Browsing by Subject "Positron emission tomography"

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  • Sun, Lihua; Aarnio, Richard; Herre, Erika Atencio; Kärnä, Salli; Palani, Senthil; Virtanen, Helena; Liljenbäck, Heidi; Virta, Jenni; Honkaniemi, Aake; Oikonen, Vesa; Han, Chunlei; Laurila, Sanna; Bucci, Marco; Helin, Semi; Yatkin, Emrah; Nummenmaa, Lauri; Nuutila, Pirjo; Tang, Jing; Roivainen, Anne (2023)
    Purpose Photoperiod determines the metabolic activity of brown adipose tissue (BAT) and affects the food intake and body mass of mammals. Sympathetic innervation of the BAT controls thermogenesis and facilitates physiological adaption to seasonal changes, but the exact mechanism remains elusive. Previous studies have shown that central opioid signaling regulates BAT thermogenesis, and that the expression of the brain mu-opioid receptor (MOR) varies seasonally. Therefore, it is important to know whether MOR expression in BAT shows seasonal variation. Methods We determined the effect of photoperiod on BAT MOR availability using [C-11] carfentanil positron emission tomography (PET). Adult rats (n = 9) were repeatedly imaged under various photoperiods in order to simulate seasonal changes. Results Long photoperiod was associated with low MOR expression in BAT (beta = -0.04, 95% confidence interval: - 0.07, - 0.01), but not in muscles. We confirmed the expression of MOR in BAT and muscle using immunofluorescence staining. Conclusion Photoperiod affects MOR availability in BAT. Sympathetic innervation of BAT may influence thermogenesis via the peripheral MOR system. The present study supports the utility of [C-11]carfentanil PET to study the peripheral MOR system.
  • Ni, Ruiqing; Gillberg, Per-Goran; Bogdanovic, Nenad; Viitanen, Matti; Myllykangas, Liisa; Nennesmo, Inger; Langstrom, Bengt; Nordberg, Agneta (2017)
    Introduction: Amyloid imaging has been integrated into diagnostic criteria for Alzheimer's disease (AD). How amyloid tracers binding differ for different tracer structures and amyloid-beta aggregates in autosomal dominant AD (ADAD) and sporadic AD is unclear. Methods: Binding properties of different amyloid tracers were examined in brain homogenates from six ADAD with APPswe, PS1 M146V, and PS1 E Delta 9 mutations, 13 sporadic AD, and 14 control cases. Results: H-3-PIB, H-3-florbetaben, H-3-AZD2184, and BTA-1 shared a high-and a varying low-affinity binding site in the frontal cortex of sporadic AD. AZD2184 detected another binding site (affinity 33 nM) in the frontal cortex of ADAD. The H-3-AZD2184 and H-3-PIB binding were significantly higher in the striatum of ADAD compared to sporadic AD and control. Polyphenol resveratrol showed strongest inhibition on H-3-AZD84 binding followed by H-3-florbetaben and minimal on H-3-PIB. Discussion: This study implies amyloid tracers of different structures detect different sites on amyloid-beta fibrils or conformations. (C) 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
  • Majala, Susanna; Vesterinen, Tiina; Seppänen, Hanna; Mustonen, Harri; Sundström, Jari; Schalin-Jäntti, Camilla; Gullichsen, Risto; Schildt, Jukka; Kemppainen, Jukka; Arola, Johanna; Kauhanen, Saila (2022)
    Purpose: The aim of this study was to correlate immunohistochemical (IHC) tissue levels of SSTR1-5 with the receptor density generated from [68Ga]Ga-DOTANOC uptake in a prospective series of NF-PNENs. Methods: Twenty-one patients with a total of thirty-five NF-PNEN-lesions and twenty-one histologically confirmed lymph node metastases (LN+) were included in this prospective study. Twenty patients were operated on, and one underwent endoscopic ultrasonography and core-needle biopsy. PET/CT with both [68Ga]Ga-DOTANOC and [18F]F-FDG was performed on all patients. All histological samples were re-classified and IHC-stained with monoclonal SSTR1-5 antibodies and Ki-67 and correlated with [68Ga]Ga-DOTANOC and [18F]F-FDG PET/CT. Results: Expression of SSTR1-5 was detected in 74%, 91%, 80%, 14%, and 77% of NF-PNENs. There was a concordance of SSTR2 IHC with positive/negative [68Ga]Ga-DOTANOC finding (Spearman’s rho 0.382, p = 0.043). All [68Ga]Ga-DOTANOC-avid tumors expressed SSTR2 or SSTR3 or SSTR5. Expression of SSTR5 was higher in tumors with a low Ki-67 proliferation index (PI) (−0.353, 95% CI −0.654–0.039, p = 0.038). The mean Ki-67 PI for SSTR5 positive tumors was 2.44 (SD 2.56, CI 1.0–3.0) and 6.38 (SD 7.25, CI 2.25–8.75) for negative tumors. Conclusion: SSTR2 was the only SSTR subtype to correlate with [68Ga]Ga-DOTANOC PET/CT. Our prospective study confirms SSTR2 to be of the highest impact for SST PET/CT signal.
  • Martikainen, Ilkka K.; Hagelberg, Nora; Jääskelainen, Satu K.; Hietala, Jarmo; Pertovaara, Antti (2018)
    Here we review the literature assessing the roles of the brain dopaminergic and serotonergic systems in the modulation of pain as revealed by in vivo human studies using positron emission tomography. In healthy subjects, dopamine D-2/D-3 receptor availability particularly in the striatum and serotonin 5-HT1A and 5-HT2A receptor availabilities in the cortex predict the subject's response to tonic experimental pain. High availability of dopamine D-2/D-3 or serotonin 5-HT2A receptors is associated with high pain intensity, whereas high availability of 5-HT1A receptors associates with low pain intensity. Chronic neuropathic pain is associated with high striatal dopamine D-2/D-3 receptor availability, for which low endogenous dopamine tone is a plausible explanation, although a compensatory increase in striatal dopamine D-2/D-3 receptor density may also contribute. In contrast, chronic musculoskeletal pain is associated with low baseline availability of striatal dopamine D-2/D-3 receptors. In healthy subjects, brain serotonin 5-HT1A as well as dopamine D-2/D-3 receptor availabilities associate with the subject's response criterion rather than the capacity to discriminate painful thermal stimuli suggesting that these neurotransmitter systems act mainly on non-sensory rather than sensory factors of thermally induced pain experience. Additionally, 5-HT1A receptor availability predicts the subject's discriminative ability but not response criterion for non-painful tactile test stimuli, while no such correlation is observed with dopamine D-2/D-3 receptors. These findings suggest that dopamine acting on striatal dopamine D-2/D-3 receptors and serotonin acting on cortical 5-HT1A and 5-HT2A receptors contribute to top-down pain regulation in humans.
  • Lindgren, Noora; Kaprio, Jaakko; Karjalainen, Tomi; Ekblad, Laura; Helin, Semi; Karrasch, Mira; Teuho, Jarmo; Rinne, Juha O.; Vuoksimaa, Eero (2021)
    We studied the association between episodic memory and cortical fibrillar β-amyloid pathology within twin pairs. Using telephone-administered cognitive screening of 1415 twin pairs in a population-based older Finnish Twin Cohort study, we identified 45 (mean [SD] age 72.9 [4.0] years, 40% women) cognitively discordant same-sex twin pairs (24 dizygotic and 21 monozygotic) without neurological or psychiatric disorders other than AD or mild cognitive impairment. In-person neuropsychological testing was conducted. Cortical amyloid was measured with carbon 11-labelled Pittsburgh compound B ([11C]PiB) positron emission tomography imaging and quantified as the average standardized uptake value ratio in cortical regions affected in AD. Larger within-twin pair differences in verbal immediate (r = -0.42) and delayed free recall (r = -0.41), and visual delayed free recall (r = -0.46) were associated with larger within-twin pair differences in [11C]PiB uptake (p's < 0.01). Correlations were not significantly different in dizygotic and monozygotic pairs suggesting that the episodic memory-cortical amyloid relationship is not confounded by genetic effects. However, larger samples are needed to draw more definitive conclusions.
  • Grönman, Maria; Tarkia, Miikka; Kiviniemi, Tuomas; Halonen, Paavo; Kuivanen, Antti; Savunen, Timo; Tolvanen, Tuula; Teuho, Jarmo; Käkelä, Meeri; Metsälä, Olli; Pietilä, Mikko; Saukko, Pekka; Ylä-Herttuala, Seppo; Knuuti, Juhani; Roivainen, Anne; Saraste, Antti (BioMed Central, 2017)
    Abstract Background Radiolabeled RGD peptides detect αvβ3 integrin expression associated with angiogenesis and extracellular matrix remodeling after myocardial infarction. We studied whether cardiac positron emission tomography (PET) with [68Ga]NODAGA-RGD detects increased αvβ3 integrin expression after induction of flow-limiting coronary stenosis in pigs, and whether αvβ3 integrin is expressed in viable ischemic or injured myocardium. Methods We studied 8 Finnish landrace pigs 13 ± 4 days after percutaneous implantation of a bottleneck stent in the proximal left anterior descending coronary artery. Antithrombotic therapy was used to prevent stent occlusion. Myocardial uptake of [68Ga]NODAGA-RGD (290 ± 31 MBq) was evaluated by a 62 min dynamic PET scan. The ischemic area was defined as the regional perfusion abnormality during adenosine-induced stress by [15O]water PET. Guided by triphenyltetrazolium chloride staining, tissue samples from viable and injured myocardial areas were obtained for autoradiography and histology. Results Stent implantation resulted in a partly reversible myocardial perfusion abnormality. Compared with remote myocardium, [68Ga]NODAGA-RGD PET showed increased tracer uptake in the ischemic area (ischemic-to-remote ratio 1.3 ± 0.20, p = 0.0034). Tissue samples from the injured areas, but not from the viable ischemic areas, showed higher [68Ga]NODAGA-RGD uptake than the remote non-ischemic myocardium. Uptake of [68Ga]NODAGA-RGD correlated with immunohistochemical detection of αvβ3 integrin that was expressed in the injured myocardial areas. Conclusions Cardiac [68Ga]NODAGA-RGD PET demonstrates increased myocardial αvβ3 integrin expression after induction of flow-limiting coronary stenosis in pigs. Localization of [68Ga]NODAGA-RGD uptake indicates that it reflects αvβ3 integrin expression associated with repair of recent myocardial injury.
  • Päivärinta, Johanna; Oikonen, Vesa; Räisänen-Sokolowski, Anne; Tolvanen, Tuula; Löyttyniemi, Eliisa; Hidehiro, Iida; Nuutila, Pirjo; Metsärinne, Kaj; Koivuviita, Niina (2019)
    Background Despite improvement in short-term outcome of kidney transplants, the long-term survival of kidney transplants has not changed over past decades. Kidney biopsy is the gold standard of transplant pathology but it's invasive. Quantification of transplant blood flow could provide a novel non-invasive method to evaluate transplant pathology. The aim of this retrospective cross-sectional pilot study was to evaluate positron emission tomography (PET) as a method to measure kidney transplant perfusion and find out if there is correlation between transplant perfusion and histopathology. Methods Renal cortical perfusion of 19 kidney transplantation patients [average time from transplantation 33 (17-54) months; eGFR 55 (47-69) ml/min] and 10 healthy controls were studied by [(15) O]H2O PET. Perfusion and Doppler resistance index (RI) of transplants were compared with histology of one-year protocol transplant biopsy. Results Renal cortical perfusion of healthy control subjects and transplant patients were 2.7 (2.4-4.0) ml min(- 1) g(- 1) and 2.2 (2.0-3.0) ml min(- 1) g(- 1), respectively (p = 0.1). Renal vascular resistance (RVR) of the patients was 47.0 (36.7-51.4) mmHg mL(- 1)min(- 1)g(- 1) and that of the healthy 32.4 (24.6-39.6) mmHg mL(- 1)min(-1)g(-1) (p = 0.01). There was a statistically significant correlation between Doppler RI and perfusion of transplants (r = - 0.51, p = 0.026). Transplant Doppler RI of the group of mild fibrotic changes [0.73 (0.70-0.76)] and the group of no fibrotic changes [0.66 (0.61-0.72)] differed statistically significantly (p = 0.03). No statistically significant correlation was found between cortical perfusion and fibrosis of transplants (p = 0.56). Conclusions [(15) O]H2O PET showed its capability as a method in measuring perfusion of kidney transplants. RVR of transplant patients with stage 2-3 chronic kidney disease was higher than that of the healthy, although kidney perfusion values didn't differ between the groups. Doppler based RI correlated with perfusion and fibrosis of transplants.
  • Majuri, Joonas; Joutsa, Juho; Johansson, Jarkko; Voon, Valerie; Parkkola, Riitta; Alho, Hannu; Arponen, Eveliina; Kaasinen, Valtteri (2017)
    Behavioral addictions, such as pathological gambling (PG) and binge eating disorder (BED), appear to be associated with specific changes in brain dopamine and opioid function, but the role of other neurotransmitter systems is less clear. Given the crucial role of serotonin in a number of psychiatric disorders, we aimed to compare brain serotonergic function among individuals with BED, PG and healthy controls. Seven BED patients, 13 PG patients and 16 healthy controls were scanned with high-resolution positron emission tomography (PET) using the serotonin transporter (SERT) tracer [C-11]MADAM. Both region-of-interest and voxel-wise whole brain analyses were performed. Patients with BED showed increased SERT binding in the parieto-occipital cortical regions compared to both PG and healthy controls, with parallel decreases in binding in the nucleus accumbens, inferior temporal gyrus and lateral orbitofrontal cortex. No differences between PG patients and controls were observed. None of the subjects were on SSRI medications at the time of imaging, and there were no differences in the level of depression between PG and BED patients. The results highlight differences in brain SERT binding between individuals with BED and PG and provide further evidence of different neurobiological underpinnings in behavioral addictions that are unrelated to the co-existing mood disorder. The results aid in the conceptualization of behavioral addictions by characterizing the underlying serotonin changes and provide a framework for additional studies to examine syndrome-specific pharmaceutical treatments. (C) 2017 Elsevier B.V. and ECNP. All rights reserved.