Early detection of heart function abnormality by native T1:a comparison of two T1 quantification methods

Objective To compare the robustness of native T1 mapping using mean and median pixel-wise quantification methods. Methods Fifty-seven consecutive patients without overt signs of heart failure were examined in clinical routine for suspicion of cardiomyopathy. MRI included the acquisition of native T1 maps by a motion-corrected modified Look-Locker inversion recovery sequence at 1.5 T. Heart function status according to four established volumetric left ventricular (LV) cardio MRI parameter thresholds was used for retrospective separation into subgroups of normal (n = 26) or abnormal heart function (n = 31). Statistical normality of pixel-wise T1 was tested on each myocardial segment and mean and median segmental T1 values were assessed. Results Segments with normally distributed pixel-wise T1 (57/58%) showed no difference between mean and median quantification in either patient group, while differences were highly significant (p <0.001) for the respective 43/42% non-normally distributed segments. Heart function differentiation between two patient groups was significant in 14 myocardial segments (p <0.001-0.040) by median quantification compared with six (p <0.001-0.042) by using the mean. The differences by median quantification were observed between the native T1 values of the three coronary artery territories of normal heart function patients (p = 0.023) and insignificantly in the abnormal patients (p = 0.053). Conclusion Median quantification increases the robustness of myocardial native T1 definition, regardless of statistical normality of the data. Compared with the currently prevailing method of mean quantification, differentiation between LV segments and coronary artery territories is better and allows for earlier detection of heart function impairment

Genome-wide association study of frontotemporal dementia identifies a <i>C9ORF72</i> haplotype with a median of 12-G4C2 repeats that predisposes to pathological repeat expansions

Genetic factors play a major role in frontotemporal dementia (FTD). The majority of FTD cannot be genetically explained yet and it is likely that there are still FTD risk loci to be discovered. Common variants have been identified with genome-wide association studies (GWAS), but these studies have not systematically searched for rare variants. To identify rare and new common variant FTD risk loci and provide more insight into the heritability of C9ORF72-related FTD, we performed a GWAS consisting of 354 FTD patients (including and excluding N = 28 pathological repeat carriers) and 4209 control subjects. The Haplotype Reference Consortium was used as reference panel, allowing for the imputation of rare genetic variants. Two rare genetic variants nearby C9ORF72 were strongly associated with FTD in the discovery (rs147211831: OR = 4.8, P = 9.2 × 10−9, rs117204439: OR = 4.9, P = 6.0 × 10−9) and replication analysis (P &lt; 1.1 × 10−3). These variants also significantly associated with amyotrophic lateral sclerosis in a publicly available dataset. Using haplotype analyses in 1200 individuals, we showed that these variants tag a sub-haplotype of the founder haplotype of the repeat expansion that was previously found to be present in virtually all pathological C9ORF72 G4C2 repeat lengths. This new risk haplotype was 10 times more likely to contain a C9ORF72 pathological repeat length compared to founder haplotypes without one of the two risk variants (~22% versus ~2%; P = 7.70 × 10−58). In haplotypes without a pathologic expansion, the founder risk haplotype had a higher number of repeats (median = 12 repeats) compared to the founder haplotype without the risk variants (median = 8 repeats) (P = 2.05 × 10−260). In conclusion, the identified risk haplotype, which is carried by ~4% of all individuals, is a major risk factor for pathological repeat lengths of C9ORF72 G4C2. These findings strongly indicate that longer C9ORF72 repeats are unstable and more likely to convert to germline pathological C9ORF72 repeat expansions.</p

Correction to: A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity

The IPDGC (The International Parkinson Disease Genomics Consortium) and EADB (Alzheimer Disease European DNA biobank) are listed correctly as an author to the article, however, they were incorrectly listed more than once

Correction to: A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer’s disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity

The IPDGC (The International Parkinson Disease Genomics Consortium) and EADB (Alzheimer Disease European DNA biobank) are listed correctly as an author to the article, however, they were incorrectly listed more than once

Semi-automated myocardial segmentation of bright blood multi-gradient echo images improves reproducibility of myocardial contours and T2* determination

OBJECTIVES: Early detection of iron loading is affected by the reproducibility of myocardial contour assessment. A novel semi-automatic myocardial segmentation method is presented on contrast-optimized composite images and compared to the results of manual drawing. MATERIALS AND METHODS: Fifty-one short-axis slices at basal, mid-ventricular and apical locations from 17 patients were acquired by bright blood multi-gradient echo MRI. Four observers produced semi-automatic and manual myocardial contours on contrast-optimized composite images. The semi-automatic segmentation method relies on vector field convolution active contours to generate the endocardial contour. After creating radial pixel clusters on the myocardial wall, a combination of pixel-wise coefficient of variance (CoV) assessment and k-means clustering establishes the epicardial contour for each segment. RESULTS: Compared to manual drawing, semi-automatic myocardial segmentation lowers the variability of T2* quantification within and between observers (CoV of 12.05 vs. 13.86% and 14.43 vs. 16.01%) by improving contour reproducibility (P < 0.001). In the presence of iron loading, semi-automatic segmentation also lowers the T2* variability within and between observers (CoV of 13.14 vs. 15.19% and 15.91 vs. 17.28%). CONCLUSION: Application of semi-automatic myocardial segmentation on contrast-optimized composite images improves the reproducibility of T2* quantification

Genome-wide association study of frontotemporal dementia identifies a C9ORF72 haplotype with a median of 12-G4C2 repeats that predisposes to pathological repeat expansions

Genetic factors play a major role in frontotemporal dementia (FTD). The majority of FTD cannot be genetically explained yet and it is likely that there are still FTD risk loci to be discovered. Common variants have been identified with genome-wide association studies (GWAS), but these studies have not systematically searched for rare variants. To identify rare and new common variant FTD risk loci and provide more insight into the heritability of C9ORF72-related FTD, we performed a GWAS consisting of 354 FTD patients (including and excluding N = 28 pathological repeat carriers) and 4209 control subjects. The Haplotype Reference Consortium was used as reference panel, allowing for the imputation of rare genetic variants. Two rare genetic variants nearby C9ORF72 were strongly associated with FTD in the discovery (rs147211831: OR = 4.8, P = 9.2 × 10 −9, rs117204439: OR = 4.9, P = 6.0 × 10 −9) and replication analysis (P < 1.1 × 10 −3). These variants also significantly associated with amyotrophic lateral sclerosis in a publicly available dataset. Using haplotype analyses in 1200 individuals, we showed that these variants tag a sub-haplotype of the founder haplotype of the repeat expansion that was previously found to be present in virtually all pathological C9ORF72 G 4C 2 repeat lengths. This new risk haplotype was 10 times more likely to contain a C9ORF72 pathological repeat length compared to founder haplotypes without one of the two risk variants (~22% versus ~2%; P = 7.70 × 10 −58). In haplotypes without a pathologic expansion, the founder risk haplotype had a higher number of repeats (median = 12 repeats) compared to the founder haplotype without the risk variants (median = 8 repeats) (P = 2.05 × 10 −260). In conclusion, the identified risk haplotype, which is carried by ~4% of all individuals, is a major risk factor for pathological repeat lengths of C9ORF72 G 4C 2. These findings strongly indicate that longer C9ORF72 repeats are unstable and more likely to convert to germline pathological C9ORF72 repeat expansions