Johan Kihlberg

Rapid T1 quantification based on 3D phase sensitive inversion recovery

BackgroundIn Contrast Enhanced Magnetic Resonance Imaging fibrotic myocardium can be distinguished from healthy tissue using the difference in the longitudinal T1 relaxation after administration of Gadolinium, the so-called Late Gd Enhancement. The purpose of this work was to measure the myocardial absolute T1 post-Gd from a single breath-hold 3D Phase Sensitivity Inversion Recovery sequence (PSIR). Equations were derived to take the acquisition and saturation effects on the magnetization into account.MethodsThe accuracy of the method was investigated on phantoms and using simulations. The method was applied to a group of patients with suspected myocardial infarction where the absolute difference in relaxation of healthy and fibrotic myocardium was measured at about 15 minutes post-contrast. The evolution of the absolute R1 relaxation rate (1/T1) over time after contrast injection was followed for one patient and compared to T1 mapping using Look-Locker. Based on the T1 maps synthetic LGE images were reconstructed and compared to the conventional LGE images.ResultsThe fitting algorithm is robust against variation in acquisition flip angle, the inversion delay time and cardiac arrhythmia. The observed relaxation rate of the myocardium is 1.2 s-1, increasing to 6 - 7 s-1 after contrast injection and decreasing to 2 - 2.5 s-1 for healthy myocardium and to 3.5 - 4 s-1 for fibrotic myocardium. Synthesized images based on the T1 maps correspond very well to actual LGE images.ConclusionsThe method provides a robust quantification of post-Gd T1 relaxation for a complete cardiac volume within a single breath-hold.

Effects of moderate red wine consumption on liver fat and blood lipids: a prospective randomized study

Abstract Background: There have been no human prospective randomized studies of the amount of alcohol that can induce hepatic steatosis. Methods: Thirty-two healthy women and twelve healthy men (34 ± 9 years of age) were randomized to consume 150 ml of red wine/day for women (16 g ethanol/day) or double that amount for men (33 g ethanol/day), or to alcohol abstention for 90 days. Participants underwent proton-nuclear magnetic-resonance spectroscopy for measurement of hepatic triglyceride content (HTGC). Blood samples for assessment of cardiovascular risk were drawn before and after the intervention. Results: After exclusion of three subjects with steatosis at baseline a trend towards increased HTGC was apparent for red wine (before median: 1.1%, range 0.2–3.9%, after median: 1.1%, range 0.5–5.2 %, P = 0.059) a difference that was statistically significant compared with abstainers (p = 0.02). However, no subject developed hepatic steatosis. Low–density lipoprotein (LDL)-cholesterol was lowered by red wine (–0.3 mmol/l, SE –0.1, 95% CI –0.6 to –0.04). Conclusions: Moderate consumption of red wine during three months increased HTGC in subjects without steatosis at baseline. However, since not a single participant developed steatosis we suggest that the threshold of alcohol consumption to define nonalcoholic fatty liver disease should not be lower than the amount in our study. Trial registration: ClinicalTrials.gov identifier: NCT00954434.

Clinical experience of strain imaging using DENSE for detecting infarcted cardiac segments.

BackgroundWe hypothesised that myocardial deformation determined with magnetic resonance imaging (MRI) will detect myocardial scar.MethodsDisplacement Encoding with Stimulated Echoes (DENSE) was used to calculate left ventricular strain in 125 patients (29 women and 96 men) with suspected coronary artery disease. The patients also underwent cine imaging and late gadolinium enhancement. 57 patients had a scar area >1 % in at least one segment, 23 were considered free from coronary artery disease (control group) and 45 had pathological findings but no scar (mixed group). Peak strain was calculated in eight combinations: radial and circumferential strain in transmural, subendocardial and epicardial layers derived from short axis acquisition, and transmural longitudinal and radial strain derived from long axis acquisitions. In addition, the difference between strain in affected segments and reference segments, “differential strain”, from the control group was analysed.ResultsIn receiver-operator-characteristic analysis for the detection of 50 % transmurality, circumferential strain performed best with area-under-curve (AUC) of 0.94. Using a cut-off value of -17 %, sensitivity was 95 % at a specificity of 80 %. AUC did not further improve with differential strain. There were significant differences between the control group and global strain circumferential direction (-17 % versus -12 %) and in the longitudinal direction (-13 % versus -10 %). Interobserver and scan-rescan reproducibility was high with an intraclass correlation coefficient (ICC) >0.93.ConclusionsDENSE-derived circumferential strain may be used for the detection of myocardial segments with >50 % scar area. The repeatability of strain is satisfactory. DENSE-derived global strain agrees with other global measures of left ventricular ejection fraction.

Characterization of shear-sensitive genes in the normal rat aorta identifies Hand2 as a major flow-responsive transcription factor.

Objective Shear forces play a key role in the maintenance of vessel wall integrity. Current understanding regarding shear-dependent gene expression is mainly based on in vitro or in vivo observations with experimentally deranged shear, hence reflecting acute molecular events in relation to flow. Our objective was to combine computational fluid dynamic (CFD) simulations with global microarray analysis to study flow-dependent vessel wall biology in the aortic wall under physiological conditions. Methods and Results Male Wistar rats were used. Animal-specific wall shear stress (WSS) magnitude and vector direction were estimated using CFD based on aortic geometry and flow information acquired by magnetic resonance imaging. Two distinct flow pattern regions were identified in the normal rat aortic arch; the distal part of the lesser curvature being exposed to low WSS and a non-uniform vector direction, and a region along the greater curvature being subjected to markedly higher levels of WSS and a uniform vector direction. Microarray analysis identified numerous novel mechanosensitive genes, including Trpc4 and Fgf12, and confirmed well-known ones, e.g. Klf2 and Nrf2. Gene ontology analysis revealed an over-representation of genes involved in transcriptional regulation. The most differentially expressed gene, Hand2, is a transcription factor previously shown to be involved in extracellular matrix remodeling. HAND2 protein was endothelial specific and showed higher expression in the regions exposed to low WSS with disturbed flow. Conclusions Microarray analysis validated the CFD-defined WSS regions in the rat aortic arch, and identified numerous novel shear-sensitive genes. Defining the functional importance of these genes in relation to atherosusceptibility may provide important insight into the understanding of vascular pathology.

Renal artery stenosis: Extracting quantitative parameters with a mathematical model fitted to magnetic resonance blood flow data

To investigate the feasibility of quantitative parameter extraction from a mathematical model fitted to renal artery magnetic resonance flow data.

Dense breast tissue in postmenopausal women is associated with a pro-inflammatory microenvironment in vivo.

ABSTRACT Inflammation is one of the hallmarks of carcinogenesis. High mammographic density has been associated with increased risk of breast cancer but the mechanisms behind are poorly understood. We evaluated whether breasts with different mammographic densities exhibited differences in the inflammatory microenvironment. Postmenopausal women attending the mammography-screening program were assessed having extreme dense, n = 20, or entirely fatty breasts (nondense), n = 19, on their regular mammograms. Thereafter, the women were invited for magnetic resonance imaging (MRI), microdialysis for the collection of extracellular molecules in situ and a core tissue biopsy for research purposes. On the MRI, lean tissue fraction (LTF) was calculated for a continuous measurement of breast density. LTF confirmed the selection from the mammograms and gave a continuous measurement of breast density. Microdialysis revealed significantly increased extracellular in vivo levels of IL-6, IL-8, vascular endothelial growth factor, and CCL5 in dense breast tissue as compared with nondense breasts. Moreover, the ratio IL-1Ra/IL-1β was decreased in dense breasts. No differences were found in levels of IL-1β, IL-1Ra, CCL2, leptin, adiponectin, or leptin:adiponectin ratio between the two breast tissue types. Significant positive correlations between LTF and the pro-inflammatory cytokines as well as between the cytokines were detected. Stainings of the core biopsies exhibited increased levels of immune cells in dense breast tissue. Our data show that dense breast tissue in postmenopausal women is associated with a pro-inflammatory microenvironment and, if confirmed in a larger cohort, suggests novel targets for prevention therapies for women with dense breast tissue.

Quantitative fat and R2* mapping in vivo to measure lipid-rich necrotic core and intraplaque hemorrhage in carotid atherosclerosis

The aim of this work was to quantify the extent of lipid‐rich necrotic core (LRNC) and intraplaque hemorrhage (IPH) in atherosclerotic plaques.

Comparing hepatic 2D and 3D magnetic resonance elastography methods in a clinical setting – Initial experiences

Purpose Continuous monitoring of liver fibrosis progression in patients is not feasible with the current diagnostic golden standard (needle biopsy). Recently, magnetic resonance elastography (MRE) has emerged as a promising method for such continuous monitoring. Since there are different MRE methods that could be used in a clinical setting there is a need to investigate whether measurements produced by these MRE methods are comparable. Hence, the purpose of this pilot study was to evaluate whether the measurements of the viscoelastic properties produced by 2D (stiffness) and 3D (elasticity and ‘Gabs,Elastic’) MRE are comparable. Materials and methods Seven patients with diffuse or suspect diffuse liver disease were examined in the same day with the two MRE methods. 2D MRE was performed using an acoustic passive transducer, with a 1.5 T GE 450 W MR system. 3D MRE was performed using an electromagnetic active transducer, with a 1.5 T Philips Achieva MR system. Finally, mean viscoelastic values were extracted from the same anatomical region for both methods by an experienced radiologist. Results Stiffness correlated well with the elasticity, R2 = 0.96 (P < 0.001; slope = 1.08, intercept = 0.61 kPa), as well as with ‘Gabs,Elastic’ R2 = 0.96 (P < 0.001; slope = 0.95, intercept = 0.28 kPa). Conclusion This pilot study shows that different MRE methods can produce comparable measurements of the viscoelastic properties of the liver. The existence of such comparable measurements is important, both from a clinical as well as a research perspective, since it allows for equipment-independent monitoring of disease progression.

Segmental variation of myocardial deformation in patients with suspected ischemic heart disease

Summary The aim of this study is to investigate if the use of individual, per segment reference values for cardiac strain allows for improved discrimination of pathological deformation. In a cohort of patients with a high likelihood of ischemic heart disease, preliminary results within the subgroup of patients without pathological findings on cardiac MRI suggest a spatial dependency of strain. Background In addition to perfusion and viability, systolic myocardial function constitutes one of the cornerstones in the evaluation of ischemic patients. Technical achievements have improved the accuracy of the quantitative assessment of myocardial function, allowing for better discrimination between healthy and diseased myocardium. These advances cannot be fully exploited without knowledge of the spatial dependency and individual variance of deformation in health and disease. Methods In an ongoing study, a large cohort of patients with moderate chest pain and a high likelihood of coronary artery disease undergo cardiac MRI including cine loops for wall motion, perfusion at rest and during adenosine stress, acquisition of myocardial deformation with displacement encoding with stimulated echo (DENSE), and late gadolinium enhancement to demonstrate scar tissue. In this preliminary study, patient demonstrating maintained perfusion, normal wall motion, and no signs of scar at late gadolinium enhancement were selected for further evaluation. Regional deformation acquired with DENSE was evaluated in terms of radial and circumferential strains. All measurements were reported according to the seventeen segment model of the AHA. The apical cap was excluded from the quantification of regional deformation. Results Preliminary results for radia la nd circumferential strain for the 11 patients without pathological findings are presented in the Figure 1. The figure demonstrates the mean and standard deviation of the strain for the individual myocardial segments. Strain in the basal segments appears to be more spatially dependent than strain in the mid-cavity segments. The strain in the apical segments showed a larger variation between the subjects. Conclusions

Practical Application of DENSE in Ischemic Heart Disease.

Background In clinical practice, perfusion, viability and systolic myocardial function are fundamental to the evaluation of ischemic patients. Deformation of muscle expresses active contraction and can be represented by strain in various directions. Improvements to the “DENSE” technique, “Displacement Encoding with Stimulated Echoes”, have shown high accuracy warranting its application to clinical patients. The purpose of this study was to explore potential differences in myocardial deformation determined in patients with various extent of myocardial scar as well as in the corresponding segments of coronary patients without scar.