Jens Steinbrink - Academia.edu (original) (raw)

Papers by Jens Steinbrink

PubMed, Jul 1, 2006

Near-infrared fluorescence (NIRF) imaging has great potential for studying physiological and path... more Near-infrared fluorescence (NIRF) imaging has great potential for studying physiological and pathophysiological processes noninvasively in several locations of the body. In this study, we evaluated the feasibility of NIRF imaging to visualize fluorescent compounds within the brains of live mice commonly used in brain research. To simulate the presence of a molecular NIRF reporter agent at the site of a lesion, we developed a new in vivo phantom model wherein capsules containing different amounts of an NIRF dye (Cy5.5) were stereotactically implanted deep into the left hemispheres of living mice. To precisely locate the implanted capsules, magnetic resonance imaging (MRI) was performed. Fluorescence reflectance imaging (FRI) and transillumination fluorescence imaging (TFI) were conducted to analyze and compare sensitivity and target-to-background ratios of the two methods. The sensitivities of FRI and TFI to background fluorescence from circulating dye was tested by imaging fluorescent capsules in mice intravenously injected with increasing amounts of long-circulating Cy5.5-dextran. The results show that capsules containing dye amounts as low as 10(-12) mol can be detected. TFI yielded significantly higher target-to-background ratios than FRI at 10(-11) mol (p < .05). Comparatively low amounts of fluorescence in the blood vessels can extinguish the signal. We conclude that keeping the signal from circulating NIRF dye low, NIRF imaging offers high sensitivity in detecting fluorochromes noninvasively within brains of mice, especially by using TFI. This encourages the application of NIRF for molecular imaging in the mouse brain using NIRF reporters.

Journal of Biomedical Optics, 2008

In vivo molecular fluorescence tomography of brain disease mouse models has two very specific dem... more In vivo molecular fluorescence tomography of brain disease mouse models has two very specific demands on the optical setup: the use of pigmented furry mice does not allow for a purely noncontact setup, and a high spatial accuracy is required on the dorsal side of the animal due to the location of the brain. We present an optimized setup and tomographic scheme that meet these criteria through a combined CW reflectance-transmittance fiber illumination approach and a charge-coupled device contactless detection scheme. To consider the anatomy of the mouse head and take short source detector separations into account, the forward problem was evaluated by a Monte Carlo simulation input with a magnetic resonance image of the animal. We present an evaluation of reconstruction performance of the setup under three different condition. ͑i͒ Using a simulated dataset, with well-defined optical properties and low noise, the reconstructed position accuracy is below 0.5 mm. ͑ii͒ Using experimental data on a cylindrical tissue-simulating phantom with well-defined optical properties, a spatial accuracy of about 1 mm was found. ͑iii͒ Finally, on an animal model with a fluorescent inclusion in the brain, the target position was reconstructed with an accuracy of 1.6 mm.

ABSTRACT We report on a time-resolved instrument for diffuse NIR-reflectance topography of the ad... more ABSTRACT We report on a time-resolved instrument for diffuse NIR-reflectance topography of the adult head. First results will be presented of time-resolved monitoring of the motor cortex area during finger tapping.

Proceedings of SPIE, Jun 30, 2005

ABSTRACT We developed a time-domain brain imager that is based on picosecond diode lasers, a mult... more ABSTRACT We developed a time-domain brain imager that is based on picosecond diode lasers, a multimode fiber switch and multi-channel time-correlated single photon counting. It allows to record time-resolved diffuse reflectance for 16 source-detector pairs within typically 1 s. Data analysis was based on the evaluation of moments of measured distributions of times of flight of photons. To show the relevance of these moments for achieving depth selectivity, three-dimensional sensitivities of integral, mean time of flight and variance to absorption changes were calculated using a perturbation approach based on the diffusion equation for photon density for a homogeneous semi-infinite medium. It turned out that variance is almost exclusively sensitive to deep layers, whereas the integral reflects changes in deep as well as in superficial layers. The lateral resolution of the imager was demonstrated by a phantom experiment. Results of a motor stimulation experiment on a healthy volunteer strongly suggest that variance reveals mainly the cerebral activation whereas the integral may additionally contain significant systemic contributions.

Advances in Experimental Medicine and Biology, Oct 24, 2009

Near-infrared spectroscopy (NIRS) of the human brain is aiming at the non-invasive determination ... more Near-infrared spectroscopy (NIRS) of the human brain is aiming at the non-invasive determination of concentration changes of oxy- and deoxyhemoglobin in the cortex. However, it usually relies on the assumption of spatially homogeneous absorption changes. To overcome this limitation we performed instrumental and methodological developments of time-resolved NIRS with the aim to achieve depth resolution. We present our recently developed time-domain near-infrared brain imager based on picosecond diode lasers and time-correlated single photon counting (TCSPC) which can be used at the bedside. To achieve depth localization of absorption changes we analysed statistical moments (integral, mean time of flight and variance) of measured time-of-flight distributions of diffusely reflected photons. In particular, variance has a selective sensitivity to deep absorptions changes and provides a suitable representation of cerebral signals. The separation of cerebral and extracerebral changes of hemoglobin concentrations is demonstrated for a motor stimulation experiment.

Journal of Neuroscience Methods, May 1, 2009

Impairment of the blood-brain barrier (BBB) after cerebral ischemia leads to extravasation of pla... more Impairment of the blood-brain barrier (BBB) after cerebral ischemia leads to extravasation of plasma constituents into the brain parenchyma. We describe a novel method using non-invasive near-infrared fluorescence (NIRF) imaging and bovine serum albumin labeled with a NIRF dye (NIRF-BSA) to detect BBB impairment after middle cerebral artery occlusion (MCAO) in mice. We first explored the time course of BBB impairment after transient MCAO using Evans blue (EB), which binds to plasma albumin in vivo. An initial BBB impairment was observed at 4-8 h and a second impairment at 12-16 h after reperfusion. No EB extravasation was detected at 8-12 h. Non-invasive NIRF imaging with NIRF-BSA confirmed biphasic BBB impairment. Upon co-injection of NIRF-BSA with EB we found a strong correlation between the detected NIRF signal and the amount of extravasated EB (r = 0.857, P = 0.00178). When MCAO mice received NIRF-BSA together with gadolinium-diethylene triamine penta-acetic acid (Gd-DTPA), T1weighted images showed Gd-DTPA enhancement at all times while NIRF imaging showed biphasic BBB impairment. In conclusion, NIRF-BSA is a suitable marker of plasma albumin extravasation in the mouse brain. Non-invasive NIRF imaging with NIRF-BSA is a useful tool to study BBB integrity in preclinical models of central nervous system pathology.

Restorative Neurology and Neuroscience, Aug 19, 2015

Background: Mirror therapy (MT) was found to improve motor function after stroke. However, there ... more Background: Mirror therapy (MT) was found to improve motor function after stroke. However, there is high variability between patients regarding motor recovery. Objectives: The following pilot study was designed to identify potential factors determining this variability between patients with severe upper limb paresis, receiving MT. Methods: Eleven sub-acute stroke patients with severe upper limb paresis participated, receiving in-patient rehabilitation. After a set of pre-assessments (including measurement of brain activity at the primary motor cortex and precuneus during the mirror illusion, using near-infrared spectroscopy as described previously), four weeks of MT were applied, followed by a set of post-assessments. Discriminant group analysis for MT responders and non-responders was performed. Results: Six out of eleven patients were defined as responders and five as non-responders on the basis of their functional motor improvement. The initial motor function and the activity shift in both precunei (mirror index) were found to discriminate significantly between responders and non-responders. Conclusions: In line with earlier results, initial motor function was confirmed as crucial determinant of motor recovery. Additionally, activity response to the mirror illusion in both precunei was found to be a candidate for determination of the efficacy of MT.

Journal of Cerebral Blood Flow and Metabolism, Aug 1, 2005

Neuronal activation leads to an increase in regional cerebral blood flow (rCBF) and blood oxygena... more Neuronal activation leads to an increase in regional cerebral blood flow (rCBF) and blood oxygenation (rCBO). The underlying mechanisms of neurovascular coupling are poorly understood. Recently a new model of activity induced vascular regulation was proposed by Stamler et al. (1997) based on the fact that nitric oxide (NO), a potent vasodilator, binds to hemoglobin in the oxygenated state (oxy-Hb) but is released upon deoxygenation of hemoglobin (deoxy-Hb). It was suggested that during cellular activity oxygen consumption locally increases which causes deoxygenation of hemoglobin and release of NO. Indeed it has recently been shown that red blood cell-bound NO mediates hypoxic vasodilation in vitro, and transpulmonary gradients of hemoglobin-bound NO are evident in patients with congestive heart failure (Datta et al., 2004). According to this elegant model of combined oxygen and NO release, blood flow will be directly matched to tissue oxygen demands. To test this model as a physiological mechanism of neurovascular coupling in the brain, we measured rCBF and rCBO responses to functional activation under hyperbaric oxygenation (3 ATA, FiO2 1.0) in the anesthetized rat. During hyperbaric oxygenation oxygen supply to tissue is entirely provided through physically dissolved oxygen. During activation no deoxygenation of hemoglobin and thus no allosteric release of NO occurs. Laser Doppler flowmetry combined with microfiber Hb-spectroscopy was performed through the thinned skull in rats to measure relative changes in rCBF and rCBO and cortical hemoglobin saturation. Averaged rCBF and rCBO responses to electrical forepaw stimulation (3 Hz, 10 s stimulation period) were recorded under normobaric normoxia and compared with responses during hyperbaric hyperoxygenation. Hyperbaric hyperoxygenation increased hemoglobin saturation within the microcirculation from 44 2 to 103 3%. The deoxy-Hb decrease normally occurring during functional activation disappeared. The oxy-Hb increase was unchanged, and the rCBF response to functional activation was increased but not decreased under hyperbaric hyperoxygenation compared with control responses. In most animals the observed increase in the rCBF response was paralleled by an increase in the amplitude of somatosensory evoked potentials. Our results suggest that in contrast to the in-vitro situation and to pathophysiological conditions of severe hypoxia rCBF regulation during physiological neuronal activation involves other mechanisms than oxygen-dependent delivery and release of NO from hemoglobin.

Journal of Cerebral Blood Flow and Metabolism, Dec 30, 2009

Recently, a universal, simple, and fail-safe mechanism has been proposed by which cerebral blood ... more Recently, a universal, simple, and fail-safe mechanism has been proposed by which cerebral blood flow (CBF) might be coupled to oxygen metabolism during neuronal activation without the need for any tissue-based mechanism. According to this concept, vasodilation occurs by local erythrocytic release of nitric oxide or ATP wherever and whenever hemoglobin is deoxygenated, directly matching oxygen demand and supply in every tissue. For neurovascular coupling in the brain, we present experimental evidence challenging this view by applying an experimental regime operating without deoxy-hemoglobin. Hyperbaric hyperoxygenation (HBO) allowed us to prevent hemoglobin deoxygenation, as the oxygen that was physically dissolved in the tissue was sufficient to support oxidative metabolism. Regional CBF and regional cerebral blood oxygenation were measured using a cranial window preparation in anesthetized rats. Hemodynamic and neuronal responses to electrical forepaw stimulation or cortical spreading depression (CSD) were analyzed under normobaric normoxia and during HBO up to 4 ATA (standard atmospheres absolute). Inconsistent with the proposed mechanism, during HBO, CBF responses to functional activation or CSD were unchanged. Our results show that activation-induced CBF regulation in the brain does not operate through the release of vasoactive mediators on hemoglobin deoxygenation or through a tissue-based oxygen-sensing mechanism.

Klinische Neurophysiologie, Mar 12, 2013

Recent interest in modeling and reconstruction algorithms for Bioluminescence Tomography (BLT) ha... more Recent interest in modeling and reconstruction algorithms for Bioluminescence Tomography (BLT) has increased and led to the general consensus that non-spectrally resolved intensity-based BLT results in a nonunique problem. However, the light emitted from, for example firefly Luciferase, is widely distributed over the band of wavelengths from 500 nm to 650 nm and above, with the dominant fraction emitted from tissue being above 550 nm. This work will demonstrate the development of a 3D model and algorithm used for multi-wavelength 3D spectrally resolved Bioluminescence Tomography (BLT) image reconstruction. It will demonstrated that through

Journal of Nuclear Materials, Feb 1, 1997

In this paper analytical expressions are given for the distributions of neutral impurity atoms in... more In this paper analytical expressions are given for the distributions of neutral impurity atoms in the plasma near the surface, which acts as the impurity source. The effects of the angular and energy distribution of the sputtered atoms, of the experiment geometry (plasma and surface size) and the plasma parameters are taken into account. Using the analytical expressions and experimentally measured photon intensities of the neutral line emission, either the flux of eroded particles or the excitation rate coefficients can be determined experimentally, by knowing one of them. In the linear plasma generator PSI-1 such an experiment with Li, for which the excitation rate coefficients are available, has been performed. The measured flux of eroded Li atoms has been compared with erosion calculations taking into account both thermal sublimation and physical sputtering.

Current Medicinal Chemistry, Oct 1, 2012

Journal of Nuclear Materials, Feb 11, 1997

Graphite is widely used inside the vacuum vessel of magnetic fusion devices and is proposed as ta... more Graphite is widely used inside the vacuum vessel of magnetic fusion devices and is proposed as target material for future machines like ITER. There are, however, uncertainties concerning the erosion of the material by chemical sputtering via hydrocarbon formation at high ion flux densities. We report on experiments at the plasma generator PSI-1 using a stationary quasi-neutral plasma beam. The ion flux densities used cover the range from 4 • 1020 to 1.2 • 1022 m 2 s i. They are thus filling the gap between the upper limit of ion beam experiments (102° m-2 s 1) and tokamak relevant values (> 1023 m 2 s-~). To suppress impurity-induced erosion the hydrogen discharges were carefully conditioned and checked for possible impurities, especially oxygen. Samples of different advanced carbon fiber composites (CFC)-including a silicon-doped one were exposed to various plasma conditions. A calibrated mass spectrometer monitored the C ~H x-formation in situ and the axial dependence of the CH-band intensities at 431 and 432.4 nm in front of the target was detected. We have studied the temperature dependence (250-700°C) of the erosion yields at ion flux densities up to more than l022 m 2 s i in hydrogen discharges. Weight loss measurements and scans with an optical profilometer were used to determine the mass loss. For Si-doped CFC an erosion yield of 1% was found, which is a factor of two less than for pure CFC.

Brain Research, Nov 1, 2006

Laser Speckle Contrast Analysis (LASCA), a novel, high-resolution blood flow imaging method, was ... more Laser Speckle Contrast Analysis (LASCA), a novel, high-resolution blood flow imaging method, was performed on rat somatosensory cortex during functional activation. In the same animals, cerebral blood flow (CBF) was measured with Laser Doppler Flowmetry. To obtain a quantitative estimate of the underlying neuronal activity, somatosensory evoked potentials were recorded simultaneously with an epidural EEG. Our results show that: 1. CBF changes measured by LASCA or LDF are nonlinearly dependent on the magnitude of electrical neural activity revealed by somatosensory evoked potentials. 2. The magnitude of relative CBF changes measured by LASCA and LDF shows a strong correlation. 3. LASCA imaging localizes the highest relative changes of CBF in microcirculatory areas, with a smaller contribution by larger vessels. This study demonstrates that LASCA is a reliable method that provides 2D-imaging of CBF changes that are comparable to LDF measurements. It further suggests that functional neuroimaging methods based on CBF enhance areas of microcirculation and thus might prove more accurate in localizing neural activity than oxygenation related methods like BOLD-fMRI.

KlinikManagement aktuell, May 1, 2022