Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism最新文献

{"title":"The cold receptor TRPM8 activation leads to attenuation of endothelium-dependent cerebral vascular functions during head cooling.","authors":"Alex L Fedinec,&nbsp;Jianxiong Liu,&nbsp;Rong Zhang,&nbsp;Mimily Harsono,&nbsp;Massroor Pourcyrous,&nbsp;Helena Parfenova","doi":"10.1177/0271678X211018035","DOIUrl":"https://doi.org/10.1177/0271678X211018035","url":null,"abstract":"<p><p>Using the cranial window technique, we investigated acute effects of head cooling on cerebral vascular functions in newborn pigs. Head cooling lowered the rectal and extradural brain temperatures to 34.3 ± 0.6°C and 26.1 ± 0.6°C, respectively. During the 3-h hypothermia period, responses of pial arterioles to endothelium-dependent dilators bradykinin and glutamate were reduced, whereas the responses to hypercapnia and an endothelium-independent dilator sodium nitroprusside (SNP) remained intact. All vasodilator responses were restored after rewarming, suggesting that head cooling did not produce endothelial injury. We tested the hypothesis that the cold-sensitive TRPM8 channel is involved in attenuation of cerebrovascular functions. TRPM8 is immunodetected in cerebral vessels and in the brain parenchyma. During normothermia, the TRPM8 agonist icilin produced constriction of pial arterioles that was antagonized by the channel blocker AMTB. Icilin reduced dilation of pial arterioles to bradykinin and glutamate but not to hypercapnia and SNP, thus mimicking the effects of head cooling on vascular functions. AMTB counteracted the impairment of endothelium-dependent vasodilation caused by hypothermia or icilin. Overall, mild hypothermia produced by head cooling leads to acute reversible reduction of selected endothelium-dependent cerebral vasodilator functions via TRPM8 activation, whereas cerebral arteriolar smooth muscle functions are largely preserved.</p>","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"2897-2906"},"PeriodicalIF":6.3,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0271678X211018035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39001356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebrospinal fluid hemoglobin drives subarachnoid hemorrhage-related secondary brain injury.","authors":"Kevin Akeret,&nbsp;Raphael M Buzzi,&nbsp;Christian A Schaer,&nbsp;Bart R Thomson,&nbsp;Florence Vallelian,&nbsp;Sophie Wang,&nbsp;Jan Willms,&nbsp;Martina Sebök,&nbsp;Ulrike Held,&nbsp;Jeremy W Deuel,&nbsp;Rok Humar,&nbsp;Luca Regli,&nbsp;Emanuela Keller,&nbsp;Michael Hugelshofer,&nbsp;Dominik J Schaer","doi":"10.1177/0271678X211020629","DOIUrl":"https://doi.org/10.1177/0271678X211020629","url":null,"abstract":"<p><p>Secondary brain injury after aneurysmal subarachnoid hemorrhage (SAH-SBI) contributes to poor outcomes in patients after rupture of an intracranial aneurysm. The lack of diagnostic biomarkers and novel drug targets represent an unmet need. The aim of this study was to investigate the clinical and pathophysiological association between cerebrospinal fluid hemoglobin (CSF-Hb) and SAH-SBI. In a cohort of 47 patients, we collected daily CSF-samples within 14 days after aneurysm rupture. There was very strong evidence for a positive association between spectrophotometrically determined CSF-Hb and SAH-SBI. The accuracy of CSF-Hb to monitor for SAH-SBI markedly exceeded that of established methods (AUC: 0.89 [0.85-0.92]). Temporal proteome analysis revealed erythrolysis accompanied by an adaptive macrophage response as the two dominant biological processes in the CSF-space after aneurysm rupture. Ex-vivo experiments on the vasoconstrictive and oxidative potential of Hb revealed critical inflection points overlapping CSF-Hb thresholds in patients with SAH-SBI. Selective depletion and in-solution neutralization by haptoglobin or hemopexin efficiently attenuated the vasoconstrictive and lipid peroxidation activities of CSF-Hb. Collectively, the clinical association between high CSF-Hb levels and SAH-SBI, the underlying pathophysiological rationale, and the favorable effects of haptoglobin and hemopexin in ex-vivo experiments position CSF-Hb as a highly attractive biomarker and potential drug target.</p>","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"3000-3015"},"PeriodicalIF":6.3,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0271678X211020629","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39075333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leptomeningeal collateral activation indicates severely impaired cerebrovascular reserve capacity in patients with symptomatic unilateral carotid artery occlusion.","authors":"Martina Sebök,&nbsp;Christiaan Hendrik Bas van Niftrik,&nbsp;Niklas Lohaus,&nbsp;Giuseppe Esposito,&nbsp;Mohamad El Amki,&nbsp;Sebastian Winklhofer,&nbsp;Susanne Wegener,&nbsp;Luca Regli,&nbsp;Jorn Fierstra","doi":"10.1177/0271678X211024373","DOIUrl":"https://doi.org/10.1177/0271678X211024373","url":null,"abstract":"<p><p>For patients with symptomatic unilateral internal carotid artery (ICA) occlusion, impaired cerebrovascular reactivity (CVR) indicates increased stroke risk. Here, the role of collateral activation remains a matter of debate, whereas angio-anatomical collateral abundancy does not necessarily imply sufficient compensatory flow provided. We aimed to further elucidate the role of collateral activation in the presence of impaired CVR. From a prospective database, 62 patients with symptomatic unilateral ICA occlusion underwent blood oxygenation-level dependent (BOLD) fMRI CVR imaging and a transcranial Doppler (TCD) investigation for primary and secondary collateral activation. Descriptive statistic and multivariate analysis were used to evaluate the relationship between BOLD-CVR values and collateral activation. Patients with activated secondary collaterals exhibited more impaired BOLD-CVR values of the ipsilateral hemisphere (p = 0.02). Specifically, activation of leptomeningeal collaterals showed severely impaired ipsilateral hemisphere BOLD-CVR values when compared to activation of ophthalmic collaterals (0.05 ± 0.09 vs. 0.12 ± 0.04, p = 0.005). Moreover, the prediction analysis showed leptomeningeal collateral activation as a strong independent predictor for ipsilateral hemispheric BOLD-CVR. In our study, ipsilateral leptomeningeal collateral activation is the sole collateral pathway associated with severely impaired BOLD-CVR in patients with symptomatic unilateral ICA occlusion.</p>","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"3039-3051"},"PeriodicalIF":6.3,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0271678X211024373","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39082190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue outcome prediction in hyperacute ischemic stroke: Comparison of machine learning models.","authors":"Joseph Benzakoun,&nbsp;Sylvain Charron,&nbsp;Guillaume Turc,&nbsp;Wagih Ben Hassen,&nbsp;Laurence Legrand,&nbsp;Grégoire Boulouis,&nbsp;Olivier Naggara,&nbsp;Jean-Claude Baron,&nbsp;Bertrand Thirion,&nbsp;Catherine Oppenheim","doi":"10.1177/0271678X211024371","DOIUrl":"https://doi.org/10.1177/0271678X211024371","url":null,"abstract":"<p><p>Machine Learning (ML) has been proposed for tissue fate prediction after acute ischemic stroke (AIS), with the aim to help treatment decision and patient management. We compared three different ML models to the clinical method based on diffusion-perfusion thresholding for the voxel-based prediction of final infarct, using a large MRI dataset obtained in a cohort of AIS patients prior to recanalization treatment. Baseline MRI (MRI₀), including diffusion-weighted sequence (DWI) and Tmax maps from perfusion-weighted sequence, and 24-hr follow-up MRI (MRI_24h) were retrospectively collected in consecutive 394 patients AIS patients (median age = 70 years; final infarct volume = 28mL). Manually segmented DWI_24h lesion was considered the final infarct. Gradient Boosting, Random Forests and U-Net were trained using DWI, apparent diffusion coefficient (ADC) and Tmax maps on MRI₀ as inputs to predict final infarct. Tissue outcome predictions were compared to final infarct using Dice score. Gradient Boosting had significantly better predictive performance (median [IQR] Dice Score as for median age, maybe you can replace the comma with an equal sign for consistency 0.53 [0.29-0.68]) than U-Net (0.48 [0.18-0.68]), Random Forests (0.51 [0.27-0.66]), and clinical thresholding method (0.45 [0.25-0.62]) (<i>P</i> < 0.001). In this benchmark of ML models for tissue outcome prediction in AIS, Gradient Boosting outperformed other ML models and clinical thresholding method and is thus promising for future decision-making.</p>","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"3085-3096"},"PeriodicalIF":6.3,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0271678X211024371","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39098281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of platelets in the pathogenesis of delayed injury after subarachnoid hemorrhage.","authors":"Ari Dienel,&nbsp;Peeyush Kumar T,&nbsp;Spiros L Blackburn,&nbsp;Devin W McBride","doi":"10.1177/0271678X211020865","DOIUrl":"https://doi.org/10.1177/0271678X211020865","url":null,"abstract":"<p><p>Aneurysmal subarachnoid hemorrhage (aSAH) patients develop delayed cerebral ischemia and delayed deficits (DCI) within 2 weeks of aneurysm rupture at a rate of approximately 30%. DCI is a major contributor to morbidity and mortality after SAH. The cause of DCI is multi-factorial with contributions from microthrombi, blood vessel constriction, inflammation, and cortical spreading depolarizations. Platelets play central roles in hemostasis, inflammation, and vascular function. Within this review, we examine the potential roles of platelets in microthrombi formation, large artery vasospasm, microvessel constriction, inflammation, and cortical spreading depolarization. Evidence from experimental and clinical studies is provided to support the role(s) of platelets in each pathophysiology which contributes to DCI. The review concludes with a suggestion for future therapeutic targets to prevent DCI after aSAH.</p>","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"2820-2830"},"PeriodicalIF":6.3,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0271678X211020865","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39082192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective intra-carotid blood cooling in acute ischemic stroke: A safety and feasibility study in an ovine stroke model.","authors":"Giorgio Fm Cattaneo,&nbsp;Andrea M Herrmann,&nbsp;Sebastian A Eiden,&nbsp;Manuela Wieser,&nbsp;Elias Kellner,&nbsp;Soroush Doostkam,&nbsp;Patrick Süß,&nbsp;Selina Kiefer,&nbsp;Lisa Fauth,&nbsp;Christoph J Maurer,&nbsp;Julia Wolfertz,&nbsp;Björn Nitzsche,&nbsp;Michael Büchert,&nbsp;Tobias Jost,&nbsp;Gabriele Ihorst,&nbsp;Jörg Haberstroh,&nbsp;Christoph Mülling,&nbsp;Christoph Strecker,&nbsp;Wolf-Dirk Niesen,&nbsp;Mukesch J Shah,&nbsp;Horst Urbach,&nbsp;Johannes Boltze,&nbsp;Stephan Meckel","doi":"10.1177/0271678X211024952","DOIUrl":"https://doi.org/10.1177/0271678X211024952","url":null,"abstract":"<p><p>Selective therapeutic hypothermia (TH) showed promising preclinical results as a neuroprotective strategy in acute ischemic stroke. We aimed to assess safety and feasibility of an intracarotid cooling catheter conceived for fast and selective brain cooling during endovascular thrombectomy in an ovine stroke model.Transient middle cerebral artery occlusion (MCAO, 3 h) was performed in 20 sheep. In the hypothermia group (n = 10), selective TH was initiated 20 minutes before recanalization, and was maintained for another 3 h. In the normothermia control group (n = 10), a standard 8 French catheter was used instead. Primary endpoints were intranasal cooling performance (feasibility) plus vessel patency assessed by digital subtraction angiography and carotid artery wall integrity (histopathology, both safety). Secondary endpoints were neurological outcome and infarct volumes.Computed tomography perfusion demonstrated MCA territory hypoperfusion during MCAO in both groups. Intranasal temperature decreased by 1.1 °C/3.1 °C after 10/60 minutes in the TH group and 0.3 °C/0.4 °C in the normothermia group (p < 0.001). Carotid artery and branching vessel patency as well as carotid wall integrity was indifferent between groups. Infarct volumes (p = 0.74) and neurological outcome (p = 0.82) were similar in both groups.Selective TH was feasible and safe. However, a larger number of subjects might be required to demonstrate efficacy.</p>","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"3097-3110"},"PeriodicalIF":6.3,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0271678X211024952","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39098282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A line through the brain: implementation of human line-scanning at 7T for ultra-high spatiotemporal resolution fMRI.","authors":"Luisa Raimondo,&nbsp;Tomas Knapen,&nbsp;Ĺcaro A F Oliveira,&nbsp;Xin Yu,&nbsp;Serge O Dumoulin,&nbsp;Wietske van der Zwaag,&nbsp;Jeroen C W Siero","doi":"10.1177/0271678X211037266","DOIUrl":"https://doi.org/10.1177/0271678X211037266","url":null,"abstract":"<p><p>Functional magnetic resonance imaging (fMRI) is a widely used tool in neuroscience to detect neurally evoked responses, e.g. the blood oxygenation level-dependent (BOLD) signal. Typically, BOLD fMRI has millimeter spatial resolution and temporal resolution of one to few seconds. To study the sub-millimeter structures and activity of the cortical gray matter, the field needs an fMRI method with high spatial and temporal resolution. Line-scanning fMRI achieves very high spatial resolution and high sampling rate, at the cost of a sacrifice in volume coverage. Here, we present a human line-scanning implementation on a 7T MRI system. First, we investigate the quality of the saturation pulses that suppress MR signal outside the line. Second, we established the best coil combination for reconstruction. Finally, we applied the line-scanning method in the occipital lobe during a visual stimulation task, showing BOLD responses along cortical depth, every 250 µm with a 200 ms repetition time (TR). We found a good correspondence of t-statistics values with 2D gradient-echo echo planar imaging (GE-EPI) BOLD fMRI data with the same temporal resolution and voxel volume (R = 0.6 ± 0.2). In summary, we demonstrate the feasibility of line-scanning in humans and this opens line-scanning fMRI for applications in cognitive and clinical neuroscience.</p>","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"2831-2843"},"PeriodicalIF":6.3,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8756483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39328995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranasal delivery of interleukin-4 attenuates chronic cognitive deficits via beneficial microglial responses in experimental traumatic brain injury.","authors":"Hongjian Pu,&nbsp;Cheng Ma,&nbsp;Yongfang Zhao,&nbsp;Yangfan Wang,&nbsp;Wenting Zhang,&nbsp;Wanying Miao,&nbsp;Fang Yu,&nbsp;Xiaoming Hu,&nbsp;Yejie Shi,&nbsp;Rehana K Leak,&nbsp;T Kevin Hitchens,&nbsp;C Edward Dixon,&nbsp;Michael Vl Bennett,&nbsp;Jun Chen","doi":"10.1177/0271678X211028680","DOIUrl":"https://doi.org/10.1177/0271678X211028680","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) is commonly followed by long-term cognitive deficits that severely impact the quality of life in survivors. Recent studies suggest that microglial/macrophage (Mi/MΦ) polarization could have multidimensional impacts on post-TBI neurological outcomes. Here, we report that repetitive intranasal delivery of interleukin-4 (IL-4) nanoparticles for 4 weeks after controlled cortical impact improved hippocampus-dependent spatial and non-spatial cognitive functions in adult C57BL6 mice, as assessed by a battery of neurobehavioral tests for up to 5 weeks after TBI. IL-4-elicited enhancement of cognitive functions was associated with improvements in the integrity of the hippocampus at the functional (<i>e.g.,</i> long-term potentiation) and structural levels (CA3 neuronal loss, diffusion tensor imaging of white matter tracts, <i>etc</i>.). Mechanistically, IL-4 increased the expression of PPARγ and arginase-1 within Mi/MΦ, thereby driving microglia toward a global inflammation-resolving phenotype. Notably, IL-4 failed to shift microglial phenotype after TBI in Mi/MΦ-specific PPARγ knockout (mKO) mice, indicating an obligatory role for PPARγ in IL-4-induced Mi/MΦ polarization. Accordingly, post-TBI treatment with IL-4 failed to improve hippocampal integrity or cognitive functions in PPARγ mKO mice. These results demonstrate that administration of exogenous IL-4 nanoparticles stimulates PPARγ-dependent beneficial Mi/MΦ responses, and improves hippocampal function after TBI.</p>","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"2870-2886"},"PeriodicalIF":6.3,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0271678X211028680","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39182420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep learning-based identification of acute ischemic core and deficit from non-contrast CT and CTA.","authors":"Chengyan Wang,&nbsp;Zhang Shi,&nbsp;Ming Yang,&nbsp;Lixiang Huang,&nbsp;Wenxing Fang,&nbsp;Li Jiang,&nbsp;Jing Ding,&nbsp;He Wang","doi":"10.1177/0271678X211023660","DOIUrl":"https://doi.org/10.1177/0271678X211023660","url":null,"abstract":"<p><p>The accurate identification of irreversible infarction and salvageable tissue is important in planning the treatments for acute ischemic stroke (AIS) patients. Computed tomographic perfusion (CTP) can be used to evaluate the ischemic core and deficit, covering most of the territories of anterior circulation, but many community hospitals and primary stroke centers do not have the capability to perform CTP scan in emergency situation. This study aimed to identify AIS lesions from widely available non-contrast computed tomography (NCCT) and CT angiography (CTA) using deep learning. A total of 345AIS patients from our emergency department were included. A multi-scale 3D convolutional neural network (CNN) was used as the predictive model with inputs of NCCT, CTA, and CTA+ (8 s delay after CTA) images. An external cohort with 108 patients was included to further validate the generalization performance of the proposed model. Strong correlations with CTP-RAPID segmentations (<i>r</i> = 0.84 for core, <i>r</i> = 0.83 for deficit) were observed when NCCT, CTA, and CTA+ images were all used in the model. The diagnostic decisions according to DEFUSE3 showed high accuracy when using NCCT, CTA, and CTA+ (0.90±0.04), followed by the combination of NCCT and CTA (0.87±0.04), CTA-alone (0.76±0.06), and NCCT-alone (0.53±0.09).</p>","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"3028-3038"},"PeriodicalIF":6.3,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0271678X211023660","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39091498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[¹¹C]PBR28 radiotracer kinetics are not driven by alterations in cerebral blood flow.","authors":"Christin Y Sander,&nbsp;Stefano Bovo,&nbsp;Angel Torrado-Carvajal,&nbsp;Daniel Albrecht,&nbsp;Hongping Deng,&nbsp;Vitaly Napadow,&nbsp;Julie C Price,&nbsp;Jacob M Hooker,&nbsp;Marco L Loggia","doi":"10.1177/0271678X211023387","DOIUrl":"https://doi.org/10.1177/0271678X211023387","url":null,"abstract":"<p><p>The positron emission tomography (PET) radiotracer [¹¹C]PBR28 has been increasingly used to image the translocator protein (TSPO) as a marker of neuroinflammation in a variety of brain disorders. Interrelatedly, similar clinical populations can also exhibit altered brain perfusion, as has been shown using arterial spin labelling in magnetic resonance imaging (MRI) studies. Hence, an unsolved debate has revolved around whether changes in perfusion could alter delivery, uptake, or washout of the radiotracer [¹¹C]PBR28, and thereby influence outcome measures that affect interpretation of TSPO upregulation. In this simultaneous PET/MRI study, we demonstrate that [¹¹C]PBR28 signal elevations in chronic low back pain patients are not accompanied, in the same regions, by increases in cerebral blood flow (CBF) compared to healthy controls, and that areas of marginal hypoperfusion are not accompanied by decreases in [¹¹C]PBR28 signal. In non-human primates, we show that hypercapnia-induced increases in CBF during radiotracer delivery or washout do not alter [¹¹C]PBR28 outcome measures. The combined results from two methodologically distinct experiments provide support from human data and direct experimental evidence from non-human primates that changes in CBF do not influence outcome measures reported by [¹¹C]PBR28 PET imaging studies and corresponding interpretations of the biological meaning of TSPO upregulation.</p>","PeriodicalId":520660,"journal":{"name":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism","volume":" ","pages":"3069-3084"},"PeriodicalIF":6.3,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0271678X211023387","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39098280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}