Jens Steinbrink
Research interests
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InterestsMRI, functional MRI, Neuroimaging, Brain Connectivity, Cognitive Neuroscience, EEG
Other
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Journal RefereeNeuroImage, JBO and others
Publications
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5.74Impact points
Somatosensory activation of two fingers can be discriminated with ultrahigh-density diffuse optical tomography.
NeuroImage. 12/2011; 59(4):3201-11.
Topographic non-invasive near infrared spectroscopy (NIRS) has become a well-established tool for functional brain imaging. Applying up to 100 optodes over the head of a subject, allows achieving a spatial resolution in the centimeter range. This resolution is poor compared to other functional imagi... [more] Topographic non-invasive near infrared spectroscopy (NIRS) has become a well-established tool for functional brain imaging. Applying up to 100 optodes over the head of a subject, allows achieving a spatial resolution in the centimeter range. This resolution is poor compared to other functional imaging tools. However, recently it was shown that diffuse optical tomography (DOT) as an extension of NIRS based on high-density (HD) probe arrays and supplemented by an advanced image reconstruction procedure allows describing activation patterns with a spatial resolution in the millimeter range. Building on these findings, we hypothesize that HD-DOT may render very focal activations accessible which would be missed by the traditionally used sparse arrays. We examined activation patterns in the primary somatosensory cortex, since its somatotopic organization is very fine-grained. We performed a vibrotactile stimulation study of the first and fifth finger in eight human subjects, using a 900-channel continuous-wave DOT imaging system for achieving a higher resolution than conventional topographic NIRS. To compare the results to a well-established high-resolution imaging technique, the same paradigm was investigated in the same subjects by means of functional magnetic resonance imaging (fMRI). In this work, we tested the advantage of ultrahigh-density probe arrays and show that highly focal activations would be missed by classical next-nearest neighbor NIRS approach, but also by DOT, when using a sparse probe array. Distinct activation patterns for both fingers correlated well with the expected neuroanatomy in five of eight subjects. Additionally we show that activation for different fingers is projected to different tissue depths in the DOT image. Comparison to the fMRI data yielded similar activation foci in seven out of ten finger representations in these five subjects when comparing the lateral localization of DOT and fMRI results.
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2.30Impact points
Non-invasive optical imaging of stroke.
Philosophical transactions. Series A, Mathematical, physical, and engineering sciences. 11/2011; 369(1955):4470-94.
The acute onset of a neurological deficit is the key clinical feature of stroke. In most cases, however, pathophysiological changes in the cerebral vasculature precede the event, often by many years. Persisting neurological deficits may also require long-term rehabilitation. Hence, stroke may be con... [more] The acute onset of a neurological deficit is the key clinical feature of stroke. In most cases, however, pathophysiological changes in the cerebral vasculature precede the event, often by many years. Persisting neurological deficits may also require long-term rehabilitation. Hence, stroke may be considered a chronic disease, and diagnostic and therapeutic efforts must include identification of specific risk factors, and the monitoring of and interventions in the acute and subacute stages, and should aim at a pathophysiologically based approach to optimize the rehabilitative effort. Non-invasive optical techniques have been experimentally used in all three stages of the disease and may complement the established diagnostic and monitoring tools. Here, we provide an overview of studies using the methodology in the context of stroke, and we sketch perspectives of how they may be integrated into the assessment of the highly dynamic pathophysiological processes during the acute and subacute stages of the disease and also during rehabilitation and (secondary) prevention of stroke.
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3.28Impact points
Contrast enhanced high-resolution diffuse optical tomography of the human brain using ICG.
Optics express. 09/2011; 19(19):18636-44.
Non-invasive diffuse optical tomography (DOT) of the adult brain has recently been shown to improve the spatial resolution for functional brain imaging applications. Here we show that high-resolution (HR) DOT is also advantageous for clinical perfusion imaging using an optical contrast agent. We pre... [more] Non-invasive diffuse optical tomography (DOT) of the adult brain has recently been shown to improve the spatial resolution for functional brain imaging applications. Here we show that high-resolution (HR) DOT is also advantageous for clinical perfusion imaging using an optical contrast agent. We present the first HR-DOT results with a continuous wave near infrared spectroscopy setup using a dense grid of optical fibers and indocyanine green (ICG) as an exogenic contrast agent. We find an early arrival of the ICG bolus in the intracerebral tissue and a delayed arrival of the bolus in the extracerebral tissue, achieving the separation of both layers. This demonstrates the method's potential for brain perfusion monitoring in neurointensive care patients.
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5.74Impact points
Enhanced performance by a hybrid NIRS-EEG brain computer interface.
NeuroImage. 08/2011; 59(1):519-29.
Noninvasive Brain Computer Interfaces (BCI) have been promoted to be used for neuroprosthetics. However, reports on applications with electroencephalography (EEG) show a demand for a better accuracy and stability. Here we investigate whether near-infrared spectroscopy (NIRS) can be used to enhance t... [more] Noninvasive Brain Computer Interfaces (BCI) have been promoted to be used for neuroprosthetics. However, reports on applications with electroencephalography (EEG) show a demand for a better accuracy and stability. Here we investigate whether near-infrared spectroscopy (NIRS) can be used to enhance the EEG approach. In our study both methods were applied simultaneously in a real-time Sensory Motor Rhythm (SMR)-based BCI paradigm, involving executed movements as well as motor imagery. We tested how the classification of NIRS data can complement ongoing real-time EEG classification. Our results show that simultaneous measurements of NIRS and EEG can significantly improve the classification accuracy of motor imagery in over 90% of considered subjects and increases performance by 5% on average (p<0:01). However, the long time delay of the hemodynamic response may hinder an overall increase of bit-rates. Furthermore we find that EEG and NIRS complement each other in terms of information content and are thus a viable multimodal imaging technique, suitable for BCI.
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5.46Impact points
Visualization of cell death in mice with focal cerebral ischemia using fluorescent annexin A5, propidium iodide, and TUNEL staining.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 01/2011; 31(5):1311-20.
To monitor stroke-induced brain damage and assess neuroprotective therapies, specific imaging of cell death after cerebral ischemia in a noninvasive manner is highly desirable. Annexin A5 has been suggested as a marker for imaging cell death under various disease conditions including stroke. In this... [more] To monitor stroke-induced brain damage and assess neuroprotective therapies, specific imaging of cell death after cerebral ischemia in a noninvasive manner is highly desirable. Annexin A5 has been suggested as a marker for imaging cell death under various disease conditions including stroke. In this study, C57BL6/N mice received middle cerebral artery occlusion (MCAO) and were injected intravenously with either active or inactive Cy5.5-annexin A5 48 hours after reperfusion. Some mice also received propidium iodide (PI), a cell integrity marker. Only in mice receiving active Cy5.5-annexin A5 were fluorescence intensities significantly higher over the hemisphere ipsilateral to MCAO than on the contralateral side. This was detected noninvasively and ex vivo 4 and 8 hours after injection. The majority of cells positive for fluorescent annexin A5 were also positive for PI and fragmented DNA as detected by terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL) staining. This study demonstrates the high specificity of annexin A5 for visualization of cell death in a mouse model of stroke. To our knowledge, this is the first study to compare the distribution of injected active and inactive annexin A5, PI, and TUNEL staining. It provides important information on the experimental and potential clinical applications of annexin A5-based imaging agents in stroke.
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Acoustic processing of temporally modulated sounds in infants: evidence from a combined near-infrared spectroscopy and EEG study.
Frontiers in psychology. 01/2011; 1:62.
Speech perception requires rapid extraction of the linguistic content from the acoustic signal. The ability to efficiently process rapid changes in auditory information is important for decoding speech and thereby crucial during language acquisition. Investigating functional networks of speech perce... [more] Speech perception requires rapid extraction of the linguistic content from the acoustic signal. The ability to efficiently process rapid changes in auditory information is important for decoding speech and thereby crucial during language acquisition. Investigating functional networks of speech perception in infancy might elucidate neuronal ensembles supporting perceptual abilities that gate language acquisition. Interhemispheric specializations for language have been demonstrated in infants. How these asymmetries are shaped by basic temporal acoustic properties is under debate. We recently provided evidence that newborns process non-linguistic sounds sharing temporal features with language in a differential and lateralized fashion. The present study used the same material while measuring brain responses of 6 and 3 month old infants using simultaneous recordings of electroencephalography (EEG) and near-infrared spectroscopy (NIRS). NIRS reveals that the lateralization observed in newborns remains constant over the first months of life. While fast acoustic modulations elicit bilateral neuronal activations, slow modulations lead to right-lateralized responses. Additionally, auditory-evoked potentials and oscillatory EEG responses show differential responses for fast and slow modulations indicating a sensitivity for temporal acoustic variations. Oscillatory responses reveal an effect of development, that is, 6 but not 3 month old infants show stronger theta-band desynchronization for slowly modulated sounds. Whether this developmental effect is due to increasing fine-grained perception for spectrotemporal sounds in general remains speculative. Our findings support the notion that a more general specialization for acoustic properties can be considered the basis for lateralization of speech perception. The results show that concurrent assessment of vascular based imaging and electrophysiological responses have great potential in the research on language acquisition.
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5.46Impact points
Neurovascular coupling in rat brain operates independent of hemoglobin deoxygenation.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 04/2010; 30(4):757-68.
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 o... [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.
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Non-invasive surface-stripping for epifluorescence small animal imaging.
Biomedical optics express. 01/2010; 1(1):97-105.
Non-invasive near-infrared fluorescence (NIRF) imaging is a powerful tool to study pathophysiology in a wide variety of animal disease models including brain diseases. However, especially in NIRF imaging of the brain or other deeper laying target sites, background fluorescence emitted from the scalp... [more] Non-invasive near-infrared fluorescence (NIRF) imaging is a powerful tool to study pathophysiology in a wide variety of animal disease models including brain diseases. However, especially in NIRF imaging of the brain or other deeper laying target sites, background fluorescence emitted from the scalp or superficial blood vessels can impede the detection of fluorescence in deeper tissue. Here, we introduce an effective method to reduce the impact of fluorescence from superficial layers. The approach uses excitation light at two different wavelengths generating two images with different depth sensitivities followed by an adapted subtraction algorithm. This technique leads to significant enhancement of the contrast and the detectability of fluorochromes located in deep tissue layers in tissue simulating phantoms and murine models with stroke.
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2.02Impact points
Time-resolved near-infrared spectroscopy and imaging of the adult human brain.
Advances in experimental medicine and biology. 01/2010; 662:143-8.
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 inst... [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.
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High-resolution optical functional mapping of the human somatosensory cortex.
Frontiers in neuroenergetics. 01/2010; 2:12.
Non-invasive optical imaging of brain function has been promoted in a number of fields in which functional magnetic resonance imaging (fMRI) is limited due to constraints induced by the scanning environment. Beyond physiological and psychological research, bedside monitoring and neurorehabilitation ... [more] Non-invasive optical imaging of brain function has been promoted in a number of fields in which functional magnetic resonance imaging (fMRI) is limited due to constraints induced by the scanning environment. Beyond physiological and psychological research, bedside monitoring and neurorehabilitation may be relevant clinical applications that are yet little explored. A major obstacle to advocate the tool in clinical research is insufficient spatial resolution. Based on a multi-distance high-density optical imaging setup, we here demonstrate a dramatic increase in sensitivity of the method. We show that optical imaging allows for the differentiation between activations of single finger representations in the primary somatosensory cortex (SI). Methodologically our findings confirm results in a pioneering study by Zeff et al. (2007) and extend them to the homuncular organization of SI. After performing a motor task, eight subjects underwent vibrotactile stimulation of the little finger and the thumb. We used a high-density diffuse-optical sensing array in conjunction with optical tomographic reconstruction. Optical imaging disclosed three discrete activation foci one for motor and two discrete foci for vibrotactile stimulation of the first and fifth finger, respectively. The results were co-registered to the individual anatomical brain anatomy (MRI) which confirmed the localization in the expected cortical gyri in four subjects. This advance in spatial resolution opens new perspectives to apply optical imaging in the research on plasticity notably in patients undergoing neurorehabilitation.
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7.18Impact points
Sensitivity of newborn auditory cortex to the temporal structure of sounds.
The Journal of neuroscience : the official journal of the Society for Neuroscience. 11/2009; 29(47):14726-33.
Understanding the rapidly developing building blocks of speech perception in infancy requires a close look at the auditory prerequisites for speech sound processing. Pioneering studies have demonstrated that hemispheric specializations for language processing are already present in early infancy. Ho... [more] Understanding the rapidly developing building blocks of speech perception in infancy requires a close look at the auditory prerequisites for speech sound processing. Pioneering studies have demonstrated that hemispheric specializations for language processing are already present in early infancy. However, whether these computational asymmetries can be considered a function of linguistic attributes or a consequence of basic temporal signal properties is under debate. Several studies in adults link hemispheric specialization for certain aspects of speech perception to an asymmetry in cortical tuning and reveal that the auditory cortices are differentially sensitive to spectrotemporal features of speech. Applying concurrent electrophysiological (EEG) and hemodynamic (near-infrared spectroscopy) recording to newborn infants listening to temporally structured nonspeech signals, we provide evidence that newborns process nonlinguistic acoustic stimuli that share critical temporal features with language in a differential manner. The newborn brain preferentially processes temporal modulations especially relevant for phoneme perception. In line with multi-time-resolution conceptions, modulations on the time scale of phonemes elicit strong bilateral cortical responses. Our data furthermore suggest that responses to slow acoustic modulations are lateralized to the right hemisphere. That is, the newborn auditory cortex is sensitive to the temporal structure of the auditory input and shows an emerging tendency for functional asymmetry. Hence, our findings support the hypothesis that development of speech perception is linked to basic capacities in auditory processing. From birth, the brain is tuned to critical temporal properties of linguistic signals to facilitate one of the major needs of humans: to communicate.
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7.18Impact points
Stimulus-induced and state-dependent sustained gamma activity is tightly coupled to the hemodynamic response in humans.
The Journal of neuroscience : the official journal of the Society for Neuroscience. 11/2009; 29(44):13962-70.
A prompt behavioral response to a stimulus depends both on the salience of the stimulus as well as the subject's preparedness. Thus, both stimulus properties and cognitive factors, such as attention, may determine the strength of neuronal synchronization in the gamma range. For a comprehensive i... [more] A prompt behavioral response to a stimulus depends both on the salience of the stimulus as well as the subject's preparedness. Thus, both stimulus properties and cognitive factors, such as attention, may determine the strength of neuronal synchronization in the gamma range. For a comprehensive investigation of stimulus-response processing through noninvasive imaging, it is, however, a crucial issue whether both kinds of gamma modulation elicit a hemodynamic response. Here, we show that, in the human visual cortex, stimulus strength and internal state modulate sustained gamma activity and hemodynamic response in close correspondence. When participants reported velocity changes of gratings varying in contrast, gamma activity (35-70 Hz) increased systematically with contrast. For stimuli of constant contrast, the amplitude of gamma activity before the behaviorally relevant velocity change was inversely correlated to the behavioral response latency. This indicates that gamma activity also reflects an overall attentive state. For both sources of variance, gamma activity was tightly coupled to the hemodynamic response measured through optical topography. Because of the close relationship between high-frequency neuronal activity and the hemodynamic signal, we conclude that both stimulus-induced and state-dependent gamma activity trigger a metabolic demand and are amenable to vascular-based imaging.
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2.30Impact points
Near-infrared fluorescence imaging with fluorescently labeled albumin: a novel method for non-invasive optical imaging of blood-brain barrier impairment after focal cerebral ischemia in mice.
Journal of neuroscience methods. 06/2009; 180(1):126-32.
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 B... [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 4-8h and a second impairment at 12-16h after reperfusion. No EB extravasation was detected at 8-12h. 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), T1-weighted 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.
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9.49Impact points
Cortical spreading ischaemia is a novel process involved in ischaemic damage in patients with aneurysmal subarachnoid haemorrhage.
Brain : a journal of neurology. 05/2009;
The term cortical spreading depolarization (CSD) describes a wave of mass neuronal depolarization associated with net influx of cations and water. Clusters of prolonged CSDs were measured time-locked to progressive ischaemic damage in human cortex. CSD induces tone alterations in resistance vessels,... [more] The term cortical spreading depolarization (CSD) describes a wave of mass neuronal depolarization associated with net influx of cations and water. Clusters of prolonged CSDs were measured time-locked to progressive ischaemic damage in human cortex. CSD induces tone alterations in resistance vessels, causing either transient hyperperfusion (physiological haemodynamic response) in healthy tissue; or hypoperfusion [inverse haemodynamic response = cortical spreading ischaemia (CSI)] in tissue at risk for progressive damage, which has so far only been shown experimentally. Here, we performed a prospective, multicentre study in 13 patients with aneurysmal subarachnoid haemorrhage, using novel subdural opto-electrode technology for simultaneous laser-Doppler flowmetry (LDF) and direct current-electrocorticography, combined with measurements of tissue partial pressure of oxygen (ptiO(2)). Regional cerebral blood flow and electrocorticography were simultaneously recorded in 417 CSDs. Isolated CSDs occurred in 12 patients and were associated with either physiological, absent or inverse haemodynamic responses. Whereas the physiological haemodynamic response caused tissue hyperoxia, the inverse response led to tissue hypoxia. Clusters of prolonged CSDs were measured in five patients in close proximity to structural brain damage as assessed by neuroimaging. Clusters were associated with CSD-induced spreading hypoperfusions, which were significantly longer in duration (up to 144 min) than those of isolated CSDs. Thus, oxygen depletion caused by the inverse haemodynamic response may contribute to the establishment of clusters of prolonged CSDs and lesion progression. Combined electrocorticography and perfusion monitoring also revealed a characteristic vascular signature that might be used for non-invasive detection of CSD. Low-frequency vascular fluctuations (LF-VF) (f < 0.1 Hz), detectable by functional imaging methods, are determined by the brain's resting neuronal activity. CSD provides a depolarization block of the resting activity, recorded electrophysiologically as spreading depression of high-frequency-electrocorticography activity. Accordingly, we observed a spreading suppression of LF-VF, which accompanied spreading depression of high-frequency-electrocorticography activity, independently of whether CSD was associated with a physiological, absent or inverse haemodynamic response. Spreading suppressions of LF-VF thus allow the differentiation of progressive ischaemia and repair phases in a fashion similar to that shown previously for spreading depressions of high-frequency-electrocorticography activity. In conclusion, it is suggested that (i) CSI is a novel human disease mechanism associated with lesion development and a potential target for therapeutic intervention in stroke; and that (ii) prolonged spreading suppressions of LF-VF are a novel 'functional marker' for progressive ischaemia.
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5.46Impact points
In vivo near-infrared fluorescence imaging of matrix metalloproteinase activity after cerebral ischemia.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 05/2009;
Matrix metalloproteinases (MMPs) have been implicated in the pathophysiology of cerebral ischemia. In this study, we explored whether MMP activity can be visualized by noninvasive near-infrared fluorescence (NIRF) imaging using an MMP-activatable probe in a mouse model of stroke. C57Bl6 mice were su... [more] Matrix metalloproteinases (MMPs) have been implicated in the pathophysiology of cerebral ischemia. In this study, we explored whether MMP activity can be visualized by noninvasive near-infrared fluorescence (NIRF) imaging using an MMP-activatable probe in a mouse model of stroke. C57Bl6 mice were subjected to transient middle cerebral artery occlusion (MCAO) or sham operation. Noninvasive NIRF imaging was performed 24 h after probe injection, and target-to-background ratios (TBRs) between the two hemispheres were determined. TBRs were significantly higher in MCAO mice injected with the MMP-activatable probe than in sham-operated mice and in MCAO mice that were injected with the nonactivatable probe as controls. Treatment with an MMP inhibitor resulted in significantly lower TBRs and lesion volumes compared to injection of vehicle. To test the contribution of MMP-9 to the fluorescence signal, MMP9-deficient (MMP9(-/-)) mice and wild-type controls were subjected to MCAO of different durations to attain comparable lesion volumes. TBRs were significantly lower in MMP9(-/-) mice, suggesting a substantial contribution of MMP-9 activity to the signal. Our study shows that MMP activity after cerebral ischemia can be imaged noninvasively with NIRF using an MMP-activatable probe, which might be a useful tool to study MMP activity in the pathophysiology of the disease.Journal of Cerebral Blood Flow & Metabolism advance online publication, 6 May 2009; doi:10.1038/jcbfm.2009.51.
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6.34Impact points
Dysferlin-deficient Muscular Dystrophy: Gadofluorine M Suitability at MR Imaging in a Mouse Model.
Radiology. 11/2008;
Purpose: To compare the usefulness of gadofluorine M with that of Gadomer in assessment of dysferlin-deficient muscular dystrophy at 7.0-T magnetic resonance (MR) imaging. Materials and Methods: All experiments were approved by local review boards. SJL/J mice (n = 24) with dysferlin-deficient muscul... [more] Purpose: To compare the usefulness of gadofluorine M with that of Gadomer in assessment of dysferlin-deficient muscular dystrophy at 7.0-T magnetic resonance (MR) imaging. Materials and Methods: All experiments were approved by local review boards. SJL/J mice (n = 24) with dysferlin-deficient muscular dystrophy and C57BL/6 control mice (n = 24) were imaged at 12-15 weeks (young) or older than 30 weeks (old) by using dynamic contrast material-enhanced imaging with inversion-prepared steady-state free-precession sequence before, during, and after administration of gadofluorine M at 2 mumol or Gadomer at 4 mumol intravenously. After imaging, regions of interest were determined from the upper extremity and left ventricular chamber; fractional extravascular extracellular volume, v(e), and permeability surface tissue density product, PSrho, were measured by using a two-compartment pharmacokinetic model. The natural history of muscular dystrophy was assessed histologically in 70 mice (seven five-mouse groups each of SJL/J mice and of control mice) at 4-week intervals from 8 to 32 weeks. In addition, three SJL/J mice and three control mice at age 33 weeks were sacrificed, and fluorescence microscopy was performed for visualization of intravenously administered carbocyanine-labeled gadofluorine M in muscle cells. Statistical analysis was performed by using the t test. Results: Gadofluorine M enhancement was significantly greater in skeletal muscle of 30-week-old mice with dysferlin-deficient muscular dystrophy, compared with control mice. Gadofluorine M demonstrated both increased rate of enhancement (PSrho sec(-1) +/- standard error of the mean: 0.004e(-)(4) +/- 3 vs 0.002e(-)(4) +/- 3; P < .05) and increased level of enhancement (v(e) +/- standard error of the mean: 0.035 +/- 0.004 vs 0.019 +/- 0.004; P < .05). Gadomer showed no differential enhancement in the two mouse groups. Histologic examination confirmed the presence of labeled gadofluorine M in muscle cells. Conclusion: Gadofluorine M-enhanced MR imaging may be of value in monitoring dysferlin-deficient muscular dystrophy disease progression in this animal model and could prove to be a useful tool in following the course of chronic muscle diseases in humans. Supplemental material: http://radiology.rsnajnls.org/cgi/content/full/2501080180/DC1 (c) RSNA, 2009.
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7.04Impact points
In vivo imaging of the inflammatory receptor CD40 after cerebral ischemia using a fluorescent antibody.
Stroke; a journal of cerebral circulation. 10/2008; 39(10):2845-52.
Brain inflammation is a hallmark of stroke, where it has been implicated in tissue damage as well as in repair. Imaging technologies that specifically visualize these processes are highly desirable. In this study, we explored whether the inflammatory receptor CD40 can be noninvasively and specifical... [more] Brain inflammation is a hallmark of stroke, where it has been implicated in tissue damage as well as in repair. Imaging technologies that specifically visualize these processes are highly desirable. In this study, we explored whether the inflammatory receptor CD40 can be noninvasively and specifically visualized in mice after cerebral ischemia using a fluorescent monoclonal antibody, which we labeled with the near-infrared fluorescence dye Cy5.5 (Cy5.5-CD40MAb). Wild-type and CD40-deficient mice were subjected to transient middle cerebral artery occlusion. Mice were either intravenously injected with Cy5.5-CD40MAb or control Cy5.5-IgGMAb. Noninvasive and ex vivo near-infrared fluorescence imaging was performed after injection of the compounds. Probe distribution and specificity was further assessed with single-plane illumination microscopy, immunohistochemistry, and confocal microscopy. Significantly higher fluorescence intensities over the stroke-affected hemisphere, compared to the contralateral side, were only detected noninvasively in wild-type mice that received Cy5.5-CD40MAb, but not in CD40-deficient mice injected with Cy5.5-CD40MAb or in wild-type mice that were injected with Cy5.5-IgGMAb. Ex vivo near-infrared fluorescence showed an intense fluorescence within the ischemic territory only in wild-type mice injected with Cy5.5-CD40MAb. In the brains of these mice, single-plane illumination microscopy demonstrated vascular and parenchymal distribution, and confocal microscopy revealed a partial colocalization of parenchymal fluorescence from the injected Cy5.5-CD40MAb with activated microglia and blood-derived cells in the ischemic region. The study demonstrates that a CD40-targeted fluorescent antibody enables specific noninvasive detection of the inflammatory receptor CD40 after cerebral ischemia using optical techniques.
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Fluorescence tomography technique optimized for noninvasive imaging of the mouse brain
Journla of Biomedical Optics. 08/2008; 13:041311.
n 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... [more] n 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. (i) Using a simulated dataset, with well-defined optical properties and low noise, the reconstructed position accuracy is below 0.5 mm. (ii) Using experimental data on a cylindrical tissue-simulating phantom with well-defined optical properties, a spatial accuracy of about 1 mm was found. (iii) Finally, on an animal model with a fluorescent inclusion in the brain, the target position was reconstructed with an accuracy of 1.6 mm.
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3.23Impact points
Evaluation of an AIF correction algorithm for dynamic susceptibility contrast-enhanced perfusion MRI.
Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. 07/2008; 60(1):102-10.
For longitudinal studies in patients suffering from cerebrovascular diseases the poor reproducibility of perfusion measurements via dynamic susceptibility-weighted contrast-enhanced MRI (DSC-MRI) is a relevant concern. We evaluate a novel algorithm capable of overcoming limitations in DSC-MRI caused... [more] For longitudinal studies in patients suffering from cerebrovascular diseases the poor reproducibility of perfusion measurements via dynamic susceptibility-weighted contrast-enhanced MRI (DSC-MRI) is a relevant concern. We evaluate a novel algorithm capable of overcoming limitations in DSC-MRI caused by partial volume and saturation issues in the arterial input function (AIF) by a blood flow stimulation-study. In 21 subjects, perfusion parameters before and after administration of blood flow stimulating L-arginine were calculated utilizing a block-circulant singular value decomposition (cSVD). A total of two different raters and three different rater conditions were employed to select AIFs: Besides 1) an AIF selection by an experienced rater, a beginner rater applied a steady state-oriented strategy, returning; 2) raw; and 3) corrected AIFs. Highly significant changes in regional cerebral blood flow (rCBF) by 9.0% (P < 0.01) could only be found when the AIF correction was performed. To further test for improved reproducibility, in a subgroup of seven subjects the baseline measurement was repeated 6 weeks after the first examination. In this group as well, using the correction algorithm decreased the SD of the difference between the two baseline measurements by 42%. Magn Reson Med 60:102-110, 2008. (c) 2008 Wiley-Liss, Inc.
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5.74Impact points
Individual alpha-frequency correlates with amplitude of visual evoked potential and hemodynamic response.
NeuroImage. 07/2008; 41(2):233-42.
In a simultaneous electroencephalography (EEG) and near-infrared spectroscopy (NIRS) study, the predictive value of the individual alpha-frequency at rest (IAF) for the amplitude of neuronal and vascular responses to visual stimulation was investigated. Across subjects, we find (i) an inverse relati... [more] In a simultaneous electroencephalography (EEG) and near-infrared spectroscopy (NIRS) study, the predictive value of the individual alpha-frequency at rest (IAF) for the amplitude of neuronal and vascular responses to visual stimulation was investigated. Across subjects, we find (i) an inverse relationship between IAF and the amplitude of the alpha-rhythm at rest. The IAF also predicts (ii) the amplitude of the visual evoked potential (VEP), as well as (iii) the amplitude of the alpha-rhythm during stimulation. Most importantly, (iv) IAF correlates with the oxygenation response to visual stimulation: A high IAF predicts a low alpha-amplitude at rest, a small VEP amplitude and a small oxygenation response. Conversely, a low IAF predicts high alpha-amplitude and larger electrophysiological and vascular responses to stimulation. Based on these findings, we assume that the relationship between IAF and neuronal and vascular response stems from the size of the network recruited for visual processing. The relation between IAF, alpha-amplitude, evoked potential and vascular response is discussed in the framework of a simple heuristic model. The results may partly explain the large intersubject variability observed in recently published concurrent EEG-fMRI studies.
Following (11)
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Till Nierhaus
Max-Planck-Institut für Kognitions- und Neurowissenschaften -
Michael Gaebler
Charité Universitätsmedizin Berlin -
Ulrike Grittner
Charité Universitätsmedizin Berlin -
Heval Benav
Eberhard-Karls-Universität Tübingen -
Benjamin Hotter
Charité Universitätsmedizin Berlin
