Citations

PurposeTo describe a model‐based reconstruction strategy for routine magnetic resonance imaging that accounts for gradient nonlinearity (GNL) during rather than after transformation to the image domain, and demonstrate that this approach reduces the spatial resolution loss that occurs during strictly image‐domain GNL‐correction.MethodsAfter reviewing conventional GNL‐correction methods, we propose a generic signal model for GNL‐affected magnetic resonance imaging acquisitions, discuss how it incorporates into contemporary image reconstruction platforms, and describe efficient nonuniform fast Fourier transform‐based computational routines for these. The impact of GNL‐correction on spatial resolution by the conventional and proposed approaches is investigated on phantom data acquired at varying offsets from gradient isocenter, as well as on fully sampled and (retrospectively) undersampled in vivo acquisitions.ResultsPhantom results demonstrate that resolution loss that occurs during GNL‐correction is significantly less for the proposed strategy than for the standard approach at distances >10 cm from isocenter with a 35 cm field‐of‐view gradient coil. The in vivo results suggest that the proposed strategy better preserves fine anatomical detail than retrospective GNL‐correction while offering comparable geometric correction.ConclusionAccounting for GNL during image reconstruction allows geometric distortion to be corrected with less spatial resolution loss than is typically observed with the conventional image domain correction strategy. Magn Reson Med 74:1019–1031, 2015. © 2014 Wiley Periodicals, Inc.

ObjectivesWe sought to determine neuroimaging patterns, ischemic mechanisms, and functional outcomes of ischemic stroke related to percutaneous coronary intervention (PCI) over a 16‐year period. Background: Stroke is a feared complication of PCI, associated with poor patient outcomes. The majority of strokes that occur after PCI are ischemic rather than hemorrhagic. However, mechanisms of cerebral ischemia in this setting are incompletely understood.MethodsWe performed a retrospective single‐center cohort study of patients with radiologically confirmed ischemic stroke occurring after PCI (PCI‐stroke), between January 1, 1994 and December 31, 2009. Using brain imaging, infarctions were subclassified by radiological pattern and arterial territory as embolic, small subcortical, or hemodynamic. Modified Rankin Scale scores were used to assess functional outcome at 3 and 6 months.ResultsRadiologically confirmed PCI‐stroke was identified in 35 patients. The majority of strokes (91%) revealed an embolic pattern, while the remaining strokes were small subcortical infarctions (9%). Watershed strokes with exclusive borderzone involvement, indicative of a hemodynamic mechanism, were not identified, despite the presence of periprocedural hypotension in 23% of patients. The middle cerebral artery (MCA) territory was affected most frequently (80%), and all patients suffering a complete MCA territorial infarction (14%) died in the hospital. Functional outcome among survivors of PCI‐stroke was typically favorable in those who had single rather than multiple vascular territory involvement.ConclusionsThe vast majority of radiologically confirmed ischemic strokes related to PCI are embolic. MCA territory strokes are most common and uniformly fatal when the entire MCA territory is affected. Functional outcomes in survivors of PCI‐stroke are improved when only a single arterial territory is affected. © 2014 Wiley Periodicals, Inc.

Abstract Pneumonia remains a leading cause of morbidity and mortality despite advances in treatment and therapy. The “Pneumonia: Treatment and Diagnosis” session of the Pittsburgh International Lung Conference examined topics related to improving care of patients with pneumonia. These topics included the process and quality of care for community-acquired pneumonia (CAP), diagnosis and treatment of emerging fungal pathogens, an overview of the strengths and weaknesses of different diagnostic modalities, and an example of how basic science is exploring immunomodulatory strategies for pneumonia treatment. Systematic health care provider and institutional improvements can decrease mortality rates in CAP, particularly in patients with increasingly complex comorbidities. Aspects of current guidelines for the diagnosis and treatment of fungal pneumonia were reviewed through a series of case presentations. Proper treatment of pneumonia hinges on correct pathogen identification but is complicated by the variety of diagnostic assays with variable specificity, sensitivity, and interpretation. In addressing this topic, Dr. Patrick Murray, Ph.D., discussed a range of diagnostic tests for a variety of pathogens and guidelines for their use. In addition to the current state of CAP treatment, Bill (Beibei) Chen, M.D., Ph.D., presented a new potential therapeutic agent called forsythin, an immunomodulatory compound derived from a plant used in traditional Chinese medicine. These topics, ranging from institution-sized policy to interactions at the molecular scale, paint a broad perspective of the efforts against pneumonia.

Abstract Background: Endometrial cancers account for over 46,000 cases and 8,100 deaths annually in the U.S. Endometrial cancers that are confined to the uterus portend an excellent prognosis, suggesting that development of early detection methods for these tumors could reduce mortality. To identify and validate markers with potential utility in early detection of endometrial cancers, we compared DNA methylation profiling data for endometrial cancer tissues collected in a population-based epidemiological study and a comparison set of benign endometrial tissues, and replicated promising candidates in a separate clinical study. Methods: We used the Illumina Golden Gate platform to profile DNA methylation of CpGs at 1536 sites (807 genes) using fixed tissues from 148 endometrial cancers included in the population-based Polish Endometrial Cancer Study (cases) and 23 benign endometrial tissues collected at Magee Women's Hospital (controls). Tissue cores (1.0-mm) removed from target-rich areas of blocks were used for DNA extraction, bisulfite treatment and profiling. We replicated top candidate markers by applying pyrosequencing assays to endometrial brushings performed prior to hysterectomy among 38 women with endometrial cancer and 37 with benign gynecological diseases treated at the Mayo Clinic and calculated odds ratios comparing the highest tertile of methylation values in controls for each marker with middle and low tertiles. In addition, we assessed discrimination across the whole range of cutoffs using Receiver Operator Characteristics (ROC) curves. Results: Methylation profiling identified 114 CpG sites with differential methylation levels between cases and controls (P≤10-7). Eight genes (ADCYAP1, ASCL2, HS3ST2, HTR1B, MME, NPY, and SOX1) which showed large case-control differences in methylation levels (≥ 0.4), and low values in controls (<0.2) were chosen for replication by pyrosequencing in pre-hysterectomy patients. In the replication study, higher methylation levels were found for 7 of 8 genes in endometrial brush samples from women with cancer as compared to women without cancer. In the replication study, odds ratios for association of methylation markers with endometrial cancer ranged from 3.6 (95%-CI: 1.35-9.47) for HTR1B to 10.9 (95%-CI: 3.23-36.91) for ASCL2. Discrimination of cases and controls was best for ADCYAP1 (area under ROC curve=0.89; 95% CI: 0.80-0.97), CDH13 (0.87; 95% CI: 0.80-0.97), and MME (0.87; 95% CI: 0.78-0.97). Conclusions: Analysis of DNA methylation markers in endometrial brushings is strongly associated with prevalent endometrial cancer at hysterectomy. Development and validation of a robust early detection marker panel for endometrial cancers, including non-endometrioid cancers and precursor lesions is ongoing. Citation Format: Nicolas A. Wentzensen, Jamie Bakkum, Keith Killian, Viji Shridhar, Lisa Adams, Richard Guido, Lori D'Ambrosio, Patricia Luhn, Joshua Sampson, Hannah Yang, Louise Brinton, Jolanta Lissowska, Karl Podratz, Mark Sherman. Discovery and validation of methylation markers for early detection of endometrial cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3477. doi:10.1158/1538-7445.AM2013-3477

Abstract Our understanding of ovarian cancer is complicated by disease heterogeneity. There are five major histological types, each with alterations in different pathways and distinct clinical outcomes. Even within these histological types there is clinical and molecular heterogeneity. The Ovarian Tumor Tissue Analysis (OTTA) consortium was established to validate prognostic markers for ovarian cancer in a large population of patients to allow stratification by histological type and molecular subtype. OTTA is currently a collaboration among 38 studies and has tissue microarrays (TMAs) from over 8,000 tumors available for immunohistochemical (IHC) analysis. In addition formalin fixed paraffin embedded (FFPE) tissue on slides or cores are available from the majority of OTTA studies for DNA and RNA analysis. Approximatley 60% of the cases are part of the Ovarian Cancer Association Consortium (OCAC) and have genotype data on over 200,000 single nucleotide polymorphisms and extensive epidemiological data. We recently performed IHC analysis of 12 markers using centralised staining and scoring to reduce heterogeneity and improve power to validate biomarkers. We showed that estrogen receptor and progesterone receptor were prognostic markers for endometrioid and high-grade serous carcinomas by performing the first robust subtype-specific analyses of these biomarkers in nearly 3000 patients. In contrast, FOLR1 expression was not associated with survival in 1507 high-grade serous carcinomas. We have shown that FFPE material from OTTA is suitable for RNA expression analysis on high through-put platforms such as the NanoString GX system. Expression analysis of 50 candidate genes in 244 high grade serous ovarian cancer cases has validated prognostic markers identified by The Cancer Genome Atlas (TCGA) project and investigated a series of novel candidate genes. IHC and RNA expression profiling from formalin fixed paraffin embedded (FFPE) tumor tissue is being used to better subclassify the ovarian tumors for further analysis. We would welcome groups with collections of ovarian tumor samples and corrsponding clinical data to join OTTA and participate in ongoing collaborative projects. Citation Format: Susan J. Ramus, Martin Köbel, Weiva Sieh, Michael S. Anglesio, Joshua Millstein, David D. Bowtell, James D. Brenton, Estrid Høgdall, Paul DP Pharoah, Ellen L. Goode, David G. Huntsman. The ovarian tumor tissue analysis (OTTA) consortium. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A27.

Objectives: To determine the relationship between lateral tibial slope and probability of early graft failure in patients who have undergone anterior cruciate ligament (ACL) reconstruction. Methods: Fifty-eight patients were initially identified who experienced graft failure following primary ACL reconstruction and were revised between 1989 and 2009. Exclusion criteria were: clinical follow-up of less than four years, graft failure occurring greater than two years from primary surgery, skeletal immaturity, deep infection, lack of availability of preoperative MRI imaging, and history of previous trauma to the proximal tibia. This left 35 cases of early (within 2 years) failure of primary ACL reconstruction. These cases were matched to 35 controls that had undergone ACL reconstruction with a minimum of 4 years of clinical follow-up and no evidence of graft failure. Patients were matched by age, gender, date of primary surgery, and graft type. Lateral tibial slope was then determined on MRI imaging in blinded fashion. Results: All 35 cases failed within 2 years of primary ACL reconstruction. Mean time to failure in this group was 1 year (range 0.6-1.4 years). Mean follow-up of the matched control group was 6.9 years (range 4.0-13.9 years). Mean lateral tibial slope in the early ACL failure group was found to be 8.4 degrees, which was significantly larger than the control group at 6.5 degrees (p=0.02). The odds ratio for failure considering a 2 degree increase in tibial slope was 1.5 (95% CI 1.02-2.2), and continued to increase to 2.2 (95% CI 1.1-4.6) and 3.3 (95% CI 1.1-10) with 4 degree and 6 degree increases in tibial slope, respectively (Fig 1). No significant association was identified between graft type and primary ACL reconstruction failure. Conclusion: Increased lateral tibial slope is associated with an increased risk for early ACL graft failure, regardless of graft type. Orthopaedic surgeons should consider measuring lateral tibial slope as part of the preoperative assessment of ACL-injured patients.