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Purpose: Multiple vendors are currently offering artificial intelligence (AI) computer-aided systems for triage detection, diagnosis, and risk prediction of breast cancer based on screening mammography. There is an imminent need to establish validation platforms that enable fair and transparent testing of these systems against external data.Approach: We developed validation of artificial intelligence for breast imaging (VAI-B), a platform for independent validation of AI algorithms in breast imaging. The platform is a hybrid solution, with one part implemented in the cloud and another in an on-premises environment at Karolinska Institute. Cloud services provide the flexibility of scaling the computing power during inference time, while secure on-premises clinical data storage preserves their privacy. A MongoDB database and a python package were developed to store and manage the data on-premises. VAI-B requires four data components: radiological images, AI inferences, radiologist assessments, and cancer outcomes.Results: To pilot test VAI-B, we defined a case-control population based on 8080 patients diagnosed with breast cancer and 36,339 healthy women based on the Swedish national quality registry for breast cancer. Images and radiological assessments from more than 100,000 mammography examinations were extracted from hospitals in three regions of Sweden. The images were processed by AI systems from three vendors in a virtual private cloud to produce abnormality scores related to signs of cancer in the images. A total of 105,706 examinations have been processed and stored in the database.Conclusions: We have created a platform that will allow downstream evaluation of AI systems for breast cancer detection, which enables faster development cycles for participating vendors and safer AI adoption for participating hospitals. The platform was designed to be scalable and ready to be expanded should a new vendor want to evaluate their system or should a new hospital wish, Funding: Regional Cancer Centers in Collaboration and Vinnova [21/00060, 2021-02617]; Medtechlabs, Stockholm, Sweden

Purpose: Multiple vendors are currently offering artificial intelligence (AI) computer-aided systems for triage detection, diagnosis, and risk prediction of breast cancer based on screening mammography. There is an imminent need to establish validation platforms that enable fair and transparent testing of these systems against external data.Approach: We developed validation of artificial intelligence for breast imaging (VAI-B), a platform for independent validation of AI algorithms in breast imaging. The platform is a hybrid solution, with one part implemented in the cloud and another in an on-premises environment at Karolinska Institute. Cloud services provide the flexibility of scaling the computing power during inference time, while secure on-premises clinical data storage preserves their privacy. A MongoDB database and a python package were developed to store and manage the data on-premises. VAI-B requires four data components: radiological images, AI inferences, radiologist assessments, and cancer outcomes.Results: To pilot test VAI-B, we defined a case-control population based on 8080 patients diagnosed with breast cancer and 36,339 healthy women based on the Swedish national quality registry for breast cancer. Images and radiological assessments from more than 100,000 mammography examinations were extracted from hospitals in three regions of Sweden. The images were processed by AI systems from three vendors in a virtual private cloud to produce abnormality scores related to signs of cancer in the images. A total of 105,706 examinations have been processed and stored in the database.Conclusions: We have created a platform that will allow downstream evaluation of AI systems for breast cancer detection, which enables faster development cycles for participating vendors and safer AI adoption for participating hospitals. The platform was designed to be scalable and ready to be expanded should a new vendor want to evaluate their system or should a new hospital wish, Funding: Regional Cancer Centers in Collaboration and Vinnova [21/00060, 2021-02617]; Medtechlabs, Stockholm, Sweden

Purpose: Multiple vendors are currently offering artificial intelligence (AI) computer-aided systems for triage detection, diagnosis, and risk prediction of breast cancer based on screening mammography. There is an imminent need to establish validation platforms that enable fair and transparent testing of these systems against external data. Approach: We developed validation of artificial intelligence for breast imaging (VAI-B), a platform for independent validation of AI algorithms in breast imaging. The platform is a hybrid solution, with one part implemented in the cloud and another in an on-premises environment at Karolinska Institute. Cloud services provide the flexibility of scaling the computing power during inference time, while secure on-premises clinical data storage preserves their privacy. A MongoDB database and a python package were developed to store and manage the data onpremises. VAI-B requires four data components: radiological images, AI inferences, radiologist assessments, and cancer outcomes. Results: To pilot test VAI-B, we defined a case-control population based on 8080 patients diagnosed with breast cancer and 36,339 healthy women based on the Swedish national quality registry for breast cancer. Images and radiological assessments from more than 100,000 mammography examinations were extracted from hospitals in three regions of Sweden. The images were processed by AI systems from three vendors in a virtual private cloud to produce abnormality scores related to signs of cancer in the images. A total of 105,706 examinations have been processed and stored in the database. Conclusions: We have created a platform that will allow downstream evaluation of AI systems for breast cancer detection, which enables faster development cycles for participating vendors and safer AI adoption for participating hospitals. The platform was designed to be scalable and ready to be expanded should a new vendor want to evaluate their system or should a new hospital wis, QC 20240301

Background: As guidelines endorse the use of computed tomography (CT) for examining coronary artery disease (CAD), it is important to compare the advantages and disadvantages of the novel photon counting detector CT (PCD-CT) technology with the established energy integrating detector CT (EID-CT). Purpose: To compare the image quality of coronary computed tomography angiography (CCTA) and the Agatston scores (AS) derived from EID-CT and PCD-CT. Material and Methods: In this prospective observational study, 28 patients underwent clinical calcium score and CCTA scans on an EID-CTand a PCD-CT scanner. CCTA images were qualitatively analyzed by five observers using visual grading characteristics. The correlation and agreement of the AS were assessed using Spearmans rank correlation and Bland-Altman plots. Results: This qualitative analyses demonstrated a high fraction of " good" or "excellent" ratings for the image criteria in both CT systems. The sharpness of the distal lumen and image quality regarding motion artifacts were rated significantly higher for EID-CT (P < 0.05). However, the sharpness of coronary calcification was rated significantly higher for PCD-CT (P < 0.05). Spearmans rank correlation and Bland-Altman plots showed good correlation (P = 0.95) and agreement regarding the AS between EID-CT and PCD-CT. Conclusion: Both CT systems exhibited high CCTA image quality. The sharpness of calcifications was rated significantly higher for PCD-CT. A good correlation was observed between the AS derived from the two systems., Funding: We thank Mats Fredriksson, PhD, Forum Ostergotland, Faculty of Medicine, Linkoping, Sweden, who provided help with the statistics. We are grateful to Bente Konst, PhD, Center for Medical Image Science and Visualization (CMIV), Linkoping University, Linkopi; Forum Ostergotland, Faculty of Medicine, Linkoping, Sweden; Center for Medical Image Science and Visualization (CMIV)

Purpose: Multiple vendors are currently offering artificial intelligence (AI) computer-aided systems for triage detection, diagnosis, and risk prediction of breast cancer based on screening mammography. There is an imminent need to establish validation platforms that enable fair and transparent testing of these systems against external data.Approach: We developed validation of artificial intelligence for breast imaging (VAI-B), a platform for independent validation of AI algorithms in breast imaging. The platform is a hybrid solution, with one part implemented in the cloud and another in an on-premises environment at Karolinska Institute. Cloud services provide the flexibility of scaling the computing power during inference time, while secure on-premises clinical data storage preserves their privacy. A MongoDB database and a python package were developed to store and manage the data on-premises. VAI-B requires four data components: radiological images, AI inferences, radiologist assessments, and cancer outcomes.Results: To pilot test VAI-B, we defined a case-control population based on 8080 patients diagnosed with breast cancer and 36,339 healthy women based on the Swedish national quality registry for breast cancer. Images and radiological assessments from more than 100,000 mammography examinations were extracted from hospitals in three regions of Sweden. The images were processed by AI systems from three vendors in a virtual private cloud to produce abnormality scores related to signs of cancer in the images. A total of 105,706 examinations have been processed and stored in the database.Conclusions: We have created a platform that will allow downstream evaluation of AI systems for breast cancer detection, which enables faster development cycles for participating vendors and safer AI adoption for participating hospitals. The platform was designed to be scalable and ready to be expanded should a new vendor want to evaluate their system or should a new hospital wish, Funding: Regional Cancer Centers in Collaboration and Vinnova [21/00060, 2021-02617]; Medtechlabs, Stockholm, Sweden

The purpose of this study was to compare the correlation and agreement between AS derived from either an energy-integrating detector CT (EID-CT) or a photon-counting detector CT (PCD-CT). Reproducibility was also compared. In total, 26 calcified coronary lesions (from five cadaveric hearts) were identified for inclusion. The hearts were positioned in a chest phantom and scanned in both an EID-CT and a prototype PCD-CT. The EID-CT and PCD-CT acquisition and reconstruction parameters were matched. To evaluate the reproducibility, the phantom was manually repositioned, and an additional scan was performed using both methods. The EID-CT reconstructions were performed using the dedicated calcium score kernel Sa36. The PCD-CT reconstructions were performed with a vendor-recommended kernel (Qr36). Several monoenergetic energy levels (50-150 keV) were evaluated to find the closest match with the EID-CT scans. A semi-automatic evaluation of calcium score was performed on a post-processing multimodality workplace. The best match with Sa36 was PCD-CT Qr36 images, at a monoenergetic level of 72 keV. Statistical analyses showed excellent correlation and agreement. The correlation and agreement with regards to the Agatston score (AS) between the two methods, for each position as well as between the two positions for each method, were assessed with the Spearman s rank correlation. The correlation coefficient, rho, was 0.98 and 0.97 respectively 0.99 and 0.98. The corresponding agreements were investigated by means of Bland-Altman plots. High correlation and agreement was observed between the AS derived from the EID-CT and a PCD-CT. Both methods also demonstrated excellent reproducibility., Funding Agencies|Linkoping University; ALF Grants, Region Ostergotland [LIO 899441]

The purpose of this study was to compare the correlation and agreement between AS derived from either an energy-integrating detector CT (EID-CT) or a photon-counting detector CT (PCD-CT). Reproducibility was also compared. In total, 26 calcified coronary lesions (from five cadaveric hearts) were identified for inclusion. The hearts were positioned in a chest phantom and scanned in both an EID-CT and a prototype PCD-CT. The EID-CT and PCD-CT acquisition and reconstruction parameters were matched. To evaluate the reproducibility, the phantom was manually repositioned, and an additional scan was performed using both methods. The EID-CT reconstructions were performed using the dedicated calcium score kernel Sa36. The PCD-CT reconstructions were performed with a vendor-recommended kernel (Qr36). Several monoenergetic energy levels (50-150 keV) were evaluated to find the closest match with the EID-CT scans. A semi-automatic evaluation of calcium score was performed on a post-processing multimodality workplace. The best match with Sa36 was PCD-CT Qr36 images, at a monoenergetic level of 72 keV. Statistical analyses showed excellent correlation and agreement. The correlation and agreement with regards to the Agatston score (AS) between the two methods, for each position as well as between the two positions for each method, were assessed with the Spearman s rank correlation. The correlation coefficient, rho, was 0.98 and 0.97 respectively 0.99 and 0.98. The corresponding agreements were investigated by means of Bland-Altman plots. High correlation and agreement was observed between the AS derived from the EID-CT and a PCD-CT. Both methods also demonstrated excellent reproducibility., Funding Agencies|Linkoping University; ALF Grants, Region Ostergotland [LIO 899441]

The purpose of this study was to compare the correlation and agreement between AS derived from either an energy-integrating detector CT (EID-CT) or a photon-counting detector CT (PCD-CT). Reproducibility was also compared. In total, 26 calcified coronary lesions (from five cadaveric hearts) were identified for inclusion. The hearts were positioned in a chest phantom and scanned in both an EID-CT and a prototype PCD-CT. The EID-CT and PCD-CT acquisition and reconstruction parameters were matched. To evaluate the reproducibility, the phantom was manually repositioned, and an additional scan was performed using both methods. The EID-CT reconstructions were performed using the dedicated calcium score kernel Sa36. The PCD-CT reconstructions were performed with a vendor-recommended kernel (Qr36). Several monoenergetic energy levels (50-150 keV) were evaluated to find the closest match with the EID-CT scans. A semi-automatic evaluation of calcium score was performed on a post-processing multimodality workplace. The best match with Sa36 was PCD-CT Qr36 images, at a monoenergetic level of 72 keV. Statistical analyses showed excellent correlation and agreement. The correlation and agreement with regards to the Agatston score (AS) between the two methods, for each position as well as between the two positions for each method, were assessed with the Spearman s rank correlation. The correlation coefficient, rho, was 0.98 and 0.97 respectively 0.99 and 0.98. The corresponding agreements were investigated by means of Bland-Altman plots. High correlation and agreement was observed between the AS derived from the EID-CT and a PCD-CT. Both methods also demonstrated excellent reproducibility., Funding Agencies|Linkoping University; ALF Grants, Region Ostergotland [LIO 899441]

The purpose of this study was to compare the correlation and agreement between AS derived from either an energy-integrating detector CT (EID-CT) or a photon-counting detector CT (PCD-CT). Reproducibility was also compared. In total, 26 calcified coronary lesions (from five cadaveric hearts) were identified for inclusion. The hearts were positioned in a chest phantom and scanned in both an EID-CT and a prototype PCD-CT. The EID-CT and PCD-CT acquisition and reconstruction parameters were matched. To evaluate the reproducibility, the phantom was manually repositioned, and an additional scan was performed using both methods. The EID-CT reconstructions were performed using the dedicated calcium score kernel Sa36. The PCD-CT reconstructions were performed with a vendor-recommended kernel (Qr36). Several monoenergetic energy levels (50-150 keV) were evaluated to find the closest match with the EID-CT scans. A semi-automatic evaluation of calcium score was performed on a post-processing multimodality workplace. The best match with Sa36 was PCD-CT Qr36 images, at a monoenergetic level of 72 keV. Statistical analyses showed excellent correlation and agreement. The correlation and agreement with regards to the Agatston score (AS) between the two methods, for each position as well as between the two positions for each method, were assessed with the Spearman s rank correlation. The correlation coefficient, rho, was 0.98 and 0.97 respectively 0.99 and 0.98. The corresponding agreements were investigated by means of Bland-Altman plots. High correlation and agreement was observed between the AS derived from the EID-CT and a PCD-CT. Both methods also demonstrated excellent reproducibility., Funding Agencies|Linkoping University; ALF Grants, Region Ostergotland [LIO 899441]

The purpose of this study was to compare the correlation and agreement between AS derived from either an energy-integrating detector CT (EID-CT) or a photon-counting detector CT (PCD-CT). Reproducibility was also compared. In total, 26 calcified coronary lesions (from five cadaveric hearts) were identified for inclusion. The hearts were positioned in a chest phantom and scanned in both an EID-CT and a prototype PCD-CT. The EID-CT and PCD-CT acquisition and reconstruction parameters were matched. To evaluate the reproducibility, the phantom was manually repositioned, and an additional scan was performed using both methods. The EID-CT reconstructions were performed using the dedicated calcium score kernel Sa36. The PCD-CT reconstructions were performed with a vendor-recommended kernel (Qr36). Several monoenergetic energy levels (50-150 keV) were evaluated to find the closest match with the EID-CT scans. A semi-automatic evaluation of calcium score was performed on a post-processing multimodality workplace. The best match with Sa36 was PCD-CT Qr36 images, at a monoenergetic level of 72 keV. Statistical analyses showed excellent correlation and agreement. The correlation and agreement with regards to the Agatston score (AS) between the two methods, for each position as well as between the two positions for each method, were assessed with the Spearman s rank correlation. The correlation coefficient, rho, was 0.98 and 0.97 respectively 0.99 and 0.98. The corresponding agreements were investigated by means of Bland-Altman plots. High correlation and agreement was observed between the AS derived from the EID-CT and a PCD-CT. Both methods also demonstrated excellent reproducibility., Funding Agencies|Linkoping University; ALF Grants, Region Ostergotland [LIO 899441]

The purpose of this study was to compare the correlation and agreement between AS derived from either an energy-integrating detector CT (EID-CT) or a photon-counting detector CT (PCD-CT). Reproducibility was also compared. In total, 26 calcified coronary lesions (from five cadaveric hearts) were identified for inclusion. The hearts were positioned in a chest phantom and scanned in both an EID-CT and a prototype PCD-CT. The EID-CT and PCD-CT acquisition and reconstruction parameters were matched. To evaluate the reproducibility, the phantom was manually repositioned, and an additional scan was performed using both methods. The EID-CT reconstructions were performed using the dedicated calcium score kernel Sa36. The PCD-CT reconstructions were performed with a vendor-recommended kernel (Qr36). Several monoenergetic energy levels (50-150 keV) were evaluated to find the closest match with the EID-CT scans. A semi-automatic evaluation of calcium score was performed on a post-processing multimodality workplace. The best match with Sa36 was PCD-CT Qr36 images, at a monoenergetic level of 72 keV. Statistical analyses showed excellent correlation and agreement. The correlation and agreement with regards to the Agatston score (AS) between the two methods, for each position as well as between the two positions for each method, were assessed with the Spearman s rank correlation. The correlation coefficient, rho, was 0.98 and 0.97 respectively 0.99 and 0.98. The corresponding agreements were investigated by means of Bland-Altman plots. High correlation and agreement was observed between the AS derived from the EID-CT and a PCD-CT. Both methods also demonstrated excellent reproducibility., Funding Agencies|Linkoping University; ALF Grants, Region Ostergotland [LIO 899441]

Understanding microbial mediation in sediment-hosted Mn deposition has gained importance in low-temperature ore genesis research. Here we report Mn oxide ores dominated by todorokite, vernadite, hollandite, and manjiroite, which cement Quaternary microbially induced sedimentary structures (MISS) developed along bedding planes of shallow-marine to tidal-flat volcaniclastic sandstones/sandy tuffs, Cape Vani paleo-hydrothermal vent field, Milos, Greece. This work aims to decipher the link between biological Mn oxide formation, low-T hydrothermalism, and, growth and preservation of Mn-bearing MISS (MnMISS). Geobiological processes, identified by microtexture petrography, scanning and transmission electron microscopy, lipid biomarkers, bulk- and lipid-specific delta(13)C(organic)composition, and field data, and, low-temperature hydrothermal venting of aqueous Mn(2+)in sunlit shallow waters, cooperatively enabled microbially-mediated Mn (II) oxidation and biomineralization. The MnMISS biomarker content and delta(13)C(org)signatures strongly resemble those of modern Mn-rich hydrothermal sediments, Milos coast. Biogenic and syngenetic Mn oxide precipitation established by electron paramagnetic resonance (EPR) spectroscopy and petrography, combined with hydrothermal fluid flow-induced pre-burial curing/diagenesis, may account for todays crystalline Mn oxide resource. Our data suggests that MISS are not unique to cyanobacteria mats. Furthermore, microbial mats inhabited by aerobic methanotrophs may have contributed significantly to the formation of the MnMISS, thus widening the spectrum of environments responsible for marine Mn biometallogenesis., Funding Agencies|National and Kapodistrian University of Athens, Special Account for Research Grants (SARG) [70/4/3373, 70/4/6425]; Biotransformations of Trace elements in Aquatic Systems (BIOTRACS): FP6-MOBILITY/Marie Curie Host Fellowships-Early stage research training (EST) [514262, MEST-CT-2004-514262]; Society of Economic Geologists (SEG) Hugh Exton McKinstry fund; Swedish Research CouncilSwedish Research Council [2012-4364, 2017-04129]; Danish National Research FoundationDanmarks Grundforskningsfond [DNRF53]; Villum Investigator (Villum Fonden) Grant [16518]; European Research CouncilEuropean Research Council (ERC) [336092]

Understanding microbial mediation in sediment-hosted Mn deposition has gained importance in low-temperature ore genesis research. Here we report Mn oxide ores dominated by todorokite, vernadite, hollandite, and manjiroite, which cement Quaternary microbially induced sedimentary structures (MISS) developed along bedding planes of shallow-marine to tidal-flat volcaniclastic sandstones/sandy tuffs, Cape Vani paleo-hydrothermal vent field, Milos, Greece. This work aims to decipher the link between biological Mn oxide formation, low-T hydrothermalism, and, growth and preservation of Mn-bearing MISS (MnMISS). Geobiological processes, identified by microtexture petrography, scanning and transmission electron microscopy, lipid biomarkers, bulk- and lipid-specific delta(13)C(organic)composition, and field data, and, low-temperature hydrothermal venting of aqueous Mn(2+)in sunlit shallow waters, cooperatively enabled microbially-mediated Mn (II) oxidation and biomineralization. The MnMISS biomarker content and delta(13)C(org)signatures strongly resemble those of modern Mn-rich hydrothermal sediments, Milos coast. Biogenic and syngenetic Mn oxide precipitation established by electron paramagnetic resonance (EPR) spectroscopy and petrography, combined with hydrothermal fluid flow-induced pre-burial curing/diagenesis, may account for todays crystalline Mn oxide resource. Our data suggests that MISS are not unique to cyanobacteria mats. Furthermore, microbial mats inhabited by aerobic methanotrophs may have contributed significantly to the formation of the MnMISS, thus widening the spectrum of environments responsible for marine Mn biometallogenesis., Funding Agencies|National and Kapodistrian University of Athens, Special Account for Research Grants (SARG) [70/4/3373, 70/4/6425]; Biotransformations of Trace elements in Aquatic Systems (BIOTRACS): FP6-MOBILITY/Marie Curie Host Fellowships-Early stage research training (EST) [514262, MEST-CT-2004-514262]; Society of Economic Geologists (SEG) Hugh Exton McKinstry fund; Swedish Research CouncilSwedish Research Council [2012-4364, 2017-04129]; Danish National Research FoundationDanmarks Grundforskningsfond [DNRF53]; Villum Investigator (Villum Fonden) Grant [16518]; European Research CouncilEuropean Research Council (ERC) [336092]

Understanding microbial mediation in sediment-hosted Mn deposition has gained importance in low-temperature ore genesis research. Here we report Mn oxide ores dominated by todorokite, vernadite, hollandite, and manjiroite, which cement Quaternary microbially induced sedimentary structures (MISS) developed along bedding planes of shallow-marine to tidal-flat volcaniclastic sandstones/sandy tuffs, Cape Vani paleo-hydrothermal vent field, Milos, Greece. This work aims to decipher the link between biological Mn oxide formation, low-T hydrothermalism, and, growth and preservation of Mn-bearing MISS (MnMISS). Geobiological processes, identified by microtexture petrography, scanning and transmission electron microscopy, lipid biomarkers, bulk- and lipid-specific delta(13)C(organic)composition, and field data, and, low-temperature hydrothermal venting of aqueous Mn(2+)in sunlit shallow waters, cooperatively enabled microbially-mediated Mn (II) oxidation and biomineralization. The MnMISS biomarker content and delta(13)C(org)signatures strongly resemble those of modern Mn-rich hydrothermal sediments, Milos coast. Biogenic and syngenetic Mn oxide precipitation established by electron paramagnetic resonance (EPR) spectroscopy and petrography, combined with hydrothermal fluid flow-induced pre-burial curing/diagenesis, may account for todays crystalline Mn oxide resource. Our data suggests that MISS are not unique to cyanobacteria mats. Furthermore, microbial mats inhabited by aerobic methanotrophs may have contributed significantly to the formation of the MnMISS, thus widening the spectrum of environments responsible for marine Mn biometallogenesis., Funding Agencies|National and Kapodistrian University of Athens, Special Account for Research Grants (SARG) [70/4/3373, 70/4/6425]; Biotransformations of Trace elements in Aquatic Systems (BIOTRACS): FP6-MOBILITY/Marie Curie Host Fellowships-Early stage research training (EST) [514262, MEST-CT-2004-514262]; Society of Economic Geologists (SEG) Hugh Exton McKinstry fund; Swedish Research CouncilSwedish Research Council [2012-4364, 2017-04129]; Danish National Research FoundationDanmarks Grundforskningsfond [DNRF53]; Villum Investigator (Villum Fonden) Grant [16518]; European Research CouncilEuropean Research Council (ERC) [336092]

Understanding microbial mediation in sediment-hosted Mn deposition has gained importance in low-temperature ore genesis research. Here we report Mn oxide ores dominated by todorokite, vernadite, hollandite, and manjiroite, which cement Quaternary microbially induced sedimentary structures (MISS) developed along bedding planes of shallow-marine to tidal-flat volcaniclastic sandstones/sandy tuffs, Cape Vani paleo-hydrothermal vent field, Milos, Greece. This work aims to decipher the link between biological Mn oxide formation, low-T hydrothermalism, and, growth and preservation of Mn-bearing MISS (MnMISS). Geobiological processes, identified by microtexture petrography, scanning and transmission electron microscopy, lipid biomarkers, bulk- and lipid-specific delta(13)C(organic)composition, and field data, and, low-temperature hydrothermal venting of aqueous Mn(2+)in sunlit shallow waters, cooperatively enabled microbially-mediated Mn (II) oxidation and biomineralization. The MnMISS biomarker content and delta(13)C(org)signatures strongly resemble those of modern Mn-rich hydrothermal sediments, Milos coast. Biogenic and syngenetic Mn oxide precipitation established by electron paramagnetic resonance (EPR) spectroscopy and petrography, combined with hydrothermal fluid flow-induced pre-burial curing/diagenesis, may account for todays crystalline Mn oxide resource. Our data suggests that MISS are not unique to cyanobacteria mats. Furthermore, microbial mats inhabited by aerobic methanotrophs may have contributed significantly to the formation of the MnMISS, thus widening the spectrum of environments responsible for marine Mn biometallogenesis., Funding Agencies|National and Kapodistrian University of Athens, Special Account for Research Grants (SARG) [70/4/3373, 70/4/6425]; Biotransformations of Trace elements in Aquatic Systems (BIOTRACS): FP6-MOBILITY/Marie Curie Host Fellowships-Early stage research training (EST) [514262, MEST-CT-2004-514262]; Society of Economic Geologists (SEG) Hugh Exton McKinstry fund; Swedish Research CouncilSwedish Research Council [2012-4364, 2017-04129]; Danish National Research FoundationDanmarks Grundforskningsfond [DNRF53]; Villum Investigator (Villum Fonden) Grant [16518]; European Research CouncilEuropean Research Council (ERC) [336092]

Understanding microbial mediation in sediment-hosted Mn deposition has gained importance in low-temperature ore genesis research. Here we report Mn oxide ores dominated by todorokite, vernadite, hollandite, and manjiroite, which cement Quaternary microbially induced sedimentary structures (MISS) developed along bedding planes of shallow-marine to tidal-flat volcaniclastic sandstones/sandy tuffs, Cape Vani paleo-hydrothermal vent field, Milos, Greece. This work aims to decipher the link between biological Mn oxide formation, low-T hydrothermalism, and, growth and preservation of Mn-bearing MISS (MnMISS). Geobiological processes, identified by microtexture petrography, scanning and transmission electron microscopy, lipid biomarkers, bulk- and lipid-specific delta(13)C(organic)composition, and field data, and, low-temperature hydrothermal venting of aqueous Mn(2+)in sunlit shallow waters, cooperatively enabled microbially-mediated Mn (II) oxidation and biomineralization. The MnMISS biomarker content and delta(13)C(org)signatures strongly resemble those of modern Mn-rich hydrothermal sediments, Milos coast. Biogenic and syngenetic Mn oxide precipitation established by electron paramagnetic resonance (EPR) spectroscopy and petrography, combined with hydrothermal fluid flow-induced pre-burial curing/diagenesis, may account for todays crystalline Mn oxide resource. Our data suggests that MISS are not unique to cyanobacteria mats. Furthermore, microbial mats inhabited by aerobic methanotrophs may have contributed significantly to the formation of the MnMISS, thus widening the spectrum of environments responsible for marine Mn biometallogenesis., Funding Agencies|National and Kapodistrian University of Athens, Special Account for Research Grants (SARG) [70/4/3373, 70/4/6425]; Biotransformations of Trace elements in Aquatic Systems (BIOTRACS): FP6-MOBILITY/Marie Curie Host Fellowships-Early stage research training (EST) [514262, MEST-CT-2004-514262]; Society of Economic Geologists (SEG) Hugh Exton McKinstry fund; Swedish Research CouncilSwedish Research Council [2012-4364, 2017-04129]; Danish National Research FoundationDanmarks Grundforskningsfond [DNRF53]; Villum Investigator (Villum Fonden) Grant [16518]; European Research CouncilEuropean Research Council (ERC) [336092]

Background: The purpose of the study is to examine the effect of metformin on oxygen metabolism and mitochondrial function in the kidney of an animal model of insulinopenic diabetes in order to isolate any renoprotective effect from any concomitant effect on blood glucose homeostasis. Methods: Sprague-Dawley rats were injected with streptozotocin (STZ) (50 mg kg(-1)) and when stable started on metformin treatment (250 mg kg(-1)) in the drinking water. Rats were prepared for in vivo measurements 25 to 30 days after STZ injection, where renal function, including glomerular filtration rate and sodium transport, was estimated in anesthetized rats. Intrarenal oxygen tension was measured using oxygen sensors. Furthermore, mitochondrial function was assessed in mitochondria isolated from kidney cortex and medulla analysed by high-resolution respirometry, and superoxide production was evaluated using electron paramagnetic resonance. Results: Insulinopenic rats chronically treated with metformin for 4 weeks displayed improved medullary tissue oxygen tension despite of no effect of metformin on blood glucose homeostasis. Metformin reduced UCP2-dependent LEAK and differentially affected medullary mitochondrial superoxide radical production in control and diabetic rats. Conclusions: Metformin attenuates diabetes-induced renal medullary tissue hypoxia in an animal model of insulinopenic type 1 diabetes. The results suggest that the mechanistic pathway to attenuate the diabetes-induced medullary hypoxia is independent of blood glucose homeostasis and includes reduced UCP2-mediated mitochondrial proton LEAK.

Background The purpose of the study is to examine the effect of metformin on oxygen metabolism and mitochondrial function in the kidney of an animal model of insulinopenic diabetes in order to isolate any renoprotective effect from any concomitant effect on blood glucose homeostasis. Methods Sprague-Dawley rats were injected with streptozotocin (STZ) (50 mg kg(-1)) and when stable started on metformin treatment (250 mg kg(-1)) in the drinking water. Rats were prepared for in vivo measurements 25 to 30 days after STZ injection, where renal function, including glomerular filtration rate and sodium transport, was estimated in anesthetized rats. Intrarenal oxygen tension was measured using oxygen sensors. Furthermore, mitochondrial function was assessed in mitochondria isolated from kidney cortex and medulla analysed by high-resolution respirometry, and superoxide production was evaluated using electron paramagnetic resonance. Results Insulinopenic rats chronically treated with metformin for 4 weeks displayed improved medullary tissue oxygen tension despite of no effect of metformin on blood glucose homeostasis. Metformin reduced UCP2-dependent LEAK and differentially affected medullary mitochondrial superoxide radical production in control and diabetic rats. Conclusions Metformin attenuates diabetes-induced renal medullary tissue hypoxia in an animal model of insulinopenic type 1 diabetes. The results suggest that the mechanistic pathway to attenuate the diabetes-induced medullary hypoxia is independent of blood glucose homeostasis and includes reduced UCP2-mediated mitochondrial proton LEAK., Funding Agencies|Lundbeck Foundation; Swedish Research Council Medicine and Health; Family Ernfors Foundation; Swedish Diabetes Foundation; Danish Diabetes Academy

The kidneys receive similar to 25% of cardiac output, which is a prerequisite to maintain sufficient glomerular filtration rate. However, both intrarenal regional renal blood flow and tissue oxygen levels are heterogeneous with decreasing levels in the inner part of the medulla. These differences, in combination with the heterogeneous metabolic activity of the different nephron segment located in the different parts of the kidney, may constitute a functional problem when challenged. The proximal tubule and the medullary thick ascending limb of Henle are considered to have the highest metabolic rate, which is related to the high mitochondria content needed to sustain sufficient ATP production from oxidative phosphorylation to support high electrolyte transport activity in these nephron segments. Interestingly, the cells located in kidney medulla function at the verge of hypoxia, and the mitochondria may have adapted to the surrounding environment. However, little is known about intrarenal differences in mitochondria function. We therefore investigated functional differences between mitochondria isolated from kidney cortex and medulla of healthy normoglycemic rats by using high-resolution respirometry. The results demonstrate that medullary mitochondria had a higher degree of coupling, are more efficient, and have higher oxygen affinity, which would make them more suitable to function in an environment with limited oxygen supply. Furthermore, these results support the hypothesis that mitochondria of medullary cells have adapted to the normal hypoxic in vivo situation as a strategy of sustaining ATP production in a suboptimal environment.

Inactin is a long lasting anesthetic agent commonly used in rat studies, but is also shown to exert physiological effects such as reducing renal blood flow, glomerular filtration rate and depressing tubular transport capacity. The effect of inactin on isolated kidney mitochondria is unknown and may be important when studying related topics in anaesthetized animals. The aim of this study was to determine whether inactin exerts effects on mitochondrial function and production of reactive oxygen species. Kidney mitochondrial function and production of reactive oxygen after acutely (5 min) or longer (1.5 hour) anesthetizing rats with inactin was evaluated using high-resolution respirometry. The results demonstrate that inactin significantly improves respiratory control ratio, inhibits complex I in the mitochondrial respiratory chain, reduce both unregulated proton leak and time dependently reduce the regulated proton leak via uncoupling protein-2 and adenine nucleotide translocase. Inactin also contributes to increased mitochondrial hydrogen peroxide production. In conclusion, inactin exerts persistent effects on mitochondrial function and these profound effects on mitochondrial function should to be considered when studying mitochondria isolated from animals anesthesized with inactin., Funding Agencies|Swedish Research Council; Swedish Diabetes Foundation; Ake Wiberg Foundation; Family Ernfors Foundation; Swedish Society for Medical Research; Lundbeck Foundation; Danish Diabetes Academy - Novo Nordisk Foundation

Inactin is a long lasting anesthetic agent commonly used in rat studies, but is also shown to exert physiological effects such as reducing renal blood flow, glomerular filtration rate and depressing tubular transport capacity. The effect of inactin on isolated kidney mitochondria is unknown and may be important when studying related topics in anaesthetized animals. The aim of this study was to determine whether inactin exerts effects on mitochondrial function and production of reactive oxygen species. Kidney mitochondrial function and production of reactive oxygen after acutely (5 min) or longer (1.5 hour) anesthetizing rats with inactin was evaluated using high-resolution respirometry. The results demonstrate that inactin significantly improves respiratory control ratio, inhibits complex I in the mitochondrial respiratory chain, reduce both unregulated proton leak and time dependently reduce the regulated proton leak via uncoupling protein-2 and adenine nucleotide translocase. Inactin also contributes to increased mitochondrial hydrogen peroxide production. In conclusion, inactin exerts persistent effects on mitochondrial function and these profound effects on mitochondrial function should to be considered when studying mitochondria isolated from animals anesthesized with inactin., Funding Agencies|Swedish Research Council; Swedish Diabetes Foundation; Ake Wiberg Foundation; Family Ernfors Foundation; Swedish Society for Medical Research; Lundbeck Foundation; Danish Diabetes Academy - Novo Nordisk Foundation

Inactin is a long lasting anesthetic agent commonly used in rat studies, but is also shown to exert physiological effects such as reducing renal blood flow, glomerular filtration rate and depressing tubular transport capacity. The effect of inactin on isolated kidney mitochondria is unknown and may be important when studying related topics in anaesthetized animals. The aim of this study was to determine whether inactin exerts effects on mitochondrial function and production of reactive oxygen species. Kidney mitochondrial function and production of reactive oxygen after acutely (5 min) or longer (1.5 hour) anesthetizing rats with inactin was evaluated using high-resolution respirometry. The results demonstrate that inactin significantly improves respiratory control ratio, inhibits complex I in the mitochondrial respiratory chain, reduce both unregulated proton leak and time dependently reduce the regulated proton leak via uncoupling protein-2 and adenine nucleotide translocase. Inactin also contributes to increased mitochondrial hydrogen peroxide production. In conclusion, inactin exerts persistent effects on mitochondrial function and these profound effects on mitochondrial function should to be considered when studying mitochondria isolated from animals anesthesized with inactin., Funding Agencies|Swedish Research Council; Swedish Diabetes Foundation; Ake Wiberg Foundation; Family Ernfors Foundation; Swedish Society for Medical Research; Lundbeck Foundation; Danish Diabetes Academy - Novo Nordisk Foundation

Inactin is a long lasting anesthetic agent commonly used in rat studies, but is also shown to exert physiological effects such as reducing renal blood flow, glomerular filtration rate and depressing tubular transport capacity. The effect of inactin on isolated kidney mitochondria is unknown and may be important when studying related topics in anaesthetized animals. The aim of this study was to determine whether inactin exerts effects on mitochondrial function and production of reactive oxygen species. Kidney mitochondrial function and production of reactive oxygen after acutely (5 min) or longer (1.5 hour) anesthetizing rats with inactin was evaluated using high-resolution respirometry. The results demonstrate that inactin significantly improves respiratory control ratio, inhibits complex I in the mitochondrial respiratory chain, reduce both unregulated proton leak and time dependently reduce the regulated proton leak via uncoupling protein-2 and adenine nucleotide translocase. Inactin also contributes to increased mitochondrial hydrogen peroxide production. In conclusion, inactin exerts persistent effects on mitochondrial function and these profound effects on mitochondrial function should to be considered when studying mitochondria isolated from animals anesthesized with inactin., Funding Agencies|Swedish Research Council; Swedish Diabetes Foundation; Ake Wiberg Foundation; Family Ernfors Foundation; Swedish Society for Medical Research; Lundbeck Foundation; Danish Diabetes Academy - Novo Nordisk Foundation

Inactin is a long lasting anesthetic agent commonly used in rat studies, but is also shown to exert physiological effects such as reducing renal blood flow, glomerular filtration rate and depressing tubular transport capacity. The effect of inactin on isolated kidney mitochondria is unknown and may be important when studying related topics in anaesthetized animals. The aim of this study was to determine whether inactin exerts effects on mitochondrial function and production of reactive oxygen species. Kidney mitochondrial function and production of reactive oxygen after acutely (5 min) or longer (1.5 hour) anesthetizing rats with inactin was evaluated using high-resolution respirometry. The results demonstrate that inactin significantly improves respiratory control ratio, inhibits complex I in the mitochondrial respiratory chain, reduce both unregulated proton leak and time dependently reduce the regulated proton leak via uncoupling protein-2 and adenine nucleotide translocase. Inactin also contributes to increased mitochondrial hydrogen peroxide production. In conclusion, inactin exerts persistent effects on mitochondrial function and these profound effects on mitochondrial function should to be considered when studying mitochondria isolated from animals anesthesized with inactin., Funding Agencies|Swedish Research Council; Swedish Diabetes Foundation; Ake Wiberg Foundation; Family Ernfors Foundation; Swedish Society for Medical Research; Lundbeck Foundation; Danish Diabetes Academy - Novo Nordisk Foundation

Inactin is a long lasting anesthetic agent commonly used in rat studies, but is also shown to exert physiological effects such as reducing renal blood flow, glomerular filtration rate and depressing tubular transport capacity. The effect of inactin on isolated kidney mitochondria is unknown and may be important when studying related topics in anaesthetized animals. The aim of this study was to determine whether inactin exerts effects on mitochondrial function and production of reactive oxygen species. Kidney mitochondrial function and production of reactive oxygen after acutely (5 min) or longer (1.5 hour) anesthetizing rats with inactin was evaluated using high-resolution respirometry. The results demonstrate that inactin significantly improves respiratory control ratio, inhibits complex I in the mitochondrial respiratory chain, reduce both unregulated proton leak and time dependently reduce the regulated proton leak via uncoupling protein-2 and adenine nucleotide translocase. Inactin also contributes to increased mitochondrial hydrogen peroxide production. In conclusion, inactin exerts persistent effects on mitochondrial function and these profound effects on mitochondrial function should to be considered when studying mitochondria isolated from animals anesthesized with inactin., Funding Agencies|Swedish Research Council; Swedish Diabetes Foundation; Ake Wiberg Foundation; Family Ernfors Foundation; Swedish Society for Medical Research; Lundbeck Foundation; Danish Diabetes Academy - Novo Nordisk Foundation

The kidneys receive similar to 25% of cardiac output, which is a prerequisite to maintain sufficient glomerular filtration rate. However, both intrarenal regional renal blood flow and tissue oxygen levels are heterogeneous with decreasing levels in the inner part of the medulla. These differences, in combination with the heterogeneous metabolic activity of the different nephron segment located in the different parts of the kidney, may constitute a functional problem when challenged. The proximal tubule and the medullary thick ascending limb of Henle are considered to have the highest metabolic rate, which is related to the high mitochondria content needed to sustain sufficient ATP production from oxidative phosphorylation to support high electrolyte transport activity in these nephron segments. Interestingly, the cells located in kidney medulla function at the verge of hypoxia, and the mitochondria may have adapted to the surrounding environment. However, little is known about intrarenal differences in mitochondria function. We therefore investigated functional differences between mitochondria isolated from kidney cortex and medulla of healthy normoglycemic rats by using high-resolution respirometry. The results demonstrate that medullary mitochondria had a higher degree of coupling, are more efficient, and have higher oxygen affinity, which would make them more suitable to function in an environment with limited oxygen supply. Furthermore, these results support the hypothesis that mitochondria of medullary cells have adapted to the normal hypoxic in vivo situation as a strategy of sustaining ATP production in a suboptimal environment., Funding Agencies|Swedish Medical Research Council; Swedish Diabetes Foundation; Swedish Research Council; Family Ernfors Foundation

Funding agencies: Swedish Research Council [2009-5430]; LiU Cancer (Linkoping University); LiU Cancer (Region Ostergotland)

Funding agencies: Swedish Research Council [2009-5430]; LiU Cancer (Linkoping University); LiU Cancer (Region Ostergotland)

Head and neck squamous cell carcinoma (HNSCC) tumours are associated with high mortality despite advances in therapy. The monoclonal antibody cetuximab (Erbitux®) has been approved for the treatment of advanced HNSCC. However, only a subset of HNSC patients receiving cetuximab actually responds to treatment, underlining the need for a means to tailor treatments of individual patients. The aim of the present study was to investigate the effect of cetuximab treatment on tumour growth, on tumour partial oxygen pressure as measured by LiPc electron paramagnetic resonance oximetry and on the expression of proteins involved in tumour growth, metabolism and hypoxia. Two HNSCC cell lines, UT-SCC-2 and UT-SCC-14, were used to generate xenografts on female BALB/c (nu/nu) nude mice. Mice with xenografts were given three injections of intraperitoneal cetuximab or phosphate-buffered saline, and the tumour volume was recorded continuously. After treatment the tumour partial oxygen pressure was measured by LiPc electron paramagnetic resonance oximetry and the expression of epidermal growth factor receptor (EGFR), phosphorylated EGFR, Ki-67, MCT1, MCT4, GLUT1, CAIX and HIF-1α were investigated by immunohistochemistry. In xenografts from both cell lines (UT-SCC-2 and UT-SCC-14) cetuximab had effect on the tumour volume but the effect was more pronounced on UT-SCC-14 xenografts. A higher tumour oxygenation was measured in cetuximab-treated tumours from both cell lines compared to untreated controls. Immunocytochemical staining after cetuximab treatment shows a significantly decreased expression of EGFR, pEGFR, Ki67, CAIX and nuclear HIF-1α in UT-SCC-14 tumours compared to untreated controls. MCT1 and GLUT1 were significantly decreased in tumours from both cell lines but more pronounced in UT-SCC-14 tumours. Taken together, our results show that cetuximab treatment decreases the tumour growth and increases the tumour partial oxygen pressure of HNSCC xenografts. Furthermore we found a, Funding agencies: Swedish Research Council [2009-5430]; LiU Cancer (Linkoping University); LiU Cancer (Region Ostergotland)

Head and neck squamous cell carcinoma (HNSCC) tumours are associated with high mortality despite advances in therapy. The monoclonal antibody cetuximab (Erbitux®) has been approved for the treatment of advanced HNSCC. However, only a subset of HNSC patients receiving cetuximab actually responds to treatment, underlining the need for a means to tailor treatments of individual patients. The aim of the present study was to investigate the effect of cetuximab treatment on tumour growth, on tumour partial oxygen pressure as measured by LiPc electron paramagnetic resonance oximetry and on the expression of proteins involved in tumour growth, metabolism and hypoxia. Two HNSCC cell lines, UT-SCC-2 and UT-SCC-14, were used to generate xenografts on female BALB/c (nu/nu) nude mice. Mice with xenografts were given three injections of intraperitoneal cetuximab or phosphate-buffered saline, and the tumour volume was recorded continuously. After treatment the tumour partial oxygen pressure was measured by LiPc electron paramagnetic resonance oximetry and the expression of epidermal growth factor receptor (EGFR), phosphorylated EGFR, Ki-67, MCT1, MCT4, GLUT1, CAIX and HIF-1α were investigated by immunohistochemistry. In xenografts from both cell lines (UT-SCC-2 and UT-SCC-14) cetuximab had effect on the tumour volume but the effect was more pronounced on UT-SCC-14 xenografts. A higher tumour oxygenation was measured in cetuximab-treated tumours from both cell lines compared to untreated controls. Immunocytochemical staining after cetuximab treatment shows a significantly decreased expression of EGFR, pEGFR, Ki67, CAIX and nuclear HIF-1α in UT-SCC-14 tumours compared to untreated controls. MCT1 and GLUT1 were significantly decreased in tumours from both cell lines but more pronounced in UT-SCC-14 tumours. Taken together, our results show that cetuximab treatment decreases the tumour growth and increases the tumour partial oxygen pressure of HNSCC xenografts. Furthermore we found a, Funding agencies: Swedish Research Council [2009-5430]; LiU Cancer (Linkoping University); LiU Cancer (Region Ostergotland)

Funding agencies: Swedish Research Council [2009-5430]; LiU Cancer (Linkoping University); LiU Cancer (Region Ostergotland)

Intrarenal tissue hypoxia has been proposed as a unifying mechanism for the development of chronic kidney disease, including diabetic nephropathy. However, hypoxia has to be present before the onset of kidney disease to be the causal mechanism. To establish whether hypoxia precedes the onset of diabetic nephropathy, we implemented a minimally invasive electron paramagnetic resonance oximetry technique using implanted oxygen sensing probes for repetitive measurements of in vivo kidney tissue oxygen tensions in mice. Kidney cortex oxygen tensions were measured before and up to 15 days after the induction of insulinopenic diabetes in male mice and compared with normoglycemic controls. On day 16, urinary albumin excretions and conscious glomerular filtration rates were determined to define the temporal relationship between intrarenal hypoxia and disease development. Diabetic mice developed pronounced intrarenal hypoxia 3 days after the induction of diabetes, which persisted throughout the study period. On day 16, diabetic mice had glomerular hyperfiltration, but normal urinary albumin excretion. In conclusion, intrarenal tissue hypoxia in diabetes precedes albuminuria thereby being a plausible cause for the onset and progression of diabetic nephropathy.

Intrarenal tissue hypoxia has been proposed as a unifying mechanism for the development of chronic kidney disease, including diabetic nephropathy. However, hypoxia has to be present before the onset of kidney disease in order to be the causal mechanism. In order to establish if hypoxia precedes the onset of diabetic nephropathy, we implemented a minimally invasive electron paramagnetic resonance oximetry technique using implanted oxygen sensing probes for repetitive measurements of in vivo kidney tissue oxygen tensions in mice. Kidney cortex oxygen tensions were measured before and up to 15 days after the induction of insulinopenic diabetes in male mice and compared to normoglycemic controls. On day 16, urinary albumin excretions and conscious glomerular filtration rates were determined in order to define the temporal relationship between intrarenal hypoxia and disease development. Diabetic mice developed pronounced intrarenal hypoxia three days after the induction of diabetes, which persisted throughout the study period. On day 16, diabetic mice had glomerular hyperfiltration, but normal urinary albumin excretion. In conclusion, intrarenal tissue hypoxia in diabetes precedes albuminuria thereby being a plausible cause for the onset and progression of diabetic nephropathy., The status of this article was previous Manuscript.Funding agencies: Swedish Research Council; Swedish Heart Lung Foundation; Swedish Diabetes Foundation

PURPOSE: The purpose of this study was to develop an X-Band electron paramagnetic resonance imaging protocol for visualization of oxidative stress in biopsies. METHODS: The developed electron paramagnetic resonance imaging protocol was based on spin trapping with the cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. Computer software was developed for deconvolution and back-projection of the EPR image. A phantom containing radicals of known spatial characteristic was used for evaluation of the developed protocol. As a demonstration of the technique electron paramagnetic resonance imaging of oxidative stress was performed in six sections of atherosclerotic plaques. Histopathological analyses were performed on adjoining sections. RESULTS: The developed computer software for deconvolution and back-projection of the EPR images could accurately reproduce the shape of a phantom of known spatial distribution of radicals. The developed protocol could successfully be used to image oxidative stress in six sections of the three ex vivo atherosclerotic plaques. CONCLUSIONS: We have shown that oxidative stress can be imaged using a combination of spin trapping with the cyclic hydroxylamine spin probe cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. A thorough and systematic evaluation on different types of biopsies must be performed in the future to validate the proposed technique. Magn Reson Med, 2014.

PURPOSE: The purpose of this study was to develop an X-Band electron paramagnetic resonance imaging protocol for visualization of oxidative stress in biopsies. METHODS: The developed electron paramagnetic resonance imaging protocol was based on spin trapping with the cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. Computer software was developed for deconvolution and back-projection of the EPR image. A phantom containing radicals of known spatial characteristic was used for evaluation of the developed protocol. As a demonstration of the technique electron paramagnetic resonance imaging of oxidative stress was performed in six sections of atherosclerotic plaques. Histopathological analyses were performed on adjoining sections. RESULTS: The developed computer software for deconvolution and back-projection of the EPR images could accurately reproduce the shape of a phantom of known spatial distribution of radicals. The developed protocol could successfully be used to image oxidative stress in six sections of the three ex vivo atherosclerotic plaques. CONCLUSIONS: We have shown that oxidative stress can be imaged using a combination of spin trapping with the cyclic hydroxylamine spin probe cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. A thorough and systematic evaluation on different types of biopsies must be performed in the future to validate the proposed technique. Magn Reson Med, 2014.

The deep biosphere of the subseafloor basalts is recognized as a major scientific frontier in disciplines like biology, geology, and oceanography. Recently, the presence of fungi in these environments has involved a change of view regarding diversity and ecology. Here, we describe fossilized fungal communities in vugs in subseafloor basalts from a depth of 936.65 metres below seafloor at the Detroit Seamount, Pacific Ocean. These fungal communities are closely associated with botryoidal Mn oxides composed of todorokite. Analyses of the Mn oxides by Electron Paramagnetic Resonance spectroscopy (EPR) indicate a biogenic signature. We suggest, based on mineralogical, morphological and EPR data, a biological origin of the botryoidal Mn oxides. Our results show that fungi are involved in Mn cycling at great depths in the seafloor and we introduce EPR as a means to easily identify biogenic Mn oxides in these environments., Funding Agencies|Swedish Research Council [2012-4364]; Danish National Research Foundation [DNRF53]

The deep biosphere of the subseafloor basalts is recognized as a major scientific frontier in disciplines like biology, geology, and oceanography. Recently, the presence of fungi in these environments has involved a change of view regarding diversity and ecology. Here, we describe fossilized fungal communities in vugs in subseafloor basalts from a depth of 936.65 metres below seafloor at the Detroit Seamount, Pacific Ocean. These fungal communities are closely associated with botryoidal Mn oxides composed of todorokite. Analyses of the Mn oxides by Electron Paramagnetic Resonance spectroscopy (EPR) indicate a biogenic signature. We suggest, based on mineralogical, morphological and EPR data, a biological origin of the botryoidal Mn oxides. Our results show that fungi are involved in Mn cycling at great depths in the seafloor and we introduce EPR as a means to easily identify biogenic Mn oxides in these environments., Funding Agencies|Swedish Research Council [2012-4364]; Danish National Research Foundation [DNRF53]

The deep biosphere of the subseafloor basalts is recognized as a major scientific frontier in disciplines like biology, geology, and oceanography. Recently, the presence of fungi in these environments has involved a change of view regarding diversity and ecology. Here, we describe fossilized fungal communities in vugs in subseafloor basalts from a depth of 936.65 metres below seafloor at the Detroit Seamount, Pacific Ocean. These fungal communities are closely associated with botryoidal Mn oxides composed of todorokite. Analyses of the Mn oxides by Electron Paramagnetic Resonance spectroscopy (EPR) indicate a biogenic signature. We suggest, based on mineralogical, morphological and EPR data, a biological origin of the botryoidal Mn oxides. Our results show that fungi are involved in Mn cycling at great depths in the seafloor and we introduce EPR as a means to easily identify biogenic Mn oxides in these environments.

PURPOSE: The purpose of this study was to develop an X-Band electron paramagnetic resonance imaging protocol for visualization of oxidative stress in biopsies. METHODS: The developed electron paramagnetic resonance imaging protocol was based on spin trapping with the cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. Computer software was developed for deconvolution and back-projection of the EPR image. A phantom containing radicals of known spatial characteristic was used for evaluation of the developed protocol. As a demonstration of the technique electron paramagnetic resonance imaging of oxidative stress was performed in six sections of atherosclerotic plaques. Histopathological analyses were performed on adjoining sections. RESULTS: The developed computer software for deconvolution and back-projection of the EPR images could accurately reproduce the shape of a phantom of known spatial distribution of radicals. The developed protocol could successfully be used to image oxidative stress in six sections of the three ex vivo atherosclerotic plaques. CONCLUSIONS: We have shown that oxidative stress can be imaged using a combination of spin trapping with the cyclic hydroxylamine spin probe cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. A thorough and systematic evaluation on different types of biopsies must be performed in the future to validate the proposed technique. Magn Reson Med, 2014.

The deep biosphere of the subseafloor basalts is recognized as a major scientific frontier in disciplines like biology, geology, and oceanography. Recently, the presence of fungi in these environments has involved a change of view regarding diversity and ecology. Here, we describe fossilized fungal communities in vugs in subseafloor basalts from a depth of 936.65 metres below seafloor at the Detroit Seamount, Pacific Ocean. These fungal communities are closely associated with botryoidal Mn oxides composed of todorokite. Analyses of the Mn oxides by Electron Paramagnetic Resonance spectroscopy (EPR) indicate a biogenic signature. We suggest, based on mineralogical, morphological and EPR data, a biological origin of the botryoidal Mn oxides. Our results show that fungi are involved in Mn cycling at great depths in the seafloor and we introduce EPR as a means to easily identify biogenic Mn oxides in these environments., Funding Agencies|Swedish Research Council [2012-4364]; Danish National Research Foundation [DNRF53]

PURPOSE: The purpose of this study was to develop an X-Band electron paramagnetic resonance imaging protocol for visualization of oxidative stress in biopsies. METHODS: The developed electron paramagnetic resonance imaging protocol was based on spin trapping with the cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. Computer software was developed for deconvolution and back-projection of the EPR image. A phantom containing radicals of known spatial characteristic was used for evaluation of the developed protocol. As a demonstration of the technique electron paramagnetic resonance imaging of oxidative stress was performed in six sections of atherosclerotic plaques. Histopathological analyses were performed on adjoining sections. RESULTS: The developed computer software for deconvolution and back-projection of the EPR images could accurately reproduce the shape of a phantom of known spatial distribution of radicals. The developed protocol could successfully be used to image oxidative stress in six sections of the three ex vivo atherosclerotic plaques. CONCLUSIONS: We have shown that oxidative stress can be imaged using a combination of spin trapping with the cyclic hydroxylamine spin probe cyclic hydroxylamine spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine and X-Band EPR imaging. A thorough and systematic evaluation on different types of biopsies must be performed in the future to validate the proposed technique. Magn Reson Med, 2014.

Interest in high dose rate (HDR) electronic brachytherapy operating at 50 kV is increasing. For quality assurance it is important to identify dosimetry systems that can measure the absorbed doses in absolute terms which is difficult in this energy region. In this work a comparison is made between two dosimetry systems, EPR lithium formate dosimeters and radiochromic EBT2 film. Both types of dosimeters were irradiated simultaneously in a PMMA phantom using the Axxent EBS. Absorbed dose to water was determined at distances of 10 mm, 30 mm and 50 mm from the EBS. Results were traceable to different primary standards as regards to absorbed dose to water (EPR) and air kerma (EBT2). Monte Carlo simulations were used in absolute terms as a third estimate of absorbed dose to water. Agreement within the estimated expanded (k = 2) uncertainties (5% (EPR), 7% (EBT2)) was found between the results at 30 mm and 50 mm from the x-ray source. The same result was obtained in 4 repetitions of irradiation, indicating high precision in the measurements with both systems. At all distances, agreement between EPR and Monte Carlo simulations was shown as was also the case for the film measurements at 30mm and 50mm. At 10mm the geometry for the film measurements caused too large uncertainty in measured values depending on the exact position (within sub-mm distances) of the EBS and the 10 mm film results were exculded from comparison. This work has demonstrated good performance of the lithium formate EPR dosimetry system in accordance with earlier experiments at higher photon energies (192Ir HDR brachytherapy). It was also highlighted that there might be issues regarding the energy dependence and intrinsic efficiency of the EBT2 film that need to be considered for measurements using low energy sources.