September 2017Detection of Immune Responses after Immunotherapy in Glioblastoma using PET and MRI.
Antonios JP, Soto H, Everson RG, Moughon DL, Wang AC, Orpilla J, Radu C, Ellingson BM, Lee JT, Cloughesy T, Phelps ME, Czernin J, Liau LM, Prins RM.
Contrast-enhanced MRI is typically used to follow treatment response and progression in patients with glioblastoma (GBM). However, differentiating tumor progression from pseudoprogression remains a clinical dilemma largely unmitigated by current advances in imaging techniques. Noninvasive imaging techniques capable of distinguishing these two conditions could play an important role in the clinical management of patients with GBM and other brain malignancies. We hypothesized that PET probes for deoxycytidine kinase (dCK) could be used to differentiate immune inflammatory responses from other sources of contrast-enhancement on MRI. Orthotopic malignant gliomas were established in syngeneic immunocompetent mice and then treated with dendritic cell (DC) vaccination and/or PD-1 mAb blockade. Mice were then imaged with [18F]-FAC PET/CT and MRI with i.v. contrast. The ratio of contrast enhancement on MRI to normalized PET probe uptake, which we term the immunotherapeutic response index, delineated specific regions of immune inflammatory activity. On postmortem examination, FACS-based enumeration of intracranial tumor-infiltrating lymphocytes directly correlated with quantitative [18F]-FAC PET probe uptake. Three patients with GBM undergoing treatment with tumor lysate-pulsed DC vaccination and PD-1 mAb blockade were also imaged before and after therapy using MRI and a clinical PET probe for dCK. Unlike in mice, [18F]-FAC is rapidly catabolized in humans; thus, we used another dCK PET probe, [18F]-clofarabine ([18F]-CFA), that may be more clinically relevant. Enhanced [18F]-CFA PET probe accumulation was identified in tumor and secondary lymphoid organs after immunotherapy. Our findings identify a noninvasive modality capable of imaging the host antitumor immune response against intracranial tumors.
September 2017Bits and Bytes: the Future of Radiology Lies in Informatics and Information Technology.
Brink JA, Arenson RL, Grist TM, Lewin JS, Enzmann D.
Advances in informatics and information technology are sure to alter the practice of medical imaging and image-guided therapies substantially over the next decade. Each element of the imaging continuum will be affected by substantial increases in computing capacity coincident with the seamless integration of digital technology into our society at large. This article focuses primarily on areas where this IT transformation is likely to have a profound effect on the practice of radiology. KEY POINTS: • Clinical decision support ensures consistent and appropriate resource utilization. • Big data enables correlation of health information across multiple domains. • Data mining advances the quality of medical decision-making. • Business analytics allow radiologists to maximize the benefits of imaging resources.
September 2017Determination of Hepatocellular Carcinoma Grade by Needle Biopsy is Unreliable for Liver Transplant Candidate Selection.
Court CM, Harlander-Locke MP, Markovic D, French SW, Naini BV, Lu DS, Raman SS, Kaldas FM, Zarrinpar A, Farmer DG, Finn RS, Sadeghi S, Tomlinson JS, Busuttil RW, Agopian VG.
The objective of this article is to evaluate the utility of preoperative needle biopsy (PNB) grading of hepatocellular carcinoma (HCC) as a biomarker for liver transplantation (LT) candidate selection. Given the prognostic significance of HCC tumor grade, PNB grading has been proposed as a biomarker for LT candidate selection. Clinicopathologic characteristics of HCC LT recipients (1989-2014) with a PNB were analyzed, and the concordance of PNB grade to explant grade and vascular invasion was assessed to determine whether incorporation of PNB grade to accepted transplant criteria improved candidate selection. Of 965 patients undergoing LT for HCC, 234 (24%) underwent PNB at a median of 280 days prior to transplant. Grade by PNB had poor concordance to final explant pathology (ĸ = 0.22; P = 0.003), and low sensitivity (29%) and positive predictive value (35%) in identifying poorly differentiated tumors. Vascular invasion was predicted by explant pathologic grade (rs= 0.24; P < 0.001) but not PNB grade (rs = -0.05; P = 0.50). Increasing explant pathology grade (P = 0.02), but not PNB grade (P = 0.65), discriminated post-LT HCC recurrence risk. The incorporation of PNB grade to the established radiologic Milan criteria (MC) did not result in improved prognostication of post-LT recurrence (net reclassification index [NRI] = 0%), whereas grade by explant pathology resulted in significantly improved reclassification of risk (NRI = 19%). Preoperative determination of HCC grade by PNB has low concordance with explant pathologic grade and low sensitivity and positive predictive value in identifying poorly differentiated tumors. PNB grade did not accurately discriminate post-LT HCC recurrence and had no utility in improving prognostication compared with the MC alone. Incorporation of PNB to guide transplant candidate selection appears unjustified. Liver Transplantation 23 1123-1132 2017 AASLD.
September 2017Ferumoxytol vs. Gadolinium Agents for Contrast-enhanced MRI: Thoughts on Evolving Indications, Risks, and Benefits.
Finn JP, Nguyen KL, Hu P.
When gadolinium contrast was first described for human use in magnetic resonance imaging (MRI) over three decades ago, many doubted the need for it. After all, the promise of MRI was that inherent soft-tissue contrast could be tweaked in limitless ways without the type of pharmaceutical fuel that was essential for computed tomography (CT). As things transpired, the clinical and commercial impact of gadolinium-based contrast agents (GBCAs) has been enormous. Recent estimates put the number of GBCA studies at 30 million annually, fueling a multibillion dollar global market. By the mid 2000s, five extracellular GBCA formulations had been introduced in the United States and for many years these agents enjoyed a blemish-free reputation, even for patients with renal impairment.
September 2017Prognostic Significance of Left Ventricular Fibrosis in Patients With Congenital Bicuspid Aortic Valve.
Lluri G, Renella P, Finn JP, Vorobiof G, Aboulhosn J, Deb A.
This study sought to evaluate the prognostic value of left ventricular (LV) fibrosis assessed by late gadolinium enhancement (LGE) of the myocardium during cardiac magnetic resonance (CMR) imaging in patients with bicuspid aortic valve (BAV), which is associated with early aortic valve fibrosis and calcification. To what degree the LV myocardial wall is affected by fibrosis and its prognostic value is currently unknown. This is a retrospective, single-center study evaluating all adult patients with BAV who had CMR and followed from March 2002 to March 2016. CMR and transthoracic echocardiogram images were reviewed. Clinical data were abstracted from the electronic medical record. A total of 29 patients were included in the study, of which 11 (38%) had CMR studies that demonstrated the presence of LGE. Patients with LGE had significantly higher aortic valve mean gradients by echocardiography when compared with LGE-negative patients (30.3 ± 7.2 mm Hg vs 14.7 ± 3.6 mm Hg, p = 0.049). They were also more likely to have LV hypertrophy. Patients with LGE were 10 times more likely to need aortic valve replacement within 1 year of the CMR study than did patients without LGE (55% vs 5.5%, p = 0.0028). In conclusion, evaluation of LGE by CMR as a marker of LV myocardial fibrosis can have additional prognostic value when evaluating patients with aortic stenosis secondary to BAV.
September 2017Unique Case of Disseminated Plague With Multifocal Osteomyelitis.
Tovar Padua L, Kamali A, Kim H, Green NM, Civen R, Schwartz B, Krogstad P, Deville J, Yeganeh N, Lugo D, Baker A, Soni P, Cho C, Svircic N, Dry S, Seeger L, Lloyd J, Deukmedjian G, Bowen R, Hale G, Zaki SR, Mead P, Nielsen-Saines K.
Plague is a disease caused by Yersinia pestis. Septicemic and pneumonic plague have a high mortality rate if untreated. Here we describe the challenges of accurately diagnosing a nonfatal pediatric case of septicemic plague with involvement of multiple organs; to our knowledge, the first documented case of multifocal plague osteomyelitis.
August 2017Interval Lung Cancer After a Negative CT Screening Examination: CT Findings and Outcomes in National Lung Screening Trial Participants.
Gierada DS, Pinsky PF, Duan F, Garg K, Hart EM, Kazerooni EA, Nath H, Watts JR Jr, Aberle DR.
OBJECTIVES: This study retrospectively analyses the screening CT examinations and outcomes of the National Lung Screening Trial (NLST) participants who had interval lung cancer diagnosed within 1 year after a negative CT screen and before the next annual screen. METHODS: The screening CTs of all 44 participants diagnosed with interval lung cancer (cases) were matched with negative CT screens of participants who did not develop lung cancer (controls). A majority consensus process was used to classify each CT screen as positive or negative according to the NLST criteria and to estimate the likelihood that any abnormalities detected retrospectively were due to lung cancer.
August 2017Self-gated 4D Multiphase, Steady-state Imaging with Contrast Enhancement (MUSIC) Using Rotating Cartesian K-space (ROCK): Validation in Children with Congenital Heart Disease.
Han F, Zhou Z, Han E, Gao Y, Nguyen KL, Finn JP, Hu P.
PURPOSE: To develop and validate a cardiac-respiratory self-gating strategy for the recently proposed multiphase steady-state imaging with contrast enhancement (MUSIC) technique. METHODS: The proposed SG strategy uses the ROtating Cartesian K-space (ROCK) sampling, which allows for retrospective k-space binning based on motion surrogates derived from k-space center line. The k-space bins are reconstructed using a compressed sensing algorithm. Ten pediatric patients underwent cardiac MRI for clinical reasons. The original MUSIC and 2D-CINE images were acquired as a part of the clinical protocol, followed by the ROCK-MUSIC acquisition, all under steady-state intravascular distribution of ferumoxytol. Subjective scores and image sharpness were used to compare the images of ROCK-MUSIC and original MUSIC.
August 2017Covariance J-resolved Spectroscopy: Theory and Application in Vivo.
Iqbal Z, Verma G, Kumar A, Thomas MA.
Magnetic resonance spectroscopy (MRS) is a powerful tool capable of investigating the metabolic status of several tissues in vivo. In particular, single-voxel-based 1H spectroscopy provides invaluable biochemical information from a volume of interest (VOI) and has therefore been used in a variety of studies. Unfortunately, typical one-dimensional MRS data suffer from severe signal overlap and thus important metabolites are difficult to distinguish. One method that is used to disentangle overlapping resonances is the two-dimensional J-resolved spectroscopy (JPRESS) experiment. Due to the long acquisition duration of the JPRESS experiment, a limited number of points are acquired in the indirect dimension, leading to poor spectral resolution along this dimension. Poor spectral resolution is problematic because proper peak assignment may be hindered, which is why the zero-filling method is often used to improve resolution as a post-processing step. However, zero-filling leads to spectral artifacts, which may affect visualization and quantitation of spectra. A novel method utilizing a covariance transformation, called covariance J-resolved spectroscopy (CovJ), was developed in order to improve spectral resolution along the indirect dimension (F1 ). Comparison of simulated data demonstrates that peak structures remain qualitatively similar between JPRESS and the novel method along the diagonal region (F1 = 0 Hz), whereas differences arise in the cross-peak (F1 ≠ 0 Hz) regions. In addition, quantitative results of in vivo JPRESS data acquired on a 3T scanner show significant correlations (r2 >0.86, p<0.001) when comparing the metabolite concentrations between the two methods. Finally, a quantitation algorithm, 'COVariance Spectral Evaluation of 1H Acquisitions using Representative prior knowledge' (Cov-SEHAR), was developed in order to quantify γ-aminobutyric acid and glutamate from the CovJ spectra. These preliminary findings indicate that the CovJ method may be used to improve spectral resolution without hindering metabolite quantitation for J-resolved spectra.
August 2017Phase I Trial of Intratumoral Injection of CCL21 Gene-Modified Dendritic Cells in Lung Cancer Elicits Tumor-Specific Immune Responses and CD8+ T-cell Infiltration.
Lee JM, Lee MH, Garon E, Goldman JW, Salehi-Rad R, Baratelli FE, Schaue D, Wang G, Rosen F, Yanagawa J, Walser TC, Lin Y, Park SJ, Adams S, Marincola FM, Tumeh PC, Abtin F, Suh R, Reckamp KL, Lee G, Wallace WD, Lee S, Zeng G, Elashoff DA, Sharma S, Dubinett SM.
Purpose: A phase I study was conducted to determine safety, clinical efficacy, and antitumor immune responses in patients with advanced non-small cell lung carcinoma (NSCLC) following intratumoral administration of autologous dendritic cells (DC) transduced with an adenoviral (Ad) vector expressing the CCL21 gene (Ad-CCL21-DC). We evaluated safety and tumor antigen-specific immune responses following in situ vaccination (ClinicalTrials.gov: NCT01574222).Experimental Design: Sixteen stage IIIB/IV NSCLC subjects received two vaccinations (1 x 106, 5 x 106, 1 x 107, or 3 x 107 DCs/injection) by CT- or bronchoscopic-guided intratumoral injections (days 0 and 7). Immune responses were assessed by tumor antigen-specific peripheral blood lymphocyte induction of IFNϒ in ELISPOT assays. Tumor biopsies were evaluated for CD8+ T cells by IHC and for PD-L1 expression by IHC and real-time PCR (RT-PCR).
August 2017Perfusion and Diffusion MRI Signatures in Histologic and Genetic Subtypes of WHO Grade II-III Diffuse Gliomas.
Leu K, Ott GA, Lai A, Nghiemphu PL, Pope WB, Yong WH, Liau LM, Cloughesy TF, Ellingson BM.
The value of perfusion and diffusion-weighted MRI in differentiating histological subtypes according to the 2007 WHO glioma classification scheme (i.e. astrocytoma vs. oligodendroglioma) and genetic subtypes according to the 2016 WHO reclassification (e.g. 1p/19q co-deletion and IDH1 mutation status) in WHO grade II and III diffuse gliomas remains controversial. In the current study, we describe unique perfusion and diffusion MR signatures between histological and genetic glioma subtypes. Sixty-five patients with 2007 histological designations (astrocytomas and oligodendrogliomas), 1p/19q status (+ = intact/- = co-deleted), and IDH1 mutation status (MUT/WT) were included in this study. In all patients, median relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) were estimated within T2 hyperintense lesions. Bootstrap hypothesis testing was used to compare subpopulations of gliomas, separated by WHO grade and 2007 or 2016 glioma classification schemes. A multivariable logistic regression model was also used to differentiate between 1p19q+ and 1p19q- WHO II-III gliomas. Neither rCBV nor ADC differed significantly between histological subtypes of pure astrocytomas and pure oligodendrogliomas. ADC was significantly different between molecular subtypes (p = 0.0016), particularly between IDHWT and IDHMUT/1p19q+ (p = 0.0013). IDHMUT/1p19q+ grade III gliomas had higher median ADC; IDHWT grade III gliomas had higher rCBV with lower ADC; and IDHMUT/1p19q- had intermediate rCBV and ADC values, similar to their grade II counterparts. A multivariable logistic regression model was able to differentiate between IDHWT and IDHMUT WHO II and III gliomas with an AUC of 0.84 (p < 0.0001, 74% sensitivity, 79% specificity). Within IDHMUT WHO II-III gliomas, a separate multivariable logistic regression model was able to differentiate between 1p19q+ and 1p19q- WHO II-III gliomas with an AUC of 0.80 (p = 0.0015, 64% sensitivity, 82% specificity). ADC better differentiated between genetic subtypes of gliomas according to the 2016 WHO guidelines compared to the classification scheme outlined in the 2007 WHO guidelines based on histological features of the tissue. Results suggest a combination of rCBV, ADC, T2 hyperintense volume, and presence of contrast enhancement together may aid in non-invasively identifying genetic subtypes of diffuse gliomas.
August 2017Estimating Patient Dose from CT Exams that Use Automatic Exposure Control: Development and Validation of Methods to Accurately Estimate Tube Current Values.
McMillan K, Bostani M, Cagnon CH, Yu L, Leng S, McCollough CH, McNitt-Gray MF.
PURPOSE: The vast majority of body CT exams are performed with automatic exposure control (AEC), which adapts the mean tube current to the patient size and modulates the tube current either angularly, longitudinally or both. However, most radiation dose estimation tools are based on fixed tube current scans. Accurate estimates of patient dose from AEC scans require knowledge of the tube current values, which is usually unavailable. The purpose of this work was to develop and validate methods to accurately estimate the tube current values prescribed by one manufacturer's AEC system to enable accurate estimates of patient dose. METHODS: Methods were developed that took into account available patient attenuation information, user selected image quality reference parameters and x-ray system limits to estimate tube current values for patient scans. Methods consistent with AAPM Report 220 were developed that used patient attenuation data that were: (a) supplied by the manufacturer in the CT localizer radiograph and (b) based on a simulated CT localizer radiograph derived from image data. For comparison, actual tube current values were extracted from the projection data of each patient. Validation of each approach was based on data collected from 40 pediatric and adult patients who received clinically indicated chest (n = 20) and abdomen/pelvis (n = 20) scans on a 64 slice multidetector row CT (Sensation 64, Siemens Healthcare, Forchheim, Germany). For each patient dataset, the following were collected with Institutional Review Board (IRB) approval: (a) projection data containing actual tube current values at each projection view, (b) CT localizer radiograph (topogram) and (c) reconstructed image data. Tube current values were estimated based on the actual topogram (actual-topo) as well as the simulated topogram based on image data (sim-topo). Each of these was compared to the actual tube current values from the patient scan. In addition, to assess the accuracy of each method in estimating patient organ doses, Monte Carlo simulations were performed by creating voxelized models of each patient, identifying key organs and incorporating tube current values into the simulations to estimate dose to the lungs and breasts (females only) for chest scans and the liver, kidney, and spleen for abdomen/pelvis scans. Organ doses from simulations using the actual tube current values were compared to those using each of the estimated tube current values (actual-topo and sim-topo).
August 2017Cardiac Involvement in Sarcoidosis: Evolving Concepts in Diagnosis and Treatment.
Sayah DM, Bradfield JS, Moriarty JM, Belperio JA, Lynch JP 3rd.
Clinically evident sarcoidosis involving the heart has been noted in at least 2 to 7% of patients with sarcoidosis, but occult involvement is much higher (> 20%). Cardiac sarcoidosis is often not recognized antemortem, as sudden death may be the presenting feature. Cardiac involvement may occur at any point during the course of sarcoidosis and may occur in the absence of pulmonary or systemic involvement. Sarcoidosis can involve any part of the heart, with protean manifestations. Prognosis of cardiac sarcoidosis is related to the extent and site(s) of involvement. Most deaths due to cardiac sarcoidosis are due to arrhythmias or conduction defects, but granulomatous infiltration of the myocardium may be lethal. The definitive diagnosis of isolated cardiac sarcoidosis is difficult. The yield of endomyocardial biopsies is low; treatment of cardiac sarcoidosis is often warranted even in the absence of histologic proof. Radionuclide scans are integral to the diagnosis. Currently, 18F-fluorodeoxyglucose–positron emission tomography/computed tomography and gadolinium-enhanced magnetic resonance imaging scans are the key imaging modalities to diagnose cardiac sarcoidosis. The prognosis of cardiac sarcoidosis is variable, but mortality rates of untreated cardiac sarcoidosis are high. Although randomized therapeutic trials have not been done, corticosteroids (alone or combined with additional immunosuppressive medications) remain the mainstay of treatment. Because of the potential for sudden cardiac death, implantable cardioverter defibrillators should be placed in any patient with cardiac sarcoidosis and serious ventricular arrhythmias or heart block, and should be considered for cardiomyopathy. Cardiac transplantation is a viable option for patients with end-stage cardiac sarcoidosis refractory to medical therapy.
August 2017Clear Cell Renal Cell Carcinoma: Identifying the Loss of the Y Chromosome on Multiphasic MDCT.
Young JR, Coy H, Douek M, Lo P, Sayre J, Pantuck AJ, Raman SS.
OBJECTIVE: The objective of our study was to investigate whether multiphasic MDCT enhancement can help identify clear cell renal cell carcinomas (RCCs) with the loss of the Y chromosome. MATERIALS AND METHODS: We derived a cohort of 43 clear cell RCCs in men who underwent preoperative four-phase renal mass MDCT from October 2000 to August 2013. Each lesion was segmented in its entirety on axial images. A computer-assisted detection algorithm selected a 0.5-cm-diameter region of maximal attenuation within each lesion in each phase. A 0.5-cm-diameter ROI was manually placed on uninvolved renal cortex in each phase. The relative attenuation of each lesion was calculated as follows: [(maximal lesion attenuation - cortex attenuation) / cortex attenuation] x 100. Absolute attenuation and relative attenuation in each phase were compared using t tests.
July 2017Quantitative Computer-aided Diagnostic Algorithm for Automated Detection of Peak Lesion Attenuation in Differentiating Clear Cell from Papillary and Chromophobe Renal Cell Carcinoma, Oncocytoma, and Fat-poor Angiomyolipoma on Multiphasic Multidetector Computed Tomography.
Coy H, Young JR, Douek ML, Brown MS, Sayre J, Raman SS.
OBJECTIVE: To evaluate the performance of a novel, quantitative computer-aided diagnostic (CAD) algorithm on four-phase multidetector computed tomography (MDCT) to detect peak lesion attenuation to enable differentiation of clear cell renal cell carcinoma (ccRCC) from chromophobe RCC (chRCC), papillary RCC (pRCC), oncocytoma, and fat-poor angiomyolipoma (fp-AML). MATERIALS AND METHODS: We queried our clinical databases to obtain a cohort of histologically proven renal masses with preoperative MDCT with four phases [unenhanced (U), corticomedullary (CM), nephrographic (NP), and excretory (E)]. A whole lesion 3D contour was obtained in all four phases. The CAD algorithm determined a region of interest (ROI) of peak lesion attenuation within the 3D lesion contour. For comparison, a manual ROI was separately placed in the most enhancing portion of the lesion by visual inspection for a reference standard, and in uninvolved renal cortex. Relative lesion attenuation for both CAD and manual methods was obtained by normalizing the CAD peak lesion attenuation ROI (and the reference standard manually placed ROI) to uninvolved renal cortex with the formula [(peak lesion attenuation ROI - cortex ROI)/cortex ROI] x 100%. ROC analysis and area under the curve (AUC) were used to assess diagnostic performance. Bland-Altman analysis was used to compare peak ROI between CAD and manual method.
July 2017Single-center Comparison of the Efficacy and Complications of Arterial Vascular Closure Devices in Interventional Radiology.
Elmasri MA, Kee ST, Moriarty JM, Gomes A, Lee EW, McWilliams JP.
INTRODUCTION: Vascular closure devices (VCDs) are commonly used to achieve hemostasis of arterial access sites, but there is little comparative data on the variety of VCDs currently in clinical use. We reviewed the VCD experience at our institution to determine the safest and most effective VCD. MATERIALS AND METHODS: Retrospective analysis of 907 consecutive arterial procedures in interventional radiology from June 2012 to June 2014 was performed. Five VCDs were used: Angio-Seal (n = 478), FISH (n = 56), Mynx (n = 56), Perclose (n = 61), and Starclose (n = 68). Patients who underwent manual compression (n = 188) without use of VCDs were also studied as a comparison group. Patient demographics and pre-procedural laboratory parameters were recorded. The technical success rate for achievement of hemostasis and complication rates were noted.
July 2017Non-water-suppressed Short-echo-time Magnetic Resonance Spectroscopic Imaging Using a Concentric ring K-space Trajectory.
Emir UE, Burns B, Chiew M, Jezzard P, Thomas MA.
Water-suppressed MRS acquisition techniques have been the standard MRS approach used in research and for clinical scanning to date. The acquisition of a non-water-suppressed MRS spectrum is used for artefact correction, reconstruction of phased-array coil data and metabolite quantification. Here, a two-scan metabolite-cycling magnetic resonance spectroscopic imaging (MRSI) scheme that does not use water suppression is demonstrated and evaluated. Specifically, the feasibility of acquiring and quantifying short-echo (TE = 14 ms), two-dimensional stimulated echo acquisition mode (STEAM) MRSI spectra in the motor cortex is demonstrated on a 3 T MRI system. The increase in measurement time from the metabolite-cycling is counterbalanced by a time-efficient concentric ring k-space trajectory. To validate the technique, water-suppressed MRSI acquisitions were also performed for comparison. The proposed non-water-suppressed metabolite-cycling MRSI technique was tested for detection and correction of resonance frequency drifts due to subject motion and/or hardware instability, and the feasibility of high-resolution metabolic mapping over a whole brain slice was assessed. Our results show that the metabolite spectra and estimated concentrations are in agreement between non-water-suppressed and water-suppressed techniques. The achieved spectral quality, signal-to-noise ratio (SNR) > 20 and linewidth <7 Hz allowed reliable metabolic mapping of five major brain metabolites in the motor cortex with an in-plane resolution of 10 x 10 mm2 in 8 min and with a Cramér-Rao lower bound of less than 20% using LCModel analysis. In addition, the high SNR of the water peak of the non-water-suppressed technique enabled voxel-wise single-scan frequency, phase and eddy current correction. These findings demonstrate that our non-water-suppressed metabolite-cycling MRSI technique can perform robustly on 3 T MRI systems and within a clinically feasible acquisition time.
July 2017Developing a Framework for Digital Objects in the Big Data to Knowledge (BD2K) Commons: Report from the Commons Framework Pilots Workshop.
Jagodnik KM, Koplev S, Jenkins SL, Ohno-Machado L, Paten B, Schurer SC, Dumontier M, Verborgh R, Bui A, Ping P, McKenna NJ, Madduri R, Pillai A, Ma'ayan A.
The volume and diversity of data in biomedical research have been rapidly increasing in recent years. While such data hold significant promise for accelerating discovery, their use entails many challenges including: the need for adequate computational infrastructure, secure processes for data sharing and access, tools that allow researchers to find and integrate diverse datasets, and standardized methods of analysis. These are just some elements of a complex ecosystem that needs to be built to support the rapid accumulation of these data. The NIH Big Data to Knowledge (BD2K) initiative aims to facilitate digitally enabled biomedical research. Within the BD2K framework, the Commons initiative is intended to establish a virtual environment that will facilitate the use, interoperability, and discoverability of shared digital objects used for research. The BD2K Commons Framework Pilots Working Group (CFPWG) was established to clarify goals and work on pilot projects that address existing gaps toward realizing the vision of the BD2K Commons. This report reviews highlights from a two-day meeting involving the BD2K CFPWG to provide insights on trends and considerations in advancing Big Data science for biomedical research in the United States.
July 2017Neoplasms of the Appendix: Pictorial Review with Clinical and Pathologic Correlation.
Leonards LM, Pahwa A, Patel MK, Petersen J, Nguyen MJ, Jude CM.
Appendiceal neoplasms are uncommon tumors of the gastrointestinal tract that may manifest with symptoms of appendicitis, right lower quadrant pain, or palpable mass, leading to imaging or surgical intervention. The majority of appendiceal masses consist of primary epithelial neoplasms and neuroendocrine tumors (NETs). Epithelial neoplasms-mucinous and nonmucinous types-are more often detected at imaging than NETs due to their larger size and propensity for peritoneal spread and metastatic disease. Epithelial mucinous neoplasms are defined by the presence of mucin, detected at radiologic and pathologic examination. A mucocele or pseudomyxoma peritonei from epithelial mucinous tumors are the two most common cross-sectional imaging findings of appendiceal mucinous neoplasms. Nonmucinous epithelial tumors are less common and manifest as masses similar to colonic-type malignancies. NETs are often discovered incidentally at appendectomy due to their small size and nonaggressive behavior. Imaging findings of primary appendiceal tumors may overlap with those of acute appendicitis. Additionally, an appendiceal mass may cause acute appendicitis, obscuring the underlying mass. Other neoplasms including lymphoma, sarcoma, mesenchymal and nerve sheath tumors, or secondary malignant involvement of the appendix are rare. Treatment depends on the histologic subtype and extent of disease. Detailed description of organ, nodal, and peritoneal involvement informs surgical management with the goal of complete cytoreduction. Novel treatments such as hyperthermic intraperitoneal chemotherapy have increased survival for patients with mucinous tumors.
July 2017Results of the ANSWER Trial Using the PulseRider for the Treatment of Broad-Necked, Bifurcation Aneurysms.
Spiotta AM, Derdeyn CP, Tateshima S, Mocco J, Crowley RW, Liu KC, Jensen L, Ebersole K, Reeves A, Lopes DK, Hanel RA, Sauvageau E, Duckwiler G, Siddiqui A, Levy E, Puri A, Pride L, Novakovic R, Chaudry MI, Turner RD, Turk AS.
BACKGROUND: The safety and probable benefit of the PulseRider (Pulsar Vascular, Los Gatos, California) for the treatment of broad-necked, bifurcation aneurysms was studied in the context of the prospective, nonrandomized, single arm clinical trial-the Adjunctive Neurovascular Support of Wide-neck aneurysm Embolization and Reconstruction (ANSWER) Trial. OBJECTIVE: To present the results of the United States cases employing the PulseRider device as part of the ANSWER clinical trial. METHODS: Aneurysms treated with the PulseRider device among sites enrolling in the ANSWER trial were prospectively studied and the results are summarized. Aneurysms arising at either the carotid terminus or basilar apex that were relatively broad necked were considered candidates for inclusion into the ANSWER study.
July 2017Mycophenolate Mofetil Versus Placebo for Systemic Sclerosis-Related Interstitial Lung Disease: An Analysis of Scleroderma Lung Studies I and II.
Volkmann ER, Tashkin DP, Li N, Roth MD, Khanna D, Hoffmann-Vold AM, Kim G, Goldin J, Clements PJ, Furst DE, Elashoff RM.
OBJECTIVE: To compare mycophenolate mofetil (MMF) with placebo for the treatment of systemic sclerosis (SSc)-related interstitial lung disease (ILD). METHODS: We included participants enrolled in the placebo arm of Scleroderma Lung Study (SLS) I and the MMF arm of SLS II. SLS I randomized participants to receive either oral cyclophosphamide (CYC) or placebo for 1 year, while SLS II randomized participants to receive either MMF for 2 years or oral CYC for 1 year followed by 1 year of placebo. Eligibility criteria for SLS I and SLS II were nearly identical. The primary outcome was % predicted forced vital capacity (FVC), and key secondary outcomes included % predicted diffusing capacity for carbon monoxide (DLco), the modified Rodnan skin thickness score (MRSS), and dyspnea. Joint models were created to evaluate the treatment effect on the course of these outcomes over 2 years.
July 2017Type 1 Papillary Renal Cell Carcinoma: Differentiation from Type 2 Papillary RCC on Multiphasic MDCT.
Young JR, Coy H, Douek M, Lo P, Sayre J, Pantuck AJ, Raman SS.
PURPOSE: To investigate whether multiphasic MDCT enhancement can help differentiate type 1 papillary renal cell carcinoma (RCC) from type 2 papillary RCC. METHODS: With IRB approval for this HIPAA-compliant retrospective study, we derived a cohort of 36 type 1 papillary RCCs and 33 type 2 papillary RCCs with preoperative multiphasic MDCT with up to four phases (unenhanced, corticomedullary, nephrographic, and excretory) from 2000 to 2013. Following segmentation, a computer-assisted detection (CAD) algorithm selected a 0.5 cm-diameter region of maximal attenuation within each lesion in each phase; a 0.5 cm-diameter region of interest was manually placed on uninvolved renal cortex in each phase. The relative attenuation of each lesion was calculated as [(Lesion attenuation-cortex attenuation)/cortex attenuation] x 100. Absolute and relative attenuation values were compared using Mann-Whitney tests with Bonferroni correction for multiple comparisons.
June 2017Multiple Calcifying Pseudoneoplasms of the Neuraxis (MCAPNON): Distinct Entity, CAPNON Variant, or Old Neurocysticercosis?
Abdaljaleel M, Mazumder R, Patel CB, Im K, Pope W, Liau LM, Vinters HV, Yong WH.
We report a case of multiple calcifying pseudoneoplasms of the neuraxis (MCAPNON) with associated multifocal perivascular microcalcifications and vascular calcinosis. Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a very rare condition that may arise in extra-axial and occasionally, in intra-axial locations. Moreover, it is nearly always a solitary mass with only one case with two lesions reported. While the etiology and pathogenesis of CAPNON remains unclear, the histopathology findings of this entity have been well described. We report a case of a 62-year-old woman with 18 calcifying radiologic lesions involving bilateral cerebral hemispheres. Histologically, these lesions have features similar to that reported for CAPNON, including nodular calcification with fibro-osseous components and peripheral histiocytic reaction. The patient had a poorly documented diagnosis of neurocyticercosis 32 years prior, although without tissue confirmation. The lack of detectable cysticercus serum antibody titers, and absence of residual larval or cyst wall tissue render multifocal calcific involution of that parasite unprovable although still plausible. We also raise the possibility of a blood-brain barrier derangement and/or a metabolic disorder as an alternative etiology. Whether this case of MCAPNON shares the same pathogenesis as the usual solitary CAPNON is unclear.
June 2017Longitudinal DSC-MRI for Distinguishing Tumor Recurrence From Pseudoprogression in Patients With a High-grade Glioma.
Boxerman JL, Ellingson BM, Jeyapalan S, Elinzano H, Harris RJ, Rogg JM, Pope WB, Safran H.
OBJECTIVE: For patients with high-grade glioma on clinical trials it is important to accurately assess time of disease progression. However, differentiation between pseudoprogression (PsP) and progressive disease (PD) is unreliable with standard magnetic resonance imaging (MRI) techniques. Dynamic susceptibility contrast perfusion MRI (DSC-MRI) can measure relative cerebral blood volume (rCBV) and may help distinguish PsP from PD. METHODS: A subset of patients with high-grade glioma on a phase II clinical trial with temozolomide, paclitaxel poliglumex, and concurrent radiation were assessed. Nine patients (3 grade III, 6 grade IV), with a total of 19 enhancing lesions demonstrating progressive enhancement (≥ increase from nadir) on postchemoradiation conventional contrast-enhanced MRI, had serial DSC-MRI. Mean leakage-corrected rCBV within enhancing lesions was computed for all postchemoradiation time points.
June 2017Sustaining Change in Radiology Education: The Need for Universal Curricula.
Heitkamp DE, Johnson KS, Suh RD, Bedi HS, Oldham SAA, Ho CP, Paladin AM.
The pace of change in today's graduate medical education (GME) environment has been swift . For the better part of a decade, organizations such as the ACGME have contributed to a massive list of new requirements for postgraduate medical training. Many of these requirements call for individual programs to create their own educational content and assessment tools without meaningful guidance or tangible resources from the organizations requiring the changes. For most programs, compliance has been challenging.
June 2017Metabolic Imaging Using Proton Magnetic Spectroscopy as a Predictor of Outcome After Surgery for Cervical Spondylotic Myelopathy.
Holly LT, Ellingson BM, Salamon N.
STUDY DESIGN: A single-center magnetic resonance spectroscopy (MRS) imaging and surgical outcome study involving 16 patients with cervical spondylotic myelopathy (CSM). OBJECTIVE: In the present study, we assess the utility of MRS to quantify metabolic changes within the spinal cord and predict surgical outcome in CSM patients. SUMMARY OF BACKGROUND DATA: MRS is an advanced spinal imaging modality that can provide pertinent metabolic and biochemical information regarding spinal cord function. Previous studies have demonstrated significant abnormalities in specific cellular metabolite concentrations in CSM patients. METHODS: Sixteen patients with CSM were evaluated. Single voxel MRS was performed in the cervical cord. N-acetyl-aspartate (NAA) and choline metabolite concentration ratios with respect to creatine were quantified, as well as the presence or absence of a lactate peak. The modified Japanese Orthopaedic Association (mJOA) scale was used as the functional assessment measure. Correlation of MRS metabolites with change in mJOA score was performed.
June 2017Radiofrequency Ablation of Hepatocellular Carcinoma as Bridge Therapy to Liver Transplantation: A 10-year Intention-to-treat Analysis.
Lee MW, Raman SS, Asvadi NH, Siripongsakun S, Hicks RM, Chen J, Worakitsitisatorn A, McWilliams J, Tong MJ, Finn RS, Agopian VG, Busuttil RW, Lu DSK.
In a long-term (10-year) study of radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) as bridging therapy in patients listed for orthotopic liver transplantation (LT), we evaluated the impact of RFA on waiting list dropout rate, post-LT tumor recurrence, and long-term intention-to-treat, disease-specific survival (DSS). From March 2004 to October 2014, RFA was performed as the initial stand-alone bridge therapy to LT for 121 patients (men/women ratio, 83:38; mean age, 60.0 years) with 156 de novo HCCs (mean size, 2.4 cm). Follow-up period from initial RFA ranged from 1.3 to 128.0 months (median, 42.9 months). We assessed the overall and tumor-specific waiting list dropout rates, post-LT tumor recurrence, and 10-year post-LT and intention-to-treat survival rates. Dropout from the waiting list due to tumor progression occurred in 7.4% of patients. HCC recurrence after LT occurred in 5.6% of patients. The post-LT overall survival (OS) rate at 5 and 10 years was 75.8% and 42.2%, respectively, and the recurrence-free survival (RFS) rate was 71.1% and 39.6%, respectively. Intention-to-treat OS, RFS, and DSS rates for the entire study population at 5 and 10 years were 63.5% and 41.2%, 60.8% and 37.7%, and 89.5% and 89.5%, respectively.
June 2017Amyloid-β-related Angiitis: a Report of 2 Cases with Unusual Presentations.
Ng DW, Magaki S, Terashima KH, Keener AM, Salamon N, Karnezis S, Macyszyn L, Vinters HV.
Amyloid-β-related angiitis (ABRA) is a rare complication of cerebral amyloid angiopathy in which amyloid-β deposition in the leptomeningeal and cortical vessels is associated with vasculitis characterized by transmural lymphohistiocytic, often granulomatous, inflammation. Patients usually present with acute to subacute cognitive dysfunction, headaches, and focal neurologic deficits. We report 2 cases of ABRA with unusual clinical presentations, including one case with fatal cerebral edema leading to herniation and Duret hemorrhages, and another associated with both lobar and deep parenchymal hemorrhages with intraventricular extension as well as hypercoagulability. Both showed extensive vascular amyloid-β deposition associated with granulomatous angiitis and foreign body-type multinucleated giant cells. One of our cases demonstrates the likely effects of ABRA on impairment of fluid regulation leading to severe cerebral edema, which is an uncommon manifestation of ABRA, and may be a result of impaired blood-brain barrier function or malfunction of the neurovascular unit.
May 2017Implementing Lung Cancer Screening: the US Experience.
The reduced lung cancer mortality observed with low-dose computed tomography (LDCT) screening in the National Lung Screening Trial (NLST) has led to annual screening in the United States as a covered benefit by both private insurers and the federal health insurance programme, the Centers for Medicare and Medicaid Services. Reimbursement for screening requires data submission to a federal registry on all individuals, whether privately or federally insured. Data must document individual patient eligibility as well as shared decision-making regarding the benefits and risks of LDCT screening, smoking cessation counselling, and the importance of annual screening. Beyond these requirements lie opportunities to maximise the benefits of screening in the radiology setting. Individuals eligible for screening account for a minority of those diagnosed with lung cancer in the US; the evidence needed to improve patient selection must be collected systematically for both screen-detected and incidentally detected lung nodules. Current nodule management and tracking guidelines reduce the false-positive rates observed in the NLST, but fall short in their ability to correctly classify nodules as benign or malignant. Smoking cessation is inadequately managed in most busy clinician practices. As a common nidus for tobacco-associated lung diseases, imagers are uniquely poised to collect the longitudinal data to better inform screening eligibility and to improve indeterminate nodule management, while maximising the setting of screening to motivate and provide smoking cessation. By re-engineering the notion of imaging practice, radiologists can be major contributors to lung cancer early detection and mortality reduction.
May 2017Irreversible Electroporation: Defining the MRI Appearance of the Ablation Zone With Histopathologic Correlation in a Porcine Liver Model.
Felker ER, Dregely I, Chung DJ, Sung K, Osuagwu FC, Lassman C, Sayre J, Wu H, Lu DS.
OBJECTIVE: The purpose of this study is to evaluate the MRI appearance of the irreversible electroporation zone in porcine liver, with histopathologic correlation. MATERIALS AND METHODS: Nine irreversible electroporation ablations were percutaneously created in two Yorkshire pigs. Irreversible electroporation was performed with a bipolar 16-gauge electrode with 3-cm exposure tip and fixed 8-mm interpolar distance. Gadoxetate disodium-enhanced 3-T MRI was performed 50 hours after irreversible electroporation. Livers were harvested immediately after MRI for histopathologic analysis. Ablation zone size was measured on each pulse sequence and correlated with pathologic ablation zone size. Qualitative MRI features of the ablation zone were assessed, and contrast-to-noise ratios (CNRs) were calculated. Statistical analysis included Pearson correlation and t tests.
May 2017De Novo Loss-of-function Variants in STAG2 are Associated with Developmental Delay, Microcephaly, and Congenital Anomalies.
Mullegama SV, Klein SD, Mulatinho MV, Senaratne TN, Singh K; UCLA Clinical Genomics Center., Nguyen DC, Gallant NM, Strom SP, Ghahremani S, Rao NP, Martinez-Agosto JA.
The cohesin complex is an evolutionarily conserved multi-subunit protein complex which regulates sister chromatid cohesion during mitosis and meiosis. Additionally, the cohesin complex regulates DNA replication, DNA repair, and transcription. The core of the complex consists of four subunits: SMC1A, SMC3, RAD21, and STAG1/2. Loss-of-function mutations in many of these proteins have been implicated in human developmental disorders collectively termed "cohesinopathies." Through clinical exome sequencing (CES) of an 8-year-old girl with a clinical history of global developmental delay, microcephaly, microtia with hearing loss, language delay, ADHD, and dysmorphic features, we describe a heterozygous de novo variant (c.205C>T; p.(Arg69*)) in the integral cohesin structural protein, STAG2. This variant is associated with decreased STAG2 protein expression. The analyses of metaphase spreads did not exhibit premature sister chromatid separation; however, delayed sister chromatid cohesion was observed. To further support the pathogenicity of STAG2 variants, we identified two additional female cases from the DECIPHER research database with mutations in STAG2 and phenotypes similar to our patient. Interestingly, the clinical features of these three cases are remarkably similar to those observed in other well-established cohesinopathies. Herein, we suggest that STAG2 is a dosage-sensitive gene and that heterozygous loss-of-function variants lead to a cohesinopathy.
May 2017Safety and Immunogenicity of Adenovirus 35 Tuberculosis Vaccine Candidate in Adults with Active or Previous Tuberculosis. A Randomized Trial.
van Zyl-Smit RN, Esmail A, Bateman ME, Dawson R, Goldin J, van Rikxoort E, Douoguih M, Pau MG, Sadoff JC, McClain JB, Snowden MA, Benko J, Hokey DA, Rutkowski KT, Graves A, Shepherd B, Ishmukhamedov S, Kagina BMN, Abel B, Hanekom WA, Scriba TJ, Bateman ED.
RATIONALE: Administration of tuberculosis (TB) vaccines in participants with previous or current pulmonary TB may have the potential for causing harmful postvaccination immunologic (Koch-type) reactions. OBJECTIVES: To assess the safety and immunogenicity of three dose levels of the AERAS-402 live, replication-deficient adenovirus 35-vectored TB candidate vaccine, containing three mycobacterial antigens, in individuals with current or previous pulmonary TB. METHODS: We performed a phase II randomized, placebo-controlled, double-blinded dose-escalation study in an HIV-negative adult South African cohort (n = 72) with active pulmonary TB (on treatment for 1-4 mo) or pulmonary TB treated at least 12 months before study entry and considered cured. Safety endpoints included clinical assessment, flow volume curves, diffusing capacity of the lung for carbon monoxide, pulse oximetry, chest radiograph, and high-resolution thoracic computerized tomography scans. Cytokine expression by CD4 and CD8 T cells, after stimulation with Ag85A, Ag85B, and TB10.4 peptide pools, was examined by intracellular cytokine staining.
April 2017Obstructive Pulmonary Disease in Patients with Previous Tuberculosis: Pathophysiology of a Community-based Cohort.
Allwood BW, Gillespie R, Galperin-Aizenberg M, Bateman M, Olckers H, Taborda-Barata L, Calligaro GL, Said-Hartley Q, Van Zyl-Smit R, Cooper CB, Van Rikxoort E, Goldin J, Beyers N, Bateman ED.
BACKGROUND: An association between chronic airflow limitation (CAL) and a history of pulmonary tuberculosis (PTB) has been confirmed in epidemiological studies, but the mechanisms responsible for this association are unclear. It is debated whether CAL in this context should be viewed as chronic obstructive pulmonary disease (COPD) or a separate phenotype. OBJECTIVE: To compare lung physiology and high-resolution computed tomography (HRCT) findings in subjects with CAL and evidence of previous (healed) PTB with those in subjects with smoking-related COPD without evidence of previous PTB. METHODS: Subjects with CAL identified during a Burden of Obstructive Lung Disease (BOLD) study performed in South Africa were studied. Investigations included questionnaires, lung physiology (spirometry, body plethysmography and diffusing capacity) and quantitative HRCT scans to assess bronchial anatomy and the presence of emphysema (<-950 HU), gas trapping (<-860 HU) and fibrosis (>-200 HU). Findings in subjects with a past history and/or HRCT evidence of PTB were compared with those in subjects without these features.
April 2017Modified Criteria for Radiographic Response Assessment in Glioblastoma Clinical Trials.
Ellingson BM, Wen PY, Cloughesy TF.
Radiographic endpoints including response and progression are important for the evaluation of new glioblastoma therapies. The current RANO criteria was developed to overcome many of the challenges identified with previous guidelines for response assessment, however, significant challenges and limitations remain. The current recommendations build on the strengths of the current RANO criteria, while addressing many of these limitations. Modifications to the current RANO criteria include suggestions for volumetric response evaluation, use contrast enhanced T1 subtraction maps to increase lesion conspicuity, removal of qualitative non-enhancing tumor assessment requirements, use of the post-radiation time point as the baseline for newly diagnosed glioblastoma response assessment, and "treatment-agnostic" response assessment rubrics for identifying pseudoprogression, pseudoresponse, and a confirmed durable response in newly diagnosed and recurrent glioblastoma trials.
April 2017Respiratory Motion-resolved, Self-gated 4D-MRI Using Rotating Cartesian K-space (ROCK).
Han F, Zhou Z, Cao M, Yang Y, Sheng K, Hu P.
PURPOSE: To propose and validate a respiratory motion resolved, self-gated (SG) 4D-MRI technique to assess patient-specific breathing motion of abdominal organs for radiation treatment planning. METHODS: The proposed 4D-MRI technique was based on the balanced steady-state free-precession (bSSFP) technique and 3D k-space encoding. A novel rotating cartesian k-space (ROCK) reordering method was designed which incorporates repeatedly sampled k-space centerline as the SG motion surrogate and allows for retrospective k-space data binning into different respiratory positions based on the amplitude of the surrogate. The multiple respiratory-resolved 3D k-space data were subsequently reconstructed using a joint parallel imaging and compressed sensing method with spatial and temporal regularization. The proposed 4D-MRI technique was validated using a custom-made dynamic motion phantom and was tested in six healthy volunteers, in whom quantitative diaphragm and kidney motion measurements based on 4D-MRI images were compared with those based on 2D-CINE images.
April 2017Risk of Vigabatrin-associated Brain Abnormalities on MRI in the Treatment of Infantile Spasms is Dose-dependent.
Hussain SA, Tsao J, Li M, Schwarz MD, Zhou R, Wu JY, Salamon N, Sankar R.
OBJECTIVE: Although the link between vigabatrin (VGB) and retinotoxicity is well known, little attention has been focused on the risk of VGB-associated brain abnormalities on magnetic resonance imaging (MRI) (VABAM), namely reversible-and largely asymptomatic-signal changes in the thalami, basal ganglia, brainstem tegmentum, and cerebellar nuclei. Using a large infantile spasms cohort, we set out to identify predictors of these phenomena. METHODS: Children with infantile spasms were retrospectively identified. Brain MRI reports were serially reviewed without knowledge of VGB exposure. Upon VABAM discovery, records were systematically reviewed to ascertain presence of symptoms attributable to VGB. Separately, progress notes were sequentially reviewed to identify and quantify VGB exposure.
April 2017Anatomic Variations in Pituitary Endocrinopathies: Implications for the Surgical Corridor.
Kuan EC, Yoo F, Kim W, Badran KW, Heineman TE, Sepahdari AR, Bergsneider M, Wang MB.
Objectives/Hypotheses Functioning pituitary adenomas may produce endocrinopathies such as acromegaly and Cushing syndrome. Both conditions lead to characteristic anatomic variations as a result of hormonally induced abnormal soft tissue deposition. We evaluate the anatomic differences between acromegalics and Cushing disease patients and compare these dimensions to controls. Design Radiographic review of preoperative magnetic resonance images (MRI) of the pituitary gland. Setting Tertiary academic medical center. Participants Patients who underwent transnasal, transsphenoidal surgery for pituitary adenomas found to have acromegaly or pituitary Cushing between January 1, 2007 and September 1, 2015. A total of 15 patients with similar MRIs and no history of pituitary or sinonasal disease were selected as controls. Main Outcome Measures Dimensions assessed were intercarotid distance; carotid canal width; piriform aperture width; distance from the piriform aperture to the anterior face of the sphenoid; sphenoid sinus height, width, and length; angle from anterior nasal spine to anteroinferior face of sphenoid sinus; choanal height; and nasal cavity height at the level of the vertical segment of the middle turbinate. Sphenoid sinus pneumatization patterns were recorded.
April 2017Myocardial T1 Mapping for Patients with Implanted Cardiac Devices Using Wideband Inversion Recovery Spoiled Gradient Echo Readout.
Shao J, Rashid S, Renella P, Nguyen KL, Hu P.
PURPOSE: To develop and validate a technique for myocardial T1 mapping in patients with implantable cardioverter defibrillators (ICDs). METHODS: A MOLLI-based pulse sequence, named Wideband-FLASH-MOLLI, was developed by incorporating a fast low angle shot (FLASH) readout and a wideband inversion pulse. The performance of Wideband-FLASH-MOLLI was evaluated using phantom studies and validated in eight healthy volunteers and ten patients with ICDs at 1.5 Tesla. Comparisons were made between Wideband-FLASH-MOLLI, FLASH-MOLLI, and bSSFP-MOLLI sequences.
April 2017In-Bore 3-T MR-guided Transrectal Targeted Prostate Biopsy: Prostate Imaging Reporting and Data System Version 2-based Diagnostic Performance for Detection of Prostate Cancer.
Tan N, Lin WC, Khoshnoodi P, Asvadi NH, Yoshida J, Margolis DJ, Lu DS, Wu H, Sung KH, Lu DY, Huang J, Raman SS.
PURPOSE: To determine the diagnostic yield of in-bore 3-T magnetic resonance (MR) imaging-guided prostate biopsy and stratify performance according to Prostate Imaging Reporting and Data System (PI-RADS) versions 1 and 2. MATERIALS AND METHODS: This study was HIPAA compliant and institution review board approved. In-bore 3-T MR-guided prostate biopsy was performed in 134 targets in 106 men who (a) had not previously undergone prostate biopsy, (b) had prior negative biopsy findings with increased prostate-specific antigen (PSA) level, or (c) had a prior history of prostate cancer with increasing PSA level. Clinical, diagnostic 3-T MR imaging was performed with in-bore guided prostate biopsy, and pathology data were collected. The diagnostic yields of MR-guided biopsy per patient and target were analyzed, and differences between biopsy targets with negative and positive findings were determined. Results of logistic regression and areas under the curve were compared between PI-RADS versions 1 and 2.
April 2017Improved Cough and Cough-Specific Quality of Life in Patients Treated for Scleroderma-Related Interstitial Lung Disease: Results of Scleroderma Lung Study II.
Tashkin DP, Volkmann ER, Tseng CH, Roth MD, Khanna D, Furst DE, Clements PJ, Theodore A, Kafaja S, Kim GH, Goldin J, Ariolla E, Elashoff RM.
BACKGROUND: Cough is a common symptom of scleroderma-related interstitial lung disease (SSc-ILD), but its relationship to other characteristics of SSc-ILD, impact on cough-specific quality of life (QoL), and response to therapy for SSc-ILD have not been well studied. METHODS: We investigated frequent cough (FC) in patients with SSc-ILD (N = 142) enrolled in the Scleroderma Lung Study II, a randomized controlled trial comparing mycophenolate mofetil (MMF) and oral cyclophosphamide (CYC) as treatments for interstitial lung disease (ILD). We determined the impact of FC on QoL (Leicester Cough Questionnaire [LCQ]), evaluated the change in FC in response to treatment for SSc-ILD, and examined the relationship between gastroesophageal reflux disease (GERD) and cough during the trial.
April 2017Aortic Volumetry at Contrast-Enhanced Magnetic Resonance Angiography: Feasibility as a Sensitive Method for Monitoring Bicuspid Aortic Valve Aortopathy.
Trinh B, Dubin I, Rahman O, Ferreira Botelho MP, Naro N, Carr JC, Collins JD, Barker AJ.
OBJECTIVES: Bicuspid aortic valve patients can develop thoracic aortic aneurysms and therefore require serial imaging to monitor aortic growth. This study investigates the reliability of contrast-enhanced magnetic resonance angiography (CEMRA) volumetry compared with 2-dimensional diameter measurements to identify thoracic aortic aneurysm growth. MATERIALS AND METHODS: A retrospective, institutional review board-approved, and Health Insurance Portability and Accountability Act-compliant study was conducted on 20 bicuspid aortic valve patients (45 ± 8.9 years, 20% women) who underwent serial CEMRA with a minimum imaging follow-up of 11 months. Magnetic resonance imaging was performed at 1.5 T with electrocardiogram-gated, time-resolved CEMRA. Independent observers measured the diameter at the sinuses of Valsalva (SOVs) and mid ascending aorta (MAA) as well as ascending aorta volume between the aortic valve annulus and innominate branch. Intraobserver/interobserver coefficient of variation (COV) and intraclass correlation coefficient (ICC) were computed to assess reliability. Growth rates were calculated and assessed by Student t test (P < 0.05, significant). The diameter of maximal growth (DMG), defined as the diameter at SOV or MAA with the faster growth rate, was recorded.
April 2017Non-uniformly Weighted Sampling for Faster Localized Two-dimensional Correlated Spectroscopy of the Brain in vivo.
Verma G, Chawla S, Nagarajan R, Iqbal Z, Albert Thomas M, Poptani H.
Two-dimensional localized correlated spectroscopy (2D L-COSY) offers greater spectral dispersion than conventional one-dimensional (1D) MRS techniques, yet long acquisition times and limited post-processing support have slowed its clinical adoption. Improving acquisition efficiency and developing versatile post-processing techniques can bolster the clinical viability of 2D MRS. The purpose of this study was to implement a non-uniformly weighted sampling (NUWS) scheme for faster acquisition of 2D-MRS. A NUWS 2D L-COSY sequence was developed for 7T whole-body MRI. A phantom containing metabolites commonly observed in the brain at physiological concentrations was scanned ten times with both the NUWS scheme of 12:48 duration and a 17:04 constant eight-average sequence using a 32-channel head coil. 2D L-COSY spectra were also acquired from the occipital lobe of four healthy volunteers using both the proposed NUWS and the conventional uniformly-averaged L-COSY sequence. The NUWS 2D L-COSY sequence facilitated 25% shorter acquisition time while maintaining comparable SNR in humans (+0.3%) and phantom studies (+6.0%) compared to uniform averaging. NUWS schemes successfully demonstrated improved efficiency of L-COSY, by facilitating a reduction in scan time without affecting signal quality.
April 2017Performance of Relative Enhancement on Multiphasic MRI for the Differentiation of Clear Cell Renal Cell Carcinoma (RCC) From Papillary and Chromophobe RCC Subtypes and Oncocytoma.
Young JR, Coy H, Kim HJ, Douek M, Lo P, Pantuck AJ, Raman SS.
OBJECTIVE: The objective of our study was to investigate the performance of relative enhancement on multiphasic MRI to differentiate clear cell renal cell carcinoma (RCC) from other RCC subtypes (papillary and chromophobe) and oncocytoma. MATERIALS AND METHODS: For this study, we derived a cohort of 34 clear cell RCCs, nine oncocytomas, 12 papillary RCCs, and 10 chromophobe RCCs with a preoperative multiphasic dynamic contrast-enhanced MRI study with up to four phases (i.e., unenhanced, corticomedullary, nephrographic, excretory) from 2005 to 2016. These groups were evaluated for multiphasic enhancement and were compared using Kruskal-Wallis and Mann-Whitney tests. ROC curves were constructed and logistic regression analyses were performed to evaluate the performance of multiphasic enhancement in differentiating clear cell RCCs from the other three groups.
April 2017The Effect of Radiation Dose Reduction on Computer-Aided Detection (CAD) Performance in a Low-dose Lung Cancer Screening Population.
Young S, Lo P, Kim G, Brown M, Hoffman J, Hsu W, Wahi-Anwar W, Flores C, Lee G, Noo F, Goldin J, McNitt-Gray M.
PURPOSE: Lung cancer screening with low-dose CT has recently been approved for reimbursement, heralding the arrival of such screening services worldwide. Computer-aided detection (CAD) tools offer the potential to assist radiologists in detecting nodules in these screening exams. In lung screening, as in all CT exams, there is interest in further reducing radiation dose. However, the effects of continued dose reduction on CAD performance are not fully understood. In this work, we investigated the effect of reducing radiation dose on CAD lung nodule detection performance in a screening population. METHODS: The raw projection data files were collected from 481 patients who underwent low-dose screening CT exams at our institution as part of the National Lung Screening Trial (NLST). All scans were performed on a multidetector scanner (Sensation 64, Siemens Healthcare, Forchheim Germany) according to the NLST protocol, which called for a fixed tube current scan of 25 effective mAs for standard-sized patients and 40 effective mAs for larger patients. The raw projection data were input to a reduced-dose simulation software to create simulated reduced-dose scans corresponding to 50% and 25% of the original protocols. All raw data files were reconstructed at the scanner with 1 mm slice thickness and B50 kernel. The lungs were segmented semi-automatically, and all images and segmentations were input to an in-house CAD algorithm trained on higher dose scans (75-300 mAs). CAD findings were compared to a reference standard generated by an experienced reader. Nodule- and patient-level sensitivities were calculated along with false positives per scan, all of which were evaluated in terms of the relative change with respect to dose. Nodules were subdivided based on size and solidity into categories analogous to the LungRADS assessment categories, and sub-analyses were performed.
March 2017Sympathetic Modulation of Electrical Activation in Normal and Infarcted Myocardium: Implications for Arrhythmogenesis.
Ajijola OA, Lux RL, Khahera A, Kwon O, Aliotta E, Ennis DB, Fishbein MC, Ardell JL, Shivkumar K.
The influence of cardiac sympathetic innervation on electrical activation in normal and chronically infarcted ventricular myocardium is not understood. Yorkshire pigs with normal hearts (NL, n = 12) or anterior myocardial infarction (MI, n = 9) underwent high-resolution mapping of the anteroapical left ventricle at baseline and during left and right stellate ganglion stimulation (LSGS and RSGS, respectively). Conduction velocity (CV), activation times (ATs), and directionality of propagation were measured. Myocardial fiber orientation was determined using diffusion tensor imaging and histology. Longitudinal CV (CVL) was increased by RSGS (0.98 ± 0.11 vs. 1.2 ± 0.14m/s, P < 0.001) but not transverse CV (CVT). This increase was abrogated by β-adrenergic receptor and gap junction (GJ) blockade. Neither CVL nor CVT was increased by LSGS. In the peri-infarct region, both RSGS and LSGS shortened ARIs in sinus rhythm (423 ± 37 vs. 322 ± 30 ms, P < 0.001, and 423 ± 36 vs. 398 ± 36 ms, P = 0.035, respectively) and altered activation patterns in all animals. CV, as estimated by mean ATs, increased in a directionally dependent manner by RSGS (14.6 ± 1.2 vs. 17.3 ± 1.6 ms, P = 0.015), associated with GJ lateralization. RSGS and LSGS inhomogeneously modulated AT and induced relative or absolute functional activation delay in parts of the mapped regions in 75 and 67%, respectively, in MI animals, and in 0 and 15%, respectively, in control animals (P < 0.001 for both). In conclusion, sympathoexcitation increases CV in normal myocardium and modulates activation propagation in peri-infarcted ventricular myocardium. These data demonstrate functional control of arrhythmogenic peri-infarct substrates by sympathetic nerves and in part explain the temporal nature of arrhythmogenesis.NEW & NOTEWORTHY This study demonstrates regional control of conduction velocity in normal hearts by sympathetic nerves. In infarcted hearts, however, not only is modulation of propagation heterogeneous, some regions showed paradoxical conduction slowing. Sympathoexcitation altered propagation in all infarcted hearts studied, and we describe the temporal arrhythmogenic potential of these findings.Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/sympathetic-nerves-and-cardiac-propagation/.
March 2017Heads Up! A Novel Provocative Maneuver to Guide Acute Ischemic Stroke Management.
Ali LK, Weng JK, Starkman S, Saver JL, Kim D, Ovbiagele B, Buck BH, Sanossian N, Vespa P, Bang OY, Jahan R, Duckwiler GR, Viñuela F, Liebeskind DS.
BACKGROUND: A common dilemma in acute ischemic stroke management is whether to pursue recanalization therapy in patients with large vessel occlusions but minimal neurologic deficits. We describe and report preliminary experience with a provocative maneuver, i.e. 90-degree elevation of the head of bed for 30 min, which stresses collaterals and facilitates decision-making. METHODS: A prospective cohort study of <7.5 h of acute anterior circulation territory ischemia patients with minimal deficits despite middle cerebral artery (MCA) or internal carotid artery (ICA) occlusive disease.
March 2017Combined Intravenous Thrombolysis and Thrombectomy vs Thrombectomy Alone for Acute Ischemic Stroke: A Pooled Analysis of the SWIFT and STAR Studies.
Coutinho JM, Liebeskind DS, Slater LA, Nogueira RG, Clark W, Dávalos A, Bonafé A, Jahan R, Fischer U, Gralla J, Saver JL, Pereira VM.
Mechanical thrombectomy (MT) improves clinical outcomes in patients with acute ischemic stroke (AIS) caused by a large vessel occlusion. However, it is not known whether intravenous thrombolysis (IVT) is of added benefit in patients undergoing MT. OBJECTIVE: To examine whether treatment with IVT before MT with a stent retriever is beneficial in patients undergoing MT. DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis used data from 291 patients treated with MT included in 2 large, multicenter, prospective clinical trials that evaluated MT for AIS (Solitaire With the Intention for Thrombectomy performed from January 1, 2010, through December 31, 2011, and Solitaire Flow Restoration Thrombectomy for Acute Revascularization from January 1, 2010, through December 31, 2012). An independent core laboratory scored the radiologic outcomes in each trial. INTERVENTIONS: Patients were treated with IVT with tissue plasminogen activator followed by MT (IVT and MT group) with the use of a stent retriever or MT with a stent retriever alone (MT group).
March 2017Reduced Expiratory Flow Rate among Heavy Smokers Increases Lung Cancer Risk. Results from the National Lung Screening Trial-American College of Radiology Imaging Network Cohort.
Hopkins RJ, Duan F, Chiles C, Greco EM, Gamble GD, Aberle D, Young RP.
RATIONALE: Although epidemiological studies consistently show that chronic obstructive pulmonary disease is associated with an increased risk of lung cancer, debate exists as to whether there is a linear relationship between the severity of airflow limitation and lung cancer risk. OBJECTIVES: We examined this in a large, prospective study of older heavy smokers from the American College of Radiology Imaging Network subcohort of the National Lung Screening Trial (ACRIN). Airflow limitation was defined by prebronchodilator spirometry subgrouped according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1-4. METHODS: In the National Lung Screening Trial-ACRIN cohort of 18,473 screening participants, 6,436 had airflow limitation (35%) and 12,037 (65%) had no airflow limitation. From these groups, 758 lung cancer cases were prospectively identified. Participants with airflow limitation were stratified according to GOLD groups 1 (n = 1,607), 2 (n = 3,528), 3 (n = 1,083), and 4 (n = 211). Lung cancer incidence at study end (mean follow-up, 6.4 yr) was compared between the GOLD groups and those with no airflow limitation (referent group).
March 2017Genomic Adequacy from Solid Tumor Core Needle Biopsies of ex Vivo Tissue and in Vivo Lung Masses: Prospective Study.
Jamshidi N, Huang D, Abtin FG, Loh CT, Kee ST, Suh RD, Yamamoto S, Das K, Dry S, Binder S, Enzmann DR, Kuo MD.
Purpose To identify the variables and factors that affect the quantity and quality of nucleic acid yields from imaging-guided core needle biopsy. Materials and Methods This study was approved by the institutional review board and compliant with HIPAA. The authors prospectively obtained 232 biopsy specimens from 74 patients (177 ex vivo biopsy samples from surgically resected masses were obtained from 49 patients and 55 in vivo lung biopsy samples from computed tomographic [CT]-guided lung biopsies were obtained from 25 patients) and quantitatively measured DNA and RNA yields with respect to needle gauge, number of needle passes, and percentage of the needle core. RNA quality was also assessed. Significance of correlations among variables was assessed with analysis of variance followed by linear regression. Conditional probabilities were calculated for projected sample yields. Results The total nucleic acid yield increased with an increase in the number of needle passes or a decrease in needle gauge (two-way analysis of variance, P < .0001 for both). However, contrary to calculated differences in volume yields, the effect of needle gauge was markedly greater than the number of passes. For example, the use of an 18-gauge versus a 20-gauge biopsy needle resulted in a 4.8-5.7 times greater yield, whereas a double versus a single pass resulted in a 2.4-2.8 times greater yield for 18- versus 20-gauge needles, respectively. Ninety-eight of 184 samples (53%) had an RNA integrity number of at least 7 (out of a possible score of 10). Conclusion With regard to optimizing nucleic acid yields in CT-guided lung core needle biopsies used for genomic analysis, there should be a preference for using lower gauge needles over higher gauge needles with more passes.
March 2017Evaluation of Encephaloduroarteriosynangiosis Efficacy Using Probabilistic Independent Component Analysis Applied to Dynamic Susceptibility Contrast Perfusion MRI.
Laiwalla AN, Kurth F, Leu K, Liou R, Pamplona J, Ooi YC, Salamon N, Ellingson BM, Gonzalez NR.
BACKGROUND AND PURPOSE: Indirect cerebral revascularization has been successfully used for treatment in Moyamoya disease and symptomatic intracranial atherosclerosis. While angiographic neovascularization has been demonstrated after surgery, measurements of local tissue perfusion are scarce and may not reflect the reported successful clinical outcomes. We investigated probabilistic independent component analysis and conventional perfusion parameters from DSC-MR imaging to measure postsurgical changes in tissue perfusion. MATERIALS AND METHODS: In this prospective study, 13 patients underwent unilateral indirect cerebral revascularization and DSC-MR imaging before and after surgery. Conventional perfusion parameters (relative cerebral blood volume, relative cerebral blood flow, and TTP) and probabilistic independent components that reflect the relative contributions of DSC signals consistent with arterial, capillary, and venous hemodynamics were calculated and examined for significant changes after surgery. Results were compared with postsurgical DSA studies to determine whether changes in tissue perfusion were due to postsurgical neovascularization.
March 2017Effects of MRI Protocol Parameters, Preload Injection Dose, Fractionation Strategies, and Leakage Correction Algorithms on the Fidelity of Dynamic-Susceptibility Contrast MRI Estimates of Relative Cerebral Blood Volume in Gliomas.
Leu K, Boxerman JL, Ellingson BM.
BACKGROUND AND PURPOSE: DSC perfusion MR imaging assumes that the contrast agent remains intravascular; thus, disruptions in the blood-brain barrier common in brain tumors can lead to errors in the estimation of relative CBV. Acquisition strategies, including the choice of flip angle, TE, TR, and preload dose and incubation time, along with post hoc leakage-correction algorithms, have been proposed as means for combating these leakage effects. In the current study, we used DSC-MR imaging simulations to examine the influence of these various acquisition parameters and leakage-correction strategies on the faithful estimation of CBV. MATERIALS AND METHODS: DSC-MR imaging simulations were performed in 250 tumors with perfusion characteristics randomly generated from the distributions of real tumor population data, and comparison of leakage-corrected CBV was performed with a theoretic curve with no permeability. Optimal strategies were determined by protocol with the lowest mean error.
March 2017Bilateral Endolymphatic Hydrops in a Patient With Migraine Variant Without Vertigo: A Case Report.
Liu IY, Ishiyama A, Sepahdari AR, Johnson K, Ishiyama G.
OBJECTIVE: To use modern high-resolution inner ear imaging modalities to evaluate for endolymphatic hydrops (EH) in a patient with migraine-associated fluctuating hearing loss without vertigo spells or dizziness. BACKGROUND: EH has been well described in patients with Meniere's disease on both human temporal bone studies and modern high-resolution imaging; however, there is no study to date, to our knowledge, that examines the presence of EH in a patient with migraine and bilateral hearing loss. We present the MRI findings using a sequence for detecting EH in a unique case of a patient experiencing migraine headaches accompanied by fluctuating hearing loss without vertigo. METHODS: Magnetic resonance imaging sequences included "cisternographic" three-dimensional T2, and delayed intravenous-enhanced three-dimensional fluid-attenuation inversion recovery (DIVE-3D-FLAIR) sequences, performed with 2350 ms (bright perilymph) and 2050 ms (bright endolymph) inversion times. The bright endolymph images were subtracted from bright perilymph images to create a composite image with bright perilymph, dark endolymph, and intermediate bone signals.
March 2017Traumatic Hemorrhagic Brain Injury: Impact of Location and Resorption on Cognitive Outcome.
Martin RM, Wright MJ, Lutkenhoff ES, Ellingson BM, Van Horn JD, Tubi M, Alger JR, McArthur DL, Vespa PM.
OBJECTIVE Hemorrhagic contusions are often the most visible lesions following traumatic brain injury. However, the incidence, location, and natural history of traumatic parenchymal hemorrhage and its impact on neurological outcome have been understudied. The authors sought to examine the location and longitudinal evolution of traumatic parenchymal hemorrhage and its association with cognitive outcome. METHODS Sixteen patients with hemorrhagic contusions due to acceleration-deceleration injuries underwent MRI in the acute (mean 6.3 days postinjury) and chronic (mean 192.9 days postinjury) phases. ImageJ was used to generate GRE and FLAIR volumes. To account for the effect of head-size variability across individuals, the authors calculated each patient's total brain tissue volume using SIENAX. GRE and FLAIR volumes were normalized to the total brain tissue volume, and values for absolute and percent lesion volume and total brain volume change were generated. Spearman's rank correlations were computed to determine associations between neuroimaging and 6-month postinjury neuropsychological testing of attention (Symbol Digit Modalities Test [SDMT], oral [O] and written [W] versions), memory (Selective Reminding Test, total learning and delayed recall), and executive function (Trail Making Test Part B [TMT-B]). RESULTS The patients' mean age was 31.4 ± 14.0 years and their mean Glasgow Coma Scale score at admission was 7.9 ± 2.8. Lesions were predominantly localized to the frontal (11 lesions) and temporal (9 lesions) lobes. The average percent reductions in GRE and FLAIR volumes were 44.2% ± 46.1% and 80.5% ± 26.3%, respectively. While total brain and frontal lesion volumes did not correlate with brain atrophy, larger temporal lobe GRE and FLAIR volumes were associated with larger volumes of atrophy (GRE: acute, -0.87, p < 0.01, chronic, -0.78, p < 0.01; FLAIR: acute, -0.81, p < 0.01, chronic, -0.88, p < 0.01). Total percent volume change of GRE lesions correlated with TMT-B (0.53, p < 0.05) and SDMT-O (0.62, p < 0.05) scores. Frontal lobe lesion volume did not correlate with neuropsychological outcome. However, robust relationships were seen in the temporal lobe, with larger acute temporal lobe GRE volumes were associated with worse scores on both oral and written versions of the SDMT (SDMT-W, -0.85, p < 0.01; SDMT-O, -0.73, p < 0.05). Larger absolute change in temporal GRE volume was strongly associated with worse SDMT scores (SDMT-W, 0.88, p < 0.01; SDMT-O, 0.75, p < 0.05). The same relationships were also seen between temporal FLAIR lesion volumes and neuropsychological outcome. CONCLUSIONS Traumatic parenchymal hemorrhages are largely clustered in the frontal and temporal lobes, and significant residual blood products are present at 6 months postinjury, a potential source of ongoing secondary brain injury. Neuropsychological outcome is closely tied to lesion volume size, particularly in the temporal lobe, where larger GRE and FLAIR volumes are associated with more brain atrophy and worse SDMT scores. Interestingly, larger volumes of hemorrhage resorption were associated with worse SDMT and TMT-B scores, suggesting that the initial tissue damage had a lasting impact on attention and executive function.
March 2017Targeted Biopsy to Detect Gleason Score Upgrading during Active Surveillance for Men with Low versus Intermediate Risk Prostate Cancer.
Nassiri N, Margolis DJ, Natarajan S, Sharma DS, Huang J, Dorey FJ, Marks LS.
PURPOSE: We sought to determine the rate of upgrading to Gleason score 4 + 3 or greater using targeted biopsy for diagnosis and monitoring in men undergoing active surveillance of prostate cancer. MATERIALS AND METHODS: Study subjects comprised all 259 men, including 196 with Gleason score 3 + 3 and 63 with Gleason score 3 + 4, who were diagnosed by magnetic resonance imaging/ultrasound fusion guided biopsy from 2009 to 2015 and underwent subsequent fusion biopsy for as long as 4 years of active surveillance. The primary end point was the discovery of Gleason score 4 + 3 or greater prostate cancer. Followup biopsies included targeting of positive sites, which were tracked in an Artemis™ device. Kaplan-Meier curves were generated to determine upgrading rates, stratified by initial Gleason score and prostate specific antigen density.
March 2017Human TERT Promoter Mutation Enables Survival Advantage from MGMT Promoter Methylation in IDH1 Wild-type Primary Glioblastoma Treated by Standard Chemoradiotherapy.
Nguyen HN, Lie A, Li T, Chowdhury R, Liu F, Ozer B, Wei B, Green RM, Ellingson BM, Wang HJ, Elashoff R, Liau LM, Yong WH, Nghiemphu PL, Cloughesy T, Lai A.
BACKGROUND: Promoter mutation in the human telomerase reverse transcriptase gene (hTERT) occurs in ~75% of primary glioblastoma (GBM). Although the mutation appears to upregulate telomerase expression and contributes to the maintenance of telomere length, its clinical significance remains unclear. METHODS: We performed hTERT promoter genotyping on 303 isocitrate dehydrogenase 1 wild-type GBM tumors treated with standard chemoradiotherapy. We also stratified 190 GBM patients from the database of The Cancer Genome Atlas (TCGA) by hTERT gene expression. We analyzed overall and progression-free survival by Kaplan-Meier and Cox regression.
March 2017MRI with Ferumoxytol: A Single Center Experience of Safety Across the Age Spectrum.
Nguyen KL, Yoshida T, Han F, Ayad I, Reemtsen BL, Salusky IB, Satou GM, Hu P, Finn JP.
PURPOSE: To summarize our single-center safety experience with the off-label use of ferumoxytol for magnetic resonance imaging (MRI) and to compare the effects of ferumoxytol on monitored physiologic indices in patients under anesthesia with those of gadofosveset trisodium. MATERIALS AND METHODS: Consecutive patients who underwent ferumoxytol-enhanced (FE) MRI exams were included. Adverse events (AEs) were classified according to the Common Terminology Criteria for Adverse Events v4.0. In a subgroup of patients examined under general anesthesia, recording of blood pressure, heart rate, oxygen saturation, and end-tidal CO2 was performed. A comparable group of 23 patients who underwent gadofosveset-enhanced (GE) MRI under anesthesia with similar monitoring was also analyzed.
March 2017Longterm Follow-up of Small Pancreatic Cystic Lesions in Liver Transplant Recipients.
Vidhyarkorn S, Siripongsakun S, Yu J, Sayre J, Agopian VG, Durazo F, Lu DS.
Incidental small pancreatic cystic lesions (PCLs) are often found on preoperative imaging in patients undergoing orthotopic liver transplantation (OLT). Although these are considered benign or of low malignant potential, the influence of immunosuppression after OLT may be of concern. The aim of this study was to observe the longterm outcome of these small PCLs in post-OLT patients. An institutional OLT database of 1778 consecutive OLT patients from January 2000 to December 2010 was analyzed. Computed tomography, magnetic resonance imaging, or endoscopic ultrasound at the time of OLT and all subsequent imaging, cytology, fluid analysis of PCLs, and patient status were evaluated. A total of 70 patients with 182 PCLs, of benign or low malignant potential, were identified with a mean follow-up time of 64 months. At initial diagnosis of PCLs in 48 patients, 7 branch duct-type intraductal papillary mucinous neoplasms (B-IPMNs), 1 serous cystadenoma (SCA), and 40 nonspecific benign cysts were identified. Final diagnosis at the end of the follow-up revealed 16 B-IPMNs, 3 SCAs, and a mixed acinar-neuroendocrine carcinoma, in which the latter developed 9 years after initial diagnosis of B-IPMN. During the follow-up time, average increase in size and number of PCLs were 4.5 mm and 1.4, respectively (P < 0.001 for both). The majority of incidental PCLs in OLT patients showed an indolent behavior despite immunosuppression. Risk of malignancy development was very low and comparable with normal population.
February 2017Percutaneous Cryoablation for the Treatment of Recurrent Malignant Pleural Mesothelioma: Safety, Early-Term Efficacy, and Predictors of Local Recurrence.
Abtin F, Quirk MT, Suh RD, Hsu W, Han SX, Kim GJ, Genshaft S, Sandberg JK, Olevsky O, Cameron RB.
PURPOSE: To determine safety and early-term efficacy of CT-guided cryoablation for treatment of recurrent mesothelioma and assess risk factors for local recurrence. MATERIALS AND METHODS: During the period 2008-2012, 24 patients underwent 110 cryoablations for recurrent mesothelioma tumors in 89 sessions. Median patient age was 69 years (range, 48-82 y). Median tumor size was 30 mm (range, 9-113 mm). Complications were graded using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). Recurrence was diagnosed on CT or positron emission tomography/CT by increasing size, nodular enhancement, or hypermetabolic activity and analyzed using the Kaplan-Meier method. Cox proportional hazards model was used to determine covariates associated with local tumor recurrence.
February 2017Light-sheet Fluorescence Imaging to Localize Cardiac Lineage and Protein Distribution.
Ding Y, Lee J, Ma J, Sung K, Yokota T, Singh N, Dooraghi M, Abiri P, Wang Y, Kulkarni RP, Nakano A, Nguyen TP, Fei P, Hsiai TK.
Light-sheet fluorescence microscopy (LSFM) serves to advance developmental research and regenerative medicine. Coupled with the paralleled advances in fluorescence-friendly tissue clearing technique, our cardiac LSFM enables dual-sided illumination to rapidly uncover the architecture of murine hearts over 10 by 10 by 10 mm3 in volume; thereby allowing for localizing progenitor differentiation to the cardiomyocyte lineage and AAV9-mediated expression of exogenous transmembrane potassium channels with high contrast and resolution. Without the steps of stitching image columns, pivoting the light-sheet and sectioning the heart mechanically, we establish a holistic strategy for 3-dimentional reconstruction of the "digital murine heart" to assess aberrant cardiac structures as well as the spatial distribution of the cardiac lineages in neonates and ion-channels in adults.
February 2017Prostate Artery Embolization for Benign Prostatic Hyperplasia: Current Status.
Mirakhur A, McWilliams JP.
Prostate artery embolization has garnered much attention as a promising treatment for lower urinary tract symptoms secondary to benign prostatic hyperplasia. We aim to provide an up-to-date review of this minimally invasive technique, including discussion of potential benefits and technical challenges. Current evidence suggests it is a safe and effective option for patients with medication-refractory urinary obstructive symptoms who are poor surgical candidates or refuse surgical therapy. Larger, randomized studies with long-term follow-up data are needed for this technique to be formally established in the treatment paradigm for benign prostatic hyperplasia.
February 2017Radiographic and Magnetic Resonance Imaging Identification of Thoracolumbar Spine Variants with Implications for the Positioning of the Conus Medullaris in Rhesus Macaques.
Ohlsson M, Nieto JH, Christe KL, Villablanca JP, Havton LA.
The anatomy of the vertebral column in mammals may differ between species and between subjects of the same species, especially with regards to the composition of the thoracolumbar spine. We investigated, using several noninvasive imaging techniques, the thoracolumbar spine of a total of 44 adult rhesus macaques of both genders. Radiographic examination of the vertebral column showed a predominant spine phenotype with 12 rib-bearing thoracic vertebrae and 7 lumbar vertebrae without ribs in 82% of subjects, whereas a subset of subjects demonstrated 13 rib-bearing thoracic vertebrae and 6 lumbar vertebrae without ribs. Computer tomography studies of the thoraco-lumbar spine in two cases with a pair of supernumerary ribs showed facet joints between the most caudal pair of ribs and the associated vertebra, supporting a thoracic phenotype. Magnetic resonance imaging (MRI) studies were used to determine the relationship between the lumbosacral spinal cord and the vertebral column. The length of the conus medullaris portion of the spinal cord was 1.5 ± 0.3 vertebral units, and its rostral and caudal positions in the spinal canal were at 2.0 ± 0.3 and 3.6 ± 0.4 vertebral units below the thoracolumbar junction, respectively (n = 44). The presence of a set of supernumerary ribs did not affect the length or craniocaudal position of the conus medullaris, and subjects with13 rib-bearing vertebrae may from a functional or spine surgical perspective be considered as exhibiting12 thoracic vertebrae and an L1 vertebra with ribs.
February 2017Bone Age and Mineral Density Assessments Using Plain Roentgenograms in Tenofovir-exposed Infants in Malawi and Brazil Enrolled in HIV Prevention Trials Network 057.
Osorio LE, Boechat MI, Mirochnick M, Kumwenda N, Kreitchmann R, Emel L, Pinto J, Joao E, Santos B, Swenson M, George K, Sato P, Mofenson L, Nielsen-Saines K; HIV Prevention Trials Network (HPTN) 057 Protocol Team..
BACKGROUND: Tenofovir disoproxil fumarate (TDF) use during pregnancy has been increasing, and studies linking bone toxicity with exposure to TDF have raised concern for its use in infants. METHODS: Hand/wrist and spine radiographs were obtained at 3 days and 12 weeks of age in infants born to HIV-infected pregnant women enrolled in the HIV Prevention Trials Network 057 pharmacokinetic study of TDF conducted in Malawi and Brazil assigned to 3 TDF dosing cohorts. In cohort 1, mothers received 600 mg of TDF during labor. In cohort 2, infants received 4 mg/kg dose on days 0, 3 and 5. In cohort 3, a 900 mg maternal dose was given during labor, followed by a 6 mg/kg infant dose on days 0, 3 and 5 of life.
February 2017Magnetic Resonance Imaging Underestimation of Prostate Cancer Geometry: Use of Patient Specific Molds to Correlate Images with Whole Mount Pathology.
Priester A, Natarajan S, Khoshnoodi P, Margolis DJ, Raman SS, Reiter RE, Huang J, Grundfest W, Marks LS.
PURPOSE: We evaluated the accuracy of magnetic resonance imaging in determining the size and shape of localized prostate cancer. MATERIALS AND METHODS: The subjects were 114 men who underwent multiparametric magnetic resonance imaging before radical prostatectomy with patient specific mold processing of the specimen from 2013 to 2015. T2-weighted images were used to contour the prostate capsule and cancer suspicious regions of interest. The contours were used to design and print 3-dimensional custom molds, which permitted alignment of excised prostates with magnetic resonance imaging scans. Tumors were reconstructed in 3 dimensions from digitized whole mount sections. Tumors were then matched with regions of interest and the relative geometries were compared.
February 2017A Bayesian Model for Estimating Multi-state Disease Progression.
Shen S, Han SX, Petousis P, Weiss RE, Meng F, Bui AA, Hsu W.
A growing number of individuals who are considered at high risk of cancer are now routinely undergoing population screening. However, noted harms such as radiation exposure, overdiagnosis, and overtreatment underscore the need for better temporal models that predict who should be screened and at what frequency. The mean sojourn time (MST), an average duration period when a tumor can be detected by imaging but with no observable clinical symptoms, is a critical variable for formulating screening policy. Estimation of MST has been long studied using continuous Markov model (CMM) with Maximum likelihood estimation (MLE). However, a lot of traditional methods assume no observation error of the imaging data, which is unlikely and can bias the estimation of the MST. In addition, the MLE may not be stably estimated when data is sparse. Addressing these shortcomings, we present a probabilistic modeling approach for periodic cancer screening data. We first model the cancer state transition using a three state CMM model, while simultaneously considering observation error. We then jointly estimate the MST and observation error within a Bayesian framework. We also consider the inclusion of covariates to estimate individualized rates of disease progression. Our approach is demonstrated on participants who underwent chest x-ray screening in the National Lung Screening Trial (NLST) and validated using posterior predictive p-values and Pearson's chi-square test. Our model demonstrates more accurate and sensible estimates of MST in comparison to MLE.
January 2017Baseline Pretreatment Contrast Enhancing Tumor Volume Including Central Necrosis is a Prognostic Factor in Recurrent Glioblastoma: Evidence from Single and Multicenter Trials.
Ellingson BM, Harris RJ, Woodworth DC, Leu K, Zaw O, Mason WP, Sahebjam S, Abrey LE, Aftab DT, Schwab GM, Hessel C, Lai A, Nghiemphu PL, Pope WB, Wen PY, Cloughesy TF.
BACKGROUND: The prognostic significance of baseline contrast enhancing tumor prior to second- or third-line therapy in recurrent glioblastoma (GBM) for overall survival (OS) remains controversial, particularly in the context of repeated surgical resection and/or use of anti-angiogenic therapy. In the current study, we examined recurrent GBM patients from both single and multicenter clinical trials to test whether baseline enhancing tumor volume, including central necrosis, is a significant prognostic factor for OS in recurrent GBM. METHODS: Included were 497 patients with recurrent GBM from 4 data sources: 2 single-center sites (University of Toronto, University of California Los Angeles) and 2 phase II multicenter trials (AVF3708G, Bevacizumab ± Irinotecan, NCT00345163; XL184-201, Cabozantinib, NCT00704288). T1 subtraction maps were used to define volume of contrast enhancing tumor, including central necrosis. Cox multivariable and univariate analyses were used to evaluate the relationship between tumor volume prior to second- or third-line therapy and OS.
January 2017Patient Size-Specific Analysis of Dose Indexes From CT Lung Cancer Screening.
Fujii K, McMillan K, Bostani M, Cagnon C, McNitt-Gray M.
OBJECTIVE: The U.S. Centers for Medicare & Medicaid Services (CMS) recently approved the use of low-dose CT for lung cancer screening and described volumetric CT dose index (CTDIvol) requirements. These were based on the National Lung Screening Trial, which used only fixed-tube-current techniques. The aim of this study was to evaluate dose index data from a lung cancer screening program using automatic exposure control (AEC) techniques to ensure compliance with requirements and to correlate dose index values with patient size. MATERIALS AND METHODS: CTDIvol, dose-length product (DLP), and body mass index (BMI) data were collected for 563 lung cancer screening examinations performed with AEC between January 1, 2014, through August 31, 2015. CTDIvol and DLP were analyzed according to the patient's BMI classification. Results were compared with the CMS requirement that the CTDIvol for a standard-sized patient (height, 170 cm; weight, 70 kg) be 3.0 mGy or less, with adjustments for patients of different sizes. For a subset of patients, the average water-equivalent diameter and size-specific dose estimate were estimated.
January 2017Percutaneous Lung Biopsy in the Molecular Profiling Era: A Survey of Current Practices.
Lee C, Guichet PL, Abtin F.
PURPOSE: This study aimed to assess the current practice patterns of radiologists performing percutaneous lung biopsies. MATERIALS AND METHODS: This cross-sectional study used a web-based survey sent to the Society of Thoracic Radiology membership from August to October 2015. Responses were collected anonymously, and results were tallied.
January 2017Multi-delay ASL Can Identify Leptomeningeal Collateral Perfusion in Endovascular Therapy of Ischemic Stroke.
Lou X, Yu S, Scalzo F, Starkman S, Ali LK, Kim D, Rao NM, Hinman JD, Vespa PM, Jahan R, Tateshima S, Gonzalez NR, Duckwiler GR, Saver JL, Yoo B, Salamon N, Lyu J, Ma L, Wang DJ, Liebeskind DS.
BACKGROUND AND PURPOSE: Multi-delay arterial spin-labeling (ASL) perfusion imaging has been used as a promising modality to evaluate cerebral perfusion. Our aim was to assess the association of leptomeningeal collateral perfusion scores based on ASL parameters with outcome of endovascular treatment in patients with acute ischemic stroke (AIS) in the middle cerebral artery (MCA) territory. MATERIALS AND METHODS: ASL data at 4 post-labeling delay (PLD) times (PLD = 1.5, 2, 2.5, 3 s) were acquired during routine clinical magnetic resonance examination on AIS patients prior to endovascular treatment. A 3-point scale of leptomeningeal collateral perfusion grade on 10 anatomic regions was determined based on arterial transit times (ATT), cerebral blood flow (CBF), and arterial cerebral blood volume (CBV), estimated by the multi-delay ASL protocol. Based on a 90-day modified Rankin Scale (mRS), the patients were dichotomized to moderate/good (mRS 0-3) and poor outcome (mRS 4-6) and the regional collateral flow scores were compared.
January 2017Utilization of Emergent Neuroimaging for Thrombolysis-Eligible Stroke Patients.
Sanossian N, Fu KA, Liebeskind DS, Starkman S, Hamilton S, Villablanca JP, Burgos AM, Conwit R, Saver JL.
BACKGROUND: Advances in diagnostic imaging of stroke include multimodal techniques such as noninvasive angiography and perfusion imaging. We aimed to characterize trends in neuroimaging utilization among acute stroke patients. Utilization of multimodal imaging for acute stroke in the community has remained largely uncharacterized despite its increased adoption at academic medical centers. METHODS: We quantified neuroimaging utilization in the emergency department (ED) for 1,700 hyperacute stroke patients presenting <2 hours after symptom onset who participated in the National Institutes of Health Field Administration of Stroke Therapy-Magnesium (FAST-MAG) study throughout Los Angeles and Orange Counties. FAST-MAG provided no recommendation as to imaging utilization.
January 2017Evaluating Small-Airways Disease in Asthmatic Patients: The Utility of Quantitative Computed Tomography.
Tashkin DP, Kim HJ, Zeidler M, Kleerup E, Goldin J.
The tracheobronchial tree comprises a branching system of airways, beginning with the trachea, in which each airway divides mostly dichotomously into 2 smaller airways of progressively smaller diameter and, in most cases, shorter length, down to the smallest airway (a respiratory bronchiole) before terminating after approximately 23 divisions in the distal air sacs and alveoli. Historically, the lower respiratory tract has been divided into large and small airways, the latter defined as airways of 2 mm in diameter or smaller and corresponding to approximately the seventh or eighth generation and beyond of branching airways. In view of the exponential increase in the number of airways with each successive generation, most of the tracheobronchial tree is comprised of small airways, the total cross-sectional area of which is much greater than that of the larger airways, resulting in a relatively low resistance to airflow in the healthy lung.
January 2017Clear Cell Renal Cell Carcinoma: Identifying the Gain of Chromosome 12 on Multiphasic MDCT.
Young JR, Coy H, Douek M, Lo P, Sayre J, Pantuck AJ, Raman SS.
PURPOSE: To determine whether multiphasic MDCT enhancement can help identify the gain of chromosome 12 in clear cell renal cell carcinomas (RCCs). METHODS: With IRB approval for this HIPAA-compliant case control study, we derived a cohort of 65 clear cell RCCs with preoperative four-phase renal mass MDCT from October 2000 to August 2013. Each lesion was segmented in its entirety on axial images in all phases. A computer-assisted detection (CAD) algorithm selected a 0.5-cm-diameter region of maximal attenuation within each lesion in each phase. Attenuation in each phase between clear cell RCCs with and without the gain of 12 was compared using t-tests.