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- Jansson, John-Olov, 1954, et al.
(författare)
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Body weight homeostat that regulates fat mass independently of leptin in rats and mice.
- 2018
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 115:2, s. 427-432
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Tidskriftsartikel (refereegranskat)abstract
- Subjects spending much time sitting have increased risk of obesity but the mechanism for the antiobesity effect of standing is unknown. We hypothesized that there is a homeostatic regulation of body weight. We demonstrate that increased loading of rodents, achieved using capsules with different weights implanted in the abdomen or s.c. on the back, reversibly decreases the biological body weight via reduced food intake. Importantly, loading relieves diet-induced obesity and improves glucose tolerance. The identified homeostat for body weight regulates body fat mass independently of fat-derived leptin, revealing two independent negative feedback systems for fat mass regulation. It is known that osteocytes can sense changes in bone strain. In this study, the body weight-reducing effect of increased loading was lost in mice depleted of osteocytes. We propose that increased body weight activates a sensor dependent on osteocytes of the weight-bearing bones. This induces an afferent signal, which reduces body weight. These findings demonstrate a leptin-independent body weight homeostat ("gravitostat") that regulates fat mass.
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| 3. |
- Dalmo, Johanna, et al.
(författare)
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Priming increases the anti-tumor effect and therapeutic window of 177Lu-octreotate in nude mice bearing human small intestine neuroendocrine tumor GOT1.
- 2017
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Ingår i: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: 177Lu-[DOTA0, Tyr3]-octreotate (177Lu-octreotate) is used for treatment of patients with somatostatin receptor (SSTR) expressing neuroendocrine tumors. However, complete tumor remission is rarely seen, and optimization of treatment protocols is needed. In vitro studies have shown that irradiation can up-regulate the expression of SSTR1, 2 and 5, and increase 177Lu-octreotate uptake. The aim of the present study was to examine the anti-tumor effect of a 177Lu-octreotate priming dose followed 24 h later by a second injection of 177Lu-octreotate compared to a single administration of 177Lu-octreotate, performed on the human small intestine neuroendocrine tumor cell line, GOT1, transplanted to nude mice. RESULTS: Priming resulted in a 1.9 times higher mean absorbed dose to the tumor tissue per administered activity, together with a reduced mean absorbed dose for kidneys. Priming gave the best overall anti-tumor effects. Magnetic resonance imaging showed no statistically significant difference in tumor response between treatment with and without priming. Gene expression analysis demonstrated effects on cell cycle regulation. Biological processes associated with apoptotic cell death were highly affected in the biodistribution and dosimetry study, via differential regulation of, e.g., APOE, BAX, CDKN1A, and GADD45A. CONCLUSIONS: Priming had the best overall anti-tumor effects and also resulted in an increased therapeutic window. Results indicate that potential biomarkers for tumor regrowth may be found in the p53 or JNK signaling pathways. Priming administration is an interesting optimization strategy for 177Lu-octreotate therapy of neuroendocrine tumors, and further studies should be performed to determine the mechanisms responsible for the reported effects.
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| 4. |
- Gustafsson, Oscar, 1989, et al.
(författare)
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An assessment of Bayesian IVIM model fitting
- 2016
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Ingår i: ISMRM 2016 Annual Meeting. 7-13 May, Singapore. - : International Society for Magnetic Resonance in Medicine.
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Konferensbidrag (refereegranskat)abstract
- Bayesian model fitting has been proposed as an alternative to the commonly used least squares fitting of the IVIM model. In this work we used Monte Carlo simulations to study the convergence of a Markov Chain Monte Carlo implementation of Bayesian model fitting and compared the resulting model parameters to two least squares model fitting methods. We saw that the convergence of the Bayesian model fitting procedure was affected by noise and compartment sizes. Bayesian model fitting was beneficial for the diffusion coefficient and the perfusion fraction, especially at low SNR
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| 6. |
- Gustafsson, Oscar, 1989, et al.
(författare)
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Impact of prior distributions and central tendency measures on Bayesian intravoxel incoherent motion model fitting
- 2018
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Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 0740-3194 .- 1522-2594. ; 79:3, s. 1674-1683
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 International Society for Magnetic Resonance in Medicine.Purpose: Bayesian model fitting has been proposed as a robust alternative for intravoxel incoherent motion (IVIM) model-fitting parameter estimation. However, consensus regarding choice of prior distribution and posterior distribution central tendency measure is needed. The aim of this study was to compare the quality of IVIM parameter estimates produced by different prior distributions and central tendency measures, and to gain knowledge about the effect of these choices. Methods: Three prior distributions (uniform, reciprocal, and lognormal) and two measures of central tendency (mean and mode) found in the literature were studied using simulations and in vivo data from a tumor mouse model. Results: Simulations showed that the uniform and lognormal priors were superior to the reciprocal prior, especially for the parameters D and f and clinically relevant SNR levels. The choice of central tendency measure had less effect on the results, but had some effects on estimation bias. Results based on simulations and in vivo data agreed well, indicating high validity of the simulations. Conclusions: Choice of prior distribution and central tendency measure affects the results of Bayesian IVIM parameter estimates. This must be considered when comparing results from different studies. The best overall quality of IVIM parameter estimates was obtained using the lognormal prior.
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| 8. |
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IVIM reveals increased blood perfusion of liver metastases after oral intake of Salovum®
- 2015
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Ingår i: Magnetic Resonance Materials in Physics, Biology and Medicine. - : Springer Science and Business Media LLC. - 0968-5243 .- 1352-8661.
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Proceedings (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
- Introduction Elevated interstitial fluid pressure (IFP) of tumours impairs perfusion, which hinders anti-cancer drugs and oxygen to reach tumour cells1-3. AF-16, a 16 amino acid long sequence from the amino terminal end of the endogenous protein Antisecretory Factor (AF), supresses IFP in animal models of solid tumours4, and could improve drug delivery to tumour cells. Salovum®, a spray-dried egg yolk powder with high content of antisecretory peptides, should be tested on humans, but requires non-invasive tumour IFP/perfusion assessment methods. The IntraVoxel Incoherent Motion (IVIM) model applied to multi-b DWI enables measurement of tissue diffusion (D), pseudo-diffusion (D*) and voxel volume fraction of actively perfused capillaries (f) 5. The aim of this study was to investigate if f could be used to monitor changes induced by Salovum® in colorectal liver metastases in vivo Subjects and Methods Previously untreated patients (n=6) with colorectal liver metastases were imaged before, and 24h after intake of Salovum®, using IVIM-MRI (3T Philips, 16‐channel receiver; Single-shot, SE‐EPI (breath-hold); FOV covering liver, 3x3x5mm3 voxels; TR/TE/NSA/SENSE=1900ms/50ms/2/2; 11 b‐values (0-600); acquisition~10 min. MATLAB-based images processing comprised 1) Inter-scan image registration (volume preserving free-form deformation6); 2) Voxelwise fitting of D and A [eq.2] to S(b200-600) (for b>200, [eq.1] reduces to [eq.2], assuming D<2cm) on DWI (b=600), transfer of ROIs to corresponding f-maps for calculation of median ROI f before and after Salovum® intake and 4) Mann-Whitney U-test for statistical significance (α-level=0.05). Results Liver and metastases were well visualised on DWIs and f-maps Median f in metastatic tissue increased after intake of Salovum® in 5/6 patients, but decreased in one patient (Fig.2) (p<0.0001). Discussion/Conclusion The increased perfusion fraction on day 2 may offer a “window of opportunity” for improved transport of drugs to tumour cells. The increase in f was small, and perhaps not clinically significant, suggesting that additional time points after Salovum® intake and dose escalation be investigated, as well as intra-tumour effect heterogeneity. The proposed IVIM approach is a promising, non-invasive method for studying Salovum® induced changes in liver metastases in vivo. Further optimisation and fractionation studies should be conducted, and IVIM derived parameters should be compared to other techniques for perfusion or IFP measurements. References 1Rofstad,E.K.,et al.,Neoplasia. 2009;11(11):1243-51. 2Milosevic,M.F.,et al.,1999;43(5):1111-23. 3Wiig, H.,et al.,1982;42(2):159-64. 4Al-Olama, M.et al., 2011;50(7):1098-104. 5Le Bihan, D., et al., 1988;168(2):497-505. 6Rueckert, D., et al., 1999;18(8):712-21.
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| 10. |
- Jalnefjord, Oscar, 1989, et al.
(författare)
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Comparison of methods for estimation of the intravoxel incoherent motion (IVIM) diffusion coefficient (D) and perfusion fraction (f)
- 2018
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Ingår i: Magnetic Resonance Materials in Physics, Biology and Medicine. - : Springer Science and Business Media LLC. - 0968-5243 .- 1352-8661. ; 31:6, s. 715-723
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Intravoxel incoherent motion (IVIM) shows great potential in many applications, e.g., tumor tissue characterization. To reduce image-quality demands, various IVIM analysis approaches restricted to the diffusion coefficient (D) and the perfusion fraction (f) are increasingly being employed. In this work, the impact of estimation approach for D and f is studied. Materials and methods: Four approaches for estimating D and f were studied: segmented IVIM fitting, least-squares fitting of a simplified IVIM model (sIVIM), and Bayesian fitting of the sIVIM model using marginal posterior modes or posterior means. The estimation approaches were evaluated in terms of bias and variability as well as ability for differentiation between tumor and healthy liver tissue using simulated and in vivo data. Results: All estimation approaches had similar variability and ability for differentiation and negligible bias, except for the Bayesian posterior mean of f, which was substantially biased. Combined use of D and f improved tumor-to-liver tissue differentiation compared with using D or f separately. Discussion: The similar performance between estimation approaches renders the segmented one preferable due to lower numerical complexity and shorter computational time. Superior tissue differentiation when combining D and f suggests complementary biologically relevant information.
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