scholarly journals Multimodal Imaging Reveals Temporal and Spatial Microglia and Matrix Metalloproteinase Activity after Experimental Stroke

2015 ◽  
Vol 35 (11) ◽  
pp. 1711-1721 ◽  
Author(s):  
Bastian Zinnhardt ◽  
Thomas Viel ◽  
Lydia Wachsmuth ◽  
Alexis Vrachimis ◽  
Stefan Wagner ◽  
...  
Keyword(s):  
Multimodal Imaging ◽  
Temporal Dynamics ◽  
Single Photon ◽  
Photon Emission ◽  
Temporal Distribution ◽  
Critical Parameters ◽  
Experimental Stroke ◽  
Emission Computed Tomography ◽  
Infarct Core ◽  
Spatio Temporal

Stroke is the most common cause of death and disability from neurologic disease in humans. Activation of microglia and matrix metalloproteinases (MMPs) is involved in positively and negatively affecting stroke outcome. Novel, noninvasive, multimodal imaging methods visualizing microglial and MMP alterations were employed. The spatio-temporal dynamics of these parameters were studied in relation to blood flow changes. Micro positron emission tomography (μPET) using [18F]BR-351 showed MMP activity within the first days after transient middle cerebral artery occlusion (tMCAo), followed by increased [18F]DPA-714 uptake as a marker for microglia activation with a maximum at 14 days after tMCAo. The inflammatory response was spatially located in the infarct core and in adjacent (penumbral) tissue. For the first time, multimodal imaging based on PET, single photon emission computed tomography, and magnetic resonance imaging revealed insight into the spatio-temporal distribution of critical parameters of poststroke inflammation. This allows further evaluation of novel treatment paradigms targeting the postischemic inflammation.

scholarly journals Meta-Analysis of Molecular Imaging of Serotonin Transporters in Major Depression

2014 ◽  
Vol 34 (7) ◽  
pp. 1096-1103 ◽  
Author(s):  
Gregor Gryglewski ◽  
Rupert Lanzenberger ◽  
Georg S Kranz ◽  
Paul Cumming
Keyword(s):  
Molecular Imaging ◽  
Temporal Dynamics ◽  
Single Photon ◽  
Meta Analysis ◽  
Photon Emission ◽  
Strong Relationship ◽  
Emission Computed Tomography ◽  
Positron Emission ◽  
Sufficient Power ◽  
Severity Of Depression

The success of serotonin-selective reuptake inhibitors has lent support to the monoamine theory of major depressive disorder (MDD). This issue has been addressed in a number of molecular imaging studies by positron emission tomography or single-photon emission computed tomography of serotonin reuptake sites (5-HTT) in the brain of patients with MDD, with strikingly disparate conclusions. Our meta-analysis of the 18 such studies, totaling 364 MDD patients free from significant comorbidities or medication and 372 control subjects, revealed reductions in midbrain 5-HTT (Hedges' g = −0.49; 95% CI: (−0.84, −0.14)) and amygdala (Hedges' g = −0.50; 95% CI: (−0.78, −0.22)), which no individual study possessed sufficient power to detect. Only small effect sizes were found in other regions with high binding (thalamus: g = −0.24, striatum: g = −0.32, and brainstem g = −0.22), and no difference in the frontal or cingulate cortex. Age emerged as an important moderator of 5-HTT availability in MDD, with more severe reductions in striatal 5-HTT evident with greater age of the study populations ( P<0.01). There was a strong relationship between severity of depression and 5-HTT reductions in the amygdala ( P = 0.01). Thus, molecular imaging findings indeed reveal widespread reductions of ˜10% in 5-HTT availability in MDD, which may predict altered spatial-temporal dynamics of serotonergic neurotransmission.

scholarly journals A Dual-Labeled Annexin A5 is not Suited for SPECT Imaging of Brain Cell Death in Experimental Murine Stroke

2014 ◽  
Vol 34 (9) ◽  
pp. e1-e7 ◽  
Author(s):  
Marietta Zille ◽  
Denise Harhausen ◽  
Marijke De Saint-Hubert ◽  
Roger Michel ◽  
Chris P Reutelingsperger ◽  
...  
Keyword(s):  
Cell Death ◽  
Fluorescence Microscopy ◽  
Single Photon ◽  
Ex Vivo ◽  
Photon Emission ◽  
Spect Imaging ◽  
Experimental Stroke ◽  
Emission Computed Tomography ◽  
Annexin A5

Cell death is one of the pathophysiological hallmarks after stroke. Markers to image cell death pathways in vivo are highly desirable. We previously showed that fluorescently labeled Annexin A5 (An×A5), which binds specifically to phosphatidylserine (PS) on dead/dying cells, can be used in experimental stroke for monitoring cell death with optical imaging. Here we investigated whether dual-labeled An×A5 (technetium and fluorescence label) can be used for single-photon emission computed tomography (SPECT) of cell death in the same model. C57Bl6/N mice were subjected to 60-minute middle cerebral artery occlusion (MCAO) and underwent SPECT imaging at 24, 48, and 72 hours afterwards. They were injected intravenously with either PS-binding An×A5 or the nonfunctional An×A5 (negative control), labeled with 99mTc and Alexa Fluor 568, respectively. After SPECT imaging, brain sections were cut for autoradiography and fluorescence microscopy. Ethanol-induced cell death in the femur muscle was used as positive control. We detected dual-labeled An×A5 in the model of ethanol-induced cell death in the femur muscle, but not after MCAO at any time point, either with SPECT or with ex vivo autoradiography or fluorescence microscopy. Dual-labeled An×A5 appears to be unsuited for visualizing death of brain cells in this MCAO model.

scholarly journals A Novel SPECT-Based Approach Reveals Early Mechanisms of Central and Peripheral Inflammation after Cerebral Ischemia

2015 ◽  
Vol 35 (12) ◽  
pp. 1921-1929 ◽  
Author(s):  
Krisztián Szigeti ◽  
Ildikó Horváth ◽  
Dániel S Veres ◽  
Bernadett Martinecz ◽  
Nikolett Lénárt ◽  
...  
Keyword(s):  
Brain Injury ◽  
Single Photon ◽  
Photon Emission ◽  
Experimental Stroke ◽  
Emission Computed Tomography ◽  
Peripheral Inflammation ◽  
Poor Outcome ◽  
Diethylene Triamine Pentaacetic Acid ◽  
Magnetic Resonance Imaging Mri

Inflammation that develops in the brain and peripheral organs after stroke contributes profoundly to poor outcome of patients. However, mechanisms through which inflammation impacts on brain injury and overall outcome are improperly understood, in part because the earliest inflammatory events after brain injury are not revealed by current imaging tools. Here, we show that single-photon emission computed tomography (NanoSPECT/CT Plus) allows visualization of blood brain barrier (BBB) injury after experimental stroke well before changes can be detected with magnetic resonance imaging (MRI). Early 99mTc-DTPA (diethylene triamine pentaacetic acid) signal changes predict infarct development and systemic inflammation preceding experimental stroke leads to very early perfusion deficits and increased BBB injury within 2 hours after the onset of ischemia. Acute brain injury also leads to peripheral inflammation and immunosuppression, which contribute to poor outcome of stroke patients. The SPECT imaging revealed early (within 2 hours) changes in perfusion, barrier function and inflammation in the lungs and the gut after experimental stroke, with good predictive value for the development of histopathologic changes at later time points. Collectively, visualization of early inflammatory changes after stroke could open new translational research avenues to elucidate the interactions between central and peripheral inflammation and to evaluate in vivo ‘multi-system’ effects of putative anti-inflammatory treatments.

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