Publications by authors named "Justin Silverman"

37 Publications

Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England.

Science 2021 04 3;372(6538). Epub 2021 Mar 3.

Centre for Mathematical Modelling of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, UK.

A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, VOC 202012/01 (lineage B.1.1.7), emerged in southeast England in September 2020 and is rapidly spreading toward fixation. Using a variety of statistical and dynamic modeling approaches, we estimate that this variant has a 43 to 90% (range of 95% credible intervals, 38 to 130%) higher reproduction number than preexisting variants. A fitted two-strain dynamic transmission model shows that VOC 202012/01 will lead to large resurgences of COVID-19 cases. Without stringent control measures, including limited closure of educational institutions and a greatly accelerated vaccine rollout, COVID-19 hospitalizations and deaths across England in the first 6 months of 2021 were projected to exceed those in 2020. VOC 202012/01 has spread globally and exhibits a similar transmission increase (59 to 74%) in Denmark, Switzerland, and the United States.
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http://dx.doi.org/10.1126/science.abg3055DOI Listing
April 2021

The Pediatric Obesity Microbiome and Metabolism Study (POMMS): Methods, Baseline Data, and Early Insights.

Obesity (Silver Spring) 2021 Mar;29(3):569-578

Department of Pediatrics, Duke University, Durham, North Carolina, USA.

Objective: The purpose of this study was to establish a biorepository of clinical, metabolomic, and microbiome samples from adolescents with obesity as they undergo lifestyle modification.

Methods: A total of 223 adolescents aged 10 to 18 years with BMI ≥95th percentile were enrolled, along with 71 healthy weight participants. Clinical data, fasting serum, and fecal samples were collected at repeated intervals over 6 months. Herein, the study design, data collection methods, and interim analysis-including targeted serum metabolite measurements and fecal 16S ribosomal RNA gene amplicon sequencing among adolescents with obesity (n = 27) and healthy weight controls (n = 27)-are presented.

Results: Adolescents with obesity have higher serum alanine aminotransferase, C-reactive protein, and glycated hemoglobin, and they have lower high-density lipoprotein cholesterol when compared with healthy weight controls. Metabolomics revealed differences in branched-chain amino acid-related metabolites. Also observed was a differential abundance of specific microbial taxa and lower species diversity among adolescents with obesity when compared with the healthy weight group.

Conclusions: The Pediatric Metabolism and Microbiome Study (POMMS) biorepository is available as a shared resource. Early findings suggest evidence of a metabolic signature of obesity unique to adolescents, along with confirmation of previously reported findings that describe metabolic and microbiome markers of obesity.
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http://dx.doi.org/10.1002/oby.23081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927749PMC
March 2021

Naught all zeros in sequence count data are the same.

Comput Struct Biotechnol J 2020 28;18:2789-2798. Epub 2020 Sep 28.

Program in Computational Biology and Bioinformatics, Duke University, Durham, NC 27708, United States.

Genomic studies feature multivariate count data from high-throughput DNA sequencing experiments, which often contain many zero values. These zeros can cause artifacts for statistical analyses and multiple modeling approaches have been developed in response. Here, we apply different zero-handling models to gene-expression and microbiome datasets and show models can disagree substantially in terms of identifying the most differentially expressed sequences. Next, to rationally examine how different zero handling models behave, we developed a conceptual framework outlining four types of processes that may give rise to zero values in sequence count data. Last, we performed simulations to test how zero handling models behave in the presence of these different zero generating processes. Our simulations showed that simple count models are sufficient across multiple processes, even when the true underlying process is unknown. On the other hand, a common zero handling technique known as "zero-inflation" was only suitable under a zero generating process associated with an unlikely set of biological and experimental conditions. In concert, our work here suggests several specific guidelines for developing and choosing state-of-the-art models for analyzing sparse sequence count data.
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http://dx.doi.org/10.1016/j.csbj.2020.09.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568192PMC
September 2020

Short-Chain Fatty Acid Production by Gut Microbiota from Children with Obesity Differs According to Prebiotic Choice and Bacterial Community Composition.

mBio 2020 08 11;11(4). Epub 2020 Aug 11.

Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, USA

Pediatric obesity remains a public health burden and continues to increase in prevalence. The gut microbiota plays a causal role in obesity and is a promising therapeutic target. Specifically, the microbial production of short-chain fatty acids (SCFA) from the fermentation of otherwise indigestible dietary carbohydrates may protect against pediatric obesity and metabolic syndrome. Still, it has not been demonstrated that therapies involving microbiota-targeting carbohydrates, known as prebiotics, will enhance gut bacterial SCFA production in children and adolescents with obesity (age, 10 to 18 years old). Here, we used an system to examine the SCFA production by fecal microbiota from 17 children with obesity when exposed to five different commercially available over-the-counter (OTC) prebiotic supplements. We found microbiota from all 17 patients actively metabolized most prebiotics. Still, supplements varied in their acidogenic potential. Significant interdonor variation also existed in SCFA production, which 16S rRNA sequencing supported as being associated with differences in the host microbiota composition. Last, we found that neither fecal SCFA concentration, microbiota SCFA production capacity, nor markers of obesity positively correlated with one another. Together, these findings suggest the hypothesis that OTC prebiotic supplements may be unequal in their ability to stimulate SCFA production in children and adolescents with obesity and that the most acidogenic prebiotic may differ across individuals. Pediatric obesity remains a major public health problem in the United States, where 17% of children and adolescents are obese, and rates of pediatric "severe obesity" are increasing. Children and adolescents with obesity face higher health risks, and noninvasive therapies for pediatric obesity often have limited success. The human gut microbiome has been implicated in adult obesity, and microbiota-directed therapies can aid weight loss in adults with obesity. However, less is known about the microbiome in pediatric obesity, and microbiota-directed therapies are understudied in children and adolescents. Our research has two important findings: (i) dietary prebiotics (fiber) result in the microbiota from adolescents with obesity producing more SCFA, and (ii) the effectiveness of each prebiotic is donor dependent. Together, these findings suggest that prebiotic supplements could help children and adolescents with obesity, but that these therapies may not be "one size fits all."
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http://dx.doi.org/10.1128/mBio.00914-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439474PMC
August 2020

Allogenic Fecal Microbiota Transplantation in Patients With Nonalcoholic Fatty Liver Disease Improves Abnormal Small Intestinal Permeability: A Randomized Control Trial.

Am J Gastroenterol 2020 07;115(7):1055-1065

Department of Microbiology and Immunology, Western University, London, Ontario, Canada.

Introduction: Nonalcoholic fatty liver disease (NAFLD) is an obesity-related disorder that is rapidly increasing in incidence and is considered the hepatic manifestation of the metabolic syndrome. The gut microbiome plays a role in metabolism and maintaining gut barrier integrity. Studies have found differences in the microbiota between NAFLD and healthy patients and increased intestinal permeability in patients with NAFLD. Fecal microbiota transplantation (FMT) can be used to alter the gut microbiome. It was hypothesized that an FMT from a thin and healthy donor given to patients with NAFLD would improve insulin resistance (IR), hepatic proton density fat fraction (PDFF), and intestinal permeability.

Methods: Twenty-one patients with NAFLD were recruited and randomized in a ratio of 3:1 to either an allogenic (n = 15) or an autologous (n = 6) FMT delivered by using an endoscope to the distal duodenum. IR was calculated by HOMA-IR, hepatic PDFF was measured by MRI, and intestinal permeability was tested using the lactulose:mannitol urine test. Additional markers of metabolic syndrome and the gut microbiota were examined. Patient visits occurred at baseline, 2, 6 weeks, and 6 months post-FMT.

Results: There were no significant changes in HOMA-IR or hepatic PDFF in patients who received the allogenic or autologous FMT. Allogenic FMT patients with elevated small intestinal permeability (>0.025 lactulose:mannitol, n = 7) at baseline had a significant reduction 6 weeks after allogenic FMT.

Discussion: FMT did not improve IR as measured by HOMA-IR or hepatic PDFF but did have the potential to reduce small intestinal permeability in patients with NAFLD.
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http://dx.doi.org/10.14309/ajg.0000000000000661DOI Listing
July 2020

Interindividual Variation in Dietary Carbohydrate Metabolism by Gut Bacteria Revealed with Droplet Microfluidic Culture.

mSystems 2020 Jun 30;5(3). Epub 2020 Jun 30.

Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, USA

Culture and screening of gut bacteria enable testing of microbial function and therapeutic potential. However, the diversity of human gut microbial communities (microbiota) impedes comprehensive experimental studies of individual bacterial taxa. Here, we combine advances in droplet microfluidics and high-throughput DNA sequencing to develop a platform for separating and assaying growth of microbiota members in picoliter droplets (MicDrop). MicDrop enabled us to cultivate 2.8 times more bacterial taxa than typical batch culture methods. We then used MicDrop to test whether individuals possess similar abundances of carbohydrate-degrading gut bacteria, using an approach which had previously not been possible due to throughput limitations of traditional bacterial culture techniques. Single MicDrop experiments allowed us to characterize carbohydrate utilization among dozens of gut bacterial taxa from distinct human stool samples. Our aggregate data across nine healthy stool donors revealed that all of the individuals harbored gut bacterial species capable of degrading common dietary polysaccharides. However, the levels of richness and abundance of polysaccharide-degrading species relative to monosaccharide-consuming taxa differed by up to 2.6-fold and 24.7-fold, respectively. Additionally, our unique dataset suggested that gut bacterial taxa may be broadly categorized by whether they can grow on single or multiple polysaccharides, and we found that this lifestyle trait is correlated with how broadly bacterial taxa can be found across individuals. This demonstration shows that it is feasible to measure the function of hundreds of bacterial taxa across multiple fecal samples from different people, which should in turn enable future efforts to design microbiota-directed therapies and yield new insights into microbiota ecology and evolution. Bacterial culture and assay are components of basic microbiological research, drug development, and diagnostic screening. However, community diversity can make it challenging to comprehensively perform experiments involving individual microbiota members. Here, we present a new microfluidic culture platform that makes it feasible to measure the growth and function of microbiota constituents in a single set of experiments. As a proof of concept, we demonstrate how the platform can be used to measure how hundreds of gut bacterial taxa drawn from different people metabolize dietary carbohydrates. Going forward, we expect this microfluidic technique to be adaptable to a range of other microbial assay needs.
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http://dx.doi.org/10.1128/mSystems.00864-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329328PMC
June 2020

Using influenza surveillance networks to estimate state-specific prevalence of SARS-CoV-2 in the United States.

Sci Transl Med 2020 07 22;12(554). Epub 2020 Jun 22.

Department of Microbiology and Immunology, Montana State University, Bozeman, MT 59717, USA.

Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections to date has relied heavily on reverse transcription polymerase chain reaction testing. However, limited test availability, high false-negative rates, and the existence of asymptomatic or subclinical infections have resulted in an undercounting of the true prevalence of SARS-CoV-2. Here, we show how influenza-like illness (ILI) outpatient surveillance data can be used to estimate the prevalence of SARS-CoV-2. We found a surge of non-influenza ILI above the seasonal average in March 2020 and showed that this surge correlated with coronavirus disease 2019 (COVID-19) case counts across states. If one-third of patients infected with SARS-CoV-2 in the United States sought care, this ILI surge would have corresponded to more than 8.7 million new SARS-CoV-2 infections across the United States during the 3-week period from 8 to 28 March 2020. Combining excess ILI counts with the date of onset of community transmission in the United States, we also show that the early epidemic in the United States was unlikely to have been doubling slower than every 4 days. Together, these results suggest a conceptual model for the COVID-19 epidemic in the United States characterized by rapid spread across the United States with more than 80% infected individuals remaining undetected. We emphasize the importance of testing these findings with seroprevalence data and discuss the broader potential to use syndromic surveillance for early detection and understanding of emerging infectious diseases.
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http://dx.doi.org/10.1126/scitranslmed.abc1126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319260PMC
July 2020

Modeling the temporal dynamics of the gut microbial community in adults and infants.

PLoS Comput Biol 2019 06 27;15(6):e1006960. Epub 2019 Jun 27.

Department of Computer Science, University of California Los Angeles, Los Angeles, California, United States of America.

Given the highly dynamic and complex nature of the human gut microbial community, the ability to identify and predict time-dependent compositional patterns of microbes is crucial to our understanding of the structure and functions of this ecosystem. One factor that could affect such time-dependent patterns is microbial interactions, wherein community composition at a given time point affects the microbial composition at a later time point. However, the field has not yet settled on the degree of this effect. Specifically, it has been recently suggested that only a minority of taxa depend on the microbial composition in earlier times. To address the issue of identifying and predicting temporal microbial patterns we developed a new model, MTV-LMM (Microbial Temporal Variability Linear Mixed Model), a linear mixed model for the prediction of microbial community temporal dynamics. MTV-LMM can identify time-dependent microbes (i.e., microbes whose abundance can be predicted based on the previous microbial composition) in longitudinal studies, which can then be used to analyze the trajectory of the microbiome over time. We evaluated the performance of MTV-LMM on real and synthetic time series datasets, and found that MTV-LMM outperforms commonly used methods for microbiome time series modeling. Particularly, we demonstrate that the effect of the microbial composition in previous time points on the abundance of taxa at later time points is underestimated by a factor of at least 10 when applying previous approaches. Using MTV-LMM, we demonstrate that a considerable portion of the human gut microbiome, both in infants and adults, has a significant time-dependent component that can be predicted based on microbiome composition in earlier time points. This suggests that microbiome composition at a given time point is a major factor in defining future microbiome composition and that this phenomenon is considerably more common than previously reported for the human gut microbiome.
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http://dx.doi.org/10.1371/journal.pcbi.1006960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597035PMC
June 2019

Establishing microbial composition measurement standards with reference frames.

Nat Commun 2019 06 20;10(1):2719. Epub 2019 Jun 20.

Department of Pediatrics, University of California, San Diego, La Jolla, CA, 92093, USA.

Differential abundance analysis is controversial throughout microbiome research. Gold standard approaches require laborious measurements of total microbial load, or absolute number of microorganisms, to accurately determine taxonomic shifts. Therefore, most studies rely on relative abundance data. Here, we demonstrate common pitfalls in comparing relative abundance across samples and identify two solutions that reveal microbial changes without the need to estimate total microbial load. We define the notion of "reference frames", which provide deep intuition about the compositional nature of microbiome data. In an oral time series experiment, reference frames alleviate false positives and produce consistent results on both raw and cell-count normalized data. Furthermore, reference frames identify consistent, differentially abundant microbes previously undetected in two independent published datasets from subjects with atopic dermatitis. These methods allow reassessment of published relative abundance data to reveal reproducible microbial changes from standard sequencing output without the need for new assays.
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http://dx.doi.org/10.1038/s41467-019-10656-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586903PMC
June 2019

Cardiac Computed Tomography for Atrial Fibrillation Patients Undergoing Ablation: Implications for the Prediction of Early Recurrence.

J Thorac Imaging 2020 May;35(3):186-192

Heart & Vascular Center, Medical University of South Carolina, Charleston, SC.

Objective: The objective of this study was to correlate early recurrence of atrial fibrillation (AF) after ablation with noninvasive imaging using cardiac computed tomography (CT).

Methods: CT image data of 260 patients who had undergone wide area circumferential ablation (WACA) between October 2005 and August 2010 as well as from 30 subjects in sinus rhythm without a history of AF (control group) were retrospectively analyzed. To evaluate early outcome of AF ablation, all AF patients underwent follow-up with a 30-day event monitor 3 to 4 months after ablation. In addition, a cardiac CT was also performed 3 to 4 months after ablation to exclude pulmonary vein (PV) stenosis. The presence of early AF was correlated with anatomic and functional PV and left atrial parameters, as assessed by cardiac CT.

Results: A total of 70 patients (26.9%) were found to have early recurrence of AF. However, we found no association between PV or left atrial anatomic or functional parameters derived from cardiac imaging with early AF recurrence. Furthermore, no correlation (P>0.05) between AF recurrence and coronary artery stenosis, anatomic origin of the sinoatrial, or atrioventricular nodal arteries was observed. Finally, PV contraction did not predict AF recurrence. However, when comparing PV contraction in WACA patients with the control group, a significant (P<0.05) reduction in left superior PV and right superior PV contractility was found in patients after radiofreqency ablation.

Conclusions: In our relatively large cohort, cardiac CT did not yield any anatomic or functional markers for the prediction of early AF recurrence after undergoing WACA. However, our data may provide insights into functional changes that occur following ablation procedures.
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http://dx.doi.org/10.1097/RTI.0000000000000425DOI Listing
May 2020

Correction to: Dynamic linear models guide design and analysis of microbiota studies within artificial human guts.

Microbiome 2018 11 27;6(1):212. Epub 2018 Nov 27.

Program in Computational Biology and Bioinformatics, Duke University, CIEMAS, Room 2171, 101 Science Drive, Box 3382, Durham, NC, 27708, USA.

AbstractFollowing publication of the original article [1], the authors noticed an error in the presentation of equations in the PDF version.
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http://dx.doi.org/10.1186/s40168-018-0601-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260730PMC
November 2018

Dynamic linear models guide design and analysis of microbiota studies within artificial human guts.

Microbiome 2018 11 12;6(1):202. Epub 2018 Nov 12.

Program in Computational Biology and Bioinformatics, Duke University, CIEMAS, Room 2171, 101 Science Drive, Box 3382, Durham, NC, 27708, USA.

Background: Artificial gut models provide unique opportunities to study human-associated microbiota. Outstanding questions for these models' fundamental biology include the timescales on which microbiota vary and the factors that drive such change. Answering these questions though requires overcoming analytical obstacles like estimating the effects of technical variation on observed microbiota dynamics, as well as the lack of appropriate benchmark datasets.

Results: To address these obstacles, we created a modeling framework based on multinomial logistic-normal dynamic linear models (MALLARDs) and performed dense longitudinal sampling of four replicate artificial human guts over the course of 1 month. The resulting analyses revealed how the ratio of biological variation to technical variation from sample processing depends on sampling frequency. In particular, we find that at hourly sampling frequencies, 76% of observed variation could be ascribed to technical sources, which could also skew the observed covariation between taxa. We also found that the artificial guts demonstrated replicable trajectories even after a recovery from a transient feed disruption. Additionally, we observed irregular sub-daily oscillatory dynamics associated with the bacterial family Enterobacteriaceae within all four replicate vessels.

Conclusions: Our analyses suggest that, beyond variation due to sequence counting, technical variation from sample processing can obscure temporal variation from biological sources in artificial gut studies. Our analyses also supported hypotheses that human gut microbiota fluctuates on sub-daily timescales in the absence of a host and that microbiota can follow replicable trajectories in the presence of environmental driving forces. Finally, multiple aspects of our approach are generalizable and could ultimately be used to facilitate the design and analysis of longitudinal microbiota studies in vivo.
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http://dx.doi.org/10.1186/s40168-018-0584-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233358PMC
November 2018

Human Gut Microbiota Predicts Susceptibility to Vibrio cholerae Infection.

J Infect Dis 2018 07;218(4):645-653

Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts.

Background: Cholera is a public health problem worldwide, and the risk factors for infection are only partially understood.

Methods: We prospectively studied household contacts of patients with cholera to compare those who were infected to those who were not. We constructed predictive machine learning models of susceptibility, using baseline gut microbiota data. We identified bacterial taxa associated with susceptibility to Vibrio cholerae infection and tested these taxa for interactions with V. cholerae in vitro.

Results: We found that machine learning models based on gut microbiota, as well as models based on known clinical and epidemiological risk factors, predicted V. cholerae infection. A predictive gut microbiota of roughly 100 bacterial taxa discriminated between contacts who developed infection and those who did not. Susceptibility to cholera was associated with depleted levels of microbes from the phylum Bacteroidetes. By contrast, a microbe associated with cholera by our modeling framework, Paracoccus aminovorans, promoted the in vitro growth of V. cholerae. Gut microbiota structure, clinical outcome, and age were also linked.

Conclusion: These findings support the hypothesis that abnormal gut microbial communities are a host factor related to V. cholerae susceptibility.
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http://dx.doi.org/10.1093/infdis/jiy192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047457PMC
July 2018

Safety of hematopoietic cell infusion in children with malignant and non-malignant diseases.

Pediatr Transplant 2017 Nov 28;21(7). Epub 2017 Aug 28.

Department of Pediatrics, Columbia University, New York, NY, USA.

HPC infusions have been associated with a variety of adverse events related to either patient or HPC product-related factors. Studies documenting infusion-related AEs in children are limited. We reviewed HPC infusion records in 354 children. Infusion-related adverse events were classified as follows: grade 0-absent, grade I-mild, grade II-moderate, grade III-severe, grade IV-life-threatening, and grade V-death. The percentage of patients with grade 0, I, and II-IV AEs was as follows: 0 = 67%, I = 23.4%, and II-V = 9.6% (one patient had fatal anaphylactic reaction to dimethyl sulfoxide). The incidence of grade II-IV hypertension was 7.1%. There was a higher incidence of AEs with infusion of allogeneic bone marrow versus allogeneic PBSCs (47.4% vs 25.3%, P = .001). Cryopreserved products had a lower incidence of infusion-associated AEs compared with fresh HPC products (24% vs 39.4%, P = .003). Allogeneic HPC infusion volume (>100 mL) was a significant risk factor for infusion-associated AEs (P < .001). Patients >10 years who received autologous HPC infusions had higher risk of AEs when compared to patients <10 years (P = .01). Our study demonstrated that despite a high incidence of infusion-associated hypertension, HPC infusion is relatively safe in children. Investigating strategies to optimize management of hypertension in the setting of HPC infusion is warranted.
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http://dx.doi.org/10.1111/petr.13038DOI Listing
November 2017

Phylogenetic factorization of compositional data yields lineage-level associations in microbiome datasets.

PeerJ 2017 9;5:e2969. Epub 2017 Feb 9.

Program for Computational Biology and Bioinformatics, Duke University, Durham, NC, United States; Center for Genomic and Computational Biology, Duke University, Durham, NC, United States; Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, United States.

Marker gene sequencing of microbial communities has generated big datasets of microbial relative abundances varying across environmental conditions, sample sites and treatments. These data often come with putative phylogenies, providing unique opportunities to investigate how shared evolutionary history affects microbial abundance patterns. Here, we present a method to identify the phylogenetic factors driving patterns in microbial community composition. We use the method, "phylofactorization," to re-analyze datasets from the human body and soil microbial communities, demonstrating how phylofactorization is a dimensionality-reducing tool, an ordination-visualization tool, and an inferential tool for identifying edges in the phylogeny along which putative functional ecological traits may have arisen.
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http://dx.doi.org/10.7717/peerj.2969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345826PMC
February 2017

A phylogenetic transform enhances analysis of compositional microbiota data.

Elife 2017 02 15;6. Epub 2017 Feb 15.

Program in Computational Biology and Bioinformatics, Duke University, Durham, United States.

Surveys of microbial communities (microbiota), typically measured as relative abundance of species, have illustrated the importance of these communities in human health and disease. Yet, statistical artifacts commonly plague the analysis of relative abundance data. Here, we introduce the PhILR transform, which incorporates microbial evolutionary models with the isometric log-ratio transform to allow off-the-shelf statistical tools to be safely applied to microbiota surveys. We demonstrate that analyses of community-level structure can be applied to PhILR transformed data with performance on benchmarks rivaling or surpassing standard tools. Additionally, by decomposing distance in the PhILR transformed space, we identified neighboring clades that may have adapted to distinct human body sites. Decomposing variance revealed that covariation of bacterial clades within human body sites increases with phylogenetic relatedness. Together, these findings illustrate how the PhILR transform combines statistical and phylogenetic models to overcome compositional data challenges and enable evolutionary insights relevant to microbial communities.
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http://dx.doi.org/10.7554/eLife.21887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328592PMC
February 2017

A Multicenter Study of Bacterial Blood Stream Infections in Pediatric Allogeneic Hematopoietic Cell Transplantation Recipients: The Role of Acute Gastrointestinal Graft-versus-Host Disease.

Biol Blood Marrow Transplant 2017 Apr 16;23(4):642-647. Epub 2017 Jan 16.

Department of Pediatrics, UCSF Benioff Children's Hospital, San Francisco, California.

Blood stream infections (BSI) caused by enteric organisms are associated with a particularly high mortality rate in allogeneic hematopoietic cell transplantation (alloHCT) recipients. We conducted a retrospective multicenter study aiming to analyze the risk factors associated with antibiotic resistance and impact of BSI on transplantation-related mortality (TRM) in children after alloHCT. During the study period from 2004 to 2014, 395 children (mean age, 9.4 years) with at least 1 BSI were included. The incidences of resistant gram-negative rods were 20.7% to piperacillin-tazobactam, 10.9% to cefepime, 21% to ceftazidime, 11.4% to levofloxacin, and 8.16% to meropenem. Thirty-eight percent of Enterococcus spp. isolates were resistant to vancomycin. More than 1 episode of BSI was associated with significant increase in the risk of resistance to piperacillin-tazobactam, cefepime, and vancomycin. On multivariate analysis of risk factors for TRM, achievement of neutrophil engraftment by day 30 was associated with lower TRM (P = .002). However, infection with an antibiotic-resistant organism was not associated with TRM. Development of enteric bacterial BSI after the onset of acute gastrointestinal graft-versus-host disease (GVHD) was the strongest predictor of TRM (hazard ratio, 4.786; 95% confidence interval, 2.833 to 8.087; P < .001). In patients with acute gastrointestinal GVHD who subsequently developed enteric bacterial BSI, the incidence of 1-year TRM was 33.4% (SE = 7%), compared with 15.3% (SE = 2%) for those without acute gastrointestinal GVHD (P = .004). Primary prevention of a first episode of BSI is arguably the most important intervention to decrease antibiotic resistance. It is also imperative that we develop strategies to maintain gastrointestinal health, especially in patients with gastrointestinal GVHD, in an effort to prevent subsequent enteric bacterial BSI and improve survival.
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http://dx.doi.org/10.1016/j.bbmt.2017.01.073DOI Listing
April 2017

Low-volume contrast medium protocol for comprehensive cardiac and aortoiliac CT assessment in the context of transcatheter aortic valve replacement.

Acad Radiol 2015 Sep 18;22(9):1138-46. Epub 2015 Jun 18.

Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina.

Rationale And Objectives: To investigate the diagnostic performance of a comprehensive computed tomography (CT) protocol for both cardiac and aortoiliac evaluation of patients considered for transcatheter aortic valve replacement (TAVR) using a single, low-volume contrast medium (CM) injection.

Materials And Methods: Forty-four TAVR candidates were retrospectively analyzed. All underwent retrospectively electrocardiogram-gated cardiac CT followed by high-pitch CT angiography of the aortoiliac vasculature using one of two single injection protocols of 320 mgI/mL iodine CM: group A (n = 22), iodine delivery rate-based (1.28 gI/s), 60-mL CM volume, 4.0 mL/s flow rate; group B (n = 22), clinical routine protocol, 100-mL CM volume, 4.0 mL/s flow rate. Mean arterial attenuation, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were calculated. Subjective image quality was assessed.

Results: Aortic root and iliofemoral dimensions could be analyzed in all cases. Patient characteristics showed no significant differences. Mean attenuation at the levels of the aortic root (285.8 ± 83.0 HU vs 327.5 ± 70.8 HU, P = .080) and the iliofemoral access route (256.8 ± 88.5 HU vs 307.5 ± 93.2 HU, P = .071), as well as SNR and CNR were nonsignificantly lower in group A compared to group B. Subjective image quality was equivalent.

Conclusions: In multimorbid TAVR patients, the performance of a combined CT protocol using a single low-volume CM bolus is feasible with maintained image quality compared to a standard protocol.
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http://dx.doi.org/10.1016/j.acra.2015.03.018DOI Listing
September 2015

Influence of technical parameters on epicardial fat volume quantification at cardiac CT.

Eur J Radiol 2015 Jun 25;84(6):1062-7. Epub 2015 Mar 25.

Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC, USA; Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital, Munich, Germany.

Objectives: To systematically analyze the influence of technical parameters on quantification of epicardial fat volume (EATV) at cardiac CT.

Methods: 153 routine cardiac CT data sets were analyzed using three-dimensional pericardial border delineation. Three image series were reconstructed per patient: (a) CTAD: coronary CT angiography (CTA), diastolic phase; (b) CTAS: coronary CTA, systolic phase; (c) CaScD: non-contrast CT, diastolic phase. EATV was calculated using three different upper thresholds (-15HU, -30 HU, -45HU). Repeated measures ANOVA, Spearman's rho, and Bland Altman plots were used.

Results: Mean EATV differed between all three image series at a -30HU threshold (CTAD 87.2 ± 38.5 ml, CTAS 90.9 ± 37.7 ml, CaScD 130.7 ± 49.5 ml, P<0.001). EATV of diastolic and systolic CTA reconstructions did not differ significantly (P=0.225). Mean EATV for contrast enhanced CTA at a -15HU threshold (CTAD15 102.4 ± 43.6 ml, CTAS15 105.3 ± 42.3 ml) could be approximated most closely by non-contrast CT at -45HU threshold (CaScD45 105.3 ± 40.8 ml). The correlation was excellent: CTAS15-CTAD15, rho=0.943; CTAD15-CaScD45, rho=0.905; CTAS15-CaScD45, rho=0.924; each P<0.001). Bias values from Bland Altman Analysis were: CTAS15-CTAD15, 4.9%; CTAD15-CaScD45, -4.3%; CTAS15-CaScD45, 0.6%.

Conclusions: Measured EATV can differ substantially between contrast enhanced and non-contrast CT studies, which can be reconciled by threshold modification. Heart cycle phase does not significantly influence EATV measurements.
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http://dx.doi.org/10.1016/j.ejrad.2015.03.018DOI Listing
June 2015

CT Evaluation of Small-Diameter Coronary Artery Stents: Effect of an Integrated Circuit Detector with Iterative Reconstruction.

Radiology 2015 Sep 17;276(3):706-14. Epub 2015 Mar 17.

From the Division of Cardiovascular Imaging, Department of Radiology and Radiological Science (L.L.G., G.R.G., C.N.D.C., M.V.H., J.R.S., A.W.K., J.M.K., A.B., U.E., P.C., U.J.S.), and Division of Cardiology, Department of Medicine (U.J.S.), Medical University of South Carolina, Heart & Vascular Center, Ashley River Tower, 25 Courtenay Dr, Charleston, SC 29425-2260; Department of Clinical Radiology, University Hospitals LMU Munich, Munich, Germany (L.L.G., F.B.); Siemens Medical Solutions, CT Division, Malvern, Pa (C.C.); Department of Cardiology and Intensive Care Medicine, Heart Center Munich-Bogenhausen, Munich, Germany (U.E.); and Department of Radiology, University of Tuebingen, Tuebingen, Germany (F.B.).

Purpose: To use suitable objective methods of analysis to assess the influence of the combination of an integrated-circuit computed tomographic (CT) detector and iterative reconstruction (IR) algorithms on the visualization of small (≤3-mm) coronary artery stents.

Materials And Methods: By using a moving heart phantom, 18 data sets obtained from three coronary artery stents with small diameters were investigated. A second-generation dual-source CT system equipped with an integrated-circuit detector was used. Images were reconstructed with filtered back-projection (FBP) and IR at a section thickness of 0.75 mm (FBP75 and IR75, respectively) and IR at a section thickness of 0.50 mm (IR50). Multirow intensity profiles in Hounsfield units were modeled by using a sum-of-Gaussians fit to analyze in-plane image characteristics. Out-of-plane image characteristics were analyzed with z upslope of multicolumn intensity profiles in Hounsfield units. Statistical analysis was conducted with one-way analysis of variance and the Student t test.

Results: Independent of stent diameter and heart rate, IR75 resulted in significantly increased xy sharpness, signal-to-noise ratio, and contrast-to-noise ratio, as well as decreased blurring and noise compared with FBP75 (eg, 2.25-mm stent, 0 beats per minute; xy sharpness, 278.2 vs 252.3; signal-to-noise ratio, 46.6 vs 33.5; contrast-to-noise ratio, 26.0 vs 16.8; blurring, 1.4 vs 1.5; noise, 15.4 vs 21.2; all P < .001). In the z direction, the upslopes were substantially higher in the IR50 reconstructions (2.25-mm stent: IR50, 94.0; IR75, 53.1; and FBP75, 48.1; P < .001).

Conclusion: The implementation of an integrated-circuit CT detector provides substantially sharper out-of-plane resolution of coronary artery stents at 0.5-mm section thickness, while the use of iterative image reconstruction mostly improves in-plane stent visualization.
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http://dx.doi.org/10.1148/radiol.15140427DOI Listing
September 2015

Reduced radiation dose and improved image quality at cardiovascular CT angiography by automated attenuation-based tube voltage selection: intra-individual comparison.

Eur Radiol 2014 Nov 24;24(11):2677-84. Epub 2014 Jul 24.

Department of Radiology and Radiological Science, Medical University of South Carolina, Ashley River Tower, MSC 226 25 Courtenay Drive, Charleston, SC, 29425, USA.

Objectives: To evaluate the effect of automated tube voltage selection on radiation dose and image quality at cardiovascular CT angiography (CTA).

Methods: We retrospectively analysed paired studies in 72 patients (41 male, 60.5 ± 16.5 years), who had undergone CTA acquisitions of the heart or aorta both before and after the implementation of an automated x-ray tube voltage selection algorithm (ATVS). All other parameters were kept identical between the two acquisitions. Subjective image quality (IQ) was rated and objective IQ was measured by image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and figure of merit (FOM). Image quality parameters and effective dose were compared between acquisitions.

Results: Overall subjective image quality improved with the percentage of cases scored as adequate or higher increasing from 79 % to 92 % after implementation of ATVS (P = 0.03). SNR (14.1 ± 5.9, 15.7 ± 6.1, P = 0.009), CNR (11.6 ± 5.3, 13.2 ± 5.6, P = 0.011), and FOM (19.9 ± 23.3, 43.8 ± 51.1, P < 0.001) were significantly higher after implementation of ATVS. Mean image noise (24.1 ± 8.4 HU, 22.7 ± 7.1 HU, P = 0.048) and mean effective dose (10.6 ± 5.9 mSv, 8.8 ± 5.0 mSv, P = 0.003) were significantly lower after implementation of ATVS.

Conclusions: Automated tube voltage selection can operator-independently optimize cardiovascular CTA image acquisition parameters with improved image quality at reduced dose.

Key Points: • Automatic tube voltage selection optimizes tube voltage for each individual patient. • In this population, overall radiation dose decreased while image quality improved. • This tool may become valuable for improving dose/quality ratio.
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http://dx.doi.org/10.1007/s00330-014-3312-9DOI Listing
November 2014

Incremental value of pharmacological stress cardiac dual-energy CT over coronary CT angiography alone for the assessment of coronary artery disease in a high-risk population.

AJR Am J Roentgenol 2014 Jul;203(1):W70-7

1 Department of Radiology and Radiological Science, Medical University of South Carolina, Ashley River Tower, MSC 226, 25 Courtenay Dr, Charleston, SC 29401.

Objective: The purpose of this article is to prospectively determine the value of stress dual-energy CT (DECT) myocardial perfusion imaging to coronary CT angiography (CTA) for the assessment of coronary artery disease (CAD) in a high-risk population.

Subjects And Methods: We prospectively enrolled 29 consecutive patients who were referred for cardiac SPECT examinations for known or suspected CAD to also undergo pharmacologic stress cardiac DECT. In 25 patients, cardiac catheterization was available as the reference standard for morphologically significant stenosis. The performance of coronary CTA alone, DECT myocardial perfusion alone, and the combination of both was assessed by calculating sensitivity, specificity, and AUC values.

Results: For morphologically significant stenosis, coronary CTA alone and myocardial DECT assessment alone had 95% sensitivity and 50% specificity. The combined approach yielded 100% sensitivity and 33% specificity if either was positive and 90% sensitivity and 67% specificity if both were positive. The AUC value was highest (0.78) if both were positive. For hemodynamically significant lesions, coronary CTA alone had 91% sensitivity and 38% specificity, and DECT alone had 95% sensitivity and 75% specificity. The combined approach yielded 100% sensitivity and 38% specificity if either was positive and 86% sensitivity and 75% specificity if both were positive. AUC values were highest for DECT alone (0.85) and the "both positive" evaluation (0.80).

Conclusion: The combined analysis of coronary CTA and DECT myocardial perfusion reduces the number of false-positives in a high-risk population for CAD and outperforms the purely anatomic test of coronary CTA alone for the detection of morphologically and hemodynamically significant CAD.
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http://dx.doi.org/10.2214/AJR.13.11772DOI Listing
July 2014

Residents' performance in the interpretation of on-call "triple-rule-out" CT studies in patients with acute chest pain.

Acad Radiol 2014 Jul;21(7):938-44

Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, South Carolina; Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital, Munich, Germany.

Rationale And Objectives: To evaluate the performance of radiology residents in the interpretation of on-call, emergency "triple-rule-out" (TRO) computed tomographic (CT) studies in patients with acute chest pain.

Materials And Methods: The study was institutional review board-approved and Health Insurance Portability and Accountability Act compliant. Data from 617 on-call TRO studies were analyzed. Dedicated software enables subspecialty attendings to grade discrepancies in interpretation between preliminary trainee reports and their final interpretation as "unlikely to be significant" (minor discrepancies) or "likely to be significant" for patient management (major discrepancies). The frequency of minor, major and all discrepancies in resident's TRO interpretations was compared to 609 emergent non-electrocardiography (ECG)-synchronized chest CT studies using Pearson χ(2) test.

Results: Minor discrepancies occurred more often in the TRO group (9.1% vs. 3.9%, P < .001), but there was no difference in the frequency of major discrepancies (2.1% vs. 2.8%, P = .55). Minor discrepancies in the TRO group most commonly resulted from missed extrathoracic findings with missed liver lesions being the most frequent. Major discrepancies mostly encompassed cardiac and extracardiac vascular findings but did not result in unnecessary interventions, significant immediate changes in management, or adverse patient outcomes.

Conclusions: On-call resident interpretation of TRO CT studies in patients with acute chest pain is congruent with final subspecialty attending interpretation in the overwhelming majority of cases. The rate of discrepancies likely to affect patient management in this domain is not different from emergent non-ECG-synchronized chest CT.
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http://dx.doi.org/10.1016/j.acra.2014.04.017DOI Listing
July 2014

Transient Ischemic Dilation of the Left Ventricle on SPECT: Correlation with Findings at Coronary CT Angiography.

J Nucl Med 2014 Jun 24;55(6):917-22. Epub 2014 Apr 24.

Heart and Vascular Center, Medical University of South Carolina, Charleston, South Carolina Department of Cardiology and Intensive Care Medicine, Heart Center Munich-Bogenhausen, Munich, Germany.

Unlabelled: Transient ischemic dilation (TID) in the setting of abnormal stress-rest cardiac SPECT myocardial perfusion imaging (MPI) has been linked with increased cardiovascular risk. However, the significance of TID in the setting of an otherwise normal SPECT MPI study has not been clearly established. In this study, cardiac CT was used to evaluate the prevalence of atherosclerotic lesions and the severity of coronary artery stenosis in patients with TID of the left ventricle with or without associated myocardial perfusion defects on SPECT MPI.

Methods: The study population consisted of 1,553 consecutive patients who had undergone both cardiac CT and SPECT MPI within 1 mo between January 1, 2006, and September 1, 2011. Patients included in the study group had a pathologic TID value defined as ≥1.18 for men and ≥1.22 for women. Coronary CT angiography was used to evaluate each coronary segment for the presence and composition of atherosclerotic plaque and the degree of coronary stenosis. TID-positive patients were compared with a 2:1 risk-factor-matched-pair control cohort without TID.

Results: TID was identified in 30 patients who were compared with TID-negative risk-factor-matched controls (n = 60). When compared with the TID-negative control cohort, TID-positive patients had no significant differences in the presence and extent of atherosclerosis, the degree of coronary artery stenosis, or the calcium score at cardiac CT. Similarly, there were no significant differences in these CT measures in TID-positive patients with a normal perfusion study (n = 20) when compared with TID-negative patients with a normal perfusion study (n = 48). In addition, there was no significant difference in the incidence of major adverse cardiac events when comparing both the TID-positive patients and the TID-negative control cohort and when comparing patients who were TID-positive with normal perfusion with patients who were TID-negative with normal perfusion.

Conclusion: The presence of TID with an otherwise normal SPECT MPI study does not translate into a greater extent of coronary artery disease as assessed by cardiac CT or increased risk for future major adverse cardiac events.
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http://dx.doi.org/10.2967/jnumed.113.125880DOI Listing
June 2014

Iterative image reconstruction techniques: cardiothoracic computed tomography applications.

J Thorac Imaging 2014 Jul;29(4):198-208

*Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC ‡Siemens Healthcare Sector, Malvern, PA †Department of Radiology, Konyang University College of Medicine, Daejeon, Korea §Department of Clinical Radiology, University Hospitals LMU, Munich, Germany Departments of ∥Medical Radiology ¶Legal Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.

Iterative image reconstruction algorithms provide significant improvements over traditional filtered back projection in computed tomography (CT). Clinically available through recent advances in modern CT technology, iterative reconstruction enhances image quality through cyclical image calculation, suppressing image noise and artifacts, particularly blooming artifacts. The advantages of iterative reconstruction are apparent in traditionally challenging cases-for example, in obese patients, those with significant artery calcification, or those with coronary artery stents. In addition, as clinical use of CT has grown, so have concerns over ionizing radiation associated with CT examinations. Through noise reduction, iterative reconstruction has been shown to permit radiation dose reduction while preserving diagnostic image quality. This approach is becoming increasingly attractive as the routine use of CT for pediatric and repeated follow-up evaluation grows ever more common. Cardiovascular CT in particular, with its focus on detailed structural and functional analyses, stands to benefit greatly from the promising iterative solutions that are readily available.
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http://dx.doi.org/10.1097/RTI.0000000000000041DOI Listing
July 2014

Monoenergetic extrapolation of cardiac dual energy CT for artifact reduction.

Acta Radiol 2015 Apr 10;56(4):413-8. Epub 2014 Mar 10.

Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, SC, USA.

Background: Monoenergetic extrapolation of cardiac dual-energy computed tomography (DECT) could be useful in artifact reduction in clinical practice.

Purpose: To evaluate the potential of monoenergetic extrapolation of cardiac DECT data for reducing artifacts from metal and high iodine contrast concentration.

Material And Methods: With IRB approval and in HIPAA compliance, 35 patients (22 men, 61 ± 12 years) underwent cardiac DECT with dual-source CT (100 kVp and 140 kVp). Contrast material injection protocols were adapted to the patient's weight using non-ionic low-osmolar 370 mgI/mL iopromide. Datasets were transferred to a stand-alone workstation and dedicated monoenergetic analysis software was used for postprocessing. Reconstructions with the following five photon energies were generated: 40 keV, 60 keV, 80 keV, 100 keV, and 120 keV. Artifact severity was graded on a 5-point Likert scale (0, massive artifact; 5, absence of artifact). The size of artifact and image noise (expressed as HU) in anatomic structures adjacent to the artifact were measured. Quantitative and subjective image quality was compared using Friedman and Wilcoxon tests.

Results: We observed artifacts arising from densely concentrated contrast material in the superior vena cava (SVC) in 18 patients, from sternal wires in 14, from bypass clips in eight, and from coronary artery stents in seven. Artifact size in monoenergetic reconstructions from 40 to 120 keV decreased from 21.3 to 19 mm for the SVC (P < 0.001), from 8.4 to 2.6 mm for sternal wires (P < 0.001), from 6.4 to 2.2 mm for bypass clips (P < 0.001), and from 5.9 to 2.7 mm for stents (P < 0.001), respectively. The quality score changed from 0.2 to 3.8 for the SVC (P < 0.001), from 0.1 to 4 for sternal wires (P < 0.001), from 0 to 3.9 for bypass clips (P < 0.001), and from 0 to 3.9 for stents (P < 0.001). Lowest noise in adjacent structures was found at 80 keV for the SVC (39.1 HU), for sternal wires (33.3), for bypass clips (26.9), and for stents (33.9).

Conclusion: A significant reduction of high-attenuation artifacts can be achieved by use of higher monoenergetic energy levels with cardiac DECT. However, image noise in anatomic structures affected by artifacts is lowest at 80 keV, which suggests an evaluation approach that makes use of multiple energy levels for a complete diagnosis.
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http://dx.doi.org/10.1177/0284185114527867DOI Listing
April 2015

Integrated cardiothoracic imaging with computed tomography.

Semin Respir Crit Care Med 2014 Feb 30;35(1):50-63. Epub 2014 Jan 30.

Department of Radiology and Radiological Science, Medical University of South Carolina, Charleston, South Carolina.

The respiratory and the cardiovascular systems are intimately connected. Because of the high degree of morphological and functional interaction, pathophysiological processes in one compartment are likely to induce adaptive changes in the other. Computed tomography (CT) plays a central role in the diagnostic work up of both thoracic and cardiac disorders. Historically, these two systems have been evaluated separately; however, CT technology has evolved remarkably over recent decades. Up-to-date advanced imaging strategies allow for a combined assessment of the cardiopulmonary unit. Besides improved techniques of electrocardiogram (ECG)-synchronization for obtaining both morphological and functional information, latest advances of dual-source CT (DSCT) have shown great promise for even more comprehensive integrated cardiothoracic imaging.
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http://dx.doi.org/10.1055/s-0033-1363451DOI Listing
February 2014

First-arterial-pass dual-energy CT for assessment of myocardial blood supply: do we need rest, stress, and delayed acquisition? Comparison with SPECT.

Radiology 2014 Mar 13;270(3):708-16. Epub 2013 Nov 13.

From the Department of Radiology and Radiological Science (F.G.M., C.N.D.C., U.J.S., J.W.N., J.R.S., T.H.) and Division of Cardiology, Department of Medicine (U.J.S., B.A.F.), Medical University of South Carolina, Ashley River Tower, MSC 226, 25 Courtenay Dr, Charleston, SC 29425; Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital, Munich, Germany (F.G.M.); Department of Radiological Sciences, Oncology and Pathology, University of Rome "Sapienza"-Polo Pontino, Latina, Italy (C.N.D.C.); the Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Baltimore, Md (J.W.N.); and Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany (T.H.).

Purpose: To compare the relative contributions of rest, stress, and delayed acquisitions with the accuracy of dual-energy (DE) computed tomography (CT) for the assessment of myocardial blood supply.

Materials And Methods: With institutional review board approval and HIPAA compliance, 55 consecutive patients (10 women, 45 men; mean age, 62 years ± 10) clinically referred for cardiac single photon emission computed tomography (SPECT) who were known to have or were suspected of having coronary artery disease were prospectively enrolled. DE CT studies were acquired during adenosine stress, at rest, and after 6-minute delay. The DE CT iodine distribution maps were visually assessed for perfusion deficits or late iodine enhancement. Per-segment agreement between modalities was investigated with κ statistics. Test characteristics for the detection of perfusion deficits were calculated for combinations of rest, stress, and delayed DE CT acquisition, with SPECT as reference standard.

Results: At SPECT, 714 segments were considered normal, 192 showed fixed perfusion defects, and 29 showed reversible perfusion deficits. Sensitivity of rest-only DE CT was 92%, and specificity was 98%. Stress-only, rest-stress, stress and delayed, and the combination of all three had a sensitivity of 99% and a specificity of 97%. Of 29 segments with reversible perfusion deficits at SPECT, 13 (45%) were misclassified by using rest-stress DE CT as fixed perfusion deficits. With stress DE CT plus delayed acquisition, 13 of 192 (7%) segments with fixed perfusion deficits at SPECT were misclassified as reversible.

Conclusion: Rest-stress acquisition should be the protocol of choice for assessment of the myocardial blood supply in DE CT. The accuracy of DE CT is not increased by the addition of a delayed DE CT acquisition, which may therefore be omitted to reduce radiation exposure. With rest-stress DE CT, almost one-half of defects that are reversible at SPECT were classified as fixed; radiologists and clinicians need to be aware of this incongruence when they interpret DE CT myocardial perfusion studies.
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http://dx.doi.org/10.1148/radiol.13131183DOI Listing
March 2014

Automated quantification of epicardial adipose tissue using CT angiography: evaluation of a prototype software.

Eur Radiol 2014 Feb 6;24(2):519-26. Epub 2013 Nov 6.

Department of Radiology and Radiological Science, Medical University of South Carolina, Ashley River Tower 25 Courtenay Drive, Charleston, SC, 29425-2260, USA.

Objectives: This study evaluated the performance of a novel automated software tool for epicardial fat volume (EFV) quantification compared to a standard manual technique at coronary CT angiography (cCTA).

Methods: cCTA data sets of 70 patients (58.6 ± 12.9 years, 33 men) were retrospectively analysed using two different post-processing software applications. Observer 1 performed a manual single-plane pericardial border definition and EFVM segmentation (manual approach). Two observers used a software program with fully automated 3D pericardial border definition and EFVA calculation (automated approach). EFV and time required for measuring EFV (including software processing time and manual optimization time) for each method were recorded. Intraobserver and interobserver reliability was assessed on the prototype software measurements. T test, Spearman's rho, and Bland-Altman plots were used for statistical analysis.

Results: The final EFVA (with manual border optimization) was strongly correlated with the manual axial segmentation measurement (60.9 ± 33.2 mL vs. 65.8 ± 37.0 mL, rho = 0.970, P < 0.001). A mean of 3.9 ± 1.9 manual border edits were performed to optimize the automated process. The software prototype required significantly less time to perform the measurements (135.6 ± 24.6 s vs. 314.3 ± 76.3 s, P < 0.001) and showed high reliability (ICC > 0.9).

Conclusions: Automated EFVA quantification is an accurate and time-saving method for quantification of EFV compared to established manual axial segmentation methods.

Key Points: • Manual epicardial fat volume quantification correlates with risk factors but is time-consuming. • The novel software prototype automates measurement of epicardial fat volume with good accuracy. • This novel approach is less time-consuming and could be incorporated into clinical workflow.
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http://dx.doi.org/10.1007/s00330-013-3052-2DOI Listing
February 2014