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Ahlström, Håkan
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Publications (10 of 193) Show all publications
von Below, C., Wassberg, C., Grzegorek, R., Kullberg, J., Gestblom, C., Sörensen, J., . . . Ahlström, H. (2018). MRI and 11C acetate PET/CT for prediction of regional lymph node metastasis in newly diagnosed prostate cancer. Radiology and Oncology, 52(1), 90-97
Open this publication in new window or tab >>MRI and 11C acetate PET/CT for prediction of regional lymph node metastasis in newly diagnosed prostate cancer
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2018 (English)In: Radiology and Oncology, ISSN 1318-2099, E-ISSN 1581-3207, Vol. 52, no 1, p. 90-97Article in journal (Refereed) Published
Abstract [en]

Background: C acetate PET/CT parameters in predicting regional lymph node (LN) metastasis of newly diagnosed prostate cancer (PCa).

Patients and methods: C acetate PET/CT (53 patients) before extended pelvic LN dissection. For each patient the visually most suspicious LN was assessed for mean apparent diffusion coefficient (ADCmean), maximal standardized uptake value (SUVmax), size and shape and the primary tumour for T stage on MRI and ADCmean and SUVmax in the index lesion. The variables were analysed in simple and multiple logistic regression analysis.

Results: All variables, except ADCmean and SUVmax of the primary tumor, were independent predictors of LN metastasis. In multiple logistic regression analysis the best model was ADCmean in combintion with MRI T-stage where both were independent predictors of LN metastasis, this combination had an AUC of 0.81 which was higher than the AUC of 0.65 for LN ADCmean alone and the AUC of 0.69 for MRI T-stage alone.

Conclusions: Several quantitative and qualitative imaging parameters are predictive of regional LN metastasis in PCa. The combination of ADCmean in lymph nodes and T-stage on MRI was the best model in multiple logistic regression with increased predictive value compared to lymph node ADCmean and T-stage on MRI alone.

Keyword
diffusion magnetic resonance imaging, lymph node excision, lymph nodes, positronemission tomography, prostatic neoplasm
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-346994 (URN)10.2478/raon-2018-0001 (DOI)29520210 (PubMedID)
Available from: 2018-03-23 Created: 2018-03-23 Last updated: 2018-04-12Bibliographically approved
Carlsson, P.-O., Espes, D., Sedigh, A., Rotem, A., Zimermann, B., Grinberg, H., . . . Korsgren, O. (2018). Transplantation of Macro-encapsulated Human Islets within the Bioartificial Pancreas β Air to Patients with Type 1 Diabetes Mellitus. American Journal of Transplantation
Open this publication in new window or tab >>Transplantation of Macro-encapsulated Human Islets within the Bioartificial Pancreas β Air to Patients with Type 1 Diabetes Mellitus
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2018 (English)In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143Article in journal (Refereed) Epub ahead of print
Abstract [en]

Macroencapsulation devices provide the dual possibility to immunoprotect transplanted cells while also being retrievable; the latter bearing importance for safety in future trials with stem-cell derived cells. However, macroencapsulation entails a problem with oxygen supply to the encapsulated cells. The βAir device solves this with an incorporated refillable oxygen tank. This phase 1 study evaluated the safety and efficacy of implanting the βAir device containing allogeneic human pancreatic islets to patients with type 1 diabetes. Four patients were transplanted with 1-2 βAir devices, each containing 155000-180000 IEQ (i.e. 1800-4600 IEQ per kg body weight), and monitored for 3-6 months, followed by the recovery of devices. Implantation of the βAir device was safe and successfully prevented immunization and rejection of the transplanted tissue. However, although beta cells survived in the device, only minute levels of circulating C-peptide were observed with no impact on metabolic control. Fibrotic tissue with immune cells was formed in capsule surroundings. Recovered devices displayed a blunted glucose-stimulated insulin response, and amyloid formation in the endocrine tissue. We conclude that the βAir device is safe and can support survival of allogeneic islets for several months, although the function of the transplanted cells was limited.

National Category
Endocrinology and Diabetes Surgery Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-337701 (URN)10.1111/ajt.14642 (DOI)29288549 (PubMedID)
Note

De två första författarna delar förstaförfattarskapet.

Available from: 2018-01-03 Created: 2018-01-03 Last updated: 2018-02-08Bibliographically approved
Johansson, E., Lubberink, M., Heurling, K., Eriksson, J. W., Skrtic, S., Ahlström, H. & Kullberg, J. (2018). Whole-Body Imaging of Tissue-specific Insulin Sensitivity and Body Composition by Using an Integrated PET/MR System: A Feasibility Study.. Radiology, 286(1), 271-278
Open this publication in new window or tab >>Whole-Body Imaging of Tissue-specific Insulin Sensitivity and Body Composition by Using an Integrated PET/MR System: A Feasibility Study.
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2018 (English)In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 286, no 1, p. 271-278Article in journal (Refereed) Published
Abstract [en]

Purpose

To develop, evaluate, and demonstrate the feasibility of a whole-body protocol for simultaneous assessment of tissue-specific insulin-mediated fluorine 18 (18F) fluorodeoxyglucose (FDG) influx rates, tissue depots, and whole-body insulin sensitivity (referred to as the M value).

Materials and Methods

An integrated positron emission tomography (PET)/magnetic resonance (MR) imaging system combined with hyperinsulinemic euglycemic clamp (HEC) was used. Dynamic whole-body PET imaging was used to determine the insulin-mediated 18F-FDG tissue influx rate (Ki) in the whole-body region by using the Patlak method. M value was determined with the HEC method at PET imaging. Tissue depots were quantified by using water-fat separated MR imaging and manual segmentations. Feasibility of the imaging protocol was demonstrated by using five healthy control participants and five patients with type 2 diabetes. Associations between M value and Ki were studied in multiple tissues by using the Pearson correlation.

Results

Positive correlations were found between M value and Ki in multiple tissues: the gluteus muscle (r = 0.875; P = .001), thigh muscle (r = 0.903; P , .001), calf muscle (r = 0.825; P = .003), and abdominal visceral adipose tissue (r = 0.820; P = .004). A negative correlation was found in the brain (r = 20.798; P = .006). The MR imaging–based method for quantification of tissue depots was feasible for determining adipose tissue volumes and fat fractions.

Conclusion

This PET/MR imaging protocol may be feasible for simultaneous assessment of tissue-specific insulin-mediated 18F-FDG influx rates, tissue depots, and M value.

National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-329272 (URN)10.1148/radiol.2017162949 (DOI)000422905200034 ()28846496 (PubMedID)
Funder
AstraZeneca
Available from: 2017-09-11 Created: 2017-09-11 Last updated: 2018-03-16Bibliographically approved
Carlbom, L., Espes, D., Lubberink, M., Martinell, M., Johansson, L., Ahlström, H., . . . Eriksson, O. (2017). [(11)C]5-Hydroxy-Tryptophan PET for Assessment of Islet Mass During Progression of Type 2 Diabetes. Diabetes, 66(5), 1286-1292
Open this publication in new window or tab >>[(11)C]5-Hydroxy-Tryptophan PET for Assessment of Islet Mass During Progression of Type 2 Diabetes
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2017 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 66, no 5, p. 1286-1292Article in journal (Refereed) Published
Abstract [en]

[(11)C]5-hydroxy-tryptophan ([(11)C]5-HTP) PET of the pancreas has been shown to be a surrogate imaging biomarker of pancreatic islet mass. The change in islet mass in different stages of type 2 diabetes (T2D) as measured by non-invasive imaging is currently unknown. Here, we describe a cross-sectional study where subjects at different stages of T2D development with expected stratification of pancreatic islet mass were examined in relation to non-diabetic individuals. The primary outcome was the [(11)C]5-HTP uptake and retention in pancreas, as a surrogate marker for the endogenous islet mass.We found that metabolic testing indicated a progressive loss of beta cell function, but that this was not mirrored by a decrease in [(11)C]5-HTP tracer accumulation in the pancreas. This provides evidence of retained islet mass despite decreased beta cell function. The results herein indicates that beta cell dedifferentiation, and not necessarily endocrine cell loss, constitute a major cause of beta cell failure in T2D.

National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-316831 (URN)10.2337/db16-1449 (DOI)000399799800022 ()28246291 (PubMedID)
Funder
Swedish Society for Medical Research (SSMF), K2015-54X-12219-19-4 K2013-64X-08268-26-3 K2013-55X-15043 921-2014-7054Novo NordiskSwedish Child Diabetes Foundation
Note

De 2 första författarna delar förstaförfattarskapet.

Available from: 2017-03-07 Created: 2017-03-07 Last updated: 2018-01-25Bibliographically approved
Strand, R., Malmberg, F., Johansson, L., Lind, L., Sundbom, M., Ahlström, H. & Kullberg, J. (2017). A concept for holistic whole body MRI data analysis, Imiomics. PLoS ONE, 12(2), Article ID e0169966.
Open this publication in new window or tab >>A concept for holistic whole body MRI data analysis, Imiomics
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 2, article id e0169966Article in journal (Refereed) Published
Abstract [en]

Purpose: To present and evaluate a whole-body image analysis concept, Imiomics (imaging omics) and an image registration method that enables Imiomics analyses by deforming all image data to a common coordinate system, so that the information in each voxel can be compared between persons or within a person over time and integrated with non-imaging data.

Methods: The presented image registration method utilizes relative elasticity constraints of different tissue obtained from whole-body water-fat MRI. The registration method is evaluated by inverse consistency and Dice coefficients and the Imiomics concept is evaluated by example analyses of importance for metabolic research using non-imaging parameters where we know what to expect. The example analyses include whole body imaging atlas creation, anomaly detection, and cross-sectional and longitudinal analysis.

Results: The image registration method evaluation on 128 subjects shows low inverse consistency errors and high Dice coefficients. Also, the statistical atlas with fat content intensity values shows low standard deviation values, indicating successful deformations to the common coordinate system. The example analyses show expected associations and correlations which agree with explicit measurements, and thereby illustrate the usefulness of the proposed Imiomics concept.

Conclusions: The registration method is well-suited for Imiomics analyses, which enable analyses of relationships to non-imaging data, e.g. clinical data, in new types of holistic targeted and untargeted big-data analysis.

National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Computerized Image Processing
Identifiers
urn:nbn:se:uu:diva-316830 (URN)10.1371/journal.pone.0169966 (DOI)000395934400002 ()28241015 (PubMedID)
Available from: 2017-02-27 Created: 2017-03-07 Last updated: 2017-11-29Bibliographically approved
Straniero, S., Rosqvist, F., Edholm, D., Ahlström, H., Kullberg, J., Sundbom, M., . . . Rudling, M. (2017). Acute caloric restriction counteracts hepatic bile acid and cholesterol deficiency in morbid obesity. Journal of Internal Medicine, 281(5), 507-517
Open this publication in new window or tab >>Acute caloric restriction counteracts hepatic bile acid and cholesterol deficiency in morbid obesity
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2017 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 281, no 5, p. 507-517Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Bile acid (BA) synthesis is regulated by BA signalling in the liver and by fibroblast growth factor 19 (FGF19), synthesized and released from the intestine. In morbid obesity, faecal excretion and hepatic synthesis of BAs and cholesterol are strongly induced and caloric restriction reduces their faecal excretion considerably. We hypothesized that the high intestinal food mass in morbidly obese subjects promotes faecal excretion of BAs and cholesterol, thereby creating a shortage of both BAs and cholesterol in the liver.

METHODS: Ten morbidly obese women (BMI 42 ± 2.6 kg m(-2) ) were monitored on days 0, 3, 7, 14 and 28 after beginning a low-calorie diet (800-1100 kcal day(-1) ). Serum was collected and liver size and fat content determined. Synthesis of BAs and cholesterol was evaluated from serum markers, and the serum levels of lipoproteins, BAs, proprotein convertase subtilisin/kexin type 9 (PCSK9), insulin, glucose and FGF19 were monitored. Fifty-four nonobese women (BMI <25 kg m(-2) ) served as controls.

RESULTS: At baseline, synthesis of both BAs and cholesterol and serum levels of BAs and PCSK9 were elevated in the obese group compared to controls. Already after 3 days on a low-calorie diet, BA and cholesterol synthesis and serum BA and PCSK9 levels normalized, whereas LDL cholesterol increased. FGF19 and triglyceride levels were unchanged, and liver volume was reduced by 10%.

CONCLUSIONS: The results suggest that hepatic BAs and cholesterol are deficient in morbid obesity. Caloric restriction rapidly counteracts these deficiencies, normalizing BA and cholesterol synthesis and circulating PCSK9 levels, indicating that overproduction of cholesterol in enlarged peripheral tissues cannot explain this phenotype. We propose that excessive food intake promotes faecal loss of BAs and cholesterol contributing to their hepatic deficiencies.

Keyword
bile acid synthesis, cholesterol synthesis, proprotein convertase subtilisin/kexin type 9
National Category
Nutrition and Dietetics
Identifiers
urn:nbn:se:uu:diva-316832 (URN)10.1111/joim.12599 (DOI)000399779700009 ()28261926 (PubMedID)
Funder
Swedish Research Council, 2015-02781Swedish Heart Lung Foundation, 20160491Stockholm County Council, ALF 20150447Swedish Diabetes Association
Available from: 2017-03-07 Created: 2017-03-07 Last updated: 2017-05-29Bibliographically approved
von Below, C., Wassberg, C., Norberg, M., Tolf, A., Kullberg, J., Ladjevardi, S., . . . Ahlström, H. (2017). Additional value of magnetic resonance-targeted biopsies to standard transrectal ultrasound-guided biopsies for detection of clinically significant prostate cancer. Scandinavian journal of urology, 51(2), 107-113
Open this publication in new window or tab >>Additional value of magnetic resonance-targeted biopsies to standard transrectal ultrasound-guided biopsies for detection of clinically significant prostate cancer
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2017 (English)In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 51, no 2, p. 107-113Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: The aim of this study was to evaluate the additional value of magnetic resonance imaging-targeted biopsy (MRI-TB) to standard transrectal ultrasound-guided biopsy (SB) for detection of clinically significant prostate cancer (PCa). An additional aim was to compare the biopsy results to MRI evaluation using a Likert scale.

MATERIALS AND METHODS: Patients with newly diagnosed localized PCa (n = 53) by clinical routine SB were prospectively included. The majority of the patients were scheduled for curative therapy before enrollment. The patients underwent multiparametric MRI (mpMRI) at 3 T using an endorectal coil followed by two MRI-TBs, using ultrasound with cognitive fusion. All included patients underwent MRI-TB, even those who had low to very low suspicion of significant PCa on mpMRI. The detection rate of significant cancer on SB versus SB + MRI-TB was compared in the 53 included patients and with whole-mounted histopathology as reference in 34 cases. Comparison of the biopsy results to MRI evaluation and interreader agreement calculation of five-point Likert score evaluation were performed.

RESULTS: In total, 32 significant (Gleason ≥7) PCa were detected by SB, while SB + MRI-TB detected an additional five significant PCa. MRI-TB alone detected 20 and missed 17 significant PCa. Ten of the significant PCa cases missed by MRI-TB had a Likert score of 3 or lower. Interreader agreement using the Likert scale was high, with a kappa value of 0.77 (95% confidence interval 0.63-0.92, p < 0.0001).

CONCLUSION: Detection of significant PCa increased by adding MRI-TB to SB. This may not be of enough clinical value to justify the use of targeted biopsies in this patient group.

Keyword
Magnetic resonance imaging, prostatic neoplasm, targeted biopsies, transrectal ultrasound-guided biopsy
National Category
Urology and Nephrology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-325563 (URN)10.1080/21681805.2017.1281346 (DOI)000403629400003 ()28635568 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2017-06-26 Created: 2017-06-26 Last updated: 2017-10-19Bibliographically 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.

Keyword
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
Kullberg, J., Hedström, A., Brandberg, J., Strand, R., Johansson, L. E., Bergström, G. & Ahlström, H. (2017). Automated analysis of liver fat, muscle and adipose tissue distribution from CT suitable for large-scale studies.. Scientific Reports, 7, Article ID 10425.
Open this publication in new window or tab >>Automated analysis of liver fat, muscle and adipose tissue distribution from CT suitable for large-scale studies.
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 10425Article in journal (Refereed) Published
Abstract [en]

Computed Tomography (CT) allows detailed studies of body composition and its association with metabolic and cardiovascular disease. The purpose of this work was to develop and validate automated and manual image processing techniques for detailed and efficient analysis of body composition from CT data. The study comprised 107 subjects examined in the Swedish CArdioPulmonary BioImage Study (SCAPIS) using a 3-slice CT protocol covering liver, abdomen, and thighs. Algorithms were developed for automated assessment of liver attenuation, visceral (VAT) and subcutaneous (SAT) abdominal adipose tissue, thigh muscles, subcutaneous, subfascial (SFAT) and intermuscular adipose tissue. These were validated using manual reference measurements. SFAT was studied in selected subjects were the fascia lata could be visually identified (approx. 5%). In addition, precision of manual measurements of intra- (IPAT) and retroperitoneal adipose tissue (RPAT) and deep- and superficial SAT was evaluated using repeated measurements. Automated measurements correlated strongly to manual reference measurements. The SFAT depot showed the weakest correlation (r = 0.744). Automated VAT and SAT measurements were slightly, but significantly overestimated (≤4.6%, p ≤ 0.001). Manual segmentation of abdominal sub-depots showed high repeatability (CV ≤ 8.1%, r ≥ 0.930). We conclude that the low dose CT-scanning and automated analysis makes the setup suitable for large-scale studies.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-329273 (URN)10.1038/s41598-017-08925-8 (DOI)000409309300013 ()28874743 (PubMedID)
Funder
Swedish Research Council, 2012-2330Swedish Heart Lung FoundationVINNOVA
Available from: 2017-09-11 Created: 2017-09-11 Last updated: 2017-12-06Bibliographically approved
Lundström, E., Strand, R., Forslund, A., Bergsten, P., Weghuber, D., Ahlström, H. & Kullberg, J. (2017). Automated segmentation of human cervical-supraclavicular adipose tissue in magnetic resonance images. Scientific Reports, 7, Article ID 3064.
Open this publication in new window or tab >>Automated segmentation of human cervical-supraclavicular adipose tissue in magnetic resonance images
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 3064Article in journal (Refereed) Published
Abstract [en]

Human brown adipose tissue (BAT), with a major site in the cervical-supraclavicular depot, is a promising anti-obesity target. This work presents an automated method for segmenting cervical-supraclavicular adipose tissue for enabling time-efficient and objective measurements in large cohort research studies of BAT. Fat fraction (FF) and R2* maps were reconstructed from water-fat magnetic resonance imaging (MRI) of 25 subjects. A multi-atlas approach, based on atlases from nine subjects, was chosen as automated segmentation strategy. A semi-automated reference method was used to validate the automated method in the remaining subjects. Automated segmentations were obtained from a pipeline of preprocessing, affine registration, elastic registration and postprocessing. The automated method was validated with respect to segmentation overlap (Dice similarity coefficient, Dice) and estimations of FF, R2* and segmented volume. Bias in measurement results was also evaluated. Segmentation overlaps of Dice = 0.93 +/- 0.03 (mean +/- standard deviation) and correlation coefficients of r > 0.99 (P < 0.0001) in FF, R2* and volume estimates, between the methods, were observed. Dice and BMI were positively correlated (r = 0.54, P = 0.03) but no other significant bias was obtained (P >= 0.07). The automated method compared well with the reference method and can therefore be suitable for time-efficient and objective measurements in large cohort research studies of BAT.

National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Computerized Image Processing
Identifiers
urn:nbn:se:uu:diva-323968 (URN)10.1038/s41598-017-01586-7 (DOI)000402865000003 ()28596551 (PubMedID)
Funder
Swedish Research CouncilEU, FP7, Seventh Framework Programme, 279153
Available from: 2017-06-08 Created: 2017-06-12 Last updated: 2017-09-19Bibliographically approved
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