| 1. |
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| 2. |
- Bernhardsson, Magnus, et al.
(author)
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Shining dead bone-cause for cautious interpretation of [F-18]NaF PET scans
- 2018
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In: Acta Orthopaedica. - : Taylor & Francis. - 1745-3674 .- 1745-3682. ; 89:1, s. 124-127
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Journal article (peer-reviewed)abstract
- Background and purpose — [18F]Fluoride ([18F]NaF) PET scan is frequently used for estimation of bone healing rate and extent in cases of bone allografting and fracture healing. Some authors claim that [18F]NaF uptake is a measure of osteoblastic activity, calcium metabolism, or bone turnover. Based on the known affinity of fluoride to hydroxyapatite, we challenged this view.Methods — 10 male rats received crushed, frozen allogeneic cortical bone fragments in a pouch in the abdominal wall on the right side, and hydroxyapatite granules on left side. [18F]NaF was injected intravenously after 7 days. 60 minutes later, the rats were killed and [18F]NaF uptake was visualized in a PET/CT scanner. Specimens were retrieved for micro CT and histology.Results — MicroCT and histology showed no signs of new bone at the implant sites. Still, the implants showed a very high [18F]NaF uptake, on a par with the most actively growing and remodeling sites around the knee joint.Interpretation — [18F]NaF binds with high affinity to dead bone and calcium phosphate materials. Hence, an [18F]NaF PET/CT scan does not allow for sound conclusions about new bone ingrowth into bone allograft, healing activity in long bone shaft fractures with necrotic fragments, or remodeling around calcium phosphate coated prostheses
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| 3. |
- Carina, Stenman, 1964-
(author)
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Standardized ultrasonography with cine-loop documentation : diagnostic variability in liver and kidney examinations
- 2015
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Doctoral thesis (other academic/artistic)abstract
- Background: Ultrasound examination of the abdomen is often a first choice at radiology departments due to the lack of ionizing radiation. For diagnostic accuracy and economic benefits there has been a need for new routines in this area that incorporate the benefits of an radiographer or sonographer performing a multitude of ultrasound examinations following strictly standardized examination protocols and documentation forms made by cine-loops that will give the radiologist access to all relevant information needed for an accurate postexamination diagnosis.Aim: The overall objective of this thesis was to evaluate the diagnostic variability in examinations of the kidneys and liver that use a standardized ultrasound method along with video documentation of the entire examination and off-line review by radiologists. More specifically, we wanted to compare the agreement between readers and between operators.Design and method: This thesis is based on four quantitative studies using standardized protocols for kidney, liver and gallbladder examinations. In paper I, including 64 patients, and paper IV, including 98 patients, the patients were prospectively enrolled and the examinations were retrospectively reviewed. The patients in papers I and IV were examined by one radiographer (sonographer) and one radiologist during the same session. In paper I, findings using the standardized ultrasound method were compared with traditional bedside assessments by a radiologist. In paper IV, the patients were examined using only the standardized method. In paper II, including 98 patients, and in paper III, including 115 patients, the patients were examined by one sonographer using the standardized method and the examinations were reviewed by two or three radiologists.Results: In paper I, no significant systematic differences were found between the findings using the standardized method and the traditional bedside assessment.Paper II showed good intra- and inter-observer agreement between three experienced radiologists when reviewing examinations conducted using the standardized method.In paper III we verified good inter-observer agreement between two radiologists reviewing ultrasound examinations using the standardized technique in patients who had undergone surgery for colorectal cancer. Intravenous contrast was used and the injection of contrast medium increased the visibility of liver lesions.In paper IV, we observed that using a standardized cine-loop technique, there was a slightly better inter-operator agreement than inter-reader agreement.Conclusion: The satisfactory agreement shown in all four studies suggests that the new workflow method using standardized ultrasound examinations and stored cine-loops, performed by a radiographer or sonographer and analyzed off-line by a radiologist, is a promising technique. The results are less affected when a radiologist examiner is replaced by a radiographer or sonographer than when the reviewer is replaced by a different radiologist.
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| 4. |
- Eriksson Bylund, Nina, et al.
(author)
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3D Wiener filtering to reduce reverberations in ultrasound image sequences
- 2003
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In: Image Analysis. - : Springer. - 3540406018 - 9783540406013 ; , s. 579-586
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Book chapter (peer-reviewed)abstract
- One of the most frequently occuring artifacts in ultrasound imaging is reverberations. These are multiple reflection echoes that result in ghost echoes in the ultrasound image. A method for reducing these unwanted artifacts using a three-dimensional (3D) Wiener filter is presented. The Wiener filter is a global filter and produces an estimate of the uncorrupted signal by minimizing the mean square error between the estimate and the uncorrupted signal in a statistical sense. The procedure works as follows: In a graphic interface the operator is displayed an image sequence. The operator marks two areas in one of the images, one area which contains a typical reverberation artifact, and one area free from artifact. Using these areas to produce noise and signal estimates, a Wiener filter is created and applied to the sequence. The 3D Wiener filters display excellent selection capabilities, and the developed method significantly reduces the magnitude of the reverberation artifact in the tested sequences.
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| 5. |
- Eriksson-Bylund, Nina, et al.
(author)
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Reverberation Reduction Using 3D Wiener Filtering
- 2003
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Conference paper (other academic/artistic)abstract
- One of the most common artifacts in ultrasound imaging is reverberations. These are multiple reflection echoes that register as coming from a deeper region than the depth of the interface that are causing them, and result in ghost echoes in the ultrasound image. A method to reduce these unwanted artifacts using a three dimensional (2D + time) Wiener filter has been developed. Two sequences of iq-data, the least processed signal possible to retrieve from the ultrasound system (Vingmed System Five), have been used to test the method: One sequence on a tissue-mimicking agar gel phantom in which bars of glass simulating ribs give rise to reverberations, and one sequence on an open-chest pig with a strong reverberation from a water-filled rubber glove used as a medium between the heart and the transducer. The procedure works as follows: In a graphic interface the operator is shown the image sequence. In one of the frames two areas must be marked out; One area which contains a typical reverberation artifact, and one area which will represent an artifact free signal. After creating the three dimensional Wiener filter post-processing of the sequence is performed. The developed method significantly reduced the magnitude of the reverberation artifact in the tested sequences.
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| 6. |
- 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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| 7. |
- Good, Elin, et al.
(author)
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18Fluorodeoxyglucose uptake in relation to fat fraction and R2*in atherosclerotic plaques, using PET/MRI : a pilot study
- 2021
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
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Journal article (peer-reviewed)abstract
- Inflammation inside Atherosclerotic plaques represents a major pathophysiological process driving plaques towards rupture. Pre-clinical studies suggest a relationship between lipid rich necrotic core, intraplaque hemorrhage and inflammation, not previously explored in patients. Therefore, we designed a pilot study to investigate the feasibility of assessing the relationship between these plaque features in a quantitative manner using PET/MRI. In 12 patients with high-grade carotid stenosis the extent of lipid rich necrotic core and intraplaque hemorrhage was quantified from fat and R2* maps acquired with a previously validated 4-point Dixon MRI sequence in a stand-alone MRI. PET/MRI was used to measure 18F-FDG uptake. T1-weighted images from both scanners were used for registration of the quantitative Dixon data with the PET images. The plaques were heterogenous with respect to their volumes and composition. The mean values for the group were as follows: fat fraction (FF) 0.17% (± 0.07), R2* 47.6 s−1 (± 10.9) and target-to-blood pool ratio (TBR) 1.49 (± 0.48). At group level the correlation between TBR and FFmean was − 0.406, p 0.19 and for TBR and R2*mean 0.259, p 0.42. The lack of correlation persisted when analysed on a patient-by-patient basis but the study was not powered to draw definitive conclusions. We show the feasibility of analysing the quantitative relationship between lipid rich necrotic cores, intraplaque haemorrhage and plaque inflammation. The 18F-FDG uptake for most patients was low. This may reflect the biological complexity of the plaques and technical aspects inherent to 18F-FDG measurements.
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| 8. |
- Kvikliene, Adriana, et al.
(author)
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Modelling of nonlinear effects and the response of ultrasound contrast micro bubbles : simulation and experiment
- 2004
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In: Ultrasonics. - : Elsevier BV. - 0041-624X .- 1874-9968. ; 42:01-Sep, s. 301-307
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Journal article (peer-reviewed)abstract
- The propagation of diagnostic ultrasonic imaging pulses in tissue and their interaction with contrast micro bubbles is a very complex physical process, which we assumed to be separable into three stages: pulse propagation in tissue, the interaction of the pulse with the contrast bubble, and the propagation of the scattered echo. The model driven approach is used to gain better knowledge of the complex processes involved. A simplified way of field simulation is chosen due to the complexity of the task and the necessity to estimate comparative contributions of each component of the process. Simulations are targeted at myocardial perfusion estimation. A modified method for spatial superposition of attenuated waves enables simulations of low intensity pulse pressure fields from weakly focused transducers in a nonlinear, attenuating, and liquid-like biological medium. These assumptions enable the use of quasi-linear calculations of the acoustic field. The simulations of acoustic bubble response are carried out with the Rayleigh-Plesset equation with the addition of radiation damping. Theoretical simulations with synthesised and experimentally sampled pulses show that the interaction of the excitation pulses with the contrast bubbles is the main cause of nonlinear scattering, and a 2-3 dB increase of second harmonic amplitude depends on nonlinear distortions of the incident pulse. (C) 2004 Elsevier B.V. All rights reserved.
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| 9. |
- 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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| 10. |
- Matic, Natasa, et al.
(author)
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In vitro measurement of glucose uptake after radiation and cetuximab treatment in head and neck cancer cell lines using 18F-FDG, gamma spectrometry and PET/CT
- 2019
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In: Oncology Letters. - : SPANDIDOS PUBL LTD. - 1792-1074 .- 1792-1082. ; 18:5, s. 5155-5162
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Journal article (peer-reviewed)abstract
- The standard treatment for head and neck squamous cell carcinoma (HNSCC) is radiotherapy, often in combination with chemotherapy or surgery. However, a novel monoclonal antibody, cetuximab (Erbitux (R)), has also been approved for patient therapy. The aim of present study was to develop an in vitro method for the measurement of 18F-fluoro-2deoxy-D-glucose (FDG) to determine if cellular 18F-FDG uptake is associated with response to radiotherapy or cetuximab treatment. In the current study, HNSCC cell lines were treated with radiation or with cetuximab. Next, the uptake of 18F-FDG was measured using a gamma spectrometer (GS). Thereafter, uptake after radiation was measured first with GS and then compared with positron emission tomography (PET)/computed tomography (CT) imaging. Furthermore, the mRNA expression of glucose transporter 1 (GLUT1) was measured following cetuximab treatment via reverse transcription-quantitative PCR. A study protocol was developed to measure the cellular uptake of 18F-FDG via gamma-ray spectrometry and comparable results were obtained with those of clinical PET/CT. The results revealed a decrease in 18F-FDG after radiation and cetuximab treatment. The uptake of 18F-FDG following cetuximab treatment was significantly lower in the cetuximab-sensitive cell line UT-SCC-14 compared with the cetuximab-resistant cell lines UT-SCC-2 and UT-SCC-45. Furthermore, after treatment with cetuximab for 24 and 48 h, a significant increase in GLUT1 expression was detected in the sensitive cell line compared with the two resistant cell lines. In conclusion, a novel yet reliable method for the measurement of intracellular 18F-FDG via GS has been developed, and our results indicate that 18F-FDG uptake is associated with radiation and cetuximab response in HNSCC.
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