Turku PET Centre

In patients with obstructive coronary artery disease, early revascularization does not improve outcomes but may reduce angina symptoms. The objective of this study was to examine whether changes in health status outcomes following revascularization are explained by the extent of myocardial perfusion defects and improvement in myocardial perfusion. Two trials enrolling stable patients with new-onset chest pain suggestive of obstructive coronary artery disease, the ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) and the Dan-NICAD (Danish Study of Noninvasive Testing in Coronary Artery Disease) trials, were analyzed. Patients with single-vessel coronary artery disease who underwent nuclear myocardial perfusion imaging (nMPI) were included. In the ISCHEMIA trial, patients with moderate/severe ischemia were randomized to either optimal medical therapy alone or optimal medical therapy and invasive angiography. The Dan-NICAD trial enrolled patients with suspected stenosis on coronary computed tomographic angiography undergoing nMPI. Test-guided revascularization blinded to nMPI was performed, and patients with initially abnormal nMPI were reassessed after 12 months. The primary outcome was the change in the Seattle Angina Questionnaire angina frequency score. In total, 584 patients were eligible. In patients with a summed difference score of 5≤10 (n=149 [25%]) and ≥10 (n=152 [26%]), revascularization was associated with an improved angina frequency score (mean change ±SD: 16.4±20.9 and 19.0±24.1). No improvement was demonstrated in patients with a summed difference score <5. In multivariable logistic regression analysis (n=91), an increase in hyperemic myocardial blood flow at follow-up was associated with freedom from angina (odds ratio, 2.89 [95% CI, 1.04-8.70]). In patients with single-vessel coronary artery disease, nMPI may identify patients more likely to experience improved symptoms from revascularization, potentially reflecting enhanced myocardial perfusion.

Background and ObjectivesThe mechanisms underlying tremor generation in Parkinson disease (PD) remain unclear. Previously, we demonstrated a connection between rest tremor amplitude and higher dopamine transporter (DAT) binding in the ipsilateral striatum among the Parkinson Progression Markers Initiative cohort. Here, we investigated the association of parkinsonian motor symptoms with striatal DAT binding in a sizable and clinically representative sample of patients with parkinsonian signs to validate the previously observed ipsilateral relationship in PD.MethodsThis observational cross-sectional study included right-handed patients referred for [123I]FP-CIT SPECT because of clinically uncertain parkinsonism or tremor at Turku University Hospital and the Helsinki and Uusimaa Hospital District, Finland. Each patient underwent a comprehensive clinical evaluation and follow-up (median 3.0 years [interquartile range (IQR) 2.5]). Associations between striatal tracer binding and symptoms were investigated using voxel-wise linear models, adjusting for age, sex, motor symptom severity, and medication. The primary outcome measure was the association between rest tremor amplitude and striatal DAT binding.ResultsAt the end of the follow-up period, of the 414 patients included (median age 68 years [IQR 14], 49.4% female), 148 were evaluated to have PD and 79 other forms of parkinsonism with striatal DAT deficit. In total, 187 patients had normal binding. Among the patients with PD, left and right rest tremor amplitudes were positively associated with ipsilateral striatal DAT binding (β = +0.12 [95% CI +0.05, +0.19] and +0.10 [+0.05, +0.15] specific binding ratio [SBR] per point; pFWE + Bonf. < 0.05, respectively). Left and right bradykinesia (β = −0.16 [−0.22, −0.09] and −0.18 [−0.25, −0.10] SBR per 5 points, pFWE + Bonf. < 0.05, respectively) and rigidity (β = −0.07 [−0.08, −0.04] and −0.08 [−0.11, −0.05] SBR per point, pFWE + Bonf. < 0.05, respectively) mainly showed a negative association with contralateral striatal DAT binding. No consistent associations were observed in non-PD groups.DiscussionThese findings confirm the positive association between rest tremor amplitude and ipsilateral striatal DAT binding in a clinical sample of PD patients. However, the non-PD groups were diagnostically heterogeneous, limiting conclusions about disease specificity.

Abstract Not required.

Alzheimer's disease (AD) has a strong genetic component, with APOE ε4 being the most established risk factor through its effects on beta-amyloid (Aβ) metabolism and microglial function. Recent genetic studies have also implicated microglial genes, such as the ABI3S209F variant, to increased AD risk. As APOE ε4 and ABI3S209F influence microglial pathways through distinct mechanisms, their combined analysis may provide novel insights into AD pathophysiology. Therefore, we investigated ABI3S209F in the Finnish FinnGen cohort and in an imaging study of cognitively healthy older adults. We used FinnGen R12 data (> 500,000 individuals), including 8,490 ABI3S209F carriers and 511,670 non-carriers, with survival analyses matched by sex and birth year. Disease endpoints (AD, dementia, neurodegenerative disorder) were defined from national health registries using harmonized ICD codes, medication, and reimbursement records. For the imaging study, 58 participants aged ≥ 50years were recruited into three genotype-based groups (ABI3S209F/APOE ε4, ABI3S209F/APOE ε3, non-carriers). All imaging participants underwent structural MRI, [11C]PiB PET for amyloid beta, [11C]PK11195 PET for microglial activity, and a comprehensive neuropsychological battery. ABI3S209F was significantly associated with increased risk of AD (OR = 1.22, p = 0.0012) and neurodegenerative disorders (OR = 1.21, p = 0.00023), but not with dementia (OR = 1.10, p = 0.06). Survival analyses indicated that ABI3S209F carriers developed AD at an earlier age than non-carriers with the same APOE genotype. The carriers of ABI3S209F and APOE ε4 had higher brain Aβ burden when compared to the ABI3S209F carriers without APOE ε4 (SUVR 2.0 (0.7) vs. 1.67 (0.5); mean (sd), p = 0.017), but there was no difference in Aβ between the ABI3S209F carriers and controls (1.67 (0.5) vs 1.75 (0.6), p = 0.75 (HST)). ABI3S209F was not associated with global neuroinflammation, although subtle regional increases in [11C]PK11195 binding were observed in ABI3S209F ε4 carriers. No differences were found in brain volumes or cognition. ABI3S209F increases AD risk and is associated with earlier disease onset. The variant alone does not significantly influence cortical Aβ deposition, neuroinflammation, or brain structure. Its effect may be pronounced in combination with APOEε4.

BackgroundParkinson's disease (PD) is associated with several behavioral and cognitive symptoms, the neurobiological background of which is not yet fully understood.ObjectivesThe aim was to investigate the association between monoamine function and four specific nonmotor symptoms in early PD using the Parkinson's Progression Markers Initiative data.Methods[123I]FP‐CIT SPECT imaging data of healthy controls (n = 166) and patients with PD at baseline (n = 349), 2‐year (n = 240), and 4‐year follow‐up (n = 140) were included. Depression, anxiety, rapid eye movement (REM) sleep behavior disorder (RBD) and cognition were evaluated using validated questionnaires. The associations between symptoms and subcortical monoamine transporter binding were analyzed voxel by voxel. Whole brain networks of symptom‐specific monoaminergic abnormalities were characterized using a functional connectome (n = 1000) and normative neurotransmitter receptor maps.ResultsCross‐sectionally, depression was associated with reduced ventral striatum (VS) binding at 2‐ and 4‐year and dorsal raphe (DRN) at 4‐year follow‐up (PFWE < 0.05); trait anxiety was associated with reduced DRN binding at 4‐year follow‐up (PFWE < 0.05). Longitudinally, lower baseline binding in these regions at baseline predicted more severe future depression and anxiety (PFWE < 0.05). RBD was most strongly linked to reduced VS binding at 2‐ and 4‐year follow‐up (nonsignificant after correction, PFWE < 0.1). Each of the symptom‐specific clusters was connected to distinct brain networks, corresponding to specific monoamine receptors: serotonin (5HT1F, 5HT2A, 5HT5A) and histamine (H3) for depression; histamine (H1), serotonin (5HT1E, 5HT1F, 5HT2A, 5HT3B), and adrenergic (α1D) for anxiety; and adrenergic (β2) and serotonin (5HT1F, 5HT2C, 5HT5A) receptors for RBD.ConclusionsThe findings provide novel information about the monoaminergic networks underlying depression, anxiety, and RBD in PD. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Interventional trials with high-density lipoprotein cholesterol (HDL-C)-raising drugs have generally failed to demonstrate a beneficial effect on cardiovascular outcomes, although low HDL-C levels confer the risk of cerebrocardiovascular diseases. Previous experimental studies indicate that HDL-C promotes angiogenesis/arteriogenesis. Therefore, we aimed to clinically investigate whether high blood HDL-C levels could clinically predict cerebral hemodynamic improvements in patients with asymptomatic carotid artery stenosis/occlusion showing cerebral hypoperfusion. This longitudinal retrospective observational study included a total of 66 hemispheres governed by asymptomatic carotid artery stenosis/occlusion in patients who underwent 2-time multi-parametric 15O-gas positron emission tomography (PET). The longitudinal changes of multiple parameters, including cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen, and oxygen extraction fraction (OEF) values were scrutinized between patients with high and low baseline blood HDL-C levels. The cerebral hemodynamic parameters were normalized to the bilateral cerebellum. The median interval between PET examinations was 212.0 and 219.0 days for patients with low and high HDL-C levels, respectively (p = 0.91). A high blood HDL-C level was an independent predictor of increasing CBF (β [mean difference]: 0.035, 95 % confidence interval [CI]: 0.010-0.060), and CBV (β: 0.26, 95 % CI: 0.023-0.50), and decreasing OEF (β: -0.041, 95 % CI: -0.077 to -0.006) in the anterior circulation territory. A high blood HDL-C level was clinically an independent predictor of cerebral hemodynamic improvement. HDL-C could be an important therapeutic target for ischemic stroke prevention by improving cerebral hemodynamic parameters presumably via angiogenesis and arteriogenesis especially in patients showing cerebral hypoperfusion.

The mechanisms underlying neurological symptoms, including epilepsy, in unruptured brain arteriovenous malformations (bAVM) remain to be elucidated. The dual-tracer basis function method (DBFM) with single-scan dual-tracer (15O2 and C15O2) approach is a novel PET imaging technique that can evaluate the hemodynamics and metabolism of brain tissue adjacent to the nidus without the influence of abundant vascular radioactivity. We aimed to clarify the relationship between neurological symptoms and hemodynamic and metabolic abnormalities using the DBFM. Cerebral blood volume (CBV), cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and oxygen extraction fraction (OEF) were compared between symptomatic and asymptomatic bAVMs and before and after treatment. Among 46 patients with unruptured bAVMs who underwent DBFM, 26 cases were included. While CBV and OEF increased in the perinidus (p < 0.01), CBF and CMRO2 decreased (p < 0.01). Symptoms were significantly associated with higher OEF (symptomatic vs. asymptomatic, ratio of perinidal to contralateral, n = 13 vs. n = 13, 1.07 ± 0.030 vs. 1.01 ± 0.080, p = 0.017). All elevated OEFs in symptomatic bAVMs with therapeutic symptom resolved in post-therapeutic PET imaging. DBFM revealed a higher OEF was associated with symptomatic bAVM. The DBFM potentially aids in predicting post-therapeutic symptom improvement.

Despite extensive research, open questions about the biological underpinnings of Alzheimer’s disease (AD) remain. Neuroimaging biomarkers based on positron emission tomography (PET) and magnetic resonance imaging (MRI) offer in vivo insights into these complex biological changes and interactions. However, most evidence to date comes from cross-sectional studies, limiting our understanding of disease progression. Longitudinal studies enable the investigation of biological changes within individuals, revealing how pathology evolves over time. With this review, we provide an overview of how longitudinal imaging biomarker studies have advanced the field and how they can contribute to future research. We highlight longitudinal biomarker studies that have provided critical insights into disease trajectories, staging, and individual variability. We further assess longitudinal multimodal studies which have elucidated interactions between AD-specific pathology, amyloid-β and tau, and broader biological changes like neurodegeneration, neuronal dysfunction, vascular disease, and inflammation. Further, we discuss associations of brain changes with symptomatology and clinical outcomes and conclude with challenges and future directions.

Short-chain fatty acids (SCFAs) produced from dietary fiber fermentation can regulate adipose tissue metabolism through signaling pathways involving G protein-coupled receptors and histone deacetylase inhibition. While preclinical studies suggest they enhance thermogenesis, their role in human brown adipose tissue (BAT) under different thermal conditions remains unclear. This study explores the associations between circulating SCFAs and human BAT metabolism at room temperature and after cold exposure. This cross-sectional study included data from 71 adults (aged 20-55 years, body mass index 19-44 kg/m2). Dynamic [15O]O2, [15O]H2O, [¹⁸F]FDG, and [¹⁸F]FTHA positron emission tomography/computed tomography scans were used to assess BAT metabolism. Serum SCFAs were quantified using liquid chromatography-mass spectrometry, and gene expression in biopsy-excised BAT samples (n = 14) was analyzed. Participants were stratified into low- and high-BAT groups based on [¹⁸F]FDG or [¹⁸F]FTHA uptakes. Cold-induced acetate and propionate were positively associated with key in vivo BAT metabolism indicators, namely nonesterified fatty acid (NEFA) uptake and oxygen consumption. Only in the high-BAT group were circulating SCFAs maintained after cold exposure. BAT transcriptome revealed that genes involved in SCFA metabolism (such as conversion to acetyl-CoA) correlated with thermogenic and lipid metabolism genes exclusively in the high-BAT group, suggesting a distinct molecular link between SCFA pathways and BAT function. Circulating SCFAs are linked with BAT oxidative metabolism and NEFA uptake during cold exposure. The observed correlations between SCFA catabolic genes and thermogenic markers suggest that metabolically active BAT may selectively engage SCFA-related pathways, pointing to a potential mechanistic role of SCFAs in supporting BAT function in humans.