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Fahlström, Markus
Publications (10 of 23) Show all publications
Fahlström, M., Lewén, A., Enblad, P., Larsson, E.-M. & Wikström, J. (2020). High Intravascular Signal Arterial Transit Time Artifacts Have Negligible Effects on Cerebral Blood Flow and Cerebrovascular Reserve Capacity Measurement Using Single Postlabel Delay Arterial Spin-Labeling in Patients with Moyamoya Disease. American Journal of Neuroradiology
Open this publication in new window or tab >>High Intravascular Signal Arterial Transit Time Artifacts Have Negligible Effects on Cerebral Blood Flow and Cerebrovascular Reserve Capacity Measurement Using Single Postlabel Delay Arterial Spin-Labeling in Patients with Moyamoya Disease
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2020 (English)In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959XArticle in journal (Refereed) Epub ahead of print
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-405377 (URN)10.3174/ajnr.A6411 (DOI)
Available from: 2020-02-27 Created: 2020-02-27 Last updated: 2020-03-05
Fahlström, M. (2020). On potentials and limitations of perfusion MRI in neurological disorders. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>On potentials and limitations of perfusion MRI in neurological disorders
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cerebral perfusion outlines several parameters which describe the status of cerebral haemodynamics. Numerous neurological diseases affect cerebral perfusion, thus the importance of diagnostic measurements. Perfusion magnetic resonance imaging (MRI) is a collection of non-ionizing magnetic resonance-based perfusion measurement techniques that can be used for clinical assessment of cerebral perfusion. The aim of this thesis was to investigate potentials and limitations of perfusion MRI used for clinical assessment of patients with neurological disorders. Patients with glioblastoma were examined with dynamic susceptibility contrast MRI (DSC-MRI) and dynamic contrast enhanced MRI (DCE-MRI) before/after treatment with fractionated radiotherapy (FRT). Radiation-induced changes in normal-appearing brain tissue were found in the form of decreased cerebral blood volume (CBV) and cerebral blood flow (CBF) measured with DSC-MRI and increased vascular permeability and increased fraction of the extravascular extracellular space measured with DCE-MRI. Papers I–II provide valuable information regarding the possibility that radiation-induced changes could be a confounder in DSC-MRI and that DCE-MRI could potentially act as a biomarker for vascular damage secondary to radiation exposure. Additionally, CBF derived from arterial spin labelling (ASL) was compared to the reference standard 15O-water positron emission tomography (PET). Simultaneous measurements were acquired with an integrated PET/MR scanner using arterial blood sampling and zero-echo time-based attenuation correction in healthy subjects and patients with epilepsy. Correlation- and Bland–Altman analysis showed fair correlation and a negative relationship with wide limits of agreement in several cortical and subcortical regions. Thus, agreement with 15O-water is insufficient for absolute quantification with ASL, but ASL provides reliable relative measures that could potentially be rescaled to absolute values. Moyamoya disease (MMD) is characterized by progressive stenosis/occlusion in large brain arteries. A limitation of ASL is the sensitivity to prolonged arterial transit times, which is common in the collateral vessels of the brain in patients with MMD. Given the non-invasiveness and non-ionizing exposure, ASL has a pronounced potential for use in diagnostic imaging in patients with MMD. ASL was performed before and after administration of acetazolamide; CBF and cerebrovascular reserve capacity were derived for large vascular regions. Artefacts originating from prolonged arterial transit times were found to have negligible effects on CBF and cerebrovascular reserve capacity derived from ASL. This thesis adds to the understanding of potential and limitations of perfusion MRI in neurological diseases. 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2020. p. 63
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1642
Keywords
Neurological disease, MRI, Perfusion, 15O-water PET
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Medical Radiophysics
Identifiers
urn:nbn:se:uu:diva-404604 (URN)978-91-513-0883-8 (ISBN)
Public defence
2020-04-17, H:Son-Holmdahlsalen, Akademiska Sjukhuset, Ing 100 2 tr, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2020-03-26 Created: 2020-03-01 Last updated: 2020-03-26
Latini, F., Fahlström, M., Berntsson, S. G., Larsson, E.-M., Smits, A. & Ryttlefors, M. (2019). A novel radiological classification system for cerebral gliomas: The Brain-Grid. PLoS ONE, 14(1), Article ID e0211243.
Open this publication in new window or tab >>A novel radiological classification system for cerebral gliomas: The Brain-Grid
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2019 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 1, article id e0211243Article in journal (Refereed) Published
Abstract [en]

PURPOSE: Standard radiological/topographical classifications of gliomas often do not reflect the real extension of the tumor within the lobar-cortical anatomy. Furthermore, these systems do not provide information on the relationship between tumor growth and the subcortical white matter architecture. We propose the use of an anatomically standardized grid system (the Brain-Grid) to merge serial morphological magnetic resonance imaging (MRI) scans with a representative tractographic atlas. Two illustrative cases are presented to show the potential advantages of this classification system.

METHODS: MRI scans of 39 patients (WHO grade II and III gliomas) were analyzed with a standardized grid created by intersecting longitudinal lines on the axial, sagittal, and coronal planes. The anatomical landmarks were chosen from an average brain, spatially normalized to the Montreal Neurological Institute (MNI) space and the Talairach space. Major white matter pathways were reconstructed with a deterministic tracking algorithm on a reference atlas and analyzed using the Brain-Grid system.

RESULTS: In all, 48 brain grid voxels (areas defined by 3 coordinates, axial (A), coronal (C), sagittal (S) and numbers from 1 to 4) were delineated in each MRI sequence and on the tractographic atlas. The number of grid voxels infiltrated was consistent, also in the MNI space. The sub-cortical insula/basal ganglia (A3-C2-S2) and the fronto-insular region (A3-C2-S1) were most frequently involved. The inferior fronto-occipital fasciculus, anterior thalamic radiation, uncinate fasciculus, and external capsule were the most frequently associated pathways in both hemispheres.

CONCLUSIONS: The Brain-Grid based classification system provides an accurate observational tool in all patients with suspected gliomas, based on the comparison of grid voxels on a morphological MRI and segmented white matter atlas. Important biological information on tumor kinetics including extension, speed, and preferential direction of progression can be observed and even predicted with this system. This novel classification can easily be applied to both prospective and retrospective cohorts of patients and increase our comprehension of glioma behavior.

National Category
Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-375437 (URN)10.1371/journal.pone.0211243 (DOI)000456700400066 ()30677090 (PubMedID)
Note

De 2 sista författarna delar sistaförfattarskapet.

Available from: 2019-01-29 Created: 2019-01-29 Last updated: 2019-03-07Bibliographically approved
Shanks, J., Bloch, K. M., Laurell, K., Cesarini, K. G., Fahlström, M., Larsson, E.-M. & Virhammar, J. (2019). Aqueductal CSF Stroke Volume Is Increased in Patients with Idiopathic Normal Pressure Hydrocephalus and Decreases after Shunt Surgery. American Journal of Neuroradiology, 40(3), 453-459
Open this publication in new window or tab >>Aqueductal CSF Stroke Volume Is Increased in Patients with Idiopathic Normal Pressure Hydrocephalus and Decreases after Shunt Surgery
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2019 (English)In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 40, no 3, p. 453-459Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND PURPOSE: Increased CSF stroke volume through the cerebral aqueduct has been proposed as a possible indicator of positive surgical outcome in patients with idiopathic normal pressure hydrocephalus; however, consensus is lacking. In this prospective study, we aimed to compare CSF flow parameters in patients with idiopathic normal pressure hydrocephalus with those in healthy controls and change after shunt surgery and to investigate whether any parameter could predict surgical outcome. MATERIALS AND METHODS: Twenty-one patients with idiopathic normal pressure hydrocephalus and 21 age- and sex-matched healthy controls were prospectively included and examined clinically and with MR imaging of the brain. Eighteen patients were treated with shunt implantation and were re-examined clinically and with MR imaging the day before the operation and 3 months postoperatively. All MR imaging scans included a phase-contrast sequence. RESULTS: The median aqueductal CSF stroke volume was significantly larger in patients compared with healthy controls (103.5 mu L; interquartile range, 69.8-142.8 mu L) compared with 62.5 mu L (interquartile range, 58.3-73.8 mu L; P < .01) and was significantly reduced 3 months after shunt surgery from 94.8 mu L (interquartile range, 81-241 mu L) to 88 mu L (interquartile range, 51.8-173.3 mu L; P < .05). Net flow in the caudocranial direction (retrograde) was present in 11/21 patients and in 10/21 controls. Peak flow and net flow did not differ between patients and controls. There were no correlations between any CSF flow parameters and surgical outcomes. CONCLUSIONS: Aqueductal CSF stroke volume was increased in patients with idiopathic normal pressure hydrocephalus and decreased after shunt surgery, whereas retrograde aqueductal net flow did not seem to be specific for patients with idiopathic normal pressure hydrocephalus. On the basis of the results, the usefulness of CSF flow parameters to predict outcome after shunt surgery seem to be limited.

Place, publisher, year, edition, pages
AMER SOC NEURORADIOLOGY, 2019
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-380474 (URN)10.3174/ajnr.A5972 (DOI)000461201600016 ()30792248 (PubMedID)
Available from: 2019-04-16 Created: 2019-04-16 Last updated: 2019-04-16Bibliographically approved
Cubo, R., Fahlström, M., Jiltsova, E., Andersson, H. & Medvedev, A. (2019). Calculating Deep Brain Stimulation Amplitudes and Power Consumption by Constrained Optimization. Journal of Neural Engineering, 16(1), Article ID 016020.
Open this publication in new window or tab >>Calculating Deep Brain Stimulation Amplitudes and Power Consumption by Constrained Optimization
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2019 (English)In: Journal of Neural Engineering, ISSN 1741-2560, E-ISSN 1741-2552, Vol. 16, no 1, article id 016020Article in journal (Refereed) Published
Abstract [en]

Objective: Deep brain stimulation (DBS) consists of delivering electrical stimuli to a brain target via an implanted lead to treat neurological and psychiatric conditions. Individualized stimulation is vital to ensure therapeutic results, since DBS may otherwise become ineffective or cause undesirable side effects. Since the DBS pulse generator is battery-driven, power consumption incurred by the stimulation is important. In this study, target coverage and power consumption are compared over a patient population for clinical and model-based patient-specific settings calculated by constrained optimization.

Approach: Brain models for five patients undergoing bilateral DBS were built. Mathematical optimization of activated tissue volume was utilized to calculate stimuli amplitudes, with and without specifying the volumes, where stimulation was not allowed to avoid side effects. Power consumption was estimated using measured impedance values and battery life under both clinical and optimized settings.

Results: It was observed that clinical settings were generally less aggressive than the ones suggested by unconstrained model-based optimization, especially under asymmetrical stimulation. The DBS settings satisfying the constraints were close to the clinical values.

Significance: The use of mathematical models to suggest optimal patient-specific DBS settings that observe technological and safety constraints can save time in clinical practice. It appears though that the considered safety constraints based on brain anatomy depend on the patient and further research into it is needed. This work highlights the need of specifying the brain volumes to be avoided by stimulation while optimizing the DBS amplitude, in contrast to minimizing general stimuli overspill, and applies the technique to a cohort of patients. It also stresses the importance of considering power consumption in DBS optimization, since it increases with the square of the stimuli amplitude and also critically affects battery life through pulse frequency and duty cycle.

Keywords
neuromodulation, deep brain stimulation, inverse problems
National Category
Control Engineering
Identifiers
urn:nbn:se:uu:diva-368330 (URN)10.1088/1741-2552/aaeeb7 (DOI)000455843600002 ()30524006 (PubMedID)
Available from: 2018-12-04 Created: 2018-12-04 Last updated: 2019-02-05Bibliographically approved
Fahlström, M., Fransson, S., Blomquist, E., Nyholm, T. & Larsson, E.-M. (2018). Dynamic Contrast-Enhanced Magnetic Resonance Imaging May Act as a Biomarker for Vascular Damage in Normal Appearing Brain Tissue after Radiotherapy in Patients with Glioblastoma. Acta Radiologica Open, 7(11)
Open this publication in new window or tab >>Dynamic Contrast-Enhanced Magnetic Resonance Imaging May Act as a Biomarker for Vascular Damage in Normal Appearing Brain Tissue after Radiotherapy in Patients with Glioblastoma
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2018 (English)In: Acta Radiologica Open, ISSN 2058-4601, Vol. 7, no 11Article in journal (Refereed) Published
Abstract [en]

Background: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a promising perfusion method and may be useful in evaluating radiation-induced changes in normal-appearing brain tissue.

Purpose: To assess whether radiotherapy induces changes in vascular permeability (Ktrans) and the fractional volume of the extravascular extracellular space (Ve) derived from DCE-MRI in normal-appearing brain tissue and possible relationships to radiation dose given.

Material and Methods: Seventeen patients with glioblastoma treated with radiotherapy and chemotherapy were included; five were excluded because of inconsistencies in the radiotherapy protocol or early drop-out. DCE-MRI, contrast-enhanced three-dimensional (3D) T1-weighted (T1W) images and T2-weighted fluid attenuated inversion recovery (T2-FLAIR) images were acquired before and on average 3.3, 30.6, 101.6, and 185.7 days after radiotherapy. Pre-radiotherapy CE T1W and T2-FLAIR images were segmented into white and gray matter, excluding all non-healthy tissue. Ktrans and Ve were calculated using the extended Kety model with the Parker population-based arterial input function. Six radiation dose regions were created for each tissue type, based on each patient's computed tomography-based dose plan. Mean Ktrans and Ve were calculated over each dose region and tissue type.

Results: Global Ktrans and Ve demonstrated mostly non-significant changes with mean values higher for post-radiotherapy examinations in both gray and white matter compared to pre-radiotherapy. No relationship to radiation dose was found.

Conclusion: Additional studies are needed to validate if Ktrans and Ve derived from DCE-MRI may act as potential biomarkers for acute and early-delayed radiation-induced vascular damages. No dose-response relationship was found.

National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-346813 (URN)10.1177/2058460118808811 (DOI)000450106500001 ()30542625 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2018-03-21 Created: 2018-03-21 Last updated: 2020-03-01Bibliographically approved
Dhara, A. K., Arids, E., Fahlström, M., Wikström, J., Larsson, E.-M. & Strand, R. (2018). Interactive segmentation of glioblastoma for post-surgical treatment follow-up. In: Proc. 24th International Conference on Pattern Recognition: . Paper presented at ICPR 2018, August 20–24, Beijing, China (pp. 1199-1204). IEEE
Open this publication in new window or tab >>Interactive segmentation of glioblastoma for post-surgical treatment follow-up
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2018 (English)In: Proc. 24th International Conference on Pattern Recognition, IEEE, 2018, p. 1199-1204Conference paper, Published paper (Refereed)
Place, publisher, year, edition, pages
IEEE, 2018
National Category
Medical Image Processing
Research subject
Computerized Image Processing
Identifiers
urn:nbn:se:uu:diva-368290 (URN)10.1109/ICPR.2018.8545105 (DOI)000455146801036 ()978-1-5386-3788-3 (ISBN)
Conference
ICPR 2018, August 20–24, Beijing, China
Note

Best paper award

Available from: 2018-12-03 Created: 2018-12-03 Last updated: 2019-02-21Bibliographically approved
Vedung, F., Lanni, F., Fahlström, M., Larsson, E.-M. & Marklund, N. (2018). Localized Injury Along White Matter Tracts In Patients With Traumatic Brain Injury Affects Memory Functions In Chronic State. Paper presented at 3rd Joint Symposium of the International-and-National-Neurotrauma-Societies-and-AANS/CNS-Section on Neurotrauma and Critical Care, AUG 11-16, 2018, Toronto, CANADA. Journal of Neurotrauma, 35(16), A140-A141
Open this publication in new window or tab >>Localized Injury Along White Matter Tracts In Patients With Traumatic Brain Injury Affects Memory Functions In Chronic State
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2018 (English)In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 35, no 16, p. A140-A141Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
MARY ANN LIEBERT, INC, 2018
Keywords
Axonal Injury, Cognition / Learning / Memory, Imaging, White Matter
National Category
Neurology Neurosciences
Identifiers
urn:nbn:se:uu:diva-363879 (URN)000441527400380 ()
Conference
3rd Joint Symposium of the International-and-National-Neurotrauma-Societies-and-AANS/CNS-Section on Neurotrauma and Critical Care, AUG 11-16, 2018, Toronto, CANADA
Available from: 2018-11-12 Created: 2018-11-12 Last updated: 2018-11-12Bibliographically approved
Fahlström, M., Blomquist, E., Nyholm, T. & Larsson, E.-M. (2018). Perfusion Magnetic Resonance Imaging Changes in Normal Appearing Brain Tissue after Radiotherapy in Glioblastoma Patients may Confound Longitudinal Evaluation of Treatment Response. Radiology and Oncology, 52(2), 143-151
Open this publication in new window or tab >>Perfusion Magnetic Resonance Imaging Changes in Normal Appearing Brain Tissue after Radiotherapy in Glioblastoma Patients may Confound Longitudinal Evaluation of Treatment Response
2018 (English)In: Radiology and Oncology, ISSN 1318-2099, E-ISSN 1581-3207, Vol. 52, no 2, p. 143-151Article in journal (Refereed) Published
Abstract [en]

Background: The aim of this study was assess acute and early delayed radiation-induced changes in normal-appearing brain tissue perfusion as measured with perfusion magnetic resonance imaging (MRI) and the dependence of these changes on the fractionated radiotherapy (FRT) dose level.

Patients and methods: Seventeen patients with glioma WHO grade III-IV treated with FRT were included in this prospective study, seven were excluded because of inconsistent FRT protocol or missing examinations. Dynamic susceptibility contrast MRI and contrast-enhanced 3D-T1-weighted (3D-T1w) images were acquired prior to and in average (standard deviation): 3.1 (3.3), 34.4 (9.5) and 103.3 (12.9) days after FRT. Pre-FRT 3D-T1w images were segmented into white- and grey matter. Cerebral blood volume (CBV) and cerebral blood flow (CBF) maps were calculated and co-registered patient-wise to pre-FRT 3D-T1w images. Seven radiation dose regions were created for each tissue type: 0-5 Gy, 5-10 Gy, 10-20 Gy, 20-30 Gy, 30-40 Gy, 40-50 Gy and 50-60 Gy. Mean CBV and CBF were calculated in each dose region and normalised (nCBV and nCBF) to the mean CBV and CBF in 0-5 Gy white- and grey matter reference regions, respectively.

Results: Regional and global nCBV and nCBF in white- and grey matter decreased after FRT, followed by a tendency to recover. The response of nCBV and nCBF was dose-dependent in white matter but not in grey matter.

Conclusions: Our data suggest that radiation-induced perfusion changes occur in normal-appearing brain tissue after FRT. This can cause an overestimation of relative tumour perfusion using dynamic susceptibility contrast MRI, and can thus confound tumour treatment evaluation.

Keywords
malignant gliomas, normal-appearing brain tissue, perfusion MRI, radiation-induced changes
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-356784 (URN)10.2478/raon-2018-0022 (DOI)000433103400004 ()30018517 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2018-08-07 Created: 2018-08-07 Last updated: 2020-03-01Bibliographically approved
Fahlström, M. (2018). Perfusion MRI of the brain after radiotherapy in patients with glioblastoma – potential and problems. (Licentiate dissertation). Uppsala: Uppsala universitet
Open this publication in new window or tab >>Perfusion MRI of the brain after radiotherapy in patients with glioblastoma – potential and problems
2018 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

Perfusion Magnetic Resonance Imaging (MRI) is a useful tool in diagnostic evaluation and treatment response assessment in patients with glioblastoma. The standard treatment regimen includes surgical resection, radiotherapy and adjuvant chemotherapy. However, prognosis is poor; relative 5-year survival is 3–5%. Radiotherapy sequelae may have considerable negative effects on the patients’ quality of life. Acute and early delayed radiation-induced injury is primarily considered damage to the cerebral vascular tissue.

 

The general aim of this study was to evaluate how perfusion MRI evaluation, based on contrast agent administration (DSC- and DCE-MRI), is affected by or can be useful to assess radiation-induced changes in normal appearing brain tissue in patients with glioblastoma after radiotherapy.

 

Paper I: Dynamic Susceptibility Contrast (DSC)-MRI is a common perfusion MRI method in clinical practice in patients with glioblastoma. Due to inherent limitations, cerebral blood volume (CBV) and cerebral blood flow (CBF) derived from DSC-MRI are normalized to contralateral normal appearing white matter. Ten patients with glioblastoma were examined. Regional and global normalized CBV and normalized CBF in white and gray matter decreased after radiotherapy, followed by a tendency to recover. The response of nCBV and nCBF was dose-dependent in white matter but not in gray matter. In conclusion, radiotherapy effects on normal appearing white matter can confound treatment evaluation with DSC-MRI in patients with glioblastoma.

 

Paper II: Dynamic Contrast Enhanced (DCE)-MRI may be useful in evaluating radiation-induced damage in normal appearing brain tissue.  DCE-MRI-derived parameters, vascular permeability (Ktrans) and the fractional volume of the extravascular extracellular space (Ve) are potential biomarkers. Twelve patients with glioblastoma were examined. A tendency toward increased Ktrans and Ve was seen, suggesting that these parameters may act as potential biomarkers for acute and early delayed radiation-induced vascular damage

Place, publisher, year, edition, pages
Uppsala: Uppsala universitet, 2018
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-346814 (URN)
Presentation
2018-04-13, Akademiska Sjukhuset, Uppsala, 12:00 (Swedish)
Supervisors
Available from: 2018-04-04 Created: 2018-04-03 Last updated: 2018-04-04Bibliographically approved
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