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  • 1
    ISSN: 1433-0458
    Keywords: Schlüsselwörter Schwerhörigkeit ; Cochlea-amplifier-Implantat ; Implantierbares Hörgerät ; TICA ; Key words Sensorineural hearing loss ; Cochlea amplifier implant ; Implantable hearing aid ; Electronic hearing implant ; TICA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary For the majority of patients with sensorineural hearing loss (SNHL) many available hearing aids often do not achieve satisfactory results. For these patients partially implantable hearing devices have been developed, allowing distortion-free hearing and speech intelligibility that may be superior to conventional hearing aids. The external parts of partial implants, however, may result in a patient’s stigmatization. Furthermore, they do not use the acoustic properties of the external auditory canal. Recently, we published the successful development of the first totally implantable hearing device for the treatment of SNHL (HNO 46 [1998] 853–863). Here we report the first implantations of this unique, totally implantable electronic hearing system in patients with SNHL: Implex TICA LZ 3001. The implant microphone is implanted subcutaneously in the outer ear canal near the ear drum. The signal is processed by a digitally programmable multichannel audioprocessor located subcutaneously on the bony skull behind the ear. A piezoelectric transducer is coupled to the body of the incus and drives the ossicular chain by vibratory actions. Energy is provided by an implantable battery. Implanted patients describe hearing as being distortion-free and transparent. Speech intelligibility and the hearing of music are improved. Patients may achieve better speech discrimination, especially in the presence of background noise. The aid can be used during sports, including swimming. To our knowledge, this is the first report of the implantation of a totally implantable electronic hearing system in patients. These results encourage further implantations of the totally implantable hearing system in the course of an ongoing clinical study.
    Notes: Zusammenfassung: Für die Mehrzahl der Innenohrschwerhörigen kann selbst mit modernster Hörgerätetechnik keine die Patienten zufriedenstellende Hörrehabilitation erzielt werden. Für diese große Zahl von Betroffenen ohne adäquate Versorgung sind teilimplantierbare Hörgeräte entwickelt worden, die konventionellen Hörgeräten besonders bei Klangtreue und Sprachverständlichkeit deutlich überlegen sein können. Allerdings können sie den Kranken durch außen an Kopf oder Körper zu tragende Teile stigmatisieren. Auch nutzen sie die Störschallunterdrückung als auch die auditorische Raumorientierung mittels des äußeren Gehörgangs noch nicht aus. Hier berichten wir über die ersten Implantationen eines neuartigen, vollständig implantierbaren Hörsystems (TICA® LZ 3001) bei Innenohrschwerhörigen. Es nimmt den Schall über ein trommelfellnahes Mikrophon durch die intakte Gehörgangshaut auf. Ein retroaurikulär subkutan implantierter, mehrkanaliger digital programmierbarer Audioprozessor verarbeitet das Signal und gibt es über einen piezoelektronischen Wandler im Mastoid an den Amboßkörper weiter. Energie wird durch eine implantierbare Batterie bereitgestellt. Implantierte Patienten empfinden das Gehörte als verzerrungsfrei und transparent. Sie verstehen Sprache und empfinden Musik besser als ohne Implantat. Insbesondere im Störlärm kann z.T. ein erheblich verbessertes Sprachverständnis erreicht werden. Die bisherigen Ergebnisse ermutigen, weitere Implantationserfahrungen mit dem vollständig implantierbaren Hörsystem zu sammeln.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1433-0458
    Keywords: Schlüsselwörter TICA ; Elektronisches Hörimplantat ; Implantierbares Mikrophon ; Schwerhörigkeit ; Key words TICA ; Implantable hearing aid ; Sensorineural hearing loss ; Auditory device ; Electromechanical transducer ; Ear
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Prerequisite to implantation of a piezoelectrical transducer of an implantable hearing aid is a shape allowing its implantation into human mastoid and middle ear. To approach this problem, a consecutive series of six transducer prototypes was created in an iterative process. Their functional geometry was evaluated in 50 human temporal bones. A shape for a functioning transducer was found which will enable implantation in 78% of the cases examined (confidence interval: 61.5%–89.2%). It will allow simultaneous implantation of the transducer into the mastoid and microphone, which is situated transmastoidal in the posterior wall of the ear canal. Furthermore, the transducer may be coupled to the ossicular chain or the perilymph.
    Notes: Zusammenfassung Voraussetzung für die Implantation eines piezoelektrischen Wandlers eines implantierbaren Hörgeräts ist seine Gestaltung in einer für das menschliche Mastoid und Mittelohr topographisch adäquaten Form, die gleichzeitig eine Funktion des Wandlers erlaubt. Dazu wurden in einem iterativen Verfahren in einer konsekutiven Serie 6 Wandlerprototypen geschaffen und ihre funktionelle Geometrie jeweils in 50 menschlichen Felsenbeinen evaluiert. Es konnte eine Form für einen funktionsfährigen Wandler gefunden werden, die es in 78% der untersuchten Fälle (Konfidenzintervall: 61,5–89,2%) erlaubt, neben dem transmastoidal in die hintere Gehörgangswand eingesetzten Mikrophon den Wandler in das Mastoid zu implantieren und an die Gehörknöchelchenkette oder die Perilymphe vibratorisch anzukoppeln. Die in der vorliegenden Studie erarbeitete Form erlaubt 1. die intramastoidale Implantation, 2. die Ankopplung an Ossikelkette oder Perilymphe, 3. einen resonanzfreien Frequenzgang bis 10 kHz, 4. eine Zunahme der Ausgangsleistung oberhalb 1 kHz sowie 5. eine geringe elektrische Leistungsaufnahme des Wandlers.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1433-0458
    Keywords: Schlüsselwörter Ohr ; Schwerhörigkeit ; TICA ; Implantierbares Hörgerät ; Mechanischer Transducer ; Implantierbares Mikrofon ; Key words Ear ; Hearing loss ; TICA ; Implantable hearing aid ; Mechanical transducer ; Implantable microphone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Recently, an implantable hearing aid for rehabilitation of sensorineural hearing loss has been developed. One component of the device is the microphone for implantation into the posterior canal wall. The membrane of the microphone can be covered by skin, cartilage, or fascia, avoiding reduction in sound transmission at the same time. In the study presented here, the microphone was implanted into 50 cadaver specimens of human temporal bone. Localization of the microphone was determined by the anatomical situation of the facial nerve. The microphone and the piezoelectric transducer could be implanted in 78% of the temporal bones after total mastoidectomy. In the final version of the microphone, the size was 4.5 mm and total weight 400 mg.
    Notes: Zusammenfassung Implantierbare Hörgeräte für Innenohrschwerhörige benötigen einen implantierbaren Schallaufnehmer in oder hinter dem Trommelfell oder subkutan in der Gehörgangswand. Das Schwingungsverhalten des Trommelfells kann individuell und frequenzabhängig extrem unterschiedlich sein, während die Gehörgangshaut reproduzierbar schwingt. Deshalb wurde in einem Verbundprojekt ein vollständig implantierbares Mikrofon für die Implantation in die hintere knöcherne Gehörgangswand in einer Form realisiert, daß Haut, Knorpel oder Fascie auf der Mikrofonmembran zu keiner klinisch relevanten Schalldämpfung führen. In der vorliegenden Studie wurde an 50 Felsenbeinen der operationstechnisch zweckmäßigste Implantationsort für ein Mikrofon erarbeitet, der 1. ausreichend trommelfellnah ist, der 2. der Gehörgangshaut flach aufliegt und der 3. gleichzeitig die intramastoidale Implantation eines Wandlers erlaubt. Die Lokalisation wurde wesentlich durch den Verlauf des N. facialis bestimmt. Gleichzeitig wurden in einem iterativen Verfahren Form und Größe des Mikrofons schrittweise an die chirurgische Anatomie des Implantatsortes sowie an die Operationstechnik angepaßt. Es konnte eine Mikrofonform gefunden werden, die die Implantation des Mikrofons als Bestandteil eines implantierbaren Hörgeräts in einer funktionell und topographisch adäquaten Form bei gemeinsamer Implantation mit dem Wandler in 78% der Felsenbeine erlaubte. In dieser Endform hat das Mikrofon einen Durchmesser der schallaufnehmenden Membran von 4,5 mm sowie ein Gesamtgewicht von 0,4 g und ist zur Implantation bei den meisten Patienten geeignet.
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  • 4
    Publication Date: 2013-03-05
    Description: The metabolites, transporters, and enzymes involved in choline metabolism are regarded as biomarkers for disease progression in a variety of cancers, but their in vivo detection is not ideal. Both magnetic resonance spectroscopy [MRS using chemical shift imaging (CSI) total choline (tCho)] and 11C-choline positron emission tomography (PET) can probe this pathway, but they have not been compared side by side. In this study, we used the spontaneous murine astrocytoma model SMA560 injected intracranially into syngeneic VM/Dk mice, analyzing animals at various postimplantation time points using dynamic microPET imaging and CSI MRS. We observed an increase in tumor volume and 11C-choline uptake between days 5 and 18. Similarly, tCho levels decreased at days 5 to 18. We found a negative correlation between the tCho and PET results in the tumor and a positive correlation between the tCho tumor-to-brain ratio and choline uptake in the tumor. PCR results confirmed expected increases in expression levels for most of the transporters and enzymes. Using MRS quantification, a good agreement was found between CSI and 11C-choline PET data, whereas a negative correlation occurred when CSI was not referenced. Thus, 11C-choline PET and MRS methods seemed to be complementary in strengths. While advancing tumor proliferation caused an increasing 11C-choline uptake, gliosis and inflammation potentially accounted for a high peritumoral tCho signal in CSI, as supported by histology and secondary ion mass spectrometry imaging. Our findings provide definitive evidence of the use of MRS, CSI, and PET for imaging tumors in vivo. Cancer Res; 73(5); 1470–80. ©2012 AACR.
    Print ISSN: 0008-5472
    Electronic ISSN: 1538-7445
    Topics: Medicine
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  • 5
    Publication Date: 2013-01-03
    Description: The aim of this work was to study the feasibility of measuring cell proliferation noninvasively in vivo during different stages of experimental arthritis using the PET proliferation tracer 3'-deoxy-3'- 18 F-fluorothymidine ( 18 F-FLT). Methods: We injected mice with serum containing glucose-6-phosphate-isomerase–specific antibodies to induce experimental arthritis, and we injected control mice with control serum. Animals injected with 18 F-FLT 1, 3, 6, and 8 d after the onset of disease were analyzed in vivo by PET, PET/CT, or PET/MR imaging followed by autoradiography analysis. The 18 F-FLT uptake in the ankles and forepaws was quantified on the basis of the PET images by drawing standardized regions of interest. To correlate the in vivo PET data with cell proliferation, we performed Ki-67 immunohistochemistry of diseased and healthy joints at the corresponding time points. Results: Analysis of the different stages of arthritic joint disease revealed enhanced 18 F-FLT uptake in arthritic ankles (2.2 ± 0.2 percentage injected dose per gram [%ID/g]) and forepaws (2.1 ± 0.3 %ID/g), compared with healthy ankles (1.4 ± 0.3 %ID/g) and forepaws (1.5 ± 0.5 %ID/g), as early as 1 d after the glucose-6-phosphate-isomerase serum injection, a time point characterized by clear histologic signs of arthritis but only slight ankle swelling. The 18 F-FLT uptake in the ankles (3.5 ± 0.3 %ID/g) reached the maximum observed level at day 8. Ki-67 immunohistochemical staining of the arthritic ankles and forepaws revealed a strong correlation with the in vivo 18 F-FLT PET data. PET/CT and PET/MR imaging measurements enabled us to identify whether the 18 F-FLT uptake was located in the bone or the soft tissue. Conclusion: Noninvasive in vivo measurement of cell proliferation in experimental arthritis using 18 F-FLT PET is a promising tool to investigate the extent of arthritic joint inflammation.
    Print ISSN: 0022-3123
    Topics: Medicine
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  • 6
    Publication Date: 2016-09-16
    Description: Differential diagnosis and therapy of heterogeneous breast tumors poses a major clinical challenge. To address the need for a comprehensive, noninvasive strategy to define the molecular and functional profiles of tumors in vivo, we investigated a novel combination of metabolic PET and diffusion-weighted (DW)-MRI in the polyoma virus middle T antigen transgenic mouse model of breast cancer. The implementation of a voxelwise analysis for the clustering of intra- and intertumoral heterogeneity in this model resulted in a multiparametric profile based on [18F]Fluorodeoxyglucose ([18F]FDG)-PET and DW-MRI, which identified three distinct tumor phenotypes in vivo, including solid acinar, and solid nodular malignancies as well as cystic hyperplasia. To evaluate the feasibility of this approach for clinical use, we examined estrogen receptor-positive and progesterone receptor-positive breast tumors from five patient cases using DW-MRI and [18F]FDG-PET in a simultaneous PET/MRI system. The postsurgical in vivo PET/MRI data were correlated to whole-slide histology using the latter traditional diagnostic standard to define phenotype. By this approach, we showed how molecular, structural (microscopic, anatomic), and functional information could be simultaneously obtained noninvasively to identify precancerous and malignant subtypes within heterogeneous tumors. Combined with an automatized analysis, our results suggest that multiparametric molecular and functional imaging may be capable of providing comprehensive tumor profiling for noninvasive cancer diagnostics. Cancer Res; 76(18); 5512–22. ©2016 AACR.
    Print ISSN: 0008-5472
    Electronic ISSN: 1538-7445
    Topics: Medicine
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  • 7
    Publication Date: 2015-01-28
    Description: T cells are key players in inflammation, autoimmune diseases, and immunotherapy. Thus, holistic and noninvasive in vivo characterizations of the temporal distribution and homing dynamics of lymphocytes in mammals are of special interest. Herein, we show that PET-based T-cell labeling facilitates quantitative, highly sensitive, and holistic monitoring of T-cell homing...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 8
    Publication Date: 2017-05-02
    Description: Hypoxia is essential for the development of autoimmune diseases such as rheumatoid arthritis (RA) and is associated with the expression of reactive oxygen species (ROS), because of the enhanced infiltration of immune cells. The aim of this study was to demonstrate the feasibility of measuring hypoxia noninvasively in vivo in arthritic ankles with PET/MRI using the hypoxia tracers 18 F-fluoromisonidazole ( 18 F-FMISO) and 18 F-fluoroazomycinarabinoside ( 18 F-FAZA). Additionally, we quantified the temporal dynamics of hypoxia and ROS stress using L-012, an ROS-sensitive chemiluminescence optical imaging probe, and analyzed the expression of hypoxia-inducible factors (HIFs). Methods: Mice underwent noninvasive in vivo PET/MRI to measure hypoxia or optical imaging to analyze ROS expression. Additionally, we performed ex vivo pimonidazole-/HIF-1α immunohistochemistry and HIF-1α/2α Western blot/messenger RNA analysis of inflamed and healthy ankles to confirm our in vivo results. Results: Mice diseased from experimental RA exhibited a 3-fold enhancement in hypoxia tracer uptake, even in the early disease stages, and a 45-fold elevation in ROS expression in inflamed ankles compared with the ankles of healthy controls. We further found strong correlations of our noninvasive in vivo hypoxia PET data with pimonidazole and expression of HIF-1α in arthritic ankles. The strongest hypoxia tracer uptake was observed as soon as day 3, whereas the most pronounced ROS stress was evident on day 6 after the onset of experimental RA, indicating that tissue hypoxia can precede ROS stress in RA. Conclusion: Collectively, for the first time to our knowledge, we have demonstrated that the noninvasive measurement of hypoxia in inflammation using 18 F-FAZA and 18 F-FMISO PET imaging represents a promising new tool for uncovering and monitoring rheumatic inflammation in vivo. Further, because hypoxic inflamed tissues are associated with the overexpression of HIFs, specific inhibition of HIFs might represent a new powerful treatment strategy.
    Print ISSN: 0022-3123
    Topics: Medicine
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  • 9
    Publication Date: 2014-02-04
    Description: Although T cells can be labeled for noninvasive in vivo imaging, little is known about the impact of such labeling on T-cell function, and most imaging methods do not provide holistic information about trafficking kinetics, homing sites, or quantification. Methods: We developed protocols that minimize the inhibitory effects of 64 Cu-pyruvaldehyde-bis( N 4-methylthiosemicarbazone) ( 64 Cu-PTSM) labeling on T-cell function and permit the homing patterns of T cells to be followed by PET. Thus, we labeled ovalbumin (OVA) T-cell receptor transgenic interferon (IFN)-–producing CD4 + T (Th1) cells with 0.7–2.2 MBq of 64 Cu-PTSM and analyzed cell viability, IFN- production, proliferation, apoptosis, and DNA double-strand breaks and identified intracellular 64 Cu accumulation sites by energy dispersive x-ray analysis. To elucidate the fate of Th1 cell homing by PET, 10 7 64 Cu-OVA-Th1 cells were injected intraperitoneally or intravenously into healthy mice. To test the functional capacities of 64 Cu-OVA-Th1 cells during experimental OVA-induced airway hyperreactivity, we injected 10 7 64 Cu-OVA-Th1 cells intraperitoneally into OVA-immunized or nonimmunized healthy mice, which were challenged with OVA peptide or phosphate-buffered saline or remained untreated. In vivo PET investigations were followed by biodistribution, autoradiography, and fluorescence-activated cell sorting analysis. Results: PET revealed unexpected homing patterns depending on the mode of T-cell administration. Within 20 min after intraperitoneal administration, 64 Cu-OVA-Th1 cells homed to the perithymic lymph nodes (LNs) of naive mice. Interestingly, intravenously administered 64 Cu-OVA-Th1 cells homed predominantly into the lung and spleen but not into the perithymic LNs. The accumulation of 64 Cu-OVA-Th1 cells in the pulmonary LNs (6.8 ± 1.1 percentage injected dose per cubic centimeter [%ID/cm 3 ]) 24 h after injection was highest in the OVA-immunized and OVA-challenged OVA airway hyperreactivity–diseased littermates 24 h after intraperitoneal administration and lowest in the untreated littermates (3.7 ± 0.4 %ID/cm 3 ). As expected, 64 Cu-OVA-Th1 cells also accumulated significantly in the pulmonary LNs of nonimmunized OVA-challenged animals (6.1 ± 0.5 %ID/cm 3 ) when compared with phosphate-buffered saline–challenged animals (4.6 ± 0.5 %ID/cm 3 ). Conclusion: Our protocol permits the detection of Th1 cells in single LNs and enables temporal in vivo monitoring of T-cell homing over 48 h. This work enables future applications for 64 Cu-PTSM–labeled T cells in clinical trials and novel therapy concepts focusing on T-cell–based immunotherapies of autoimmune diseases or cancer.
    Print ISSN: 0022-3123
    Topics: Medicine
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