| 1. |
- Agerskov, Simon, et al.
(författare)
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MRI diffusion and perfusion alterations in the mesencephalon and pons as markers of disease and symptom reversibility in idiopathic normal pressure hydrocephalus
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:10
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Core symptomatology in idiopathic normal pressure hydrocephalus (iNPH) points at dysfunction in the mesencephalon and pons indicating pathological changes in these regions, but only a few studies have addressed the issue. The aim of this study was to investigate diffusion (ADC) and perfusion patterns pre- and postoperatively in these areas in iNPH. Methods Twenty iNPH patients and 15 healthy controls were included. Patients underwent a clinical examination and brain MRI pre- and 3-6 months postoperatively. The MRI-scan included diffusion and dynamic susceptibility contrast perfusion weighted sequences. Regions of interest in the mesencephalon and pons were drawn on a FLAIR sequence and co-registered to ADC maps and perfusion data. Results There were no significant differences in pre or postoperative ADC compared to the control group, however postoperative ADC increased by 10% (p = 0.026) in the mesencephalon and 6% (p = 0.016) in the pons in all patients and also in the subgroup of shunt responders by 11% (p = 0.021) and 4% (p = 0.020), respectively. Preoperative relative cerebral blood flow (rCBF) was similar in iNPH patients and controls. Postoperatively, rCBF increased in shunt responders by 6% (p = 0.02) in the mesencephalon and 11% (p = 0.004) in the pons. This increase correlated with the degree of clinical improvement (r(s)= 0.80, p = 0.031 and r(s)= 0.66, p = 0.021, respectively). Conclusion The postoperative increase in ADC and the correlation between postoperative increase in rCBF and clinical improvement in the mesencephalon and pons shown in this study point at an involvement of these areas in the core pathophysiology and its reversibility in iNPH.
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| 2. |
- Ahmed, Laeeq, et al.
(författare)
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Predicting target profiles with confidence as a service using docking scores
- 2020
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Ingår i: Journal of Cheminformatics. - : Springer Nature. - 1758-2946. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Identifying and assessing ligand-target binding is a core component in early drug discovery as one or more unwanted interactions may be associated with safety issues. Contributions: We present an open-source, extendable web service for predicting target profiles with confidence using machine learning for a panel of 7 targets, where models are trained on molecular docking scores from a large virtual library. The method uses conformal prediction to produce valid measures of prediction efficiency for a particular confidence level. The service also offers the possibility to dock chemical structures to the panel of targets with QuickVina on individual compound basis. Results: The docking procedure and resulting models were validated by docking well-known inhibitors for each of the 7 targets using QuickVina. The model predictions showed comparable performance to molecular docking scores against an external validation set. The implementation as publicly available microservices on Kubernetes ensures resilience, scalability, and extensibility.
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| 3. |
- Alvarsson, Jonathan, 1981-, et al.
(författare)
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Predicting With Confidence : Using Conformal Prediction in Drug Discovery
- 2021
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier. - 0022-3549 .- 1520-6017. ; 110:1, s. 42-49
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Forskningsöversikt (refereegranskat)abstract
- One of the challenges with predictive modeling is how to quantify the reliability of the models' predictions on new objects. In this work we give an introduction to conformal prediction, a framework that sits on top of traditional machine learning algorithms and which outputs valid confidence estimates to predictions from QSAR models in the form of prediction intervals that are specific to each predicted object. For regression, a prediction interval consists of an upper and a lower bound. For classification, a prediction interval is a set that contains none, one, or many of the potential classes. The size of the prediction interval is affected by a user-specified confidence/significance level, and by the nonconformity of the predicted object; i.e., the strangeness as defined by a nonconformity function. Conformal prediction provides a rigorous and mathematically proven framework for in silico modeling with guarantees on error rates as well as a consistent handling of the models' applicability domain intrinsically linked to the underlying machine learning model. Apart from introducing the concepts and types of conformal prediction, we also provide an example application for modeling ABC transporters using conformal prediction, as well as a discussion on general implications for drug discovery.
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| 4. |
- Arvidsson, Jonathan
(författare)
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Advancements in DSC and BOLD perfusion imaging: Acquisition, analysis and clinical application
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is focused on perfusion MRI techniques and topics related to image acquisition, analysis and clinical applications. The first half of the thesis is focused on dynamic susceptibility contrast (DSC) MRI, a technique which is based on the contrast enhancements caused by an intravenously administered paramagnetic contrast agent. The second half of this thesis is focused on blood oxygen level dependent (BOLD) MRI, which leverages a signal effect caused by paramagnetic properties of venous blood. For application in peripheral muscle, this signal effect can be enhanced by restricting the blood flow of a feeding artery to the studied tissue. In papers I and III, it is shown that the duration of the contrast agent injection and the duration of the flow restriction, indeed affects the measures of perfusion produced with these techniques. The pathophysiology of normal pressure hydrocephalus (iNPH) is not completely understood, but symptoms point toward brain stem regions. In paper II, DSC-MRI and diffusion MRI was applied to patients with iNPH, pre and post shunt-surgery, showing the possible involvement of these regions in iNPH symptoms and disease reversibility. In paper IV peripheral muscle BOLD was applied to patients with peripheral artery disease (PAD) and controls, in an exploratory study. Perfusion related measures derived from acquired BOLD curves were able to separate between PAD patients and controls, in accordance with previous studies. Further data exploration found a number of curve traits that could be indicative of potential disease phenotypes, and these have now been documented. As the technique continues to develop towards individual prognostication, these curve traits may be of value for establishing disease severity. In conclusion, this work has made advancements of the common knowledge base within the field of perfusion imaging, spanning from the well-studied area of DSC-MRI to the comparatively new technique of peripheral muscle BOLD imaging and their application to clinically relevant patient cohorts.
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| 5. |
- Arvidsson, Jonathan, et al.
(författare)
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Arterial occlusion duration affects the cuff-induced hyperemic response in skeletal muscle BOLD perfusion imaging as shown in young healthy subjects
- 2023
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Ingår i: Magnetic Resonance Materials in Physics Biology and Medicine. - 1352-8661. ; 36:6, s. 897-910
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Tidskriftsartikel (refereegranskat)abstract
- Objective Dynamic BOLD MRI with cuff compression, inducing ischemia and post-occlusive hyperemia in skeletal mus-cle, has been pointed out as a potential diagnostic tool to assess peripheral limb perfusion. The objective was to explore the robustness of this technique and its sensitivity to the occlusion duration. Materials and methods BOLD images were acquired at 3 T in 14 healthy volunteers. T*2-imaging with 5-and 1.5-min occlu-sions were acquired and several semi-quantitative BOLD parameters were derived from ROI-based T*2-time curves. Differ-ences in parameters from the two different occlusion durations were evaluated in the gastrocnemius and soleus muscles using non-parametrical tests. Intra-and inter-scan repeatability were evaluated with coefficient of variation.Results Longer occlusion duration resulted in an increased hyperemic signal effect yielding significantly different values (p < 0.05) in gastrocnemius for all parameters describing the hyperemic response, and in soleus for two of these parameters. Specifically, 5-min occlusion yielded steeper hyperemic upslope in gastrocnemius (41.0%; p < 0.05) and soleus (59.7%; p = 0.03), shorter time to half peak in gastrocnemius (46.9%; p = 0.00008) and soleus (33.5%; p = 0.0003), and shorter time to peak in gastrocnemius (13.5%; p = 0.02). Coefficients of variation were lower than percentage differences that were found significant. Discussion Findings show that the occlusion duration indeed influences the hyperemic response and thus should play a part in future methodological developments.
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| 6. |
- Arvidsson, Jonathan, 1986, et al.
(författare)
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Automated estimation of in-plane nodule shape in chest tomosynthesis images
- 2015
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Ingår i: International Federation for Medical and Biological Engineering Proceedings. - Cham : Springer International Publishing. - 1680-0737. - 9783319129679 ; 48, s. 20-23
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Konferensbidrag (refereegranskat)abstract
- The purpose of this study was to develop an automated segmentation method for lung nodules in chest tomo-synthesis images. A number of simulated nodules of different sizes and shapes were created and inserted in two different locations into clinical chest tomosynthesis projections. The tomosynthesis volumes were then reconstructed using standard cone beam filtered back projection, with 1 mm slice interval. For the in-plane segmentation, the central plane of each nodule was selected. The segmentation method was formulated as an optimization problem where the nodule boundary corresponds to the minimum of the cost function, which is found by dynamic programming. The cost function was composed of terms related to pixel intensities, edge strength, edge direction and a smoothness constraint. The segmentation results were evaluated using an overlap measure (Dice index) of nodule regions and a distance measure (Hausdorff distance) between true and segmented nodule. On clinical images, the nodule segmentation method achieved a mean Dice index of 0.96 ± 0.01, and a mean Hausdorff distance of 0.5 ± 0.2 mm for isolated nodules and for nodules close to other lung structures a mean Dice index of 0.95 ± 0.02 and a mean Hausdorff distance of 0.5 ± 0.2 mm. The method achieved an acceptable accuracy and may be useful for area estimation of lung nodules.
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| 7. |
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| 8. |
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| 9. |
- Arvidsson, Jonathan, et al.
(författare)
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Effects of bolus injection duration on perfusion estimates in dynamic CT and dynamic susceptibility contrast MRI
- 2023
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Ingår i: Magnetic Resonance Materials in Physics, Biology and Medicine. - : Springer Science and Business Media LLC. - 0968-5243 .- 1352-8661. ; 36:1, s. 95-106
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Tidskriftsartikel (refereegranskat)abstract
- Estimates of cerebral blood flow (CBF) and tissue mean transit time (MTT) have been shown to differ between dynamic CT perfusion (CTP) and dynamic susceptibility contrast MRI (DSC-MRI). This study investigates whether these discrepancies regarding CBF and MTT between CTP and DSC-MRI can be attributed to the different injection durations of these techniques. Five subjects were scanned using CTP and DSC-MRI. Region-wise estimates of CBF, MTT, and cerebral blood volume (CBV) were derived based on oscillatory index regularized singular value decomposition. A parametric model that reproduced the shape of measured time curves and characteristics of resulting perfusion parameter estimates was developed and used to simulate data with injection durations typical for CTP and DSC-MRI for a clinically relevant set of perfusion scenarios and noise levels. In simulations, estimates of CBF/MTT showed larger negative/positive bias and increasing variability for CTP when compared to DSC-MRI, especially for high CBF levels. While noise also affected estimates, at clinically relevant levels, the injection duration effect was larger. There are several methodological differences between CTP and DSC-MRI. The results of this study suggest that the injection duration is among those that can explain differences in estimates of CBF and MTT between these bolus tracking techniques.
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| 10. |
- Arvidsson, Jonathan, et al.
(författare)
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Image Fusion of Reconstructed Digital Tomosynthesis Volumes From a Frontal and a Lateral Acquisition
- 2016
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Ingår i: Radiation protection dosimetry. - : Oxford University Press (OUP). - 1742-3406 .- 0144-8420. ; 169:1-4, s. 410-415
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Tidskriftsartikel (refereegranskat)abstract
- Digital tomosynthesis (DTS) has been used in chest imaging as a low radiation dose alternative to computed tomography (CT). Traditional DTS shows limitations in the spatial resolution in the out-of-plane dimension. As a first indication of whether a dual-plane dual-view (DPDV) DTS data acquisition can yield a fair resolution in all three spatial dimensions, a manual registration between a frontal and a lateral image volume was performed. An anthropomorphic chest phantom was scanned frontally and laterally using a linear DTS acquisition, at 120 kVp. The reconstructed image volumes were resampled and manually co-registered. Expert radiologist delineations of the mediastinal soft tissues enabled calculation of similarity metrics in regard to delineations in a reference CT volume. The fused volume produced the highest total overlap, implying that the fused volume was a more isotropic 3D representation of the examined object than the traditional chest DTS volumes.
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