Higher resolution cine imaging with compressed sensing for accelerated clinical left ventricular evaluation.

PURPOSE: To assess the clinical feasibility of a compressed sensing cine magnetic resonance imaging (MRI) sequence of both high temporal and spatial resolution (CS_bSSFP) in comparison to a balanced steady-state free precession cine (bSSFP) sequence for reliable quantification of left ventricular (LV) volumes and mass. MATERIALS AND METHODS: Segmented MRI cine images were acquired on a 1.5T scanner in 50 patients in the LV short-axis stack orientation using a retrospectively gated conventional bSSFP sequence (generalized autocalibrating partially parallel acquisition [GRAPPA] acceleration factor 2), followed by a prospectively triggered CS_bSSFP sequence with net acceleration factor of 8. Image quality was assessed by published criteria. Comparison of sequences was made in LV volumes and mass, image quality score, quantitative regional myocardial wall motion, and imaging time using Pearson's correlation, Bland-Altman and paired 2-tailed Student's t-test. RESULTS: Differences (bSSFP minus CS_bSSFP, mean ± SD) and Pearson's correlations were 14.8 ± 16.3 (P = 0.31) and r = 0.98 (P < 0.0001) for end-diastolic volume (EDV), 8.4 ± 11.3 (P = 0.54) and r = 0.99 (P < 0.0001) for end-systolic volume (ESV), -0.4 ± 2.5 (P = 0.87) and r = 0.97 (P < 0.0001) for EF, and -0.9 ± 11.8 (P = 0.92) and r = 0.97 (P < 0.0001) for LV mass. Bland-Altman analyses [bias and (limits of agreement)] revealed strong agreement in LVEDV [8.7 ml, (-12.1, 29.6)], LVESV [4.3 ml, (-11.9, 20.6)], LVEF [-0.02%, (-5.37, 5.33)], and myocardial mass [-6.1 g, (-14.7, 26.9)]. Image quality was comparable with a similar mean score (P = 0.42), with a good correlation in image quality observed (r = 0.68, P < 0.0001). Quantitative regional myocardial wall motion demonstrated strong correlation between the sequences (r = 0.87, P < 0.0001). Imaging time was significantly shorter for the CS_bSSFP sequence (1.1 ± 0.5 versus 5.6 ± 1.6 min, P < 0.0001). CONCLUSION: The novel high-resolution cine CS_bSSFP accurately and reliably quantitates LV volumes and mass, shortens acquisition times, and is clinically feasible. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;45:1693-1699.

Validation of a proliferation-based expression signature as prognostic marker in early stage lung adenocarcinoma.

PURPOSE: New prognostic markers to guide treatment decisions in early stage non-small cell lung cancer are necessary to improve patient outcomes. In this report, we assess the utility of a predefined mRNA expression signature of cell-cycle progression genes (CCP score) to define 5-year risk of lung cancer-related death in patients with early stage lung adenocarcinoma. EXPERIMENTAL DESIGN: A CCP score was calculated from the mRNA expression levels of 31 proliferation genes in stage I and stage II tumor samples from two public microarray datasets [Director's Consortium (DC) and GSE31210]. The same gene set was tested by quantitative PCR in 381 formalin-fixed paraffin-embedded (FFPE) primary tumors. Association of the CCP score with outcome was assessed by Cox proportional hazards analysis. RESULTS: In univariate analysis, the CCP score was a strong predictor of cancer-specific survival in both the Director's Consortium cohort (P = 0.00014; HR = 2.08; 95% CI, 1.43-3.02) and GSE31210 (P = 0.0010; HR = 2.25; 95% CI, 1.42-3.56). In multivariate analysis, the CCP score remained the dominant prognostic marker in the presence of clinical variables (P = 0.0022; HR = 2.02; 95% CI, 1.29-3.17 in Director's Consortium, P = 0.0026; HR = 2.16; 95% CI, 1.32-3.53 in GSE31210). On a quantitative PCR platform, the CCP score maintained highly significant prognostic value in FFPE-derived mRNA from clinical samples in both univariate (P = 0.00033; HR = 2.10; 95% CI, 1.39-3.17) and multivariate analyses (P = 0.0071; HR = 1.92; 95% CI, 1.18-3.10). CONCLUSIONS: The CCP score is a significant predictor of lung cancer death in early stage lung adenocarcinoma treated with surgery and may be a valuable tool in selecting patients for adjuvant treatment.

TBC1D1 is a candidate for a severe obesity gene and evidence for a gene/gene interaction in obesity predisposition.

The molecular etiology of obesity predisposition is largely unknown. Here, we present evidence that genetic variation in TBC1D1 confers risk for severe obesity in females. We identified a coding variant (R125W) in TBC1D1 that segregated with the disease in 4p15-14-linked obesity pedigrees. In cases derived from pedigrees with the strongest linkage evidence, the variant was significantly associated with obesity (P=0.000007) and chromosomes carrying R125W accounted for the majority of the evidence that originally linked 4p15-14 with the disease. In addition, by selecting families that segregated R125W with obesity, we were able to generate highly significant linkage evidence for an obesity predisposition locus at 4q34-35. This result provides additional and confirming evidence that R125W affects obesity susceptibility, delimits the location of an obesity gene at 4q34-35 and identifies a gene/gene interaction that influences the risk for obesity predisposition. Finally, although the function of TBC1D1 is unknown, the protein is structurally similar to a known regulator of insulin-mediated Glut4 translocation.

Effect of cardiac motion on body surface electrocardiographic potentials: an MRI-based simulation study.

This paper describes an electrical model of cardiac ventricles incorporating real geometry and motion. The heart anatomy and its motion through the cardiac cycle are obtained from segmentations of multiple-slice MRI time sequences; the special conduction system is constructed using an automated mapping procedure from an existing static heart model. The heart model is mounted in an anatomically realistic voxel model of the human body. The cardiac electrical source and surface potentials are determined numerically using both a finite-difference scheme and a boundary-element method with the incorporation of the motion of the heart. The electrocardiograms (ECG) and body surface potential maps are calculated and compared to the static simulation in the resting heart. The simulations demonstrate that introducing motion into the cardiac model modifies the ECG signals, with the most obvious change occurring during the T-wave at peak contraction of the ventricles. Body surface potential maps differ in some local positions during the T-wave, which may be of importance to a number of cardiac models, including those incorporating inverse methods.

Modified RV short axis series--a new method for cardiac MRI measurement of right ventricular volumes.

PURPOSE: The current standard image orientation employed in the MRI assessment of right ventricular volumes uses a series of short axis cine acquisitions located with respect to a horizontal long axis view with the first slice placed across the atrio-ventricular valve plane at end diastole. Inherent inaccuracies are encountered with the use of this image orientation due to difficulty in defining the tricuspid valve and the border between atrium and ventricle on the resultant images. Our experience indicates that because the tricuspid valve is usually not in-plane in the slice the atrio-ventricular margin is difficult to distinguish. This leads to inaccuracies in measurements at the base of the RV and miscalculation of the RV volume. The purpose of this study was to assess an alternative method of image orientation aimed at increasing the accuracy of RV volume measurements using current commercially available CMRI sequences. This technique, the modified RV short axis series, is oriented to the outflow tract of the right ventricle. METHOD: We undertook a prospective study of 50 post cardiac transplant patients. A series of LV short axis multi-slice cine acquisition FIESTA images was acquired using the current standard technique. From this data set, LV and RV stroke volumes were derived on an Advantage Windows workstation using planimetry of the endocardial and epicardial borders in end systole and end diastole. Our new technique involved obtaining a set of multi-slice cine acquisition FIESTA images in a plane perpendicular to a line from the centre of the pulmonary valve to the apex of the RV. Planimetry of the RV was then performed and a stroke volume calculated using the same method of analysis. RV stroke volumes obtained from both techniques were compared with LV stroke volumes. Three operators independently derived RV data sets. RESULTS: On the images acquired with the new technique, the tricuspid valve was easier to define leading to more accurate and reproducible planimetry of ventricular borders. RV stroke volumes calculated from the new method showed better agreement with LV stroke volumes than with the current method. These results were consistent across the three operators. CONCLUSIONS: This new method improves visualisation of the tricuspid valve and makes analysis easier and less prone to operator error than the current standard technique for MRI assessment of RV volumes.

Right Ventricle Extraction by Low level and Model-based algorithm.

In this paper we present an algorithm as the combination of a low level morphological operation and model based global circular shortest path scheme to explore the segmentation of the right ventricle. Traditional morphological operations were employed to obtain the region of interest, and adjust it to generate a mask. The image cropped by the mask is then partitioned into a few overlapping regions. Global circular shortest path algorithm is then applied to extract the contour from each partition. The final step is to re-assemble the partitions to create the whole contour. The technique is deemed quite reliable and robust, as this is illustrated by a very good agreement between the extracted contour and the expert manual drawing output.

Eye shape in emmetropia and myopia.

PURPOSES: To determine axial, vertical, and horizontal eye dimensions in myopic and emmetropic eyes by using magnetic resonance imaging (MRI) and to relate these to different ocular expansion models of myopia development. METHODS: The internal length (cornea to retina), height and width (both retina to retina) were measured in emmetropic and myopic eyes (up to -12 D) of 88 participants aged 18 to 36 years. Participants were positioned supine in a clinical MRI scanner. The fixation target was imaged straight ahead of the subject by an overhead 45 degrees inclined mirror. Eye images were acquired with a 7.5-cm receive-only radio frequency surface coil. Axial (horizontal through middle of eye) and sagittal (vertical through visual axis) sections were taken with a T(1)-weighted fast spin-echo sequence. RESULTS: With an increase in myopic refractive correction, myopic eyes became much larger in all three dimensions, but more so in length (0.35 mm/D, 95% confidence interval [CI] 0.28-0.40) than in height (0.19 mm/D, 95% CI 0.09-0.29) and more so in height than in width (0.10 mm/D, 95% CI 0.01-0.20). Based on height and length dimensions, 25% and 29% of myopic eyes exclusively fitted global expansion and axial elongation models, respectively. Based on width and length dimensions, 17% and 39% of myopic eyes exclusively fitted the global expansion and axial elongation models, respectively. CONCLUSIONS: Although there are considerable individual variations, in general myopic eyes are elongated relative to emmetropic eyes, more in length than in height and even less in width. Approximately a quarter of the myopic participants fitted each of the global expansion or axial elongation model exclusively. The small proportions are due primarily to the large variability in the dimensions of emmetropic eyes.

Identification of a congenic mouse line with obesity and body length phenotypes.

Our primary objective was to discover simplified mouse models corresponding to human obesity linkages. We used the B10.UW- H3(b) we Pax1(un) a(t)/Sn (B10.UW) congenic strain, a subcongenic strain with a reduced UW strain donor region, and their C57BL/10SnJ background strain. The congenic and subcongenic UW strain donor regions are on mouse Chr 2. We measured body length [anal-nasal (AN) length], summed fat depot weights normalized for body weight (Adiposity Index, AI), and percentage of body weight that is lipid. The B10.UW congenic and subcongenic strains have significantly smaller AN lengths ( p < 0.0001) and have a significantly lower AI and percentage of body weight as fat than the background strain ( p < 0.0001). In an F(2) intercross of the congenic and background strains, AN and AI were both linked to the distal half of the donor region with LOD scores greater than 19 and 5, respectively. F(2) haplotypes identified a minimal region for AN linkage of 0.8 megabases (Mb) that is estimated to express four genes in the current Celera mouse genome assembly. We narrowed the most likely location of the obesity gene to 15 Mb whose homologous genes are all located on human Chr 20 in the region surrounding the centromere. Since a previous study identified human obesity linkage peaking near the centromere, then the B10.UW mice may exhibit obesity due to the homologous gene.

A major predisposition locus for severe obesity, at 4p15-p14.

Although the predisposition to morbid obesity is heritable, the identities of the disease-causing genes are largely unknown. Therefore, we have conducted a genomewide search with 628 markers, using multigenerational Utah pedigrees to identify genes involved in predisposition to obesity. In the genomewide search, we identified a highly significant linkage to high body-mass index in female patients, at D4S2632, with a multipoint heterogeneity LOD (HLOD) score of 6.1 and a nonparametric linkage (NPL) score of 5.3. To further delineate the linkage, we increased both the marker density around D4S2632 and the size of our pedigree data set. As a result, the linkage evidence increased to a multipoint HLOD score of 9.2 (at D4S3350) and an NPL score of 11.3. Evidence from almost half of the families in this analysis support this linkage, and therefore the gene in this region might account for a significant percentage of the genetic predisposition to severe obesity in females. However, further studies are necessary to clarify the effect that this gene has in males and in the general population.