Simultaneous visualization of tumour oxygenation, neovascularization and contrast agent perfusion by real-time three-dimensional optoacoustic tomography.
OBJECTIVE
Intravital imaging within heterogenic solid tumours is important for understanding blood perfusion profiles responsible for establishment of multiple parameters within the tumour mass, such as hypoxic and nutrition gradients, cell viability, proliferation and drug response potentials.


METHODS
Herein, we developed a method based on a volumetric multispectral optoacoustic tomography (vMSOT) for cancer imaging in preclinical models and explored its capacity for three-dimensional imaging of anatomic, vascular and functional tumour profiles in real time.


RESULTS
In contrast to methods based on cross-sectional (2D) image acquisition as a basis for 3D rendering, vMSOT has attained concurrent observations from the entire tumour volume at 10 volumetric frames per second. This truly four dimensional imaging performance has enabled here the simultaneous assessment of blood oxygenation gradients and vascularization in solid breast tumours and revealed different types of blood perfusion profiles in-vivo.


CONCLUSIONS
The newly introduced capacity for high-resolution three-dimensional tracking of fast tumour perfusion suggests vMSOT as a powerful method in preclinical cancer research and theranostics. As the imaging setup can be equally operated in both stationary and handheld mode, the solution is readily translatable for perfusion monitoring in a clinical setting.


CONCLUSIONS
• vMSOT visualizes 3D anatomic, vascular and functional tumour profiles in real time. • Three types of blood perfusion profiles are revealed in breast tumour model. • The method is readily adaptable to operate in a handheld clinical mode.
Institute for Biological and Medical Imaging (IBMI), Helmholtz Center Munich, Ingolstädter Landstraβe 1, 85764, Neuherberg, Germany.|Faculty of Medicine, Technical University of Munich, Ismaninger Straβe 22, 81675, Munich, Germany.
Vladimir
V
Ermolayev
Institute for Biological and Medical Imaging (IBMI), Helmholtz Center Munich, Ingolstädter Landstraβe 1, 85764, Neuherberg, Germany.
Xose Luis
XL
Dean-Ben
Institute for Biological and Medical Imaging (IBMI), Helmholtz Center Munich, Ingolstädter Landstraβe 1, 85764, Neuherberg, Germany.
Subhamoy
S
Mandal
Institute for Biological and Medical Imaging (IBMI), Helmholtz Center Munich, Ingolstädter Landstraβe 1, 85764, Neuherberg, Germany.|Faculty of Medicine, Technical University of Munich, Ismaninger Straβe 22, 81675, Munich, Germany.
Vasilis
V
Ntziachristos
Institute for Biological and Medical Imaging (IBMI), Helmholtz Center Munich, Ingolstädter Landstraβe 1, 85764, Neuherberg, Germany. dr@tum.de.|Faculty of Medicine, Technical University of Munich, Ismaninger Straβe 22, 81675, Munich, Germany. dr@tum.de.
Daniel
D
Razansky
D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods; D007208:Indocyanine Green / Q000493:pharmacokinetics; D015674:Mammary Neoplasms, Animal / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000473:pathology; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging*; D010101:Oxygen Consumption; D010477:Perfusion; D061088:Photoacoustic Techniques / Q000379:methods*; D014054:Tomography / Q000379:methods
D003287:Contrast Media; D007208:Indocyanine Green
3D Optoacoustic tomography; Breast cancer; Molecular imaging; Nanoparticles; Neovascularization