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Eckerbom, P., Hansell, P., Cox, E., Buchanan, C., Weis, J., Palm, F., . . . Liss, P. (2019). Multiparametric assessment of renal physiology in healthy volunteers using noninvasive magnetic resonance imaging. American Journal of Physiology - Renal Physiology, 316(4), F693-F702
Open this publication in new window or tab >>Multiparametric assessment of renal physiology in healthy volunteers using noninvasive magnetic resonance imaging
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2019 (English)In: American Journal of Physiology - Renal Physiology, ISSN 1931-857X, E-ISSN 1522-1466, Vol. 316, no 4, p. F693-F702Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
ASL, BOLD, Diffusion, Kidney, MRI
National Category
Radiology, Nuclear Medicine and Medical Imaging Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-374891 (URN)10.1152/ajprenal.00486.2018 (DOI)000463879600010 ()30648907 (PubMedID)
Funder
Swedish Diabetes AssociationSwedish Child Diabetes FoundationSwedish Research CouncilErnfors Foundation
Available from: 2019-01-24 Created: 2019-01-24 Last updated: 2019-05-03Bibliographically approved
Espes, D., Manell, E., Rydén, A., Carlbom, L., Weis, J., Jensen-Waern, M., . . . Eriksson, O. (2019). Pancreatic perfusion and its response to glucose as measured by simultaneous PET/MRI. Acta Diabetologica, 56(10), 1113-1120
Open this publication in new window or tab >>Pancreatic perfusion and its response to glucose as measured by simultaneous PET/MRI
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2019 (English)In: Acta Diabetologica, ISSN 0940-5429, E-ISSN 1432-5233, Vol. 56, no 10, p. 1113-1120Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Springer, 2019
Keywords
Diabetes, Hybrid scanner, PET/MRI scanner, Pancreas perfusion
National Category
Endocrinology and Diabetes Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-383433 (URN)10.1007/s00592-019-01353-2 (DOI)000486160600003 ()31028528 (PubMedID)
Funder
Ernfors FoundationGöran Gustafsson Foundation for promotion of scientific research at Uppala University and Royal Institute of TechnologySwedish Diabetes AssociationSwedish Child Diabetes FoundationEXODIAB - Excellence of Diabetes Research in SwedenScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
Available from: 2019-05-14 Created: 2019-05-14 Last updated: 2019-10-31Bibliographically approved
Weis, J., Ahlström, H. & Korsgren, O. (2019). Proton MR spectroscopy of human pancreas allografts. Magnetic Resonance Materials in Physics, Biology and Medicine, 32(4), 511-517
Open this publication in new window or tab >>Proton MR spectroscopy of human pancreas allografts
2019 (English)In: Magnetic Resonance Materials in Physics, Biology and Medicine, ISSN 0968-5243, E-ISSN 1352-8661, Vol. 32, no 4, p. 511-517Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
1H-MRS, Intracellular fat, Pancreas graft, Relaxation times, Total fat
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-382935 (URN)10.1007/s10334-019-00740-8 (DOI)000476510700009 ()30937576 (PubMedID)
Funder
Swedish Research Council, VR K2013-64X-08268-26-3Swedish Research Council, 921-2014-7054Swedish Research Council, K2015-54X-12219-19-4Ernfors FoundationSwedish Child Diabetes FoundationSwedish Diabetes AssociationEXODIAB - Excellence of Diabetes Research in Sweden
Available from: 2019-05-07 Created: 2019-05-07 Last updated: 2019-09-20Bibliographically approved
Eriksson, J., Roy, T., Sawadjoon, S., Bachmann, K., Sköld, C., Larhed, M., . . . Odell, L. R. (2019). 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. Nuclear Medicine and Biology, 71, 1-10
Open this publication in new window or tab >>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
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2019 (English)In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 71, p. 1-10Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Organic Chemistry Medicinal Chemistry
Identifiers
urn:nbn:se:uu:diva-381559 (URN)10.1016/j.nucmedbio.2019.04.002 (DOI)000475837000001 ()
Funder
Swedish Research Council, 2018-05133Knut and Alice Wallenberg FoundationSwedish Child Diabetes FoundationGöran Gustafsson Foundation for Research in Natural Sciences and Medicine
Available from: 2019-04-11 Created: 2019-04-11 Last updated: 2019-09-13Bibliographically approved
Nelander, M., Hannsberger, D., Sundström Poromaa, I., Bergman, L., Weis, J., Åkerud, H., . . . Wikström, A.-K. (2018). Assessment of cerebral perfusion and edema in preeclampsia with intravoxel incoherent motion MRI.. Acta Obstetricia et Gynecologica Scandinavica, 97(10), 1212-1218
Open this publication in new window or tab >>Assessment of cerebral perfusion and edema in preeclampsia with intravoxel incoherent motion MRI.
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2018 (English)In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 97, no 10, p. 1212-1218Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: Cerebral complications are the main reasons for morbidity and mortality in preeclampsia and eclampsia. As yet, we do not know whether the pathophysiology entails hypo- or hyperperfusion of the brain, or how and when edema emerges, due to the difficulty of examining the cerebral circulation.

MATERIAL AND METHODS: We have used a non-invasive diffusion weighted-magnetic resonance imaging 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 5 different regions. These points were chosen to represent blood supply areas of both the carotid and vertebrobasilar arteries, and to include both white and gray matter.

RESULTS: Except 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 than in either normal pregnancy (P = .01 and P = .03, respectively) or non-pregnant women (both P = .02). No differences in edema were detected between study groups.

CONCLUSION: The cerebral perfusion measures were comparable between the study groups, except for a portion of the basal ganglia where hypoperfusion was detected in preeclampsia but not in normal pregnancy or non-pregnant women.

Keywords
cerebral circulation, eclampsia, edema, intravoxel incoherent motion, magnetic resonance imaging, perfusion, preeclampsia
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-357423 (URN)10.1111/aogs.13383 (DOI)000444070900010 ()29786833 (PubMedID)
Funder
Swedish Research Council, 2014-3561
Available from: 2018-08-16 Created: 2018-08-16 Last updated: 2018-11-14Bibliographically approved
Nelander, M., Wikström, A.-K., Weis, J., Bergman, L., Larsson, A., Sundström Poromaa, I. & Wikström, J. (2018). Cerebral osmolytes and plasma osmolality in pregnancy and preeclampsia: a proton magnetic resonance spectroscopy study. American Journal of Hypertension, 31(7), 847-853
Open this publication in new window or tab >>Cerebral osmolytes and plasma osmolality in pregnancy and preeclampsia: a proton magnetic resonance spectroscopy study
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2018 (English)In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 31, no 7, p. 847-853Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
Preeclampsia, eclampsia, proton magnetic resonance spectroscopy, cerebral osmolytes, glutamate
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
urn:nbn:se:uu:diva-341642 (URN)10.1093/ajh/hpy019 (DOI)000435458800015 ()29415199 (PubMedID)
Funder
Swedish Research Council, 2014-3561
Available from: 2018-02-12 Created: 2018-02-12 Last updated: 2018-08-29Bibliographically approved
Weis, J., Kullberg, J. & Ahlström, H. (2018). Multiple breath-hold proton spectroscopy of human liver at 3T: Relaxation times and concentrations of glycogen, choline, and lipids. Journal of Magnetic Resonance Imaging, 47, 410-417
Open this publication in new window or tab >>Multiple breath-hold proton spectroscopy of human liver at 3T: Relaxation times and concentrations of glycogen, choline, and lipids
2018 (English)In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 47, p. 410-417Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
choline, glycogen, liver, magnetic resonance spectroscopy, quantification, relaxation times
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-322145 (URN)10.1002/jmri.25734 (DOI)000419991000011 ()28419608 (PubMedID)
Available from: 2017-05-16 Created: 2017-05-16 Last updated: 2018-05-09Bibliographically approved
Tammela, T. L., Häggman, M., Ladjevardi, S., Taari, K., Isotalo, T., Lennernäs, H., . . . Ahlström, H. (2017). An Intraprostatic Modified Release Formulation of Antiandrogen 2-Hydroxyflutamide for Localized Prostate Cancer. Journal of Urology, 198(6), 1333-1339
Open this publication in new window or tab >>An Intraprostatic Modified Release Formulation of Antiandrogen 2-Hydroxyflutamide for Localized Prostate Cancer
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2017 (English)In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 198, no 6, p. 1333-1339Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
NanoZolid, Prostate cancer, bioresorbable, calcium sulphate, local treatment, modified-release
National Category
Medical and Health Sciences Urology and Nephrology Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-327250 (URN)10.1016/j.juro.2017.07.072 (DOI)000417150900023 ()28736321 (PubMedID)
Available from: 2017-08-07 Created: 2017-08-07 Last updated: 2018-03-06Bibliographically approved
Nelander, M., Weis, J., Bergman, L., Larsson, A., Wikström, A.-K. & Wikström, J. (2017). Cerebral Magnesium Levels in Preeclampsia; A Phosphorus Magnetic Resonance Spectroscopy Study. American Journal of Hypertension, 30(7), 667-672
Open this publication in new window or tab >>Cerebral Magnesium Levels in Preeclampsia; A Phosphorus Magnetic Resonance Spectroscopy Study
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2017 (English)In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 30, no 7, p. 667-672Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
31P-magnetic resonance spectroscopy, blood pressure, eclampsia, hypertension, magnesium, magnetic resonance, preeclampsia.
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-319608 (URN)10.1093/ajh/hpx022 (DOI)000407115100009 ()28338765 (PubMedID)
Funder
Swedish Research Council, 2014-3561
Available from: 2017-04-06 Created: 2017-04-06 Last updated: 2018-02-22Bibliographically approved
Carlbom, L., Weis, J., Johansson, L., Korsgren, O. & Ahlström, H. (2017). Pre-transplantation ³¹P-magnetic resonance spectroscopy for quality assessment of human pancreatic grafts: A feasibility study. Magnetic Resonance Imaging, 39, 98-102
Open this publication in new window or tab >>Pre-transplantation ³¹P-magnetic resonance spectroscopy for quality assessment of human pancreatic grafts: A feasibility study
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2017 (English)In: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 39, p. 98-102Article in journal (Refereed) Published
Abstract [en]

Objective: To investigate the feasibility of using (31)P-MRS for objective non-invasive quality assessment of human pancreas grafts prior to transplantation or islet isolation.

Materials and methods: Pancreata from 5 human donors, 3 males and 2 females, aged 49-78years, with body mass index (BMI) 22-31kg/m(2), were included. Pancreata were perfused with histidine-tryptophan-ketoglutarate solution during procurement and stored in hypothermic condition (4°C) for 21-44h. During the period of hypothermic storage repeated spectra were obtained for each graft by (31)P-MRS (1.5Tesla) to measure the cold ischemia time (CIT) dependent changes of the phosphorous metabolites adenosine triphosphate (ATP), phosphomonoesters (PME), phosphodiesters (PDE) and inorganic phosphate (Pi), in the grafts. Graft temperature was measured immediately before and after MR-examination. Reference spectrum for non-viable tissue was obtained after graft exposure to room temperature.

Results: PME/Pi, PDE/Pi and ATP/Pi spectral intensities ratios decreased with increasing CIT, reflecting the decreased viability of the grafts. PME/Pi ratio was the most discriminatory variable at prolonged CIT. (31)P-MRS could be performed without significantly increasing graft temperature.

Conclusions: (31)P-MRS may provide quantitative parameters for evaluating graft viability ex vivo, and is a promising tool for objective non-invasive assessment of the quality of human pancreas grafts prior to transplantation or islet isolation.

Keywords
P-31-MR spectroscopy, Organ viability, Pancreas transplantation, Cold ischemia, ATP, PME
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-315894 (URN)10.1016/j.mri.2017.02.004 (DOI)000401051200012 ()28188872 (PubMedID)
Funder
Swedish Research Council, K2013-64X-08268-26-3Swedish Research Council, 921-2014-7054Swedish Research Council, K2015-54X-12219-19-4Swedish Child Diabetes FoundationSwedish Diabetes AssociationEXODIAB - Excellence of Diabetes Research in Sweden
Note

Title in WOS: Pre-transplantation P-31-magnetic resonance spectroscopy for quality assessment of human pancreatic grafts - A feasibility study

Available from: 2017-02-22 Created: 2017-02-22 Last updated: 2018-01-25Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-2448-9245

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