Preoperative navigated transcranial magnetic stimulation in patients with motor-eloquent brain lesions

Navigated transcranial magnetic stimulation (nTMS) of the motor cortex is a non-invasive technique which allows for preoperative determination of motor-eloquent cortical areas. Including this information into surgical planning of motor-eloquent brain lesions is expected to allow for better resection rates while preserving motor function. To test this hypothesis, this thesis retrospectively evaluates all patients receiving preoperative nTMS mapping of the motor cortex at the Department of Neurosurgery since its introduction in June 2013 to December 2018 (nTMS-group). This group includes 127 patients with motor-eloquent brain lesions (glioma, metastases, meningioma and cavernoma). A control collective of 379 patients with lesions of the same entities, who were treated between 2009 and 2018 without nTMS-mapping, was retrospectively established. Out of this group, a 1:1 match collective was selected (control group). The outcome of both cohorts was compared with respect to motor function, resection status, craniotomy size, duration of surgery, and hospital stay. Pair-matching demonstrated a homogeneous distribution of demographic characteristics (age, sex), preoperative motor function, and brain lesion (histology, location, tumour size). In the nTMS-group gross total resection was achieved significantly more frequently (84.3 % vs. 73.2 %, p = 0.02), while motor outcome was similar in both groups. Size of craniotomy, duration of surgery and hospital stay were also comparable in both groups. The subgroup analysis by lesion entity shows that the significantly improved resection rate mainly originates from the subgroup of malignant glioma WHO°III/IV (nTMS group 72.3 % vs. control-group 53.2 %, p = 0.049). Consequently, overall survival was analysed for patients with malignant glioma. Univariate analysis demonstrated a prognostic effect of patient age < 60 years, resection status, and intact motor function (no preoperative paresis). In the multivariate analysis, patient age and gross total resection were independently associated with survival of patients with malignant glioma. Multivariate analysis demonstrated that the use of preoperative nTMS-motor mapping, better preoperative motor function and comparatively smaller brain lesions were independent prognostic factors for achieving gross total resection. The subgroups of patients with metastases, meningiomas and cavernous malformations did not show any differences for gross total resection rate, postoperative motor function, craniotomy size, duration of surgery or hospital stay between the nTMS and control groups. Taken together, the results highlight that in the subgroup of patients with malignant glioma, preoperative nTMS-mapping of the motor cortex allows for significantly improved gross total resection rates without compromising motor outcome. The increased resection rate is a critical factor for the survival of patients with malignant glioma. Hence, implementing nTMS-mapping in the resection of motor-eloquent brain lesions, particularly malignant glioma, contributes to better surgical outcome and likely improved prognosis.Die navigierte transkranielle Magnetstimulation des Motor-Kortex ist eine nicht-invasive Technik, die eine präoperative Kartierung motor-eloquenter kortikaler Areale erlaubt. Die Einbeziehung dieser Information bei der Resektion motor-eloquent gelegener Hirnläsionen soll eine bessere Resektionsrate ermöglichen, ohne die motorische Funktion zusätzlich zu schädigen. Um diese Hypothese zu überprüfen, wird in dieser Arbeit retrospektiv das Kollektiv von Patienten mit durchgeführter nTMS-Kartierung des Motor-Kortex untersucht, die seit der Einführung der nTMS-Technik im Juni 2013 bis Ende des Jahres 2018 an der Klinik für Neurochirurgie operiert wurden (nTMS-Gruppe). Dies waren insgesamt 127 Patienten mit motor-eloquenten zerebralen Raumforderungen (Gliome, Metastasen, Meningeome und Kavernome). Ein Kontroll-Kollektiv von 379 Patienten mit Läsionen aus der gleichen Entitätsgruppe, die zwischen 2009 und 2018 ohne nTMS-Untersuchung behandelt wurden, wurde retrospektiv erstellt. Aus diesem wurde ein 1:1 Match-Kollektiv gebildet (Kontroll-Gruppe). Das Outcome beider Kohorten wurde anhand der Parameter Kraftgrad, Resektionsstatus, Größe der Kraniotomie, OP-Dauer und Krankenhausaufenthalt verglichen. Nach durchgeführtem Pair-matching zeigten sich zwei homogene Kollektive mit vergleichbarer Demographie (Alter, Geschlecht), präoperativer motorischer Funktion und Hirnläsionen (Histologie, Lokalisation, Tumorgröße). In der nTMS-Gruppe konnte signifikant häufiger eine Komplettresektion erreicht werden als in der Kontroll-Gruppe (84,3 % vs. 73,2 %, p = 0,02), wobei die motorische Funktion in beiden Gruppen vergleichbar war. Die Größe der Kraniotomie, OP-Dauer und der Krankenhaus-aufenthalt waren in beiden Gruppen ebenfalls vergleichbar. In der Subgruppen-Analyse getrennt nach Histologie zeigte sich, dass die signifikant verbesserte Resektionsrate durch die Subgruppe der malignen Gliome WHO°III/IV abgebildet wurde (nTMS-Gruppe 72,3 % vs. Kontroll-Gruppe 53,2 %, p = 0,049). Daher wurde das Gesamtüberleben der Patienten mit malignen Gliomen untersucht. Die univariate Analyse zeigte eine prognostische Assoziation des Gesamtüberlebens mit den Parametern Patientenalter < 60 Jahren, Komplettresektion und Intaktheit des motorischen Systems (keine präoperative Parese). In der multivariaten Analyse zeigten sich Patientenalter und Komplettresektion als unabhängige Faktoren für ein signifikant verbessertes Überleben bei Patienten mit malignen Gliomen. Prädiktoren für das Erreichen einer Komplettresektion waren in der multivariaten Analyse die Verwendung der präoperativen nTMS-Kartierung, die präoperative motorische Funktion und die Tumorgröße. Für die Subgruppen der Patienten mit Metastasen, Meningeomen und Kavernomen konnten keine Unterschiede bezüglich der Resektionsrate, postoperativen motorischen Funktion, Kraniotomiegröße, OP-Dauer oder Krankenhausaufenthalt festgestellt werden. In Zusammenschau zeigen die Ergebnisse, dass in der Subgruppe der malignen Gliome mit Hilfe der nTMS-Kartierung eine signifikant bessere Resektionsrate erreicht wird, ohne die motorische Funktion hierbei zu beeinträchtigen. Die verbesserte Resektionsrate ist ein kritischer Faktor für das Überleben von Patienten mit malignen Gliomen. Die Implementierung der nTMS-Kartierung in die Resektion motor-eloquenter Läsionen, insbesondere maligner Gliome, kann daher zu einem verbesserten chirurgischen Ergebnis und verbesserter Prognose dieser Patienten beitragen

On the likelihood of future eruptions in the Chilean Southern Volcanic Zone: interpreting the past century's eruption record based on statistical analyses

A sequence of 150 explosive eruptions recorded during the past century at the Chilean Southern Volcanic Zone (SVZ) is subjected to statistical time series analysis. The exponential, Weibull, and log-logistic distribution functions are fit to the eruption record, separately for literature-assigned volcanic explosivity indices (VEI) ≥2 and VEI ≥3. Since statistical tests confirm the adequacy of all the fits to describe the data, all models are used to estimate the likelihood of future eruptions. Only small differences are observed between the different distribution functions with regard to the eruption forecast, whereby the log-logistic distribution predicts the lowest probabilities. There is a 50% probability for VEI ≥2 eruptions to occur in the SVZ within less than a year, and 90% probability to occur within the next 2-3 years. For the larger VEI ≥3 eruptions, the 50% probability is reached in 3-4 years, while the 90% level is reached in 9-11 year

Seismic evidence of a link between subducted oceanic faults and volcanism: A case study from South Central Chile

The south-central Chilean subduction zone was investigated at 39-40°S by a passive seismic experiment. The investigation area comprises the maximum slip of the great 1960 Mw 9.5 Valdivia earthquake. The incoming Nazca plate is permeated by a number of major fault zones including the Valdivia fault zone and the Mocha fault zone which seem to have behaved as a barriers for the rupture propagation of large earthquakes in the past. The investigated sector is also home to the Villarrica volcano - one of South America’s most active volcanoes. In the extension of the Valdiva fault zone we observed a cluster of increased seismicity in the subducting plate at depths between 80 km and 120 km, where dehydration of the subducting plate occurs. The focal plane solutions of this cluster show predominantly strike-slip motion. Tomographic images show decreased P- and S-velocity and increased ratio between the seismic cluster and the volcanic center of Villarrica, Quetrupillán and Lanin, corresponding to an increased content of fluids or melt. Additional geochemical investigations show that the magma of Villarrica volcano has an enhanced fluid signal compared to the other volcanoes of the Southern Volcanic Zone of Chile. It can be assumed that the Valdivia fault zone serves as the source for the fluids. Before the plate subducts, water can penetrate the plate through faults within the Valdivia fault zone. Serpentinization would build the water into minerals. Inside the subduction zone the Valdiva fault zone is reactivated by dehydration reactions at a depth of about 100 km. The released fluids rise towards the volcanic center causing the tomographic anomalies. At the end this leads to an increased degree of melting and a higher activity of Villarrica volcano

A receiver function study of Southern Costa Rica : indications of steep Cocos Ridge subduction

Central America is characterized by the subduction of the oceanic Cocos Plate underneath the Caribbean Plate and Panama Microplate along the Middle America Trench, in a setting that is transitional between oceanic island arc and continental active margin subduction. In addition to providing an interesting comparison with purely oceanic or continental subduction zones, the Central American subduction zone is particularly fascinating owing to its pronounced lateral variability regarding the nature of the overriding plate, subducting plate, seismicity, volcanism and geochemistry. To explore the deep structure of the subduction zone, a transect of broadband seismometers across the Talamanca Range (Southern Costa Rica) was operated from spring 2005 to spring 2007. This region is characterized by the subduction of the aseismic Cocos Ridge, which has been observed to dip at an angle of 18 deg down to depths of about 40 km. Based on this shallow subduction angle, it has been speculated that shallow underplating of the Cocos Ridge is responsible for the gap in active volcanism and strong uplift in the Cordillera de Talamanca region. A receiver function analysis of 522 teleseismic earthquakes was performed, yielding 1777 receiver functions. The data from the Talamanca Transect stations was complemented by short-period data recorded at the Quepos network land-stations, adding another 100 receiver functions for 39 events. The Moho of the overriding plate is imaged around 35 km depth, and an intracrustal discontinuity is observed at about 20 km depth, in good agreement with previous active seismic studies. Contrary to expectations, the migrated sections clearly show a steeply dipping (ca. 60 deg) conversion down to more than 150 km depth, interpreted as the subducting slab. 3d-representations based on the migrated profiles do not indicate significant shallowing of the subducting plate towards the Cordillera de Talamanca. These results indicate for the first time that the Cocos Ridge may be subducting beneath Southern Costa Rica at a considerably larger angle and to greater depths than previously thought, opening new questions about the mechanism causing the gap in active volcanism and strong uplift in the Cordillera de Talamanca. Possible explanations include a compressional regime hindering the ascent of magmas to the surface or an anhydrous part of the subducting slab, preventing fluid-induced melting in the mantle wedge. Alternatives may be combined subduction/underplating scenarios or a transitional regime. Modelling studies confirm that the dipping feature observed in the migrated receiver functions can be caused by a slab dipping at approximately the same angle. Possible anisotropy scenarios, such as corner-flow and the resulting olivine lattice-preferred orientation, are also investigated. The results point to the existence of mantle-wedge corner-flow, with possible additional arc-parallel flow

Clinically relevant investigation of flattening filter-free skin dose

As flattening filter-free (FFF) photon beams become readily available for treatment delivery in techniques such as SBRT, thorough investigation of skin dose from FFF photon beams is necessary under clinically relevant conditions. Using a parallel-plate PTW Markus chamber placed in a custom water-equivalent phantom, surface-dose measurements were taken at 2 × 2, 3 × 3, 4 × 4, 6 × 6, 8 × 8, 10 × 10, 20 × 20, and 30 × 30 cm2 field sizes, at 80, 90, and 100 cm source-to-surface distances (SSDs), and with fields defined by jaws and multileaf collimator (MLC) using multiple beam energies (6X, 6XFFF, 10X, and 10XFFF). The same set of measurements was repeated with the chamber at a reference depth of 10 cm. Each surface measurement was normalized by its corresponding reference depth measurement for analysis. The FFF surface doses at 100 cm SSD were higher than flattened surface doses by 45% at 2 × 2 cm2 to 13% at 20 × 20 cm2 for 6 MV energy. These surface dose differences varied to a greater degree as energy increased, ranging from +63% at 2 × 2 cm2 to -2% at 20 × 20 cm2 for 10 MV. At small field sizes, higher energy increased FFF surface dose relative to flattened surface dose; while at larger field sizes, relative FFF surface dose was higher for lower energies. At both energies investigated, decreasing SSD caused a decrease in the ratios of FFF-to-flattened surface dose. Variability with SSD of FFF-to flattened surface dose differences increased with field size and ranged from 0% to 6%. The field size at which FFF and flattened beams gave the same skin dose increased with decreasing beam energy. Surface dose was higher with MLC fields compared to jaw fields under most conditions, with the difference reaching its maximum at a field size between 4 × 4 cm2 and 6 × 6 cm2 for a given energy and SSD. This study conveyed the magnitude of surface dose in a clinically meaningful manner by reporting results normalized to 10 cm depth dose instead of depth of dose maximum

Eine Receiver-Funktions-Studie von Süd-Costa Rica: Hinweise auf steile Subduktion des Cocos-Rückens

Central America is characterized by the subduction of the oceanic Cocos Plate underneath the Caribbean Plate and Panama Microplate along the Middle America Trench, in a setting that is transitional between oceanic island arc and continental active margin subduction. In addition to providing an interesting comparison with purely oceanic or continental subduction zones, the Central American subduction zone is particularly fascinating owing to its pronounced lateral variability regarding the nature of the overriding plate, subducting plate, seismicity, volcanism and geochemistry. To explore the deep structure of the subduction zone, a transect of broadband seismometers across the Talamanca Range (Southern Costa Rica) was operated from spring 2005 to spring 2007. This region is characterized by the subduction of the aseismic Cocos Ridge, which has been observed to dip at an angle of 18 deg down to depths of about 40 km. Based on this shallow subduction angle, it has been speculated that shallow underplating of the Cocos Ridge is responsible for the gap in active volcanism and strong uplift in the Cordillera de Talamanca region. A receiver function analysis of 522 teleseismic earthquakes was performed, yielding 1777 receiver functions. The data from the Talamanca Transect stations was complemented by short-period data recorded at the Quepos network land-stations, adding another 100 receiver functions for 39 events. The Moho of the overriding plate is imaged around 35 km depth, and an intracrustal discontinuity is observed at about 20 km depth, in good agreement with previous active seismic studies. Contrary to expectations, the migrated sections clearly show a steeply dipping (ca. 60 deg) conversion down to more than 150 km depth, interpreted as the subducting slab. 3d-representations based on the migrated profiles do not indicate significant shallowing of the subducting plate towards the Cordillera de Talamanca. These results indicate for the first time that the Cocos Ridge may be subducting beneath Southern Costa Rica at a considerably larger angle and to greater depths than previously thought, opening new questions about the mechanism causing the gap in active volcanism and strong uplift in the Cordillera de Talamanca. Possible explanations include a compressional regime hindering the ascent of magmas to the surface or an anhydrous part of the subducting slab, preventing fluid-induced melting in the mantle wedge. Alternatives may be combined subduction/underplating scenarios or a transitional regime. Modelling studies confirm that the dipping feature observed in the migrated receiver functions can be caused by a slab dipping at approximately the same angle. Possible anisotropy scenarios, such as corner-flow and the resulting olivine lattice-preferred orientation, are also investigated. The results point to the existence of mantle-wedge corner-flow, with possible additional arc-parallel flow.Die tektonische Situation in Mittelamerika ist gekennzeichnet durch die Subduktion der ozeanischen Cocos-Platte unter der karibischen Platte und der Panama-Mikroplatte entlang des mittelamerikanischen Grabens. Dabei handelt es sich um eine Übergangssituation zwischen aktiven Kontinentalrändern und ozeanischen Vulkanbögen. Zusätzlich zu dem interessanten Vergleich mit rein ozeanischer oder kontinentaler Subduktion ist die mittelamerikanische Subduktionszone besonders interessant aufgrund ihrer starken lateralen Variabilität, was die Natur der subduzierenden und der darüberliegenden Platte, die Seismizität, den Vulkanismus und die geochemischen Signaturen betrifft. Um die Tiefenstruktur dieser Subduktionszone zu erforschen, wurde ein Transect von Breitbandseismometern durch das Talamanca-Gebirge (Süd-Costa Rica) aufgebaut und von Frühling 2005 bis Frühling 2007 betrieben. Diese Region ist geprägt durch die Subduktion des aseismischen Cocos-Rücken, der mit einem Winkel von 18 deg bis zu etwa 40 km Tiefe abtaucht. Basierend auf diesem flachen Subduktionswinkel wurde spekuliert, dass die sehr flache Subduktion des Cocos-Rückens verantwortlich ist fuer die Unterbrechung des aktiven Vulkanismus und die Hebung des Talamanca-Gebirges. Eine Receiver-Funktions-Analyse von 522 teleseismischen Erdbeben wurde durchgeführt und lieferte 1777 Receiver-Funktionen. Die Daten der Talamanca-Transect-Stationen wurden ergänzt durch kurzperiodische Daten, die von den Landstationen des Quepos-Netzwerks aufgenommen wurden. Dies ergab weitere 100 Receiver-Funktionen zu 39 Ereignissen. Die Moho der oberen Platte wird bei etwa 35 km Tiefe beobachtet, und eine inner-krustale Diskontinuität liegt bei ca. 20 km Tiefe, in guter übereinstimmung mit früheren aktiv-seismischen Studien. Entgegen den Erwartungen zeigen die migrierten Profilschnitte klar eine steil abtauchende (60 deg) Konversion bis zu mehr als 150 km Tiefe, die als die subduzierende Cocos-Platte interpretiert wird. 3d-Darstellungen basierend auf den Migrationsprofilen deuten nicht auf einen significanten übergang zu flacheren Subduktionswinkeln in der Nähe des Talamanca-Gebirges hin. Diese Ergebnisse deuten zum ersten Mal darauf hin, dass der Cocos-Rücken unter Süd-Costa Rica mit erheblich steilerem Winkel und zu größeren Tiefen subduziert, als bisher angenommen wurde. Dies eröffnet neue Fragen über den Mechanismus, der die Unterbrechung des aktiven Vulkanismus und starke Hebung des Talamanca-Gebirges herbeiführt. Mögliche Erklärungen sind unter anderem ein Kompressionsregime, das den Aufstieg von Magmen an die Oberfläche verhindert oder ein Mangel an Fluiden in der subduzierenden Platte, so dass es nicht zu fluid-induziertem Schmelzen des Mantelkeils kommen kann. Alternativen könnten kombinierte Subduktions/Underplating-Modelle oder ein übergangsregime zwischen zwei verschiedenen Subduktionsstilen sein. Modellierungs-Studien bestätigen, dass das beobachtete, als abtauchtende Platte interpretierte positive Signal durch eine im ähnlichen Winkel subduzierende Platte hervorgerufen werden kann. Mögliche Anisotropie-Scenarien, wie ``corner-flow'' und die daraus resultierende bevorzugte Gitter-Orientierung von Olivine, werden ebenso untersucht. Die Ergebnisse deuten auf die Existenz von corner-flow im Mantelkeil hin, evtl. mit zusätzlichem Mantelfluss parallel zum Vulkanbogen

Geochemical, Geophysical and Morphological Results from the Chilean Southern Volcanic Zone: The Role of Fluids in Generating the Highest Magmatic Output

In the Collaborative Research Center (SFB574), which studies the role of volatiles and fluids in subduction zones, we have compiled a comprehensive geochemical data set from the Chilean Southern Volcanic Zone. Here we focus on the middle volcanic front (MVF from 34.5-38°S) and the southern volcanic front (SVF from 38-43°S). We also have data from the behind the VF (BVF) volcanism in Argentina. This data set is augmented by calculations of volcano volume, a seismic profile from the forearc through the VF between 39-40°S and geophysical studies offshore the SVF. On the Sr vs Nd isotope diagram, the MVF almost completely overlaps the BVF samples. On Pb isotope diagrams, the MVF falls on the radiogenic end of the positive backarc array. On 206Pb/204Pb vs Sr and Nd isotope diagrams, the unradiogenic end of the BVF array has an EMORB type composition, suggesting an EMORB type of mantle wedge composition. The VF lavas can be explained largely by two component mixing of trench sediments (+/- subducting slab) and an EMORB type of mantle wedge. Combined with higher erupted volumes over shorter time scales for the SVF compared to the MVF (Völker et al., 2011, JVGR), the higher fluid mobile to fluid immobile (e.g. U/Th, Pb/Ce and Ba/Nb) ratios point to a higher fluid flux, whereas the lower more to less immobile incompatible (e.g. La/Yb, La/Sm, Th/Yb, Ta/Yb) element ratios are consistent with higher degrees of melting. On the Sr vs Nd and 206Pb/204Pb vs Sr and Nd isotope ratio diagrams, the SVF is shifted to higher Sr and Nd isotope ratios. We interpret these variations to indicate derivation of the fluids from seawater altered oceanic crust and/or mantle and sediments. The Pb isotopic composition of the SVF is identical to the MVF and is clearly dominated by the composition of the trench sediments. Delta 18O of olivine correlates inversely with U/Th and Nd isotope ratios, extending to lower and higher d18O than found in olivines in mantle peridotites. The low d18O and high U/Th and Nd isotope component present in the SVF (in Llaima and Villarrica) is interpreted to reflect fluids derived from hydrothermally altered oceanic crust and serpentinized upper mantle of the incoming plate, whereas the high d18O endmember primarily in the MVF points to fluids derived from subducted sediments. Beneath the VF between 39-40°S, where Villarrica, one of South America’s most active volcanoes, is located, a low-velocity seismic anomaly, together with high Vp/Vs ratios, is interpreted to reflect greater fluid ascent above the subducting Valdivia Fracture Zone. The combined morphologic (volume), geochemical and geophysical data suggest an enhanced fluid presence beneath much of the SVF (Llaima, Villarrica and Puyehue Volcanoes), probably caused by a stronger hydration of the incoming plate around and between the Valdivia and Chiloe Fracture Zones

Measuring out-of-field dose to the hippocampus in common radiotherapy indications

Background The high susceptibility of the hippocampus region to radiation injury is likely the causal factor of neurocognitive dysfunctions after exposure to ionizing radiation. Repetitive exposures with even low doses have been shown to impact adult neurogenesis and induce neuroinfammation. We address the question whether the out-offeld doses during radiotherapy of common tumour entities may pose a risk for the neuronal stem cell compartment in the hippocampus. Methods The dose to the hippocampus was determined for a single fraction according to diferent treatment plans for the selected tumor entities: Point dose measurements were performed in an anthropomorphic Alderson phantom and the out-of-feld dose to the hippocampus was measured using thermoluminescence dosimeters. Results For carcinomas in the head and neck region the dose exposure to the hippocampal region for a single fraction ranged from to 37.4 to 154.8 mGy. The hippocampal dose was clearly diferent for naso-, oro- and hypopharynx, with maximal values for nasopharynx carcinoma. In contrast, hippocampal dose levels for breast and prostate cancer ranged between 2.7 and 4.1 mGy, and therefore signifcantly exceeded the background irradiation level. Conclusion The mean dose to hippocampus for treatment of carcinomas in the head and neck region is high enough to reduce neurocognitive functions. In addition, care must be taken regarding the out of feld doses. The mean dose is mainly related to scattering efects, as is confrmed by the data from breast or prostate treatments, with a very diferent geometrical set-up but similar dosimetric results