Prof. Vasilis Ntziachristos, Msc PhD
Direktor, des Instituts für Biologische und Medizinische Bildgebung und Direktor des Departments für Bioengineering.Unsere Forschung am Helmholtz München wird von unserem Interesse angetrieben, Lösungen zu bieten, die kritische ungedeckte medizinische Bedürfnisse adressieren und das Gesundheitswesen sowie das Wohl der Gesellschaft positiv beeinflussen.
Unsere Forschung am Helmholtz München wird von unserem Interesse angetrieben, Lösungen zu bieten, die kritische ungedeckte medizinische Bedürfnisse adressieren und das Gesundheitswesen sowie das Wohl der Gesellschaft positiv beeinflussen.
Akademische Laufbahn und Forschungsgebiete
Die Forschung von Vasilis Ntziachristos konzentriert sich auf die Entwicklung neuer Methoden zur Verbesserung des Wohlbefindens und zur Beschleunigung von Entdeckungen. Sein Schwerpunkt liegt auf der Entwicklung neuartiger Methoden zur Prävention und Früherkennung von Krankheiten, die auch als Mittel zur Verabreichung effizienterer Behandlungen dienen. Seine Expertise umfasst die Bereiche Bildgebung, Sensorik und Berechnung, und seine Aktivitäten decken das gesamte Spektrum von theoretischen und methodischen Entwicklungen und grundlegenden Entdeckungen bis hin zur klinischen Umsetzung und Unternehmertum ab. Beispiele für seine Arbeit sind die Entwicklung der Fluoreszenzmolekularbildgebung zur Verbesserung der Führung bei Operationen und der Leistung der diagnostischen Endoskopie sowie die Entwicklung von optoakustischen Bildgebungs- und Mikroskopiemethoden zur Förderung von Entdeckungen und zur Beeinflussung des Gesundheitswesens. Er ist Gründer mehrerer Unternehmen, darunter SurgVision BV, das Fluoreszenzbildgebungslösungen für die Chirurgie kommerzialisiert und jetzt unter Bracco SpA steht, und iThera Medical GmbH, ein Unternehmen, das optoakustische Technologie kommerzialisiert.
Professor Vasilis Ntziachristos studierte Elektrotechnik an der Aristoteles-Universität in Thessaloniki. Nach seinem M.Sc. und Ph.D. am Department of Bioengineering der University of Pennsylvania wurde er zum Assistant Professor und Direktor des Laboratory for Bio-Optics and Molecular Imaging an der Harvard University und dem Massachusetts General Hospital ernannt. Seit 2007 ist er Professor für Medizin und Elektrotechnik und Lehrstuhlinhaber für Biologische Bildgebung an der Technischen Universität München sowie Direktor des Instituts für Biologische und Medizinische Bildgebung am Helmholtz München. Prof. Ntziachristos ist derzeit auch Direktor des Bioengineering am Helmholtz Pioneer Campus und Leiter der Abteilung für Bioengineering am Helmholtz München.
Arbeits- und Fachgebiete
Biomedizinische Technik PhotonikBildgebungMikroskopieOptoakustikKlinische Umsetzung Computational Methoden Machinelles Lernen
Datenanalyse Biologische Ingenieurwissenschaften
Beruflicher Hintergrund
Dozent an der Harvard University und dem Massachusetts General Hospital
Assistenzprofessor und Direktor des Labors für Bio-Optik und Molekulare Bildgebung, Harvard University und Massachusetts General Hospital
Ordentlicher Professor C4/W3 für Medizin und Elektrotechnik, Lehrstuhl für Biologische Bildgebung an der Technischen Universität München, Direktor des Instituts für Biologische und Medizinische Bildgebung
Publikationen
Weiterlesen2025 Wissenschaftlicher Artikel 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 Wissenschaftlicher Artikel 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 Wissenschaftlicher Artikel 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 Wissenschaftlicher Artikel 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 Wissenschaftlicher Artikel 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 Wissenschaftlicher Artikel 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.
