Optoaccoustic Tomography – good news for microcirculatory research

Tomographic imaging is a well established technology in preventive medicine and biomedical research, although not without limitations and concerns. Optoacoustic tomography (OAT) is a recent development that bridges optical and sonographic techniques to solve spatial resolution in deep-tissue imaging. In addition to safety advantages, OAT allows multiple wavelength readings for natural thermoelastic chromophores. In this study, we explore Multi Spectral Optoacoustic Tomography (MSOT) capacities to simultaneously acquire three independent chromophores – deoxygenated haemoglobin (Hb), oxygenated haemoglobin (HbO2), and melanin, from healthy human volunteers, with maximal molar extinction of HbO2 at 950 nm, Hb at 750 nm and melanin at 680 nm. Later we demonstrate how image stability during acquisition is fundamental for optimal resolution, precision and consistency of high throughout MSOT data collection. From recorded scans, a workflow is layered for data evaluation. With the MSOT dedicated software results were extracted from 3D image analysis of deep (15 mm3) vessels. The possibilities offered by this new system, specially in vascular pathophysiology, are immense and can be extended beyond current knowledge.

Optoaccoustic Tomography – good news for microcirculatory research

Tomographic imaging is a well established technology in preventive medicine and biomedical research, although not without limitations and concerns. Optoacoustic tomography (OAT) is a recent development that bridges optical and sonographic techniques to solve spatial resolution in deep-tissue imaging. In addition to safety advantages, OAT allows multiple wavelength readings for natural thermoelastic chromophores. In this study, we explore Multi Spectral Optoacoustic Tomography (MSOT) capacities to simultaneously acquire three independent chromophores – deoxygenated haemoglobin (Hb), oxygenated haemoglobin (HbO2), and melanin, from healthy human volunteers, with maximal molar extinction of HbO2 at 950 nm, Hb at 750 nm and melanin at 680 nm. Later we demonstrate how image stability during acquisition is fundamental for optimal resolution, precision and consistency of high throughout MSOT data collection. From recorded scans, a workflow is layered for data evaluation. With the MSOT dedicated software results were extracted from 3D image analysis of deep (15 mm3) vessels. The possibilities offered by this new system, specially in vascular pathophysiology, are immense and can be extended beyond current knowledge.

Imaging of peripheral vascular malformations — current concepts and future perspectives

Vascular Malformations belong to the spectrum of orphan diseases and can involve all segments of the vascular tree: arteries, capillaries, and veins, and similarly the lymphatic vasculature. The classification according to the International Society for the Study of Vascular Anomalies (ISSVA) is of major importance to guide proper treatment. Imaging plays a crucial role to classify vascular malformations according to their dominant vessel type, anatomical extension, and flow pattern. Several imaging concepts including color-coded Duplex ultrasound/contrast-enhanced ultrasound (CDUS/CEUS), 4D computed tomography angiography (CTA), magnetic resonance imaging (MRI) including dynamic contrast-enhanced MR-angiography (DCE-MRA), and conventional arterial and venous angiography are established in the current clinical routine. Besides the very heterogenous phenotypes of vascular malformations, molecular and genetic profiling has recently offered an advanced understanding of the pathogenesis and progression of these lesions. As distinct molecular subtypes may be suitable for targeted therapies, capturing certain patterns by means of molecular imaging could enhance non-invasive diagnostics of vascular malformations. This review provides an overview of subtype-specific imaging and established imaging modalities, as well as future perspectives of novel functional and molecular imaging approaches. We highlight recent pioneering imaging studies including thermography, positron emission tomography (PET), and multispectral optoacoustic tomography (MSOT), which have successfully targeted specific biomarkers of vascular malformations.

A H2O2-activatable nanoprobe for diagnosing interstitial cystitis and liver ischemia-reperfusion injury via multispectral optoacoustic tomography and NIR-II fluorescent imaging

Developing high-quality NIR-II fluorophores (emission in 1000–1700 nm) for in vivo imaging is of great significance. Benzothiadiazole-core fluorophores are an important class of NIR-II dyes, yet ongoing limitations such as aggregation-caused quenching in aqueous milieu and non-activatable response are still major obstacles for their biological applications. Here, we devise an activatable nanoprobe to address these limitations. A molecular probe named BTPE-NO2 is synthesized by linking a benzothiadiazole core with two tetraphenylene groups serving as hydrophobic molecular rotors, followed by incorporating two nitrophenyloxoacetamide units at both ends of the core as recognition moieties and fluorescence quenchers. An FDA-approved amphiphilic polymer Pluronic F127 is then employed to encapsulate the molecular BTPE-NO2 to render the nanoprobe BTPE-NO2@F127. The pathological levels of H2O2 in the disease sites cleave the nitrophenyloxoacetamide groups and activate the probe, thereby generating strong fluorescent emission (950~1200 nm) and ultrasound signal for multi-mode imaging of inflammatory diseases. The nanoprobe can therefore function as a robust tool for detecting and imaging the disease sites with NIR-II fluorescent and multispectral optoacoustic tomography (MSOT) imaging. Moreover, the three-dimensional MSOT images can be obtained for visualizing and locating the disease foci.

Multi-parametric characterization of brain-wide hemodynamic and calcium responses to sensory stimulation in mice

Modern optical neuroimaging approaches are expanding our 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 tools. We devised a hybrid fluorescence optoacoustic tomography (FLOT) platform combined with a custom data processing pipeline based on statistical parametric mapping, accomplishing the first simultaneous noninvasive observation of both direct and indirect brain-wide activation patterns with optical contrast. Correlated changes in the oxy- and deoxygenated hemoglobin, total hemoglobin, oxygen saturation and rapid GCaMP6f fluorescence signals were observed in response to peripheral sensory stimulation. While the concurrent epifluorescence served to corroborate and complement the functional optoacoustic observations, the latter further aided 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.