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Rask-Andersen, Helge
Publications (10 of 129) Show all publications
Schart-Moren, N., Agrawal, S. K., Ladak, H. M., Li, H. & Rask-Andersen, H. (2019). Effects of Various Trajectories on Tissue Preservation in Cochlear Implant Surgery: A Micro-Computed Tomography and Synchrotron Radiation Phase-Contrast Imaging Study. Ear and Hearing, 40(2), 393-400
Open this publication in new window or tab >>Effects of Various Trajectories on Tissue Preservation in Cochlear Implant Surgery: A Micro-Computed Tomography and Synchrotron Radiation Phase-Contrast Imaging Study
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2019 (English)In: Ear and Hearing, ISSN 0196-0202, E-ISSN 1538-4667, Vol. 40, no 2, p. 393-400Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES:

The purpose of this study was to evaluate the three-dimensional (3D) anatomy and potential damage to the hook region of the human cochlea following various trajectories at cochlear implantation (CI). The goal was to determine which of the approaches can avoid lesions to the soft tissues, including the basilar membrane and its suspension to the lateral wall. Currently, there is increased emphasis on conservation of inner ear structures, even in nonhearing preservation CI surgery.

DESIGN:

Micro-computed tomography and various CI approaches were made in an archival collection of macerated and freshly fixed human temporal bones. Furthermore, synchrotron radiation phase-contrast imaging was used to reproduce the soft tissues. The 3D anatomy was investigated using bony and soft tissue algorithms, and influences on inner ear structures were examined.

RESULTS:

Micro-computed tomography with 3D rendering demonstrated the topography of the round window (RW) and osseous spiral laminae, while synchrotron imaging allowed reproduction of soft tissues such as the basilar membrane and its suspension around the RW membrane. Anterior cochleostomies and anteroinferior cochleostomies invariably damaged the intracochlear soft tissues while inferior cochleostomies sporadically left inner ear structures unaffected.

CONCLUSIONS:

Results suggest that cochleostomy approaches often traumatize the soft tissues at the hook region at CI surgery. For optimal structural preservation, the RW approach is, therefore, recommended.

National Category
Otorhinolaryngology
Identifiers
urn:nbn:se:uu:diva-373492 (URN)10.1097/AUD.0000000000000624 (DOI)000459769700016 ()29952804 (PubMedID)
Available from: 2019-01-14 Created: 2019-01-14 Last updated: 2019-06-19Bibliographically approved
Liu, W., Kämpfe Nordström, C., Danckwardt-Lillieström, N. & Rask-Andersen, H. (2019). Human Inner Ear Immune Activity: A Super-Resolution Immunohistochemistry Study. Frontiers in Neurology, 10, Article ID 728.
Open this publication in new window or tab >>Human Inner Ear Immune Activity: A Super-Resolution Immunohistochemistry Study
2019 (English)In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 10, article id 728Article in journal (Refereed) Published
Abstract [en]

Background: Like the brain, the human inner ear was long thought to be devoid of immune activity. Only the endolymphatic sac (ES) was known to be endowed with white blood cells that could process antigens and serve as an immunologic defense organ for the entire inner ear. Unexpectedly, the cochlear and vestibular organs, including the eighth cranial nerve, were recently shown to contain macrophages whose functions and implication in ear disease are somewhat undefined. Here, we review recent inner ear findings in man and extend the analyses to the vestibular nerve using super-resolution structured illumination microscopy (SR-SIM).

Materials and Methods: Human ESs and cochleae were collected during surgery to treat patients with vestibular schwannoma and life-threatening petro-clival meningioma compressing the brainstem. The ESs and cochleae were placed in fixative, decalcified, and rapidly frozen and cryostat sectioned. Antibodies against ionized calcium-binding adaptor molecule 1-expressing cells (IBA1 cells), laminin beta 2 and type IV collagen TUJ1, cytokine fractalkine (CX3CL1), toll-like receptor 4 (TLR4), CD68, CD11b, CD4, CD8, the major histocompatibility complex type II (MHCII), and the microglial marker TEME119 were used.

Results: IBA1-positive cells were present in the ESs, the cochlea, central and peripheral axons of the cochlear nerve, and the vestibular nerve trunk. IBA1 cells were found in the cochlear lateral wall, spiral limbus, and spiral ganglion. Notable variants of IBA1 cells adhered to neurons with "synapse-like" specializations and cytoplasmic projections. Slender IBA1 cells occasionally protracted into the basal lamina of the Schwann cells and had intimate contact with surrounding axons.

Discussion: The human eighth nerve may be under the control of a well-developed macrophage cell system. A small number of CD4+ and CD8+ cells were found in the ES and occasionally in the cochlea, mostly located in the peripheral region of Rosenthal's canal. A neuro-immunologic axis may exist in the human inner ear that could play a role in the protection of the auditory nerve. The implication of the macrophage system during disease, surgical interventions, and cell-based transplantation should be further explored.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA, 2019
Keywords
human, inner ear, IBA1, macrophages, structured illumination microscopy
National Category
Neurosciences Otorhinolaryngology
Identifiers
urn:nbn:se:uu:diva-390794 (URN)10.3389/fneur.2019.00728 (DOI)000474785100001 ()31354608 (PubMedID)
Available from: 2019-08-14 Created: 2019-08-14 Last updated: 2019-08-14Bibliographically approved
Kämpfe Nordström, C., Danckwardt-Lillieström, N., Laurell, G., Liu, W. & Rask-Andersen, H. (2019). The Human Endolymphatic Sac and Inner Ear Immunity: Macrophage Interaction and Molecular Expression. Frontiers in Immunology, 9, Article ID 3181.
Open this publication in new window or tab >>The Human Endolymphatic Sac and Inner Ear Immunity: Macrophage Interaction and Molecular Expression
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2019 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 9, article id 3181Article in journal (Refereed) Published
Abstract [en]

Background: The endolymphatic sac (ES) is endowed with a multitude of white blood cells that may trap and process antigens that reach the inner ear from nearby infection-prone areas, it thus serves as an immunologic defense organ. The human ES, and unexpectedly the rest of the inner ear, has been recently shown to contain numerous resident macrophages. In this paper, we describe ES macrophages using super-resolution structured fluorescence microscopy (SR-SIM) and speculate on these macrophages' roles in human inner ear defense.

Material and Methods: After ethical permission was obtained, human vestibular aqueducts were collected during trans-labyrinthine surgery for acoustic neuroma removal. Tissues were placed in fixative before being decalcified, rapidly frozen, and cryostat sectioned. Antibodies against IBA1, cytokine fractalkine (CX3CL1), toll-like receptor 4 (TLR4), cluster of differentiation (CD) 68, CD11b, CD4, CD8, and the major histocompatibility complex type II (MHCII) were used for immunohistochemistry.

Results: A large number of IBA1-positive cells with different morphologies were found to reside in the ES; the cells populated surrounding connective tissue and the epithelium. Macrophages interacted with other cells, showed migrant behavior, and expressed immune cell markers, all of which suggest their active role in the innate and adaptive inner ear defense and tolerance.

Discussion: High-resolution immunohistochemistry shows that antigens reaching the ear may be trapped and processed by an immune cell machinery located in the ES. Thereby inflammatory activity may be evaded near the vulnerable inner ear sensory structures. We speculate on the immune defensive link between the ES and the rest of the inner ear.

Keywords
human, cochlea, macrophages, IBA1, structured illumination microscopy
National Category
Otorhinolaryngology Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-377333 (URN)10.3389/fimmu.2018.03181 (DOI)000457362000001 ()30774637 (PubMedID)
Available from: 2019-02-25 Created: 2019-02-25 Last updated: 2019-02-25Bibliographically approved
Mei, X., Schart-Moren, N., Li, H., Ladak, H. M., Agrawal, S., Behr, R. & Rask-Andersen, H. (2019). Three-dimensional imaging of the human internal acoustic canal and arachnoid cistern: a synchrotron study with clinical implications. Journal of Anatomy, 234(3), 316-326
Open this publication in new window or tab >>Three-dimensional imaging of the human internal acoustic canal and arachnoid cistern: a synchrotron study with clinical implications
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2019 (English)In: Journal of Anatomy, ISSN 0021-8782, E-ISSN 1469-7580, Vol. 234, no 3, p. 316-326Article in journal (Refereed) Published
Abstract [en]

A thorough knowledge of the gross and micro-anatomy of the human internal acoustic canal (IAC) is essential in vestibular schwannoma removal, cochlear implantation (CI) surgery, vestibular nerve section, and decompression procedures. Here, we analyzed the acoustic-facial cistern of the human IAC, including nerves and anastomoses using synchrotron phase contrast imaging (SR-PCI). A total of 26 fresh human temporal bones underwent SR-PCI. Data were processed using volume-rendering software to create three-dimensional (3D) reconstructions allowing soft tissue analyses, orthogonal sectioning, and cropping. A scalar opacity mapping tool was used to enhance tissue surface borders, and anatomical structures were color-labeled for improved 3D comprehension of the soft tissues. SR-PCI reproduced, for the first time, the variable 3D anatomy of the human IAC, including cranial nerve complexes, anastomoses, and arachnoid membrane invagination (acoustic-facial cistern; an extension of the cerebellopontine cistern) in unprocessed, un-decalcified specimens. An unrecognized system of arachnoid pillars and trabeculae was found to extend between the arachnoid and cranial nerves. We confirmed earlier findings that intra-meatal vestibular schwannoma may grow unseparated from adjacent nerves without duplication of the arachnoid layers. The arachnoid pillars may support and stabilize cranial nerves in the IAC and could also play a role in local fluid hydrodynamics.

Place, publisher, year, edition, pages
WILEY, 2019
Keywords
human, micro-computerized tomography, synchrotron phase contrast imaging, temporal bone, Uppsala collection
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-378632 (URN)10.1111/joa.12926 (DOI)000458542900003 ()30565214 (PubMedID)
Funder
Swedish Research Council, 2017-03801
Available from: 2019-03-11 Created: 2019-03-11 Last updated: 2019-03-11Bibliographically approved
Glueckert, R., Chacko, L. J., Rask-Andersen, H., Liu, W., Handschuh, S. & Schrott-Fischer, A. (2018). Anatomical basis of drug delivery to the inner ear. Hearing Research, 368, 10-27
Open this publication in new window or tab >>Anatomical basis of drug delivery to the inner ear
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2018 (English)In: Hearing Research, ISSN 0378-5955, E-ISSN 1878-5891, Vol. 368, p. 10-27Article, review/survey (Refereed) Published
Abstract [en]

The isolated anatomical position and blood-labyrinth barrier hampers systemic drug delivery to the mammalian inner ear. Intratympanic placement of drugs and permeation via the round-and oval window are established methods for local pharmaceutical treatment. Mechanisms of drug uptake and pathways for distribution within the inner ear are hard to predict. The complex microanatomy with fluid filled spaces separated by tight-and leaky barriers compose various compartments that connect via active and passive transport mechanisms. Here we provide a review on the inner ear architecture at light-and electron microscopy level, relevant for drug delivery. Focus is laid on the human inner ear architecture. Some new data add information on the human inner ear fluid spaces generated with high resolution microcomputed tomography at 15 urn resolution. Perilymphatic spaces are connected with the central modiolus by active transport mechanisms of mesothelial cells that provide access to spiral ganglion neurons. Reports on leaky barriers between scala tympani and the so-called cortilymph compartment likely open the best path for hair cell targeting. The complex barrier system of tight junction proteins such as occludins, claudins and tricellulin isolates the endolymphatic space for most drugs. Comparison of relevant differences of barriers, target cells and cell types involved in drug spread between main animal models and humans shall provide some translational aspects for inner ear drug applications. (C) 2018 The Authors. Published by Elsevier B.V.

Place, publisher, year, edition, pages
Elsevier, 2018
National Category
Otorhinolaryngology
Identifiers
urn:nbn:se:uu:diva-370045 (URN)10.1016/j.heares.2018.06.017 (DOI)000447547100003 ()30442227 (PubMedID)
Available from: 2019-01-07 Created: 2019-01-07 Last updated: 2019-01-07Bibliographically approved
Liu, W., Loewenheim, H., Santi, P. A., Glueckert, R., Schrott-Fischer, A. & Rask-Andersen, H. (2018). Expression of trans-membrane serine protease 3 (TMPRSS3) in the human organ of Corti. Cell and Tissue Research, 372(3), 445-456
Open this publication in new window or tab >>Expression of trans-membrane serine protease 3 (TMPRSS3) in the human organ of Corti
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2018 (English)In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 372, no 3, p. 445-456Article in journal (Refereed) Published
Abstract [en]

TMPRSS3 (Trans-membrane Serine Protease 3) is a type II trans-membrane serine protease that has proteolytic activity essential for hearing. Mutations in the gene cause non-syndromic autosomal recessive deafness (DFNB8/10) in humans. Knowledge about its cellular distribution in the human inner ear may increase our understanding of its physiological role and involvement in deafness, ultimately leading to therapeutic interventions. In this study, we used super-resolution structured illumination microscopy for the first time together with transmission electron microscopy to localize the TMPRSS3 protein in the human organ of Corti. Archival human cochleae were dissected out during petroclival meningioma surgery. Microscopy with Zeiss LSM710 microscope achieved a lateral resolution of approximately 80 nm. TMPRSS3 was found to be associated with actin in both inner and outer hair cells. TMPRSS3 was located in cell surface-associated cytoskeletal bodies (surfoskelosomes) in inner and outer pillar cells and Deiters cells and in subcuticular organelles in outer hair cells. Our results suggest that TMPRSS3 proteolysis is linked to hair cell sterociliary mechanics and to the actin/microtubule networks that support cell motility and integrity.

Keywords
Cochlea, Trans-membrane Serine Protease 3 (TMPRSS3), Immunohistochemistry, Super-resolution structured illumination microscopy (SR-SIM), Human
National Category
Cell Biology
Identifiers
urn:nbn:se:uu:diva-356851 (URN)10.1007/s00441-018-2793-2 (DOI)000432109000001 ()29460002 (PubMedID)
Projects
OTOSTEM
Available from: 2018-08-16 Created: 2018-08-16 Last updated: 2018-08-16Bibliographically approved
Mei, X., Atturo, F., Wadin, K., Larsson, S., Agrawal, S., Ladak, H. M., . . . Rask-Andersen, H. (2018). Human inner ear blood supply revisited: the Uppsala collection of temporal bone - an international resource of education and collaboration. Upsala Journal of Medical Sciences, 123(3), 131-142
Open this publication in new window or tab >>Human inner ear blood supply revisited: the Uppsala collection of temporal bone - an international resource of education and collaboration
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2018 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 3, p. 131-142Article in journal (Refereed) Published
Abstract [en]

Background: The Uppsala collection of human temporal bones and molds is a unique resource for education and international research collaboration. Micro-computerized tomography (micro-CT) and synchrotron imaging are used to investigate the complex anatomy of the inner ear. Impaired microcirculation is etiologically linked to various inner ear disorders, and recent developments in inner ear surgery promote examination of the vascular system. Here, for the first time, we present three-dimensional (3D) data from investigations of the major vascular pathways and corresponding bone channels.

Methods: We used the archival Uppsala collection of temporal bones and molds consisting of 324 inner ear casts and 113 macerated temporal bones. Micro-CT was used to investigate vascular bone channels, and 26 fresh human temporal bones underwent synchrotron radiation phase contrast imaging (SR-PCI). Data were processed by volume-rendering software to create 3D reconstructions allowing orthogonal sectioning, cropping, and soft tissue analyses.

Results: Micro-CT with 3D rendering was superior in reproducing the anatomy of the vascular bone channels, while SR-PCI replicated soft tissues. Arterial bone channels were traced from scala vestibuli (SV) arterioles to the fundus, cochlea, and vestibular apparatus. Drainage routes along the aqueducts were examined.

Conclusion: Human inner ear vessels are difficult to study due to the adjoining hard bone. Micro-CT and SR-PCI with 3D reconstructions revealed large portions of the micro-vascular system in un-decalcified specimens. The results increase our understanding of the organization of the vascular system in humans and how altered microcirculation may relate to inner ear disorders. The findings may also have surgical implications.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2018
Keywords
Human, micro-computerized tomography, synchrotron phase contrast imaging, temporal bone, Uppsala collection
National Category
Medical Image Processing
Identifiers
urn:nbn:se:uu:diva-368772 (URN)10.1080/03009734.2018.1492654 (DOI)000446977000001 ()30204028 (PubMedID)
Available from: 2018-12-10 Created: 2018-12-10 Last updated: 2018-12-10Bibliographically approved
Liu, W., Molnar, M., Garnham, C., Benav, H. & Rask-Andersen, H. (2018). Macrophages in the Human Cochlea: Saviors or Predators-A Study Using Super-Resolution Immunohistochemistry. Frontiers in Immunology, 9, Article ID 223.
Open this publication in new window or tab >>Macrophages in the Human Cochlea: Saviors or Predators-A Study Using Super-Resolution Immunohistochemistry
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2018 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 9, article id 223Article in journal (Refereed) Published
Abstract [en]

The human inner ear, which is segregated by a blood/labyrinth barrier, contains resident macrophages [CD163, ionized calcium-binding adaptor molecule 1 (IBA1)-, and CD68-positive cells] within the connective tissue, neurons, and supporting cells. In the lateral wall of the cochlea, these cells frequently lie close to blood vessels as perivascular macrophages. Macrophages are also shown to be recruited from blood-borne monocytes to damaged and dying hair cells induced by noise, ototoxic drugs, aging, and diphtheria toxin-induced hair cell degeneration. Precise monitoring may be crucial to avoid self-targeting. Macrophage biology has recently shown that populations of resident tissue macrophages may be fundamentally different from circulating macrophages. We removed uniquely preserved human cochleae during surgery for treating petroclival meningioma compressing the brain stem, after ethical consent. Molecular and cellular characterization using immunofluorescence with antibodies against IBA1, TUJ1, CX3CL1, and type IV collagen, and super-resolution structured illumination microscopy (SR-SIM) were made together with transmission electron microscopy. The super-resolution microscopy disclosed remarkable phenotypic variants of IBA1 cells closely associated with the spiral ganglion cells. Monitoring cells adhered to neurons with "synapse-like" specializations and protrusions. Active macrophages migrated occasionally nearby damaged hair cells. Results suggest that the human auditory nerve is under the surveillance and possible neurotrophic stimulation of a well-developed resident macrophage system. It may be alleviated by the non-myelinated nerve soma partly explaining why, in contrary to most mammals, the human's auditory nerve is conserved following deafferentiation. It makes cochlear implantation possible, for the advantage of the profoundly deaf. The IBA1 cells may serve additional purposes such as immune modulation, waste disposal, and nerve regeneration. Their role in future stem cell-based therapy needs further exploration.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA, 2018
Keywords
human, cochlea, macrophages, ionized calcium-binding adaptor molecule 1, structured illumination microscopy, immunohistochemistry
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-348109 (URN)10.3389/fimmu.2018.00223 (DOI)000424911600001 ()29487598 (PubMedID)
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscienceEU, FP7, Seventh Framework Programme, 603029
Available from: 2018-04-11 Created: 2018-04-11 Last updated: 2018-04-11Bibliographically approved
Schart-Moren, N., Hallin, K., Agrawal, S. K., Ladak, H. M., Eriksson, P.-O., Li, H. & Rask-Andersen, H. (2018). Peri-operative electrically evoked auditory brainstem response assessment of facial nerve/cochlea interaction at cochlear implantation. Cochlear Implants International, 19(6), 324-329
Open this publication in new window or tab >>Peri-operative electrically evoked auditory brainstem response assessment of facial nerve/cochlea interaction at cochlear implantation
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2018 (English)In: Cochlear Implants International, ISSN 1467-0100, E-ISSN 1754-7628, Vol. 19, no 6, p. 324-329Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Dehiscence between the cochlear otic capsule and the facial nerve canal is a rare and relatively newly described pathology. In cochlear implantation (CI), this dehiscence may lead to adverse electric facial nerve stimulation (FNS) already at low levels, rendering its use impossible. Here, we describe an assessment technique to foresee this complication.

METHODS: Pre- and postoperative computed tomography (CT) scans and intraoperative electrically evoked auditory brainstem response (e-ABR) measurements were analyzed in two patients with cochlear-facial dehiscence (CFD).

RESULTS: Because of the relatively low resolution, the confirmation of CFD with a clinical CT was difficult. The e-ABR displayed a large potential with 6 and 7.5 ms latency, respectively, which did not occur otherwise.

DISCUSSION: Potential strategies to resolve and manage FNS are described.

CONCLUSION: Prediction of FNS by assessing the distance between the labyrinthine portion of the facial nerve and the cochlea is difficult using conventional CT scans. A large evoked late myogenic potential at low stimulation levels during intraoperative e-ABR measurement may foresee FNS at CI activation.

Keywords
Cochlea, Cochlear implantation, Dehiscence, Facial nerve stimulation
National Category
Otorhinolaryngology
Identifiers
urn:nbn:se:uu:diva-373491 (URN)10.1080/14670100.2018.1481179 (DOI)29877144 (PubMedID)
Available from: 2019-01-14 Created: 2019-01-14 Last updated: 2019-05-27Bibliographically approved
Hjort, K., Rask-Andersen, H. & Li, H. (2018). Softer, thinner and more compliant implants. In: : . Paper presented at 8th IEEE Int. Nanoelectronics Conf, INEC2018.
Open this publication in new window or tab >>Softer, thinner and more compliant implants
2018 (English)Conference paper, Oral presentation with published abstract (Refereed)
Abstract [en]

Tissue irritation is caused by two main reasons – chemical and mechanical. In recent years, material chemical biocompatibility has been much improved but most implants used in soft tissue still have low compliance. This is especially severe in the brain, where the tissue often has a compliance of a soft hydrogel and ordinary silicone materials like PDMS have an elastic modulus up to 1,000 times higher, i.e. like a wooden stick irritating your skin. Starting from the remaining challenges of the highly successful Cochlear Implants and recent work on stretchable electronics this review conclude on the merits with soft stretchable printed circuitboards, with components of fluids, gels, and sprinkled with a smart dust of small chips.

Keywords
stretchable electronics, Cochlear implant, PCB, liquid alloy
National Category
Other Medical Engineering Other Electrical Engineering, Electronic Engineering, Information Engineering
Research subject
Engineering Science with specialization in Microsystems Technology; Oto-Rhino-Laryngology
Identifiers
urn:nbn:se:uu:diva-338013 (URN)
Conference
8th IEEE Int. Nanoelectronics Conf, INEC2018
Projects
Mjukare, tunnare och mer följsamma cocleaimplantat
Funder
Swedish Research Council, 2017-03801
Available from: 2018-01-06 Created: 2018-01-06 Last updated: 2018-10-19Bibliographically approved
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