20 research outputs found

    Is ATP Elevated in Patients With GAMT Deficiency?

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    Impact of dynamic computed tomographic angiography on endograft sizing for endovascular aneurysm repair.

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    Contains fulltext : 80349.pdf (publisher's version ) (Open Access)PURPOSE: To quantify dynamic changes in aortoiliac dimensions using dynamic electrocardiographically (ECG)-gated computed tomographic angiography (CTA) and to investigate any potential impact on preoperative endograft sizing in relation to observer variability. METHODS: Dynamic ECG-gated CTA was performed in 18 patients with abdominal aortic aneurysms. Postprocessing resulted in 11 datasets per patient: 1 static CTA and 10 dynamic CTA series. Vessel diameter, length, and angulation were measured for all phases of the cardiac cycle. The differences between diastolic and systolic aneurysm dimensions were analyzed for significance using paired t tests. To assess intraobserver variability, 20 randomly selected datasets were analyzed twice. Intraobserver repeatability coefficients (RC) were calculated using Bland-Altman analysis. RESULTS: Mean aortic diameter at the proximal neck was 21.4+/-3.0 mm at diastole and 23.2+/-2.9 mm at systole, a mean increase of 1.8+/-0.4 mm (8.5%, p<0.01). The RC for the aortic diameter at the level of the proximal aneurysm neck was 1.9 mm (8.9%). At the distal sealing zones, the mean increase in diameter was 1.7+/-0.3 mm (14.1%, p<0.01) for the right and 1.8+/-0.5 mm (14.2%, p<0.01) for the left common iliac artery (CIA). At both distal sealing zones, the mean increase in CIA diameter exceeded the RC (10.0% for the right CIA and 12.6% for the left CIA). CONCLUSION: The observed changes in aneurysm dimension during the cardiac cycle are small and in the range of intraobserver variability, so dynamic changes in proximal aneurysm neck diameter and aneurysm length likely have little impact on preoperative endograft selection. However, changes in diameter at the distal sealing zones may be relevant to sizing, so distal oversizing of up to 20% should be considered to prevent distal type I endoleak

    Magnetic Resonance Spectroscopy of creatine-related energy metabolism in skeletal muscle and brain.

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    Contains fulltext : 49201.pdf (publisher's version ) (Open Access)Magnetic Resonance Spectroscopy (MRS) is a powerful technique to study transgenic animals in vivo, in particular when substrates of the enzymes involved show signals in the MR spectra. This thesis focuses on the role of creatine kinase (CK) and adenylate kinase (AK) in a number of strongly interconnected energetics pathways, i.e. the creatine (Cr)-CK system, the AK system, glycolysis, the mitochondrial TCA cycle and oxidative phosphorylation. Disabling one or more enzymes may lead to rerouting of fluxes through the remaining energy pathways. First, a study on postnatal development of mice lacking CK in muscle was performed to gain insight into the origin of the phosphocreatine signal that was somewhat unexpectedly observed in earlier studies of mice with complete CK deficiency. Furthermore, we studied energy provision in muscle of mice with a combined CK and AK deletion during an ischemic challenge and upon recovery. Comparing the results of this study with similar studies in cytosolic muscle-CK and AK single knock-out mice gives a new perspective on the interaction between the CK and AK enzyme systems in vivo. To study whether CK absence in brain also results in an up-regulation of glycolysis, similar to the situation in muscle, 13C MRS techniques were developed which were applied to mice that lack CK in the brain. Using 13C MRS, we compared conversion of glucose, formation of lactate and synthesis of other substances including several neurotransmitters between brain CK double knock-out and wt animals with high temporal resolution. Transgenic mice are investigated which lack guanidinoacetate methyltransferase (GAMT) and, as a result, lack creatine. These animals serve as a faithful model for GAMT deficiency in humans, but were also expected to provide important information on the role of Cr/CK circuit, additional to the data obtained from CK deficient mice. The last chapter, deals with the visibility of Cr in human 1H MRS.RU Radboud Universiteit Nijmegen, 10 oktober 2005Promotores : Heerschap, A., Wieringa, B.213 p

    Spectroscopic imaging of the mouse brain.

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    Item does not contain fulltextMagnetic resonance spectroscopic imaging (MRSI) of the mouse brain reveals a wealth of metabolic information, not only from a single region of interest (single voxel), but spatially mapped over potentially the entire brain. However, MRSI requires challenging methods before the data can be obtained accurately. When applied in vivo, MRSI is generally combined with volume-selective spin perturbation to exclude artifact originating from outside the volume of interest. To obtain good magnetic field (B (0)) uniformity at this volume, accurate B (0) shimming is required. Finally, the immensely large signals originating from water spins need to be suppressed to prevent sidebands that contaminate the spectra, or even saturate the dynamic range of the MR receiver. This chapter describes solutions for these challenges and ends with a rationale between single-voxel MRS versus MRSI

    Is ATP elevated in patients with GAMT deficiency?

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    Contains fulltext : 69608.pdf (publisher's version ) (Closed access

    In vivo magnetic resonance spectroscopy of transgenic mouse models with altered high-energy phosphoryl transfer metabolism.

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    Contains fulltext : 53041.pdf (publisher's version ) (Closed access)Studies of transgenic mice provide powerful means to investigate the in vivo biological significance of gene products. Mice with an under- or overexpression of enzymes involved in high-energy phosphoryl transfer (approximately P) are particulary attractive for in vivo MR spectroscopy studies as the substrates of these enzymes are metabolites that are visible in MR spectra. This review provides a brief overview of the strategies used for generation and study of genetically altered mice and introduces the reader to some practical aspects of in vivo MRS studies on mice. The major part of the paper reviews results of in vivo MRS studies on transgenic mice with alterations in the expression of enzymes involved in approximately P metabolism, such as creatine kinase, adenylate kinase and guanidinoacetate methyl transferase. The particular metabolic consequences of these enzyme deficiencies in skeletal muscle, brain, heart and liver are addressed. Additionally, the use of approximately P systems as markers of gene expression by MRS, such as after viral transduction of genes, is described. Finally, a compilation of tissue levels of metabolites in skeletal muscle, heart and brain of wild-type and transgenic mice, as determined by in vivo MRS, is given. During the last decade, transgenic MRS studies have contributed significantly to our understanding of the physiological role of phosphotransfer enzymes, and to the view that these enzymes together build a much larger metabolic energy network that is highly versatile and can dynamically adapt to intrinsic genotoxic and extrinsic physiological challenges

    Short TE CSI at 7 T of the mouse brain

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    A Segmentation Method for Stentgrafts in the Abdominal Aorta from ECG-gated CTA Data

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    Endovascular aortic replacement (EVAR) is an established technique, which uses stentgrafts to treat aortic aneurysms in patients at risk of aneurysm rupture. The long-term durability of a stentgraft is affected by the stresses and hemodynamic forces applied to it, and may be reflected by the movements of the stentgraft itself during the cardiac cycle. A conventional CT scan (which results in a 3D volume) is not able to visualize these movements. However, applying ECG-gating does provide insight in the motion of the stentgraft caused by hemodynamic forces at different phases of the cardiac cycle. The amount of data obtained is a factor of ten larger compared to conventional CT, but the radiation dose is kept similar for patient safety. This causes the data to be noisy, and streak artifacts are more common. Algorithms for automatic stentgraft detection must be able to cope with this. Segmentation of the stentgraft is performed by examining slices perpendicular to the centreline. Regions with high CT-values exist at the locations where the metallic frame penetrates the slice. These regions are well suited for detection and sub-pixel localization. Spurious points can be removed by means of a clustering algorithm, leaving only points on the contour of the stent. We compare the performance of several different point detection methods and clustering algorithms. The position of the stent’s centreline is calculated by fitting a circle through these points. The proposed method can detect several stentgraft types, and is robust against noise and streak artifacts

    In-vivo imaging of changes in abdominal aortic aneurysm thrombus volume during the cardiac cycle.

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    Contains fulltext : 80262.pdf (publisher's version ) (Open Access)PURPOSE: To evaluate in-vivo thrombus compressibility in abdominal aortic aneurysms (AAAs) to hopefully shed light on the biomechanical importance of intraluminal thrombus. METHODS: Dynamic electrocardiographically-gated computed tomographic angiography was performed in 17 AAA patients (15 men; mean age 73 years, range 69-76): 11 scheduled for surgical repair and 6 under routine surveillance. The volumes of intraluminal thrombus, the lumen, and the total aneurysm were quantified for each phase of the cardiac cycle. Thrombus compressibility was defined as the percent change in thrombus volume between diastole and peak systole. Continuous data are presented as medians and interquartile ranges (IQR). RESULTS: A substantial interpatient variability was observed in thrombus compressibility, ranging from 0.4% to 43.6% (0.2 to 13.5 mL, respectively). Both thrombus and lumen volumes varied substantially during the cardiac cycle. As lumen volume increased (5.2%, IQR 2.8%-8.8%), thrombus volume decreased (3.0%, IQR 1.0%-4.6%). Total aneurysm volume remained relatively constant (1.3%, IQR 0.4-1.9%). Changes in lumen volume were inversely correlated with changes in thrombus volume (r = -0.73; p = 0.001). CONCLUSION: In-vivo thrombus compressibility varied from patient to patient, and this variation was irrespective of aneurysm size, pulse pressure, and thrombus volume. This suggests that thrombus might act as a biomechanical buffer in some, while it has virtually no effect in others. Whether differences in thrombus compressibility alter the risk of rupture will be the focus of future research
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