Background: Despite advancements in percutaneous coronary intervention, a significant proportion of ST-elevation myocardial infarction (STEMI) survivors develop long-term adverse left ventricular ... Show moreBackground: Despite advancements in percutaneous coronary intervention, a significant proportion of ST-elevation myocardial infarction (STEMI) survivors develop long-term adverse left ventricular (LV) remodelling, which is associated with poor prognosis. Adverse remodelling is difficult to predict, however four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) can measure various aspects of LV intra-cavity flow beyond LV ejection fraction and is well equipped for exploring the underlying mechanical processes driving remodelling. The aim for this study was to compare acute 4D flow CMR parameters between patients who develop adverse remodelling with patients who do not. Methods: Fifty prospective 'first-event' STEMI patients underwent CMR 5 days post-reperfusion, which included cine-imaging, and 4D flow for assessing in-plane kinetic energy (KE), residual volume, peak-E and peak-A wave KE (indexed for LV end-diastolic volume [LVEDV]). All subjects underwent follow-up cine CMR imaging at 12 months to identify adverse remodelling (defined as 20% increase in LVEDV from baseline). Quantitative variables were compared using unpaired student's t-test. Tests were deemed statistically significant when p < 0.05. Results: Patients who developed adverse LV remodelling by 12 months had significantly higher in-plane KE (54 +/- 12 vs 42 +/- 10%, p = 0.02), decreased proportion of direct flow (27 +/- 9% vs 11 +/- 4%, p < 0.01), increased proportion of delayed ejection flow (22 +/- 9% vs 12 +/- 2, p < 0.01) and increased proportion of residual volume after 2 consecutive cardiac cycles (64 +/- 14 vs 34 +/- 14%, p < 0.01), in their acute scan. Conclusion: Following STEMI, increased in-plane KE, reduced direct flow and increased residual volume in the acute scan were all associated with adverse LV remodelling at 12 months. Our results highlight the clinical utility of acute 4D flow in prognostic stratification in patients following myocardial infarction. Show less
Ben-Arzi, H.; A. das; Kelly, C.; Geest, R.J. van der; Plein, S.; Dall'Armellina, E. 2021
Background Four-dimensional (4D) flow cardiac magnetic resonance (cardiac MR) imaging provides quantification of intracavity left ventricular (LV) flow kinetic energy (KE) parameters in three... Show moreBackground Four-dimensional (4D) flow cardiac magnetic resonance (cardiac MR) imaging provides quantification of intracavity left ventricular (LV) flow kinetic energy (KE) parameters in three dimensions. ST-elevation myocardial infarction (STEMI) patients have been shown to have altered intracardiac blood flow compared to controls; however, how 4D flow parameters change over time has not been explored previously. Purpose Measure longitudinal changes in intraventricular flow post-STEMI and ascertain its predictive relevance of long-term cardiac remodeling. Study Type Prospective. Population Thirty-five STEMI patients (M:F = 26:9, aged 56 +/- 9 years). Field Strength/Sequence A 3 T/3D EPI-based, fast field echo (FFE) free-breathing 4D-flow sequence with retrospective cardiac gating. Assessment Serial imaging at 3-7 days (V1), 3-months (V2), and 12-months (V3) post-STEMI, including the following protocol: functional imaging for measuring volumes and 4D-flow for calculating parameters including systolic and peakE-wave LVKE, normalized to end-diastolic volume (iEDV) and stroke volume (iSV). Data were analyzed by H.B. (3 years experience). Patients were categorized into two groups: preserved ejection fraction (pEF, if EF > 50%) and reduced EF (rEF, if EF < 50%). Statistical Tests Independent sample t-tests were used to detect the statistical significance between any two cohorts. P < 0.05 was considered statistically significant. Results Across the cohort, systolic KEi(sv) was highest at V1 (28.0 +/- 4.4 mu J/mL). Patients with rEF retained significantly higher systolic KEi(sv) than patients with pEF at V2 (18.2 +/- 3.4 mu J/mL vs. 6.9 +/- 0.6 mu J/mL, P < 0.001) and V3 (21.6 +/- 5.1 mu J/mL vs. 7.4 +/- 0.9 mu J/mL, P < 0.001). Patients with pEF had significantly higher peakE-wave KEi(EDV) than rEF patients throughout the study (V1: 25.4 +/- 11.6 mu J/mL vs. 18.1 +/- 9.9 mu J/mL, P < 0.03, V2: 24.0 +/- 10.2 mu J/mL vs. 17.2 +/- 12.2 mu J/mL, P < 0.05, V3: 27.7 +/- 14.8 mu J/mL vs. 15.8 +/- 7.6 mu J/mL, P < 0.04). Data Conclusion Systolic KE increased acutely following MI; in patients with pEF, this decreased over 12 months, while patients with rEF, this remained raised. Compared to patients with pEF, persistently lower peakE-wave KE in rEF patients is suggestive of early and fixed impairment in diastolic function. Evidence Level 1 Technical Efficacy Stage 3 Show less
Male breast cancer (BCa) is a rare disease accounting for less than 1% of all breast cancers and 1% of all cancers in males. The clinical management is largely extrapolated from female BCa. Several... Show moreMale breast cancer (BCa) is a rare disease accounting for less than 1% of all breast cancers and 1% of all cancers in males. The clinical management is largely extrapolated from female BCa. Several multigene assays are increasingly used to guide clinical treatment decisions in female BCa, however, there are limited data on the utility of these tests in male BCa. Here we present the gene expression results of 381 M0, ER+ve, HER2-ve male BCa patients enrolled in the Part 1 {retrospective analysis) of the International Male Breast Cancer Program. Using a custom NanoString (TM) panel comprised of the genes from the commercial risk tests Prosigna (R), OncotypeDX (R), and MammaPrint (R), risk scores and intrinsic subtyping data were generated to recapitulate the commercial tests as described by us previously. We also examined the prognostic value of other risk scores such as the Genomic Grade Index (GGI), IHC4-mRNA and our prognostic 95-gene signature. In this sample set of male BCa, we demonstrated prognostic utility on univariate analysis. Across all signatures, patients whose samples were identified as low-risk experienced better outcomes than intermediate-risk, with those classed as high risk experiencing the poorest outcomes. As seen with female BCa, the concordance between tests was poor, with C-index values ranging from 40.3% to 78.2% and Kappa values ranging from 0.17 to 0.58. To our knowledge, this is the largest study of male breast cancers assayed to generate risk scores of the current commercial and academic risk tests demonstrating comparable clinical utility to female BCa. Show less
Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common... Show moreAlthough it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a priori hypotheses. Resting-state functional MRI (R-fMRI) constitutes a candidate approach capable of addressing this challenge. Imaging the brain during rest reveals large-amplitude spontaneous low-frequency (< 0.1 Hz)fluctuations in the fMRI signal that are temporally correlated across functionally related areas. Referred to as functional connectivity, these correlations yield detailed maps of complex neural systems, collectively constituting an individual's "functional connectome." Reproducibility across datasets and individuals suggests the functional connectome has a common architecture, yet each individual's functional connectome exhibits unique features, with stable, meaningful interindividual differences in connectivity patterns and strengths. Comprehensive mapping of the functional connectome, and its subsequent exploitation to discern genetic influences and brain-behavior relationships, will require multicenter collaborative datasets. Here we initiate this endeavor by gathering R-fMRI data from 1,414 volunteers collected independently at 35 international centers. We demonstrate a universal architecture of positive and negative functional connections, as well as consistent loci of inter-individual variability. Age and sex emerged as significant determinants. These results demonstrate that independent R-fMRI datasets can be aggregated and shared. High-throughput R-fMRI can provide quantitative phenotypes for molecular genetic studies and biomarkers of developmental and pathological processes in the brain. To initiate discovery science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon_1000/. Show less
