Blood vessels are the only system to provide nutrients and oxygen to every part of the body. Many diseases can have significant effects on blood vessel formation, so the vascular network can be a cue to assess malicious tumor and ischemic tissues. Various imaging techniques can visualize the blood vessel structure, but their applications are often constrained by either expensive costs, contrast agents, ionizing radiations, or a combination of the above.

To achieve images of the vasculature using exogenous contrast agents, contrast-enhanced ultrasound (CEUS) can be employed. Microbubbles are injected and flow throughout the blood stream; using a volumetric ultrasound probe and harmonic imaging it is then possible to acquire images that show mainly where the microbubbles are located, hence the vasculature.

To achieve completely non-invasive vasculature imaging using endogenous contrast, Power Doppler ultrasound imaging can be employed, although it is limited in resolution and noisy. Another very viable option is biomedical optical imaging. Using scattering contrast, optical coherence tomography angiography (OCTA) can detect blood vessels, enabling non-invasive, in vivo, high-resolution, cross-sectional imaging in biological tissues, with a penetration depth limit to ~1–2 mm. Photoacoustic (PA) imaging combines the high-contrast and spectroscopic-based specificity of optical imaging with the high spatial resolution of ultrasound imaging. PA imaging operates in the scattering regime, but its resolution is not limited by scattering and the image contrast depends on optical absorption, making it capable of mapping blood vessels that are situated deeper in biological tissues, while still maintaining its non-invasive quality.

From the acquired volumes of these imaging modalities, a 3D map of the vasculature can be qualitatively appreciated and, more importantly, quantitative parameters can be extracted to assess the complexity of the vascular network. To do so, segmentation and skeletonization techniques are applied to the volumes and morphological and tortuosity parameters can be computed, such as the number of vascular trees, number of branches, vascular density, distance metric, inflection count metric and sum of angles metric. These parameters have shown to be able to quantitatively characterize the vascular network which can assess microenvironmental changes related to disease progression, and have been studied in our research group particularly in terms of clinical imaging of skin cancers (OCTA) and thyroid nodules (CEUS+Power Doppler), and preclinical tumor (CEUS) and burn wound healing (PA) assessment over time.


  • Filippo Molinari (Full Professor)
  • Kristen M. Meiburger (Assistant Professor with time contract (RTD/a))
  • Collaborators:

  • Prof. Wolfgang Drexler, Mengyang Liu - Medical University of Vienna
  • Funded project:

  • REAP - Revealing drug tolerant persister cells in cancer using contrast enhanced optical coherence and photoacoustic tomography

  • Recent publications:

  • Automatic skin lesion area determination of basal cell carcinoma using optical coherence tomography angiography and a skeletonization approach: Preliminary results
      Kristen M. Meiburger, Zhe Chen, Christoph Sinz, Erich Hoover, Michael Minneman, Jason Ensher, Harald Kittler, Rainer A. Leitgeb, Wolfgang Drexler, Mengyang Liu
      Journal of Biophotonics
  • Quantitative analysis of thyroid tumors vascularity: A comparison between 3‐D contrast‐enhanced ultrasound and 3‐D Power Doppler on benign and malignant thyroid nodules
      Cristina Caresio, Marco Caballo, Maurilio Deandrea, Roberto Garberoglio, Alberto Mormile, Ruth Rossetto, Paolo Limone, Filippo Molinari
      Medical Physics
  • Non-invasive multimodal optical coherence and photoacoustic tomography for human skin imaging
      Zhe Chen, Elisabet Rank, Kristen M. Meiburger, Christoph Sinz, Andreas Hodul, Edward Zhang, Erich Hoover, Micheal Minneman, Jason Ensher, Paul C. Beard, Harald Kittler, Rainer A. Leitgeb, Wolfgang Drexler, Mengyang Liu
      Scientific Reports
  • Skeletonization algorithm-based blood vessel quantification using in vivo 3D photoacoustic imaging
      Kristen M. Meiburger, Seung Yun Nam, Eunna Chung, Laura J. Suggs5, Stanislav Y. Emelianov, Filippo Molinari
      Physics in Medicine and Biology
  • Quantitative Assessment of Cancer Vascular Architecture by Skeletonization of High-Resolution 3-D Contrast-Enhanced Ultrasound Images: Role of Liposomes and Microbubbles
      Filippo Molinari, Kristen M. Meiburger, Pierangela Giustetto, Silvia Rizzitelli, Cinzia Boffa, Mauro Castano, Enzo Terreno
      Technology in Cancer Research and Treatment