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  • 1.
    Holmgren, Madelene
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Holmlund, Petter
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Stoverud, Karen-Helene
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Department of Health Research, SINTEF Digital, NO, Trondheim, Norway.
    Zarrinkoob, Laleh
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Wåhlin, Anders
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Prediction of cerebral perfusion pressure during carotid surgery: A computational fluid dynamics approach2022In: Clinical Biomechanics, ISSN 0268-0033, E-ISSN 1879-1271, Vol. 100, article id 105827Article in journal (Refereed)
    Abstract [en]

    Background: Maintaining cerebral perfusion pressure in the brain when a carotid artery is closed during vascular surgery is critical for avoiding intraoperative hypoperfusion and risk of ischemic stroke. Here we propose and evaluate a method based on computational fluid dynamics for predicting patient-specific cerebral perfusion pressures at carotid clamping during carotid endarterectomy.

    Methods: The study consisted of 22 patients with symptomatic carotid stenosis who underwent carotid endarterectomy (73 ± 5 years, 59–80 years, 17 men). The geometry of the circle of Willis was obtained preoperatively from computed tomography angiography and corresponding flow rates from four-dimensional flow magnetic resonance imaging. The patients were also classified as having a present or absent ipsilateral posterior communicating artery based on computed tomography angiography. The predicted mean stump pressures from computational fluid dynamics were compared with intraoperatively measured stump pressures from carotid endarterectomy.

    Findings: On group level, there was no difference between the predicted and measured stump pressures (−0.5 ± 13 mmHg, P = 0.86) and the pressures were correlated (r = 0.44, P = 0.039). Omitting two outliers, the correlation increased to r = 0.78 (P < 0.001) (−1.4 ± 8.0 mmHg, P = 0.45). Patients with a present ipsilateral posterior communicating artery (n = 8) had a higher measured stump pressure than those with an absent artery (n = 12) (P < 0.001).

    Interpretation: The stump pressure agreement indicates that the computational fluid dynamics approach was promising in predicting cerebral perfusion pressures during carotid clamping, which may prove useful in the preoperative planning of vascular interventions.

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  • 2.
    Holmgren, Madelene
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Holmlund, Petter
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Støverud, Karen-Helene
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Zarrinkoob, Laleh
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Computational fluid dynamics for prediction of measured carotid stump pressure during carotid endarterectomyManuscript (preprint) (Other academic)
  • 3.
    Holmgren, Madelene
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Stoverud, Karen-Helene
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Zarrinkoob, Laleh
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Middle cerebral artery pressure laterality in patients with symptomatic ICA stenosis2021In: PLOS ONE, E-ISSN 1932-6203, Vol. 16, no 1, article id e0245337Article in journal (Refereed)
    Abstract [en]

    An internal carotid artery (ICA) stenosis can potentially decrease the perfusion pressure to the brain. In this study, computational fluid dynamics (CFD) was used to study if there was a hemispheric pressure laterality between the contra- and ipsilateral middle cerebral artery (MCA) in patients with a symptomatic ICA stenosis. We further investigated if this MCA pressure laterality (ΔPMCA) was related to the hemispheric flow laterality (ΔQ) in the anterior circulation, i.e., ICA, proximal MCA and the proximal anterior cerebral artery (ACA). Twenty-eight patients (73±6 years, range 59–80 years, 21 men) with symptomatic ICA stenosis were included. Flow rates were measured using 4D flow MRI data (PC-VIPR) and vessel geometries were obtained from computed tomography angiography. The ΔPMCA was calculated from CFD, where patient-specific flow rates were applied at all input- and output boundaries. The ΔPMCA between the contra- and ipsilateral side was 6.4±8.3 mmHg (p<0.001) (median 3.9 mmHg, range -1.3 to 31.9 mmHg). There was a linear correlation between the ΔPMCA and ΔQICA (r = 0.85, p<0.001) and ΔQACA (r = 0.71, p<0.001), respectively. The correlation to ΔQMCA was weaker (r = 0.47, p = 0.011). In conclusion, the MCA pressure laterality obtained with CFD, is a promising physiological biomarker that can grade the hemodynamic disturbance in patients with a symptomatic ICA stenosis.

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  • 4.
    Holmlund, Petter
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Stoverud, Karen-Helene
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Department of Health Research, SINTEF Digital, Trondheim, Norway.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Mathematical modelling of the CSF system: effects of microstructures and posture on optic nerve subarachnoid space dynamics2022In: Fluids and Barriers of the CNS, E-ISSN 2045-8118, Vol. 19, no 1, article id 67Article in journal (Refereed)
    Abstract [en]

    Background: The pressure difference between the eye and brain in upright postures may be affected by compartmentalization of the optic nerve subarachnoid space (ONSAS). Both pressure and deformation will depend on the microstructures of the ONSAS, and most likely also on ocular glymphatic clearance. Studying these factors could yield important knowledge regarding the translaminar pressure difference, which is suspected to play a role in normal-tension glaucoma.

    Methods: A compartment model coupling the ONSAS with the craniospinal CSF system was used to investigate the effects of microstructures on the pressure transfer through the ONSAS during a posture change from supine to upright body postures. ONSAS distensibility was based on MRI measurements. We also included ocular glymphatic flow to investigate how local pressure gradients alter this flow with changes in posture.

    Results: A compartmentalization of the ONSAS occurred in the upright posture, with ONSAS porosity (degree of microstructural content) affecting the ONSAS pressure (varying the supine/baseline porosity from 1.0 to 0.75 yielded pressures between − 5.3 and − 2 mmHg). Restricting the minimum computed porosity (occurring in upright postures) to 0.3 prevented compartmentalization, and the ONSAS pressure could equilibrate with subarachnoid space pressure (− 6.5 mmHg) in ≤ 1 h. The ocular glymphatics analysis predicted that substantial intraocular-CSF flows could occur without substantial changes in the ONSAS pressure. The flow entering the ONSAS in supine position (both from the intraocular system and from the cranial subarachnoid space) exited the ONSAS through the optic nerve sheath, while in upright postures the flow through the ONSAS was redirected towards the cranial subarachnoid space.

    Conclusions: Microstructures affect pressure transmission along the ONSAS, potentially contributing to ONSAS compartmentalization in upright postures. Different pathways for ocular glymphatic flow were predicted for different postures.

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  • 5.
    Holmlund, Petter
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Stoverud, Karen-Helene
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Wahlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Author Response: Posture-Dependent Collapse of the Optic Nerve Subarachnoid Space: A Combined MRI and Modeling Study2021In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 62, no 15, article id 15Article in journal (Other academic)
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  • 6.
    Holmlund, Petter
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Stoverud, Karen-Helene
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Posture-dependent collapse of the optic nerve subarachnoid space: A combined MRI and modeling study2021In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 62, no 4, article id 26Article in journal (Refereed)
    Abstract [en]

    PURPOSE: We hypothesize that a collapse of the optic nerve subarachnoid space (ONSAS) in the upright posture may protect the eyes from large translamina cribrosa pressure differences (TLCPD) believed to play a role in various optic nerve diseases (e.g., glaucoma). In this study, we combined magnetic resonance imaging (MRI) and mathematical modeling to investigate this potential ONSAS collapse and its effects on the TLCPD.

    METHODS: First, we performed MRI on six healthy volunteers in 6° head-down tilt (HDT) and 13° head-up tilt (HUT) to assess changes in ONSAS volume (measured from the eye to the optic canal) with changes in posture. The volume change reflects optic nerve sheath (ONS) distensibility. Second, we used the MRI data and mathematical modeling to simulate ONSAS pressure and the potential ONSAS collapse in a 90° upright posture.

    RESULTS: The MRI showed a 33% decrease in ONSAS volume from the HDT to HUT (P < 0.001). In the upright posture, the simulations predicted an ONSAS collapse 25 mm behind lamina cribrosa, disrupting the pressure communication between the ONSAS and the intracranial subarachnoid space. The collapse reduced the simulated postural increase in TLCPD by roughly 1 mm Hg, although this reduction was highly sensitive to ONS distensibility, varying between 0 and 4.8 mm Hg when varying the distensibility by ± 1 SD.

    CONCLUSIONS: The ONSAS volume along the optic nerve is posture dependent. The simulations supported the hypothesized ONSAS collapse in the upright posture and showed that even small changes in ONS stiffness/distensibility may affect the TLCPD.

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  • 7.
    Rohlén, Robin
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Stoverud, Karen-Helene
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Yu, Jun
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Grönlund, Christer
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Segmentation of Motor Unit Territories in Ultrasound Image Sequences of Contracting Skeletal Muscle Tissue2017Conference paper (Other academic)
    Abstract [en]

    Ultrasound medical imaging can be used to visualize and quantify anatomical and functional aspects of internal tissues and organs of the human body. Skeletal muscle tissue is functionally composed by motor units, which are the smallest voluntarily activatable units. In order to capture a transient phenomenon, such as the contraction mechanism, a high sample rate is required. There has been a lot of research on whole-muscle aspects in terms of skeletal muscle contraction characteristics, neuromuscular disorders, and inter-muscle segmentation. Previous studies have shown that small-scale muscle twitches can be detected using ultrasound and there are several reports on ultrasound-based detection of electro-stimulated motor unit activity. However, methods for intra-muscular ultrasound-based analysis of muscle tissue are largely underdeveloped, in particular regarding the level of motor units.Diagnostics of skeletal muscle tissue is based on analyzing features of these units by invasive, non-imaging electrophysiological methods. Here,we make progress by using non-invasive ultrasound imaging to segment motor units, which have the potential to be a non-invasive substitute and where the imaging provides an important contribution.

  • 8.
    Rohlén, Robin
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Stålberg, Erik
    Department of Clinical Neurophysiology, Department of Neurosciences, University Hospital, Uppsala University, Sweden.
    Stoverud, Karen-Helene
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Yu, Jun
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Grönlund, Christer
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    A Method for Identification of Mechanical Response of Motor Units in Skeletal Muscle Voluntary Contractions using Ultrafast Ultrasound Imaging: Simulations and Experimental Tests2020In: IEEE Access, E-ISSN 2169-3536, Vol. 8, p. 50299-50311Article in journal (Refereed)
    Abstract [en]

    The central nervous system coordinates movement through forces generated by motor units (MUs) in skeletal muscles. To analyze MUs function is essential in sports, rehabilitation medicine applications, and neuromuscular diagnostics. The MUs and their function are studied using electromyography. Typically, these methods study only a small muscle volume (1 mm3) or only a superficial (< 1 cm) volume of the muscle. Here we introduce a method to identify so-called mechanical units, i.e., the mechanical response of electrically active MUs, in the whole muscle (4x4 cm, cross-sectional) under voluntary contractions by ultrafast ultrasound imaging and spatiotemporal decomposition. We evaluate the performance of the method by simulation of active MUs' mechanical response under weak contractions. We further test the experimental feasibility on eight healthy subjects. We show the existence of mechanical units that contribute to the tissue dynamics in the biceps brachii at low force levels and that these units are similar to MUs described by electromyography with respect to the number of units, territory sizes, and firing rates. This study introduces a new potential neuromuscular functional imaging method, which could be used to study a variety of questions on muscle physiology that previously were difficult or not possible to address.

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  • 9.
    Rohlén, Robin
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Stålberg, Erik
    Uppsala University.
    Stoverud, Karen-Helene
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Yu, Jun
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Grönlund, Christer
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Ultrasound-based Imaging of Motor Units in Skeletal Muscle Tissue2018Conference paper (Other academic)
    Abstract [en]

    Neuromuscular diseases hinder muscle function and may be the outcome of damage and dysfunction of the smallest voluntarily activatable units in skeletal muscle tissue, the so-called motor units (MUs). MUs generate electrical signals and analyzing these signals gives a basis to assess and diagnose MUs. The signals are captured using needle electromyography, which is an invasive and non-imaging method. Here, we showultrasound-basedimaging of MUs, via an ultrasound-based spatiotemporal decomposition framework.

  • 10.
    Stoverud, Karen-Helene
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Center for Biomedical Computing, Simula Research Laboratory and Department of Informatics, University of Oslo, Oslo, Norway.
    Langtangen, Hans Petter
    Ringstad, Geir Andre
    Eide, Per Kristian
    Mardal, Kent-Andre
    Computational Investigation of Cerebrospinal Fluid Dynamics in the Posterior Cranial Fossa and Cervical Subarachnoid Space in Patients with Chiari I Malformation2016In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 10, article id e0162938Article in journal (Refereed)
    Abstract [en]

    Purpose Previous computational fluid dynamics (CFD) studies have demonstrated that the Chiari malformation is associated with abnormal cerebrospinal fluid (CSF) flow in the cervical part of the subarachnoid space (SAS), but the flow in the SAS of the posterior cranial fossa has received little attention. This study extends previous modelling efforts by including the cerebellomedullary cistern, pontine cistern, and 4th ventricle in addition to the cervical subarachnoid space. Methods The study included one healthy control, Con1, and two patients with Chiari I malformation, P1 and P2. Meshes were constructed by segmenting images obtained from T2-weighted turbo spin-echo sequences. CFD simulations were performed with a previously verified and validated code. Patient-specific flow conditions in the aqueduct and the cervical SAS were used. Two patients with the Chiari malformation and one control were modelled. Results The results demonstrated increased maximal flow velocities in the Chiari patients, ranging from factor 5 in P1 to 14.8 in P2, when compared to Con1 at the level of Foramen Magnum (FM). Maximal velocities in the cervical SAS varied by a factor 2.3, while the maximal flow in the aqueduct varied by a factor 3.5. The pressure drop from the pontine cistern to the cervical SAS was similar in Con1 and P1, but a factor two higher in P2. The pressure drop between the aqueduct and the cervical SAS varied by a factor 9.4 where P1 was the one with the lowest pressure jump and P2 and Con1 differed only by a factor 1.6. Conclusion This pilot study demonstrates that including the posterior cranial fossa is feasible and suggests that previously found flow differences between Chiari I patients and healthy individuals in the cervical SAS may be present also in the SAS of the posterior cranial fossa.

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  • 11. Vinje, Vegard
    et al.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Mardal, Kent-Andre
    Rognes, Marie E.
    Stoverud, Karen-Helene
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Intracranial pressure elevation alters CSF clearance pathways2020In: Fluids and Barriers of the CNS, E-ISSN 2045-8118, Vol. 17, no 1, article id 29Article in journal (Refereed)
    Abstract [en]

    Background: Infusion testing is a common procedure to determine whether shunting will be beneficial in patients with normal pressure hydrocephalus. The method has a well-developed theoretical foundation and corresponding mathematical models that describe the CSF circulation from the choroid plexus to the arachnoid granulations. Here, we investigate to what extent the proposed glymphatic or paravascular pathway (or similar pathways) modifies the results of the traditional mathematical models.

    Methods: We used a compartment model to estimate pressure in the subarachnoid space and the paravascular spaces. For the arachnoid granulations, the cribriform plate and the glymphatic circulation, resistances were calculated and used to estimate pressure and flow before and during an infusion test. Finally, different variations to the model were tested to evaluate the sensitivity of selected parameters.

    Results: At baseline intracranial pressure (ICP), we found a very small paravascular flow directed into the subarachnoid space, while 60% of the fluid left through the arachnoid granulations and 40% left through the cribriform plate. However, during the infusion, 80% of the fluid left through the arachnoid granulations, 20% through the cribriform plate and flow in the PVS was stagnant. Resistance through the glymphatic system was computed to be 2.73 mmHg/(mL/min), considerably lower than other fluid pathways, giving non-realistic ICP during infusion if combined with a lymphatic drainage route.

    Conclusions: The relative distribution of CSF flow to different clearance pathways depends on ICP, with the arachnoid granulations as the main contributor to outflow. As such, ICP increase is an important factor that should be addressed when determining the pathways of injected substances in the subarachnoid space. Our results suggest that the glymphatic resistance is too high to allow for pressure driven flow by arterial pulsations and at the same time too small to allow for a direct drainage route from PVS to cervical lymphatics.

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