Novel concepts for lipid identification from shotgun mass spectra using a customized query language

Lipids are the main component of semipermeable cell membranes and linked to several important physiological processes. Shotgun lipidomics relies on the direct infusion of total lipid extracts from cells, tissues or organisms into the mass spectrometer and is a powerful tool to elucidate their molecular composition. Despite the technical advances in modern mass spectrometry the currently available software underperforms in several aspects of the lipidomics pipeline. This thesis addresses these issues by presenting a new concept for lipid identification using a customized query language for mass spectra in combination with efficient spectra alignment algorithms which are implemented in the open source kit “LipidXplorer”

First- and Second-Order Analysis for Optimization Problems with Manifold-Valued Constraints

We consider optimization problems with manifold-valued constraints. These generalize classical equality and inequality constraints to a setting in which both the domain and the codomain of the constraint mapping are smooth manifolds. We model the feasible set as the preimage of a submanifold with corners of the codomain. The latter is a subset which corresponds to a convex cone locally in suitable charts. We study first- and second-order optimality conditions for this class of problems. We also show the invariance of the relevant quantities with respect to local representations of the problem

Fenchel Duality Theory and A Primal-Dual Algorithm on Riemannian Manifolds

This paper introduces a new notion of a Fenchel conjugate, which generalizes the classical Fenchel conjugation to functions defined on Riemannian manifolds. We investigate its properties, e.g.,~the Fenchel--Young inequality and the characterization of the convex subdifferential using the analogue of the Fenchel--Moreau Theorem. These properties of the Fenchel conjugate are employed to derive a Riemannian primal-dual optimization algorithm, and to prove its convergence for the case of Hadamard manifolds under appropriate assumptions. Numerical results illustrate the performance of the algorithm, which competes with the recently derived Douglas--Rachford algorithm on manifolds of nonpositive curvature. Furthermore, we show numerically that our novel algorithm even converges on manifolds of positive curvature

Mesh Denoising and Inpainting using the Total Variation of the Normal

In this paper we present a novel approach to solve surface mesh denoising and inpainting problems. The purpose is not only to remove noise while preserving important features such as sharp edges, but also to fill in missing parts of the geometry. A discrete variant of the total variation of the unit normal vector field serves as a regularizing functional to achieve this goal. In order to solve the resulting problem, we present a novel variant of the split Bregman (ADMM) iteration. Numerical examples are included demonstrating the performance of the method with some complex 3D geometries

Non-invasive assessment of coronary artery disease with CT coronary angiography and SPECT: a novel dose-saving fast-track algorithm

Purpose: To validate a new low-dose and rapid stepwise individualized algorithm for non-invasive assessment of ischemic coronary artery disease by sequential use of prospectively ECG-triggered low-dose CT coronary angiography (CTCA) and low-dose single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI). Methods: Forty patients referred for elective invasive coronary angiography (CA) were prospectively enrolled to undergo a comprehensive non-invasive evaluation with low-dose CTCA and a dose-reduced stress/rest SPECT-MPI scan (using dedicated reconstruction algorithms for low count scans). The following algorithm was reviewed: CTCA first, followed by a stress-only MPI if a coronary stenosis (≥ 50% diameter narrowing) or equivocal findings were observed. Only abnormal stress MPI scans were followed by rest MPI. The accuracy of the individualized algorithm to predict coronary revascularization and its mean effective radiation dose were assessed. Results: CTCA documented CAD in 18 and equivocal findings in two patients, thus, requiring additional stress MPI scans. Of these, 16 were abnormal, therefore requiring a rest MPI scan, revealing ischemia in 15 patients. Sensitivity, specificity, negative and positive predictive value, and accuracy of the individualized algorithm for predicting coronary revascularization was 93.3%, 96.0%, 96.0%, 93.3% and 95.0% on a per-patient base. The mean effective radiation dose was significantly lower for the individualized (4.8 ± 3.4mSv) versus the comprehensive method (8.1 ± 1.5mSv) resulting in a total population radiation dose reduction of 132.6mSv. Conclusion: This new individualized low-dose algorithm allows rapid and accurate prediction of invasive CA findings and of treatment decision with minimized radiation dos

Myocardial perfusion imaging with real-time respiratory triggering: Impact of inspiration breath-hold on left ventricular functional parameters

Background: The latest gamma-camera generation with cadmium-zinc-telluride (CZT) detectors allows myocardial perfusion imaging (MPI) with respiratory triggering at breath-hold. We assessed its impact on functional left ventricular (LV) parameters. Methods: Twenty-eight consecutive patients underwent a one-day 99mTc-tetrofosmin pharmacologic stress/rest imaging protocol on a novel CZT camera. Electrocardiogram-gated high-dose (rest) MPI was performed without and with real-time respiratory triggering by intermittent scanning confined to breath-hold at deep inspiration. We studied the effect of respiratory triggering at deep inspiration levels on LV wall motion, wall thickening, LV volumes and ejection fraction (LVEF) compared to regular MPI without respiratory triggering. Results: Compared to regular MPI without respiratory triggering, systolic and diastolic LV volumes and stroke volumes decreased significantly (P<0.05) when respiratory triggering was applied. By contrast, there was no significant change in LVEF, with a high correlation (r=.939, P<0.001) between the two measurements. Furthermore, respiratory triggering introduced a significant change (P<0.05) in regional LV wall motion. Conclusions: Respiratory-triggered MPI with breath-hold at deep inspiration levels introduces significant changes to the measured LV volumes, stroke volumes and regional wall motion but does not significantly affect global LVEF when compared to regular MPI with normal breathin

Coronary calcium score scans for attenuation correction of quantitative PET/CT 13N-ammonia myocardial perfusion imaging

Purpose: The aim of this study was to evaluate whether ECG-triggered coronary calcium scoring (CCS) scans can be used for attenuation correction (AC) to quantify myocardial blood flow (MBF) and coronary flow reserve (CFR) assessed by PET/CT with 13N-ammonia. Methods: Thirty-five consecutive patients underwent a 13N-ammonia PET/CT scan at rest and during standard adenosine stress. MBF values were calculated using AC maps obtained from the ECG-triggered CCS scan during inspiration and validated against MBF values calculated using standard non-gated transmission scans for AC. CFR was calculated as the ratio of hyperaemic over resting MBF. In all 35 consecutive patients intraobserver variability was assessed by blinded repeat analysis for both AC methods. Results: There was an excellent correlation between CT AC and CCS for global MBF values at rest (n = 35, r = 0.94, p < 0.001) and during stress (n = 35, r = 0.97, p < 0.001) with narrow Bland-Altman (BA) limits of agreement (−0.21 to 0.10ml/min per g and −0.41 to 0.30ml/min per g) as well as for global CFR (n = 35, r = 0.96, p < 0.001, BA −0.27 to 0.34). The excellent correlation was preserved on the segmental MBF analysis for both rest and stress (n = 1190, r = 0.93, p < 0.001, BA −0.60 to 0.50) and for CFR (n = 595, r = 0.87, p < 0.001, BA −0.71 to 0.74). In addition, reproducibility proved excellent for global CFR by CT AC (n = 35, r = 0.91, p < 0.001, BA −0.42-0.58) and CCS scans (n = 35, r = 0.94, p < 0.001, BA −0.34-0.45). Conclusion: Use of attenuation maps from CCS scans allows accurate quantitative MBF and CFR assessment with 13N-ammonia PET/C