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1.	Heil, Jan, et al. (author) Sarcopenia predicts reduced liver growth and reduced resectability in patients undergoing portal vein embolization before liver resection-A DRAGON collaborative analysis of 306 patients 2022 In: HPB. - : ELSEVIER SCI LTD. - 1365-182X .- 1477-2574. ; 24:3, s. 413-421 Journal article (peer-reviewed)abstract Background: After portal vein embolization (PVE) 30% fail to achieve liver resection. Malnutrition is a modifiable risk factor and can be assessed by radiological indices. This study investigates, if sarcopenia affects resectability and kinetic growth rate (KGR) after PVE. Methods: A retrospective study was performed of the outcome of PVE at 8 centres of the DRAGON collaborative from 2010 to 2019. All malignant tumour types were included. Sarcopenia was defined using gender, body mass and skeletal muscle index. First imaging after PVE was used for liver volumetry. Primary and secondary endpoints were resectability and KGR. Risk factors impacting liver growth were assessed in a multivariable analysis. Results: Eight centres identified 368 patients undergoing PVE. 62 patients (17%) had to be excluded due to unavailability of data. Among the 306 included patients, 112 (37%) were non-sarcopenic and 194 (63%) were sarcopenic. Sarcopenic patients had a 21% lower resectability rate (87% vs. 66%, p < 0.001) and a 23% reduced KGR (p = 0.02) after PVE. In a multivariable model dichotomized for KGR >2.3% standardized FLR (sFLR)/week, only sarcopenia and sFLR before embolization correlated with KGR. Conclusion: In this largest study of risk factors, sarcopenia was associated with reduced resectability and KGR in patients undergoing PVE.
2.	Al-Amiry, Bariq, 1976-, et al. (author) Does body mass index affect restoration of femoral offset, leg length and cup positioning after total hip arthroplasty? : a prospective cohort study 2019 In: BMC Musculoskeletal Disorders. - : BioMed Central (BMC). - 1471-2474. ; 20 Journal article (peer-reviewed)abstract Background: In obese patients, total hip arthroplasty (THA) can be technically demanding with increased perioperative risks. The aim of this prospective cohort study is to evaluate the effect of body mass index (BMI) on radiological restoration of femoral offset (FO) and leg length as well as acetabular cup positioning.Methods: In this prospective study, patients with unilateral primary osteoarthritis (OA) treated with THA between September 2010 and December 2013 were considered for inclusion. The perioperative plain radiographs were standardised and used to measure the preoperative degree of hip osteoarthritis, postoperative FO, leg length discrepancy (LLD), acetabular component inclination and anteversion.Results: We included 213 patients (74.5% of those considered for inclusion) with a mean BMI of 27.7 (SD 4.5) in the final analysis. The postoperative FO was improper in 55% and the LLD in 15%, while the cup inclination and anteversion were improper in 13 and 23% of patients respectively. A multivariable logistic regression model identified BMI as the only factor that affected LLD. Increased BMI increased the risk of LLD (OR 1.14, 95% CI 1.04 to 1.25). No other factors included in the model affected any of the primary or secondary outcomes.Conclusion: Increased BMI showed a negative effect on restoration of post-THA leg length but not on restoration of FO or positioning of the acetabular cup. Age, gender, OA duration or radiological severity and surgeon’s experience showed no relation to post-THA restoration of FO, leg length or cup positioning.
3.	Al-Amiry, Bariq Sh. 1976-, et al. (author) The Influence of Radiological Severity and Symptom Duration of Osteoarthritis on Postoperative Outcome After Total Hip Arthroplasty : A Prospective Cohort Study 2018 In: The Journal of Arthroplasty. - : CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS. - 0883-5403 .- 1532-8406. ; 33:2, s. 436-440 Journal article (peer-reviewed)abstract Background: We aimed to investigate the influence of preoperative radiological severity and symptom duration of hip osteoarthritis (OA) on the postoperative functional outcome, quality of life, as well as abductor muscle strength after total hip arthroplasty (THA). Methods: In this prospective cohort study, we studied 250 patients. Preoperatively, we evaluated the function with the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and quality of life with euroqol-5D (EQ-5D). At 1 year after THA, the same scores and also hip abductor muscle strength were measured in 222 patients. We divided the cohort twice, first according to the radiological OA severity [Kellgren-Lawrence classification (KL)] and then according to the OA symptom duration. We investigated whether the preoperative KL class and symptom duration influenced the 1-year WOMAC (primary outcome measure) or EQ-5D and abductor muscle strength (secondary outcome measures). Results: The crude results showed that KL class and symptom duration had no influence (P = .90 and P = .20, respectively) on the 1-yearWOMAC. Younger age, male gender, and lower body mass index were associated with a better function. Regarding 1-year EQ-5D, the crude results showed that body mass index and KL class had no influence (P = .83 and P = .39, respectively). The adjusted results showed that only age and gender influenced the postoperative EQ-5D. No influence of the tested factors was found on the 1-year abductor muscle strength. Conclusion: Preoperative radiological OA severity and symptom duration had no influence on the outcome of THA and should probably not affect the decision about timing the operative intervention.
4.	Barrefelt, Asa, et al. (author) Fluorescence labeled microbubbles for multimodal imaging 2015 In: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 464:3, s. 737-742 Journal article (peer-reviewed)abstract Air-filled polyvinyl alcohol microbubbles (PVA-MBs) were recently introduced as a contrast agent for ultrasound imaging. In the present study, we explore the possibility of extending their application in multimodal imaging by labeling them with a near infrared (NIR) fluorophore, VivoTag-680. PVA-MBs were injected intravenously into FVB/N female mice and their dynamic biodistribution over 24 h was determined by 3D-fluorescence imaging co-registered with 3D-mu CT imaging, to verify the anatomic location. To further confirm the biodistribution results from in vivo imaging, organs were removed and examined histologically using bright field and fluorescence microscopy. Fluorescence imaging detected PVA-MB accumulation in the lungs within the first 30 min post-injection. Redistribution to a low extent was observed in liver and kidneys at 4 h, and to a high extent mainly in the liver and spleen at 24 h. Histology confirmed PVA-MB localization in lung capillaries and macrophages. In the liver, they were associated with Kupffer cells; in the spleen, they were located mostly within the marginal-zone. Occasional MBs were observed in the kidney glomeruli and interstitium. The potential application of PVA-MBs as a contrast agent was also studied using ultrasound (US) imaging in subcutaneous and orthotopic pancreatic cancer mouse models, to visualize blood flow within the tumor mass. In conclusion, this study showed that PVA-MBs are useful as a contrast agent for multimodal imaging. (C) 2015 Elsevier Inc. All rights reserved.
5.	Barrefelt, Åsa, et al. (author) Biodistribution, kinetics, and biological fate of SPION microbubbles in the rat 2013 In: International Journal of Nanomedicine. - 1176-9114 .- 1178-2013. ; 8, s. 3241-3254 Journal article (peer-reviewed)abstract Background: In the present investigation, we studied the kinetics and biodistribution of a contrast agent consisting of poly(vinyl alcohol) (PVA) microbubbles containing superparamagnetic iron oxide (SPION) trapped between the PVA layers (SPION microbubbles). Methods: The biological fate of SPION microbubbles was determined in Sprague-Dawley rats after intravenous administration. Biodistribution and elimination of the microbubbles were studied in rats using magnetic resonance imaging for a period of 6 weeks. The rats were sacrificed and perfusion-fixated at different time points. The magnetic resonance imaging results obtained were compared with histopathologic findings in different organs. Results: SPION microbubbles could be detected in the liver using magnetic resonance imaging as early as 10 minutes post injection. The maximum signal was detected between 24 hours and one week post injection. Histopathology showed the presence of clustered SPION microbubbles predominantly in the lungs from the first time point investigated (10 minutes). The frequency of microbubbles declined in the pulmonary vasculature and increased in pulmonary, hepatic, and splenic macrophages over time, resulting in a relative shift from the lungs to the spleen and liver. Meanwhile, macrophages showed increasing signs of cytoplasmic iron accumulation, initially in the lungs, then followed by other organs. Conclusion: The present investigation highlights the biological behavior of SPION microbubbles, including organ distribution over time and indications for biodegradation. The present results are essential for developing SPION microbubbles as a potential contrast agent and/or a drug delivery vehicle for specific organs. Such a vehicle will facilitate the use of multimodality imaging techniques, including ultrasound, magnetic resonance imaging, and single positron emission computed tomography, and hence improve diagnostics, therapy, and the ability to monitor the efficacy of treatment.
6.	Barrefelt, Åsa, et al. (author) DYNAMIC MR IMAGING, BIODISTRIBUTION AND PHARMACOKINETICS OF POLYMER SHELLED MICROBUBBLES CONTAINING SPION 2014 In: NANO. - 1793-2920. ; 9:6, s. 1450069- Journal article (peer-reviewed)abstract Magnetic Resonance Imaging (MRI) is a noninvasive diagnostic method that provides information on morphological and physiological changes of the internal organs over time. Imaging and measurements can be repeated on the same subject, thereby reducing inter-individual variability effects and hence the number of subjects required. A potential MRI contrast agent consisting of microbubbles embedded with superparamagnetic iron oxide nanoparticles (SPION) in the shell (SPION MBs) was injected intravenously into rats to determine their biodistribution and pharmacokinetics using MR imaging. Agarose phantoms containing SPION MBs were scanned using 3 T MRI to construct a standard curve. Rats were injected with SPION MBs, free SPION or plain MBs and scanned dynamically at 3 T using a clinical MR scanner. The relaxation rate (R2) was studied over time as a measure of the iron oxide concentrations to enable calculation of the pharmacokinetic parameters. The kinetics of SPION MBs in the liver was fitted to a one-compartment model. Furthermore, the biological fate of SPION MBs was examined via a histological survey of tissue samples using Perls' Prussian blue staining and immunohistochemistry (IHC). 1.2 h after injection of SPION MBs, T2 of the liver had decreased to its minimum. The elimination half-life of SPION MBs was 598.2 +/- 97.3 h, while the half-life for SPION was 222.6 +/- 26.4 h. Moreover, our study showed that SPION MBs were taken up by the macrophages in the lungs, spleen and liver. MBs labeled with SPION can be used for MR imaging. Moreover, MRI is a reliable and noninvasive tool that can be utilized in pharmacokinetic investigations of future contrast agents using SPION MBs and SPION in the rat.
7.	Brismar, Torkel B (author) Assessment of skeletal structure by MR relaxometry 1999 Doctoral thesis (other academic/artistic)abstract Introduction: More than 40 per cent of all women older than 50 years will suffer from a hip, wrist or vertebral fracture. Most of these fractures are related to bone fragility, osteoporosis. If the disease is diagnosed and treated at an early stage the risk of fracture can be decreased. Traditional methods in clinical use primarily use the absorption of X-ray energy to evaluate bone quality. However, these methods do not evaluate the micro-structure of the bone, which has a major influence on biomechanical strength. This thesis evaluates a method to study the micro structure of trabecular bone by magnetic resonance (MR) relaxometry. Methods: Magnetic inhomogeneity arise at the interface between trabecular bone and bone marrow. The magnetic inhomogeneity results in decreased signal intensity in gradient echo images. The rate of the signal decrease can be used as an indirect measure of the trabecular bone structure called R2* (= 1/T2). The trabecular bone is embedded in bone marrow containing fat and water. To evaluate the influence of fat and water content on T2 measurements the signal behaviour as a function of TE was studied in porcine lumbar vertebrae and fat emulsions. T2* values were related to biomechanical strength tested experimentally. A new method to study trabecular bone orientation by MR relaxometry was developed. MR relaxometric values of human vertebrae were related to the amount of bone mineral in vitro. The obtained MR relaxometric values of spine, hip and calcaneus were related to values obtained by dual X-ray absorptiometry (DXA) and by quantitative ultrasound QUS). Results: There was a relationship between fat content and T2. As fat and water have different spin-lattice relaxation times (Tl) TR will theoretically also affect T2 measurements. The sagittal imaging plane is advantageous when performing MR relaxometry of the spine. Under experimental conditions MR relaxometry can predict biomechanical strength. Trabecular bone orientation studied by MR relaxometry in vitro can be calculated by rotation of the studied object in three orientations orthogonal to the external magnetic field. A relationship between results obtained by MR relaxometry and by bone mineral absorptiometry measurements was observed in vitro. Also in vivo MR relaxometry was related to absorptiometry of hip and to QUS of calcaneus. Conclusion: MR relaxometry is an accurate method to evaluate trabecular bone structure in vivo. The technique will be of interest not only for research purposes, but also for diagnosis and for treatment control at various diseases affecting the skeleton.
8.	Brismar, Torkel B., et al. (author) Magnetite Nanoparticles Can Be Coupled to Microbubbles to Support Multimodal Imaging 2012 In: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 13:5, s. 1390-1399 Journal article (peer-reviewed)abstract Microbubbles (MBs) are commonly used as injectable ultrasound contrast agent (UCA) in modern ultrasonography. Polymer-shelled UCAs present additional potentialities with respect to marketed lipid-shelled UCAs. They are more robust; that is, they have longer shelf and circulation life, and surface modifications are quite easily accomplished to obtain enhanced targeting and local drug delivery. The next generation of UCAs will be required to support not only ultrasound-based imaging methods but also other complementary diagnostic approaches such as magnetic resonance imaging or computer tomography. This work addresses the features of MBs that could function as contrast agents for both ultrasound and magnetic resonance imaging. The results indicate that the introduction of iron oxide nanoparticles (SPIONs) in the poly(vinyl alcohol) shell or on the external surface of the MBs does not greatly decrease the echogenicity of the host MBs compared with the unmodified one. The presence of SPIONs provides enough magnetic susceptibility to the MBs to accomplish good detectability both in vitro and in vivo. The distribution of SPIONs on the shell and their aggregation state seem to be key factors for the optimization of the transverse relaxation rate.
9.	Dubbelboer, Ilse R, et al. (author) Reply to "Comment on 'In Vivo Drug Delivery Performance of Lipiodol-Based Emulsion or Drug-Eluting Beads in Patients with Hepatocellular Carcinoma'" 2018 In: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 15:1, s. 336-340 Journal article (peer-reviewed)
10.	Erlandsson, Helen, et al. (author) Scoring of medial arterial calcification predicts cardiovascular events and mortality after kidney transplantation 2022 In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 291:6, s. 813-823 Journal article (peer-reviewed)abstract Background Progression of vascular calcification causes cardiovascular disease, which is the most common cause of death in chronic kidney failure and after kidney transplantation (KT). The prognostic impact of the extent of medial vascular calcification at KT is unknown. Methods In this prospective cohort study, we investigated the impact of medial calcification compared to a mix of intimal and medial calcification represented by coronary artery calcification (CAC score) and aortic valve calcification in 342 patients starting on kidney failure replacement therapy. The primary outcomes were cardiovascular events (CVE) and death. The median follow-up time was 6.4 years (interquartile range 3.7-9.6 years). Exposure was CAC score and arteria epigastrica medial calcification scored as none, mild, moderate, or severe by a pathologist at time of KT (n = 200). We divided the patients according to kidney failure replacement therapy during follow-up, that is, living donor KT, deceased donor KT, or dialysis. Results Moderate to severe medial calcification in the arteria epigastrica was associated with higher mortality (p = 0.001), and the hazard ratio for CVE was 3.1 (95% confidence interval [CI] 1.12-9.02, p < 0.05) compared to no or mild medial calcification. The hazard ratio for 10-year mortality in the dialysis group was 33.6 (95% CI, 10.0-113.0, p < 0.001) compared to living donor recipients, independent of Framingham risk score and prevalent CAC. Conclusion Scoring of medial calcification in the arteria epigastrica identified living donor recipients as having 3.1 times higher risk of CVE, independent of traditional risk factors. The medial calcification score could be a reliable method to identify patients with high and low risk of CVE and mortality following KT.
11.	Gardin, Anna, et al. (author) Dynamic contrast enhanced magnetic resonance imaging in chronic Achilles tendinosis 2013 In: BMC Medical Imaging. - : Springer Science and Business Media LLC. - 1471-2342. ; 13, s. 39- Journal article (peer-reviewed)abstract Background: Chronic Achilles tendinosis is a common problem. When evaluating and comparing different therapies there is a need for reliable imaging methods. Our aim was to evaluate if chronic Achilles tendinosis affects the dynamic contrast-enhancement in the tendon and its surroundings and if short-term eccentric calf-muscle training normalizes the dynamic contrast-enhancement. Methods: 20 patients with chronic Achilles tendinopathy were included. Median duration of symptoms was 31 months (range 6 to 120 months). Both Achilles tendons were examined with dynamic contrast enhanced MRI before and after a 12-week exercise programme of eccentric calf-muscle training. The dynamic MRI was evaluated in tendon, vessel and in fat ventrally of tendon. Area under the curve (AUC), time to peak of signal, signal increase per second (SI/s) and increase in signal between start and peak as a percentage (SI%) was calculated. Pain and performance were evaluated using a questionnaire. Results: In the fat ventrally of the tendon, dynamic contrast enhancement was significantly higher in the symptomatic leg compared to the contralateral non-symptomatic leg before but not after treatment. Despite decreased pain and improved performance there was no significant change of dynamic contrast enhancement in symptomatic tendons after treatment. Conclusion: In Achilles tendinosis there is an increased contrast enhancement in the fat ventrally of the tendon. The lack of correlation with symptoms and the lack of significant changes in tendon contrast enhancement parameters do however indicate that dynamic enhanced MRI is currently not a useful method to evaluate chronic Achilles tendinosis.
12.	Golembiewska, Edyta, et al. (author) Copeptin is independently associated with vascular calcification in chronic kidney disease stage 5 2020 In: BMC Nephrology. - Stockholm : Karolinska Institutet, Dept of Clinical Science, Intervention and Technology. - 1471-2369. Journal article (peer-reviewed)abstract Background: Vascular calcification (VC) is an independent predictor of cardiovascular disease (CVD) present in 30– 70% of patients with chronic kidney disease (CKD). Copeptin is a sensitive surrogate marker of arginine vasopressin (AVP), which is involved in many pathophysiologic processes in CKD. The aim of the present study was to explore the association of copeptin with VC in CKD stage 5. Methods: Copeptin was investigated in conjunction with living donor kidney transplantation in 149 clinically stable CKD stage 5 patients (CKD5), including 53 non-dialyzed (CKD5-ND) and 96 dialysis patients treated by peritoneal dialysis (PD) (n = 43) or hemodialysis (HD) (n = 53). We analyzed the association of copeptin with presence and extent of VC ascertained both histologically in biopsies from the inferior epigastric artery (n = 137) and by coronary artery calcification (CAC) score measured by computed tomography. Results: Patients with higher copeptin were older, had higher systolic blood pressure, higher prevalence of CVD and their preceding time on chronic dialysis was longer. In Spearman’s rank correlations (Rho), copeptin concentrations were significantly associated with CAC score (Rho = 0.27; p = 0.003) and presence of medial VC (Rho = 0.21; p = 0.016). Multivariate logistic regression analysis showed that 1-SD higher age, male gender, diabetes and 1-SD higher copeptin were significantly associated with the presence of moderate-extensive VC. Conclusions: High circulating levels of copeptin in CKD5 patients are independently associated with the degree of medial calcification ascertained by histology of arterial biopsies. Thus, plasma copeptin may serve as a marker of the uremic calcification process.
13.	Grishenkov, Dmitry, 1983-, et al. (author) Acoustic properties of polymer-shelled ultrasound contrast agents. Bulk volume vs. microcapillary 2009 In: 16th International Congress on Sound and Vibration 2009, ICSV 2009. - Krakow. - 9781615677368 ; , s. 2515-2522 Conference paper (peer-reviewed)abstract The focus of contrast-enhanced ultrasound research has developed beyond detecting the blood pool to new areas such as perfusion imaging, drug and gene therapy, and targeted imaging. Polymer-shelled microbubbles are proposed as a new generation of ultrasound contrast agents (UCAs) which fulfil the requirements of these applications. With a shelf-life of several months and possibility to conjugate pharmacological molecules to their surface, these UCAs will allow not only to enhance the contrast of ultrasound images, but also to function as carriers of drugs to be delivered locally. In this study, the results of an experimental investigation of three types of UCAs stabilized by thick poly vinyl alcohol (PVA) shell are presented. These UCAs are synthesized from a PVA aqueous solution under varied pH values and temperature. The UCAs differ from each other in their average diameter, shell thickness and polydispersity. Knowledge of the peak negative pressure at which the solid shell fractures is paramount for a proper use of UCAs. Therefore, the dependence of this quantity on temperature and number of cycles in the incident pulse is examined. Much of the blood volume resides in the microcirculation, with capillaries playing a particularly important role in patho-physiology and drug delivery. In this sense in vitro characterization of the UCAs oscillation was moved from bulk volume to the capillary scale, where tissue-bubble interaction takes place. The main conclusion to be drawn from these results is that the shell of the UCAs begin to fracture at values of mechanical index (MI) approved for clinical applications. The fatigue, i.e. the accumulation of damage within the shell of the UCAs, is found to play an important role in fracturing the shell. Finally adhesion of the UCAs to the elastic wall is studied and correlated with estimates of the shell’s visco-elastic constants. Open questions arising from this comparison are briefly discussed.
14.	Grishenkov, Dmitry, 1983-, et al. (author) Characterization of Acoustic Properties of PVA-Shelled Ultrasound Contrast Agents 2010 In: Ultrasound Contrast Agents. - Italia : Springer-Verlag. - 9788847014930 ; , s. 99-108 Book chapter (other academic/artistic)abstract This work examines the acoustic behavior of ultrasound contrast agents made of poly (vinyl alcohol) (PVA) shelled microbubbles manufactured at three different pH and temperature conditions. Backscattering amplitude, attenuation coefficient and phase velocity of ultrasonic waves propagating through suspensions of PVA contrast agents were measured at temperature values ranging between 24 oC and 37 oC in a frequency range from 3 MHz to 13 MHz. A significant enhancement of the backscattering amplitude and displaying a weak dependence on temperature were observed. Attenuation and phase velocity, on the other hand, showed higher sensitivity to temperature variations. The dependence on system parameters such as the number of cycles, frequency, and exposure of the peak negative pressure, Pthr, at which ultrasound contrast agents fracture was also investigated. The effects of temperature, blood, and, wherever data are available, of the dimension of the microbubbles on Pthr are also considered. The large shell thickness notwithstanding, the results of this investigation show that at room temperature PVA contrast agents fracture at negative peak pressure values within the recommended safety limit. Furthermore, Pthr decreases with increasing temperature, radius of the microbubbles, and number of cycles of the incident wave. In conclusion, these results suggest that PVA-shelled microbubbles may offer a potentially viable system to be employed for both imaging and therapeutic purposes.
15.	Grishenkov, Dmitry, 1983-, et al. (author) Characterization of acoustic properties of PVA-shelled ultrasound contrast agents : linear properties (Part I) 2009 In: Ultrasound in Medicine and Biology. - : Elsevier BV. - 0301-5629 .- 1879-291X. ; 35:7, s. 1127-1138 Journal article (peer-reviewed)abstract This work examines the linear acoustic behavior of ultrasound contrast agents made of three types of poly (vinyl alcohol) (PVA) shelled microbubbles manufactured at different pH and temperature conditions. Back-scattered power, attenuation coefficient and phase velocity of ultrasonic waves propagating through suspensions of PVA contrast agents were measured at temperature values ranging between 24 degrees C and 37 degrees C in a frequency range from 3 MHz to 13 MHz. Enhancement of the backscattered power higher than 20 dB and displaying a weak dependence on temperature was observed. Attenuation and phase velocity, on the other hand, showed higher sensitivity to temperature variations. A modified version of the Church model, which accounts for the dispersion of the dynamic modulus of the PVA shells, was developed to simultaneously fit the attenuation and phase velocity data at 24 degrees C. The frequency dependence of the storage modulus was found to be that of semiflexible polymeric networks. On the other hand, the frequency dependence of the dynamic loss modulus suggests that additional mechanisms, which may be related to the finite dimensions of the shell and/or to its inhomogeneity, may play a significant role in the dissipation of the acoustic energy. For the microbubbles of interest, this model predicts frequency dependent resonance frequency higher than 100 MHz.
16.	Grishenkov, Dmitry, 1983-, et al. (author) Characterization of acoustic properties of PVA-shelled ultrasound contrast agents : ultrasound-induced fracture (Part II) 2009 In: Ultrasound in Medicine and Biology. - : Elsevier BV. - 0301-5629 .- 1879-291X. ; 35:7, s. 1139-1147 Journal article (peer-reviewed)abstract Knowledge of the magnitude of the peak negative pressure, P-thr, at which ultrasound contrast agents fracture is relevant for using these microbubbles both as devices for contrast enhancement purposes, as well as carriers of drugs to be delivered locally. In the second part of this communication, the acoustic properties of three types of microbubbles stabilized by poly (vinyl alcohol) (PVA) shells are further investigated. In particular, the dependence of P-thr on system parameters such as the number of cycles, frequency and exposure is examined. The effects of temperature, blood and, wherever data are available, of the dimension of the microbubbles on P-thr are also considered. The large shelf thickness notwithstanding, the results of this investigation show that at room temperature, PVA contrast agents fracture at negative peak pressure values within the recommended safety limit. Furthermore, P-thr decreases with increasing temperature, radius of the microbubbles and number of cycles of the incident wave. Fatigue seems to be a physical mechanism playing a dominant role in the fracture process. The effect of blood on P-thr varies according to condition under which the microbubbles have been synthesized, although stiffening of the shell is observed in most cases. In conclusion, these results suggest that PVA-shelled microbubbles may offer a potentially viable system to be employed for both imaging and therapeutic purposes.
17.	Grishenkov, Dmitry, 1983-, et al. (author) In vitro contrast-enhanced ultrasound measurements of capillary microcirculation : Comparison between polymer- and phospholipid-shelled microbubbles 2011 In: Ultrasonics. - : Elsevier BV. - 0041-624X .- 1874-9968. ; 51:1, s. 40-48 Journal article (peer-reviewed)abstract The focus of contrast-enhanced ultrasound research has developed beyond visualizing the blood pool and its flow to new areas such as perfusion imaging, drug and gene therapy, and targeted imaging. In this work comparison between the application of polymer- and phospholipid-shelled ultrasound contrast agents (UCAs) for characterization of the capillary microcirculation is reported. All experiments are carried out using a microtube as a vessel phantom. The first set of experiments evaluates the optimal concentration level where backscattered signal from microbubbles depends on concentration linearly. For the polymer-shelled UCAs the optimal concentration level is reached at a value of about 2 x 10(4) MB/ml, whereas for the phospholipid-shelled UCAs the optimal level is found at about 1 x 10(5) MB/ml.Despite the fact that the polymer shell occupies 30% of the radius of microbubble, compared to 0.2% of the phospholipid-shelled bubble, approximately 5-fold lower concentration of the polymer UCA is needed for investigation compared to phospholipid-shelled analogues. In the second set of experiments, destruction/replenishment method with varied time intervals ranging from 2 ms to 3 s between destructive and monitoring pulses is employed. The dependence of the peak-to-peak amplitude of backscattered wave versus pulse interval is fitted with an exponential function of the time gamma = A( 1 - exp(-beta t)) where A represents capillary volume and the time constant beta represents velocity of the flow. Taking into account that backscattered signal is linearly proportional to the microbubble concentration, for both types of the UCAs it is observed that capillary volume is linearly proportional to the concentration of the microbubbles, but the estimation of the flow velocity is not affected by the change of the concentration. Using the single capillary model, for the phospholipid-shelled UCA a delay of about 0.2-0.3 s in evaluation of the perfusion characteristics is found while polymer-shelled UCA provide response immediately. The latter at the concentration lower than 3.6 x 10(5) MB/ml have no statistically significant delay (p < 0.01), do not cause any attenuation of the backscattered signal or saturation of the receiving part of the system. In conclusion, these results suggest that the novel polymer-shelled microbubbles have a potential to be used for perfusion evaluation.
18.	Grishenkov, Dmitry, 1983-, et al. (author) On comparison between polymer- and phospholipid-shelled microbubbles for contrast-enhanced ultrasound measurements of capillary microcirculation. 2011 In: Proceedings of the 34<sup>th</sup> Scandinavian Symposium on Physical Acoustics. Conference paper (peer-reviewed)abstract The focus of contrast-enhanced ultrasound research has developed beyond visualizing the blood circulation to new areas such as perfusion and molecular imaging, drug and gene therapy. This work compares the application of polymer- and phospholipid-shelled ultrasound contrast agents (UCAs) employed for characterization of the capillary microcirculation. To quantify microcirculation destruction/replenishment technique with varied time intervals between destructive and monitoring pulses is used. The dependence of the peak-to-peak amplitude of backscattered wave versus pulse interval is fitted with an exponential function of the time y=A(1-exp(-βt)) , where A represents capillary volume and the time constant β represents velocity of the flow. Working under assumption that backscattered signal is linearly proportional to the microbubble concentration, for both types of the UCAs it is observed that capillary volume, A, is in linearly relationship with the concentration, and the flow velocity, β, remain unchanged. Using 500 µm diameter microtube as a vessel phantom a delay of about 0.25 s in evaluation of the perfusion characteristics is found for the phospholipid-shelled UCA, while polymer-shelled UCA provide response immediately. In conclusion, these results suggest that the novel polymer-shelled microbubbles have a potential to be used for perfusion evaluation.
19.	Grishenkov, Dmitry, 1983-, et al. (author) On the acoustic properties of polymer-shell ultrasonic contrast agents. 2008 Conference paper (other academic/artistic)abstract Polymer-shelled microbubbles have become the focus of intense research for their enhanced shelf life and demonstrated chemical versatility. These are properties highly sought after in the ultrasonic contrast agents (UCAs) of the next generation, which will be engineered not only to enhance the contrast of ultrasound-based images, but also to function as carriers of drugs to be delivered locally. Here, the results of an experimental investigation of three potentially new UCAs are presented. These microbubbles are stabilized by thick poly (vinyl alcohol) shells. These UCAs differ from each other in their dimensions and shell thickness (order of 0.5 microns). Fundamental to their use as drug carrier is the knowledge of the pressure threshold at which the shell of these UCAs fractures. Therefore, the dependence of this quantity on temperature, number of cycles of the incident pulse, nominal central frequency and pulse repetition frequency of the emitting transducer is examined. The effect of using blood instead of deionized water is also considered. The main conclusion to be drawn from these results is that their thick shell notwithstanding, these microbubbles begin to fracture at values of MI which can be acceptable in clinical applications. This claim is supported also by images acquired by means of commercially available imaging systems. Finally, these values of the pressure threshold are correlated with estimates of the shells’ visco-elastic constants obtained by fitting Church’s model to the frequency-dependent attenuation coefficient and phase velocity. Open questions arising from this comparison are briefly discussed.
20.	Gärdin, Anna, et al. (author) T2 * relaxation time in Achilles tendinosis and controls and its correlation with clinical score 2016 In: Journal of Magnetic Resonance Imaging. - : Wiley. - 1053-1807 .- 1522-2586. ; 43:6, s. 1417-1422 Journal article (peer-reviewed)abstract PURPOSE: To investigate if the T2 * of Achilles tendons can discriminate between chronic Achilles tendinosis and healthy controls; to correlate with clinical score; to evaluate its short-term repeatability; and to estimate minimal detectable change.MATERIALS AND METHODS: Twenty patients, with chronic mid-portion Achilles tendinosis, and 10 controls without history of Achilles tendon symptoms, were examined with a 3T MR scanner with a 3D flash ultrashort time to echo sequence with five different echo times. The sequence was run twice to test repeatability. The tendon border was delineated on axial slices at three different levels in the calculated T2 * maps. The clinical severity of Achilles tendinosis was measured by a VISA-A questionnaire.RESULTS: There was a significant difference in mean T2 * between symptomatic and control tendons (P < 0.001). In patients with unilateral symptoms no significant difference in T2 * was found between symptomatic and contralateral asymptomatic tendons (P = 0.19). There was no significant correlation between clinical severity and T2 * (r = -0.28, P = 0.22). The short-term repeatability of T2 * showed a coefficient of variation of 18%, a least significant change of 50%, and the intraclass correlation coefficient had an average consistency of 0.99.CONCLUSION: T2 * may help to differentiate between chronic Achilles tendinosis and healthy controls but was not associated with the clinical score. However, and notably, the reproducibility of the method was low and the number of patients was small.
21.	Jakola, Asgeir Store, et al. (author) Quantitative texture analysis in the prediction of IDH status in low-grade gliomas. 2018 In: Clinical neurology and neurosurgery. - : Elsevier BV. - 1872-6968 .- 0303-8467. ; 164, s. 114-120 Journal article (peer-reviewed)abstract Molecular markers provide valuable information about treatment response and prognosis in patients with low-grade gliomas (LGG). In order to make this important information available prior to surgery the aim of this study was to explore if molecular status in LGG can be discriminated by preoperative magnetic resonance imaging (MRI).All patients with histopathologically confirmed LGG with available molecular status who had undergone a preoperative standard clinical MRI protocol using a 3T Siemens Skyra scanner during 2008-2015 were retrospectively identified. Based on Haralick texture parameters and the segmented LGG FLAIR volume we explored if it was possible to predict molecular status.In total 25 patients (nine women, average age 44) fulfilled the inclusion parameters. The textural parameter homogeneity could discriminate between LGG patients with IDH mutation (0.12, IQR 0.10-0.15) and IDH wild type (0.07, IQR 0.06-0.09, p=0.005). None of the other four analyzed texture parameters (energy, entropy, correlation and inertia) were associated with molecular status. Using ROC curves, the area under curve for predicting IDH mutation was 0.905 for homogeneity, 0.840 for tumor volume and 0.940 for the combined parameters of tumor volume and homogeneity. We could not predict molecular status using the four other chosen texture parameters (energy, entropy, correlation and inertia). Further, we could not separate LGG with IDH mutation with or without 1p19q codeletion.In this preliminary study using Haralick texture parameters based on preoperative clinical FLAIR sequence, the homogeneity parameter could separate IDH mutated LGG from IDH wild type LGG. Combined with tumor volume, these diagnostic properties seem promising.
22.	Klintström, Eva, et al. (author) Direct estimation of human trabecular bone stiffness using cone beam computed tomography 2018 In: Oral surgery, oral medicine, oral pathology and oral radiology. - : ELSEVIER SCIENCE INC. - 2212-4403 .- 2212-4411. ; 126:1, s. 72-82 Journal article (peer-reviewed)abstract Objectives. The aim of this study was to evaluate the possibility of estimating the biomechanical properties of trabecular bone through finite element simulations by using dental cone beam computed tomography data. Study Design. Fourteen human radius specimens were scanned in 3 cone beam computed tomography devices: 3-D Accuitomo 80 (J. Morita MFG., Kyoto, Japan), NewTom 5 G (QR Verona, Verona, Italy), and Verity (Planmed, Helsinki, Finland). The imaging data were segmented by using 2 different methods. Stiffness (Young modulus), shear moduli, and the size and shape of the stiffness tensor were studied. Corresponding evaluations by using micro-CT were regarded as the reference standard. Results. The 3-D Accuitomo 80 (J. Morita MFG., Kyoto, Japan) showed good performance in estimating stiffness and shear moduli but was sensitive to the choice of segmentation method. Newtom 5 G (QR Verona, Verona, Italy) and Verity (Planmed, Helsinki, Finland) yielded good correlations, but they were not as strong as Accuitomo 80 U. Morita MFG., Kyoto, Japan). The cone beam computed tomography devices overestimated both stiffness and shear compared with the micro-CT estimations. Conclusions. Finite element-based calculations of biomechanics from cone beam computed tomography data are feasible, with strong correlations for the Accuitomo 80 scanner a. Morita MFG., Kyoto, Japan) combined with an appropriate segmentation method. Such measurements might be useful for predicting implant survival by in vivo estimations of bone properties.
23.	Klintström, Eva, et al. (author) Predicting Trabecular Bone Stiffness from Clinical Cone-Beam CT and HR-pQCT Data; an In Vitro Study Using Finite Element Analysis 2016 In: PLOS ONE. - : PLOS one. - 1932-6203. ; 11:8 Journal article (peer-reviewed)abstract Stiffness and shear moduli of human trabecular bone may be analyzed in vivo by finite element (FE) analysis from image data obtained by clinical imaging equipment such as high resolution peripheral quantitative computed tomography (HR-pQCT). In clinical practice today, this is done in the peripheral skeleton like the wrist and heel. In this cadaveric bone study, fourteen bone specimens from the wrist were imaged by two dental cone beam computed tomography (CBCT) devices and one HR-pQCT device as well as by dual energy X-ray absorptiometry (DXA). Histomorphometric measurements from micro-CT data were used as gold standard. The image processing was done with an in-house developed code based on the automated region growing (ARG) algorithm. Evaluation of how well stiffness (Young's modulus E3) and minimum shear modulus from the 12, 13, or 23 could be predicted from the CBCT and HR-pQCT imaging data was studied and compared to FE analysis from the micro-CT imaging data. Strong correlations were found between the clinical machines and micro-CT regarding trabecular bone structure parameters, such as bone volume over total volume, trabecular thickness, trabecular number and trabecular nodes (varying from 0.79 to 0.96). The two CBCT devices as well as the HR-pQCT showed the ability to predict stiffness and shear, with adjusted R-2-values between 0.78 and 0.92, based on data derived through our in-house developed code based on the ARG algorithm. These findings indicate that clinically used CBCT may be a feasible method for clinical studies of bone structure and mechanical properties in future osteoporosis research.
24.	Kälvesten, Johan, et al. (author) Potential sources of quantification error when retrospectively assessing metacarpal bone loss from historical radiographs by using digital X-ray radiogrammetry : an experimental study 2014 In: Journal of clinical densitometry. - : Elsevier. - 1094-6950 .- 1559-0747. ; 17:1, s. 104-108 Journal article (peer-reviewed)abstract During the past 15 yr, digital X-ray radiogrammetry (DXR) has been used to measure metacarpal bone mineral density (BMD). BMD is often measured in existing cohorts where X-ray images were not acquired in accordance with the DXR imaging protocol (DIP). The purpose of the present study was to analyze how deviations from DIP in historical radiographs may affect the reproducibility of DXR-BMD measurements. Cadaver hand phantoms were used to conduct repeat measurements of deviations from DIP with respect to voltage, exposure, lateral displacement, supination, combination of lateral displacement and supination or rotation, extension of the wrist, and edge enhancement. Direct digital radiography (Aristos; Siemens Healthcare, Erlangen, Germany) was used for image acquisition and dxr-online (Sectra, Linkoping, Sweden) for DXR-BMD measurements. The influence of the tested deviations from DIP ranged from 0 to 32.5 mg/cm(2) (0-6.8%). On repetition with the same specimen, none of the deviations resulted in a within-specimen reproducibility error greater than 2 mg/cm(2) (0.4%, equivalent to a T-score of 0.042). Among the tested deviations, all except tube voltage had a magnitude greater than the normal measurement noise for the technique and must therefore be considered when planning a study based on historical images.
25.	Laucyte-Cibulskiene, Agne, et al. (author) Role of GDF-15, YKL-40 and MMP 9 in patients with end-stage kidney disease : focus on sex-specific associations with vascular outcomes and all-cause mortality 2021 In: Biology of Sex Differences. - : Springer Science and Business Media LLC. - 2042-6410. ; 12:1 Journal article (peer-reviewed)abstract Background: Sex differences are underappreciated in the current understanding of cardiovascular disease (CVD) in association with chronic kidney disease (CKD). A hallmark of CKD is vascular aging that is characterised, amongst others, by; systemic inflammation, microbiota disbalance, oxidative stress, and vascular calcification—features linked to atherosclerosis/arteriosclerosis development. Thus, it is the necessary to introduce novel biomarkers related to athero-/arteriosclerotic damage for better assessment of vascular ageing in patients CKD. However, little is known about the relationship between uraemia and novel CVD biomarkers, such as growth differentiation factor-15 (GDF-15), cartilage glycoprotein-39 (YKL-40) and matrix metalloproteinase-9 (MMP-9). Therefore, we hypothesise that there are sex-specific relationships between GDF-15, YKL-40, MMP-9 levels in end-stage kidney disease (ESKD) patients in relation to gut microbiota, vascular calcification, inflammation, comorbidities, and all-cause mortality. Methods: ESKD patients, males (n = 151) and females (n = 79), not receiving renal replacement therapy were selected from two ongoing prospective ESKD cohorts. GDF-15, YKL-40 and MMP9 were analysed using enzyme-linked immunosorbent assay kits. Biomarker levels were analysed in the context of gut microbiota-derived trimethylamine N-oxide (TMAO), vascular calcification, inflammatory response, oxidative stress, comorbidities, and all-cause mortality. Results: Increased GDF-15 correlated with higher TMAO in females only, and with higher coronary artery calcification and IL-6. In females, diabetes was associated with elevated GDF-15 and MMP-9, whilst males with diabetes only had elevated GDF-15. No associations were found between biomarkers and CVD comorbidity. Deceased males and females had higher GDF-15 concentrations (p = 0.01 and p < 0.001, respectively), meanwhile only YKL-40 was increased in deceased males (p = 0.02). Conclusions: In conclusion, in males GDF-15 and YKL-40 were related to vascular calcification, inflammation, and oxidative stress, whilst in females GDF-15 was related to TMAO. Increased levels of YKL-40 and GDF-15 in males, and only GDF-15 in females, were associated with all-cause mortality. Our findings suggest that sex-specific associations of novel CVD biomarkers have a potential to affect development of cardiovascular complications in patients with ESKD.

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