Impact of dobutamine stress on diastolic energetic efficiency of healthy left ventricle: an kinetic energy analysis.

The total kinetic energy (KE) of blood can be decomposed into mean KE (MKE) and turbulent KE (TKE), which are associated with the phase-averaged fluid velocity field and the instantaneous velocity fluctuations, respectively. The aim of this study was to explore the effects of pharmacologically induced stress on MKE and TKE in the left ventricle (LV) in a cohort of healthy volunteers. 4D Flow MRI data were acquired in eleven subjects at rest and after dobutamine infusion, at a heart rate that was ∼60% higher than the one in rest conditions.

Pipelines and Systems for Threshold-Avoiding Quantification of LC-MS/MS Data.

The accurate processing of complex liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) data from biological samples is a major challenge for metabolomics, proteomics, and related approaches. Here, we present the pipelines and systems for threshold-avoiding quantification (PASTAQ) LC-MS/MS preprocessing toolset, which allows highly accurate quantification of data-dependent acquisition LC-MS/MS datasets. PASTAQ performs compound quantification using single-stage (MS1) data and implements novel algorithms for high-performance and accurate quantification, retention time alignment, feature detection, and linking annotations from multiple identification engines.

The human melanoma proteome atlas-Defining the molecular pathology.

The MM500 study is an initiative to map the protein levels in malignant melanoma tumor samples, focused on in-depth histopathology coupled to proteome characterization. The protein levels and localization were determined for a broad spectrum of diverse, surgically isolated melanoma tumors originating from multiple body locations. More than 15,500 proteoforms were identified by mass spectrometry, from which chromosomal and subcellular localization was annotated within both primary and metastatic melanoma.

The Human Melanoma Proteome Atlas-Complementing the melanoma transcriptome.

The MM500 meta-study aims to establish a knowledge basis of the tumor proteome to serve as a complement to genome and transcriptome studies. Somatic mutations and their effect on the transcriptome have been extensively characterized in melanoma. However, the effects of these genetic changes on the proteomic landscape and the impact on cellular processes in melanoma remain poorly understood.

MSIWarp: A General Approach to Mass Alignment in Mass Spectrometry Imaging.

Mass spectrometry imaging (MSI) is a technique that provides comprehensive molecular information with high spatial resolution from tissue. Today, there is a strong push toward sharing data sets through public repositories in many research fields where MSI is commonly applied; yet, there is no standardized protocol for analyzing these data sets in a reproducible manner. Shifts in the mass-to-charge ratio (/) of molecular peaks present a major obstacle that can make it impossible to distinguish one compound from another.

The Hidden Story of Heterogeneous B-raf V600E Mutation Quantitative Protein Expression in Metastatic Melanoma-Association with Clinical Outcome and Tumor Phenotypes.

In comparison to other human cancer types, malignant melanoma exhibits the greatest amount of heterogeneity. After DNA-based detection of the BRAF V600E mutation in melanoma patients, targeted inhibitor treatment is the current recommendation. This approach, however, does not take the abundance of the therapeutic target, i.

Novel functional proteins coded by the human genome discovered in metastases of melanoma patients.

In the advanced stages, malignant melanoma (MM) has a very poor prognosis. Due to tremendous efforts in cancer research over the last 10 years, and the introduction of novel therapies such as targeted therapies and immunomodulators, the rather dark horizon of the median survival has dramatically changed from under 1 year to several years. With the advent of proteomics, deep-mining studies can reach low-abundant expression levels.

Clusterwise Peak Detection and Filtering Based on Spatial Distribution To Efficiently Mine Mass Spectrometry Imaging Data.

Mass spectrometry imaging (MSI) has the potential to reveal the localization of thousands of biomolecules such as metabolites and lipids in tissue sections. The increase in both mass and spatial resolution of today's instruments brings on considerable challenges in terms of data processing; accurately extracting meaningful signals from the large data sets generated by MSI without losing information that could be clinically relevant is one of the most fundamental tasks of analysis software. Ion images of the biomolecules are generated by visualizing their intensities in 2-D space using mass spectra collected across the tissue section.

Improved survival prognostication of node-positive malignant melanoma patients utilizing shotgun proteomics guided by histopathological characterization and genomic data.

Metastatic melanoma is one of the most common deadly cancers, and robust biomarkers are still needed, e.g. to predict survival and treatment efficiency.

Clinical protein science in translational medicine targeting malignant melanoma.

Melanoma of the skin is the sixth most common type of cancer in Europe and accounts for 3.4% of all diagnosed cancers. More alarming is the degree of recurrence that occurs with approximately 20% of patients lethally relapsing following treatment.

Test-retest variability of left ventricular 4D flow cardiovascular magnetic resonance measurements in healthy subjects.

Background: Quantification and visualisation of left ventricular (LV) blood flow is afforded by three-dimensional, time resolved phase contrast cardiovascular magnetic resonance (CMR 4D flow). However, few data exist upon the repeatability and variability of these parameters in a healthy population. We aimed to assess the repeatability and variability over time of LV 4D CMR flow measurements.

Fixed volume particle trace emission for the analysis of left atrial blood flow using 4D Flow MRI.

4D Flow MRI has been used to quantify normal and deranged left ventricular blood flow characteristics on the basis of functionally distinct flow components. However, the application of this technique to the atria is challenging due to the presence of continuous inflow. This continuous inflow necessitates plane-based emission of particle traces from the inlet veins, leading to particles that represents different amounts of blood, and related quantification errors.

Mechanical dyssynchrony alters left ventricular flow energetics in failing hearts with LBBB: a 4D flow CMR pilot study.

The impact of left bundle branch block (LBBB) related mechanical dyssynchrony on left ventricular (LV) diastolic function remains unclear. 4D flow cardiovascular magnetic resonance (CMR) has provided reliable markers of LV dysfunction: reduced volume and kinetic energy (KE) of the portion of LV inflow which passes directly to outflow (Direct Flow) has been demonstrated in failing hearts compared to normal hearts. We sought to investigate the impact of mechanical dyssynchrony on diastolic function by comparing 4D flow in myopathic LVs with and without LBBB.

Left ventricular hemodynamic forces as a marker of mechanical dyssynchrony in heart failure patients with left bundle branch block.

Left bundle branch block (LBBB) causes left ventricular (LV) dyssynchrony which is often associated with heart failure. A significant proportion of heart failure patients do not demonstrate clinical improvement despite cardiac resynchronization therapy (CRT). How LBBB-related effects on LV diastolic function may contribute to those therapeutic failures has not been clarified.

Merging clinical chemistry biomarker data with a COPD database - building a clinical infrastructure for proteomic studies.

Background: Data from biological samples and medical evaluations plays an essential part in clinical decision making. This data is equally important in clinical studies and it is critical to have an infrastructure that ensures that its quality is preserved throughout its entire lifetime. We are running a 5-year longitudinal clinical study, KOL-Örestad, with the objective to identify new COPD (Chronic Obstructive Pulmonary Disease) biomarkers in blood.

Creating hemodynamic atlases of cardiac 4D flow MRI.

Purpose: Hemodynamic atlases can add to the pathophysiological understanding of cardiac diseases. This study proposes a method to create hemodynamic atlases using 4D Flow magnetic resonance imaging (MRI). The method is demonstrated for kinetic energy (KE) and helicity density (H ).

Altered Diastolic Flow Patterns and Kinetic Energy in Subtle Left Ventricular Remodeling and Dysfunction Detected by 4D Flow MRI.

Aims: 4D flow magnetic resonance imaging (MRI) allows quantitative assessment of left ventricular (LV) function according to characteristics of the dynamic flow in the chamber. Marked abnormalities in flow components' volume and kinetic energy (KE) have previously been demonstrated in moderately dilated and depressed LV's compared to healthy subjects. We hypothesized that these 4D flow-based measures would detect even subtle LV dysfunction and remodeling.

Assessment of left ventricular hemodynamic forces in healthy subjects and patients with dilated cardiomyopathy using 4D flow MRI.

We hypothesized that the direction of global left ventricular (LV) hemodynamic forces during diastolic filling are concordant with the main flow axes in normal LVs, but that this pattern would be altered in dilated and dysfunctional LVs. Therefore, we aimed to assess the LV hemodynamic filling forces in a group of healthy subjects and compare them to the results from a group of patients with dilated cardiomyopathy (DCM). Ten healthy subjects and 10 DCM patients were enrolled.

Atlas-based analysis of 4D flow CMR: automated vessel segmentation and flow quantification.

Background: Flow volume quantification in the great thoracic vessels is used in the assessment of several cardiovascular diseases. Clinically, it is often based on semi-automatic segmentation of a vessel throughout the cardiac cycle in 2D cine phase-contrast Cardiovascular Magnetic Resonance (CMR) images. Three-dimensional (3D), time-resolved phase-contrast CMR with three-directional velocity encoding (4D flow CMR) permits assessment of net flow volumes and flow patterns retrospectively at any location in a time-resolved 3D volume.

4D flow MRI can detect subtle right ventricular dysfunction in primary left ventricular disease.

Purpose: To investigate whether 4D flow magnetic resonance imaging (MRI) can detect subtle right ventricular (RV) dysfunction in primary left ventricular (LV) disease.

Materials And Methods: 4D flow and morphological 3T MRI data were acquired in 22 patients with mild ischemic heart disease who were stratified into two groups based on LV end-diastolic volume index (EDVI): lower-LVEDVI and higher-LVEDVI, as well as in 11 healthy controls. The RV volume was segmented at end-diastole (ED) and end-systole (ES).

Spatial heterogeneity of four-dimensional relative pressure fields in the human left ventricle.

Purpose: To assess the spatial heterogeneity of the four-dimensional (4D) relative pressure fields in the healthy human left ventricle (LV) and provide reference data for normal LV relative pressure.

Methods: Twelve healthy subjects underwent a cardiac MRI examination where 4D flow and morphological data were acquired. The latter data were segmented and used to define the borders of the LV for computation of relative pressure fields using the pressure Poisson equation.

Turbulent kinetic energy in normal and myopathic left ventricles.

Purpose: To assess turbulent kinetic energy (TKE) within the left ventricle (LV) of healthy subjects using novel 4D flow magnetic resonance imaging (MRI) methods and to compare TKE values to those from a limited group of patients with a spectrum of dilated cardiomyopathy (DCM).

Materials And Methods: 4D flow and morphological MRI data were acquired in 11 healthy subjects and 9 patients with different degrees of diastolic dysfunction. TKELV was calculated within the LV at each diastolic timeframe.

Four-dimensional blood flow-specific markers of LV dysfunction in dilated cardiomyopathy.

Aims: Patients with mild heart failure (HF) who are clinically compensated may have normal left ventricular (LV) stroke volume (SV). Despite this, altered intra-ventricular flow patterns have been recognized in these subjects. We hypothesized that, compared with normal LVs, flow in myopathic LVs would demonstrate a smaller proportion of inflow volume passing directly to ejection and diminished the end-diastolic preservation of the inflow kinetic energy (KE).

4-D blood flow in the human right ventricle.

Right ventricular (RV) function is a powerful prognostic indicator in many forms of heart disease, but its assessment remains challenging and inexact. RV dysfunction may alter the normal patterns of RV blood flow, but those patterns have been incompletely characterized. We hypothesized that, based on anatomic differences, the proportions and energetics of RV flow components would differ from those identified in the left ventricle (LV) and that the portion of the RV inflow passing directly to outflow (Direct Flow) would be prepared for effective systolic ejection as a result of preserved kinetic energy (KE) compared with other RV flow components.

Quantification of presystolic blood flow organization and energetics in the human left ventricle.

Intracardiac blood flow patterns are potentially important to cardiac pumping efficiency. However, these complex flow patterns remain incompletely characterized both in health and disease. We hypothesized that normal left ventricular (LV) blood flow patterns would preferentially optimize a portion of the end-diastolic volume (LVEDV) for effective and rapid systolic ejection by virtue of location near and motion towards the LV outflow tract (LVOT).