22 research outputs found
Nanopartikkelit magneettikuvauksen varjoaineina : Käytettävyys solujen leimauksessa, akuutin sydänlihasinfarktin kuvantamisessa ja nivelruston kuvantamisessa
No full textAbstractAcute myocardial infarction (AMI) and osteoarthritis (OA) are both diseases of tissues with poor regenerative capacities. Stem cell therapies administered post-AMI have shown therapeutic potential. With the previously used approaches, the engraftment of the cells in the myocardium has been low and the mechanisms behind the observed therapeutic effects are thought to involve multifactorial processes. It has been hypothesized that the earliest biochemical changes, mainly proteoglycan depletion, of OA, might be reversible. Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) has been shown to be a sensitive way to assess proteoglycan depletion in OA, however the use of gadolinium has now raised safety concerns.Magnetic resonance (MR) imaging is currently the preferred method for assessing the label in vivo. The label contrast is attributable to the high magnetic moment of the label which shortens the T1 and T2 relaxation times. Superparamagnetic iron oxide (SPIO) nanoparticles have shown some potential for stem cell labelling however there are interpretational challenges with the contrast and those labelling methods that are considered to be safe are time consuming.The object of the present work was to develop labels and labelling methods for cellular MR imaging. The usability of a novel fast rotation incubation SPIO labelling method for labelling bone marrow mononuclear cells (BMMNC) and the evaluation of cell homing in an experimental AMI model were studied. The labelling method appeared to be feasible for acute phase cell tracking. The transplantation of BMMNCs seemed to improve the ejection fraction at three weeks’ post-AMI.Novel manganese oxide (MnO) labels were developed to overcome the signal interpretational problems associated with the SPIO label. Amorphous MnO (MnOx) was observed to have better relaxometric properties than crystalline MnO, although both compounds appeared to be safe, high in relaxivity and suitable for cellular imaging in vitro. The usability of MnOx in assessing the proteoglycan content in OA was investigated. The relaxation of MnOx seemed higher than the corresponding phenomenon with gadolinium and the behavior of MnOx was observed to mimic that of dGEMRIC.In conclusion, both the novel fast labelling method and the novel label were demonstrated to be feasible and functional in these experimental models.Original papersOriginal papers are not included in the electronic version of the dissertation.Korpi, R. M., Alestalo, K., Ruuska, T., Lammentausta, E., Borra, R., Yannopoulos, F., … Blanco Sequieros, R. (2017). Two novel direct SPIO labels and in vivo MRI detection of labeled cells after acute myocardial infarct. Acta Radiologica Open, 6(8), 205846011771840. https://doi.org/10.1177/2058460117718407Self-archived versionAlestalo, K., Korpi, R., Mäkelä, J., Lehtonen, S., Mäkelä, T., Yannopoulos, F., … Lehenkari, P. (2015). High number of transplanted stem cells improves myocardial recovery after AMI in a porcine model. Scandinavian Cardiovascular Journal, 49(2), 82–94. https://doi.org/10.3109/14017431.2015.1018311Rosenholm, J. M., Korpi, R. M., Lammentausta, E., Lehtonen, S., Lehenkari, P., Niemi, R., … Blanco Sequeiros, R. (2015). Novel, fast-processed crystalline and amorphous manganese oxide nanoparticles for stem cell labeling. Inorganic Chemistry Frontiers, 2(7), 640–648. https://doi.org/10.1039/c5qi00033eKorpi, R., Ahola, S., Behrouz, G., Lammentausta, E., Karhula, S., Saarakkala, S., … Telkki, V. (2020). Diffusion of amorphous manganese oxide nanoparticles into articular cartilage. Manuscript submitted for publication.TiivistelmäAkuutti sydäninfarkti ja artroosi ovat molemmat huonosti uusiutumiskykyisissä kudoksissa ilmeneviä tauteja. Kantasoluhoidot sydänlihasinfarktin jälkeen ovat osoittautuneet terapeuttisiksi. Solujen kudosintegraation sijaan terapeuttinen vaikutus näyttää kuitenkin olevan monitekijäinen ja edelleen solujen kohtalo tunnetaan huonosti. Artroosin mekaaniset muutokset rustossa ovat palautumattomia, mutta on esitetty hypoteesi, että näitä edeltävät biokemialliset muutokset, pääasiassa proteoglygaanipitoisuuden lasku, olisi mahdollista parantaa. Magneettikuvaus käyttäen myöhäistä gadolinium-tehostusta on osoittautunut herkäksi menetelmäksi määrittää proteoglygaanipitoisuus rustossa. Nykykäsityksen mukaan lineaariset gadoliniumia sisältävät varjoaineet ovat kuitenkin myrkyllisiä.Magneettikuvaus on käytetyin solukuvantamismenetelmä. Varjoaineen kontrasti perustuu aineen korkeaan magneettiseen momenttiin, mikä lyhentää T1 ja T2 aikaa. Rautaa sisältävät nanopartikkelit ovat osoittautuneet lupaavaksi varjoaineeksi, vaikkakin niiden tiedetään aiheuttavan tulkinnan vaikeutta T2 relaksaatioaikaa lyhentävien elimistön omien prosessien kanssa. Lisäksi, leimamenetelmät ovat aikaa vieviä.Työn tavoitteena oli kehittää solukuvantamisen varjoaineita ja leimausmenetelmiä. Uuden nopean leimausmenetelmän käytettävyyttä kantasolujen leimaukseen ja käytettävyyteen kokeellisessa sydäninfarktimallissa tutkittiin. Menetelmä vaikutti turvalliselta ja näytti soveltuvan akuuttivaiheen siirrettyjen solujen havainnointiin. Soluhoidetuilla eläimillä sydämen iskutilavuus parani kolmen viikon kohdalla sydäninfarktista.Uusi mangaania sisältävä varjoaine kehitettiin tarkoituksena voittaa rautaa sisältävän varjoaineen tulkinnan päällekkäisyydet. Amorfinen mangaanioksidi vaikutti relaksaatiometrisiltä ominaisuuksilta käytetympää kiteistä muotoa paremmalta, relaksiivisuudeltaan korkealta ja turvalliselta. Leimatut solut olivat havaittavissa sekä 3 T että 7.1 T. Amorfisen mangaanioksidin käytettävyyttä proteoglykaanimäärän arvioimiseksi nivelrustossa tutkittiin. Mangaanin relaksiivisuus oli korkeampi kuin gadoliniumin ja käyttäytyminen muistutti gadolinium-mallin käytöstä nivelrustossa.Molemmat kehitellyt leima-aine ja leimamenetelmä vaikuttivat lupaavilta soluleimaukseen ja molemmat vaikuttivat turvallisilta ja käyttökelpoisilta käytetyissä koeasetelmissa.OsajulkaisutOsajulkaisut eivät sisälly väitöskirjan elektroniseen versioon.Korpi, R. M., Alestalo, K., Ruuska, T., Lammentausta, E., Borra, R., Yannopoulos, F., … Blanco Sequieros, R. (2017). Two novel direct SPIO labels and in vivo MRI detection of labeled cells after acute myocardial infarct. Acta Radiologica Open, 6(8), 205846011771840. https://doi.org/10.1177/2058460117718407Rinnakkaistallennettu versioAlestalo, K., Korpi, R., Mäkelä, J., Lehtonen, S., Mäkelä, T., Yannopoulos, F., … Lehenkari, P. (2015). High number of transplanted stem cells improves myocardial recovery after AMI in a porcine model. Scandinavian Cardiovascular Journal, 49(2), 82–94. https://doi.org/10.3109/14017431.2015.1018311Rosenholm, J. M., Korpi, R. M., Lammentausta, E., Lehtonen, S., Lehenkari, P., Niemi, R., … Blanco Sequeiros, R. (2015). Novel, fast-processed crystalline and amorphous manganese oxide nanoparticles for stem cell labeling. Inorganic Chemistry Frontiers, 2(7), 640–648. https://doi.org/10.1039/c5qi00033eKorpi, R., Ahola, S., Behrouz, G., Lammentausta, E., Karhula, S., Saarakkala, S., … Telkki, V. (2020). Diffusion of amorphous manganese oxide nanoparticles into articular cartilage. Manuscript submitted for publication.Academic dissertation to be presented with the assent of the Doctoral Training Committee of Health and Biosciences of the University of Oulu for public defence in the Helene Schjerfbeck auditorium (Hotel Kämp, Helsinki) on 22 May 2020, at 12 noonAbstract
Acute myocardial infarction (AMI) and osteoarthritis (OA) are both diseases of tissues with poor regenerative capacities. Stem cell therapies administered post-AMI have shown therapeutic potential. With the previously used approaches, the engraftment of the cells in the myocardium has been low and the mechanisms behind the observed therapeutic effects are thought to involve multifactorial processes. It has been hypothesized that the earliest biochemical changes, mainly proteoglycan depletion, of OA, might be reversible. Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) has been shown to be a sensitive way to assess proteoglycan depletion in OA, however the use of gadolinium has now raised safety concerns.
Magnetic resonance (MR) imaging is currently the preferred method for assessing the label in vivo. The label contrast is attributable to the high magnetic moment of the label which shortens the T1 and T2 relaxation times. Superparamagnetic iron oxide (SPIO) nanoparticles have shown some potential for stem cell labelling however there are interpretational challenges with the contrast and those labelling methods that are considered to be safe are time consuming.
The object of the present work was to develop labels and labelling methods for cellular MR imaging. The usability of a novel fast rotation incubation SPIO labelling method for labelling bone marrow mononuclear cells (BMMNC) and the evaluation of cell homing in an experimental AMI model were studied. The labelling method appeared to be feasible for acute phase cell tracking. The transplantation of BMMNCs seemed to improve the ejection fraction at three weeks’ post-AMI.
Novel manganese oxide (MnO) labels were developed to overcome the signal interpretational problems associated with the SPIO label. Amorphous MnO (MnOx) was observed to have better relaxometric properties than crystalline MnO, although both compounds appeared to be safe, high in relaxivity and suitable for cellular imaging in vitro. The usability of MnOx in assessing the proteoglycan content in OA was investigated. The relaxation of MnOx seemed higher than the corresponding phenomenon with gadolinium and the behavior of MnOx was observed to mimic that of dGEMRIC.
In conclusion, both the novel fast labelling method and the novel label were demonstrated to be feasible and functional in these experimental models.Tiivistelmä
Akuutti sydäninfarkti ja artroosi ovat molemmat huonosti uusiutumiskykyisissä kudoksissa ilmeneviä tauteja. Kantasoluhoidot sydänlihasinfarktin jälkeen ovat osoittautuneet terapeuttisiksi. Solujen kudosintegraation sijaan terapeuttinen vaikutus näyttää kuitenkin olevan monitekijäinen ja edelleen solujen kohtalo tunnetaan huonosti. Artroosin mekaaniset muutokset rustossa ovat palautumattomia, mutta on esitetty hypoteesi, että näitä edeltävät biokemialliset muutokset, pääasiassa proteoglygaanipitoisuuden lasku, olisi mahdollista parantaa. Magneettikuvaus käyttäen myöhäistä gadolinium-tehostusta on osoittautunut herkäksi menetelmäksi määrittää proteoglygaanipitoisuus rustossa. Nykykäsityksen mukaan lineaariset gadoliniumia sisältävät varjoaineet ovat kuitenkin myrkyllisiä.
Magneettikuvaus on käytetyin solukuvantamismenetelmä. Varjoaineen kontrasti perustuu aineen korkeaan magneettiseen momenttiin, mikä lyhentää T1 ja T2 aikaa. Rautaa sisältävät nanopartikkelit ovat osoittautuneet lupaavaksi varjoaineeksi, vaikkakin niiden tiedetään aiheuttavan tulkinnan vaikeutta T2 relaksaatioaikaa lyhentävien elimistön omien prosessien kanssa. Lisäksi, leimamenetelmät ovat aikaa vieviä.
Työn tavoitteena oli kehittää solukuvantamisen varjoaineita ja leimausmenetelmiä. Uuden nopean leimausmenetelmän käytettävyyttä kantasolujen leimaukseen ja käytettävyyteen kokeellisessa sydäninfarktimallissa tutkittiin. Menetelmä vaikutti turvalliselta ja näytti soveltuvan akuuttivaiheen siirrettyjen solujen havainnointiin. Soluhoidetuilla eläimillä sydämen iskutilavuus parani kolmen viikon kohdalla sydäninfarktista.
Uusi mangaania sisältävä varjoaine kehitettiin tarkoituksena voittaa rautaa sisältävän varjoaineen tulkinnan päällekkäisyydet. Amorfinen mangaanioksidi vaikutti relaksaatiometrisiltä ominaisuuksilta käytetympää kiteistä muotoa paremmalta, relaksiivisuudeltaan korkealta ja turvalliselta. Leimatut solut olivat havaittavissa sekä 3 T että 7.1 T. Amorfisen mangaanioksidin käytettävyyttä proteoglykaanimäärän arvioimiseksi nivelrustossa tutkittiin. Mangaanin relaksiivisuus oli korkeampi kuin gadoliniumin ja käyttäytyminen muistutti gadolinium-mallin käytöstä nivelrustossa.
Molemmat kehitellyt leima-aine ja leimamenetelmä vaikuttivat lupaavilta soluleimaukseen ja molemmat vaikuttivat turvallisilta ja käyttökelpoisilta käytetyissä koeasetelmissa
Two novel direct SPIO labels and in vivo MRI detection of labeled cells after acute myocardial infarct
No full textBACKGROUND: Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality worldwide. Cellular decay due hypoxia requires rapid and validated methods for possible therapeutic cell transplantation. PURPOSE: To develop direct and rapid superparamagnetic iron oxide (SPIO) cell label for a large-animal model and to assess in vivo cell targeting by magnetic resonance imaging (MRI) in an experimental AMI model. MATERIAL AND METHODS: Bone marrow mononuclear cells (BMMNCs) were labeled with SPIO particles using two novel direct labeling methods (rotating incubation method and electroporation). Labeling, iron incorporation in cells and label distribution, cellular viability, and proliferation were validated in vitro. An AMI porcine model was used to evaluate the direct labeling method (rotating incubation method) by examining targeting of labeled BMMNCs using MRI and histology. RESULTS: Labeling (1 h) did not alter either cellular differentiation potential or viability of cells in vitro. Cellular relaxation values at 9.4 T correlated with label concentration and MRI at 1.5 T showing 89 ± 4% signal reduction compared with non-labeled cells in vitro. In vivo, a high spatial correlation between MRI and histology was observed. The extent of macroscopic pathological myocardial changes (hemorrhage) correlated with altered function detected on MRI. CONCLUSION: We demonstrated two novel direct SPIO labeling methods and demonstrated the feasibility of clinical MRI for monitoring targeting of the labeled cells in animal models of AMI
Usability of Amorphous Manganese Oxide for Assessing the Proteoglycan Content in Articular Cartilage
No full textAbstract
Osteoarthritis (OA) is a highly common chronic disease that decreases functional capacity and can cause disability. The early detection of the disease could help to develop treatments that may reduce the progression if not cure the disease. Proteoglycan depletion is known to occur at an early state of OA and the delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) is currently considered as one of the most accurate methods for analyzing the depletion in articular cartilage (AC) despite the toxicity-related issues with gadolinium contrast agents. The aim of this study was to investigate the usability of amorphous manganese oxide (MnOx) for assessing the proteoglycan content in AC. The relaxation times of MnOx were determined at various fields and compared with the effect of gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) at 7.1 T. The diffusion of MnOx and Gd-DTPA into AC was analyzed ex vivo and followed for 24 h. Cartilage degeneration was evaluated with two histological scoring systems (OARSI and Mankin) to assess the relationship between OA severity and MnOx concentration. Relaxivity of MnOx was high and diffusion to the AC was faster than that of Gd-DTPA at 7.1 T. Using MnOx, T1 followed histological optical density (OD) of stained proteoglycans and correspondingly the concentration profiles followed in reverse the OD profiles in each human sample in a similar manner to Gd-DTPA in dGEMRIC. This pilot study showed some preliminary superiority in relaxation and diffusion into AC of MnOx in relation to Gd-DTPA.Abstract
Osteoarthritis (OA) is a highly common chronic disease that decreases functional capacity and can cause disability. The early detection of the disease could help to develop treatments that may reduce the progression if not cure the disease. Proteoglycan depletion is known to occur at an early state of OA and the delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) is currently considered as one of the most accurate methods for analyzing the depletion in articular cartilage (AC) despite the toxicity-related issues with gadolinium contrast agents. The aim of this study was to investigate the usability of amorphous manganese oxide (MnOx) for assessing the proteoglycan content in AC. The relaxation times of MnOx were determined at various fields and compared with the effect of gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) at 7.1 T. The diffusion of MnOx and Gd-DTPA into AC was analyzed ex vivo and followed for 24 h. Cartilage degeneration was evaluated with two histological scoring systems (OARSI and Mankin) to assess the relationship between OA severity and MnOx concentration. Relaxivity of MnOx was high and diffusion to the AC was faster than that of Gd-DTPA at 7.1 T. Using MnOx, T1 followed histological optical density (OD) of stained proteoglycans and correspondingly the concentration profiles followed in reverse the OD profiles in each human sample in a similar manner to Gd-DTPA in dGEMRIC. This pilot study showed some preliminary superiority in relaxation and diffusion into AC of MnOx in relation to Gd-DTPA
The Pierre Auger Observatory Scaler Mode for the Study of the Modulation of Galactic Cosmic Rays due to Solar Activity
No full textSince data-taking began in January 2004, the Pierre Auger Observatory has been
recording the count rates of low energy secondary cosmic ray particles for the self-calibration
of the ground detectors of its surface detector array. After correcting for atmospheric effects, modulations
of galactic cosmic rays due to solar activity and transient events are observed. Temporal
variations related with the activity of the heliosphere can be determined with high accuracy due to
the high total count rates. In this study, the available data are presented together with an analysis
focused on the observation of Forbush decreases, where a strong correlation with neutron monitor
data is found
The Lateral Trigger Probability function for UHE Cosmic Rays Showers detected by the Pierre Auger Observatory
No full textIn this paper we introduce the concept of Lateral Trigger Probability (LTP) function, i.e., the probability for
an Extensive Air Shower (EAS) to trigger an individual detector of a ground based array as a function of
distance to the shower axis, taking into account energy, mass and direction of the primary cosmic ray. We
apply this concept to the surface array of the Pierre Auger Observatory consisting of a 1.5 km spaced grid
of about 1600 water Cherenkov stations. Using Monte Carlo simulations of ultra-high energy showers the
LTP functions are derived for energies in the range between 10^17 and 10^19 eV and zenith angles up to 65 degree.
A parametrization combining a step function with an exponential is found to reproduce them very well in
the considered range of energies and zenith angles. The LTP functions can also be obtained from data
using events simultaneously observed by the fluorescence and the surface detector of the Pierre Auger
Observatory (hybrid events). We validate the Monte Carlo results showing how LTP functions from data
are in good agreement with simulations
The fluorescence detector of the Pierre Auger Observatory
No full textThe Pierre Auger Observatory is a hybrid detector for ultra-high energy cosmic rays. It combines a surface array to measure secondary particles at ground level together with a fluorescence detector to measure the development of air showers in the atmosphere above the array. The fluorescence detector comprises 24 large telescopes specialized for measuring the nitrogen fluorescence caused by charged particles of cosmic ray air showers. In this paper we describe the components of the fluorescence detector including its optical system, the design of the camera, the electronics, and the systems for relative and absolute calibration. We also discuss the operation and the monitoring of the detector. Finally, we evaluate the detector performance and precision of shower reconstructions. (C) 2010 Elsevier B.V All rights reserved
The Lateral Trigger Probability function for UHE Cosmic Rays Showers detected by the Pierre Auger Observatory
No full textIn this paper we introduce the concept of Lateral Trigger Probability (LTP) function, i.e., the probability for
an Extensive Air Shower (EAS) to trigger an individual detector of a ground based array as a function of
distance to the shower axis, taking into account energy, mass and direction of the primary cosmic ray. We
apply this concept to the surface array of the Pierre Auger Observatory consisting of a 1.5 km spaced grid
of about 1600 water Cherenkov stations. Using Monte Carlo simulations of ultra-high energy showers the
LTP functions are derived for energies in the range between 10^17 and 10^19 eV and zenith angles up to 65 degree.
A parametrization combining a step function with an exponential is found to reproduce them very well in
the considered range of energies and zenith angles. The LTP functions can also be obtained from data
using events simultaneously observed by the fluorescence and the surface detector of the Pierre Auger
Observatory (hybrid events). We validate the Monte Carlo results showing how LTP functions from data
are in good agreement with simulations
The Pierre Auger Observatory Scaler Mode for the Study of the Modulation of Galactic Cosmic Rays due to Solar Activity
No full textSince data-taking began in January 2004, the Pierre Auger Observatory has been
recording the count rates of low energy secondary cosmic ray particles for the self-calibration
of the ground detectors of its surface detector array. After correcting for atmospheric effects, modulations
of galactic cosmic rays due to solar activity and transient events are observed. Temporal
variations related with the activity of the heliosphere can be determined with high accuracy due to
the high total count rates. In this study, the available data are presented together with an analysis
focused on the observation of Forbush decreases, where a strong correlation with neutron monitor
data is found
Search for signatures of magnetically-induced alignment in the arrival directions measured by the Pierre Auger Observatory
No full textWe present the results of an analysis of data recorded at the Pierre Auger Observatory in which we search for groups of directionally-aligned events (or 'multiplets') which exhibit a correlation between arrival direction and the inverse of the energy. These signatures are expected from sets of events coming from the same source after having been deflected by intervening coherent magnetic fields. The observation of several events from the same source would open the possibility to accurately reconstruct the position of the source and also measure the integral of the component of the magnetic field orthogonal to the trajectory of the cosmic rays. We describe the largest multiplets found and compute the probability that they appeared by chance from an isotropic distribution. We find no statistically significant evidence for the presence of multiplets arising from magnetic deflections in the present data. © 2011 Elsevier B.V. All rights reserved.P. Abreu... K. B. Barber... J. A. Bellido... R. W. Clay... A. E. Herve... et al.http://www.journals.elsevier.com/astroparticle-physics
The fluorescence detector of the Pierre Auger Observatory
No full textThe Pierre Auger Observatory is a hybrid detector for ultra-high energy cosmic rays. It combines a surface array to measure secondary particles at ground level together with a fluorescence detector to measure the development of air showers in the atmosphere above the array. The fluorescence detector comprises 24 large telescopes specialized for measuring the nitrogen fluorescence caused by charged particles of cosmic ray air showers. In this paper we describe the components of the fluorescence detector including its optical system, the design of the camera, the electronics, and the systems for relative and absolute calibration. We also discuss the operation and the monitoring of the detector. Finally, we evaluate the detector performance and precision of shower reconstructions. © 2010 Elsevier B.V. All rights reserved.J. Abraham... K.B. Barber... J.A. Bellido... R.W. Clay... B.R. Dawson... V.C. Holmes... A.G.K. Smith... J. Sorokin... P. Wahrlich... B.J. Whelan... N. Wild... M.G.Winnick... et al
