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- Al-Mashat, Mariam
(författare)
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Assessment of Pulmonary Blood Flow in Heart Failure. Using Novel and Non-Invasive Diagnostic Methods.
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In heart failure (HF), the heart is unable to pump effectively in order to satisfy the demands of the body. The elevated filling pressure seen in HF leads to accumulation of fluid in the lungs, i.e pulmonary congestion. While investigation with chest X-ray is recommended, it has limitations in detecting pulmonary congestion. Ventilation/perfusion single-photon emission computed tomography (V/P SPECT), i.e tomographic lung scintigraphy, is a promising method to diagnose and quantify pulmonary congestion in HF but needs to be validated by invasive right-heart catheterization. The variation of the blood volume in the pulmonary circulation measured by magnetic resonance imaging (MRI) may also have the potential to quantify the severity of HF.The general aim of this thesis was to develop and validate new non-invasive methods to diagnose and quantify pulmonary congestion and variation of the pulmonary blood flow in patients with HF, as well as to follow-uppulmonary congestion.Paper I revealed that the degree of pulmonary congestion in HF could be diagnosed and quantified using V/P SPECT. It was validated with right-heart catheterization. V/P SPECT was more accurate than chest X-ray in diagnosing pulmonary congestion in HF.In Paper II V/P SPECT showed that the pulmonary perfusion pattern was improved and that V/P SPECT could be used to follow treatment effect after heart transplantation in patients with HF and quantify the degree of pulmonarycongestion. It was validated with right-heart catheterization.Paper III demonstrated that V/P SPECT could be used to follow treatment effect and assess the degree of pulmonary congestion in patients with HF after receiving cardiac resynchronization therapy (CRT). V/P SPECT was associated with improvement in patients’ symptoms.Paper IV showed that the pulmonary blood volume variation differed between patients with HF and healthy controls. In patients with HF, approximately 40% of the variation could be explained by the left ventricular longitudinal contribution to stroke volume and the phase shift between the in- and outflow to the pulmonary circulation. The remaining variation (60%) likely occur on a small vessel level.In summary, pulmonary congestion in HF is difficult to quantify objectively. The non-invasive methods V/P SPECT and MRI might add complementary information in the diagnosis of HF. V/P SPECT can be used to follow treatment effects after heart transplantation and CRT and may have a role in avoiding invasive right-heart catheterization in selected cases and aid in treatment decision.
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- Al-Mashat, Mariam, et al.
(författare)
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Increased pulmonary blood volume variation in patients with heart failure compared to healthy controls; a non-invasive, quantitative measure of heart failure
- 2020
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Ingår i: Journal of Applied Physiology. - : American Physiological Society. - 1522-1601 .- 8750-7587. ; 128:2, s. 324-337
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Tidskriftsartikel (refereegranskat)abstract
- Variation of the blood content of the pulmonary vascular bed during a heartbeat can be quantified by pulmonary blood volume variation (PBVV) using magnetic resonance imaging (MRI). The aim was to evaluate if PBVV differs in patients with heart failure compared to healthy controls and investigate the mechanisms behind the PBVV. Forty-six patients and 10 controls underwent MRI. PBVV was calculated from blood flow measurements in the main pulmonary artery and a pulmonary vein, defined as the maximum difference in cumulative PBV over one heartbeat. PBVV was indexed to stroke volume (SV) in the main pulmonary artery (PBVVSV). Patients displayed higher PBVVSV than controls (58±14% vs 43±7%, p<0.001). The change in PBVVSV could be explained by left ventricular (LV) longitudinal contribution to SV (R2=0.15, p=0.02) and the phase shift between in- and outflow (R2=0.31, p<0.001) in patients. Both variables contributed to the multiple regression analysis model and predicted PBVVSV (R2=0.38), however, the phase shift alone explained about ~30% of the variation in PBVVSV. No correlation was found between PBVVSV and large vessel area. In conclusion, PBVVSV was higher in patients compared to controls. Approximately 40% of the variation of PBVVSV in patients can be explained by the LV longitudinal contribution to SV and the phase shift between pulmonary in- and outflow, where the phase shift alone accounts for ~30%. The remaining variation, (60-70%), most likely occurs on small vessel level. Future studies are needed to show the clinical added value of PBVVSV compared to right heart catheterization.
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- Al-Mashat, Mariam, et al.
(författare)
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Pulmonary perfusion and NYHA classification improve after cardiac resynchronization therapy
- 2022
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Ingår i: Journal of Nuclear Cardiology. - : Springer Science and Business Media LLC. - 1071-3581 .- 1532-6551. ; 29:6, s. 2974-2983
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evaluation of cardiac resynchronization therapy (CRT) often includes New York Heart Association (NYHA) classification, and echocardiography. However, these measures have limitations. Perfusion gradients from ventilation/perfusion single-photon emission computed tomography (V/P SPECT) are related to left-heart filling pressures and have been validated against invasive right-heart catheterization. The aim was to assess if changes in perfusion gradients are associated with improvements in heart failure (HF) symptoms after CRT, and if they correlate with currently used diagnostic methods in the follow-up of patients with HF after receiving CRT. Methods and results: Nineteen patients underwent V/P SPECT, echocardiography, NYHA classification, and the quality-of-life scoring system “Minnesota living with HF” (MLWHF), before and after CRT. CRT caused improvement in perfusion gradients from V/P SPECT which were associated with improvements in NYHA classification (P =.0456), whereas improvements in end-systolic volume (LVESV) from echocardiography were not. After receiving CRT, the proportion of patients who improved was lower using LVESV (n = 7/19, 37%) than perfusion gradients (n = 13/19, 68%). Neither change in perfusion gradients nor LVESV was associated with changes in MLWHF (P = 1.0, respectively). Conclusions: Measurement of perfusion gradients from V/P SPECT is a promising quantitative user-independent surrogate measure of left-sided filling pressure in the assessment of CRT response in patients with HF.
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- Bryl-Górecka, Paulina, et al.
(författare)
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Effect of exercise on the plasma vesicular proteome : A methodological study comparing acoustic trapping and centrifugation
- 2018
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Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 18:20, s. 3101-3111
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular vesicles (EVs) are a heterogeneous group of actively released vesicles originating from a wide range of cell types. Characterization of these EVs and their proteomes in the human plasma provides a novel approach in clinical diagnostics, as they reflect physiological and pathological states. However, EV isolation is technically challenging with the current methods having several disadvantages, requiring large sample volumes, and resulting in loss of sample and EV integrity. Here, we use an alternative, non-contact method based on a microscale acoustic standing wave technology. Improved coupling of the acoustic resonator increased the EV recovery from 30% in earlier reports to 80%, also displaying long term stability between experiment days. We report a pilot study, with 20 subjects who underwent physical exercise. Plasma samples were obtained before and 1 h after the workout. Acoustic trapping was compared to a standard high-speed centrifugation protocol, and the method was validated by flow cytometry (FCM). To monitor the device stability, the pooled frozen plasma from volunteers was used as an internal control. A key finding from the FCM analysis was a decrease in CD62E+ (E-selectin) EVs 1 h after exercise that was consistent for both methods. Furthermore, we report the first data that analyse differential EV protein expression before and after physical exercise. Olink-based proteomic analysis showed 54 significantly changed proteins in the EV fraction in response to physical exercise, whereas the EV-free plasma proteome only displayed four differentially regulated proteins, thus underlining an important role of these vesicles in cellular communication, and their potential as plasma derived biomarkers. We conclude that acoustic trapping offers a fast and efficient method comparable with high-speed centrifugation protocols. Further, it has the advantage of using smaller sample volumes (12.5 μL) and rapid contact-free separation with higher yield, and can thus pave the way for future clinical EV-based diagnostics.
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- Cheimariotis, Grigorios Aris, et al.
(författare)
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Automatic lung segmentation in functional SPECT images using active shape models trained on reference lung shapes from CT
- 2018
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Ingår i: Annals of Nuclear Medicine. - : Springer Science and Business Media LLC. - 0914-7187 .- 1864-6433. ; 32:2, s. 94-104
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Image segmentation is an essential step in quantifying the extent of reduced or absent lung function. The aim of this study is to develop and validate a new tool for automatic segmentation of lungs in ventilation and perfusion SPECT images and compare automatic and manual SPECT lung segmentations with reference computed tomography (CT) volumes. Methods: A total of 77 subjects (69 patients with obstructive lung disease, and 8 subjects without apparent perfusion of ventilation loss) performed low-dose CT followed by ventilation/perfusion (V/P) SPECT examination in a hybrid gamma camera system. In the training phase, lung shapes from the 57 anatomical low-dose CT images were used to construct two active shape models (right lung and left lung) which were then used for image segmentation. The algorithm was validated in 20 patients, comparing its results to reference delineation of corresponding CT images, and by comparing automatic segmentation to manual delineations in SPECT images. Results: The Dice coefficient between automatic SPECT delineations and manual SPECT delineations were 0.83 ± 0.04% for the right and 0.82 ± 0.05% for the left lung. There was statistically significant difference between reference volumes from CT and automatic delineations for the right (R = 0.53, p = 0.02) and left lung (R = 0.69, p < 0.001) in SPECT. There were similar observations when comparing reference volumes from CT and manual delineations in SPECT images, left lung (bias was − 10 ± 491, R = 0.60, p = 0.005) right lung (bias 36 ± 524 ml, R = 0.62, p = 0.004). Conclusion: Automated segmentation on SPECT images are on par with manual segmentation on SPECT images. Relative large volumetric differences between manual delineations of functional SPECT images and anatomical CT images confirms that lung segmentation of functional SPECT images is a challenging task. The current algorithm is a first step towards automatic quantification of wide range of measurements.
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| 8. |
- Gilje, Patrik, et al.
(författare)
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The association between plasma miR-122-5p release pattern at admission and all-cause mortality or shock after out-of-hospital cardiac arrest
- 2019
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Ingår i: Biomarkers. - 1354-750X. ; 24:1, s. 29-35
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Tidskriftsartikel (refereegranskat)abstract
- Background: Data suggests that the plasma levels of the liver-specific miR-122-5p might both be a marker of cardiogenic shock and a prognostic marker of out-of-hospital cardiac arrest (OHCA). Our aim was to characterize plasma miR-122-5p at admission after OHCA and to assess the association between miR-122-5p and relevant clinical factors such all-cause mortality and shock at admission after OHCA. Methods: In the pilot trial, 10 survivors after OHCA were compared to 10 age- and sex-matched controls. In the main trial, 167 unconscious survivors of OHCA from the Targeted Temperature Management (TTM) trial were included. Results: In the pilot trial, plasma miR-122-5p at admission after OHCA was 400-fold elevated compared to controls. In the main trial, plasma miR-122-5p at admission was independently associated with lactate and bystander cardiopulmonary resuscitation. miR-122-5p at admission was not associated with shock at admission (p = 0.14) or all-cause mortality (p = 0.35). Target temperature (33 °C vs 36 °C) was not associated with miR-122-5p levels at any time point. Conclusions: After OHCA, miR-122-5p demonstrated a marked acute increase in plasma and was independently associated with lactate and bystander resuscitation. However, miR-122-5p at admission was not associated with all-cause mortality or shock at admission.
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| 9. |
- Gilje, Patrik, et al.
(författare)
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The brain-enriched microRNA miR-124 in plasma predicts neurological outcome after cardiac arrest
- 2014
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 18:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Early prognostication after successful cardiopulmonary resuscitation is difficult, and there is a need for novel methods to estimate the extent of brain injury and predict outcome. In this study, we evaluated the impact of the cardiac arrest syndrome on the plasma levels of selected tissue-specific microRNAs (miRNAs) and assessed their ability to prognosticate death and neurological disability. Methods: We included 65 patients treated with hypothermia after cardiac arrest in the study. Blood samples were obtained at 24 hours and at 48 hours. For miRNA-screening purposes, custom quantitative polymerase chain reaction (qPCR) panels were first used. Thereafter individual miRNAs were assessed at 48 hours with qPCR. miRNAs that successfully predicted prognosis at 48 hours were further analysed at 24 hours. Outcomes were measured according to the Cerebral Performance Category (CPC) score at 6 months after cardiac arrest and stratified into good (CPC score 1 or 2) or poor (CPC scores 3 to 5). Results: At 48 hours, miR-146a, miR-122, miR-208b, miR-21, miR-9 and miR-128 did not differ between the good and poor neurological outcome groups. In contrast, miR-124 was significantly elevated in patients with poor outcomes compared with those with favourable outcomes (P < 0.0001) at 24 hours and 48 hours after cardiac arrest. Analysis of receiver operating characteristic curves at 24 and 48 hours after cardiac arrest showed areas under the curve of 0.87 (95% confidence interval (CI) = 0.79 to 0.96) and 0.89 (95% CI = 0.80 to 0.97), respectively. Conclusions: The brain-enriched miRNA miR-124 is a promising novel biomarker for prediction of neurological prognosis following cardiac arrest.
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| 10. |
- Grigorios-Aris, Cheimariotis, et al.
(författare)
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Automatic segmentation of lungs in SPECT images using active shape model trained by meshes delineated in CT images
- 2016
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Ingår i: 2016 38th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2016. - 9781457702204 ; 2016-October, s. 1280-1283
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Konferensbidrag (refereegranskat)abstract
- This paper presents a fully automated method for segmentation of 3D SPECT ventilation and perfusion images. It relies on statistical information on lung shape derived by CT manual segmentation and its main processing steps are: shape model extraction, binary segmentation, positioning of mean shape in SPECT images and iterative shape adaptation based on intensity profiles and on what is considered 'plausible' lung shape. The Active Shape Model is used to generate accurate anatomic results in SPECT images with functional information and thus unclear borders, especially in the case of pathologies. The method was compared against ground truth manual segmentation on CT images, using volumetric, difference dice coefficient, sensitivity and precision.
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