Remote Assessment of the Cardiovascular Function Using Camera-Based Photoplethysmography

Camera-based photoplethysmography (cbPPG) is a novel measurement technique that allows the continuous monitoring of vital signs by using common video cameras. In the last decade, the technology has attracted a lot of attention as it is easy to set up, operates remotely, and offers new diagnostic opportunities. Despite the growing interest, cbPPG is not completely established yet and is still primarily the object of research. There are a variety of reasons for this lack of development including that reliable and autonomous hardware setups are missing, that robust processing algorithms are needed, that application fields are still limited, and that it is not completely understood which physiological factors impact the captured signal. In this thesis, these issues will be addressed. A new and innovative measuring system for cbPPG was developed. In the course of three large studies conducted in clinical and non-clinical environments, the system’s great flexibility, autonomy, user-friendliness, and integrability could be successfully proven. Furthermore, it was investigated what value optical polarization filtration adds to cbPPG. The results show that a perpendicular filter setting can significantly enhance the signal quality. In addition, the performed analyses were used to draw conclusions about the origin of cbPPG signals: Blood volume changes are most likely the defining element for the signal's modulation. Besides the hardware-related topics, the software topic was addressed. A new method for the selection of regions of interest (ROIs) in cbPPG videos was developed. Choosing valid ROIs is one of the most important steps in the processing chain of cbPPG software. The new method has the advantage of being fully automated, more independent, and universally applicable. Moreover, it suppresses ballistocardiographic artifacts by utilizing a level-set-based approach. The suitability of the ROI selection method was demonstrated on a large and challenging data set. In the last part of the work, a potentially new application field for cbPPG was explored. It was investigated how cbPPG can be used to assess autonomic reactions of the nervous system at the cutaneous vasculature. The results show that changes in the vasomotor tone, i.e. vasodilation and vasoconstriction, reflect in the pulsation strength of cbPPG signals. These characteristics also shed more light on the origin problem. Similar to the polarization analyses, they support the classic blood volume theory. In conclusion, this thesis tackles relevant issues regarding the application of cbPPG. The proposed solutions pave the way for cbPPG to become an established and widely accepted technology

Spatio-temporal analysis of blood perfusion by imaging photoplethysmography

Imaging photoplethysmography (iPPG) has attracted much attention over the last years. The vast majority of works focuses on methods to reliably extract the heart rate from videos. Only a few works addressed iPPGs ability to exploit spatio-temporal perfusion pattern to derive further diagnostic statements. This work directs at the spatio-temporal analysis of blood perfusion from videos. We present a novel algorithm that bases on the two-dimensional representation of the blood pulsation (perfusion map). The basic idea behind the proposed algorithm consists of a pairwise estimation of time delays between photoplethysmographic signals of spatially separated regions. The probabilistic approach yields a parameter denoted as perfusion speed. We compare the perfusion speed versus two parameters, which assess the strength of blood pulsation (perfusion strength and signal to noise ratio). Preliminary results using video data with different physiological stimuli (cold pressure test, cold face test) show that all measures are in fluenced by those stimuli (some of them with statistical certainty). The perfusion speed turned out to be more sensitive than the other measures in some cases. However, our results also show that the intraindividual stability and interindividual comparability of all used measures remain critical points. This work proves the general feasibility of employing the perfusion speed as novel iPPG quantity. Future studies will address open points like the handling of ballistocardiographic effects and will try to deepen the understanding of the predominant physiological mechanisms and their relation to the algorithmic performance

Contact-free optical assessment of changes in the chest wall perfusion after coronary artery bypass grafting by imaging photoplethysmography

Imaging photoplethysmography (iPPG) is a contact-free monitoring of the cutaneous blood volume pulse by RGB (red-green-blue) cameras. It detects vital parameters from skin areas and is associated to cutaneous perfusion. This study investigated the use of iPPG to quantify changes in cutaneous perfusion after major surgery. Patients undergoing coronary artery bypass grafting (CABG) were scanned before surgery and in three follow-up measurements. Using an industrial-grade RGB camera and usual indoor lighting, a contact-free imaging plethysmogram from the chest was obtained. Changes of the iPPG signal strength were evaluated in view of both the operation itself as well as the unilateral preparation of the internal thoracic artery (ITA) for coronary artery grafting, which is the main blood source of the chest wall. iPPG signal strength globally decreased after surgery and recovered partially during the follow up measurements. The ITA preparation led to a deeper decrease and an attenuated recovery of the iPPG signal strength compared to the other side of the chest wall. These results comply with the expected changes of cutaneous perfusion after CABG using an ITA graft. iPPG can be used to assess cutaneous perfusion and its global changes after major surgery as well as its local changes after specific surgical procedures

New outcomes of Lewis base addition to diboranes(4): electronic effects override strong steric disincentives

Two surprising new outcomes of the reaction of Lewis bases with dihalodiboranes(4) are presented, including sp2–sp3 diboranes in which the Lewis base unit is bound to a highly sterically congested boron atom, and a rearranged double base adduct. The results provide a fuller understanding of the reactivity of diboranes, a poorly-understood class of molecule of critical importance to synthetic organic chemistry

Aggressive PDACs show hypomethylation of repetitive elements and the execution of an intrinsic IFN program linked to a ductal cell of origin

Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive desmoplasia, which challenges the molecular analyses of bulk tumor samples. Here we FACS-purified epithelial cells from human PDAC and normal pancreas and derived their genome-wide transcriptome and DNA methylome landscapes. Clustering based on DNA methylation revealed two distinct PDAC groups displaying different methylation patterns at regions encoding repeat elements. Methylation(low) tumors are characterized by higher expression of endogenous retroviral (ERV) transcripts and dsRNA sensors which leads to a cell intrinsic activation of an interferon signature (IFNsign). This results in a pro-tumorigenic microenvironment and poor patient outcome. Methylation(low)/IFNsign(high) and Methylation(high)/IFNsign(low) PDAC cells preserve lineage traits, respective of normal ductal or acinar pancreatic cells. Moreover, ductal-derived Kras(G12D)/Trp53(−/−) mouse PDACs show higher expression of IFNsign compared to acinar-derived counterparts. Collectively, our data point to two different origins and etiologies of human PDACs, with the aggressive Methylation(low)/IFNsign(high) subtype potentially targetable by agents blocking intrinsic IFN-signaling

Placentation defects are highly prevalent in embryonic lethal mouse mutants.

Large-scale phenotyping efforts have demonstrated that approximately 25-30% of mouse gene knockouts cause intrauterine lethality. Analysis of these mutants has largely focused on the embryo and not the placenta, despite the crucial role of this extraembryonic organ for developmental progression. Here we screened 103 embryonic lethal and sub-viable mouse knockout lines from the Deciphering the Mechanisms of Developmental Disorders program for placental phenotypes. We found that 68% of knockout lines that are lethal at or after mid-gestation exhibited placental dysmorphologies. Early lethality (embryonic days 9.5-14.5) is almost always associated with severe placental malformations. Placental defects correlate strongly with abnormal brain, heart and vascular development. Analysis of mutant trophoblast stem cells and conditional knockouts suggests that a considerable number of factors that cause embryonic lethality when ablated have primary gene function in trophoblast cells. Our data highlight the hugely under-appreciated importance of placental defects in contributing to abnormal embryo development and suggest key molecular nodes that govern placenta formation