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Munchen, Germany

Wu W.,Nanjing University | Driessen W.,iThera Medical | Jiang X.,Nanjing University
Journal of the American Chemical Society | Year: 2014

Dendrimers have several featured advantages over other nanomaterials as drug carriers, such as well-defined structure, specific low-nanometer size, and abundant peripheral derivable groups, etc. However, these advantages have not been fully exploited yet to optimize their biological performance, especially tumor penetration, which is a shortcoming of current nanomaterials. Here we show the syntheses of a new class of oligo(ethylene glycol) (OEG)-based thermosensitive dendrimers up to the fourth generation. Each dendrimer shows monodisperse structure. OEG/poly(ethylene glycol) (PEG) moieties with different precise lengths were introduced to the periphery of the fourth-generation dendrimer followed by an antitumor agent, gemcitabine (GEM). The biodistributions of the GEM-conjugated dendrimers were investigated by micro positron emission tomography and multispectral optoacoustic tomography imaging techniques and compared with that of GEM-conjugated poly(amidoamine) (PAMAM). The GEM-conjugated dendrimer with the longest peripheral PEG segments exhibited the most desirable tumor accumulation and penetration and thus had significantly higher antitumor activity than the GEM-conjugated PAMAM. © 2014 American Chemical Society.

Buehler A.,Helmholtz Center Munich | Kacprowicz M.,iThera Medical | Taruttis A.,Helmholtz Center Munich | Taruttis A.,TU Munich | And 2 more authors.
Optics Letters | Year: 2013

Multispectral optoacoustic tomography (MSOT) of functional and molecular contrast has the potential to find broad deployment in clinical practice. We have developed the first handheld MSOT imaging device with fast wavelength tuning achieving a frame rate of 50 Hz. In this Letter, we demonstrate its clinical potential by dynamically resolving multiple disease-relevant tissue chromophores, including oxy-/deoxyhemoglobin, and melanin, in human volunteers. © 2013 Optical Society of America.

Tzoumas S.,Helmholtz Center Munich | Deliolanis N.,Helmholtz Center Munich | Deliolanis N.,Fraunhofer Project Group for Automation in Medicine and Biotechnology | Morscher S.,Helmholtz Center Munich | And 2 more authors.
IEEE Transactions on Medical Imaging | Year: 2014

Detection of intrinsic or extrinsically administered chromophores and photo-absorbing nanoparticles has been achieved by multi-spectral optoacoustic tomography (MSOT). The detection sensitivity of MSOT depends not only on the signal to noise ratio considerations, as in conventional optoacoustic (photoacoustic) tomography implementations, but also on the ability to resolve the molecular targets of interest from the absorbing tissue background by means of spectral unmixing or sub-pixel detection methods. However, it is not known which unmixing methods are optimally suited for the characteristics of multispectral optoacoustic images. In this work we investigated the performance of different sub-pixel detection methods, typically used in remote sensing hyperspectral imaging, within the context of MSOT. A quantitative comparison of the different algorithmic approaches was carried out in an effort to identify methods that operate optimally under the particulars of molecular imaging applications. We find that statistical sub-pixel detection methods can demonstrate a unique detection performance with up to five times enhanced sensitivity as compared to linear unmixing approximations, under the condition that the optical agent of interest is sparsely present within the tissue volume, as common when using targeted agents and reporter genes. © 1982-2012 IEEE.

Dima A.,Helmholtz Center Munich | Gateau J.,Helmholtz Center Munich | Claussen J.,iThera Medical | Wilhelm D.,TU Munich | Ntziachristos V.,Helmholtz Center Munich
Journal of Biophotonics | Year: 2013

Reliably assessing tissue viability during surgery is of major importance in surgical procedures. The most basic requirement for viability is sufficient oxygen supply to the tissue. Therefore it is highly desirable to visualize in real-time the dynamic process of blood perfusion up to and within the microvasculature. A modality sensitive to structures in the range of few hundred micrometers and offering high contrast to the embedding tissue is then needed. To this end, a number of methods have been developed, but have had no significant impact on the clinical routine due to various deficiencies. In this paper we demonstrate the applicability of optoacoustic imaging, which combines ultrasonic resolution with strong optical contrast. A method for optoacoustic perfusion assessment, based on a local and repeatable injection of saline, was proposed and assessed ex-vivo on large pig bowels and in-vivo in mouse tails. The obtained dynamic perfusion images highlight the method's potential to enable immediate and quantitative assessment of tissue viability during surgery. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dima A.,Helmholtz Center Munich | Dima A.,TU Munich | Burton N.C.,iThera Medical | Ntziachristos V.,Helmholtz Center Munich | Ntziachristos V.,TU Munich
Journal of Biomedical Optics | Year: 2014

Optoacoustic (photoacoustic) imaging has already showcased the capacity to offer high-resolution small animal visualization in vivo in a variety of cancer, cardiovascular, or neuroimaging applications. In particular, multispectral optoacoustic tomography (MSOT) has shown imaging along the spectral and the time dimensions, enabling sensing of multiple molecules over time and, more recently, in real time. Furthermore, cross-sectional imaging of at least 20 mm diameter has been showcased in vivo in animals and humans using 64-element curved transducers placed along a single curved line. Herein, we investigated the imaging improvements gained by utilizing a larger number of detectors and inquired whether more detectors will result in measurable image quality improvements. For this reason, we implemented MSOT using 64-, 128-, and 256-element transducers and imaged the same phantoms and animals under similar conditions. Further, corroborated by numerical simulation analysis, our findings quantify the improvements in resolution and overall image quality for the increasing number of detectors used pointing to significant improvements in image quality for the 256 detector array, over 64 or 128 detectors. © 2014 Society of Photo-Optical Instrumentation Engineers.

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