| 1. |
- Blystad, Ida, et al.
(författare)
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Quantitative MRI for Analysis of Active Multiple Sclerosis Lesions without Gadolinium-Based Contrast Agent
- 2016
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Ingår i: American Journal of Neuroradiology. - : American Society of Neuroradiology (ASNR). - 0195-6108 .- 1936-959X. ; 37:1, s. 94-100
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Contrast-enhancing MS lesions are important markers of active inflammation in the diagnostic work-up of MS and in disease monitoring with MR imaging. Because intravenous contrast agents involve an expense and a potential risk of adverse events, it would be desirable to identify active lesions without using a contrast agent. The purpose of this study was to evaluate whether pre-contrast injection tissue-relaxation rates and proton density of MS lesions, by using a new quantitative MR imaging sequence, can identify active lesions.MATERIALS AND METHODS: Forty-four patients with a clinical suspicion of MS were studied. MR imaging with a standard clinical MS protocol and a quantitative MR imaging sequence was performed at inclusion (baseline) and after 1 year. ROIs were placed in MS lesions, classified as nonenhancing or enhancing. Longitudinal and transverse relaxation rates, as well as proton density were obtained from the quantitative MR imaging sequence. Statistical analyses of ROI values were performed by using a mixed linear model, logistic regression, and receiver operating characteristic analysis.RESULTS: Enhancing lesions had a significantly (P < .001) higher mean longitudinal relaxation rate (1.22 ± 0.36 versus 0.89 ± 0.24), a higher mean transverse relaxation rate (9.8 ± 2.6 versus 7.4 ± 1.9), and a lower mean proton density (77 ± 11.2 versus 90 ± 8.4) than nonenhancing lesions. An area under the receiver operating characteristic curve value of 0.832 was obtained.CONCLUSIONS: Contrast-enhancing MS lesions often have proton density and relaxation times that differ from those in nonenhancing lesions, with lower proton density and shorter relaxation times in enhancing lesions compared with nonenhancing lesions.
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| 2. |
- Plattén, Michael, et al.
(författare)
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MRI-Based Manual versus Automated Corpus Callosum Volumetric Measurements in Multiple Sclerosis
- 2019
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Ingår i: Journal of Neuroimaging. - : John Wiley & Sons. - 1051-2284 .- 1552-6569.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSECorpus callosum atrophy is a neurodegenerative biomarker in multiple sclerosis (MS). Manual delineations are gold standard but subjective and labor intensive. Novel automated methods are promising but require validation. We aimed to compare the robustness of manual versus automatic corpus callosum segmentations based on FreeSurfer.METHODSNine MS patients (6 females, age 38 ± 13 years, disease duration 7.3 ± 5.2 years) were scanned twice with repositioning using 3‐dimensional T1‐weighted magnetic resonance imaging on three scanners (two 1.5 T and one 3.0 T), that is, six scans/patient, on the same day. Normalized corpus callosum areas were measured independently by a junior doctor and neuroradiologist. The cross‐sectional and longitudinal streams of FreeSurfer were used to segment the corpus callosum volume.RESULTSManual measurements had high intrarater (junior doctor .96 and neuroradiologist .96) and interrater agreement (.94), by intraclass correlation coefficient (P < .001). The coefficient of variation was lowest for longitudinal FreeSurfer (.96% within scanners; 2.0% between scanners) compared to cross‐sectional FreeSurfer (3.7%, P = .001; 3.8%, P = .058) and the neuroradiologist (2.3%, P = .005; 2.4%, P = .33). Longitudinal FreeSurfer was also more accurate than cross‐sectional (Dice scores 83.9 ± 7.5% vs. 78.9 ± 8.4%, P < .01 relative to manual segmentations). The corpus callosum measures correlated with physical disability (longitudinal FreeSurfer r = –.36, P < .01; neuroradiologist r = –.32, P < .01) and cognitive disability (longitudinal FreeSurfer r = .68, P < .001; neuroradiologist r = .64, P < .001).CONCLUSIONSFreeSurfer's longitudinal stream provides corpus callosum measures with better repeatability than current manual methods and with similar clinical correlations. However, due to some limitations in accuracy, caution is warranted when using FreeSurfer with clinical data.
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| 3. |
- Uhlén, Mathias, et al.
(författare)
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The human secretome
- 2019
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Ingår i: Science Signaling. - : American Association for the Advancement of Science (AAAS). - 1945-0877 .- 1937-9145. ; 12:609
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Tidskriftsartikel (refereegranskat)abstract
- The proteins secreted by human cells (collectively referred to as the secretome) are important not only for the basic understanding of human biology but also for the identification of potential targets for future diagnostics and therapies. Here, we present a comprehensive analysis of proteins predicted to be secreted in human cells, which provides information about their final localization in the human body, including the proteins actively secreted to peripheral blood. The analysis suggests that a large number of the proteins of the secretome are not secreted out of the cell, but instead are retained intracellularly, whereas another large group of proteins were identified that are predicted to be retained locally at the tissue of expression and not secreted into the blood. Proteins detected in the human blood by mass spectrometry-based proteomics and antibody-based immuno-assays are also presented with estimates of their concentrations in the blood. The results are presented in an updated version 19 of the Human Protein Atlas in which each gene encoding a secretome protein is annotated to provide an open-access knowledge resource of the human secretome, including body-wide expression data, spatial localization data down to the single-cell and subcellular levels, and data about the presence of proteins that are detectable in the blood.
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| 4. |
- Buist, Mirka, et al.
(författare)
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Novel Wearable Device for Mindful Sensorimotor Training: Integrating Motor Decoding and Somatosensory Stimulation for Neurorehabilitation
- 2024
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Ingår i: IEEE Transactions on Neural Systems and Rehabilitation Engineering. - : Institute of Electrical and Electronics Engineers (IEEE). - 1558-0210 .- 1534-4320. ; 32, s. 1515-1523
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Tidskriftsartikel (refereegranskat)abstract
- Sensorimotor impairment is a prevalent condition requiring effective rehabilitation strategies. This study introduces a novel wearable device for Mindful Sensorimotor Training (MiSMT) designed for sensory and motor rehabilitation. Our MiSMT device combines motor training using myoelectric pattern recognition along sensory training using two tactile displays. This device offers a comprehensive solution, integrating electromyography and haptic feedback, lacking in existing devices. The device features eight electromyography channels, a rechargeable battery, and wireless Bluetooth or Wi-Fi connectivity for seamless communication with a computer or mobile device. Its flexible material allows for adaptability to various body parts, ensuring ease of use in diverse patients. The two tactile displays, with 16 electromagnetic actuators each, provide touch and vibration sensations up to 250 Hz. In this proof-of-concept study, we show improved two-point discrimination after 5 training sessions in participants with intact limbs (p=0.047). We also demonstrated successful acquisition, processing, and decoding of myoelectric signals in offline and online evaluations. In conclusion, the MiSMT device presents a promising tool for sensorimotor rehabilitation by combining motor execution and sensory training benefits. Further studies are required to assess its effectiveness in individuals with sensorimotor impairments. Integrating mindful sensory and motor training with innovative technology can enhance rehabilitation outcomes and improve the quality of life for those with sensorimotor impairments.
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| 5. |
- Mardinoglu, Adil, et al.
(författare)
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The Potential Use of Metabolic Cofactors in Treatment of NAFLD
- 2019
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Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 11:7
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Forskningsöversikt (refereegranskat)abstract
- Non-alcoholic fatty liver disease (NAFLD) is caused by the imbalance between lipid deposition and lipid removal from the liver, and its global prevalence continues to increase dramatically. NAFLD encompasses a spectrum of pathological conditions including simple steatosis and non-alcoholic steatohepatitis (NASH), which can progress to cirrhosis and liver cancer. Even though there is a multi-disciplinary effort for development of a treatment strategy for NAFLD, there is not an approved effective medication available. Single or combined metabolic cofactors can be supplemented to boost the metabolic processes altered in NAFLD. Here, we review the dosage and usage of metabolic cofactors including l-carnitine, Nicotinamide riboside (NR), l-serine, and N-acetyl-l-cysteine (NAC) in human clinical studies to improve the altered biological functions associated with different human diseases. We also discuss the potential use of these substances in treatment of NAFLD and other metabolic diseases including neurodegenerative and cardiovascular diseases of which pathogenesis is linked to mitochondrial dysfunction.
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| 6. |
- Lindberg, Frida, 1982-, et al.
(författare)
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Assessment of intramuscular activation patterns using ultrasound M-mode strain
- 2013
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Ingår i: Journal of Electromyography & Kinesiology. - : Elsevier BV. - 1050-6411 .- 1873-5711. ; 23:4, s. 879-885
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Tidskriftsartikel (refereegranskat)abstract
- The intramuscular activation pattern can be connected to the motor unit recruitment strategy of force generation and fatigue resistance. Electromyography has earlier been used in several studies to quantify the spatial inhomogeneity of the muscle activation. We applied ultrasound M-mode strain to study the activation pattern through the tissue deformation. Correlation values of the strain at different force levels were used to quantify the spatial changes in the activation. The assessment was done including the biceps brachii muscle of 8 healthy subjects performing isometric elbow flexion contractions ranging from 0% to 80% of maximum voluntary contraction. The obtained results were repeatable and demonstrated consistent changes of the correlation values during force regulation, in agreement with previously presented EMG-results. Both intra-subject and inter-subject activation patterns of strain were considered along and transverse the fiber direction. The results suggest that ultrasound M-mode strain can be used as a complementary method to study intramuscular activation patterns with high spatial resolution.(C) 2013 Elsevier Ltd. All rights reserved.
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| 7. |
- Elcadi, Guilherme H., 1966-, et al.
(författare)
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Shoulder and forearm oxygenation and myoelectric activity in patients with work related muscle pain and healthy subjects
- 2013
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Ingår i: European Journal of Applied Physiology. - New York : Springer. - 1439-6319 .- 1439-6327. ; 113:5, s. 1103-1115
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Tidskriftsartikel (refereegranskat)abstract
- We tested hypotheses of (i) reduced oxygen usage, oxygen recovery, blood flow and oxygen consumption; and (ii) increased muscle activity for patients diagnosed with work related muscle pain in comparison to healthy controls. Oxygenation was measured with near infrared spectroscopy (NIRS), and muscle activity with EMG for the extensor carpi radialis (ECR) and trapezius descendens (TD) muscles. Eighteen patients with diffuse neck-shoulder-arm pain and seventeen controls (matched in age and sex) were equipped with NIRS and EMG probes. After determining an individual’s maximum voluntary contraction (MVC) force, short term (20 sec) isometric contractions for the ECR and TD of 10%, 30%, 50% and 70% MVC generated ∆StO2% and StO2% recovery (Rslope) from NIRS, and RMS%max from EMG signals. In addition, upper arm venous (VO) and arterial (AO) occlusions generated slopes of total hemoglobin (HbTslope) and deoxyhemoglobin (HHbslope) for the resting ECR as surrogates of blood flow and oxygen consumption, respectively. Mixed Model analyses, t-tests, and Mann-Whitney test were used to assess differences between groups. There was no significant difference in MVC between groups for either muscle. Also, ∆StO2%, Rslope for either muscle, and ECR-HbTslope were not different between groups, thus our hypotheses of reduced oxygen use, recovery, and blood flow for patients were not confirmed. However, patients had a significantly lower ECR-HHbslope confirming our hypothesis of reduced consumption. Further, there was no difference in RMS%max during contractions meaning that the hypothesis of increased activity for patients was not confirmed. When taking into account the number of NIRS variables studied, differences we found between our patient group and healthy controls (i.e. in forearm oxygen consumption and shoulder oxygen saturation level) may be considered modest. Overall our findings may have been impacted by the fact that our patients and controls were similar in muscle strength, which is in contrast to previous studies.
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| 8. |
- Faresjö, Rebecca, et al.
(författare)
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Transferrin Receptor Binding BBB-Shuttle Facilitates Brain Delivery of Anti-Aβ-Affibodies
- 2022
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Ingår i: Pharmaceutical research. - : Springer Nature. - 0724-8741 .- 1573-904X. ; 39:7, s. 1509-1521
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Tidskriftsartikel (refereegranskat)abstract
- Affibodies targeting amyloid-beta (Aβ) could potentially be used as therapeutic and diagnostic agents in Alzheimer’s disease (AD). Affibodies display suitable characteristics for imaging applications such as high stability and a short biological half-life. The aim of this study was to explore brain delivery and retention of Aβ protofibril-targeted affibodies in wild-type (WT) and AD transgenic mice and to evaluate their potential as imaging agents. Two affibodies, Z5 and Z1, were fused with the blood–brain barrier (BBB) shuttle single-chain variable fragment scFv8D3. In vitro binding of 125I-labeled affibodies with and without scFv8D3 was evaluated by ELISA and autoradiography. Brain uptake and retention of the affibodies at 2 h and 24 h post injection was studied ex vivo in WT and transgenic (tg-Swe and tg-ArcSwe) mice. At 2 h post injection, [125I]I-Z5 and [125I]I-Z1 displayed brain concentrations of 0.37 ± 0.09% and 0.46 ± 0.08% ID/g brain, respectively. [125I]I-scFv8D3-Z5 and [125I]I-scFv8D3-Z1 showed increased brain concentrations of 0.53 ± 0.16% and 1.20 ± 0.35%ID/g brain. At 24 h post injection, brain retention of [125I]I-Z1 and [125I]I-Z5 was low, while [125I]I-scFv8D3-Z1 and [125I]I-scFv8D3-Z5 showed moderate brain retention, with a tendency towards higher retention of [125I]I-scFv8D3-Z5 in AD transgenic mice. Nuclear track emulsion autoradiography showed greater parenchymal distribution of [125I]I-scFv8D3-Z5 and [125I]I-scFv8D3-Z1 compared with the affibodies without scFv8D3, but could not confirm specific affibody accumulation around Aβ deposits. Affibody-scFv8D3 fusions displayed increased brain and parenchymal delivery compared with the non-fused affibodies. However, fast brain washout and a suboptimal balance between Aβ and mTfR1 affinity resulted in low intrabrain retention around Aβ deposits.
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| 9. |
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| 10. |
- Abdellah, Tebani, et al.
(författare)
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Annotation of pituitary neuroendocrine tumors with genome-wide expression analysis
- 2021
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Ingår i: Acta neuropathologica communications. - : BioMed Central (BMC). - 2051-5960. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Pituitary neuroendocrine tumors (PitNETs) are common, generally benign tumors with complex clinical characteristics related to hormone hypersecretion and/or growing sellar tumor mass. PitNETs can be classified based on the expression pattern of anterior pituitary hormones and three main transcriptions factors (TF), SF1, PIT1 and TPIT that regulate differentiation of adenohypophysial cells. Here, we have extended this classification based on the global transcriptomics landscape using tumor tissue from a well-defined cohort comprising 51 PitNETs of different clinical and histological types. The molecular profiles were compared with current classification schemes based on immunohistochemistry. Our results identified three main clusters of PitNETs that were aligned with the main pituitary TFs expression patterns. Our analyses enabled further identification of specific genes and expression patterns, including both known and unknown genes, that could distinguish the three different classes of PitNETs. We conclude that the current classification of PitNETs based on the expression of SF1, PIT1 and TPIT reflects three distinct subtypes of PitNETs with different underlying biology and partly independent from the expression of corresponding hormones. The transcriptomic analysis reveals several potentially targetable tumor-driving genes with previously unknown role in pituitary tumorigenesis.
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