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  • 1
    Online Resource
    Online Resource
    Large-scale characterization of the microvascular geometry in development and disease by tissue clearing and quantitative ultramicroscopy
    SAGE Publications ; 2021
    In:  Journal of Cerebral Blood Flow & Metabolism Vol. 41, No. 7 ( 2021-07), p. 1536-1546
    Details
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 41, No. 7 ( 2021-07), p. 1536-1546
    Abstract: Three-dimensional assessment of optically cleared, entire organs and organisms has recently become possible by tissue clearing and selective plane illumination microscopy (“ultramicroscopy”). Resulting datasets can be highly complex, encompass over a thousand images with millions of objects and data of several gigabytes per acquisition. This constitutes a major challenge for quantitative analysis. We have developed post-processing tools to quantify millions of microvessels and their distribution in three-dimensional datasets from ultramicroscopy and demonstrate the capabilities of our pipeline within entire mouse brains and embryos. Using our developed acquisition, segmentation, and analysis platform, we quantify physiological vascular networks in development and the healthy brain. We compare various geometric vessel parameters (e.g. vessel density, radius, tortuosity) in the embryonic spinal cord and brain as well as in different brain regions (basal ganglia, corpus callosum, cortex). White matter tract structures (corpus callosum, spinal cord) showed lower microvascular branch densities and longer vessel branch length compared to grey matter (cortex, basal ganglia). Furthermore, we assess tumor neoangiogenesis in a mouse glioma model to compare tumor core and tumor border. The developed methodology allows rapid quantification of three-dimensional datasets by semi-automated segmentation of fluorescently labeled objects with conventional computer hardware. Our approach can aid preclinical investigations and paves the way towards “quantitative ultramicroscopy”.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    URL: Article
    DOI: 10.1177/0271678X20961854
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
    detail.hit.zdb_id: 2039456-1
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  • 2
    Online Resource
    Online Resource
    Individualized blood pressure management during endovascular treatment of acute ischemic stroke under procedural sedation (INDIVIDUATE) – An explorative randomized controlled trial
    SAGE Publications ; 2021
    In:  European Stroke Journal Vol. 6, No. 3 ( 2021-09), p. 276-282
    Details
    In: European Stroke Journal, SAGE Publications, Vol. 6, No. 3 ( 2021-09), p. 276-282
    Abstract: Optimal blood pressure is not well established during endovascular therapy of acute ischemic stroke. Applying standardized blood pressure target values for every stroke patient might be a suboptimal approach. Aim To assess whether an individualized intraprocedural blood pressure management with individualized blood pressure target ranges might pose a better strategy for the outcome of the patients than standardized blood pressure targets. Sample size: Randomization of 250 patients 1:1 to receive either standard or individualized blood pressure management approach. Methods and design We conduct an explorative single-center randomized controlled trial with a PROBE (parallel-group, open-label randomized controlled trial with blinded endpoint evaluation) design. In the control group, intraprocedural systolic blood pressure target range is 140–180 mmHg. The intervention group is the individualized approach, which is maintaining the intraprocedural systolic blood pressure at the level on presentation (±10 mmHg). Study outcomes: The primary endpoint is the modified Rankin scale assessed 90 days +/− 2 weeks after stroke onset, dichotomized by 0–2 (favorable outcome) to 3–6 (unfavorable outcome). Secondary endpoints include early neurological improvement, infarction size, and systemic physiology monitor parameters. Discussion An individualized approach for blood pressure management during thrombectomy could lead to a better outcome for stroke patients. The trial is registered at clinicaltrials.gov as ‘Individualized Blood Pressure Management During Endovascular Stroke Treatment (INDIVIDUATE)’ under NCT04578288.
    Type of Medium: Online Resource
    ISSN: 2396-9873 , 2396-9881
    URL: Article
    DOI: 10.1177/23969873211000879
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
    detail.hit.zdb_id: 2851287-X
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  • 3
    Online Resource
    Online Resource
    Diagnostic value of gadolinium contrast administration for spinal cord magnetic resonance imaging in multiple sclerosis patients and correlative markers of lesion enhancement
    SAGE Publications ; 2021
    In:  Multiple Sclerosis Journal - Experimental, Translational and Clinical Vol. 7, No. 4 ( 2021-10), p. 205521732110479-
    Details
    In: Multiple Sclerosis Journal - Experimental, Translational and Clinical, SAGE Publications, Vol. 7, No. 4 ( 2021-10), p. 205521732110479-
    Abstract: Magnetic resonance imaging is essential for monitoring people with multiple sclerosis, but the diagnostic value of gadolinium contrast administration in spine magnetic resonance imaging is unclear. Objective To assess the diagnostic value of gadolinium contrast administration in spine magnetic resonance imaging follow-up examinations and identify imaging markers correlating with lesion enhancement. Methods A total of 65 multiple sclerosis patients with at least 2 spinal magnetic resonance imaging follow-up examinations were included. Spine magnetic resonance imaging was performed at 3 Tesla with a standardized protocol (sagittal and axial T2-weighted turbo spin echo and T1-weighted post-contrast sequences). T2 lesion load and enhancing lesions were assessed by two independent neuroradiologists for lesion size, localization, and T2 signal ratio (T2 signal lesion /T2 signal normal appearing spinal cord ). Results A total of 68 new spinal T2 lesions and 20 new contrast-enhancing lesions developed during follow-up. All enhancing lesions had a discernable correlate as a new T2 lesion. Lesion enhancement correlated with a higher T2 signal ratio compared to non-enhancing lesions (T2 signal ratio: 2.0 ± 0.4 vs. 1.4 ± 0.2, **** p 〈 0.001). Receiver operating characteristics analysis showed an optimal cutoff value of signal ratio 1.78 to predict lesion enhancement (82% sensitivity and 97% specificity). Conclusion Gadolinium contrast administration is dispensable in follow-up spine magnetic resonance imaging if no new T2 lesions are present. Probability of enhancement correlates with the T2 signal ratio.
    Type of Medium: Online Resource
    ISSN: 2055-2173 , 2055-2173
    URL: Article
    DOI: 10.1177/20552173211047978
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2021
    detail.hit.zdb_id: 2841884-0
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  • 4
    Online Resource
    Online Resource
    Assessment of tumor oxygenation and its impact on treatment response in bevacizumab-treated recurrent glioblastoma
    SAGE Publications ; 2017
    In:  Journal of Cerebral Blood Flow & Metabolism Vol. 37, No. 2 ( 2017-02), p. 485-494
    Details
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 37, No. 2 ( 2017-02), p. 485-494
    Abstract: Antiantiogenic therapy with bevacizumab in recurrent glioblastoma is currently understood to both reduce microvascular density and to prune abnormal tumor microvessels. Microvascular pruning and the resulting vascular normalization are hypothesized to reduce tumor hypoxia and increase supply of systemic therapy to the tumor; however, the underlying pathophysiological changes and their timing after treatment initiation remain controversial. Here, we use a novel dynamic susceptibility contrast MRI-based method, which allows simultaneous assessment of tumor net oxygenation changes reflected by the tumor metabolic rate of oxygen and vascular normalization represented by the capillary transit time heterogeneity. We find that capillary transit time heterogeneity, and hence the oxygen extraction fraction combine with the tumoral blood flow (cerebral blood flow) in such a way that the overall tumor oxygenation appears to be worsened despite vascular normalization. Accordingly, hazards for both progression and death are found elevated in patients with a greater reduction of tumor metabolic rate of oxygen in response to bevacizumab and patients with higher intratumoral tumor metabolic rate of oxygen at baseline. This implies that tumors with a higher degree of angiogenesis prior to bevacizumab-treatment retain a higher level of angiogenesis during therapy despite a greater antiangiogenic effect of bevacizumab, hinting at evasive mechanisms limiting bevacizumab efficacy in that a reversal of their biological behavior and relative prognosis does not occur.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    URL: Article
    DOI: 10.1177/0271678X16630322
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2017
    detail.hit.zdb_id: 2039456-1
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