Multiscale Functional and Molecular Imaging Group
Principal Investigator: Prof. Dr. Daniel Razansky
We work at the interface of engineering, biology and medicine to devise novel tools for high performance functional and molecular imaging. The focus is on tools that can broadly impact pre-clinical research and clinical practice by delivering information presently not attainable with existing state-of-the-art imaging modalities. In particular, new imaging paradigms based on biomedical optics, optoacoustics, ultrasound and their synergistic combinations are developed to enable multi-scale observations with unprecedented spatio-temporal resolution and penetration of several millimeters to centimeters into living intact organisms. We contribute to the creation of these new technologies in several diverse ways, from the establishment of solid theoretical background, inverse methods, and instrumentation to the development of in-vivo imaging methodologies and contrast enhancement approaches. We are also actively engaged in clinical trials involving the newly-developed imaging technology. Examples of projects include development of volumetric real-time tomography systems for preclinical molecular imaging, ultrafast microscopy for deep-tissue functional neuroimaging, handheld clinical diagnostics systems, development of novel image reconstruction and visualization techniques for high throughput imaging systems.
Real-time microscopy and functional neuroimaging
Fluorescent microscopy have become essential tool for studying life at the cellular and sub-cellular level, re-defining ways in which we investigate biology. Indeed, optical spectrum is particularly attractive for biological interrogations as it can impart highly versatile contrast of cellular and sub-cellular function as well as employ highly specific contrast agents and markers not available for other modalities. However, technical limitations arising from intense light scattering in living tissues bound the main-stream of high resolution optical imaging applications to microscopic studies at shallow depths that do not allow the exploration of the full potential of novel classes of agents for volumetric imaging of entire organs, small animals or human tissues. We develop multispectral optoacoustic microscopy techniques capable of ultrafast volumetric imaging of functional and molecular contrast deep within highly light-scattering living organisms and at high spatial resolution. Key applications include functional neuroimaging, study of hemodynamic responses and fast neuronal activation.
3D/4D/5D handheld tomography and fast inverse methods
Optoacoustic phenomenon is unique in a way it allows to generate complete volumetric tomographic dataset from the imaged object using a single interrogating laser pulse. Yet, multiple technical limitations, related to lack of appropriate detection technology, digital sampling and processing capacities, and efficient inverse methods, make implementation of real-time imaging and tomography challenging. Here we undertake substantial technological steps that bring optoacoustic imaging to a real-time volumetric performance and enable imaging several millimeters to centimeters into tissues using both handheld and stationary tomography designs. We were the first to demonstrate simultaneous acquisition, processing and visualization of five-dimensional (volumetric, multispectral, time-resolved) optoacoustic data, thus offering unparallel imaging capacities among the current bioimaging modalities. This unprecedented performance renders optoacoustics as a superior and gold standard method for attaining high dynamic contrast in intact living tissues and an ideal candidate for both intrinsic and targeted biomarker-based high performance imaging in pre-clinical research and the clinics. Applications include fast functional cardiac imaging, whole-organ and whole-body studies of kinetics and biodistribution, volumetric handheld clinical diagnostics. These developments are greatly supported by our algorithmic research into inverse theory and fast GPU-accelerated image reconstruction techniques. We are further addressing the challenges of quantitative image reconstruction by development of multi-spectral processing algorithms, light propagation modeling and artifact reduction methods.
Multi-modal and hybrid imaging
Due to its hybrid nature, which involves both light and sound, optoacoustic imaging can be seamlessly integrated with other pure optical and ultrasonic imaging techniques to provide complementary contrast advantages and capitalize on the particular strengths of each modality. In this way, it can for instance fill the gap existing between the high-resolution optical microscopy, which can only image up to a several hundreds of microns in most tissues, and the low-resolution deep tissue imaging approaches based on diffuse optics. On the other hand, information retrieved with optoacoustics can be used to improve image quality and quantification abilities of pure optical or ultrasonic methods or vice versa. For instance, the absorption maps, delivered by tomographic optoacoustic reconstructions, can be subsequently used to better normalize images acquired with fluorescence molecular tomography. Another example is using ultrasound as a calibration technique for reducing optoacoustic imaging artifacts due to acoustic heterogeneities.
Monitoring of thermal ablation treatments and laser surgery
Treatments generating ablation and coagulation of tissues by applying lasers, microwaves, radiofrequency currents or focused ultrasound have many advantages over scalpel-based and other mechanistic surgical methods. This includes lack of contact of surgical instruments with clean areas, the potential for unrivaled precision and selectivity, minimal thermal and mechanical side effects, and the possibility of simultaneous cutting and/or coagulation of tissue. These advantages have consequently motivated the clinical application of the various ablation techniques in a myriad of medical specialties, including oncology, electrophysiology, ophthalmology, dermatology, dentistry, plastic surgery, and otolaryngology. Despite these advances, most procedures are not done with an appropriate feedback control, resulting in difficulties discerning the critical parameters of the created lesion during the ablation process, such as depth, size, precise map of the temperature rise and thermal damage, the coagulation margin, as well as type of the ablated and the surrounding tissues. Our overall goal is development of appropriate imaging and dynamic feedback approaches that can precisely monitor and control the ablation parameters with high temporal and spatial resolution during the treatment, ultimately increasing efficacy and safely or these treatments and reducing numbers of redo procedures.
- Steven Ford (Postdoc)
- Jake Turner (PhD student)
- Christian Lutzweiler (PhD student)
- Moritz Kneipp (PhD student)
- Genny Pang (Postdoc)
- Gali Sela (Postdoc)
- Erwin Bay (PhD student)
- Magesh Sadasivam (PhD student)
- Erdem Baseqmez (Bachelor student)
- Andreas Buehler (Postdoc)
- Rui Ma (PhD student)
- Amir Hajiaboli (Postdoc)
- Martin Distel (Postdoc)
- Ali Özbek (Master student)
- Yuxiang Gong (Master student)
- Michael Zwack (Master student)
- Andrii Kravtsiv (Master stuent)
- Vishvanath Pamulakanty Sudarshan (Master student)
- Lilian Kettner (Master student)
- Sebastian Soengen (Master student)
S. Gottschalk et al., Non-invasive real-time visualization of multiple cerebral hemodynamic parameters in whole mouse brains using five-dimensional optoacoustic tomography, J Cerebral Blood Flow Metab 35, 531-535 (2015)
X. L. Deán-Ben and D. Razansky, Adding fifth dimension to optoacoustic imaging: volumetric time-resolved spectrally-enriched tomography, Light: Sci & Appl (Nature) 3, e137 (2014)
D. Razansky et al, Volumetric real-time multispectral optoacoustic tomography of biomarkers, Nature Prot 6(8), 1121-1129 (2011)
V. Ntziachristos and D. Razansky, Molecular imaging by means of multispectral opto-acoustic tomography (MSOT), Chem Rev 110(5), 2783-2794 (2010)
D. Razansky et al., Multi-spectral optoacoustic tomography of deep-seated fluorescent proteins in-vivo, Nature Phot 3(7), 412-417 (2009)
C. Vinegoni et al., Live imaging of drosophila melanogaster pupae with mesoscopic fluorescence tomography, Nature Meth 5(1), 45-47 (2008)