Dirk Grosenick

Physikalisch-Technische Bundesanstalt, Brunswyck, Lower Saxony, Germany

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Publications (58)73.74 Total impact

  • Journal of Biomedical Optics 05/2015; 20(5):51025. · 2.75 Impact Factor
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    ABSTRACT: We hypothesize that combining quantitative near-infrared spectroscopy (NIRS) with established invasive techniques will enable advanced insights into renal hemodynamics and oxygenation in small animal models. We developed a NIRS technique to monitor absolute values of oxygenated and deoxygenated hemoglobin and of oxygen saturation of hemoglobin within the renal cortex of rats. This NIRS technique was combined with invasive methods to simultaneously record renal tissue oxygen tension and perfusion. The results of test procedures including occlusions of the aorta or the renal vein, hyperoxia, hypoxia, and hypercapnia demonstrated that the combined approach, by providing different but complementary information, enables a more comprehensive characterization of renal hemodynamics and oxygenation.
    Biomedical Optics Express 02/2015; 6(2). · 3.50 Impact Factor
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    ABSTRACT: Renal tissue hypoperfusion and hypoxia are key elements in the pathophysiology of acute kidney injury and its progression to chronic kidney disease. Yet, in vivo assessment of renal haemodynamics and tissue oxygenation remains a challenge. Many of the established approaches are invasive, hence not applicable in humans. Blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) offers an alternative. BOLD-MRI is non-invasive and indicative of renal tissue oxygenation. Nonetheless recent (pre-)clinical studies revived the question as to how bold renal BOLD-MRI really is. This review aims to deliver some answers. It is designed to inspire the renal physiology, nephrology, and imaging communities to foster explorations into the assessment of renal oxygenation and haemodynamics by exploiting the powers of MRI. For this purpose the specifics of renal oxygenation and perfusion are outlined. The fundamentals of BOLD-MRI are summarized. The link between tissue oxygenation and the oxygenation sensitive MR biomarker T2* is outlined. The merits and limitations of renal BOLD-MRI in animal and human studies are surveyed together with their clinical implications. Explorations into detailing the relation between renal T2* and renal tissue partial pressure of oxygen (pO2) are discussed with a focus on factors confounding the T2* versus tissue pO2 relation. Multi-modality in vivo approaches suitable for detailing the role of the confounding factors that govern T2* are considered. A schematic approach describing the link between renal perfusion, oxygenation, tissue compartments and renal T2* is proposed. Future directions of MRI assessment of renal oxygenation and perfusion are explored.This article is protected by copyright. All rights reserved.
    Acta Physiologica 09/2014; · 4.25 Impact Factor
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    ABSTRACT: In the present contribution we investigate the images of CW diffusely reflected light for a point-like source, registered by a CCD camera imaging a turbid medium containing an absorbing lesion. We show that detection of μa variations (absorption anomalies) is achieved if images are normalized to background intensity. A theoretical analysis based on the diffusion approximation is presented to investigate the sensitivity and the limitations of our proposal and a novel procedure to find the location of the inclusions in 3D is given and tested. An analysis of the noise and its influence on the detection capabilities of our proposal is provided. Experimental results on phantoms are also given, supporting the proposed approach.
    Biomedical Optics Express 05/2014; 5(5):1336-54. · 3.50 Impact Factor
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    ABSTRACT: We investigate the correction of fluorescence intensities in epi-illumination imaging by normalization to absorption images. Experiments on custom lymph node phantoms reveal improved estimation of dye concentration for superficial nodes.
    Biomedical Optics; 04/2014
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    ABSTRACT: We have developed a method to quantify hemoglobin concentration and oxygen saturation within the renal cortex by near-infrared spectroscopy. A fiber optic probe was used to transmit the radiation of three semiconductor lasers at 690 nm, 800 nm and 830 nm to the tissue, and to collect diffusely remitted light at source-detector separations from 1 mm to 4 mm. To derive tissue hemoglobin concentration and oxygen saturation of hemoglobin the spatial dependence of the measured cw intensities was fitted by a Monte Carlo model. In this model the tissue was assumed to be homogeneous. The scaling factors between measured intensities and simulated photon flux were obtained by applying the same setup to a homogeneous semi-infinite phantom with known optical properties and by performing Monte Carlo simulations for this phantom. To accelerate the fit of the tissue optical properties a look-up table of the simulated reflected intensities was generated for the needed range of absorption and scattering coefficients. The intensities at the three wavelengths were fitted simultaneously using hemoglobin concentration, oxygen saturation, the reduced scattering coefficient at 800 nm and the scatter power coefficient as fit parameters. The method was employed to study the temporal changes of renal hemoglobin concentration and blood oxygenation on an anesthetized rat during a short period of renal ischemia induced by aortic occlusion and during subsequent reperfusion.
  • Bernd Ebert, Dirk Grosenick
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    ABSTRACT: Optical imaging offers a high potential for noninvasive detection of cancer in humans. Recent advances in instrumentation for diffuse optical imaging have led to new capabilities for the detection of cancer in highly scattering tissue such as the female breast. We review recent developments in the detection of breast cancer in humans by fluorescent contrast agents. So far, the unspecific contrast agents indocyanine green (ICG) and omocyanine have been applied, whereas molecular probes for direct targeted imaging of this disease are still in preclinical research. We discuss recent improvements in the differentiation of malignant and benign lesions with ICG based on its enhanced extravasation in breast cancer. Whereas fluorescence imaging in thick tissue layers is hampered by strong light scattering, tissue surfaces can be investigated with high spatial resolution. As an example for superficial tumors, lesions of the gastrointestinal tract (GI) are discussed. In these investigations, protoporphyrin IX is used as a tumor-specific (due to its strong enhancement in tumor cells) target for spectroscopic identification and imaging. We present a time-gated method for fluorescence imaging and spectroscopy with strong suppression of tissue autofluorescence and show results on patients with Barrett's esophagus and with colitis ulcerosa.
    Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer 01/2013; 187:331-50.
  • Bernd Ebert, Dirk Grosenick, Heidrun Wabnitz
    Journal of Near Infrared Spectroscopy 01/2012; 20(1):203-. · 1.48 Impact Factor
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    ABSTRACT: To assess early- and late-fluorescence near-infrared imaging, corresponding to the vascular (early-fluorescence) and extravascular (late-fluorescence) phases of indocyanine green (ICG) enhancement, for breast cancer detection and benign versus malignant breast lesion differentiation. The study was approved by the ethical review board; all participants provided written informed consent. Twenty women with 21 breast lesions were examined with near-infrared imaging before, during, and after intravenous injection of ICG. Absorption and fluorescence projection mammograms were recorded simultaneously on a prototype near-infrared imaging unit. Two blinded readers independently assessed the images and assigned visibility scores to lesions seen on the absorption and absorption-corrected fluorescence mammograms. Imaging results were compared with histopathologic findings. Lesion contrast and diameter on the fluorescence mammograms were measured, and Cohen κ, Mann-Whitney U, and Spearman ρ tests were conducted. The absorption-corrected fluorescence ratio mammograms showed high contrast (contrast value range, 0.25-0.64) between tumors and surrounding breast tissue. Malignant lesions were correctly defined in 11 (reader 1) and 12 (reader 2) of 13 cases, and benign lesions were correctly defined in six (reader 1) and five (reader 2) of eight cases with late-fluorescence imaging. Lesion visibility scores for malignant and benign lesions were significantly different on the fluorescence ratio mammograms (P = .003) but not on the absorption mammograms (P = .206). Mean sensitivity and specificity reached 92% ± 8 (standard error of mean) and 75% ± 16, respectively, for fluorescence ratio imaging compared with 100% ± 0 and 25% ± 16, respectively, for conventional mammography alone. Preliminary data suggest that early- and late-fluorescence ratio imaging after ICG administration can be used to distinguish malignant from benign breast lesions.
    Radiology 02/2011; 258(2):409-16. · 6.21 Impact Factor
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    ABSTRACT: We present a scanning time-domain fluorescence mammograph capable to image the distribution of a fluorescent contrast agent within a female breast, slightly compressed between two parallel glass plates, with high sensitivity. Fluorescence of the contrast agent is excited using a near infrared picosecond diode laser module. Four additional picosecond diode lasers with emission wavelengths between 660 and 1066 nm allow to measure the intrinsic optical properties of the breast tissue. By synchronously moving a source fiber and seven detection fiber bundles across the breast, distributions of times of flight of photons are recorded simultaneously for selected source-detector combinations in transmission and reflection geometry either at the fluorescence wavelength or at the selected laser wavelengths. To evaluate the performance of the mammograph, we used breastlike rectangular phantoms comprising fluorescent and absorbing objects using the fluorescent dye Omocyanine as contrast agent excited at 735 nm. We compare two-dimensional imaging of the phantom based on transmission and reflection data. Furthermore, we developed an improved tomosynthesis algorithm which permits three-dimensional reconstruction of fluorescence and absorption properties of lesions with good spatial resolution. For illustration, we present fluorescence mammograms of one patient recorded 30 min after administration of the contrast agent indocyanine green showing the carcinoma at high contrast originating from fluorescence of the extravasated dye, excited at 780 nm.
    The Review of scientific instruments 02/2011; 82(2):024302. · 1.58 Impact Factor
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    ABSTRACT: We have investigated twenty patients with suspicious breast lesions by fluorescence mammography using ICG as contrast agent. Differences in early and late fluorescence mammograms offer the chance to distinguish malignant from benign lesions.
    Biomedical Optics; 04/2010
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    ABSTRACT: We have developed a prototype mammograph for simultaneous acquisition of tomographic and time-resolved data at fluorescence and laser wavelengths in slab geometry. System performance was tested on phantoms and on a volunteer.
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    ABSTRACT: We report on the nonlinear reconstruction of local absorption and fluorescence contrast in tissuelike scattering media from measured time-domain diffuse reflectance and transmittance of laser as well as laser-excited fluorescence radiation. Measurements were taken at selected source-detector offsets using slablike diffusely scattering and fluorescent phantoms containing fluorescent heterogeneities. Such measurements simulate in vivo data that would be obtained employing a scanning, time-domain fluorescence mammograph, where the breast is gently compressed between two parallel glass plates, and source and detector optical fibers scan synchronously at various source-detector offsets, allowing the recording of laser and fluorescence mammograms. The diffusion equations modeling the propagation of the laser and fluorescence radiation were solved in frequency domain by the finite element method simultaneously for several modulation frequencies using Fourier transformation and preprocessed experimental data. To reconstruct the concentration of the fluorescent contrast agent, the Born approximation including higher-order reconstructed photon densities at the excitation wavelength was used. Axial resolution was determined that can be achieved by various detection schemes. We show that remission measurements increase the depth resolution significantly.
    Applied Optics 09/2009; 48(24):4651-62. · 1.69 Impact Factor
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    ABSTRACT: Using scanning time-domain instrumentation we recorded fluorescence projection mammograms on few breast cancer patients prior, during and after infusion of indocyanine green (ICG), while monitoring arterial ICG concentration by transcutaneous pulse densitometry. Late-fluorescence mammograms recorded after ICG had been largely cleared from the blood by the liver, showed invasive carcinomas at high contrast over a rather homogeneous background, whereas benign lesions did not produce (focused) fluorescence contrast. During infusion, tissue concentration contrast and hence fluorescence contrast is determined by intravascular contributions, whereas late-fluorescence mammograms are dominated by contributions from protein-bound ICG extravasated into the interstitium, reflecting relative microvascular permeabilities of carcinomas and normal breast tissue. We simulated intravascular and extravascular contributions to ICG tissue concentration contrast within a two-compartment unidirectional pharmacokinetic model.
    Optics Express 09/2009; 17(19):17016-33. · 3.53 Impact Factor
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    ABSTRACT: We developed a method to record artifact-free diffuse reflectance in a parallel plate scanning fluorescence mammograph and used reflection data together with transmission data for reconstruction based fluorescence imaging at improved axial resolution.
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    ABSTRACT: We present a new method to reconstruct arbitrary large volumes in (fluorescence) diffuse optical tomography by splitting the volume of reconstruction into sub-volumes. This allows to perform nonlinear reconstruction on large grids with a larger number of measurement data and more grid nodes than conventional reconstruction schemes, where images are reconstructed on a single grid. We investigate how the reconstructed spatial distributions of diffusion and absorption coefficients using the new method depend on the size of the sub-volumes, compare the convergence to the conventional nonlinear approach, and present an error estimation.
    Proc SPIE 03/2008;
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    ABSTRACT: Time-domain perturbation theory of photon diffusion up to third order was evaluated for its accuracy in deducing optical properties of breast tumors using simulated and physical phantoms and by analyzing 141 projection mammograms of 87 patients with histology-validated tumors that had been recorded by scanning time-domain optical mammography. The slightly compressed breast was modeled as (partially) homogeneous diffusely scattering infinite slab containing a scattering and absorbing spherical heterogeneity representing the tumor. Photon flux densities were calculated from densities of transmitted photons, assuming extended boundary conditions. Explicit formulas are provided for second-order changes in transmitted photon density due to the presence of absorbers or scatterers. The results on phantoms obtained by perturbation theory carried up to third order were compared with measured temporal point spread functions, with numerical finite-element method (FEM) simulations of transmitted photon flux density, with results obtained from the diffraction of diffuse photon density waves, and from Padé approximants. The breakdown of first-, second-, and third-order perturbation theory is discussed for absorbers and a general expression was derived for the convergence of the Born series in this case. Taking tumor optical properties derived by the diffraction model as reference we conclude that estimates of tumor absorption coefficients by perturbation theory agree with reference values within +/-25% in only 65% (first order), 66% (second order), and 77% (third order) of all mammograms analyzed. In the remaining cases tumor absorption is generally underestimated due to the breakdown of perturbation theory. On average the empirical Padé approximants yield tumor absorption coefficients similar to third-order perturbation theory, yet at noticeable lower computational efforts.
    Physical Review E 01/2008; 76(6 Pt 1):061908. · 2.33 Impact Factor
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    ABSTRACT: In this study we have theoretically and experimentally investigated the behavior of first order approximation contrast function when purely scattering inhomogeneities located at different depths inside a turbid thick slab are considered. Results of model predictions have been compared with Finite element method simulations and tested on phantoms. To this aim, we have developed for the first time to our knowledge a fitting algorithm for estimating both the scattering perturbation parameter and the shift of the inhomogeneity from the middle plane, allowing one to reduce the uncertainties due to depth. This is important for optical mammography because effects of the depth can cause uncertainties in the derived tumor optical properties that are above 20% and the scattering properties of tumors differ from those of the sourrounding healthy tissue by a comparable extent. OCIS codes: (170.3660) light propagation in tissues; (170.5280) photon migration; (170.6510) spectroscopy, tissue diagnostics; (290.1990) diffusion; (290.7050) turbid media., "In-vivo tissue optical properties derived by linear perturbation theory for edge-corrected time-domain mammograms,-resolved contrast function and optical char-acterization of spatially varying absorptive inclusions at different depths in diffusing media," Phys. Rev. E 69, 031901 (2004).
    Optics Express 01/2008; 7(11-16):2043-2045. · 3.53 Impact Factor
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    ABSTRACT: We studied the free precession of the nuclear magnetization of hyperpolarized 129Xe gas in external magnetic fields as low as B0 = 4.5 nT, using SQUIDs as magnetic flux detectors. The transverse relaxation was mainly caused by the restricted diffusion of 129Xe in the presence of ambient magnetic field gradients. Its pressure dependence was measured in the range from 30mbar to 850mbar and compared quantitatively to theory. Motional narrowing was observed at low pressure, yielding transverse relaxation times of up to 8000s.
    The European Physical Journal D 04/2007; 42(2):197-202. · 1.40 Impact Factor
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    ABSTRACT: We report on the reconstruction of absorption and fluorescence from measured time-domain diffuse reflectance and transmittance of laser and fluorescence radiation. Measurements were taken on slab-like, diffusely scattering and fluorescent phantoms containing fluorescent inhomogeneities, using fs laser pulses (lambda = 730 nm) and time correlated single photon counting. The source was scanned across the entrance face of the phantom, and at each source position data were collected in transmission and reflection at various detector positions. These measurements simulate in vivo data that will be obtained employing a scanning, time-domain fluorescence mammograph, where the breast is gently compressed between two parallel glass plates, and source and detector optical fibers scan synchronously at various source-detector offsets, allowing to record laser and fluorescence mammograms. The diffusion equations for the propagation of the laser and fluorescence radiation were solved in frequency domain by the finite element method. Measured time-resolved phantom data were Fourier-transformed to frequency domain prior to image reconstruction. Signal-to-noise ratios were high enough to use several data sets simultaneously in the reconstruction process belonging to various modulation frequencies up to several hundred MHz. To obtain the spatial distribution of the fluorescent contrast agent the Born approximation of the fluorescence diffusion equation was used.
    Proc SPIE 03/2007;

Publication Stats

925 Citations
73.74 Total Impact Points


  • 1996–2014
    • Physikalisch-Technische Bundesanstalt
      • Division of Medical Physics and Metrological Information Technology
      Brunswyck, Lower Saxony, Germany
  • 2005
    • Charité Universitätsmedizin Berlin
      Berlín, Berlin, Germany