Novel Functional and Molecular Imaging Methods with Clinical Translation Potential

Functional Neuroimaging and Microscopy


Neuroscience has an urgent need for new large-scale neural recording technologies to ensure rapid progress in the understanding of brain function, diagnosis and treatment of neurological disorders. At present, real-time visualization of large-scale neural dynamics is hindered with the existing neuroimaging methods due to lack of capacity for direct imaging of neural activity in large tissue volumes and at high speeds. We develop novel optoacoustic and ultrasound functional neuroimaging tools to volumetrically monitor activity of large distributed neuronal populations in whole mammalian brains with unprecedented spatial and temporal resolution. 

Recent publications:

X. L. Deán-Ben et al., Functional optoacoustic neuro-tomography (FONT) for scalable whole-brain monitoring of calcium indicators,         Nature LSA 5, e16201 (2016)

Gottschalk et al, ”Non-invasive real-time visualization of multiple cerebral hemodynamic parameters in whole mouse brains using five-dimensional optoacoustic tomography”, J Cereb Blood Flow Metab 35, 531-535 (2015)

- Estrada et al, "Real-time optoacoustic brain microscopy with hybrid optical and acoustic resolution”, Las Phys Lett11, 045601 (2014) 

- Kneipp et al, “Functional real-time optoacoustic imaging of middle cerebral artery occlusion in mice”, PLoS ONE  9(4):e96118 (2014)


3D/4D/5D Handheld Tomography

The optoacoustic phenomenon is unique in the way in which it allows to generate complete volumetric tomographic datasets from the imaged object using a single interrogating laser pulse. Yet, multiple technical limitations, related to a lack of appropriate detection technology, digital sampling, 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 level and enable imaging several millimetres to centimetres into tissues using both handheld and stationary tomography designs. We were the first to demonstrate simultaneous acquisition, processing and visualisation of five-dimensional (volumetric, multispectral, time-resolved) optoacoustic data, thus offering unparalleled 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 clinics. Applications include fast functional cardiac imaging, whole-organ and whole-body studies of kinetics and biodistribution and 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 artefact reduction methods.

Recent publications:

- Deán-Ben et al. Optoacoustic microtomography at 100 volumes per second. Scientific Reports 7, 6850 (2017)

- X. L. Deán-Ben, and D. Razansky, Adding fifth dimension to optoacoustic imaging: volumetric time-resolved spectrally-enriched tomography, Nature LSA 3, e137 (2014)

C. Lutzweiler et al, Real-time optoacoustic tomography of indocyanine green perfusion in human vasculature. Opt Lett  39(14), 4061-4064 (2014)

- X. L. Deán-Ben et al, Volumetric real-time tracking of periferal human vasculature with GPU-accelerated three-dimensional optoacoustic tomography. IEEE Trans Med Imag 232(11), 2050-2055 (2013)


Multimodal and Hybrid Imaging

Due to its hybrid nature, which involves both light and sound, optoacoustic imaging can be seamlessly integrated with other purely optical and ultrasonic imaging techniques. This provides complementary contrast advantages and capitalises on the particular strengths of each modality. In this way, it can for instance fill the gap existing between 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 purely 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 artefacts due to acoustic heterogeneities or using in vivo real-time synergetic epifluorescence and optoacoustic imaging for biomedical applications. In the latter case this would then be used to exploit highly complex multiscale biological dynamics, such as neuron/brain activity, disease progression and pharmacokinetics.

Recent publications:

- Z. Chen et al. Performance of optoacoustic and fluorescence imaging in detecting deep-seated fluorescent agents. Biomedical Optics Express, Vol. 9, Issue 5, pp. 2229-2239 (2018)

- E. Merčep et al. Combined pulse-echo ultrasound and multispectral optoacoustic tomography with a multi-segment detector array. IEEE Transactions on Medical Imaging, 36(10), 2129-2137 (2017)

T. Fehm et al, Four dimensional hybrid ultrasound and optoacoustic imaging based on passive element optical excitation in a hand-held optoacoustic probe. Appl Phys Lett 105, 173505 (2014)

- H. Estrada et al, Hybrid optoacoustic and ultrasound biomicroscopy monitors laser-induced tissue modifications. Las Phys Lett 11, 125601 (2014)

N. C. Deliolanis, Deep-tissue reporter-gene imaging with fluorescence and optoacoustic tomography: a performance overview. Mol Imag Biol 16(5), pp. 652-660 (2014)


Monitoring of Thermal Treatments

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 a lack of contact of surgical instruments with clean areas, the potential for unrivalled 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 specialities, 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 mapping of the temperature rise and thermal damage, the coagulation margin, as well as the type of ablated and surrounding tissues. Our overall goal is the 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. This will ultimately increase efficacy and safety of these treatments and reduce the number of redo procedures.

Recent publications:

- Oyaga Landa et al. Volumetric optoacoustic temperature mapping in photothermal therapy. Scientific Reports 7, 9695 (2017)

G. Pang et al, Three-dimensional optoacoustic monitoring of lesion formation in real time during radiofrequency catheter ablation. J Cardiovas Electrophysiol,  DOI: 10.1111/jce.12584 (2015)

E. Bay et al, Real-time monitoring of incision profile during laser surgery using shock wave detection. J Biophoton 8(1), 102-111 (2015)

E. Bay et al, Optoacoustic monitoring of cutting efficiency and thermal damage during laser ablation. Lasers Med Sci  29(3), 1029-1035 (2014)