Multimodal optoacoustic imaging: methods and contrast materials.

Optoacoustic (OA) imaging offers powerful capabilities for interrogating biological tissues with rich optical absorption contrast while maintaining high spatial resolution for deep tissue observations. The spectrally distinct absorption of visible and near-infrared photons by endogenous tissue chromophores facilitates extraction of diverse anatomic, functional, molecular, and metabolic information from living tissues across various scales, from organelles and cells to whole organs and organisms. The primarily blood-related contrast and limited penetration depth of OA imaging have fostered the development of multimodal approaches to fully exploit the unique advantages and complementarity of the method. We review the recent hybridization efforts, including multimodal combinations of OA with ultrasound, fluorescence, optical coherence tomography, Raman scattering microscopy and magnetic resonance imaging as well as ionizing methods, such as X-ray computed tomography, single-photon-emission computed tomography and positron emission tomography. Considering that most molecules absorb light across a broad range of the electromagnetic spectrum, the OA interrogations can be extended to a large number of exogenously administered small molecules, particulate agents, and genetically encoded labels. This unique property further makes contrast moieties used in other imaging modalities amenable for OA sensing.

Volumetric registration framework for multimodal functional magnetic resonance and optoacoustic tomography of the rodent brain.

Optoacoustic tomography (OAT) provides a non-invasive means to characterize cerebral hemodynamics across an entire murine brain while attaining multi-parametric readouts not available with other modalities. This unique capability can massively impact our understanding of brain function. However, OAT largely lacks the soft tissue contrast required for unambiguous identification of brain regions. Hence, its accurate registration to a reference brain atlas is paramount for attaining meaningful functional readings. Herein, we capitalized on the simultaneously acquired bi-modal data from the recently-developed hybrid magnetic resonance optoacoustic tomography (MROT) scanner in order to devise an image coregistration paradigm that facilitates brain parcellation and anatomical referencing. We evaluated the performance of the proposed methodology by coregistering OAT data acquired with a standalone system using different registration methods. The enhanced performance is further demonstrated for functional OAT data analysis and characterization of stimulus-evoked brain responses. The suggested approach enables better consolidation of the research findings thus facilitating wider acceptance of OAT as a powerful neuroimaging tool to study brain functions and diseases.

Simultaneous Functional Magnetic Resonance and Optoacoustic Imaging of Brain-Wide Sensory Responses in Mice.

Functional magnetic resonance imaging (fMRI) has massively contributed to the understanding of mammalian brain function. However, the origin and interpretation of the blood oxygen level-dependent (BOLD) signals retrieved by fMRI remain highly disputed. This article reports on the development of a fully hybridized system enabling concurrent functional magnetic resonance optoacoustic tomography (MROT) measurements of stimulus-evoked brain-wide sensory responses in mice. The highly complementary angiographic and soft tissue contrasts of both modalities along with simultaneous multi-parametric readings of stimulus-evoked hemodynamic responses are leveraged in order to establish unequivocal links between the various counteracting physiological and metabolic processes in the brain. The results indicate that the BOLD signals are highly correlated, both spatially and temporally, with the total hemoglobin readings resolved with volumetric multi-spectral optoacoustic tomography. Furthermore, the differential oxygenated and deoxygenated hemoglobin optoacoustic readings exhibit superior sensitivity as compared to the BOLD signals when detecting stimulus-evoked hemodynamic responses. The fully hybridized MROT approach greatly expands the neuroimaging toolset to comprehensively study neurovascular and neurometabolic coupling mechanisms and related diseases.

Hybrid magnetic resonance and optoacoustic tomography (MROT) for preclinical neuroimaging.

Multi-modal imaging is essential for advancing our understanding of brain function and unraveling pathophysiological processes underlying neurological and psychiatric disorders. Magnetic resonance (MR) and optoacoustic (OA) imaging have been shown to provide highly complementary contrasts and capabilities for preclinical neuroimaging. True integration between these modalities can thus offer unprecedented capabilities for studying the rodent brain in action. We report on a hybrid magnetic resonance and optoacoustic tomography (MROT) system for concurrent noninvasive structural and functional imaging of the mouse brain. Volumetric OA tomography was designed as an insert into a high-field MR scanner by integrating a customized MR-compatible spherical transducer array, an illumination module, and a dedicated radiofrequency coil. A tailored data processing pipeline has been developed to mitigate signal crosstalk and accurately register image volumes acquired with T1-weighted, angiography, and blood oxygenation level-dependent (BOLD) sequences onto the corresponding vascular and oxygenation data recorded with the OA modality. We demonstrate the concurrent acquisition of dual-mode anatomical and angiographic brain images with the scanner, as well as real-time functional readings of multiple hemodynamic parameters from animals subjected to oxygenation stress. Our approach combines the functional and molecular imaging advantages of OA with the superb soft-tissue contrast of MR, further providing an excellent platform for cross-validation of functional readings by the two modalities.

Multimodal Noninvasive Functional Neurophotonic Imaging of Murine Brain-Wide Sensory Responses.

Modern optical neuroimaging approaches are expanding the ability to elucidate complex brain function. Diverse imaging contrasts enable direct observation of neural activity with functional sensors along with the induced hemodynamic responses. To date, decoupling the complex interplay of neurovascular coupling and dynamical physiological states has remained challenging when employing single-modality functional neuroimaging readings. A hybrid fluorescence optoacoustic tomography platform combined with a custom data processing pipeline based on statistical parametric mapping is devised, attaining the first noninvasive observation of simultaneous calcium and hemodynamic activation patterns using optical contrasts. Correlated changes in the oxy- and deoxygenated hemoglobin, total hemoglobin, oxygen saturation, and rapid GCaMP6f fluorescence signals are observed in response to peripheral sensory stimulation. While the concurrent epifluorescence serves to corroborate and complement the functional optoacoustic observations, the latter further aids in decoupling the rapid calcium responses from the slowly varying background in the fluorescence recordings mediated by hemodynamic changes. The hybrid imaging platform expands the capabilities of conventional neuroimaging methods to provide more comprehensive functional readings for studying neurovascular and neurometabolic coupling mechanisms and related diseases.