Search

Individual tumor characterization and treatment response monitoring based on current medical imaging methods remain challenging. This work investigates hyperpolarized 13 C compounds in an orthotopic rat hepatocellular carcinoma (HCC) model system before and after transcatheter arterial embolization (TAE). HCC ranks amongst the top six most common cancer types in humans and accounts for one-third of cancer-related deaths worldwide. Early therapy response monitoring could aid in the development of personalized therapy approaches and novel therapeutic concepts. Measurements with selectively 13 C -labeled and hyperpolarized urea, pyruvate and fumarate were performed in tumor-bearing rats before and after TAE. Two-dimensional, slice-selective MRSI was used to obtain spatially resolved maps of tumor perfusion, cell energy metabolic conversion rates and necrosis, which were additionally correlated with immunohistochemistry. All three injected compounds, taken together with their respective metabolites, exhibited similar signal distributions. TAE induced a decrease in blood flow into the tumor and thus a decrease in tumor to muscle and tumor to liver ratios of urea, pyruvate and its metabolites, alanine and lactate, whereas conversion rates remained stable or increased on TAE in tumor, muscle and liver tissue. Conversion from fumarate to malate successfully indicated individual levels of necrosis, and global malate signals after TAE suggested the washout of fumarase or malate itself on necrosis. This study presents a combination of three 13 C compounds as novel candidate biomarkers for a comprehensive characterization of genetically and molecularly diverse HCC using hyperpolarized MRSI, enabling the simultaneous detection of differences in tumor perfusion, metabolism and necrosis. If, as in this study, bolus dynamics are not required and qualitative perfusion information is sufficient, the desired information could be extracted from hyperpolarized fumarate and pyruvate alone, acquired at higher fields with better spectral separation. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose The metabolism of acetate in the heart resembles fatty acid metabolism, which is altered in several diseases like ischemia, diabetes mellitus, and heart failure. A signal-to-noise ratio (SNR) optimized imaging framework for in vivo measurements of hyperpolarized [1-13C]acetate and its metabolic product [1-13C]acetylcarnitine (ALCAR) in rats at 3 Tesla (T) is presented in this work. Methods A spectrospatial pulse was combined with IDEAL encoding to acquire well separated metabolic maps. The influence of dobutamine induced stress onto this metabolic system was investigated in spectra and in an imaging study. Results An increase of the ALCAR to acetate ratio with dobutamine induced stress was shown in slice selective spectra containing the rat hearts and skeletal muscles. Metabolic maps of acetate and ALCAR were acquired with an acceptable SNR. Quantification of the apparent conversion rate showed stable results in the heart in a time-window of 30 s. The effect of dobutamine on the signal intensities was shown to originate mainly from skeletal than cardiac muscles. Conclusion The acetate activation was mapped with hyperpolarized [1-13C]acetate in a clinical 3T system. Quantitative measurement of the activity was possible in the heart, indicating that dobutamine induced stress does not improve the ALCAR SNR in the heart. Magn Reson Med 74:1011-1018, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

In the metabolism of acetate several enzymes are involved, which play an important role in free fatty acid oxidation. Fatty acid metabolism is altered in diabetes patients and therefore acetate might serve as a marker for pathological changes in the fuel selection of cells, as these changes occur in diabetes patients. Acetylcarnitine is a metabolic product of acetate, which enables its transport into the mitochondria for energy production. This study investigates whether the ratio of acetylcarnitine to acetate, measured by noninvasive hyperpolarized [1-13C]acetate magnetic resonance spectroscopy, could serve as a marker for myocardial, hepatic, and renal metabolic changes in rats with Streptozotocin ( STZ)-induced diabetes in vivo. We demonstrate that the conversion of acetate to acetylcarnitine could be detected and quantified in all three organs of interest. More interestingly, we found that the hyperpolarized acetylcarnitine to acetate ratio was independent of blood glucose levels and prolonged hyperglycemia following diabetes induction in a type-1 diabetes model. [ABSTRACT FROM AUTHOR]

The aim of this study was to characterise and compare widely used acquisition strategies for hyperpolarised 13C imaging. Free induction decay chemical shift imaging (FIDCSI), echo-planar spectroscopic imaging (EPSI), IDEAL spiral chemical shift imaging (ISPCSI) and spiral chemical shift imaging (SPCSI) sequences were designed for two different regimes of spatial resolution. Their characteristics were studied in simulations and in tumour-bearing rats after injection of hyperpolarised [1-13C]pyruvate on a clinical 3-T scanner. Two or three different sequences were used on the same rat in random order for direct comparison. The experimentally obtained lactate signal-to-noise ratio (SNR) in the tumour matched the simulations. Differences between the sequences were mainly found in the encoding efficiency, gradient demand and artefact behaviour. Although ISPCSI and SPCSI offer high encoding efficiencies, these non-Cartesian trajectories are more prone than EPSI and FIDCSI to artefacts from various sources. If the encoding efficiency is sufficient for the desired application, EPSI has been proven to be a robust choice. Otherwise, faster spiral acquisition schemes are recommended. The conclusions found in this work can be applied directly to clinical applications. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Quantitative Kernspintomographie: Ein paramagnetisches Gadolinium ‐ beladenes Liposom für MRI ‐ Studien der Aktivität der Matrixmetalloproteinase ‐ 2 (MMP ‐ 2) wird beschrieben. Die Messung beruht auf dem Verhältnis R2p/R1p zwischen den transversalen und longitudinalen paramagnetischen Beiträgen der Relaxationsgeschwindigkeit des Wasserprotons. Die Methode ist unabhängig von der Gesamtkonzentration an Gadolinium. [ABSTRACT FROM AUTHOR]

Parametric MRI: A paramagnetic gadolinium‐loaded liposome for the MRI assessment of the activity of matrix metalloproteinase‐2 (MMP‐2) is described. The assessment relies on a procedure that involves the ratio R2p/R1p between the transverse and longitudinal paramagnetic contributions to the water proton relaxation rate. This method is independent of the total gadolinium concentration. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Carnitine Acyltransferases and Their Influence on CoA pools in Health and Disease" by V. A. Zammit and colleagues in the 2016 issue.