| 1. |
- Eckerbom, Per, 1974-, et al.
(författare)
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Circadian variation in renal blood flow and kidney function in healthy volunteers monitored with noninvasive magnetic resonance imaging
- 2020
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Ingår i: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 1931-857X .- 1522-1466. ; 319:6, s. F966-F978
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Tidskriftsartikel (refereegranskat)abstract
- Circadian regulation of kidney function is involved in maintaining whole body homeostasis, and dysfunctional circadian rhythm can potentially be involved in disease development. Magnetic resonance imaging (MRI) provides reliable and reproducible repetitive estimates of kidney function noninvasively without the risk of adverse events associated with contrast agents and ionizing radiation. The purpose of this study was to estimate circadian variations in kidney function in healthy human subjects with MRI and to relate the findings to urinary excretions of electrolytes and markers of kidney function. Phase-contrast imaging, arterial spin labeling, and blood oxygen level-dependent transverse relaxation rate (R2*) mapping were used to assess total renal blood flow and regional perfusion as well as intrarenal oxygenation in eight female and eight male healthy volunteers every fourth hour during a 24-h period. Parallel with MRI scans, standard urinary and plasma parameters were quantified. Significant circadian variations of total renal blood flow were found over 24 h, with increasing flow from noon to midnight and decreasing flow during the night. In contrast, no circadian variation in intrarenal oxygenation was detected. Urinary excretions of electrolytes, osmotically active particles, creatinine, and urea all displayed circadian variations, peaking during the afternoon and evening hours. In conclusion, total renal blood flow and kidney function, as estimated from excretion of electrolytes and waste products, display profound circadian variations, whereas intrarenal oxygenation displays significantly less circadian variation.
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| 2. |
- Guath, Mona, et al.
(författare)
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Pupil dilation during negative prediction errors is related to brain choline concentration and depressive symptoms in adolescents
- 2023
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 436
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Tidskriftsartikel (refereegranskat)abstract
- Depressive symptoms are associated with altered pupillary responses during learning and reward prediction as well as with changes in neurometabolite levels, including brain concentrations of choline, glutamate and gamma-aminobutyric acid (GABA). However, the full link between depressive symptoms, reward-learning-related pupillary responses and neurometabolites is yet to be established as these constructs have not been assessed in the same individuals. The present pilot study, investigated these relations in a sample of 24 adolescents aged 13 years. Participants completed the Revised Child Anxiety and Depression Scale (RCADS) and underwent a reward learning task while measuring pupil dilation and a single voxel dorsal anterior cingulate cortex (dACC) MEGA-PRESS magnetic resonance spectroscopy scan assessing choline, glutamate and GABA concentrations. Pupil dilation was related to prediction errors (PE) during learning, which was captured by a prediction error-weighted pupil dilation response index (PE-PDR) for each individual. Higher PE-PDR scores, indicating larger pupil dilations to negative prediction errors, were related to lower depressive symptoms and lower dACC choline concentrations. Dorsal ACC choline was positively associated with depressive symptoms, whereas glutamate and GABA were not related to PE-PDR or depressive symptoms. The findings support notions of cholinergic involvement in depressive symptoms and cholinergic influence on reward-related pupillary response, suggesting that pupillary responses to negative prediction errors may hold promise as a biomarker of depressive states.
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| 3. |
- Luther, Tomas, et al.
(författare)
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Decreased renal perfusion during acute kidney injury in critical COVID-19 assessed by magnetic resonance imaging : a prospective case control study
- 2022
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Ingår i: Critical Care. - : Springer Nature. - 1364-8535 .- 1466-609X. ; 26
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Tidskriftsartikel (refereegranskat)abstract
- Renal hypoperfusion has been suggested to contribute to the development of acute kidney injury (AKI) in critical COVID-19. However, limited data support this. In this prospective case-control study we aimed to investigate differences in renal perfusion, oxygenation and water diffusion using multiparametric magnetic resonance imaging (mpMRI) in critically ill COVID-19 patients with and without AKI. Nineteen patients without prior kidney disease treated in intensive care for respiratory failure were examined. Ten patients had AKI and nine patients did not have AKI using Kidney Disease: Improving Global Outcomes Creatinine criteria. Age and baseline Plasma-Creatinine were similar in both groups. Total renal blood flow was lower in patients with AKI compared with patients without (median 645 quartile range [423-753] vs. 859 [746-920] ml/min, P = 0.037). Regional perfusion was reduced in both cortex (76 [51-112] vs. 146 [123-169] mL/100g/min, P = 0.015) and medulla (28 [18-47] vs. 47 [38-73] mL/100g/min, P = 0.03). Renal venous saturation was similar in both groups (72% [64-75] vs. 72% [63-84], ns.), as was regional oxygenation (R2*) in cortex (17 [16-19] vs. 17 [16-18] 1/s, ns.) and medulla (29 [24-39] vs. 27 [23-29] 1/s, ns.). We conclude that in critically ill COVID-19 patients with AKI, the total, cortical and medullary renal blood flow are reduced compared with similar patients without AKI, whereas no differences in renal oxygenation were demonstrable in this setting.
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| 4. |
- Oroujeni, Maryam, PhD, 1982-, et al.
(författare)
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The Use of a Non-Conventional Long-Lived Gallium Radioisotope Ga-66 Improves Imaging Contrast of EGFR Expression in Malignant Tumours Using DFO-ZEGFR:2377 Affibody Molecule
- 2021
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Ingår i: Pharmaceutics. - : MDPI AG. - 1999-4923 .- 1999-4923. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- Epidermal growth factor receptor (EGFR) is overexpressed in many malignancies. EGFR-targeted therapy extends survival of patients with disseminated cancers. Radionuclide molecular imaging of EGFR expression would make EGFR-directed treatment more personalized and therefore more efficient. A previous study demonstrated that affibody molecule [Ga-68]Ga-DFO-ZEGFR:2377 permits specific positron-emission tomography (PET) imaging of EGFR expression in xenografts at 3 h after injection. We anticipated that imaging at 24 h after injection would provide higher contrast, but this is prevented by the short half-life of Ga-68 (67.6 min). Here, we therefore tested the hypothesis that the use of the non-conventional long-lived positron emitter Ga-66 (T-1/2 = 9.49 h, beta(+) = 56.5%) would permit imaging with higher contrast. Ga-66 was produced by the Zn-66(p,n)Ga-66 nuclear reaction and DFO-ZEGFR:2377 was efficiently labelled with Ga-66 with preserved binding specificity in vitro and in vivo. At 24 h after injection, [Ga-66]Ga-DFO-ZEGFR:2377 provided 3.9-fold higher tumor-to-blood ratio and 2.3-fold higher tumor-to-liver ratio than [Ga-68]Ga-DFO-ZEGFR:2377 at 3 h after injection. At the same time point, [Ga-66]Ga-DFO-ZEGFR:2377 provided 1.8-fold higher tumor-to-blood ratio, 3-fold higher tumor-to-liver ratio, 1.9-fold higher tumor-to-muscle ratio and 2.3-fold higher tumor-to-bone ratio than [Zr-89]Zr-DFO-ZEGFR:2377. Biodistribution data were confirmed by whole body PET combined with magnetic resonance imaging (PET/MRI). The use of the positron emitter Ga-66 for labelling of DFO-ZEGFR:2377 permits PET imaging of EGFR expression at 24 h after injection and improves imaging contrast.
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| 5. |
- Persson, Jonas, 1983-, et al.
(författare)
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Inhibitory and excitatory neurotransmitter systems in depressed and healthy : A positron emission tomography and magnetic resonance spectroscopy study
- 2021
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Ingår i: Psychiatry Research. - : Elsevier. - 0925-4927 .- 1872-7506. ; 315
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Tidskriftsartikel (refereegranskat)abstract
- The Gamma-aminobutyric acid (GABA) and glutamate (Glu) neurotransmitter systems are implicated in depression. While previous studies found reduced GABA levels, and a tendency towards reduced Glu, using proton (H-1) magnetic resonance spectroscopy (H-1-MRS), little is known about GABA(A) receptor availability in depression. Here, the aim was to characterize GABA and Glu-levels in dorsal anterior cingulate cortex (dACC), whole-brain GABA(A) availability, and their relationship in patients with depression compared to healthy controls. Forty-two patients and 45 controls underwent H-1-MRS using a MEGA-PRESS sequence to quantify dACC GABA+ and Glu (contrasted against creatine [Cr]). Immediately preceding the H-1-MRS, a subsample of 28 patients and 15 controls underwent positron emission tomography (PET) with [C-11]Flumazenil to assess whole-brain GABA(A) receptor availability. There were no differences in dACC GABA+/Cr or Glu/Cr ratios between patients and controls. The same was true for whole-brain GABA(A) receptor availability. However, there was a significant negative relationship between GABA+/Cr ratio and receptor availability in ACC, in a whole-brain voxel-wise analysis across patients and controls, controlling for group or depressive symptoms. This relatively large study did not support the GABA-deficit hypothesis in depression, but shed light on GABA-system functioning, suggesting a balance between neurotransmitter concentration and receptor availability in dACC.
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| 6. |
- Rosestedt, Maria, et al.
(författare)
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Radiolabelling and positron emission tomography imaging of a high-affinity peptide binder to collagen type 1
- 2021
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Ingår i: Nuclear Medicine and Biology. - : Elsevier. - 0969-8051 .- 1872-9614. ; 93, s. 54-62
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionPathological formation of fibrosis, is an important feature in many diseases. Fibrosis in liver and pancreas has been associated to metabolic disease including type 1 and 2 diabetes. The current methods for detecting and diagnosing fibrosis are either invasive, or their sensitivity to detect fibrosis in early stage is limited. Therefore, it is crucial to develop non-invasive methods to detect, stage and study the molecular processes that drive the pathology of liver fibrosis. The peptide LRELHLNNN was previously identified as a selective binder to collagen type I with an affinity of 170 nM. Radiolabelled LRELHLNNN thus constitute a potential PET tracer for fibrosis.MethodLRELHLNNN was conjugated to a DOTA/NOTA moiety via a PEG2-linker. DOTA-PEG2-LRELHLNNN was labelled with Gallium-68 and NOTA- PEG2-LRELHLNNN with aluminium fluoride-18. Biodistribution of [68Ga]Ga-DOTA-PEG2-LRELHLNNN and [18F]AlF-NOTA-PEG2-LRELHLNNN was performed in healthy rats ex vivo and in vivo. The 68Ga-labelled analogue was evaluated in a mouse model of liver fibrosis by PET/MRI-imaging. The human predicted dosimetry of the tracers was extrapolated from rat ex vivo biodistribution studies at 10, 20, 40, 60, 120, 180 min (only fluoride-18) post-injection.ResultsThe peptides were successfully radiolabelled with gallium-68 and aluminium fluoride-18, respectively. The biodistribution of [68Ga]Ga-DOTA-PEG2-LRELHLNNN and [18F]AlF-NOTA-PEG2-LRELHLNNN was favorable showing rapid clearance and low background binding in organs where fibrosis may develop. Binding of [68Ga]Ga-DOTA-PEG2-LRELHLNNN to fibrotic liver was higher than surrounding tissues in mice with induced hepatic fibrosis. However, the binding was in the range of SUV 0.3, indicating limited targeting of the tracer to liver. The extrapolated human predicted dosimetric profiles of [68Ga]Ga-DOTA-PEG2-LRELHLNNN and [18F]AlF-NOTA-PEG2-LRELHLNNN were beneficial, potentially allowing at least three PET examinations annually.ConclusionsWe describe the modification, radiolabelling and evaluation of the collagen type I binding peptide LRELHLNNN. The resulting radiotracer analogues demonstrated suitable biodistribution and dosimetry. [68Ga]Ga-DOTA-PEG2-LRELHLNNN exhibited binding to hepatic fibrotic lesions and is a promising tool for PET imaging of fibrosis.Advances in knowledgeValidation of a new collagen targeting PET tracer.Implications for patient careEarly, non-invasive diagnosis and stratification of fibrosis in order to improve the diagnosis, staging and treatment of patients with diseases involving fibrosis.
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| 7. |
- Vedung, Fredrik, et al.
(författare)
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Chronic cerebral blood flow alterations in traumatic brain injury and sports-related concussions
- 2022
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Ingår i: Brain Injury. - : Taylor & Francis Group. - 0269-9052 .- 1362-301X.
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Tidskriftsartikel (refereegranskat)abstract
- Primary ObjectiveTraumatic brain injury (TBI) and sports-related concussion (SRC) may result in chronic functional and neuroanatomical changes. We tested the hypothesis that neuroimaging findings (cerebral blood flow (CBF), cortical thickness, and 1H-magnetic resonance (MR) spectroscopy (MRS)) were associated to cognitive function, TBI severity, and sex.Research DesignEleven controls, 12 athletes symptomatic following ≥3SRCs and 6 patients with moderate-severe TBI underwent MR scanning for evaluation of cortical thickness, brain metabolites (MRS), and CBF using pseudo-continuous arterial spin labeling (ASL). Cognitive screening was performed using the RBANS cognitive test battery.Main Outcomes and ResultsRBANS-index was impaired in both injury groups and correlated with the injury severity, although not with any neuroimaging parameter. Cortical thickness correlated with injury severity (p = 0.02), while neuronal density, using the MRS marker ((NAA+NAAG)/Cr, did not. On multivariate analysis, injury severity (p = 0.0003) and sex (p = 0.002) were associated with CBF. Patients with TBI had decreased gray (p = 0.02) and white matter (p = 0.02) CBF compared to controls. CBF was significantly lower in total gray, white matter and in 16 of the 20 gray matter brain regions in female but not male athletes when compared to female and male controls, respectively.ConclusionsInjury severity correlated with CBF, cognitive function, and cortical thickness. CBF also correlated with sex and was reduced in female, not male, athletes. Chronic CBF changes may contribute to the persistent injury mechanisms in TBI and rSRC.
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| 8. |
- Weis, Jan, 1956-, et al.
(författare)
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GABA quantification in human anterior cingulate cortex
- 2021
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Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- γ-Aminobutyric acid (GABA) is a primary inhibitory neurotransmitter in the human brain. It has been shown that altered GABA concentration plays an important role in a variety of psychiatric and neurological disorders. The main purpose of this study was to propose a combination of PRESS and MEGA-PRESS acquisitions for absolute GABA quantification and to compare GABA estimations obtained using total choline (tCho), total creatine (tCr), and total N-acetyl aspartate (tNAA) as the internal concentration references with water referenced quantification. The second aim was to demonstrate the fitting approach of MEGA-PRESS spectra with QuasarX algorithm using a basis set of GABA, glutamate, glutamine, and NAA in vitro spectra. Thirteen volunteers were scanned with the MEGA-PRESS sequence at 3T. Interleaved water referencing was used for quantification, B0 drift correction and to update the carrier frequency of RF pulses in real time. Reference metabolite concentrations were acquired using a PRESS sequence with short TE (30 ms) and long TR (5000 ms). Absolute concentration were corrected for cerebrospinal fluid, gray and white matter water fractions and relaxation effects. Water referenced GABA estimations were significantly higher compared to the values obtained by metabolite references. We conclude that QuasarX algorithm together with the basis set of in vitro spectra improves reliability of GABA+ fitting. The proposed GABA quantification method with PRESS and MEGA-PRESS acquisitions enables the utilization of tCho, tCr, and tNAA as internal concentration references. The use of different concentration references have a good potential to improve the reliability of GABA estimation.
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| 9. |
- Weis, Jan, 1956-, et al.
(författare)
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Phosphorus MRS of healthy human spleen.
- 2022
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Ingår i: NMR in Biomedicine. - : John Wiley & Sons. - 0952-3480 .- 1099-1492. ; 35:10
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Tidskriftsartikel (refereegranskat)abstract
- Phosphorus (31 P-) MRS in vivo enables detection and quantification of important phosphorus-containing metabolites in biological tissues. 31 P-MRS of the normal spleen is challenging due to the relatively small volume and the larger distance between the spleen and surface coil. However, reference spectra of the healthy spleen are invaluable in studies of splenic malignancies and benign causes of splenomegaly, as well as in the study of its physiology. The purpose of this work was to investigate the feasibility of localized 31 P-MRS of healthy spleen in situ in a clinically acceptable measurement time using a clinical 3 T MR scanner. In this work, 31 P spectra of five healthy volunteers were measured using single-voxel image-selected in vivo spectroscopy (ISIS). The measurement sequence was augmented by broadband proton decoupling and nuclear Overhauser effect enhancement. It is demonstrated that localized 31 P-MRS of the spleen in situ using single-voxel ISIS is feasible on a clinical 3 T scanner in a clinically acceptable acquisition time. However, results have to be corrected for the transmitter excitation profile, and chemical shift displacement errors need to be taken into consideration during placement of the volume of interest. Results presented here could be used as a reference in future studies of splenomegaly caused by haematological malignancies.
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| 10. |
- Widegren, Ebba, et al.
(författare)
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The influence of anterior cingulate GABA+ and glutamate on emotion regulation and reactivity in adolescents and adults
- 2024
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Ingår i: Developmental Psychobiology. - : John Wiley & Sons. - 0012-1630 .- 1098-2302. ; 66:4
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Tidskriftsartikel (refereegranskat)abstract
- During adolescence, emotion regulation and reactivity are still developing and are in many ways qualitatively different from adulthood. However, the neurobiological processes underpinning these differences remain poorly understood, including the role of maturing neurotransmitter systems. We combined magnetic resonance spectroscopy in the dorsal anterior cingulate cortex (dACC) and self-reported emotion regulation and reactivity in a sample of typically developed adolescents (n = 37; 13-16 years) and adults (n = 39; 30-40 years), and found that adolescents had higher levels of glutamate to total creatine (tCr) ratio in the dACC than adults. A glutamate i age group interaction indicated a differential relation between dACC glutamate levels and emotion regulation in adolescents and adults, and within-group follow-up analyses showed that higher levels of glutamate/tCr were related to worse emotion regulation skills in adolescents. We found no age-group differences in gamma-aminobutyric acid+macromolecules (GABA+) levels; however, emotion reactivity was positively related to GABA+/tCr in the adult group, but not in the adolescent group. The results demonstrate that there are developmental changes in the concentration of glutamate, but not GABA+, within the dACC from adolescence to adulthood, in accordance with previous findings indicating earlier maturation of the GABA-ergic than the glutamatergic system. Functionally, glutamate and GABA+ are positively related to emotion regulation and reactivity, respectively, in the mature brain. In the adolescent brain, however, glutamate is negatively related to emotion regulation, and GABA+ is not related to emotion reactivity. The findings are consistent with synaptic pruning of glutamatergic synapses from adolescence to adulthood and highlight the importance of brain maturational processes underlying age-related differences in emotion processing.
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