5D quantitative microscopy for real-time monitoring of Engineered Heart Tissue

A micro-world exists, waiting to be uncovered by cutting-edge technology. Optical microscopy and tomography act as gateways to this microscopic realm, where tiny details come into view. At the heart of this exploration is optical microscopy, utilizing light to illuminate the unseen. From simple microscopes to advanced high-resolution techniques, these instruments act as windows into that cellular landscape, revealing details never seen before. These imaging methods can be used across different disciplines to reveal the cell's secrets and investigate biological processes. In cardiovascular research, advanced microscopy and tomography technology play a crucial role by providing insight into underlying mechanisms and finding potential drug targets. Despite their importance, navigating the microscopic landscape presents challenges, with ongoing efforts to overcome resolution limitations and push the boundaries of what is achievable in optical microscopy and tomography. Dr. Azeem Ahmad leads the development of innovative label-free quantitative microscopy and tomography at the Department of Physics and Technology at UiT. In this project, he aims to develop a new quantitative microscopy method called 5D-QUIP for imaging dynamic processes in thick samples such as engineered heart tissue (EHT). With increasing interest in the use of engineered tissue for healthcare, 5D-QUIP will become a crucial tool that can provide a ground-breaking detailed picture of disease progression. Its ability to take 5D images could help researchers identify new drug targets and improve treatments for heart disease. In collaboration with the Department of Clinical Medicine (UiT), this project will explore the feasibility and usefulness of 5D-QUIP in EHT research, with a focus on capturing the dynamic phenomena of heartbeats in several EHT samples for a thorough analysis.

Fluorescence-based advanced optical microscopy, despite its increasing popularity, faces limitations due to intrusive labeling processes. Photobleaching hinders prolonged imaging of living cells, and the photochemical toxicity of fluorescence disrupts the delicate biology being studied, limiting its true impact. These challenges are aggravated in thick tissues. The longstanding goal of microscopy and life science communities is to "decode life in its natural state". This underscores the necessity for imaging tools that can visualize and study delicate biological systems in an unperturbed state with minimal interference, driving rapid development in the field of label-free optical microscopy. To date significant progress has been made in 3D label-free imaging, allowing researchers to observe complex structures with more detail. However, the current state-of-the-art techniques for imaging thick tissue samples have pros and cons in terms of either temporal and spatial resolution (in the case of medical imaging) or imaging depth (in the case of microscopy imaging). This creates a technology gap for high-speed and high-resolution quantitative imaging of thick tissue specimens. We propose a novel technique and coined it as 5D quantitative microscopy (5D-QUIP) which aims to bridge the gap between label-free microscopy techniques and medical imaging techniques providing high-temporal and spatial resolution with larger imaging depth. This will enable high-speed time-lapse imaging, allowing observation of dynamic processes over time with unprecedented details inside thick samples, such as beating in engineered heart tissue (EHT), the targeted application of this project.