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

{"title":"EXPRESS: Risk factors and predictive model for non-aspiration stroke-associated infections in patients with acute ischemic stroke followed by intravenous thrombolysis.","authors":"Xuanyue Yu, Ziqi Han, Dong Chen, Wen Zhao, Phyo Myint, Shuya Cai, Tie-Ping Fan, Chunpeng Gao, Lichao Zhao, Han Liu, Dirk M Hermann, Shiyao Wang, Yi Liu","doi":"10.1177/0271678X261487851","DOIUrl":"https://doi.org/10.1177/0271678X261487851","url":null,"abstract":"<p><strong>Objective: </strong>To analyze clinical characteristics, risk factors, and a predictive model for non-aspiration stroke-associated infections (NASAI) in acute ischemic stroke (AIS) patients receiving intravenous alteplase thrombolysis.</p><p><strong>Methods: </strong>This prospective cohort study included AIS patients from the DATIS cohort (Jan 2018-Jul 2024) who received rt-PA thrombolysis. NASAI was defined as stroke-associated infection without evidence of aspiration. Patients were randomized 7:3 into training (n=1171) and validation (n=503) sets. LASSO and logistic regression were used to select predictors. Model performance was assessed by ROC curve, calibration curve (CC), and decision curve analysis (DCA).</p><p><strong>Results: </strong>Among 1828 patients, NASAI prevalence was 10.72% (196/1828), accounting for 56% of all SAI cases. Independent risk factors included older age (OR 1.62), hypertension (1.64), higher admission NIHSS (4.03), heart rate (1.06), and white blood cell count (1.16). The nomogram showed AUCs of 0.80 (training) and 0.78 (validation), with good calibration and net benefit on DCA.</p><p><strong>Conclusion: </strong>A nomogram based on five easily accessible variables demonstrated strong predictive performance for NASAI, offering a practical tool for early risk assessment in thrombolyzed AIS patients.</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":"271678X261487851"},"PeriodicalIF":4.5,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148877196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EXPRESS: Brain energy metabolism and metabolic water in ageing, Alzheimer's, and other neurological diseases.","authors":"Martin Lauritzen, Gerald Dienel","doi":"10.1177/0271678X261486145","DOIUrl":"https://doi.org/10.1177/0271678X261486145","url":null,"abstract":"<p><strong>Background/hypothesis: </strong>Glucose oxidation is the brain's main way of producing the energy needed for neuronal signaling and essential maintenance tasks. When the brain cannot produce or use energy efficiently, neurons become less functional and more vulnerable. Although ageing is thought to affect brain metabolism, precise measurements of oxidative glucose use are still limited.</p><p><strong>Methods/results: </strong>This review brings together current evidence on how brain energy metabolism changes during healthy ageing, dementia, and major neurological disorders, using absolute measurements of oxygen consumption. Overall, the data show that oxidative glucose metabolism stays stable in healthy brain ageing. In contrast, it drops by up to ~40% in Alzheimer's disease, more with greater disease severity, and by ~ 25% in multiple sclerosis and hydrocephalus. These declines reduce the amount of ATP available for both signaling and basic cellular functions, which are essential for perception and cognition. Metabolic water production is proportionately reduced when CMRO2 decreases in diseased brain, and its secretion into interstitial fluid is diminished.</p><p><strong>Conclusion/interpretation: </strong>In disease, lower oxidative metabolic activity reduces metabolic water production, which may in turn affect brain fluid dynamics, including processes involved in neuroprotection and waste clearance.</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":"271678X261486145"},"PeriodicalIF":4.5,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EXPRESS: HOW TO IMPROVE RECOVERY AFTER INTRACEREBRAL HEMORRHAGE - HEMATOMA CLEARANCE AS A THERAPEUTIC TARGET.","authors":"Shun-Ming Ting, Jaroslaw Aronowski","doi":"10.1177/0271678X261485752","DOIUrl":"https://doi.org/10.1177/0271678X261485752","url":null,"abstract":"<p><p>Hemolysis products are very highly cerebrotoxic. However, surgical approaches to evacuate hematoma-containing hemolysis products after intracerebral hemorrhage (ICH) surprisingly showed mixed therapeutic effects. Thus, alternative non-invasive approaches, e.g., those that improve hematoma clearance by endogenous phagocytes, have been experimentally tested and, to date, show highly promising therapeutic benefit for post-ICH recovery. Resident microglia (MG) and monocyte-derived macrophages (together MΦ), important components of the innate immune system, are two highly related professional scavenger cell types that mediate hematoma clearance after ICH. MΦ readily conduct phagocytosis/endocytosis of extravasated blood components, dead/apoptotic cells, and various cellular debris. Unless removed from the brain, these elements induce cytotoxicity and lingering inflammation and form a physical barrier to neuronal re-connectivity, thereby impeding recovery after ICH. Hence, evaluating new therapeutic approaches to improve the efficacy of MΦ-mediated hematoma cleanup could provide a promising strategy to promote post-ICH repair and recovery. The mechanistic bases for these cleanup approaches include: (1) enhancing the expression of scavenger receptors and other phagocytosis-assisting proteins in the MΦ'; (2) blocking the molecules that provide \"do not eat me\" (anti-phagocytic) signals presenting on the surface of apoptotic cells/debris to be phagocytosed; and (3) protecting the intra-MΦ \"health\" to sustain effective debris engulfment and degradation, without injuring the phagocytes themselves. We will primarily focus on MΦ-mediated erythrophagocytosis and the detoxification of hemolytic products (hemoglobin, heme, and iron) in the ICH-affected brain. By providing numerous pre-clinical examples, we will demonstrate that the regulation of cleanup is a potential clinically relevant therapeutic target for ICH.</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":"271678X261485752"},"PeriodicalIF":4.5,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent elevation of neutrophil extracellular traps is an independent predictor for non-ambulatory functional outcome in acute ischemic stroke patients with successful recanalization post-endovascular therapy.","authors":"Yige Zhang, Liyuan Wang, Yuwan Cui, Guangshuo Li, Yahui Hao, Zhixin Cao, Zhixin Li, Ganghua Feng, Hao Wang, Xinmin Fu, Ziqi Xu, Wenhua Liu, Hongchao Shi, Xiangliang Chen, Bruce Cv Campbell, Yongjun Wang, Yunyun Xiong","doi":"10.1177/0271678X261478950","DOIUrl":"10.1177/0271678X261478950","url":null,"abstract":"<p><p>Neutrophil extracellular traps (NETs) contribute to microvascular dysfunction and may predict poor outcomes after successful endovascular treatment (EVT) for acute ischemic stroke (AIS). We investigated dynamic changes in NETs biomarkers (myeloperoxidase-associated DNA complexes (MPO-DNA) and citrullinated histone H3 (CitH3)) and their prognostic value for non-ambulatory functional outcome. In this prospective multicenter cohort, 114 AIS patients with successful recanalization after EVT underwent serial biomarkers measurement at baseline, at 24 h post-EVT and at 7 days/discharge. Primary outcome was non-ambulatory functional outcome (90 days modified Rankin Scale (mRS) 4-6). Generalized estimating equation (GEE) assessed trajectory differences between outcome groups. Logistic regression identified independent predictors. MPO-DNA increased from baseline (341.34 (280.72-442.81)) to 24 h (472.29 (386.35-571.09); <i>p</i> < 0.01) and decline at 7 days/discharge (327.74 (268.17-397.99); <i>p</i> < 0.01 vs at 24 h). CitH3 showed non-significant increase at 24 h (14.022 (9.322-25.783)) vs baseline (12.107 (8.810-21.327); <i>p</i> = 0.16) but significant decrease at 7 days/discharge (11.302 (2.824-21.540); <i>p</i> = 0.01 vs at 24 h post-EVT). GEE revealed a significant time-by-group interaction for CitH3 (<i>p</i> = 0.01), but not for MPO-DNA (<i>p</i> = 0.18). Elevated CitH3 7 days/24 h ratio was independently associated with non-ambulatory functional outcome after multivariable adjustment (aOR = 1.99, 95% CI: 1.06-3.72, <i>p</i> = 0.03) with age, baseline National Institutes of Health Stroke Scale (NIHSS), ischemic core volume, and hemoglobin A1c (HbA1c) >6.0% as covariates. Persistent elevation of NETs during 24 h to 7 days is independently associated with post-EVT non-ambulatory functional outcome.</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":"271678X261478950"},"PeriodicalIF":4.5,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13525116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148842739","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":"EXPRESS: The microdialysis-derived lactate-pyruvate gradient indicates anaerobic activity after brain injury.","authors":"Michael Steven Baker, Joshua M Heihre, Tomasz Benedykt Kuliński, Claudia Ann Smith, Berfin Barlas, Chisomo Zimphango, Ivan Timofeev, Koby Baranes, Keri L H Carpenter, Mark Kotter, Mathew R Guilfoyle, Elham Rostami, Peter Hutchinson, Adel Helmy","doi":"10.1177/0271678X261485404","DOIUrl":"https://doi.org/10.1177/0271678X261485404","url":null,"abstract":"<p><strong>Background: </strong>Cerebral microdialysis (CMD) after traumatic brain injury (TBI) has focused on lactate/pyruvate ratio (LPR), overlooking lactate-pyruvate gradient (LPG, the linear regression slope within a time segment of CMD datapoints) as a proxy for anaerobic activity.</p><p><strong>Methods: </strong>We retrospectively applied changepoint detection to the linear lactate-pyruvate relationship (L = mP + b) over time within patients from two independent CMD-monitored TBI cohorts (Cambridge, n = 510; Uppsala, n = 81), estimating per-segment LPG (m) and intercept (b, capturing metabolic variance). In vitro, we tested whether rotenone-induced mitochondrial dysfunction increases LPG in hiPSC-derived neurons, as expected if LPG tracks anaerobic activity.</p><p><strong>Results: </strong>In the Cambridge cohort, a median of two linear segments were identified per patient (median LPG = 19.83; median b = 0.54 mM). Between segments, LPR tracked LPG with heavy attenuation (β = 0.255). LPG was negatively associated with cerebral microdialysate glucose (p < 0.001) and 6-month GOSE (p = 0.039). Uppsala data confirmed pipeline robustness and replicated the LPG-glucose association (p = 0.022). LPG was higher in rotenone-treated neurons than controls (32.9 vs. 14.2, p < 0.001).</p><p><strong>Conclusion: </strong>LPG calculated per time segment provides a more accurate, outcome-associated proxy for anaerobic activity than datapoint-level LPR.</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":"271678X261485404"},"PeriodicalIF":4.5,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EXPRESS: Disentangling MRI-derived blood-brain barrier leakage into vascular permeability and surface area.","authors":"Damon Verstappen, Joost J A de Jong, Paulien H Voorter, Maud van Dinther, Robert J van Oostenbrugge, Julie Staals, Jacobus F A F A Jansen, Walter H Backes","doi":"10.1177/0271678X261485415","DOIUrl":"https://doi.org/10.1177/0271678X261485415","url":null,"abstract":"<p><strong>Background: </strong>In neurovascular and neurodegenerative diseases, blood-brain barrier (BBB) disruption can be subtle, diffuse, and MRI-derived measures are confounded by microvascular architecture. Therefore, we aimed to disentangle MRI-derived blood-brain barrier leakage rate (K_i) into intrinsic vascular permeability (P) and surface area (S).</p><p><strong>Methods: </strong>In this cross-sectional study, 45 patients with cSVD and 26 elderly controls underwent dynamic contrast-enhanced (DCE) MRI to determine K_i and vessel architecture imaging (VAI) to estimate S. These measures were used to calculate P.</p><p><strong>Results: </strong>Compared to normal-appearing white matter (NAWM), K_i was higher in WMH (β=0.297, p<0.001) and deep gray matter (DGM) (β=0.210, p=0.007). P was higher in WMH (β=0.410, p<0.001) and similar between NAWM and DGM. S was smaller in WMH (β=-0.467, p<0.001) and larger in DGM (β=0.540, p<0.001). K_i (β=0.289, p=0.007) and P (β=0.249, p=0.021) were only higher in patients than controls in concentric shells surrounding WMH. S was smaller in WMH of patients than controls (β=-0.085, p=0.049). With age, K_i (β=0.260, p=0.008) and P increased (β=0.273, p<0.001), while S decreased (β=-0.079, p=0.025).</p><p><strong>Conclusion: </strong>Disentangling P and S from the BBB leakage rate provides two biologically more specific and interpretable measures, which have counteracting effects on the BBB leakage in aging and disease.</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":"271678X261485415"},"PeriodicalIF":4.5,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EXPRESS: Beyond structural fragility in germinal matrix hemorrhage: a protease-threshold model of developmental cerebral microvascular failure.","authors":"Leandro Castaneyra-Ruiz, Alexandra Latini, Brian W Hanak, Michael Muhonen","doi":"10.1177/0271678X261483569","DOIUrl":"https://doi.org/10.1177/0271678X261483569","url":null,"abstract":"<p><p>Germinal matrix hemorrhage (GMH) is a localized form of developmental cerebral microvascular failure and a major cause of mortality and long-term neurological disability in preterm infants. The GM is a highly angiogenic, protease-active developmental niche that operates near the limits of vascular stability under tightly regulated intrauterine conditions. Preterm birth disrupts this balance by removing late-gestational immune modulation and exposing protease-primed GM vessels to exaggerated inflammatory activation. Dysregulated innate immune responses amplify endothelial junctional cleavage and basement-membrane degradation and reprogram the local myeloid environment toward neutrophil-derived protease release. We propose a unified protease-threshold framework in which GMH occurs when inflammatory amplification drives proteolytic activity beyond the structural resilience of the immature GM vasculature. This model may help account for the timing, localization, and heterogeneity of GMH and provides a testable framework for studying developmental neurovascular vulnerability, biomarker discovery, and preventive strategies.</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":"271678X261483569"},"PeriodicalIF":4.5,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148805228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EXPRESS: Following the curvature: sulcal versus gyral cortical localization of cerebral microbleeds in Cerebral Amyloid Angiopathy.","authors":"Manon Roxanne Schipper, Thijs Wijnzen van Harten, Emma Koemans, Jelle J Goeman, Marieke Wermer, Matthias J Van Osch, Marianne A A van Walderveen","doi":"10.1177/0271678X261482016","DOIUrl":"https://doi.org/10.1177/0271678X261482016","url":null,"abstract":"<p><p>Cerebrospinal fluid (CSF) mediated brain clearance and inflammation are known features of Cerebral Amyloid Angiopathy (CAA), that may be affected by the cortical gyrencephalic structure. Considering these processes in the development of cerebral microbleeds (CMB), we compared sulcal and gyral cortical CMBs in sporadic and Dutch-type hereditary CAA (sCAA and D-CAA).CMBs were manually annotated on 3 Tesla (3T) susceptibility weighted imaging. Sulcal and gyral cortex-maps were created using FreeSurfer's curvature analysis of 3T T1-weighted scans. Sulcal and gyral CMB densities were compared using a generalized mixed linear model. Sensitivity analyses examined the influence of disease type and mixed pathology (presence of deep CMBs) on regional effect.The study included 28 participants (17/11 sCAA/D-CAA, mean age 70/53 years, and 54%/73% female, respectively). Sulcal CMB density was higher than gyral CMB density (B=0.618, exp(B)=1.86, p<0.001). Sensitivity analyses showed sulcal CMB predominance also when taking disease type into account (B=0.499, exp(B)=1.65, p=0.019), with higher CMB densities in sCAA (B=1.326, exp(B)=3.77, p=0.033) and robust sulcal CMB predominance when analyzing only participants with strictly cortical CMBs (B=0.583, exp(B)=1.79, p<0.001).Increased sulcal CMB density in CAA may indicate varying hemorrhagic vulnerability along the cortex, potentially arising from anatomy-based variations in inflammation and CSF flow dynamics.</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":"271678X261482016"},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148805279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EXPRESS: Spleen-mediated inflammation in ischemic stroke: mechanisms and targeted therapeutic strategies.","authors":"Si Wu, Ling Hui Luo, Yu Gao, Guangxian Nan","doi":"10.1177/0271678X261482070","DOIUrl":"10.1177/0271678X261482070","url":null,"abstract":"<p><p>Stroke is a leading cause of death and disability worldwide. Emerging evidence from animal studies and clinical observations suggests that peripheral immune responses amplify neuroinflammation after acute ischemic stroke. This review briefly summarizes the interactions between peripheral immune responses and the ischemic brain, with a focus on the brain-spleen axis. Specifically, we dissect the mechanisms underlying spleen-mediated immune effects on the ischemic brain. We then critically summarize current spleen-targeted therapeutic strategies, ranging from physical and pharmacological interventions to stem cell-based approaches that reprogram splenic immune landscapes. Collectively, these insights aim to inform future immunomodulatory strategies targeting the brain-spleen axis.</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":"271678X261482070"},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148805264","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":"Deuteration enhances UV-induced hyperpolarization of [1-¹³C]pyruvate to trityl-level performance in vitro and in vivo.","authors":"Maiko Ono, Andrea Capozzi, Kosei Hirata, Chikara Yamauchi, Keita Saito, Mor Mishkovsky, Yuhei Takado","doi":"10.1177/0271678X261482014","DOIUrl":"10.1177/0271678X261482014","url":null,"abstract":"<p><p>Dissolution dynamic nuclear polarization (dDNP) using UV-irradiated, non-persistent radicals has recently emerged as a filtration-free alternative to trityl-based methods; however, its performance for in vivo metabolic imaging remains insufficiently evaluated. Here, we systematically assessed UV-induced hyperpolarized (HP) [1-¹³C]pyruvate and its deuterated analog in the mouse brain, a technically demanding target for HP ¹³C MRI, and directly compared the results with conventional OX063-based dDNP. UV-induced HP [1-¹³C]pyruvate yielded lactate-to-pyruvate and bicarbonate-to-pyruvate ratios equivalent to those obtained with OX063-polarized preparations, and demonstrated good test-retest reproducibility. Deuteration substantially improved the polarization levels of UV-irradiated samples to values comparable to trityl-based dDNP, while preserving comparable in vivo metabolic readouts. Building on this methodological validation, awake ¹³C MRSI using HP [1-¹³C, d₄]pyruvate, as applied in the present study, was used as a proof-of-concept in an Alzheimer's disease mouse model, where increased pyruvate-to-lactate conversion was detected in hippocampus-including regions of 3-month-old APP^NL-G-F knock-in mice. Together, these results support UV-induced, deuterated HP pyruvate as a practical alternative to trityl-based dDNP and demonstrate its feasibility for preclinical HP ¹³C MRI studies of brain metabolism.</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":"271678X261482014"},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148805235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}