Hokkaido University (北海道大学) / 博士 / 医学

Mit der palliativen transarteriellen Chemoembolisation (TACE) läßt sich eine Verkleinerung von malignen Lebertumoren und eine Verlängerung des Überlebens erreichen. Im Verlauf des Therapiezyklus diente die Phosphor-Magnetresonanzspektroskopie mittels Chemical-Shift-Imaging einem nichtinvasiven Einblick in den zellulären Energie- und Membranstoffwechsel. Eine Differenzierung zwischen primären und sekundären Lebertumoren war anhand der 31P-Spektren nicht möglich. Posttherapeutisch zeigten die Patienten einen Anstieg des anorganischen Phosphats bei Abfall des ß-NTP-Signals, die sich während des sechswöchigen Intervalls vor der nächsten Intervention wieder normalisierten. Therapieansprechen und -versagen zeigten während des Therapiezyklus unterschiedliche spektroskopische Quotientenverläufe. Eine deutliche Volumenreduktion als auch eine homogene und dauerhafte Lipiodoleinlagerung im Tumor gehen zuverlässig mit einem spektroskopischen Therapieansprechen einher. Dies zeigte sich bei der ersten Patientengruppe während der Untersuchung direkt nach der Embolisation und bei der zweiten Gruppe erst vor der nächsten Intervention. Therapieversagen, Tumorprogression und geringe Lipiodoleinlagerung bzw. rasche Entspeicherung im Verlauf ließen sich spektroskopisch nach-weisen. Schwierig bleibt die Zuordnung der Patienten mit uneinheitlichen Quotienten-verläufen. Die MRS kann früher als die klinische Routinediagnostik eine Aussage über das Therapieansprechen treffen. Für den Patienten ergibt sich die Vermeidung einer ineffektiven Therapie. Bei nachgewiesenem Ansprechen hingegen profitiert der Patient durch die wiederholte Anwendung der TACE. Der hohe personelle, technische und zeitliche Aufwand für die Phosphorspektroskopie verhindert bisher den klinischen Routineeinsatz dieses Verfahrens. Im Rahmen der klinischen Forschung, insbe-sondere in der onkologischen Therapiekontrolle, hat die MRS als nichtinvasive Methode heute einen großen Stellenwert. / Using palliative transarterial chemoembolization (TACE) a reduction of malignant liver neoplasms and a prolongation of survival time can be achieved. During the course of therapy phosphorous magnetic resonance spectroscopy by means of chemical-shift-imaging was used for noninvasive examination of the cellular metabolism of energy and membranes. Differentiation between primary and secondary liver tumors was not feasible using 31P-spectra. After therapy patients had shown increased inorganic phosphate signal and reduction of the ß-NTP-signals, which normalized during six week intervall before next intervention. Response and non-response to therapy showed different courses of spectroscopic quotients during therapy cycle. Prominent reduction of volume as well as homogeneous and continous retention of lipiodol within the tumor are reliable combined with spectroscopic response to therapy. The first group of patients showed these signs at the examination immediately after embolization whereas patients of the second group showed these signs not before next intervention. Failure of therapy, progression of tumor and slight retention of lipiodol or rapid elemination during course of therapy were detectable by spectroscopy. Categorization of patients with non-uniform courses of quotients remains difficult. Magnetic resonance spectroscopy is able to determine response to therapy earlier than standard diagnostic methods. As a result ineffective therapy is avoided for the patient. On the other hand the patient profits from repeated administration of TACE. Great expense of personnel, equipment and time so far prevents clinical use of phosphorous spectroscopy as a matter of routine. In conjunction with clinical research MRS is an important non-invasive method especially for oncological therapy monitoring.

Magnetic resonance imaging (MRI) is one of the most important diagnostic tools of modern healthcare. The signal in medical MRI predominantly originates from water and fat molecules. Separation of the two components into water-only and fat-only images can improve diagnosis, and is the premier non-invasive method for measuring the amount and distribution of fatty tissue. Fat-water imaging (FWI) enables fast fat/water separation by model-based estimation from chemical shift encoded data, such as multi-echo acquisitions. Qualitative FWI is sufficient for visual separation of the components, while quantitative FWI also offers reliable estimates of the fat percentage in each pixel. The major problems of current FWI methods are long acquisition times, long reconstruction times, and reconstruction errors that degrade image quality. In this thesis, existing FWI methods were reviewed, and novel fully automatic methods were developed and evaluated, with a focus on fast 3D image reconstruction. All MRI data was acquired on standard clinical scanners. A triple-echo qualitative FWI method was developed for the specific application of 3D whole-body imaging. The method was compared with two reference methods, and demonstrated superior image quality when evaluated in 39 volunteers. The problem of qualitative FWI by dual-echo data with unconstrained echo times was solved, allowing faster and more flexible image acquisition than conventional FWI. Feasibility of the method was demonstrated in three volunteers and the noise performance was evaluated. Further, a quantitative multi-echo FWI method was developed. The signal separation was based on discrete whole-image optimization. Fast 3D image reconstruction with few reconstruction errors was demonstrated by abdominal imaging of ten volunteers. Lastly, a method was proposed for quantitative mapping of average fatty acid chain length and degree of saturation. The method was validated by imaging different oils, using gas-liquid chromatography (GLC) as the reference. The degree of saturation agreed well with GLC, and feasibility of the method was demonstrated in the thigh of a volunteer. The developed methods have applications in clinical settings, and are already being used in several research projects, including studies of obesity, dietary intervention, and the metabolic syndrome.