anterior circulation occlusion who have received intravenous tissue plasminogen activator, treatment with Solitaire revascularization devices reduces degree of disability 3 months post stroke. DESIGN: The study is a global multicenter, two-arm, prospective, randomized, open, blinded end-point trial comparing functional outcomes in acute ischemic stroke patients who are treated with either intravenous tissue plasminogen activator alone or intravenous tissue plasminogen activator in combination with the Solitaire device. Up to 833 patients will be enrolled. PROCEDURES: Patients who have received intravenous tissue plasminogen activator are randomized to either continue with intravenous tissue plasminogen activator alone or additionally proceed to neurothrombectomy using the Solitaire device within six-hours of symptom onset.


April 2015

Characterization of the NanoDot OSLD Dosimeter in CT.

Scarboro SB, Cody D, Alvarez P, Followill D, Court L, Stingo FC, Zhang D, McNitt-Gray M, Kry SF.

PURPOSE: The extensive use of computed tomography (CT) in diagnostic procedures is accompanied by a growing need for more accurate and patient-specific dosimetry techniques. Optically stimulated luminescent dosimeters (OSLDs) offer a potential solution for patient-specific CT point-based surface dosimetry by measuring air kerma. The purpose of this work was to characterize the OSLD nanoDot for CT dosimetry, quantifying necessary correction factors, and evaluating the uncertainty of these factors. METHODS: A characterization of the Landauer OSL nanoDot (Landauer, Inc., Greenwood, IL) was conducted using both measurements and theoretical approaches in a CT environment. The effects of signal depletion, signal fading, dose linearity, and angular dependence were characterized through direct measurement for CT energies (80-140 kV) and delivered doses ranging from ~5 to >1000 mGy. Energy dependence as a function of scan parameters was evaluated using two independent approaches: direct measurement and a theoretical approach based on Burlin cavity theory and Monte Carlo simulated spectra. This beam-quality dependence was evaluated for a range of CT scanning parameters.


April 2015

Complementary Radial Tagging for Improved Myocardial Tagging Contrast.

Wang Z, Nasiraei-Moghaddam A, Reyhan ML, Srinivasan S, Finn JP, Ennis DB.

PURPOSE: To develop and evaluate complementary radial tagging (CRT) for improved myocardial tagging contrast. METHODS: We sought to develop and evaluate CRT, which aims to preserve the radial tag contrast throughout the cardiac cycle. Similar to complementary spatial modulation of magnetization, CRT acquires two sets of images with a phase shift in the tag pattern. The combination of a ramped imaging flip angle and image subtraction enhances tag contrast throughout the cardiac cycle. The proposed CRT technique uses a small table shift away from the isocenter to improve the uniformity of the radial tag pattern. We provide a mathematical solution for the optimal table shift and validate the solution in using a retrospective analysis of images from 500 patients in the Cardiac Atlas Project database.


April 2015

Postischemic Hyperperfusion on Arterial Spin Labeled Perfusion MRI is Linked to Hemorrhagic Transformation in Stroke.

Yu S, Liebeskind DS, Dua S, Wilhalme H, Elashoff D, Qiao XJ, Alger JR, Sanossian N, Starkman S, Ali LK, Scalzo F, Lou X, Yoo B, Saver JL, Salamon N, Wang DJ; for UCLA Stroke Investigators.

The purpose of this study was to investigate the relationship between hyperperfusion and hemorrhagic transformation (HT) in acute ischemic stroke (AIS). Pseudo-continuous arterial spin labeling (ASL) with background suppressed 3D GRASE was performed during routine clinical magnetic resonance imaging (MRI) on AIS patients at various time points. Arterial spin labeling cerebral blood flow (CBF) maps were visually inspected for the presence of hyperperfusion. Hemorrhagic transformation was followed during hospitalization and was graded on gradient recalled echo (GRE) scans into hemorrhagic infarction (HI) and parenchymal hematoma (PH). A total of 361 ASL scans were collected from 221 consecutive patients with middle cerebral artery stroke from May 2010 to September 2013. Hyperperfusion was more frequently detected posttreatment (odds ratio (OR)=4.8, 95% confidence interval (CI) 2.5 to 8.9, P<0.001) and with high National Institutes of Health Stroke Scale (NIHSS) scores at admission (P<0.001). There was a significant association between having hyperperfusion at any time point and HT (OR=3.5, 95% CI 2.0 to 6.3, P<0.001). There was a positive relationship between the grade of HT and time-hyperperfusion with the Spearman's rank correlation of 0.44 (P=0.003). Arterial spin labeling hyperperfusion may provide an imaging marker of HT, which may guide the management of AIS patients post tissue-type plasminogen activator (tPA) and/or endovascular treatments. Late hyperperfusion should be given more attention to prevent high-grade HT.


March 2015

Representing and Extracting Lung Cancer Study Metadata: Study Objective and Study Design.

Garcia-Gathright JI, Oh A, Abarca PA, Han M, Sago W, Spiegel ML, Wolf B, Garon EB, Bui AA, Aberle DR.

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 2015

Multifocality and Prostate Cancer Detection by Multiparametric Magnetic Resonance

Le JD, Tan N, Shkolyar E, Lu DY, Kwan L, Marks LS, Huang J, Margolis DJ, Raman SS, Reiter RE.

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 2015

Emerging Potential of Natural Products for Targeting Mucins for Therapy Against Inflammation and Cancer.

Macha MA, Krishn SR, Jahan R, Banerjee K, Batra SK, Jain M.

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 2015

Catheter Ablation of Accessory Pathways Near the Coronary Sinus: Value of Defining Coronary Arterial Anatomy.

Mao J, Moriarty JM, Mandapati R, Boyle NG, Shivkumar K, Vaseghi M.

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 2015

Diagnostic and Interventional Radiology for Liver Diseases.

Murata S, Niggemann P, Lee EW, Hol PK.

Diseases of the liver are common and often chronic. Moreover, the mortality rate associated with chronic liver diseases remains high, despite the constant development of novel diagnostic and therapeutic modalities; therefore, numerous efforts are being made to improve imaging techniques, especially in this decade. Currently available imaging procedures allow us to ascertain the morphology, circulation, metabolism, parenchymal texture, fibrosis, and/or tumor viability in the liver. New modalities and protocols, such as magnetic resonance (MR) perfusion, MR elastography, and dual-energy computed tomography (CT), enable the potential evaluation of liver function via imaging studies. Thus, the utilization of advanced imaging techniques and contemporary interventional radiology (IR) devices has realized novel multimodality treatments for liver diseases, resulting in promising outcomes in many patients who cannot be surgically treated.


March 2015

High-resolution, Whole-body Vascular Imaging with Ferumoxytol as an Alternative to Gadolinium Agents in a Pediatric Chronic Kidney Disease Cohort.

Nayak AB, Luhar A, Hanudel M, Gales B, Hall TR, Finn JP, Salusky IB, Zaritsky J.

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 2015

Management of Hepatocellular Carcinoma with Portal Vein Thrombosis.

Quirk M, Kim YH, Saab S, Lee EW.

Management of hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) is complex and requires an understanding of multiple therapeutic options. PVT is present in 10%-40% of HCC at the time of diagnosis, and is an adverse prognostic factor. Management options are limited, as transplantation is generally contraindicated, and surgical resection is only rarely performed in select centers. Systemic medical therapy with sorafenib has been shown to modestly prolong survival. Transarterial chemoembolization has been performed in select cases but has shown a high incidence of complications. Emerging data on treatment of PVT with Y-90 radioembolization suggest that this modality is well-tolerated and associated with favorable overall survival. Current society guidelines do not yet specifically recommend radioembolization for patients with PVT, but this may change with the development of newer staging systems and treatment algorithms. In this comprehensive literature review, we present current and available management options with the relative advantages, disadvantages and contraindications of these treatment options with summarized data on overall survival.


March 2015

Novel Technique for Characterizing Prostate Cancer Utilizing MRI Restriction Spectrum Emaging: Proof of Principle and Initial Clinical Experience with Extraprostatic Extension.

Rakow-Penner RA, White NS, Parsons JK, Choi HW, Liss MA, Kuperman JM, Schenker-Ahmed N, Bartsch H, Mattrey RF, Bradley WG, Shabaik A, Huang J, Margolis DJ, Raman SS, Marks L, Kane CJ, Reiter RE, Karow DS, Dale AM.

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 2015

Optimal Flip Angle for High Contrast Balanced SSFP Cardiac Cine Imaging.

Srinivasan S, Ennis DB.

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 2015

Alvarado Score: Can it Reduce Unnecessary CT Scans for Evaluation of Acute Appendicitis?

Apisarnthanarak P, Suvannarerg V, Pattaranutaporn P, Charoensak A, Raman SS, Apisarnthanarak A.

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 2015

Correlation of Clot Imaging with Endovascular Recanalization in Internal Carotid Artery Terminus Occlusion.

Fujimoto M, Salamon N, Takemoto K, Takao H, Song L, Tateshima S, Viñuela F.

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 2015

A Novel Bicompartmental Mathematical Model of Glioblastoma Multiforme.

Hathout L, Ellingson BM, Cloughesy T, Pope WB.

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 2015

Native Renal Biopsy: the Perfect Storm.

McWilliams JP, Kee ST.

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 2015

Frequency of Nonthromboembolic Imaging Abnormalities in Pregnant Women Referred for Computed Tomography Pulmonary Arteriography.

Moriarty JM, Bolster F, O'Connor C, Fitzpatrick P, Lawler LP, Kavanagh EC, MacMahon PJ, Murray JG.

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 2015

White Matter Ischemic Changes in Hyperacute Ischemic Stroke: Voxel-Based Analysis Using Diffusion Tensor Imaging and MR Perfusion.

Nael K, Trouard TP, Lafleur SR, Krupinski EA, Salamon N, Kidwell CS.

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 2015

Genomics of Brain Tumor Imaging.

Pope WB.

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 2015

Neuroimaging Abnormalities, Neurocognitive Function, and Fatigue in Patients with Hepatitis C.

Thames AD, Castellon SA, Singer EJ, Nagarajan R, Sarma MK, Smith J, Thaler NS, Truong JH, Schonfeld D, Thomas MA, Hinkin CH.

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 2015

Phase Contrast MRI with Flow Compensation View Sharing.

Wang D, Shao J, Rapacchi S, Middione MJ, Ennis DB, Hu P.

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 2015

The Hangman Technique: a Modified Loop Snare Technique for the Retrieval of Inferior Vena Cava Filters with Embedded Hooks.

Al-Hakim R, McWilliams JP, Derry W, Kee ST.

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 2015

Radiogenomics and Imaging Phenotypes in Glioblastoma: Novel Observations and Correlation with Molecular Characteristics.

Ellingson BM.

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 2015

Impact of 68Ga-DOTATATE PET/CT on the Management of Neuroendocrine Tumors: The Referring Physician's Perspective.

Herrmann K, Czernin J, Wolin EM, Gupta P, Barrio M, Gutierrez A, Schiepers C, Mosessian S, Phelps ME, Allen-Auerbach MS.

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 2015

Comparison of the Quantitative CT Imaging Biomarkers of Idiopathic Pulmonary Fibrosis at Baseline and Early Change with an Interval of 7 Months.

Kim HJ, Brown MS, Chong D, Gjertson DW, Lu P, Kim HJ, Coy H, Goldin JG.

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 2015

Nitroxoline Induces Apoptosis and Slows Glioma Growth in vivo.

Lazovic J, Guo L, Nakashima J, Mirsadraei L, Yong W, Kim HJ, Ellingson B, Wu H, Pope WB.

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 2015

Y90 Selective Internal Radiation Therapy.

Lee EW, Thakor AS, Tafti BA, Liu DM.

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 2015

Biomimetic Scaffolds Facilitate Healing of Critical-sized Segmental Mandibular Defects.

Lee MK, DeConde AS, Lee M, Walthers CM, Sepahdari AR, Elashoff D, Grogan T, Bezouglaia O, Tetradis S, St John M, Aghaloo T.

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 2015

High-field MR Imaging in Pediatric Congenital Heart Disease: Initial Results.

Nguyen KL, Khan SN, Moriarty JM, Mohajer K, Renella P, Satou G, Ayad I, Patel S, Boechat MI, Finn JP.

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 2015

Delayed Intravenous Contrast-enhanced 3D FLAIR MRI in Meniere's Disease: Correlation of Quantitative Measures of Endolymphatic Hydrops with Hearing.

Sepahdari AR, Ishiyama G, Vorasubin N, Peng KA, Linetsky M, Ishiyama A.

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 2015

Fine Needle Elastography (FNE) Device for Biomechanically Determining Local Variations of Tissue Mechanical Properties.

Wickramaratne D, Wilkinson P, Rao J, Ragavendra N, Sharma S, Gimzewski JK.

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.


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