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- Etminani, Kobra, 1984-, et al.
(author)
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A 3D deep learning model to predict the diagnosis of dementia with Lewy bodies, Alzheimers disease, and mild cognitive impairment using brain 18F-FDG PET
- 2022
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In: European Journal of Nuclear Medicine and Molecular Imaging. - New York : Springer. - 1619-7070 .- 1619-7089. ; 49, s. 563-584
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Journal article (peer-reviewed)abstract
- Purpose The purpose of this study is to develop and validate a 3D deep learning model that predicts the final clinical diagnosis of Alzheimers disease (AD), dementia with Lewy bodies (DLB), mild cognitive impairment due to Alzheimers disease (MCI-AD), and cognitively normal (CN) using fluorine 18 fluorodeoxyglucose PET (18F-FDG PET) and compare models performance to that of multiple expert nuclear medicine physicians readers. Materials and methods Retrospective 18F-FDG PET scans for AD, MCI-AD, and CN were collected from Alzheimers disease neuroimaging initiative (556 patients from 2005 to 2020), and CN and DLB cases were from European DLB Consortium (201 patients from 2005 to 2018). The introduced 3D convolutional neural network was trained using 90% of the data and externally tested using 10% as well as comparison to human readers on the same independent test set. The models performance was analyzed with sensitivity, specificity, precision, F1 score, receiver operating characteristic (ROC). The regional metabolic changes driving classification were visualized using uniform manifold approximation and projection (UMAP) and network attention. Results The proposed model achieved area under the ROC curve of 96.2% (95% confidence interval: 90.6-100) on predicting the final diagnosis of DLB in the independent test set, 96.4% (92.7-100) in AD, 71.4% (51.6-91.2) in MCI-AD, and 94.7% (90-99.5) in CN, which in ROC space outperformed human readers performance. The network attention depicted the posterior cingulate cortex is important for each neurodegenerative disease, and the UMAP visualization of the extracted features by the proposed model demonstrates the reality of development of the given disorders. Conclusion Using only 18F-FDG PET of the brain, a 3D deep learning model could predict the final diagnosis of the most common neurodegenerative disorders which achieved a competitive performance compared to the human readers as well as their consensus.
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- Matić, Nataša, 1977-
(author)
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Biomarkers in the tumor microenvironment with impact on treatment response and survival in head and neck cancer
- 2022
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Doctoral thesis (other academic/artistic)abstract
- Head and neck squamous cell cancer (HNSCC) is the sixth most common cancer type worldwide and disease detects at a locally advanced stage in approximately 60% of all patients with HNSCC. Despite the advances in both diagnosis and treatment of cancer, therapy failure with local recurrence and second primary tumors as consequences is still a huge problem. Furthermore, HNSCC is heterogeneous disease and treatment response differs largely within this patient’s group. Owing to such heterogeneity, the individually designed treatment approach, based on biomarkers predicting treatment response is needed. The personalized treatment strategy is a new and promising form of cancer therapy to improve effectiveness of anti-cancer treatment and reduce suffering in patients diagnosed with HNSCC.The main aim of this thesis was to search for new predictive biomarkers with potential to foresee treatment response in HNSCC patients by investigating components and properties of the tumor microenvironment, such as metabolism, hypoxia and cancer-associated fibroblasts (CAF).In paper I we developed an in vitro method for the measurement of intracellular glucose (18F FDG) uptake with gamma spectrometry (GS). Quantity of glucose uptake was associated with treatment (radiation or cetuximab) response, where the radiosensitive cell line and the most cetuximab-sensitive cell lines showed a significant decrease of glucose uptake after treatment. The results were compared with those of a clinical PET/CT scanner and the results in glucose uptake between radiated cells and controls were similar in both methods. Furthermore, we investigated GLUT1 mRNA expression in cell lines after cetuximab treatment and our analysis showed a significant increase of GLUT1 mRNA expression.In paper II, we found a negative impact of hypoxia on radiotherapy response in HNSCC cells and enhanced expression of epithelial–mesenchymal transition (EMT)- and cancer stem cells (CSC)-associated genes during culturing cells in hypoxic conditions. With cDNA microarrays analysis we identified a number of hypoxia regulated genes that were involved in multiple biological functions as well as support growth and proliferation of cancer cells. Furthermore, with use of siRNA silencing, we investigated a possible impact of a panel of hypoxia-responsive genes (HIF-1α, CDH2, CA9, SERPINE1, AREG and EREG) on radiotherapy treatment. Nevertheless, downregulation of these hypoxia regulated genes did not affect the sensitivity to radiotherapy of the investigated HNSCC cell lines.In the following study (paper III) we continued to investigate the most hypoxia-dysregulated genes from previous study (CA9, CASP14, LOX, GLUT3, SERPINE1, AREG, EREG, CCNB1 and KIF14), and their impact on the survival of HNSCC patients treated with radiotherapy. Patients with high KIF14 mRNA expression showed significantly longer overall survival (OS) compared with patients with low KIF14 mRNA expression. Moreover, HNSCC patients with high mRNA expression of KIF14 and low mRNA expression of CA9 (hypoxia marker) showed better OS compared with those with the opposite mRNA expression.In paper IV, we investigated the influence of cancer-associated fibroblasts (CAFs) on tumor cell gene expression profile. Cells were cultured in 2D and 3D models where HNSCC cells and CAFs derived from the same tumor were co-cultured. The microarray analysis revealed a higher number of CAF-regulated genes in tumor cells grown in spheroids compared to tumor cells grown in 2D. Next, the expression pattern of most changed CAF-regulated genes (MMP1, MMP9, POSTN, GREM1, FMOD, COL1A2, GREM1, IVL) was analyzed in normal oral tissue and in pretreatment biopsies from HNSCC patients treated with radiotherapy showing differences in gene expression between HNSCC tumor tissue and normal oral tissue. High mRNA expression of MMP9 and FMOD were found to be significantly associated with better overall survival (OS) in patients treated with radiotherapy.Taken together, we developed a reliable in vitro method for the measurement of intracellular glucose uptake with gamma spectrometry and glucose uptake was associated with treatment response. Furthermore, we found that hypoxia has a negative impact on radiotherapy in HNSCC cells and we identified a panel of hypoxia-dysregulated genes involved in the multiple biological functions in cancer cells, however downregulation of single hypoxia-regulated genes did not affect response to radiotherapy. Further analysis indicated KIF14 mRNA as potential predictor of radiotherapy response but more studies with a larger patient cohort are required. Beside hypoxia, CAFs have an important role in cancer progression. The gene expression profile in HNSCC cell lines was found to be dysregulated by CAF-derived signals in vitro. Additionally, CAF-regulated genes, MMP9 and FMOD are potential candidates as biomarkers of OS in HNSCC patients treated with radiotherapy, however more studies must be undertaken to investigate our hypothesis.
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- Norén, Bengt, 1955-, et al.
(author)
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Absolute quantification of human liver metabolite concentrations by localized in vivo 31P NMR spectroscopy in diffuse liver disease
- 2005
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In: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 15:1, s. 148-157
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Journal article (peer-reviewed)abstract
- Phosphorus-31 NMR spectroscopy using slice selection (DRESS) was used to investigate the absolute concentrations of metabolites in the human liver. Absolute concentrations provide more specific biochemical information compared to spectrum integral ratios. Nine patients with histopathologically proven diffuse liver disease and 12 healthy individuals were examined in a 1.5-T MR scanner (GE Signa LX Echospeed plus). The metabolite concentration quantification procedures included: (1) determination of optimal depth for the in vivo measurements, (2) mapping the detection coil characteristics, (3) calculation of selected slice and liver volume ratios using simple segmentation procedures and (4) spectral analysis in the time domain. The patients had significantly lower concentrations of phosphodiesters (PDE), 6.3±3.9 mM, and ATP-β, 3.6±1.1 mM, (P<0.05) compared with the control group (10.0±4.2 mM and 4.2±0.3 mM, respectively). The concentrations of phosphomonoesters (PME) were higher in the patient group, although this was not significant. Constructing an anabolic charge (AC) based on absolute concentrations, [PME]/([PME] + [PDE]), the patients had a significantly larger AC than the control subjects, 0.29 vs. 0.16 (P<0.005). Absolute concentration measurements of phosphorus metabolites in the liver are feasible using a slice selective sequence, and the technique demonstrates significant differences between patients and healthy subjects.
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- Ressner, Marcus, 1967-, et al.
(author)
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Effects of ultrasound contrast agents on Doppler tissue velocity estimation
- 2006
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In: Journal of the American Society of Echocardiography. - : Elsevier BV. - 0894-7317 .- 1097-6795. ; 19:2, s. 154-164
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Journal article (peer-reviewed)abstract
- The combination of Doppler tissue imaging and myocardial contrast echocardiography has the potential to provide information about motion and perfusion of the myocardium in a single examination. The purpose of this study was to establish how the presence of ultrasound contrast agent (UCA) affects measurements of Doppler tissue velocities in vivo and in vitro. We performed echocardiography in 12 patients with ischemic heart disease before and immediately after a slow intravenous infusion of the UCA Optison, using color Doppler tissue imaging to examine the effect of contrast agents in vivo. The myocardial peak systolic velocities and their integrals were analyzed in digitally stored cineloops before and after contrast administration. To distinguish between methodologic and physiologic factors affecting the measurement of tissue velocity in vitro, experiments with a rotating disk and a flow cone phantom were also carried out for the 3 contrast agents: Optison, Sonovue, and Sonazoid. in vivo results show that the values for peak systolic velocity increased by about 10% during contrast infusion, from mean 5.2 +/- 1.8 to 5.7 +/- 2.3 cm/s (P = .02, 95% confidence interval 2%-16%). The increase in myocardial peak systolic velocities was verified in experimental models in which the UCA increased the estimated mean velocity in the order of 5% to 20% for the motion interval of 5 to 7 cm/s, corresponding to the myocardial velocities studied in vivo. The response was similar for all 3 contrast agents and was not affected by moderate variations in concentration of the agent. We have shown that the presence UCA will affect Doppler tissue measurements in vivo and in vitro. The observed bias is presumed to be an effect of harmonic signal contribution from rupturing contrast agent microbubbles and does not indicate biologic or physiologic effects.
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| 9. |
- Ressner, Marcus, 1967-, et al.
(author)
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Ultrasound contrast for perfusion studies
- 2005
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In: Nordic Baltic Conference Biomedical Engineering and Medical Physics,2005. - Umeå : IFMBE. ; , s. 107-
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Conference paper (peer-reviewed)
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