Introduction Since its development by Al Wolf and colleagues in the 1970s1, [11C]cyanide has been a useful synthon for a wide variety of reactions, most notably those producing [1-11C]-labeled amino acids2. However, despite its position as rote gas-phase product, the catalytic synthesis is difficult to optimize and often only perfunctorily dis-cussed in the radiochemical literature. Recently, [11C]CN– has been used in the synthesis of indole-3-[1-11C]acetic acid ([11C]IAA), the principal phytohormone responsible for a wide variety of growth and development functions in plants3. The University of Wisconsin has expertise in cyclotron production and radiochemistry of 11C and previous experience in the PET imaging of plants4,5. In this abstract, we present work on optimizing [11C]CN– production for the synthesis of [11C]IAA and the PET imaging of auxin transport in living plants. Material and Methods [11C]CH4 was produced by irradiating 270 psi of 90% N2, 10% H2 with 30 µA of 16.1 MeV protons from a GE PETtrace cyclotron. After irradiation, the [11C]CH4 was converted to [11C]CN– by passing through a quartz tube containing 3.0 g of Pt wire and powder between quartz wool frits inside a 800–1000 ˚C Carbolite tube furnace. The constituents and flow rate of the [11C]CH4 carrier gas were varied in an effort to optimize the oven\'s catalytic production of [11C]CN– from CH4 and NH3. The following conditions were investigated: i. Directly flowing irradiated target gas versus trapping, purging and releasing [11C]CH4 from a −178 ˚C HayeSep D column in He through the Pt furnace. ii. Varying the amount of anhydrous NH3 (99.995%) mixed with the [11C]CH4 carrier gas prior to the Pt furnace. Amounts varied from zero to 35 % of gas flow. iii. Varying the purity of the added NH3 gas with the addition of a hydride gas purifier (Entegris model 35KF), reducing O2 and H2O impurities to < 12 ppb. iv. Varying the flow rate of He gas carrying trapped, purged and released [11C]CH4. After flowing through the Pt furnace, the gas stream was bubbled through 300 µL of DMSO containing IAA precursor gramine (1 mg), then passed through a 60×5 cm column containing ascarite to absorb [11C]CO2, followed by a −178˚C Porapak Q column to trap [11C]CH4 and [11C]CO. After bubbling, the DMSO/gramine vial was heated to 140 ˚C to react the gramine with [11C]CN–, forming the intermediate indole-3-[1-11C]acetonitrile ([11C]IAN), which was subsequently purified by solid phase extraction (SPE). The reaction mixture was diluted into 20 mL water and loaded onto a Waters Sep-Pak light C18 cartridge, followed by rinsing with 5 mL of 0.1% HCl : acetonitrile (99 : 1) and 10 mL of the same mixture in ratio 95 : 5, and finally eluted with 0.5 mL of diethyl ether. The ether was subsequently evaporated under argon flow, followed by the hydrolysis of [11C]IAN to [11C]IAA with the addition of 300 µL 1 M NaOH and heating to 140 ˚C for 5 minutes. After hydrolysis, the solution was neutralized with 300 µL 1 M HCl and purified using preparative high-performance liquid chromatography (HPLC) using a Phenomenex Luna C18 (10μ, 250×10mm) column with a mobile phase acetonitrile : 0.1% formic acid in H2O (35 : 65) at flow rate of 3 mL/min. The [11C]IAA peak, eluting at 12 minutes, was collected and rotary evaporated to dryness, then again after the addition of 5 mL acetonitrile, followed by its reconstitution in 50 µL of water. Analytical HPLC was performed on the [11C]IAA before and after this evaporation procedure using a Phenomenex Kinetex C18 (2.6μ, 75× 4.6 mm) column with a linear gradient elution over 20 minutes of 10 : 90–30 : 70 (acetonitrile : 0.1% formic acid) at a 1 mL/min flow rate, eluting at 7.6 minutes. The transport of [11C]IAA was monitored following administration through the severed petiole of rapid cycling Brassica oleracea (rcBo) using a Siemens microPET P4 scanner. Transport was compared following administration to the first true leaf versus the final fully formed leaf in plants with and without exposure to the polar auxin transport inhibitor naphthylphthalamic acid (NPA). Results and Conclusion Optimization of the [11C]CN– gas phase chemistry was performed using two key metrics for measuring conversion yield. First is the fraction of total produced radioactivity that trapped in the DMSO/gramine solution (denoted %DMSO), and second, the fraction of DMSO/gramine-trapped activity that was able to react with gramine to form [11C]IAN (denoted %CN–). Under certain conditions, the former of these metrics experienced significant losses due to unconverted [11C]CH4 or through combustion, forming [11C]CO2 or [11C]CO. The latter metric experienced losses due to production of incomplete oxidation products of the CH4-NH3 reaction, such as methylamine. Total [11C]CH4 to [11C]CN– con-version yields is reported by the product of the two metrics. It was initially hypothesized that the irradiation of a 90% N2, 10% H2 target gas would produce sufficient in-target-hot-atom-produced NH3 to convert [11C]CH4 to [11C]CN– in the Pt furnace. However, conversion yields were found to be low and highly variable, with 13 ± 8 % trapping in DMSO/gramine, 9 ± 9 % of which reacted as CN– (n = 15). While in disagreement with previous reports1, this is likely as a result the batch irradiation conditions resulting ammonia losses in the target chamber and along the tubing walls. Yields and reproducibility were improved when combining the target gas with a stream of anhydrous NH3 gas flow with conversion yields reported in TABLE 1. However, these yields remained undesirably low, potentially as a result of the 10% H2 carrier gas having an adverse effect on the oxidative conversion of [11C]CH4 to [11C]CN–. To remedy this, the irradiated target gas was trapped, purged, released in He and combined with NH3 gas before flowing through the Pt furnace. Initial experiments using 99.995% anhydrous NH3 gas resulted in very poor (< 0.1%) [11C]CN– yields as a result of nearly quantitative combustion forming [11C]CO2. Installation of a hydride gas purifier to reduce O2 and H2O impurities in NH3 improved yields for CH4 in He, but did not significantly affect those from [11C]CH4 in N2/H2 target gas. In disagreement with previous reports2, conversion yields were found to be highly sensitive to overall carrier gas flow rate, with lower flow rates giving the best yields, as shown in TABLE 1. Optimization experiments are continuing. The total decay-corrected yield for the 1 hour synthesis of [11C]IAA in 50 µL of water is 2.3 ± 0.7 %, based on the total produced [11C]CH4 with a specific activity ranging from 1–100 GBq/µmol. The principal radiochemical impurity was determined to be indole-3-carboxylic acid. The SPE procedure isolating the [11C]IAN intermediate product was optimized to minimize this impurity in the final sample. After a rapid distribution of the administered [11C]IAA through the cut petiole and throughout the rcBO plant, upward vascular transport of auxin and downward polar auxin transport was visualized through time-activity curves (TACs) of regions of interest along the shoot. Comparison of these TACS with and without exposure to NPA yields insight into the fundamental physiological process of polar auxin transport in plants. In conclusion, the Pt-catalyzed oxidative conversion of [11C]CH4 and NH3 to [11C]CN– is a challenging process to optimize and highly sensitive to carrier gas composition and flow rate. Optimization for our experimental conditions yielded several results which disagreed with previous reports. [11C]IAA produced using [11C]CN– is well suited for PET imaging of polar auxin transport in living plants.

In der vorliegenden Arbeit wird der Hypothalamus, eine kleine, aber bedeutsame Struktur des Zwischenhirns untersucht. Er spielt unter anderem eine Rolle bei der Regulation des Schlaf-Wach-Rhythmus, des Sexualverhaltens, der Stimmungslage, autonomer und Stoffwechsel-Funktionen. Veränderungen einzelner oder mehrerer spezifischer Kerngruppen sind bei neuropsychiatrischen bzw. -endokrinologischen Erkrankungen, wie Narkolepsie, Schizophrenie, affektiver Störung, Demenz, Borderline-Persönlichkeitsstörung, Pädophilie oder Adipositas zu beobachten. Die Substrukturierung und Darstellung der einzelnen Kerngruppen gelang bisher nur in Postmortem-Studien. Im Rahmen dieser Studie konnte mit Hilfe der Diffusions-Tensor-Bildgebung erstmals eine in-vivo Substrukturierung des Hypothalamus konsistent bei zehn gesunden Probanden vorgenommen werden. Dabei wurden nach einem Algorithmus zunächst die Segmentierung und anschließend die Parzellierung durchgeführt, woraus sich drei konsistente Cluster ergaben. Der topografische Vergleich der erhaltenen Cluster mit Postmortem-Studien der Literatur ergab vergleichbare und anatomisch plausible Korrelate. Mit der von uns entwickelten Methode könnten anhand einer größeren Patientengruppe pathophysiologische Zusammenhänge neuropsychiatrischer und –endokrinologischer Störungen genauer eruiert werden und zu einem besseren Verständnis des Krankheitsverlaufs und der Therapie beitragen.

Techn. Hochsch., Diss., 2001--Aachen.

Matrix assisted laser desorption/ionization mass spectrometry (MALDI MS) and the corresponding visualization technique MALDI MS Imaging (MSI) have emerged as important analytical tools in biochemical sciences, e.g., for drug development or to trace the metabolomic changes in cancerous tissues. Initially developed for the detection of high molecular weight compounds (HMWC; M > 1000 Da), in recent years the reliable and reproducible detection of low molecular weight compounds (LMWC; M < 1000 Da) has gained high attention, e.g., in the research fields of metabolomics and lipidomics. By using a protective matrix, the MALDI technique is capable of soft ionization of analytes to prevent their fragmentation or degradation. This matrix is responsible for the spatial separation of the analyte molecules, their protection from the strong laser shots, and their ionization. Commonly used matrices are small organic matrices (SOMs; M < 500 Da), which are utilized in HMWC analytics and recently also in LMWC analytics since they show sufficient absorption of the laser radiation, high crystallinity, and good ionization efficiency. However, their utilization can cause several drawbacks: (i) High background interferences below m/z = 1000 (not MALDI silent), which is disadvantageous specifically for LMWC analytics; (ii) low vacuum stability, which is especially problematic for standard instruments operated under high vacuum (HV); (iii) challenging homogeneous thin-layer coating, potentially causing inconsistent measurement conditions; and (iv) usually no suitability for dual polarity mode experiments, i.e., carrying out positive and negative mode measurements with the same matrix. Polymeric materials are promising candidates for MALDI silent matrices, as the large variety of possible molecular layouts potentially allows to meet all prerequisites of a MALDI matrix: (a) Sufficient ultra-violet (UV) laser radiation absorption, implemented by introducing conjugated π-electron systems in the polymer backbone or side chains; (b) high ionization efficiency, enhanced by adding acidic and/or basic functional groups to the polymer’s molecular structure, potentially also allowing dual polarity mode measurements; (c) MALDI silence, enabled by the high molar mass of the polymer chains; (d) high vacuum stability, also granted by the polymer’s molar mass; and (e) homogeneous thin-films, achieved by multiple available coating methods. Yet, despite their high potential only a handful of polymeric matrices were reported in literature and so far, investigations to develop conscious design strategies are missing. The target of this thesis is to contribute to the field of MALDI silent matrices by developing and investigating different polymers as macromolecular MALDI MS and MSI matrices for LMWC analytics. Therefore, two different strategies were explored: (i) Investigating conjugated polymers, and (ii) polymerizing SOMs. For the first strategy, five conjugated polymers were tested as MALDI matrices for the detection of various LMWCs. Among these, four were found to be excellent matrices, with sufficient ionization efficiencies and rare dual polarity mode suitability and allowed LMWC detection with low background interferences (MALDI silent). A high crystallinity of the matrix (SOM) is reported to be crucial to ensure successful measurements, yet conjugated polymer matrices (CPMs) are semi-crystalline, i.e., they contain crystalline and amorphous domains. Hence, the analytes are expected to be incorporated in the crystalline domains of the CPMs, depending on their degree of crystallization. Therefore, two amorphous CPMs were synthesized and tested, showing similar matrix performances (e.g., ionization efficiencies, dual polarity mode, MALDI silence) as a structurally related semi-crystalline CPM. This indicates that the analytes are incorporated in the amorphous parts of the CPM. The second strategy towards polymeric matrices (PMs) is the polymerization of standard SOMs. As the matrix performance of the corresponding SOMs is known, the performance of the respective polymerized SOMs (P(SOMs)) can be validated against this benchmark. At the same time, polymerization can induce the properties needed to enable efficient LMWC analytics. Therefore, two standard SOMs were modified and polymerized, resulting in P(SOMs), which were vacuum stable and MALDI silent, and showed similar optical properties, analyte scopes and ionization efficiencies in benchmark tests with their respective SOMs. For the fast and facile comparison of the matrix performances of PMs and standard matrices, the graphing software OriginPro was used to visualize, process, and evaluate the acquired mass spectra. To automatize these tasks, a script was programmed using the OriginPro-native programming languages LabTalk and OriginC: X Functions.

Im Rahmen des vorliegenden Dissertationsprojektes wurde der Zusammenhang zwischen Ausprägung des regulativen Temperaments und SERT-Verfügbarkeit als Indikator für die Funktionalität des zentralen serotonergen Systems mittels Positronen-Emissions-Tomographie (PET) bei adipösen im Vergleich zu normalgewichtigen Personen untersucht.

Introduction 76Br is of interest for in vivo PET imaging applications. Its relatively long half-life (16.1 h) allows use not only on small molecules but also proteins which have slow excretion as carrier molecules. Irradiation using a low energy proton beam (~ 20 MeV) on an enriched Cu276Se target, followed by dry distillation with thermal chromatography, is one of the best methods to obtain sufficient amounts of 76Br for clinical applications1,2. However, the thermal chromatography is plagued by poor reproducibility and appears unsuitable for automation of its production, leading us to remove the thermal chroma-tography from the dry distillation. In this investigation we employed H2O solution to collect 76Br and optimized the distillation condition using a small amount of 77Br (57.0 h). We also produced large amount of 76Br under the optimized conditions to evaluate the dry distillation method. Material and Methods Target preparation and dry distillation were conducted based on the methods described in previous reports1,2. To produce 77Br, Cu2natSe target was irradiated with 20 MeV proton beams (5 µA) accelerated by AVF cyclotron in the Japan Atomic Energy Agency. The following two systems were used in the dry distillation optimization studies; (1) an initial system was composed of two furnaces, a main and an auxiliary furnace. Temperature of each furnace was set at 1050 °C (main) and 200 °C (auxiliary) respectively; (2) the second system was made of one large furnace composed of heating and cooling area. Temperature of the heating area was varied from 1050 to 1120 °C. In both systems PTFE tubing, leading to a H2O solution (15 mL), was inserted into the apparatus. The irradiated target was heated under streaming Ar gas (30 mL/min.). An enriched Cu276Se target (76Se enrichment: 99.67%) was used for 76Br production. Radioactivity was measured on a high-purity germanium (HPGe) detector coupled to a multichannel analyzer. TLC analyses were conducted on Al2O3 plates (Merck) using 7:1 acetone:H2O as the eluting solvent. Results and Conclusion Low efficiency (33 %) of 77Br recovery was ob-served in the initial system. Distribution of radioactivity inside the apparatus showed that 35 % was trapped in the PTFE tube and the quartz tube. The recovery yield was increased up to 54 % when the auxiliary furnace was turned off, indicating that the temperature gradient inside the quartz tube is suitable to carry 77Br effectively to the H2O trap. We initially used a quartz boat to place the irradiated target in the furnace, but found that using a reusable tungsten backing was better. However, we found that recovery yield was dramatically reduced to 18 %. The studies where the temperature was varied showed that releasing efficiency was increased up to 100 % at the temperature of 1120 °C. Good recovery yield (~ 77 %) was achieved after optimizing the temperature gradient (FIG. 1b). Using the optimized setup, 76Br production runs (n = 6) have been conducted, allowing us to recover up to 39.8 MBq/µAh (EOB) of 76Br. High specific activity (~4400 GBq/µmol) was obtained in the final solution. TLC analysis showed that chemical form obtained was bromide. We concluded that the dry distillation using H2O trap is capable of providing enough high purity 76Br for clinical applications.

Introduction The 80kD glycoprotein transferrin (TF) and its related receptor (TFR1) play a major role in the recruitment by cancer cells of factors for their multiplication, adhesion, invasion and metastatic potential. Though primarily designed to bind iron and then be internalised into cells with its receptor, TF can also bind most transition metals such as Co, Cr, Mn, Zr, Ni, Cu, V, In & Ga. Under certain conditions TF binds Ti (IV) even more tightly than it does Fe and that this occurs at the N-lobe (as distinct from C) of apoTF. Further, under physiological conditions the species Fe(C)Ti(N)-TF may provide the route for Ti entry into cells via TFR1 (1). Thus, the radiometal PET reporter isotope 45Ti with an ‘intermediate’ (~hrs) half-life suited to tracking cell-focused biological mechanisms is an attractive option for elucidating cellular mechanisms involving TF binding and internalisation, at least in (preclinical) animal models. 45Ti (T½ = 3.08 hr; + branching ratio = 85 %; mean β+ energy = 439keV, no significant dose-conferring non-511keV γ-emissions) was produced using the reaction 45Sc(p,n)45Ti by irradiating (monoisotopic) scandium discs with an energy-degraded proton beam produced by an 18MeV isochronous medical cyclotron. Separation and purification was achieved with an hydroxylamine hydrochloride functionalised resin. Comparative microPET imaging was performed in an immunodeficient mouse model, measuring biodistributions of the radiolabels 45Ti-oxalate and 45Ti-human-TF (45Ti-h-TF), out to 6hr post-injection. Materials and Methods High purity 15mm diameter scandium disc foils (99.5%, Goodfellow, UK) each thickness 0.100 ± 0.005 mm (55 mg) were loaded into an in-house constructed solid-targetry system mounted on a 300mm external beam line utilising helium-gas and chilled water to cool the target body (2). The proton beam was degraded to 11.7 MeV using a graphite disc integrated into the graphite collimator. This energy abolishes the competing ‘contaminant’ reactions 45Sc(p,n+p)44Sc and 45Sc(p,2n)44Ti. Beam current was measured using the well documented 65Cu(p,n)65Zn reaction. Calculations showed that the chosen energy is close to the optimal primary energy (~12 MeV) for maximising the (thin-target) yield from a 0.100 mm thick target. For separation of Ti from the Sc target two methods were examined; (i) ion exchange column separation using 2000 mg AG 50W-X8 resin conditioned with 10mL 9M HCl. Disc is dissolved in 1 mL of 9M HCl, which at completion of reaction is pipetted into column. Successive 1 mL volumes of 9M HCl are added, and subsequent elutions collected. (ii) Following Gagnon et al., (3) a method employing hydroxylamine hydro-chloride functionalised resin (’hydroxamate method’) was applied, similar to its use in our hands for purification and separation of 89Zr (2) following its original description for 89Zr by Holland et al., (4). Disc dissolved in 2mL 6M HCl, then diluted to 2M. Elute through column to waste fraction 1 (w1 – see FIG. 1). Then elute 6 mL of 2M HCl through column to w2, followed by 6 mL of traceSELECT H2O to w3. Finally, elute Ti into successive 1 mL product fractions (p1, 2 etc.) using 5 mL of 1M oxalic acid. This procedure takes approximate 1 hr. 45Ti in elution vials was measured using γ-spectroscopy. Sc in the same vials was determined later using ICP-MS. Results A typical production run using a beam current of 40 μA for 60min on a 0.100mm-thick disc produced an activity of 1.83 GBq. Radionuclidic analysis of an irradiated disc using calibrated cryo-HPGe γ-spectroscopy revealed T½ = 2.97–3.19 hr (95% CI) for 45Ti, and with contaminant 44Sc < 0.19 %, with no other isotopes detected. Despite systematic adjustments to column conditions satisfactory chemical separation was not achieved using the ion exchange column method (i), despite previous reports of its success (5). Typical results of separation using the successful hydroxamate method (ii) are shown on the FIGURE 1. It is seen that significant portion of 45Ti is lost in the initial washing steps leading to waste collection. N = 4 replicate experiments showed a variation (SD) of 10 % of the mean in each elu-tion fraction. Subsequent ICP-MS of the same elutions for (cold) Sc showed approximately 80 % by mass appeared in w1 and 20 % in w2, with negligible total mass (total fraction ~1/6000) of Sc in product (p1–4) vials. However, the FIG. 1 shows that a total of only 30% of the original activity of 45Ti (corrected to EOB) is available in the product vials, with the vial of highest specific activity (p1) containing 14 %. However, using a stack of 2×0.100mm thick Sc discs as a target yields isotope of adequate specific activity with-out need for concentration, for subsequent labelling and small-animal imaging purposes. In a ‘proof-of-principle’ experiment, two groups of healthy Balb/c-nu/nu female adult mice were administered with 45Ti radiotracers. The first group (N = 3) received approximately 20 MBq IP of 45Ti-oxalate buffered to pH = 7.0, and under-went microPET/CT imaging (Super Argus PET, Sedecal, Spain) out to 6hr post-injection, plus biodistribution analysis of radioactivity by dis-section at sacrifice (6hr). The second group (N = 3) received approximately 20 MBq IP of 45Ti-h-TF and were also studied to 6hr post-injection, followed by radioactive analysis after dissection at sacrifice. Organ and tissue biodistributions of the two groups at 6hr were similar but with 45Ti-oxalate showing slightly greater affinity for bone. Biodistribution by dissection results broadly confirmed the findings from PET images. However, TLC results suggested that similarity of radiolabel biodistributions of the two groups may be due to contamination of the TF radiolabel with non-conjugated Ti at time of injection. An alternative explanation is dechelation in vivo of 45Ti from 45Ti-h-TF. Conclusion Despite significant loss of 45Ti to the waste fractions of the separation process (total 53 %, corrected to EOB), 45Ti of acceptable specific activity and high radionuclidic purity has been produced from the reaction 45Sc(p,n)45Ti, with separation and purification of the product by hydroxamate column chemistry, confirming an earlier report. Though microPET in vivo imaging using 45Ti-based radiolabels was shown to be feasible, the similarity in the results for the label 45Ti-h-TF compared with ‘raw’ 45Ti-oxalate suggests further investigations. These may include a direct comparison of in vivo 45Ti-h-TF small-animal imaging plus post-dissection biodistribution with the same procedures using 89Zr labelled h-apotransferrin (6).

No description available.

In dieser Arbeit untersuchten wir die Beziehung zwischen somatosensibel evozierten Potenzialen (SSEP) und die von mittels Diffusions-Tensor MRT erfassten mikrostrukturellen Veränderungen der weißen Substanz des Gehirns von Patientinnen und Patienten mit Multipler Sklerose. Hierzu korrelierten wir SSEP-Latenzen, explizit die N20- und CCT-Latenzen (Central Conducting Time), mit den durch die DTI gewonnenen Parametern fraktionelle Anisotropie (FA), radiale Diffusivität (RD) und axiale Diffusivität (AD). Die Untersuchungen wurden als retrospektive Subgruppenanalyse an den Datensätzen von 46 Patienten durchgeführt, die als Teil einer prospektiven Single-Center Studie (rhGh-Studie) erfasst wurden. Die Auswertung der Daten erfolgte mit dem FSL-Softwarepaket (FSL, FMRIB, Oxford). Wir fanden signifikante negative Korrelationen mit FA, als Marker für strukturelle Integrität, sowie signifikante positive Korrelation mit RD, als Parameter für Demyelinisierung, in zahlreichen Regionen der weißen Substanz. Insbesondere in Regionen der somatosensiblen Bahnen, in Bereichen sowohl mit als auch ohne morphologisch sichtbar MS-bedingten Läsionen, zeigten sich ausgeprägte Korrelationen für mN20-Latenzen (mean N20, der Mittelwert zwischen links und rechts), wohingegen wir für mCCT-Latenzen (mean CCT) lediglich Korrelationen für FA, jedoch nicht für RD fanden. Für nur linksseitig gemessene N20-Latenzen zeigten sich sowohl mit FA als auch für RD deutlich stärkere Korrelationen in mehr anatomischen Regionen mit größeren Clustern, als dies für mN20- und nur rechtsseitig gemessene N20-Latenzen der Fall war. Zudem zeigte sich eine Tendenz zu signifikanteren Korrelationen in der gegenseitigen Hemisphäre sowohl bei nur rechts-, als auch bei nur linksseitigen N20-Latenzen. Wir fanden keine Korrelationen zwischen SSEP und AD als Marker der axonalen Integrität. Generell fanden wir mehr Korrelationen von DTI-Parametern zu mN20-Latenzen als zu mCCT-Latenzen. Diese zeigten zudem höhere Signifikanzniveaus als auch größere Cluster in mehr Regionen. Ein Grund dafür könnte sein, dass längere SSEP, die Anteile des Rückenmarks in ihrem Verlauf beinhalten, besser mit DTI-Parametern korrelieren. In einer weiteren Auswertung unserer Daten fokussierten wir uns auf Hirnregionen, die somatsosensible Fasern führen. In unserer Studie fand sich die Region mit den höchsten Korrelationen (p<.004), die Teil des somatsensiblen Systems ist, in der Corona radiata posterior (PCR). Sowohl mN20 als auch mCCT-Latenzen zeigten starke Korrelationen in dieser Region. Hier verlaufen aszendierende und deszendierende sensible Fasern zum Gyrus postcentralis und motorische Fasern zum Gyrus präcentralis. Die in unserer Studie gezeigte signifikante und starke Korrelation mit SSEP in dieser anatomischen Region unterstreicht deren Bedeutung als einfach zu erhebender klinischer Surrogatmarker für mikrostrukturelle Veränderungen der weißen Substanz bereits in einem frühen Stadium der Erkrankung. Einen Aspekt unserer Ergebnisse konnten wir nicht abschließend klären: die ausgeprägten Seitenunterschiede in rechts- und linksseitigen N20-Latenzen in den Korrelationen mit FA und RD. Diese Unterschiede zeigten sich auch im Ansatz bei rechts- und linksseitigen CCT-Latenzen, erreichten jedoch nicht das geforderte Signifikanzniveau. Wir beobachteten mehr signifikante Voxel mit höheren p-Werten und stärkeren Korrelationen in kontralateralen Regionen der abgeleiteten SSEP. Als mögliche Erklärung für die gezeigten Seitenunterschiede könnte die Händigkeit der Probanden als Erklärung dienen, bei der es mehr Rechtshänder in einer Population als Linkshänder gibt. Dies konnten wir jedoch retrospektiv nicht sicher nachvollziehen, sodass dies nur vermutet werden kann.

No description available.