Magnetic resonance imaging (MRI) is the preferred imaging modality for visualization of intracranial soft tissues. Surgical planning, and increasingly surgical navigation, use high resolution 3-D patient-specific structural maps of the brain. However, the process of MRI is a multi-parameter tomographic technique where high resolution imagery competes against high contrast and reasonable acquisition times. Resolution enhancement techniques based on super-resolution are particularly well suited in solving the problems of resolution when high contrast with reasonable times for MRI acquisitions are needed. Super-resolution is the concept of reconstructing a high resolution image from a set of low-resolution images taken at dierent viewpoints or foci. The MRI encoding techniques that produce high resolution imagery are often sub-optimal for the desired contrast needed for visualization of some structures in the brain. A novel super-resolution reconstruction framework for MRI is proposed in this thesis. Its purpose is to produce images of both high resolution and high contrast desirable for image-guided minimally invasive brain surgery. The input data are multiple 2-D multi-slice Inversion Recovery MRI scans acquired at orientations with regular angular spacing rotated around a common axis. Inspired by the computed tomography domain, the reconstruction is a 3-D volume of isotropic high resolution, where the inversion process resembles a projection reconstruction problem. Iterative algorithms for reconstruction are based on the projection onto convex sets formalism. Results demonstrate resolution enhancement in simulated phantom studies, and in ex- and in-vivo human brain scans, carried out on clinical scanners. In addition, a novel motion correction method is applied to volume registration using an iterative technique in which super-resolution reconstruction is estimated in a given iteration following motion correction in the preceding iteration. A comparison study of our method with previously published methods in super-resolution shows favorable characteristics of the proposed approach.

Židininiai kepenų pakitimai (ŽKP) – vieni dažnesnių patologinių radinių tiriant pacientus dėl įvairių virškinimo ar kitų organizmo sistemų ligų. Įvairių spindulinės diagnostikos metodų dėka nustačius patologinius židinius kepenyse ypač svarbi jų klinikinė diferencinės diagnostikos reikšmė. ŽKP diferencinės diagnostikos esmė yra kiek įmanoma tikslesnis židinio kepenyse kraujotakos nustatymas ir aprašymas. Šios problemos sprendime naujų galimybių įgyja santykinai nauja ir Lietuvoje niekur kitur dar neatliekama UG tyrimo su i/v kontrastavimu metodika, kurios metu gaunami rezultatai lyginami su dominuojančių įprastų KT ir MRT kontrastinių tyrimų rezultatais. Tikslas: nustatyti radiologinių tyrimų vertę diagnozuojant židininius kepenų pakitimus (ŽKP) Uždaviniai: 1. Nustatyti įprastinio UG, UG su i/v kontrastavimu ir KT su i/v kontrastavimu diagnostikos metodų tikslumo rodiklius nepiktybiniams ir piktybiniams ŽKP. 2. Nustatyti UG ir KT su i/v kontrastavimu vertingiausius diagnostikos kriterijus vertinant židininių kepenų pokyčių prigimtį. 3. Palyginti tarpusavyje UG ir KT su i/v kontrastavimu nustatytų židininių kepenų pakitimų diagnostikos metodų tikslumo rodiklius nepiktybiniams ir piktybiniams ŽKP. 4. Įvertinti kepenų hemangiomų radiologinių diagnostikos metodų tikslumo vertę. / Focal hepatic lesions (FHL) are one of the most common pathological findings in patients who are examined for gastrointestinal or other diseases. The rigorous description of blood circulation in the hepatic focus is essential in differential diagnosis of FHL. US with i/v contrast enhancement is a new imaging method enabling definition of nature of FHL, follow-up, treatment efficacy and monitoring for possible relapse of the process. This study is conducted solely in the Radiology Department of Kaunas University of Medicine Hospital. Aim of the study To evaluate and compare the value of ‘bolus’ contrast-enhanced CT and contrast-enhanced US in diagnostics of focal hepatic lesions. Tasks of the study 1. To determine rates of diagnostic accuracy of conventional US, US with i/v contrast enhancement and ‘bolus’ contrast-enhanced CT in diagnosis of benign and malingnant FHL. 2. To establish the main and most effective diagnostic criteria of US and CT with i/v contrast enhancement for the assessment of nature of focal hepatic lesions. 3. To compare rates of diagnostic accuracy of US with i/v contrast enhancement and ‘bolus’ contrast-enhanced CT in diagnosis of benign and malingnant FHL. 4. To assess the reliability of radiological diagnostics of hemangioma, comparing the results of US, CT, and MRI.

Since its introduction, contrast-enhanced ultrasonography (CEUS) has significantly extended the value of ultrasonography (US). CEUS can be used to more accurately determine pancreatic lesions compared to conventional US or to characterize lesions already detectable by US. Thus, CEUS can aid in the differential diagnosis of pancreatic tumors. Using US contrast media, it is possible to visually detect microvessels in the majority of pancreatic ductal adenocarcinomas. Thus, the use of quantitatively evaluated transabdominal CEUS can help in the differentiation of patients with mass-forming pancreatitis from patients with pancreatic adenocarcinomas. In neuroendocrine pancreatic tumors, different enhancement patterns can be observed in relation to the tumor mass: larger ones show a rapid early enhancement sometimes combined with necrotic central structures, and smaller ones disclose a capillary-blush enhancement. Pseudocysts, the most widespread cystic lesions of the pancreas, are not vascularized. They do not show any signal in CEUS and remain entirely anechoic in all phases, while true cystic pancreatic tumors usually have vascularized septa and parietal nodules. In summary, CEUS is effective for differentiating solid pancreatic tumors in most cases. CEUS is safe and cost effective and can better discriminate solid from cystic pancreatic lesions, thereby directing further imaging modalities. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

The aim of this project is the application of Dual Energy technique in breast phantoms using Complimentary-Metal-Oxide-Semiconductor (CMOS)Active-Pixel-Sensor (APS). This includes both, lab experimentation on developed breast phantoms, as well as simulations validating the results. Initially, phantoms were carefully prepared simulating the properties of real breast tissue and were imaged using X-ray unit. The next step in this project involved image processing and data representation. Using the dual energy technique, different concentrations of contrast agent (Iodine) were measured to relate clinical to medium kinetic measurements. With respect to this projects‟ clinical application, the implementation of this technique can be used to evaluate the iodine projected thickness (mg/cm2) using Contrast Enhanced Digital Mammography (CEDM) based on Dual Energy technique for the breast cancer detection. / Ο στόχος του εργασίας αυτής είναι η εφαρμογή της τεχνικής Διπλής Ενέργειας σε ομοιώματα μαστού χρησιμοποιώντας Complimentary-Metal-Oxide-Semiconductor (CMOS) Active-Pixel-Sensor (APS). Αυτό περιλαμβάνει, τον πειραματισμό σε αναπτυγμένα ομοιώματα μαστού, καθώς και προσομοιώσεις για την επικύρωση των αποτελεσμάτων. Αρχικά, κατασκευάστηκαν προσεκτικά τα ομοιώματα μαστού όπου προσομοιώνουν τις πραγματικές ιδιότητες των ιστών του μαστού και στη συνέχεια απεικονίστηκαν με χρήση μονάδων ακτίνων-Χ . Το επόμενο βήμα σε αυτό την εργασία ήταν η επεξεργασία εικόνας και παρουσίαση δεδομένων. Χρησιμοποιώντας την τεχνική της διπλής ενέργειας, διαφορετικές συγκεντρώσεις σκιαγραφικού (ιώδιο) μετρήθηκαν ώστε να σχετίζουν κλινικά την μέτρηση της αγγειογένεσης εν συναρτήση του χρόνου. Η εφαρμογή αυτής της τεχνικής μπορεί να χρησιμοποιηθεί για να αξιολογήσει το προβλεπόμενο πάχος του ιωδίου (mg/cm^2) χρησιμοποιώντας Ενίσχυση Αντίθεσης στην Ψηφιακή Μαστογραφία βασίσμένη στην τεχνική της διπλής ενέργειας για την ανίχνευση του καρκίνου του μαστού.

<b>Background:</b> Systemic chemotherapy and radiotherapy play an important role in the treatment of colorectal cancer. Tumour perfusion and oxygenation is known to influence radiosensitivity and chemosensitivity. In this thesis, I propose that the evaluation of changes in tumour perfusion using perfusion CT (pCT) and dynamic contrast-enhanced (Dce) MRI can guide the rational sequencing of drugs and radiation. <b>Methods:</b> Dce-MRI and pCT scans were incorporated into a clinical trial of hypofractionated pelvic radiotherapy and nelfinavir in 10 patients with rectal cancer. Toxicity and tissue biomarkers (tumour cell density, microvessel density, CAIX, HIF1-alpha, phospho-Akt and phospho-PRAS40) were evaluated. pCT liver scans were incorporated into an imaging study in patients with colorectal liver metastases randomised to receive either oxaliplatin/ 5FU chemotherapy or oxaliplatin/ 5FU chemotherapy plus selective internal radiotherapy. <b>Results:</b> After 7 days of nelfinavir concurrent with hypo-fractionated pelvic radiotherapy, there was a mean 42&percnt; increase in median K^trans (P=0.03, paired t test) on Dce-MRI and a median 30&percnt; increase in mean blood flow on pCT (P=0.028, Wilcoxon Rank Sum), although no statistically significant changes in perfusion parameters were demonstrated after 7 days of nelfinavir prior to radiotherapy. The feasibility of evaluating tumour cell density in rectal biopsies before and after radiotherapy and a radiosensitising drug as an early endpoint of response was demonstrated. In patients with colorectal liver metastases who received oxaliplatin and modified de Gramont chemotherapy alone, after 4 cycles of chemotherapy, a 28&percnt; decrease in the mean hepatic arterial fraction was observed (P=0.018, paired t test). Between pCT scans 2 days before SIRT and 39-47 days following SIRT and continued 2-weekly chemotherapy, there was a mean 62&percnt; (P=0.009) reduction in Blood Flow and 61&percnt; (P=0.006) reduction in Blood Volume (paired t test). <b>Conclusions</b> This research does not support the hypothesis that nelfinavir before radiotherapy improves blood flow to human rectal cancer. Increases in rectal tumour perfusion during radiotherapy and concurrent nelfinavir are likely to be primarily explained by the acute biological effects of radiation. Four or more cycles of oxaliplatin and modified de Gramont chemotherapy may result in changes in tumour perfusion of colorectal liver metastases which would be detrimental to subsequent radiotherapy. Selective internal radiotherapy resulted in substantial reductions in tumour perfusion 39-47 days after the treatment. Perfusion imaging can be used to detect changes in tumour perfusion in response to radiotherapy and systemic therapy which have implications for the sequencing of therapies.

La distinction entre les fœtus constitutionnellement petits de ceux qui présentent une réelle restriction de croissance liée à une insuffisance placentaire n’est pas aisée avec les mesures échographiques utilisées en pratique courante. Le retard de croissance intra-utérin (RCIU) est responsable d’une part importante de la prématurité induite, et d’une augmentation du risque de mortalité et de morbidité néonatales. C’est pourquoi, l’amélioration de la connaissance de la vascularisation placentaire est indispensable pour mieux identifier et prendre en charge les situations d’hypoxie chroniques foetales associées à l’insuffisance placentaire.Pour quantifier la vascularisation les modalités d’imagerie de perfusion disponibles sont l’échographie et l’IRM. Les études évaluant la quantification de la perfusion placentaire par échographie de contraste sont peu nombreuses. Les avantages et les limites de cet examen ont été évalués sur un modèle murin de RCIU par ligature vasculaire. Ainsi, l’échographie de contraste permettait de quantifier une baisse de la perfusion placentaire sur un modèle de RCIU sans que l’on puisse observer de passage d’agents de contraste ultrasonores au travers la barrière placentaire. Les résultats obtenus ont été comparés aux données obtenues par l’IRM de perfusion. Les paramètres quantitatifs obtenus à partir des courbes de cinétiques du contraste pour chacune des deux modalités d’imagerie étaient comparables sur un modèle identique de RCIU murin. Enfin, une méthode d’étude de l’oxygénation placentaire par imagerie photoacoustique a été évaluée. Cette modalité d’imagerie non invasive permettait d’obtenir en temps réel l’oxygénation placentaire, avec cependant une profondeur limitée d’exploration. Le placenta semblait se comporter comme une réserve en oxygène au cours de l’étude d’une séquence hypoxie – hyperoxygénation maternelle avec une désaturation moins importante que celle observée dans les autres tissus maternels. / To identify fetuses small for their gestational-age who have reached their appropriate growth potential from growth-restricted fetuses due to placental insufficiency is uneasy. Intra Uterine Growth Restriction (IUGR) increases the risk for indicated preterm delivery, neonatal mortality and morbidity. Therefore, improving the knowledge of the placental perfusion is essential to better identify and manage fetal chronic oxygen deprivation associated with placental insufficiency.Contrast Enhanced Ultrasound (CEUS) and MRI are two imaging modalities available to quantify placental perfusion. However, few studies focus on the quantification of placental perfusion with CEUS. First, the advantages and limitations of CEUS were presented in an IUGR rat model by uterine ligation. The placental perfusion observed by CEUS was significantly decreased in the ligated horn. No contrast enhancement was observed in the umbilical vein or the fetus. Then, we compared the CEUS parameters to results obtained by MRI perfusion. Perfusion parameters were obtained from the signal intensity decay curve for the two imaging modalities. Results of such perfusion parameters were comparable in the same IUGR rat model. Finally, we evaluated the response of the placenta to oxygenation by photoacoustic imaging. PA imaging is a real-time, non-invasive method to evaluate placental oxygenation without contrast agents. Our results suggesting that placenta is less affected than maternal tissue by the decline in maternal oxygenation. The placenta may play an important role in protecting the feus against hypoxia.

This diploma thesis deals with DCE-MRI (Dynamic Contrast-Enhanced Magnetic Resonance Imaging) thus one of the contrast magnetic resonance imaging methods. It describes the principle of conventional continuous DCE-MRI, which uses single bolus of contrast agent and further it focuses on the dual bolus contrast agent techniques, especially the interleaved acquisition. The graphical interface for processing Bruker systems data was made. Synthetic data were used to evaluate the influence of this method on the perfusion parameters estimation. Simulations proved that the further the second bolus is from the first one, the better results are. Simulations of acquisition interruption did not lead to the clear result. However, two statements, which are expected to lead to as good estimation of perfusion parameters as possible, were formulated

Since its introduction, contrast-enhanced ultrasonography (CEUS) has significantly extended the value of ultrasonography (US). CEUS can be used to more accurately determine pancreatic lesions compared to conventional US or to characterize lesions already detectable by US. Thus, CEUS can aid in the differential diagnosis of pancreatic tumors. Using US contrast media, it is possible to visually detect microvessels in the majority of pancreatic ductal adenocarcinomas. Thus, the use of quantitatively evaluated transabdominal CEUS can help in the differentiation of patients with mass-forming pancreatitis from patients with pancreatic adenocarcinomas. In neuroendocrine pancreatic tumors, different enhancement patterns can be observed in relation to the tumor mass: larger ones show a rapid early enhancement sometimes combined with necrotic central structures, and smaller ones disclose a capillary-blush enhancement. Pseudocysts, the most widespread cystic lesions of the pancreas, are not vascularized. They do not show any signal in CEUS and remain entirely anechoic in all phases, while true cystic pancreatic tumors usually have vascularized septa and parietal nodules. In summary, CEUS is effective for differentiating solid pancreatic tumors in most cases. CEUS is safe and cost effective and can better discriminate solid from cystic pancreatic lesions, thereby directing further imaging modalities. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Diffusion weighted imaging (DWI) and dynamic susceptibility contrast-enhanced (DSC) perfusion-weighted imaging (PWI) are commonly employed in clinical practice and in research to give pathophysiological information for patients with acute ischemic stroke. DWI is thought to roughly reflect the severely damaged infarct core, while DSC-PWI reflects the area of hypoperfusion. The volumetric difference between DWI and DSC-PWI is termed the PWI/DWI-mismatch, and has been suggested as an MRI surrogate of the ischemic penumbra. However, due to the application of a contrast agent, which has potentially severe side-effects (e.g., nephrogenic systemic fibrosis), the DSC-PWI precludes repetitive examinations for monitoring purposes. New approaches are being sought to overcome this shortcoming. BOLD (blood oxygen-level dependent) signal can reflect the metabolism of blood oxygen in the brain and hemodynamics can be assessed with resting-state fMRI. The aim of this thesis was to use resting-state fMRI as a new approach to give similar information as DSC-PWI. This thesis comprises two studies: In the first study (see Chapter 2), two resting-state fMRI methods, local methods which compare low frequency amplitudes between two hemispheres and a k-means clustering approach, were applied to investigate the functional damage of patients with acute ischemic stroke both in the time domain and frequency domain. We found that the lesion areas had lower amplitudes than contralateral homotopic healthy tissues. We also differentiated the lesion areas from healthy tissues using a k-means clustering approach. In the second study (see Chapter 3), time-shift analysis (TSA), which assesses time delays of the spontaneous low frequency fluctuations of the resting-state BOLD signal, was applied to give similar pathophysiological information as DSC-PWI in the acute phase of stroke. We found that areas which showed a pronounced time delay to the respective mean time course were very similar to the hypoperfusion area. In summary, we suggest that the resting-state fMRI methods, especially the time-shift analysis (TSA), may provide comparable information to DSC-PWI and thus serve as a useful diagnostic tool for stroke MRI without the need for the application of a contrast agent.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20564号 / 医博第4249号 / 新制||医||1022(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 増永 慎一郎, 教授 妹尾 浩, 教授 鈴木 実 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM