Self-Navigation with Compressed Sensing for 2D Translational Motion Correction in Free-Breathing Coronary MRI: A Feasibility Study

Purpose

Respiratory motion correction remains a challenge in coronary magnetic resonance imaging (MRI) and current techniques, such as navigator gating, suffer from sub-optimal scan efficiency and ease-of-use. To overcome these limitations, an image-based self-navigation technique is proposed that uses “sub-images” and compressed sensing (CS) to obtain translational motion correction in 2D. The method was preliminarily implemented as a 2D technique and tested for feasibility for targeted coronary imaging.

Methods

During a 2D segmented radial k-space data acquisition, heavily undersampled sub-images were reconstructed from the readouts collected during each cardiac cycle. These sub-images may then be used for respiratory self-navigation. Alternatively, a CS reconstruction may be used to create these sub-images, so as to partially compensate for the heavy undersampling. Both approaches were quantitatively assessed using simulations and in vivo studies, and the resulting self-navigation strategies were then compared to conventional navigator gating.

Results

Sub-images reconstructed using CS showed a lower artifact level than sub-images reconstructed without CS. As a result, the final image quality was significantly better when using CS-assisted self-navigation as opposed to the non-CS approach. Moreover, while both self-navigation techniques led to a 69% scan time reduction (as compared to navigator gating), there was no significant difference in image quality between the CS-assisted self-navigation technique and conventional navigator gating, despite the significant decrease in scan time.

Conclusions

CS-assisted self-navigation using 2D translational motion correction demonstrated feasibility of producing coronary MRA data with image quality comparable to that obtained with conventional navigator gating, and does so without the use of additional acquisitions or motion modeling, while still allowing for 100% scan efficiency and an improved ease-of-use. In conclusion, compressed sensing may become a critical adjunct for 2D translational motion correction in free-breathing cardiac imaging with high spatial resolution. An expansion to modern 3D approaches is now warranted.     

两种心衰模型大鼠心功能的比较

目的　比较两种心衰模型大鼠心功能的特点。方法　用腹主动脉、下腔静脉穿刺造瘘法及冠脉结扎法建立不同的心衰模型 ,用Doppler超声心动图及心脏称重的方法比较其心功能的各项参数。结果　两组大鼠的相对心脏重量均有所增高。造瘘组射血分数有所下降 ,但心输出量、血压维持正常 ,而冠脉结扎组术后 3周射血分散、心输出量和平均动脉压均明显下降 ,等容舒张期延长。结论　腹主动脉、下腔静脉穿刺造瘘所造成的是高输出量心衰 ,而冠脉结扎法所造成的是低输出量心衰 ,其心衰程度更为严重。Doppler超声心动图为大鼠心功能的检测提供了一种简单、可靠、可随访的无创伤性检查方法。     

Impact of Thoracic Surgery on Cardiac Morphology and Function in Small Animal Models of Heart Disease: A Cardiac MRI Study in Rats

Background

Surgical procedures in small animal models of heart disease might evoke alterations in cardiac morphology and function. The aim of this study was to reveal and quantify such potential artificial early or long term effects in vivo, which might account for a significant bias in basic cardiovascular research, and, therefore, could potentially question the meaning of respective studies.

Methods

Female Wistar rats (n = 6 per group) were matched for weight and assorted for sham left coronary artery ligation or control. Cardiac morphology and function was then investigated in vivo by cine magnetic resonance imaging at 7 Tesla 1 and 8 weeks after the surgical procedure. The time course of metabolic and inflammatory blood parameters was determined in addition.

Results

Compared to healthy controls, rats after sham surgery showed a lower body weight both 1 week (267.5±10.6 vs. 317.0±11.3 g, n<0.05) and 8 weeks (317.0±21.1 vs. 358.7±22.4 g, n<0.05) after the intervention. Left and right ventricular morphology and function were not different in absolute measures in both groups 1 week after surgery. However, there was a confined difference in several cardiac parameters normalized to the body weight (bw), such as myocardial mass (2.19±0.30/0.83±0.13 vs. 1.85±0.22/0.70±0.07 mg left/right per g bw, p<0.05), or enddiastolic ventricular volume (1.31±0.36/1.21±0.31 vs. 1.14±0.20/1.07±0.17 µl left/right per g bw, p<0.05). Vice versa, after 8 weeks, cardiac masses, volumes, and output showed a trend for lower values in sham operated rats compared to controls in absolute measures (782.2±57.2/260.2±33.2 vs. 805.9±84.8/310.4±48.5 mg, p<0.05 for left/right ventricular mass), but not normalized to body weight. Matching these findings, blood testing revealed only minor inflammatory but prolonged metabolic changes after surgery not related to cardiac disease.

Conclusion

Cardio-thoracic surgical procedures in experimental myocardial infarction cause distinct alterations upon the global integrity of the organism, which in the long term also induce circumscribed repercussions on cardiac morphology and function. This impact has to be considered when analyzing data from respective animal studies and transferring these findings to conditions in patients.     

Assessment of Cardiac Function and Myocardial Morphology Using Small Animal Look-locker Inversion Recovery (SALLI) MRI in Rats

Small animal magnetic resonance imaging is an important tool to study cardiac function and changes in myocardial tissue. The high heart rates of small animals (200 to 600 beats/min) have previously limited the role of CMR imaging. Small animal Look-Locker inversion recovery (SALLI) is a T1 mapping sequence for small animals to overcome this problem ¹. T1 maps provide quantitative information about tissue alterations and contrast agent kinetics. It is also possible to detect diffuse myocardial processes such as interstitial fibrosis or edema ^1-6. Furthermore, from a single set of image data, it is possible to examine heart function and myocardial scarring by generating cine and inversion recovery-prepared late gadolinium enhancement-type MR images ¹.The presented video shows step-by-step the procedures to perform small animal CMR imaging. Here it is presented with a healthy Sprague-Dawley rat, however naturally it can be extended to different cardiac small animal models.     

Comparison between Different Methods for Biomechanical Assessment of Ex Vivo Fracture Callus Stiffness in Small Animal Bone Healing Studies

For ex vivo measurements of fracture callus stiffness in small animals, different test methods, such as torsion or bending tests, are established. Each method provides advantages and disadvantages, and it is still debated which of those is most sensitive to experimental conditions (i.e. specimen alignment, directional dependency, asymmetric behavior). The aim of this study was to experimentally compare six different testing methods regarding their robustness against experimental errors. Therefore, standardized specimens were created by selective laser sintering (SLS), mimicking size, directional behavior, and embedding variations of respective rat long bone specimens. For the latter, five different geometries were created which show shifted or tilted specimen alignments. The mechanical tests included three-point bending, four-point bending, cantilever bending, axial compression, constrained torsion, and unconstrained torsion. All three different bending tests showed the same principal behavior. They were highly dependent on the rotational direction of the maximum fracture callus expansion relative to the loading direction (creating experimental errors of more than 60%), however small angular deviations (<15°) were negligible. Differences in the experimental results between the bending tests originate in their respective location of maximal bending moment induction. Compared to four-point bending, three-point bending is easier to apply on small rat and mouse bones under realistic testing conditions and yields robust measurements, provided low variation of the callus shape among the tested specimens. Axial compressive testing was highly sensitive to embedding variations, and therefore cannot be recommended. Although it is experimentally difficult to realize, unconstrained torsion testing was found to be the most robust method, since it was independent of both rotational alignment and embedding uncertainties. Constrained torsional testing showed small errors (up to 16.8%, compared to corresponding alignment under unconstrained torsion) due to a parallel offset between the specimens’ axis of gravity and the torsional axis of rotation.     

New Approach of Plasmonically Induced Reflectance in a Planar Metamaterial for Plasmonic Sensing Applications

We theoretically demonstrate and investigate plasmonically induced reflectance (PIR) in a new planar metamaterial with two completely different approaches. Here, we not only show that broken symmetry is a general strategy to create electromagnetically induced reflectance (EIR)-like effect but also demonstrate that the nanoplasmonic EIR can be realized even without broken symmetry via the excitation of the higher-order plasmonic modes in the same designed planar metamaterial. In nanophotonics, plasmonic structures enable large field strengths within small mode volumes. Therefore, combining EIR with nanoplasmonics would open up the way toward ultracompact sensors with extremely high sensitivity. In the second approach of creating the PIR of our proposed nanostructure, the restrictions on size are partially relaxed, making fabrication much easier. Their interactions and coupling between plasmonic modes are investigated in detail by analyzing field distributions and spectral responses. Also, we show that the PIR frequency position depended very sensitively on the dielectric surrounding. Furthermore, the narrow and fully modulated PIR features due to the extraordinary reduction of damping may serve for designing novel devices in the field of chemical and biomedical sensing.

     

Staining methods for Calcium—a Comparison Based on Reactions Shown by Cardiac Calcinosis in DBA Mice

Spontaneous calcification, which occurs frequently in hearts of mice of the DBA strain, has been used to compare effectiveness of calcium stains. Three fixatives (1) 80% ethanol, (2) 10% formalin and 3.5% acetic acid in 95% ethanol (modified Lavdowsky's) and (3) a 1:1 mixture of concentrated formalin and absolute ethanol were tested for their subsequent effects on staining. Stains for Ca included purpurin, von Kossa's, phthalocyanin, and glyoxal bis(2-hydroxyanil). These, with appropriate counterstaining, were compared among each other, with hematoxylin-eosin (H-E), and with the periodic acid-Schiff (PAS) reaction. Fixatives (1) and (3) did not affect results appreciably, but the von Kossa technic was unsatisfactory after (2). All stain demonstrated sites of Ca deposits, but purpurin and von Kossa's gave greatest sharpness of definition and were the simplest to perform. H-E and PAS with Alcian blue showed the same Ca sites in addition to details of the surrounding tissue.     

Performance of Droplet Digital PCR in Non-Invasive Fetal RHD Genotyping - Comparison with a Routine Real-Time PCR Based Approach

Detection and characterization of circulating cell-free fetal DNA (cffDNA) from maternal circulation requires an extremely sensitive and precise method due to very low cffDNA concentration. In our study, droplet digital PCR (ddPCR) was implemented for fetal RHD genotyping from maternal plasma to compare this new quantification alternative with real-time PCR (qPCR) as a golden standard for quantitative analysis of cffDNA. In the first stage of study, a DNA quantification standard was used. Clinical samples, including 10 non-pregnant and 35 pregnant women, were analyzed as a next step. Both methods’ performance parameters—standard curve linearity, detection limit and measurement precision—were evaluated. ddPCR in comparison with qPCR has demonstrated sufficient sensitivity for analysing of cffDNA and determination of fetal RhD status from maternal circulation, results of both methods strongly correlated. Despite the more demanding workflow, ddPCR was found to be slightly more precise technology, as evaluated using quantitative standard. Regarding the clinical samples, the precision of both methods equalized with decreasing concentrations of tested DNA samples. In case of cffDNA with very low concentrations, variance parameters of both techniques were comparable. Detected levels of fetal cfDNA in maternal plasma were slightly higher than expected and correlated significantly with gestational age as measured by both methods (ddPCR r = 0.459; qPCR r = 0.438).     

A Model for Adjusting for Nonignorable Verification Bias in Estimation of the ROC Curve and Its Area with Likelihood‐Based Approach

Summary In estimation of the ROC curve, when the true disease status is subject to nonignorable missingness, the observed likelihood involves the missing mechanism given by a selection model. In this article, we proposed a likelihood‐based approach to estimate the ROC curve and the area under the ROC curve when the verification bias is nonignorable. We specified a parametric disease model in order to make the nonignorable selection model identifiable. With the estimated verification and disease probabilities, we constructed four types of empirical estimates of the ROC curve and its area based on imputation and reweighting methods. In practice, a reasonably large sample size is required to estimate the nonignorable selection model in our settings. Simulation studies showed that all four estimators of ROC area performed well, and imputation estimators were generally more efficient than the other estimators proposed. We applied the proposed method to a data set from research in Alzheimer's disease.     

Estimation of Incremental Unit Risks for Inhaled Nickel Subsulfide and Nickel Oxide,Based on a Combination of Human and Animal Data

Both animal and human exposure–response data are used to estimate the incremental unit risks (IURs) of lung cancer for Ni₃S₂ and NiO, which are constituent compounds of nickel refinery dust. The animal experiments are used to determine relative lung cancer potencies for Ni₃S₂ and NiO, and the human epidemiological data are used as the best estimate of overall risk for refinery dust exposure. The animal data for Ni₃S₂ are fit with a linear model, while the nonlinear animal data for NiO are fit with a Weibull model. The lower 95% confidence limit at a 5% point of departure is used to calculate a tumorigenic potency ratio of Ni₃S₂ to NiO of 5.6. Analyses of actual nickel refinery dust indicate the weight% of Ni₃S₂ and NiO to be 82% and 9%, respectively. This information is used with the previously determined IUR for nickel refinery dust to calculate IUR_NiO = 5.1 × 10^?5 (μg Ni/m³)^?1 and IUR_Ni3S2 = 2.9 × 10^?4 (μg Ni/m³)^?1.     

Population-Based Resequencing of APOA1 in 10,330 Individuals: Spectrum of Genetic Variation,Phenotype, and Comparison with Extreme Phenotype Approach

Rare genetic variants, identified by in-detail resequencing of loci, may contribute to complex traits. We used the apolipoprotein A-I gene (APOA1), a major high-density lipoprotein (HDL) gene, and population-based resequencing to determine the spectrum of genetic variants, the phenotypic characteristics of these variants, and how these results compared with results based on resequencing only the extremes of the apolipoprotein A-I (apoA-I) distribution. First, we resequenced APOA1 in 10,330 population-based participants in the Copenhagen City Heart Study. The spectrum and distribution of genetic variants was determined as a function of the number of individuals resequenced. Second, apoA-I and HDL cholesterol phenotypes were determined for nonsynonymous (NS) and synonymous (S) variants and were validated in the Copenhagen General Population Study (n = 45,239). Third, observed phenotypes were compared with those predicted using an extreme phenotype approach based on the apoA-I distribution. Our results are as follows: First, population-based resequencing of APOA1 identified 40 variants of which only 7 (18%) had minor allele frequencies >1%, and most were exceedingly rare. Second, 0.27% of individuals in the general population were heterozygous for NS variants which were associated with substantial reductions in apoA-I (up to 39 mg/dL) and/or HDL cholesterol (up to 0.9 mmol/L) and, surprisingly, 0.41% were heterozygous for variants predisposing to amyloidosis. NS variants associated with a hazard ratio of 1.72 (1.09–2.70) for myocardial infarction (MI), largely driven by A164S, a variant not associated with apoA-I or HDL cholesterol levels. Third, using the extreme apoA-I phenotype approach, NS variants correctly predicted the apoA-I phenotype observed in the population-based resequencing. However, using the extreme approach, between 79% (screening 0–1^st percentile) and 21% (screening 0–20^th percentile) of all variants were not identified; among these were variants previously associated with amyloidosis. Population-based resequencing of APOA1 identified a majority of rare NS variants associated with reduced apoA-1 and HDL cholesterol levels and/or predisposing to amyloidosis. In addition, NS variants associated with increased risk of MI.     

Gated F-18 FDG PET for Assessment of Left Ventricular Volumes and Ejection Fraction Using QGS and 4D-MSPECT in Patients with Heart Failure: A Comparison with Cardiac MRI

Purpose

Ventricular function is a powerful predictor of survival in patients with heart failure (HF). However, studies characterizing gated F-18 FDG PET for the assessment of the cardiac function are rare. The aim of this study was to prospectively compare gated F-18 FDG PET and cardiac MRI for the assessment of ventricular volume and ejection fraction (EF) in patients with HF.

Methods

Eighty-nine patients with diagnosed HF who underwent both gated F-18 FDG PET/CT and cardiac MRI within 3 days were included in the analysis. Left ventricular (LV) end-diastolic volume (EDV), end-systolic volume (ESV), and EF were obtained from gated F-18 FDG PET/CT using the Quantitative Gated SPECT (QGS) and 4D-MSPECT software.

Results

LV EDV and LV ESV measured by QGS were significantly lower than those measured by cardiac MRI (both P<0.0001). In contrast, the corresponding values for LV EDV for 4D-MSPECT were comparable, and LV ESV was underestimated with borderline significance compared with cardiac MRI (P = 0.047). LV EF measured by QGS and cardiac MRI showed no significant differences, whereas the corresponding values for 4D-MSPECT were lower than for cardiac MRI (P<0.0001). The correlations of LV EDV, LV ESV, and LV EF between gated F-18 FDG PET/CT and cardiac MRI were excellent for both QGS (r = 0.92, 0.92, and 0.76, respectively) and 4D-MSPECT (r = 0.93, 0.94, and 0.75, respectively). However, Bland-Altman analysis revealed a significant systemic error, where LV EDV (−27.9±37.0 mL) and ESV (−18.6±33.8 mL) were underestimated by QGS.

Conclusion

Despite the observation that gated F-18 FDG PET/CT were well correlated with cardiac MRI for assessing LV function, variation was observed between the two imaging modalities, and so these imaging techniques should not be used interchangeably.     

Spatial Distribution of Soil Organic Carbon and Total Nitrogen Based on GIS and Geostatistics in a Small Watershed in a Hilly Area of Northern China

The spatial variability of soil organic carbon (SOC) and total nitrogen (STN) levels is important in both global carbon-nitrogen cycle and climate change research. There has been little research on the spatial distribution of SOC and STN at the watershed scale based on geographic information systems (GIS) and geostatistics. Ninety-seven soil samples taken at depths of 0–20 cm were collected during October 2010 and 2011 from the Matiyu small watershed (4.2 km²) of a hilly area in Shandong Province, northern China. The impacts of different land use types, elevation, vegetation coverage and other factors on SOC and STN spatial distributions were examined using GIS and a geostatistical method, regression-kriging. The results show that the concentration variations of SOC and STN in the Matiyu small watershed were moderate variation based on the mean, median, minimum and maximum, and the coefficients of variation (CV). Residual values of SOC and STN had moderate spatial autocorrelations, and the Nugget/Sill were 0.2% and 0.1%, respectively. Distribution maps of regression-kriging revealed that both SOC and STN concentrations in the Matiyu watershed decreased from southeast to northwest. This result was similar to the watershed DEM trend and significantly correlated with land use type, elevation and aspect. SOC and STN predictions with the regression-kriging method were more accurate than those obtained using ordinary kriging. This research indicates that geostatistical characteristics of SOC and STN concentrations in the watershed were closely related to both land-use type and spatial topographic structure and that regression-kriging is suitable for investigating the spatial distributions of SOC and STN in the complex topography of the watershed.     

Transferability of Material Composition Indicators for Residential Buildings: A Conceptual Approach Based on a German‐Japanese Comparison

Most anthropogenic material stocks and flows are associated with the building sector. Several recent studies have developed material composition indicators (MCIs) suitable for calculating material stocks and flows of the building sector using bottom‐up approaches, which hold great potential to provide information to support resource efficiency policies. A major limitation is the lack of country‐specific MCIs. This study aims to introduce a concept for a better transferability of MCI across different contexts by proposing requirements for defining MCIs and to discuss options and limits of the transferability. We take existing MCIs for residential buildings in Germany and Japan as case studies and make them comparable by applying harmonization methods. Based on that, similarities and differences are systematically identified and discussed, considering their socioeconomic, cultural, technical, and environmental factors. Our results indicate significant limitations to the transferability of MCIs for detached houses, while bigger apartment complexes show greater homogeneity despite the very different environments in which they are constructed. This indicates that while it is possible to assume foreign MCIs as plausible for large constructions, local coefficients need to be estimated for smaller single‐family homes.     

Comparison of Methods to Account for Relatedness in Genome-Wide Association Studies with Family-Based Data

Approaches based on linear mixed models (LMMs) have recently gained popularity for modelling population substructure and relatedness in genome-wide association studies. In the last few years, a bewildering variety of different LMM methods/software packages have been developed, but it is not always clear how (or indeed whether) any newly-proposed method differs from previously-proposed implementations. Here we compare the performance of several LMM approaches (and software implementations, including EMMAX, GenABEL, FaST-LMM, Mendel, GEMMA and MMM) via their application to a genome-wide association study of visceral leishmaniasis in 348 Brazilian families comprising 3626 individuals (1972 genotyped). The implementations differ in precise details of methodology implemented and through various user-chosen options such as the method and number of SNPs used to estimate the kinship (relatedness) matrix. We investigate sensitivity to these choices and the success (or otherwise) of the approaches in controlling the overall genome-wide error-rate for both real and simulated phenotypes. We compare the LMM results to those obtained using traditional family-based association tests (based on transmission of alleles within pedigrees) and to alternative approaches implemented in the software packages MQLS, ROADTRIPS and MASTOR. We find strong concordance between the results from different LMM approaches, and all are successful in controlling the genome-wide error rate (except for some approaches when applied naively to longitudinal data with many repeated measures). We also find high correlation between LMMs and alternative approaches (apart from transmission-based approaches when applied to SNPs with small or non-existent effects). We conclude that LMM approaches perform well in comparison to competing approaches. Given their strong concordance, in most applications, the choice of precise LMM implementation cannot be based on power/type I error considerations but must instead be based on considerations such as speed and ease-of-use.