Prof. Vasilis Ntziachristos, Msc PhD
Director, Institute for Biological and Medical Imaging and Director, Bioengineering DepartmentOur research at Helmholtz Munich is driven by our interest to provide solutions that address critical unmet medical need and positively impact healthcare and the well-being of society.
Our research at Helmholtz Munich is driven by our interest to provide solutions that address critical unmet medical need and positively impact healthcare and the well-being of society.
Academic Career and Research Areas
Vasilis Ntziachristos’ research focuses on the development of new methods for advancing well-being and accelerating discovery. His focus is the development of novel methods for prevention and early detection of disease, also serving as the means of administering more efficient treatment. His expertise span the fields of imaging, sensing and computation and his activities cover the entire spectrum from theoretical and methodological developments and basic discovery to clinical translation and entrepreneurship. Examples of his work involve the development of Fluorescent Molecular Imaging as means to improve guidance in surgery and the performance of diagnostic endoscopy as well as the development of Optoacoustic Imaging and Microscopy methods for advancing discovery and impacting healthcare. He is the founder of several companies including SurgVision BV which commercializes fluorescence imaging solutions for surgery, now under Bracco SpA, and iThera Medical GmbH, a company that commercializes optoacoustic technology.
Professor Vasilis Ntziachristos studied electrical engineering at Aristotle University in Thessaloniki. Following his M.Sc. and Ph.D. in the Department of Bioengineering at the University of Pennsylvania, he was then appointed Assistant Professor and Director of the Laboratory for Bio-Optics and Molecular Imaging at Harvard University and Massachusetts General Hospital. Since 2007, he has served as Professor of Medicine and Electrical Engineering and the Chair of Biological Imaging at the Technical University of Munich and Director of the Institute of Biological and Medical Imaging at Helmholtz Munich. Prof. Ntziachristos is also currently Director of Bioengineering at the Helmholtz Pioneer Campus and the Head of the Bioengineering Department at Helmholtz Munich.
Fields of Work and Expertise
Biomedical Engineering PhotonicsImagingMicroscopyOptoacousticsClinical Translation Computational Methods Machine Learning
Data Analytics Biological Engineering
Professional Background
Instructor, Harvard University and Massachusetts General Hospital
Assistant Professor and Director of the Laboratory of Bio-optics and Molecular Imaging, Harvard University and Massachusetts General Hospital
Full Professor C4/W3 of Medicine and Electrical Engineering, Chair of Biological Imaging at the Technical University of Munich Director, Institute for Biological and Medical Imaging
Publications
Read more2025 Scientific Article in Photoacoustics
Scale-equivariant deep model-based optoacoustic image reconstruction.
Model-based reconstruction provides state-of-the-art image quality for multispectral optoacoustic tomography. However, optimal regularization of in vivo data necessitates scan-specific adjustments of the regularization strength to compensate for fluctuations of the signal magnitudes between different sinograms. Magnitude fluctuations within in vivo data also pose a challenge for supervised deep learning of a model-based reconstruction operator, as training data must cover the complete range of expected signal magnitudes. In this work, we derive a scale-equivariant model-based reconstruction operator that i) automatically adjusts the regularization strength based on the L2 norm of the input sinogram, and ii) facilitates supervised deep learning of the operator using input singorams with a fixed norm. Scale-equivariant model-based reconstruction applies appropriate regularization to sinograms of arbitrary magnitude, achieves slightly better accuracy in quantifying blood oxygen saturation, and enables more accurate supervised deep learning of the operator.
Deciphering the spectra of breast cancer in multispectral optoacoustic tomography.
Multispectral optoacoustic tomography (MSOT) has been utilized to non-invasively resolve morphological changes like angiogenesis and metabolic parameters like hemoglobin concentration and oxygenation in breast tumors. Compared to other optical methods, MSOT provides higher spatial resolution, higher penetration depth and does not require the use of contrast agents. Thus, MSOT could aid the non-invasive diagnosis and treatment monitoring of breast cancer. Because MSOT illuminates tissue at multiple wavelengths, the acquired data contains spectral information about the chromophores contained in tissue. This spectral data may serve as additional dimension to infer cancer biomarkers. Recent advances in data processing and image reconstruction enable the spectroscopic analysis of MSOT data. However, effects like fluence attenuation and spectral coloring alter the spectral data hampering the identification of chromophores. Hence, it is necessary to analyze and understand spectral MSOT data—"MSOT spectra”—to not draw wrong conclusions. In this work, we showcase MSOT spectra of healthy and cancerous breast tissue in four patients between 680 nm and 1100 nm for the first time. We investigate trends and variations in MSOT spectra of tumor, tumor core, tumor rim, tumor perimeter and healthy background tissue with respect to different regions of interest and with respect to the tumors’ molecular subtypes. Moreover, we showcase effects of spectral coloring which are observed in the in-vivo MSOT spectra. Our work provides a new perspective on MSOT imaging of breast cancer. We lay the foundation to derive novel, spectral MSOT biomarkers of breast cancer aiding the clinical translation.
Multi-parametric standards for performance assessment and quality control of fluorescence molecular imaging and endoscopy systems.
Fluorescence molecular imaging (FMI) and endoscopy (FME) are technologies with great potential for image-guided surgical or diagnostic interventions. However, FMI and FME still present challenges that can confound real-time decision making for disease management and/or treatment. Importantly, the markedly different systems hurdle the repeatability of measurements, the unbiased readout interpretation, and the wide clinical acceptability of FMI and FME. Herein we present different multi-parametric standards to perform quality control and performance assessment of FMI and FME systems. Moreover, we discuss examples illustrating how data analysis and the design of fluorescence standards influence performance assessment outcomes, potentially affecting comparisons between systems or studies. We, also, show the first standard tailored to the requirements of FME and demonstrate its use for quality control of a fiberscope-based FME system. The discussed performance assessment and quality control framework can accelerate the clinical translation of fluorescence molecular imaging and endoscopy and steer further developments in the field.
2025 Scientific Article in Light: Science & Applications
Nonlinearity of optoacoustic signals and a new contrast mechanism for imaging.
Optoacoustic signals behave nonlinearly at light fluences above a few mJ/cm2, which may affect the interpretation and quantification of measurements. It has been proposed that optoacoustic nonlinearity arises from the heat-induced formation of nanobubbles or changes in local thermo-physical parameters. However, such explanations are only valid at much higher fluences than typically used in biomedical optoacoustic imaging (> 20 mJ/cm2) or in the presence of materials with high absorption coefficients such as gold nanoparticles. We propose herein that electromagnetic permittivity changes in response to photon absorption are major source of optoacoustic signal nonlinearity at low fluences. We provide theoretical and experimental evidence that supports this postulation and show that optoacoustic pressure responses due to permittivity changes, which are function of thermally excited third-order nonlinear susceptibility, can explain the nonlinear behavior of the optoacoustic signal. Since different materials exhibit different thermally excited third-order nonlinear susceptibility, this property could function as a new contrast mechanism that can identify the sensitivity of a substance's dielectric constant to photon-induced temperature changes. Consequently, we propose an imaging method based on nonlinear optoacoustic signals that exploits this newly identified contrast mechanism. These findings may have far-reaching implications for improving the accuracy of optoacoustics and utilizing the proposed new contrast mechanism would advance our understanding of cellular and tissue functionality.
2025 Scientific Article in Aerosol Science and Technology
An optoacoustic black carbon sensor for ship emission monitoring.
Black carbon (BC) emitted from ship exhaust has negative impacts on both human health and the climate. Monitoring BC emissions and, potentially, introducing a regulatory framework, will depend on the availability of reliable techniques for the measurement of its emission. Current sensors enabling continuous monitoring are too expensive and require frequent maintenance. We have recently developed a low-cost optoacoustic (OptA) BC sensor, which spatially separates OptA detection from OptA excitation, and demonstrated its performance in the laboratory. The unique chamber-based design of the sensor allows for the spatial separation of its delicate quartz tuning fork (QTF) detector from BC particles, while reaching high sensitivity without the need for filters. In this work, we examine for the first time the sensor operation in a real environment, by implementing it on-board a roll-on-roll-off (RoRo) ferry transporting cargo and passengers (RoPax). We present longitudinal measurements of BC concentrations within the ship’s exhaust. We observe a strong linear correlation (R2 = 0.9) between our OptA sensor to an aerosol absorption photometer, used for comparison. BC concentrations of the ships exhaust were measured directly from the funnel and BC emission factors were estimated based on simultaneously measured CO2 content of the exhaust and the carbon content of the fuel. BC concentrations were found to vary depending on the fuel used, namely, marine gas oil (MGO) and methanol. For the latter significantly reduced BC concentrations were observed. We finally discuss the implications of the technology for low-cost and low-maintenance sensors for on-board BC monitoring and beyond.
2025 Review in Reviews of Modern Physics
The need for optoacoustic microscopy.
Optoacoustic (photoacoustic) microscopy resolves optical absorption in cells and tissues, thus offering a complementary contrast mechanism to optical microscopy. Yet, the marked advances in optical microscopy techniques and their widespread use beg the question of the particular need and utility of an additional microscopy modality that resolves optical absorption. Recent advances that point to advantageous features and uses of optoacoustic microscopy in biological and clinical interrogation are presented. How these advances can be manifested as part of hybrid implementations using optical, optoacoustic, and possibly other forms of microscopy to enhance the ability of the microscopic interrogation is reviewed. Further examined are developments in the miniaturized optical detection of ultrasound, which can transform any optical microscope into a hybrid optical-optoacoustic system. In addition, recent progress with label-free molecular sensing and with new classes of novel reporters that expand the visualization capacity of the optoacoustic method are presented. Finally, how hybrid optical-optoacoustic microscopy offers a next step in multimodal interrogations, thereby impacting biological and clinical readings, is discussed.
2025 Review in Diabetes Research and Clinical Practice
Raster Scan optoacoustic Mesoscopy for detecting microvascular complications in diabetes mellitus: A narrative brief review.
Diabetes mellitus (DM) may lead to microvascular and macrovascular complications. Screening for these complications is crucial and non-invasive methods with high-dissemination potential are needed. Diabetic peripheral neuropathy (DPN) is particularly challenging to screen due to the lack of reliable clinical markers and endpoints. In this context, Raster Scan Optoacoustic Mesoscopy (RSOM) emerges as a highly promising technique that offers hybrid, non-invasive imaging of optical absorption using light-induced ultrasound waves within tissue without the use of contrast agents. RSOM provides high-resolution visualisation of micro-vasculature, other tissue structures and functional information. The technique has already assessed microvasculature loss as a function of diabetes progression and used it to characterise DPN severity. RSOM has also shown that cutaneous vessels in the mesoscopic range (mean diameters of 30-40 µm) are most prominently affected by DM and that the mean number of cutaneous vessels was lower in subjects with DM than in healthy participants (p < 0.001 and p < 0.05, respectively). Although experience is still limited, we present an overview of the novel technique in relation to its potential for detecting early DM onset and development of mircovascular complications.
2025 Editorial in Nature metabolism
A future without needles: Non-invasive glucose measurements in patients with diabetes.
Optical measurements through the skin are challenging because they usually represent averages across the various layers of skin that are illuminated. A study in Nature Metabolism uses a depth-selective variant of Raman spectroscopy to probe glucose levels specifically in the skin vasculature, and thereby achieves improved glucose sensing in humans.
2025 Scientific Article in Acta Biomaterialia
Photoswitching protein-XTEN fusions as injectable optoacoustic probes.
Optoacoustic imaging (OAI) is a unique in vivo imaging technique combining deep tissue penetration with high resolution and molecular sensitivity. OAI relying on strong intrinsic contrast, such as blood hemoglobin, already shows its value in medical diagnostics. However, OAI sensitivity to current extrinsic contrast agents is insufficient and limits its role in detecting disease-related biomarkers. The recently introduced concept of photoswitching and temporal unmixing techniques for OAI allows detecting extrinsic contrast with high sensitivity, allowing the visualization of small populations of cells labeled with photoswitching proteins deep within the tissue. However, transgene modification might not be permitted in some cases, such as for diagnostic use. Therefore, it is desirable to leverage the concept of photoswitching OAI towards injectable formulations. Since photoswitchable synthetic dyes are mainly excited by blue wavelengths unsuited for imaging in tissue, we propose exploiting the addition of XTENs to photoswitching proteins towards yielding injectable agents. The addition of XTEN to a protein enhances its plasma half-life and bioavailability, thus allowing its use, for example, in targeted labeling approaches. In this pilot study, we show that intravenously injected near-infrared absorbing photoswitchable proteins, ReBphP-PCM, coupled to XTEN, allow highly sensitive optoacoustic visualization of a tumor xenograft in vivo. The sensitivity to XTENs-ReBphP-PCM determined by ex vivo analysis of labeled cells is one to two orders of magnitude beyond conventional synthetic dyes used currently in OAI. The enhanced sensitivity afforded by photoswitching OAI, in combination with the increased bioavailability and biocompatibility of XTENs-ReBphP-PCM, makes this fusion protein a promising tool for facilitating sensitive detection of biomarkers in OAI with a potential for future use in diagnostics. STATEMENT OF SIGNIFICANCE: Optoacoustic imaging (OAI) is a unique in vivo imaging technique that combines deep tissue penetration with high resolution. OAI, which relies on intrinsic contrast, such as blood hemoglobin, could already be valuable in medical diagnostics. However, the use of extrinsic contrast agents to augment disease-related biomarkers in research and diagnostics suffers from very limited sensitivity of the generated contrast agent. We present an intravenously injected photoswitchable protein, ReBphP-PCM, coupled to XTEN, allowing highly sensitive OAI. The sensitivity is one to two orders of magnitude greater than that of conventional synthetic dyes used currently in OA imaging. The high sensitivity afforded by photoswitching together with the enhanced bioavailability and biocompatibility of the XTENs-ReBphP-PCM make this a standard agent for high-quality detection of OAI with potential for clinical use.
A primer on current status and future opportunities of clinical optoacoustic imaging.
Despite its introduction in the 1970’s, it is only recent technology advances that have propelled growth in clinical optoacoustic (photoacoustic) imaging over the past decade. We analytically present the broad landscape of clinical optoacoustic applications in the context of these key technology advances, the unique contrast achieved, and the tissue biomarkers resolved. We then discuss current challenges and future opportunities to address the unmet clinical needs.
2025 Scientific Article in Redox Biology
Radiosensitizing capacity of fenofibrate in glioblastoma cells depends on lipid metabolism.
Despite advances in multimodal therapy approaches such as resection, chemotherapy and radiotherapy, the overall survival of patients with grade 4 glioblastoma (GBM) remains extremely poor (average survival time <2 years). Altered lipid metabolism, which increases fatty acid synthesis and thereby contributes to radioresistance in GBM, is a hallmark of cancer. Therefore, we explored the radiosensitizing effect of the clinically approved, lipid-lowering drug fenofibrate (FF) in different GBM cell lines (U87, LN18). Interestingly, FF (50 μM) significantly radiosensitizes U87 cells by inducing DNA double-strand breaks through oxidative stress and impairing mitochondrial membrane integrity, but radioprotects LN18 cells by reducing the production of reactive oxygen species (ROS) and stabilizing the mitochondrial membrane potential. A comparative protein and lipid analysis revealed striking differences in the two GBM cell lines: LN18 cells exhibited a significantly higher membrane expression density of the fatty acid (FA) cluster protein transporter CD36 than U87 cells, a higher expression of glycerol-3-phosphate acyltransferase 4 (GPAT4) which supports the production of large lipid droplets (LDs), and a lower expression of diacylglycerol O-acyltransferase 1 (DGAT1) which regulates the formation of small LDs. Consequently, large LDs are predominantly found in LN18 cells, whereas small LDs are found in U87 cells. After a combined treatment of FF and irradiation, the number of large LDs significantly increased in radioresistant LN18 cells, whereas the number of small LDs decreased in radiosensitive U87 cells. The radioprotective effect of FF in LN18 cells could be associated with the presence of large LDs, which act as a sink for the lipophilic drug FF. To prevent uptake of FF by large LDs and to ameliorate its function as a radiosensitizer, FF was encapsulated in biomimetic cell membrane extracellular lipid vesicles (CmEVs) which alter the intracellular trafficking of the drug. In contrast to the free drug, CmEV-encapsulated FF was predominantly enriched in the lysosomal compartment, causing necrosis by impairing lysosomal membrane integrity. Since the stability of plasma and lysosomal membranes is maintained by the presence of the stress-inducible heat shock protein 70 (Hsp70) which has a strong affinity to tumor-specific glycosphingolipids, necrosis occurs predominantly in LN18 cells having a lower membrane Hsp70 expression density than U87 cells. In summary, our findings indicate that the lipid metabolism of tumor cells can affect the radiosensitizing capacity of FF when encountered either as a free drug or as a drug loaded in biomimetic lipid vesicles.
2025 Scientific Article in Journal of Biomedical Optics
Impact of signal-to-noise ratio and contrast definition on the sensitivity assessment and benchmarking of fluorescence molecular imaging systems.
SIGNIFICANCE: Standardization of fluorescence molecular imaging (FMI) is critical for ensuring quality control in guiding surgical procedures. To accurately evaluate system performance, two metrics, the signal-to-noise ratio (SNR) and contrast, are widely employed. However, there is currently no consensus on how these metrics can be computed. AIM: We aim to examine the impact of SNR and contrast definitions on the performance assessment of FMI systems. APPROACH: We quantified the SNR and contrast of six near-infrared FMI systems by imaging a multi-parametric phantom. Based on approaches commonly used in the literature, we quantified seven SNRs and four contrast values considering different background regions and/or formulas. Then, we calculated benchmarking (BM) scores and respective rank values for each system. RESULTS: We show that the performance assessment of an FMI system changes depending on the background locations and the applied quantification method. For a single system, the different metrics can vary up to ∼ 35 dB (SNR), ∼ 8.65 a . u . (contrast), and ∼ 0.67 a . u . (BM score). CONCLUSIONS: The definition of precise guidelines for FMI performance assessment is imperative to ensure successful clinical translation of the technology. Such guidelines can also enable quality control for the already clinically approved indocyanine green-based fluorescence image-guided surgery.
2024 Editorial in Nature Reviews Bioengineering
Addressing unmet clinical need with optoacoustic imaging.
Optoacoustic (photoacoustic) imaging has seen considerable growth in technological advances and clinical application over the past decade. This piece critically discusses whether optoacoustic imaging can become a mainstream clinical modality.
2024 Scientific Article in Photoacoustics
Multiscale optoacoustic assessment of skin microvascular reactivity in carotid artery disease.
Microvascular endothelial dysfunction may provide insights into systemic diseases, such as carotid artery disease. Raster-scan optoacoustic mesoscopy (RSOM) can produce images of skin microvasculature during endothelial dysfunction challenges via numerous microvascular features. Herein, RSOM was employed to image the microvasculature of 26 subjects (13 patients with single carotid artery disease, 13 healthy participants) to assess the dynamics of 18 microvascular features at three scales of detail, i.e., the micro- (<100 μm), meso- (≈100–1000 μm) and macroscale (<1000 μm), during post-occlusive reactive hyperemia challenges. The proposed analysis identified a subgroup of 9 features as the most relevant to carotid artery disease because they achieved the most efficient classification (AUC of 0.93) between the two groups in the first minute of hyperemia (sensitivity/specificity: 0.92/0.85). This approach provides a non-invasive solution to microvasculature quantification in carotid artery disease, a main form of cardiovascular disease, and further highlights the possible link between systemic disease and microvascular dysfunction.
2024 Scientific Article in Journal of Biophotonics
Hybrid Raman and partial wave spectroscopy microscope for the characterization of molecular and structural alterations in tissue.
We present a hybrid Raman spectroscopy (RS) and partial wave spectroscopy (PWS) microscope for the characterization of molecular and structural tissue alterations. The PWS performance was assessed with surface roughness standards, while the Raman performance with a silicon crystal standard. We also validated the system on stomach and intestinal mouse tissues, two closely-related tissue types, and demonstrate that the addition of PWS information improves RS data classification for these tissue types from R2 = 0.892 to R2 = 0.964 (norm of residuals 0.863 and 0.497, respectively). Then, in a proof-of-concept experiment, we show that the hybrid system can detect changes in intestinal tissues harvested from a tumorigenic Villin-Cre, Apcfl/wt mouse. We discuss how the hybrid modality offers new abilities to identify the relative roles of PWS morphological features and Raman molecular fingerprints, possibly allowing for their combination to enhance the study of carcinogenesis and early cancer diagnostics in the future.
2024 Review in Molecular Imaging and Biology
Neurotoxin-derived optical probes for elucidating molecular and developmental biology of neurons and synaptic connections : Toxin-derived optical probes for neuroimaging.
Botulinum neurotoxins (BoNTs) and tetanus toxin (TeTX) are the deadliest biological substances that cause botulism and tetanus, respectively. Their astonishing potency and capacity to enter neurons and interfere with neurotransmitter release at presynaptic terminals have attracted much interest in experimental neurobiology and clinical research. Fused with reporter proteins or labelled with fluorophores, BoNTs and TeTX and their non-toxic fragments also offer remarkable opportunities to visualize cellular processes and functions in neurons and synaptic connections. This study presents the state-of-the-art optical probes derived from BoNTs and TeTX and discusses their applications in molecular and synaptic biology and neurodevelopmental research. It reviews the principles of the design and production of probes, revisits their applications with advantages and limitations and considers prospects for future improvements. The versatile characteristics of discussed probes and reporters make them an integral part of the expanding toolkit for molecular neuroimaging, promoting the discovery process in neurobiology and translational neurosciences.
2024 Scientific Article in NPJ Cardiovascular Health
Intravascular ICG-enhanced NIRF-IVUS imaging to assess progressive atherosclerotic lesions in excised human coronary arteries.
Indocyanine green (ICG)-enhanced intravascular near-infrared fluorescence (NIRF) imaging enhances the information obtained with intravascular ultrasound (IVUS) by visualizing pathobiological characteristics of atherosclerotic plaques. To advance our understanding of this hybrid method, we aimed to assess the potential of NIRF-IVUS to identify different stages of atheroma progression by characterizing ICG uptake in human pathological specimens. After excision, 15 human coronary specimens from 13 adult patients were ICG-perfused and imaged with NIRF-IVUS. All specimens were then histopathologically and immunohistochemically assessed. NIRF-IVUS imaging revealed colocalization of ICG-deposition to plaque areas of lipid accumulation, endothelial disruption, neovascularization and inflammation. Moreover, ICG concentrations were significantly higher in advanced coronary artery disease stages (p < 0.05) and correlated significantly to plaque macrophage burden (r = 0.67). Current intravascular methods fail to detect plaque biology. Thus, we demonstrate how human coronary atheroma stage can be assessed based on pathobiological characteristics uniquely captured by ICG-enhanced intravascular NIRF.
Controlling the sound of light: photoswitching optoacoustic imaging.
Optoacoustic (photoacoustic) imaging advances allow high-resolution optical imaging much deeper than optical microscopy. However, while label-free optoacoustics have already entered clinical application, biological imaging is in need of ubiquitous optoacoustic labels for use in ways that are similar to how fluorescent proteins propelled optical microscopy. We review photoswitching advances that shine a new light or, in analogy, 'bring a new sound' to biological optoacoustic imaging. Based on engineered labels and novel devices, switching uses light or other energy forms and enables signal modulation and synchronous detection for maximizing contrast and detection sensitivity over other optoacoustic labels. Herein, we explain contrast enhancement in the spectral versus temporal domains and review labels and key concepts of switching and their properties to modulate optoacoustic signals. We further outline systems and applications and discuss how switching can enable optoacoustic imaging of cellular or molecular contrast at depths and resolutions beyond those of other optical methods.
2024 Scientific Article in Nature Communications
Bragg grating etalon-based optical fiber for ultrasound and optoacoustic detection.
Fiber-based interferometers receive significant interest as they lead to miniaturization of optoacoustic and ultrasound detectors without the quadratic loss of sensitivity common to piezoelectric elements. Nevertheless, in contrast to piezoelectric crystals, current fiber-based ultrasound detectors operate with narrow ultrasound bandwidth which limits the application range and spatial resolution achieved in imaging implementations. We port the concept of silicon waveguide etalon detection to optical fibers using a sub-acoustic reflection terminator to a Bragg grating embedded etalon resonator (EER), uniquely implementing direct and forward-looking access to incoming ultrasound waves. Precise fabrication of the terminator is achieved by continuously recording the EER spectrum during polishing and fitting the spectra to a theoretically calculated spectrum for the selected thickness. Characterization of the EER inventive design reveals a small aperture (10.1 µm) and an ultra-wide bandwidth (160 MHz) that outperforms other fiber resonators and enables an active detection area and overall form factor that is smaller by more than an order of magnitude over designs based on piezoelectric transducers. We discuss how the EER paves the way for the most adept fiber-based miniaturized sound detection today, circumventing the limitations of currently available designs.
2024 Scientific Article in Photoacoustics
Non-invasive optoacoustic imaging of dermal microcirculatory revascularization in diet-induced obese mice undergoing exercise intervention.
Microcirculatory dysfunction has been observed in the dermal white adipose tissue (dWAT) and subcutaneous white adipose tissue (scWAT) of obese humans and has been proposed as an early prediction marker for cardio-metabolic disease progression. In-vivo visualization and longitudinal monitoring of microvascular remodeling in these tissues remains challenging. We compare the performance of two optoacoustic imaging methods, i.e. multi-spectral optoacoustic tomography (MSOT) and raster-scanning optoacoustic mesoscopy (RSOM) in visualizing lipid and hemoglobin contrast in scWAT and dWAT in a mouse model of diet-induced obesity (DIO) undergoing voluntary wheel running intervention for 32 weeks. MSOT visualized lipid and hemoglobin contrast in murine fat depots in a quantitative manner even at early stages of DIO. We show for the first time to our knowledge that RSOM allows precise visualization of the dWAT microvasculature and provides quantitative readouts of skin layer thickness and vascular density in dWAT and dermis. Combination of MSOT and RSOM resolved exercise-induced morphological changes in microvasculature density, tissue oxygen saturation, lipid and blood volume content in dWAT and scWAT. The combination of MSOT and RSOM may allow precise monitoring of microcirculatory dysfunction and intervention response in dWAT and scWAT in a mouse model for DIO. Our findings have laid out the foundation for future clinical studies using optoacoustic-derived vascular readouts from adipose tissues as a biomarker for monitoring microcirculatory function in metabolic disease.