(AJ) The three aims of the work were as follows: 1. Comparison of prostate magnetic resonance (MR) examination results from 1.5 T and 3 T scanners in patients with prostate carcinoma (PCa). MR findings of 103 patients (ages 44-72 years) were compared with histopathological results after radical prostatectomy. The work was focused on the accuracy of predicting local cancer staging and determining prostate tumour location. Patients were divided into three groups (A, B and C) based on the type of MR scanner and protocol used. Patient groups A and B were examined in 1.5T and 3T MR scanners equipped with surface coils in the identical multiparametric MR imaging protocol included dynamic contrast examination (DCE). Patient group C was examined in a 3T MR scanner without DCE. The highest accuracy of predicting the stage of PCa was seen in patients examined in 3 T MR scanner with DCE included in the protocol, however, no significant differences were seen between results from 1.5 T and 3.T MR scanners. No significant difference was also found in the accuracy of determining the location of prostate tumour between 1.5 T and 3T MR examinations, however, there were significant differences between sequences used, with the highest accuracy attained by using a combination of T2 weighted sequences and diffusion...

The dissertation is concerned to in vivo phosphorus MR spectroscopy (31 P MRS) and 1 H MR imaging (MRI) of muscle in combination with physical workload. The theoretical part of the thesis describes methodology of 31 P MRS measurement and its clinical use in research of metabolic changes in diabetes, heart failure and peripheral artery disease (PAD). The results of the thesis are divided into methodical and clinical parts. Methodical results deal with the construction of experimental equipment, software modification and development, and show of the reproducibility of the dynamic 31 P MRS. The MRI after exercise was used to the describe involvement of the individual calf muscles to muscle contraction during pedal movement in MR compatible ergometer. The first part of the clinical results of the thesis describes changes in muscle metabolism during diabetes and critical ischemia. In patients with critical ischemia the effect of treatment by angioplasty or transplantation of mesenchymal stem cells was evaluated. In the second part of the clinical results the metabolism of patients with heart failure complicated by sideropenia was studied. In these patients the effect of experimental treatment by iron carboxymaltose was described.

Einleitung: Mit der vorliegenden Studie wurden zum ersten Mal beim Menschen die Auswirkungen von Dehydration (Dehy) und anschließender Rehydratation (Rehy) auf cerebrale volumenregulatorische Metabolite (myo-Inosit (mI), N-Azetylaspartat+N-Azetylaspartylglutamat (tNAA), Kreatin (Cr), Glyzerophosphocholin+Phosphocholin (Cho) und Glutamat+Glutamin (Glx)) sowie auf Flüssigkeitsverschiebungen untersucht. Methoden: 14 Radsportler (26.6 (22.7/29.8) Jahre, Median und 25./75. Perzentile) wurden mittels 1H-Spektroskopie (1H-MRS) in der okzipitoparietalen grauen Substanz (GM) und parietalen weißen Substanz rechts (WMR) und links (WML) untersucht (GE Signa Horizon 3T94; PRESS: TE 30ms, TR 6000ms, VOI 8ml). Die Messungen erfolgten vor, direkt nach Dehy und nach Rehy (180min, Zufuhr von 150\% der verlorenen Körpermasse (KM)). Zusätzlich wurde durch T2-Relaxationsmessungen der Atrophieindex alpha (Verhältnis cerebrales Gewebewasser (HW) zu Liquor (CSF)) bestimmt. Resultate: Die KM der Probanden reduzierte sich durch Dehy um 3.7 (3.4/4.1)% und stieg durch Rehy wieder um 4.5 (3.7/5.3)% an (Wilcoxon: p / Introduction: In the present study the influence of Dehy on cerebral volume regulatory metabolites (myo-Inositol (mI), N-Acetyl-aspartata+N-Acetyl-aspartyl-glutamate (tNAA), Creatine (Cr), Glycerophosphocholine+Phosphocholine (Cho) and Glutamate+Glutamine (Glx)) and fluid shifts has been investigated for the first time in humans. Methods: 14 cyclists (26.6 (22.7/29.8) y, median and 25./75. percentile) have been examined with proton NMR spectroscopy in the occipito-parietal gray matter (GM) and the right (WMR) and left (WML) parietal with matter (GE Signa Horizon 3T94; PRESS: TE 30ms, TR 6000ms, VOI 8ml). Spectra were acquired before, immediately after Dehy and after rehydration (Rehy). Rehy took place during 180min and 150% of lost body weight (BW) was substituted. Additionally the atrophy index alpha (ratio between cerebral water and liquor) was assessed (T2 signal decay as a function of echo time). Results: BW of volunteers has been decreased 3.7 (3.4/4.1)% after Dehy and increased 4.5 (3.7/5.3)% after Rehy (Wilcoxon: p

Diese Schrift faßt in zwei Abschnitten eigene Beiträge zur Einführung der lokalisierten Magnetresonanzspektroskopie (MRS) und der funktionellen Magnetresonanztomografie (fMRT) in die diagnostische Medizin zusammen. Im ersten Teil wird beschrieben, wie die biochemischen Metabolite N-Azetylaspartat, Kreatin und Phosphokreatin, cholin-enthaltende Verbindungen und Laktat durch die Einführung der stimulierten Echo-Akquisitionsmethode (STEAM) als Lokalisationstechnik in die diagnostische Magnetresonanzspektroskopie in definierten Hirnregionen gesunder Versuchspersonen nichtinvasiv zugänglich gemacht und erstmals in Form von In-vivo-Konzentrationen quantifiziert werden konnten. Daraufhin wird gezeigt, wie die Weiterentwicklung der robusten STEAM-Technik zu kurzen Echozeiten das Signal-zu-Rauschverhältnis und damit die Messung kleinerer Untersuchungsvolumina erheblich verbesserte. Zudem wurde dadurch die Erkennung und Quantifizierung weiterer Metabolite wie z. B. des myo- und scyllo-Inosits, des Glutamats und Glutamins, des N-Azetylaspartylglutamats und der Glukose ermöglicht. Diese Methode setzte damit zusammen mit der verwendeten linearen Kombinationsmethode (LCModel) zur Konzentrationsbestimmung den spektralen Qualitätsstandard des gesamten letzten Jahrzehnts. Ferner werden die parallelen Pionierarbeiten zu Hirnerkrankungen fokaler und generalisierter Art beleuchtet. Diese Anwendungen der lokalisierten STEAM-Protonenspektroskopie in Einzelvolumentechnik zur Messung umschriebener Prozesse umfassen zerebrale Tumore und Infarkte, Plaques der multiplen Sklerose sowie andere entzündliche und degenerative Läsionen. Auch die lokalisierte STEAM-Phosphorspektroskopie und nichtzerebrale Anwendungen wie die lokalisierte Protonenspektroskopie von Faserbündeln des Skelettmuskels und der Niere bauen weitgehend auf diesem Fortschritt in der Methode auf. Zusätzlich werden Anwendungen bei generalisierten Erkrankungen gestreift, speziell angeborenen Stoffwechselerkrankungen des Kindesalters wie mitochondrialen und lysosomalen Defekten, Stoffwechselentgleisungen bei Diabetes mellitus und Leberzirrhose, psychiatrischen Erkrankungen wie der Alzheimer-Demenz. Die weitere Verbreitung dieser Erkenntnisse in die klinische Diagnostik wird entscheidend von der Beachtung des hier eingeführten Qualitätsmaßstabs und der darauf aufbauenden absoluten Metabolitquantifizierung abhängen. Der zweite Teil dieser Arbeit faßt ausgehend von funktionellen protonenspektroskopischen Untersuchungen des visuellen Kortex bei photischer Aktivierung Fortschritte zusammen, die bei der Entwicklung und Anwendung der suszeptibilitätsempfindlichen MR-Tomografie zur Messung physiologischer Hirnaktivierung mit dem Modell der visuellen Stimulation erzielt wurden. Während die Belastung des Energiestoffwechsels im angeregten striatären Kortex anhand abgesunkener Gewebespiegel von Glukose und angestiegener Laktatkonzentrationen mithilfe der zeitaufgelösten Spektroskopie beobachtet werden konnte, gelang die Demarkierung der Ausdehnung der Hirngewebeaktivierung mithilfe der T2*-gewichteten FLASH-MRT, die begleitende Verminderungen des paramagnetischen Desoxyhämoglobins im funktionell aktiven Gewebe mit Anstiegen der Bildsignalintensität wiedergibt. Schließlich werden Untersuchungen beschrieben, die die Empfindlichkeit dieses endogenen, sauerstoffspiegelabhängigen Suszeptibilitätskontrastes für die Wirkung verschiedener Medikamente bzw. pharmakologischer Stimulantien zeigen, die direkt oder indirekt über bestimmte vaskuläre Rezeptoren wirken. Diese Untersuchungen befördern wiederum ein neues Gebiet der Bildgebung, die pharmakologische MRT. / This work has two main parts that summarize pioneering contributions to localized magnetic resonance spectroscopy (MRS), functional magnetic resonance tomography (fMRI), and the introduction of these modalities into diagnostic medicine. First, it is described how biochemical metabolites such as the intracellular pools of N-acetylaspartate, creatine and phosphocreatine, choline-containing compounds, and lactate have been made accessible to noninvasive detection and to the quantification of their respective concentrations in vivo in defined cerebral regions of healthy subjects by utilizing the stimulated echo-acquisition mode (STEAM) localization technique. Then it is shown that further development of the robust STEAM technique to short echo times not only increased the signal-to-noise of the measurement, thereby providing access to smaller volumes-of-interest, but also allowed for the detection and quantification of additional metabolites such as myo- and scyllo-inositol, glutamate, glutamine, N-acetylaspartylglutamate, and glucose. Thus, together with the adoption of the linear combination method (LCModel) for concentration calculation, this method has set the standard for spectroscopic state-of-the-art in the field well over the last decade. Moreover, pioneering achievements have been highlighted with regard to applications in brain diseases of focal and generalized nature. Pertinent applications of localized single-volume STEAM proton spectroscopy to circumscribed processes include cerebral tumors, cerebral infarction, multiple sclerosis plaques, and other inflammatory and degenerative lesions. Also localized STEAM phosphorus spectroscopy and non-cerebral applications including localized proton spectroscopy of skeletal muscle and kidney largely depend on the short-echo time STEAM technique. In addition, applications in generalized disorders have been explored, which include inborn errors of metabolism in childhood, such as mitochondrial and lysosomal defects, metabolic disturbances in diabetes mellitus and liver cirrhosis, and psychiatric diseases such as Alzheimer's dementia. The further utilization of these novel methods in clinical diagnostics will heavily depend on quality measures and the mastering of a true quantification procedure as demonstrated. Second, this work summarizes achievements made in developing and applying both proton MR spectroscopy and susceptibility-sensitized MR imaging to measure physiologic brain activation using visual stimulation as a model. Whereas metabolic stress, brought upon the bioenergetic steady state in the responding striate cortex, was detected by decreased parenchymal glucose and increased lactate using time-resolved spectroscopy, mapping the extent of parenchymal activation was found to be possible by increases of image intensity in T2*-weighted FLASH MRI made sensitive to concomitant decreases of paramagnetic deoxyhemoglobin in the functionally active tissue. Finally, studies are described, which show the sensitivity of this endogenous, susceptibility-sensitive contrast, now generally known as BOLD effect, to various drugs or pharmacologic stimuli acting either directly or indirectly on vascular receptors. These latter studies open up again a new field of imaging, dubbed pharmacologic MRI.

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Proton MR spectroscopy is a non-invasive tool for measuring in vivo concentrations of several metabolites. The aim of this thesis was to test its applicability and reliability in neurosurgical praxis. In the first part of the study multiple MR spectroscopy methods were applied in a group of patients after surgery and oncologic treatment for high-grade glioma to test which method performed best in discriminating recurrent tumor from radionecrosis in the presence of a new enhancing lesion. The best diagnostic yield was achieved by comparison of choline, creatine and lactate between lesion and contralateral side (sensitivity 93.3%, specificity 78.6%). Creatine was significantly decreased in patients compared to controls. The inhibiting effect of ongoing oncologic treatment on cerebral and tumoral metabolism makes differential diagnosis trickier. Therefore, a diagnosis of radionecrosis assessed during ongoing radio- and chemotherapy should be confirmed after its completion. In the second part of the study MR spectroscopy data was compared with MR hippocampal volumetry and transcranial doppler examination in a cohort of patients with unilateral occlusion of the internal carotid artery. The N-acetylaspartate/choline ratio and hippocampal volume were significantly lower in both hemispheres of patients...

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.