Quantification of Fat Content and Fatty Acid Composition Using Magnetic Resonance Imaging

In obesity and several other disease scenarios, the measurement of fat accumulation in various organs and tissues has become a sought-after technique in clinical diagnostics and research. Especially, quantitative and non-invasive techniques which also provide images of accumulated fat throughout the body would be valuable. In the typical hospital, magnetic resonance imaging (MRI) is the only technique available which has the potential for these types of measurements and out of techniques suggested, Water/Fat Imaging is particularly promising. Water/Fat Imaging is based on the separation of water and fat, the two main contributors to the MRI signal, with the use of the frequency separation between their signals. The field has inspired a wide range of research and is by now well established, especially for investigations of fatty liver. However, in this and several other applications there is a continued need for method development. The fat concentrations in skeletal muscle are expected to be very low. Thus, for this application, there is an increased demand for measurement precision. The results presented in this thesis indicate that fat concentrations below 1 % are possible to measure using Water/Fat Imaging. In addition, precision may be increased using a higher flip angle if a pure fat reference is used for quantification, without compromising quantification accuracy. (Papers I and II) Water/Fat Imaging has become an appreciated technique for abdominal applications in which breath-hold is necessary for acceptable image quality. The use of a bipolar acquisition scheme may be used to reduce the total scan time, but is associated with issues which are detrimental to fat quantification. Using a built-in correction approach, it is demonstrated that accurate and noise efficient fat quantification is possible using a bipolar acquisition. (Paper III) The basic ideas of Water/Fat Imaging may be extended to not only quantify the fat concentration, but also the fatty acid composition. In this thesis, a reconstruction algorithm is suggested and its accuracy is demonstrated in a wide range of fat concentrations and fatty acid compositions. In addition, a number of potential sources of bias are investigated. Out of these, accurate modeling of the individual T2 values of fat and water is especially important in fat/water mixtures, whereas some T1 weighting may be allowed with small impact on quantification accuracy. (Papers IV and V

MRI-Based Quantification of Intra-Myocellular Fat Content

"Introduction Cardiac steatosis, or overstorage of fat in the cardiac muscle cells, is a possible side effect from drugs treating diabetes mellitus. Therefore, a non-invasive means of fat quantification is needed during drug development. The aim of this master thesis is to develop a method to quantify the fraction intra-myocellular fat in the cardiac muscle of rats using magnetic resonance imaging (MRI). Simulations, in vitro experiments on phantoms and in vivo experiments on rats were conducted during development and the quantification accuracy of the method was compared to that of magnetic resonance spectroscopy (MRS). Theory Multi-echo imaging is based on the Dixon technique which is a method for fat/water separation. The method uses the chemical shift between water and fat to separate the species from a number of acquired gradient echoes with different TEs. The reconstruction includes built-in corrections for T2*-relaxation, off-resonance effects and the multi-resonance signal of fat. To obtain a quantitative measure of the volume fat fraction, corrections for bias from differences in relaxation times and proton density are included. Material and methods Initially, simulations were performed in Matlab to learn more about the method and its properties. Intralipid phantoms were created with volume fat fractions ranging from 0 % to 21.7 % and measured with multi-echo imaging and spectroscopy at 1.5 T and 3 T Siemens scanners. The method was also tested in vivo by animal experiments on rats fed with a steatosis-inducing drug using a 4.7 T Bruker system. Results Simulations showed that the use of a lower magnetic field strength and a fewer number of echoes is less sensitive to inaccuracies in the modelled fat spectrum. In vitro, the method successfully quantified fat fractions as low as 0.2 % with quantification accuracy similar to that of spectroscopy. In vivo, however, no correlation could be detected between spectroscopy and imaging results. Conclusion Although the method is still to be successfully tested in vivo, it does show potential to be applicable also in living tissue. This potential may be greater in organs were the fat content is higher and the movements less problematic than in the heart."Jag har i detta arbete tagit fram en metod för att mäta mängden fett i muskelceller som vare sig kräver vävnadsprover eller nålstick. Metoden ger också en bild av fettfördelningen i vävnaden. Detta kan vara mycket användbart vid utveckling av läkemedel, men också vid diabetes- och fetmaforskning. Muskelceller innehåller ett bränsleförråd i form av en droppe fett. För diabetespatienter och som en biverkning av diabetesmedicin kan denna fettlagring överdrivas. Om detta sker i hjärtmuskeln kan detta ha negativa effekter på hjärtats funktion. För att övervaka fettinlagring vid utveckling av nya läkemedel behövs en metod för att bestämma mängden fett i muskelceller. Metoden som utvecklats här använder sig av magnetresonans med vars hjälp fettmängden kan mätas utifrån kroppen. Under djurförsöken som krävs vid utvecklandet av diabetesläkemedel skulle denna metod innebära att färre djur kan följas under en längre tid då djur inte skulle behöva offras vid varje mätning. En magnetresonans-kamera består av en mycket stark magnet. Med hjälp av en spole som placeras runt det område av kroppen som ska undersökas, sänds radiovågor in i kroppen. Väte i kroppens vävnader reagerar annorlunda på dessa radiovågor i magnetfältet beroende på vilken vävnad de tillhör och skickar tillbaka olika starka signaler som kan användas för att skapa skiktbilder av kroppen. På samma sätt beter sig vätet i vatten- och fettmolekyler på olika sätt vilket kan användas för att beräkna mängden fett jämfört med mängden vatten i muskelceller tack vare deras skilda och speciella signaler. Det finns dock en mängd svårigheter med detta. Exempelvis varierar magnetfältets styrka i kroppen vilket stör de signaler som ska mätas. Signalen från fett består dessutom av en mängd olika delar som måste tolkas på rätt sätt. Förutom detta är mängden fett i musklerna väldigt liten vilket gör metoden känslig för variationer och problem i mätningarna. Under detta projekt har jag arbetat med att pröva anfallsvinklar som undviker och minskar dessa problem. Genom mätningar på blandningar av fett och vatten i provrör har jag kunnat visa att min metod fungerar; även för mycket små mängder fett. På grund av de stora svårigheter som följer under mätningar av hjärtat har detta goda resultat än så länge inte kunnat upprepas i levande vävnad. Metoden ger mycket goda resultat vid mätningar på provrör, men det återstår att testa den på djur och människor. Trots de små mängderna fett, är jag övertygad om att magnetresonanskameran och denna metod kan vara viktiga hjälpmedel vid läkemedelsutveckling, men också vid diabetes- och fetmaforskning

Simultaneous quantification of fat content and fatty acid composition using MR imaging.

Not only the fat content but also the composition of fatty acids (FAs) in stored triglycerides might be of interest in the research on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. In this study, a novel reconstruction approach is proposed that uses theoretical knowledge of the chemical structure of FAs to simultaneously quantify the fat fraction (FF) and the FAs composition (chain length cl, number of double bonds ndb, and number of methylene-interrupted double bonds nmidb) from multiple gradient echo images. Twenty phantoms with various fat contents (FF = 9-100%) and FA compositions (cl = 12.1-17.9, ndb = 0.23-5.10, and nmidb = 0.04-2.39) were constructed and imaged in a 3-T Siemens scanner. In addition, spectra were acquired in each phantom. Slopes and "standard deviations from true values" were used to investigate the accuracy of the two methods. The imaging method holds well in a comparison to the previously suggested spectroscopy method and showed similar overall accuracy. The in vivo feasibility was demonstrated in the thigh adipose tissue of a healthy volunteer. In conclusion, our developed method is a promising tool for FF and FA composition quantification. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc

MR for Quantitative Fat Imaging

An absolute measure of the fat content in various organs is an important part of diagnostics in obesity and diabetes. Fat quantification using MR-imaging is a non-invasive technique which provides both quantitative and spatial information on fat accumulation. However, for absolute quantification, it is necessary to address the various sources of contrast in MR-imaging. This paper summarizes basic MR fat quantification techniques and discusses the main parameters affecting absolute fat quantification

T2 relaxation time bias in gagCEST at 3T and 7T : comparison of saturation schemes

Purpose: To characterize the effects of water T2 relaxation time in the glycosaminoglycan chemical exchange saturation transfer method (gagCEST) and compare them between 3T and 7T as well as between various saturation schemes. Methods: Simulations and a phantom experiment were conducted at 3T and 7T in a range of water T2 values and GAG concentrations using various saturation schemes. For both simulations and MRI measurements, unsaturated signal as well as the saturated Z-spectrum were generated, and the magnetization transfer ratio asymmetry at 1 parts per million was used as a measure of the gagCEST effect size. Results: The simulations and phantom experiment results showed a clear GAG concentration and T2 dependence of the gagCEST effect size. Whereas the gagCEST effect size was much larger at 7T, the impact of the T2 bias was more pronounced at 3T. The saturation train length, duty cycle, and average B1 all had clear impact on both the gagCEST effect size and T2 bias. Conclusion: The water T2 relaxation is important to consider in gagCEST, especially at 3T. The T2 differences can introduce a pronounced bias, which may obscure the gagCEST effect when using low duty cycles and long saturation trains

Quantitative 1H MRI and MRS of fatty acid composition

Adipose tissue as well as other depots of fat (triglycerides) are increasingly being recognized as active contributors to the human function and metabolism. In addition to the fat concentration, also the fatty acid chemical composition (FAC) of the triglyceride molecules may play an important part in diseases such as obesity, insulin resistance, hepatic steatosis, osteoporosis, and cancer. MR spectroscopy and chemical-shift-encoded imaging (CSE-MRI) are established methods for non-invasive quantification of fat concentration in tissue. More recently, similar techniques have been developed for assessment also of the FAC in terms of the number of double bonds, the fraction of saturated, monounsaturated, and polyunsaturated fatty acids, or semi-quantitative unsaturation indices. The number of papers focusing on especially CSE-MRI-based techniques has steadily increased during the past few years, introducing a range of acquisition protocols and reconstruction algorithms. However, a number of potential sources of bias have also been identified. Furthermore, the measures used to characterize the FAC using both MRI and MRS differ, making comparisons between different techniques difficult. The aim of this paper is to review MRS- and MRI-based methods for in vivo quantification of the FAC. We describe the chemical composition of triglycerides and discuss various potential FAC measures. Furthermore, we review acquisition and reconstruction methodology and finally, some existing and potential applications are summarized. We conclude that both MRI and MRS provide feasible non-invasive alternatives to the gold standard gas chromatography for in vivo measurements of the FAC. Although both are associated with gas chromatography, future studies are warranted

Quantitative 1

Adipose tissue as well as other depots of fat (triglycerides) are increasingly being recognized as active contributors to the human function and metabolism. In addition to the fat concentration, also the fatty acid chemical composition (FAC) of the triglyceride molecules may play an important part in diseases such as obesity, insulin resistance, hepatic steatosis, osteoporosis, and cancer. MR spectroscopy and chemical-shift-encoded imaging (CSE-MRI) are established methods for non-invasive quantification of fat concentration in tissue. More recently, similar techniques have been developed for assessment also of the FAC in terms of the number of double bonds, the fraction of saturated, monounsaturated, and polyunsaturated fatty acids, or semi-quantitative unsaturation indices. The number of papers focusing on especially CSE-MRI-based techniques has steadily increased during the past few years, introducing a range of acquisition protocols and reconstruction algorithms. However, a number of potential sources of bias have also been identified. Furthermore, the measures used to characterize the FAC using both MRI and MRS differ, making comparisons between different techniques difficult. The aim of this paper is to review MRS- and MRI-based methods for in vivo quantification of the FAC. We describe the chemical composition of triglycerides and discuss various potential FAC measures. Furthermore, we review acquisition and reconstruction methodology and finally, some existing and potential applications are summarized. We conclude that both MRI and MRS provide feasible non-invasive alternatives to the gold standard gas chromatography for in vivo measurements of the FAC. Although both are associated with gas chromatography, future studies are warranted

Relaxation effects in MRI-based quantification of fat content and fatty acid composition.

Purpose: To investigate various sources of bias in MRI-based quantification of fat fraction (FF) and fatty acid composition (FAC) using chemical shift-encoded techniques. Methods: Signals from various FFs and FACs and individual relaxation rates of all signal components were simulated. From these signals, FF and FAC parameters were estimated with and without correction for differences in individual relaxation rates. In addition, phantom experiments were conducted with various flip angles and number of echoes to validate the simulations. Results: As expected, T1 weighting resulted in an overestimation of the FF, but had much smaller impact on the FAC parameters. Differences in T2 values of the signal components resulted in overestimation of the FAC parameters in fat/water mixtures, whereas the estimation in pure oil was largely unaffected. This bias was corrected using a simplified signal model with different T2 values of water and fat, where the accuracy of the modeled T2 of water was critical. The results of the phantom experiment were in agreement with simulations. Conclusion: T1 weighting has only a minor effect on FAC quantification in both fat/water mixtures and pure oils. T2 weighting is mainly a concern in fat/water mixtures but may be corrected using a simplified model. Magn Reson Med, 2013. © 2013 Wiley Periodicals, Inc