| 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. |
- Eckerbom, Per, 1974-, et al.
(författare)
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Multiparametric assessment of renal physiology in healthy volunteers using noninvasive magnetic resonance imaging
- 2019
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Ingår i: American Journal of Physiology - Renal Physiology. - : American Physiological Society. - 1931-857X .- 1522-1466. ; 316:4, s. F693-F702
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Tidskriftsartikel (refereegranskat)abstract
- Non-invasive methods of magnetic resonance imaging (MRI) can quantify parameters of kidney function. The main purpose of this study was to determine baseline values of such parameters in healthy volunteers. In 28 healthy volunteers (15 females, 13 males), Arterial Spin Labeling (ASL) to estimate regional renal perfusion, Blood Oxygen Level Dependent (BOLD) transverse relaxation rate (R2*) to estimate oxygenation, and Apparent Diffusion Coefficient (ADC), true diffusion (D) and longitudinal relaxation time (T1) to estimate tissue properties were determined bilaterally in the cortex, outer and inner medulla. Additionally, phase contrast (PC) MRI was applied in the renal arteries to quantify total renal blood flow. The results demonstrated profound gradients of perfusion, ADC and D with highest values in the kidney cortex and a decrease towards the inner medulla. R2* and T1 were lowest in kidney cortex and increased towards the inner medulla. Total renal blood flow correlated with body surface area, body mass index and renal volume. Similar patterns in all investigated parameters were observed in females and males. In conclusion, non-invasive MRI provides useful tools to evaluate intra renal differences in blood flow, perfusion, diffusion, oxygenation and structural properties of the kidney tissue. As such, this experimental approach has the potential to advance our current understanding regarding normal physiology and the pathological processes associated with acute and chronic kidney disease.
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| 3. |
- Eriksson, Jonas, et al.
(författare)
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Synthesis and preclinical evaluation of the CRTH2 antagonist [11C]MK-7246 as a novel PET tracer and potential surrogate marker for pancreatic beta-cell mass
- 2019
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Ingår i: Nuclear Medicine and Biology. - : Elsevier BV. - 0969-8051 .- 1872-9614. ; 71, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: MK-7246 is a potent and selective antagonist for chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). Within the pancreas CRTH2 is selectively expressed in pancreatic β-cells where it is believed to play a role in insulin release. Reduction in β-cell mass and insufficient insulin secretion in response to elevated blood glucose levels is a hallmark for type 1 and type 2 diabetes. Reported here is the synthesis of [11C]MK-7246 and initial preclinical evaluation towards CRTH2 imaging. The aim is to develop a method to quantify β-cell mass with PET and facilitate non-invasive studies of disease progression in individuals with type 2 diabetes.Methods: The precursor N-desmethyl-O-methyl MK-7246 was synthesized in seven steps and subjected to methylation with [11C]methyl iodide followed by hydrolysis to obtain [11C]MK-7246 labelled in the N-methyl position. Preclinical evaluation included in vitro radiography and immune-staining performed in human pancreatic biopsies. Biodistribution studies were performed in rat by PET-MRI and in pig by PET-CT imaging. The specific tracer uptake was examined in pig by scanning before and after administration of MK-7246 (1 mg/kg). Predicted dosimetry of [11C]MK-7246 in human males was estimated based on the biodistribution in rat.Results: [11C]MK-7246 was obtained with activities sufficient for the current investigations (270±120 MBq) and a radiochemical purity of 93±2%. The tracer displayed focal binding in areas with insulin positive islet of Langerhans in human pancreas sections. Baseline uptake in pig was significantly reduced in CRTH2-rich areas after administration of MK-7246; pancreas (66% reduction) and spleen (88% reduction). [11C]MK-7246 exhibited a safe human predicted dosimetry profile as extrapolated from the rat biodistribution data.Conclusions: Initial preclinical in vitro and in vivo evaluation of [11C]MK-7246 show binding and biodistribution properties suitable for PET imaging of CRTH2. Further studies are warranted to assess its potential in β-cell mass imaging and CRTH2 drug development.
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| 4. |
- Espes, Daniel, 1985-, et al.
(författare)
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Pancreatic perfusion and its response to glucose as measured by simultaneous PET/MRI
- 2019
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Ingår i: Acta Diabetologica. - : Springer. - 0940-5429 .- 1432-5233. ; 56:10, s. 1113-1120
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Perfusion of the pancreas and the islets of Langerhans is sensitive to physiological stimuli and is dysregulated in metabolic disease. Pancreatic perfusion can be assessed by both positron emission tomography (PET) and magnetic resonance imaging (MRI), but the methods have not been directly compared or benchmarked against the gold-standard microsphere technique.METHODS: Pigs (n = 4) were examined by [15O]H2O PET and intravoxel incoherent motion (IVIM) MRI technique simultaneously using a hybrid PET/MRI scanner. The pancreatic perfusion was measured both at basal conditions and after intravenous (IV) administration of up to 0.5 g/kg glucose.RESULTS: Pancreatic perfusion increased by 35%, 157%, and 29% after IV 0.5 g/kg glucose compared to during basal conditions, as assessed by [15O]H2O PET, IVIM MRI, and microspheres, respectively. There was a correlation between pancreatic perfusion as assessed by [15O]H2O PET and IVIM MRI (r = 0.81, R2 = 0.65, p < 0.01). The absolute quantification of pancreatic perfusion (ml/min/g) by [15O]H2O PET was within a 15% error of margin of the microsphere technique.CONCLUSION: Pancreatic perfusion by [15O]H2O PET was in agreement with the microsphere technique assessment. The IVIM MRI method has the potential to replace [15O]H2O PET if the pancreatic perfusion is sufficiently large, but not when absolute quantitation is required.
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| 5. |
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| 6. |
- 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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| 7. |
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| 8. |
- 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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| 9. |
- Luther, Tomas, et al.
(författare)
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Plasma expansion and renal perfusion in critical COVID-19 with AKI: a prospective case control study
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: A decrease in renal perfusion during acute kidney injury (AKI) due to critical COVID-19 have previously been demonstrated. The objective of this study was to compare the effects of plasma expansion with a standardized fluid bolus on renal perfusion in critically ill patients with AKI compared to similar patients without AKI. Methods: A case control study design was used to investigate group differences before and after a standardized intervention. ICU-treated COVID-19 patients without underlying kidney disease were assigned to two groups based on KDIGO Creatinine criteria for AKI. Renal perfusion was assessed by magnetic resonance imaging using phase contrast and arterial spin labeling before and directly after plasma expansion with 7.5ml/kg Ringer’s Acetate (Baxter). Mean arterial pressure (MAP) was recorded before plasma infusion and compared with maximum value after. Data was analyzed with a mixed model repeated measures ANOVA for all kidneys using a random effect to account for research subjects. Results: Nine patients with AKI and eight without were included in the study. The hemodynamic response to plasma expansion was similar in both groups with increases in MAP by 18 mmHg (CI 8-28) and 20 mmHg (CI 10-31) in patients with and without AKI respectively. Total renal perfusion and cortical perfusion was not significantly changed by plasma expansion in either group. There were however there was a reduction of medullary perfusion in patients without AKI from 55 (CI 39-79) to 34 (CI 24-48) ml/min/100g (P = 0.0027).Conclusion: Plasma expansion with a standardized fluid bolus did not increase renal perfusion in critically ill patients with COVID-19.
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| 10. |
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| 11. |
- Nelander, Maria, et al.
(författare)
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Assessment of cerebral perfusion and edema in preeclampsia with intravoxel incoherent motion MRI
- 2018
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 97:10, s. 1212-1218
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCerebral complications are the main reasons for morbidity and mortality in preeclampsia and eclampsia. Still we do not know if the pathophysiology entails hypo- or hyperperfusion of the brain, or how and when edema emerges, due to the difficulty to examine the cerebral circulation.Material and methodsWe have used a non-invasive diffusion weighted magnetic resonance imaging (MRI) technique, intravoxel incoherent motion, to study cerebral perfusion on the capillary level and cerebral edema in women with preeclampsia (n=30), normal pregnancy (n=32) and non-pregnant women (n=16). Estimates of cerebral blood volume, blood flow and edema were measured in five different regions. These points were chosen to represent blood supply areas of both the carotid and vertebrobasilar arteries, and to include both white and grey matter.ResultsExcept for the caudate nucleus, we did not detect any differences in cerebral perfusion measures on a group level. In the caudate nucleus we found lower cerebral blood volume and lower blood flow in preeclampsia compared to both normal pregnancy (p=0.01 and p=0.03, respectively) and non-pregnant women (both p=0.02). No differences in edema were detected between study groups.ConclusionThe cerebral perfusion measures were comparable between the study groups, except for a portion of the basal ganglia where hypoperfusion was detected in preeclampsia compared to normal pregnancy and non-pregnant women.
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| 12. |
- Nelander, Maria, et al.
(författare)
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Cerebral Magnesium Levels in Preeclampsia; A Phosphorus Magnetic Resonance Spectroscopy Study
- 2017
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Ingår i: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 30:7, s. 667-672
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Magnesium sulfate (MgSO4) is used as a prophylaxis for eclamptic seizures. The exact mechanism of action is not fully established. We used phosphorus magnetic resonance spectroscopy (31P-MRS) to investigate if cerebral magnesium (Mg2+) levels differ between women with preeclampsia, normal pregnant, and nonpregnant women.METHODS: This cross-sectional study comprised 28 women with preeclampsia, 30 women with normal pregnancies in corresponding gestational week (range: 23-41 weeks) and 11 nonpregnant healthy controls. All women underwent 31P-MRS from the parieto-occipital region of the brain and were interviewed about cerebral symptoms. Differences between groups were assessed by analysis of variance and Tukey's post-hoc test. Correlations between Mg2+ levels and specific neurological symptoms were estimated with Spearman's rank test.RESULTS: Mean maternal cerebral Mg2+ levels were lower in women with preeclampsia (0.12 mM ± 0.02) compared to normal pregnant controls (0.14 mM ± 0.03) (P = 0.04). Nonpregnant and normal pregnant women did not differ in Mg2+ levels. Among women with preeclampsia, lower Mg2+ levels correlated with presence of visual disturbances (P = 0.04). Plasma levels of Mg2+ did not differ between preeclampsia and normal pregnancy.CONCLUSIONS: Women with preeclampsia have reduced cerebral Mg2+ levels, which could explain the potent antiseizure prophylactic properties of MgSO4. Within the preeclampsia group, women with visual disturbances have lower levels of Mg2+ than those without such symptoms.
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| 13. |
- Nelander, Maria, 1974-, et al.
(författare)
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Cerebral osmolytes and plasma osmolality in pregnancy and preeclampsia : a proton magnetic resonance spectroscopy study
- 2018
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Ingår i: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 31:7, s. 847-853
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cerebral complications contribute substantially to mortality in preeclampsia. Pregnancy calls for extensive maternal adaptations, some associated with increased propensity for seizures, but the pathophysiology behind the eclamptic seizures is not fully understood. Plasma osmolality and sodium levels are lowered in pregnancy. This could result in extrusion of cerebral organic osmolytes, including the excitatory neurotransmitter glutamate, but this remains to be determined. The hypothesis of this study was that cerebral levels of organic osmolytes are decreased during pregnancy, and that this decrease is even more pronounced in women with preeclampsia.Method: We used proton magnetic resonance spectroscopy to compare levels of cerebral organic osmolytes, in women with preeclampsia (n=30), normal pregnancy (n=32) and non-pregnant controls (n=16). Cerebral levels organic osmolytes were further correlated to plasma osmolality, and plasma levels of glutamate and sodium.Results: Compared to non-pregnant women, women with normal pregnancy and preeclampsia had lower levels of the cerebral osmolytes myo-inositol, choline and creatine (p=0.001 or less), and all these metabolites correlated with each other (p<0.05). Women with normal pregnancies and preeclampsia had similar levels of osmolytes, except for glutamate, which was significantly lower in preeclampsia. Cerebral and plasma glutamate levels were negatively correlated with each other (p<0.008), and cerebral myo-inositol, choline and creatine levels were all positively correlated with both plasma osmolality and sodium levels (p<0.05).Conclusion: Our results indicate that pregnancy is associated with extrusion of cerebral organic osmolytes. This includes the excitatory neurotransmitter glutamate, which may be involved in the pathophysiology of seizures in preeclampsia.
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| 14. |
- 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. ; 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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| 15. |
- 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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| 16. |
- 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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| 17. |
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| 18. |
- Sohlberg, Sara, 1977-, et al.
(författare)
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MRI estimated placental perfusion in fetal growth assessment
- 2015
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Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 46:6, s. 700-705
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveThis study aimed to evaluate placental perfusion fraction estimated by magnetic resonance imaging (MRI) in vivo as a marker of placental function.MethodsThe study population included 35 pregnant women, of whom 13 had preeclampsia, examined at gestational weeks 22 to 40. Each woman underwent, within a 24 hour period: a MRI diffusion-weighted sequence (from which we calculated the placental perfusion fraction); venous blood sampling; and an ultrasound examination including estimation of fetal weight, amniotic fluid index and Doppler velocity measurements. We compared the perfusion fraction in pregnancies with and without fetal growth restriction and estimated correlations between the perfusion fraction and ultrasound estimates and plasma markers with linear regression. The associations between the placental perfusion fraction and ultrasound estimates were modified by the presence of preeclampsia (p < 0.05) and therefore we included an interaction term between preeclampsia and the covariates in the models.ResultsThe median placental perfusion fraction in pregnancies with and without fetal growth restriction was 21% and 32%, respectively (p = 0.005). The correlations between the placental perfusion fraction and ultrasound estimates and plasma markers were highly significant (p-values 0.002 to 0.0001). The highest coefficient of determination (R2= 0.56) for placental perfusion fraction was found for a model including pulsatility index in ductus venosus, plasma level of sFlt1, estimated fetal weight and presence of preeclampsia.ConclusionThe placental perfusion fraction has potential to contribute to the clinical assessment in cases of placental insufficiency.
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| 19. |
- Tammela, T L, et al.
(författare)
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An Intraprostatic Modified Release Formulation of Antiandrogen 2-Hydroxyflutamide for Localized Prostate Cancer
- 2017
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 198:6, s. 1333-1339
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate tolerability, safety and antitumor effects of a novel intra-prostatic depot formulation of antiandrogen 2-hydroxyflutamide (2-HOF in NanoZolid(®)) in men with localized prostate cancer (PCa).MATERIALS AND METHODS: Two clinical trials, LPC-002 and LPC-003, were conducted on a total of 47 men. The formulation was injected transrectally into the prostate with ultrasound guidance. In LPC-002 the effects on prostate specific antigen (PSA) and prostate volume (PV) were measured over 6 months on 24 patients. In LPC-003, antitumor effects were evaluated with histopathology, magnetic resonance imaging (MRI) including spectroscopy (MRS) during 6 or 8 weeks on 23 patients. In both studies, testosterone and 2-HOF in plasma were measured, as well as quality-of-life parameters.RESULTS: In LPC-002 (mean dose 690 mg) a reduction in PSA and PV was observed. The nadir values for PSA and PV were on average 24.9 % and 14.0 % below baseline, respectively. When increasing the dose in LPC-003 (920 mg and 1740 mg), the average PSA dropped 16 % and 23 %, respectively, after 6 and 8 weeks. MRI/MRS showed morphological changes and a global drop in metabolite concentrations following treatment indicating an antitumor response. The injections did not result in hormone related side effects. In total, three serious adverse events were reported, all resolved by oral antibiotic treatment.CONCLUSIONS: The intraprostatic injections of 2-HOF depot formulations indicated anti-tumor effects and proved safe and tolerable. However, for better anti-cancer effects higher doses and better dose distribution are suggested.
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| 20. |
- 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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| 21. |
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| 22. |
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| 23. |
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| 24. |
- 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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| 29. |
- Weis, Jan, 1956-, et al.
(författare)
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Multiple breath-hold proton spectroscopy of human liver at 3T : Relaxation times and concentrations of glycogen, choline, and lipids
- 2018
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Ingår i: Journal of Magnetic Resonance Imaging. - : Wiley. - 1053-1807 .- 1522-2586. ; 47, s. 410-417
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Tidskriftsartikel (refereegranskat)abstract
- Purpose:To evaluate the feasibility of an expiration multiple breath-hold H-1-MRS technique to measure glycogen (Glycg), choline-containing compounds (CCC), and lipid relaxation times T-1, T-2, and their concentrations in normal human liver.Materials and Methods:Thirty healthy volunteers were recruited. Experiments were performed at 3T. Multiple expiration breath-hold single-voxel point-resolved spectroscopy (PRESS) technique was used for localization. Water-suppressed spectra were used for the estimation of Glycg, CCC, lipid methylene (CH2)(n) relaxation times and concentrations. Residual water lines were removed by the Hankel Lanczos singular value decomposition filter. After phase correction and frequency alignment, spectra were averaged and processed by LCModel. Summed signals of Glycg resonances H2H4', H3, and H5 between 3.6 and 4ppm were used to estimate their apparent relaxation times and concentration. Glycg, CCC, and lipid content were estimated from relaxation corrected spectral intensity ratios to unsuppressed water line.Results:Relaxation times were measured for liver Glycg (T-1, 892 +/- 126 msec; T-2, 134 msec), CCC (T-1, 842 +/- 75 msec; T-2, 505 msec), lipid (CH2)(n) (T-1, 402 +/- 19 msec; T-2, 52 +/- 3 msec), and water (T-1, 990 +/- 89 msec; T-2, 30 +/- 2 msec). Mean CCC and lipid concentrations of healthy liver were 7.8 +/- 1.3 mM and 15.8 +/- 23.6 mM, respectively. Glycg content was found lower in the morning (48 +/- 21 mM) compared to the afternoon (145 +/- 50 mM).Conclusion:Multiple breath-hold H-1-MRS together with dedicated postprocessing is a feasible technique for the quantification of liver Glycg, CCC, and lipid relaxation times and concentrations.
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| 30. |
- 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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| 31. |
- Weis, Jan, 1956-, et al.
(författare)
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Proton MR spectroscopy of human pancreas allografts
- 2019
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Ingår i: Magnetic Resonance Materials in Physics, Biology and Medicine. - : Springer Science and Business Media LLC. - 0968-5243 .- 1352-8661. ; 32:4, s. 511-517
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To estimate pancreas graft relaxation times and concentrations of total fat, and the intracellular lipids of non-adipose pancreatic cells (NAPC) using proton (1H) magnetic resonance spectroscopy (MRS) during cold preservation.MATERIALS AND METHODS: Grafts from 11 human donors were investigated. Each pancreas was perfused in situ with histidine-tryptophan-ketoglutarate (HTK) or with University of Wisconsin solution and placed into a transport container. Temperature of the grafts was maintained at 4 ± 2 °C during transport to our hospital and MR scanning. A 1.5 T clinical scanner was used for the measurements. Single-voxel PRESS spectra were acquired using transmit-receiver head coil.RESULTS: Relaxation times were measured for lipid (-CH2-)n (T1, 287 ± 60 ms; T2, 27 ± 4 ms), and tissue water (T1, 670 ± 69 ms; T2, 77 ± 17 ms). Average total fat, and intracellular lipids of NAPC concentrations were 79.2 ± 100.8 (range 2.4-304.4), and 2.9 ± 1.2 mmol/kg ww, respectively.CONCLUSION: We have shown that 1H-MRS is a useful tool for the estimation of pancreas graft lipid concentrations. Total pancreatic fat and especially content of intracellular lipids of NAPC are valuable measures for inspection of graft quality prior to transplantation or islet of Langerhans isolation.
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| 32. |
- Weis, Jan, 1956-, et al.
(författare)
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Quantification of metabolite concentrations in benign and malignant prostate tissues using 3D proton MR spectroscopic imaging
- 2017
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Ingår i: Journal of Magnetic Resonance Imaging. - : Wiley. - 1053-1807 .- 1522-2586. ; 45:4, s. 1232-1240
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To estimate concentrations of choline (Cho), spermine (Spm), and citrate (Cit) in prostate tissue using 3D proton magnetic resonance spectroscopic imaging (MRSI) with water as an internal concentration reference as well as to assess the relationships between the measured metabolites and also between the metabolites and apparent diffusion coefficient (ADC).MATERIALS AND METHODS: Forty-six prostate cancer patients were scanned at 3T. Spectra were acquired with the point-resolved spectroscopy (PRESS) localization technique. Single-voxel spectra of four healthy volunteers were used to estimate T1 relaxation time of Spm. Spm, Cho concentrations, and ADC values of benign prostate tissues were correlated with Cit content.RESULTS: The T1 value, 708 ± 132 msec, was estimated for Spm. Mean concentrations in the benign peripheral zone (PZ) were Cho, 4.5 ± 1 mM, Spm, 13.0 ± 4.4 mM, Cit, 64.4 ± 16.1 mM. Corresponding values in the benign central gland (CG) were Cho, 3.6 ± 1 mM, Spm, 13.3 ± 4.5 mM, Cit, 34.3 ± 12.9 mM. Concentrations of Cit and Spm were positively correlated in the benign PZ zone (r = 0.730) and CG (r = 0.664). Positive correlation was found between Cit and Cho in the benign CG (r = 0.705). Whereas Cit and ADC were positively correlated in the benign PZ (r = 0.673), only low correlation was found in CG (r = 0.265).CONCLUSION: We have shown that it is possible to perform water-referenced quantitative 3D MRSI of the prostate at the cost of a relatively short prolongation of the acquisition time. The individual metabolite concentrations provide additional information compared to the previously used metabolite-to-citrate ratios.
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| 33. |
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| 35. |
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| 36. |
- Weis, Jan, et al.
(författare)
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Two-dimensional spectroscopic imaging for pretreatment evaluation of prostate cancer : comparison with the step-section histology after radical prostatectomy
- 2009
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Ingår i: Magnetic Resonance Imaging. - : Elsevier BV. - 0730-725X .- 1873-5894. ; 27:1, s. 87-93
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To minimize user and vendor dependence of the spectrum processing of prostate spectra, to measure the ratio of choline (Cho) plus creatine (Cr) to citrate (Cit) in the prostate tissue of normal volunteers and cancer patients, and to compare the results with pathologic findings after radical prostatectomy. MATERIALS AND METHODS: Four healthy volunteers and 13 patients with prostate cancer were measured. Measurements were performed using two-dimensional magnetic resonance spectroscopic imaging (MRSI) and endorectal coil. A standard vendor's spectrum processing approach has been modified. An original feature of this methodology was the combination of vendor-optimized and user-independent spectrum preprocessing in the scanner and user-independent quantitation in the environment of an MRUI software package. (Cho+Cr)/Cit ratio was used for the classification of prostate tissue. Results were compared with histopathology after radical prostatectomy. RESULTS: Eight of 13 cancer patients were classified as suspicious or very suspicious for cancer at spectroscopy, three were ambiguous for cancer and two patients were evaluated as false negative. A considerable overlap of metabolite ratios at various Gleason score was found. CONCLUSION: The proposed spectrum processing has the potential to improve the accuracy and user independency of the (Cho+Cr)/Cit quantitation. This study confirmed the previous results that a considerable overlap of (Cho+Cr)/Cit ratios exists at various Gleason score levels.
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| 37. |
- 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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| 38. |
- 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
-
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 Í 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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