Optimizing SNR for multi-metabolite hyperpolarized carbon-13 MRI using a hybrid flip-angle scheme

Purpose: To improve the SNR of hyperpolarized carbon-13 MRI of [1-13C]pyruvate using a multispectral variable flip angle (msVFA) scheme in which the spectral profile and flip angle vary dynamically with time. Methods: Each image acquisition in a time-resolved imaging experiment used a unique spectrally varying RF pulse shape for msVFA. Therefore, the flip angle for every acquisition was optimized for pyruvate and each of its metabolites to yield the highest SNR across the acquisition. Multispectral VFA was compared with a spectrally varying constant flip-angle excitation model through simulations and in vivo. A modified broadband chemical shift-encoded gradient-echo sequence was used for in vivo experiments on six pregnant guinea pigs. Regions of interest placed in the placentae, maternal liver, and maternal kidneys were used as areas for SNR measurement. Results: In vivo experiments showed significant increases in SNR for msVFA relative to constant flip angle of up to 250% for multiple metabolites. Conclusion: Hyperpolarized carbon-13 imaging with msVFA excitation produces improved SNR for all metabolites in organs of interest

In vivo magnetic resonance imaging of glucose - initial experience

A new noninvasive, nonradioactive approach for glucose imaging using spin hyperpolarization technology and stable isotope labeling is presented. A glucose analog labeled with 13C at all six positions increased the overall hyperpolarized imaging signal; deuteration at all seven directly bonded proton positions prolonged the spin-lattice relaxation time. High-bandwidth 13C imaging overcame the large glucose carbon chemical shift dispersion. Hyperpolarized glucose images in the live rat showed time-dependent organ distribution patterns. At 8s after the start of bolus injection, the inferior vena cava was demonstrated at angiographic quality. Distribution of hyperpolarized glucose in the kidneys, vasculature, and heart was demonstrated at 12 and 20s. The heart-to-vasculature intensity ratio at 20s suggests myocardial uptake. Cancer imaging, currently performed with 18F-deoxyglucose positron emission tomography (FDG-PET), warrants further investigation, and glucose imaging could be useful in a vast range of clinical conditions and research fields where the radiation associated with the FDG-PET examination limits its use. © 2012 John Wiley & Sons, Ltd

In Vivo Magnetic Resonance Spectroscopy of Hyperpolarized [1-

BACKGROUND: Alterations in glycolysis are central to the increasing incidence of non-alcoholic fatty liver disease (NAFLD), highlighting a need for in vivo, non-invasive technologies to understand the development of hepatic metabolic aberrations. PURPOSE: To use hyperpolarized magnetic resonance spectroscopy (MRS) and proton density fat fraction (PDFF) magnetic resonance imaging (MRI) techniques to investigate the effects of a chronic, life-long exposure to the Western diet (WD) in an animal model resulting in NAFLD; to investigate the hypothesis that exposure to the WD will result in NAFLD in association with altered pyruvate metabolism. STUDY TYPE: Prospective. ANIMAL MODEL: Twenty-eight male guinea pigs weaned onto a control diet (N = 14) or WD (N = 14). FIELD STRENGTH/SEQUENCE: 3 T; T1-weighted gradient echo, T2-weighted spin-echo, three-dimensional gradient multi-echo fat-water separation (IDEAL-IQ), and broadband point-resolved spectroscopy (PRESS) chemical-shift sequences. ASSESSMENT: Median PDFF was calculated in the liver and hind limbs. [1- STATISTICAL TESTS: Unpaired Student\u27s t-tests were used to determine differences in measurements between the two diet groups. The Pearson correlation coefficient was calculated to determine correlations between measurements. RESULTS: Life-long WD consumption resulted in significantly higher liver PDFF and elevated triglyceride content in the liver. The WD group exhibited a decreased TTP for lactate production, and ex vivo analysis highlighted increased liver lactate dehydrogenase (LDH) activity. DATA CONCLUSION: PDFF MRI results suggest differential fat deposition patterns occurring in animals fed a life-long WD characteristic of lean, or lacking excessive subcutaneous fat, NAFLD. The decreased liver lactate TTP and increased ex vivo LDH activity suggest lipid accumulation occurs in association with a shift from oxidative metabolism to anaerobic glycolytic metabolism in WD-exposed livers. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 1

In Vivo Magnetic Resonance Spectroscopy of Hyperpolarized [1-\u3csup\u3e13\u3c/sup\u3eC]Pyruvate and Proton Density Fat Fraction in a Guinea Pig Model of Non-Alcoholic Fatty Liver Disease Development After Life-Long Western Diet Consumption

Background: Alterations in glycolysis are central to the increasing incidence of non-alcoholic fatty liver disease (NAFLD), highlighting a need for in vivo, non-invasive technologies to understand the development of hepatic metabolic aberrations. Purpose: To use hyperpolarized magnetic resonance spectroscopy (MRS) and proton density fat fraction (PDFF) magnetic resonance imaging (MRI) techniques to investigate the effects of a chronic, life-long exposure to the Western diet (WD) in an animal model resulting in NAFLD; to investigate the hypothesis that exposure to the WD will result in NAFLD in association with altered pyruvate metabolism. Study Type: Prospective. Animal Model: Twenty-eight male guinea pigs weaned onto a control diet (N = 14) or WD (N = 14). Field Strength/Sequence: 3 T; T1-weighted gradient echo, T2-weighted spin-echo, three-dimensional gradient multi-echo fat-water separation (IDEAL-IQ), and broadband point-resolved spectroscopy (PRESS) chemical-shift sequences. Assessment: Median PDFF was calculated in the liver and hind limbs. [1-13C]pyruvate dynamic MRS in the liver was quantified by the time-to-peak (TTP) for each metabolite. Animals were euthanized and tissue was analyzed for lipid and cholesterol concentration and enzyme level and activity. Statistical Tests: Unpaired Student\u27s t-tests were used to determine differences in measurements between the two diet groups. The Pearson correlation coefficient was calculated to determine correlations between measurements. Results: Life-long WD consumption resulted in significantly higher liver PDFF and elevated triglyceride content in the liver. The WD group exhibited a decreased TTP for lactate production, and ex vivo analysis highlighted increased liver lactate dehydrogenase (LDH) activity. Data Conclusion: PDFF MRI results suggest differential fat deposition patterns occurring in animals fed a life-long WD characteristic of lean, or lacking excessive subcutaneous fat, NAFLD. The decreased liver lactate TTP and increased ex vivo LDH activity suggest lipid accumulation occurs in association with a shift from oxidative metabolism to anaerobic glycolytic metabolism in WD-exposed livers. Level of Evidence: 2. Technical Efficacy Stage: 1

Optimizing SNR for multi‐metabolite hyperpolarized carbon‐13 MRI using a hybrid flip‐angle scheme

Purpose: To improve the SNR of hyperpolarized carbon-13 MRI of [1-13C]pyruvate using a multispectral variable flip angle (msVFA) scheme in which the spectral profile and flip angle vary dynamically with time. Methods: Each image acquisition in a time-resolved imaging experiment used a unique spectrally varying RF pulse shape for msVFA. Therefore, the flip angle for every acquisition was optimized for pyruvate and each of its metabolites to yield the highest SNR across the acquisition. Multispectral VFA was compared with a spectrally varying constant flip-angle excitation model through simulations and in vivo. A modified broadband chemical shift-encoded gradient-echo sequence was used for in vivo experiments on six pregnant guinea pigs. Regions of interest placed in the placentae, maternal liver, and maternal kidneys were used as areas for SNR measurement. Results: In vivo experiments showed significant increases in SNR for msVFA relative to constant flip angle of up to 250% for multiple metabolites. Conclusion: Hyperpolarized carbon-13 imaging with msVFA excitation produces improved SNR for all metabolites in organs of interest

In Vivo Magnetic Resonance Spectroscopy of Hyperpolarized [ 1‐ 13

BACKGROUND: Alterations in glycolysis are central to the increasing incidence of non-alcoholic fatty liver disease (NAFLD), highlighting a need for in vivo, non-invasive technologies to understand the development of hepatic metabolic aberrations. PURPOSE: To use hyperpolarized magnetic resonance spectroscopy (MRS) and proton density fat fraction (PDFF) MRI techniques to investigate the effects of a chronic, life-long exposure to the Western Diet (WD) in an animal model resulting in NAFLD; to investigate the hypothesis that exposure to the WD will result in NAFLD in association with altered pyruvate metabolism. STUDY TYPE: Prospective ANIMAL MODEL: 28 male guinea pigs weaned onto a control diet (n = 14) or WD (n = 14). FIELD STRENGTH/SEQUENCE: 3T; T1-weighted gradient echo, T2-weighted spin echo, 3D gradient multi-echo fat-water separation (IDEAL-IQ) and broadband point-resolved spectroscopy (PRESS) chemical-shift sequences. ASSESSMENT: Median PDFF was calculated in the liver and hind limbs. [1-(13)C]pyruvate dynamic MRS in the liver was quantified by the time to peak (TTP) for each metabolite. Animals were euthanized and tissue was analyzed for lipid and cholesterol concentration and enzyme level and activity. STATISTICAL TESTS: Unpaired Student’s t-tests were used to determine differences in measurements between the two diet groups. The Pearson correlation coefficient was calculated to determine correlations between measurements. RESULTS: Life-long WD consumption resulted in significantly higher liver PDFF and elevated triglyceride content in the liver. The WD group exhibited a decreased TTP for lactate production, and ex vivo analysis highlighted increased liver lactate dehydrogenase (LDH) activity. DATA CONCLUSION: PDFF MRI results suggest differential fat deposition patterns occurring in animals fed a life-long WD characteristic of lean, or lacking excessive subcutaneous fat, NAFLD. The decreased liver lactate TTP and increased ex vivo LDH activity suggest lipid accumulation occurs in association with a shift from oxidative metabolism to anaerobic glycolytic metabolism in WD-exposed livers

Quantification of fetal organ volume and fat deposition following <i>in utero</i> exposure to maternal Western Diet using MRI

<div><p>Purpose</p><p>To examine the feasibility of using MRI to identify differences in liver size and fat deposition in fetal guinea pigs exposed to an <i>in utero</i> environment influenced by maternal consumption of a Western diet.</p><p>Materials and methods</p><p>Female guinea pigs fed either an energy-dense Western Diet (WD), comprised of increased saturated fats and simple sugars, or a Control Diet (CD) from weaning through pregnancy, underwent MR scanning near term (~ 60 days; term ~ 69 days). Maternal weights were collected at mating and at MR scanning. T₁-weighted, T₂-weighted, and IDEAL water-fat images were acquired at 3 Tesla. The images were used to segment maternal adipose tissue, fetal liver, fetal brain, fetal adipose tissue, and total fetal volumes and to measure maternal and fetal hepatic fat fractions.</p><p>Results</p><p>Weights of WD sows were lower prior to pregnancy (<i>P</i> = .04), however their weight gain over pregnancy did not differ from the CD group (<i>P</i> = .98). The WD sows had less total adipose tissue (TAT) at MR scanning (<i>P</i> = .04), while hepatic fat content was significantly elevated (<i>P</i> = .04). When controlling for litter size, WD fetuses had larger livers (<i>P</i> = .02), smaller brains (<i>P</i> = .01), and increased total adipose tissue volume (<i>P</i> = .01) when normalized by fetal volume. The WD fetuses also had increased hepatic fat fractions compared to CD fetal livers (<i>P</i> < .001).</p><p>Conclusion</p><p>Maternal Western Diet consumption prior to and during pregnancy induces differences in maternal liver fat content, fetal liver volume and liver fat storage, as well as changes in fetal adipose tissue deposition that can be measured <i>in utero</i> using MRI.</p></div

Weight and fat deposition measurements for Control Diet and Western Diet sows.

<p>(A) Weight measurements taken before pregnancy, on the MR scan date, and weight change during pregnancy (CD: <i>n</i> = 4; WD: <i>n</i> = 4). (B) Total adipose tissue volumes (CD: <i>n</i> = 4; WD: <i>n</i> = 4). (C) Hepatic proton density fat fraction (CD: <i>n</i> = 4; WD: <i>n</i> = 4). Data are presented as box and whisker plots as described in the methods section for CD (black) and WD (grey) sows. *<i>P</i> < .05.</p

Coronal images of a pregnant guinea pig on a lifetime Western Diet.

<p>(A) T₁-weighted image with fetuses contoured in yellow and fetal livers denoted by white arrows. (B) T₂-weighted images with fetal brains contoured in yellow. (C) IDEAL fat-only image. (D) IDEAL fat fraction map. Images have been cropped to highlight the fetuses.</p

Fetal fat deposition for Control Diet and Western Diet fetuses.

<p>(A) Total adipose tissue (TAT) to fetal volume ratio and intra-abdominal adipose tissue (IAAT) volume to fetal volume ratio. (B) IAAT to TAT volume ratio. (C) Fetal hepatic proton density fat fraction. Data are presented as box and whisker plots as described in the methods section for CD (black) and WD (grey) fetuses. <i>n</i> = 11 and 9 for CD and WD, respectively. *<i>P</i> < .05.</p