Highly reproducible values of ADC and FA were obtained with the polygonal method on intra-rater (coefficients of variation

OBJECTIVEWeight loss through lifestyle changes is recommended for nonalcoholic fatty liver disease (NAFLD). However, its efficacy in patients with type 2 diabetes is unproven.RESEARCH DESIGN AND METHODSLook AHEAD (Action for Health in Diabetes) is a 16-center clinical trial with 5,145 overweight or obese adults with type 2 diabetes, who were randomly assigned to an intensive lifestyle intervention (ILI) to induce a minimum weight loss of 7% or a control group who received diabetes support and education (DSE). In the Fatty Liver Ancillary Study, 96 participants completed proton magnetic resonance spectroscopy to quantify hepatic steatosis and tests to exclude other causes of liver disease at baseline and 12 months. We defined steatosis >5.5% as NAFLD.RESULTSParticipants were 49% women and 68% white. The mean age was 61 years, mean BMI was 35 kg/m2, mean steatosis was 8.0%, and mean aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were 20.5 and 24.2 units/l, respectively. After 12 months, participants assigned to ILI (n = 46) lost more weight (−8.5 vs. −0.05%; P < 0.01) than those assigned to DSE and had a greater decline in steatosis (−50.8 vs. −22.8%; P = 0.04) and in A1C (−0.7 vs. −0.2%; P = 0.04). There were no significant 12-month changes in AST or ALT levels. At 12 months, 26% of DSE participants and 3% (1 of 31) of ILI participants without NAFLD at baseline developed NAFLD (P < 0.05).CONCLUSIONSA 12-month intensive lifestyle intervention in patients with type 2 diabetes reduces steatosis and incident NAFLD.

KeywordsBrain tumors; magnetic resonance spectroscopy; spectroscopic imaging; metabolites IntroductionLocalized proton MR spectroscopy (MRS) of the human brain, first reported more than 20 years ago,(1-3) is a mature methodology that is used clinically in many medical centers worldwide for the evaluation of brain tumors.(4) While there have been studies of human brain tumors using heteronuclei such as phosphorus ( 31 P) and sodium ( 11 Na),(5,6) by far the most spectroscopy studies use the proton ( 1 H) nucleus, because of both its high sensitivity and ease of implementation on commercial MRI scanners. This review will therefore focus on proton MRS in human brain tumors.There are two classes of spatial localization techniques for MR spectroscopy; single-voxel (SV) techniques (commonly used methods includes 'PRESS'(7) and 'STEAM'(8)) which record spectra from one region of the brain at a time, or multi-voxel techniques ('MR spectroscopic imaging' (MRSI), also called 'Chemical Shift Imaging' (CSI)(9)) which simultaneously record spectra from multiple regions and thereby map out the spatial distribution of metabolites within the brain. MRSI is typically performed in 2-or 3-dimensions, but does not usually include full brain coverage. While SV-MRS and MRSI each have their own advantages and disadvantages (e.g. in terms of spectral quality, scan time, spatial resolution, spatial coverage, and ease of use/interpretation), a key consideration for brain tumors is their metabolic inhomogeneity. For instance, the spectrum from the necrotic core of a high-grade brain tumor is quite different from a spectrum from the actively growing rim, while peri-tumoral edema is different from tumor invasion into surrounding brain tissue; for these reasons and others, high-resolution MRSI is often favored for evaluating brain tumor metabolism. For a detailed discussion of the relative merits of SV-MRS and MRSI, please see reference. (10) © 2010 Elsevier Inc. All rights reserved. 2 Author for Correspondence: Professor, Russell H Morgan Department of Radiology and Radiological Science, Department of Radiology, Park 367B, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Baltimore, MD 21287, Phone (410) 955-1740, FAX (410) pbarker2@jhmi.edu. 1 Phone (410) 614-2707, FAX (410) 502-6076, ahorska@jhmi.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroimaging Clin N Am. Author manuscript; available in PMC 2011 August 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptEarly in the development of human brain proto...

Fructose consumption predicts increased hepatic fibrosis in those with nonalcoholic fatty liver disease (NAFLD). Due to its ability to lower hepatic adenosine triphosphate (ATP) levels, habitual fructose consumption could result in more hepatic ATP depletion and impaired ATP recovery. The degree of ATP depletion following an intravenous fructose challenge test in low versus high fructose consumers was assessed. We evaluated diabetic adults enrolled in the Look AHEAD Fatty Liver Ancillary Study (n=244) for whom dietary fructose consumption estimated by a 130-item Food Frequency questionnaire, hepatic ATP measured by phosphorus MRS (31P MRS) and uric acid (UA) levels were performed (n=105). In a subset of participants (n=25), an intravenous fructose challenge was utilized to assess change in hepatic ATP content. The relationships between dietary fructose, UA and hepatic ATP depletion at baseline and following intravenous fructose challenge was evaluated in low (<15 g/d) vs. high (≥15 g/d) fructose consumers. High dietary fructose consumers had slightly lower baseline hepatic ATP levels and a greater absolute change in hepatic α-ATP/Pi ratio (0.08 vs. 0.03, p=0.05) and γ-ATP /Pi ratio following an intravenous fructose challenge (0.03 vs. 0.06, p=0.06). Patients with high UA (≥5.5 mg/dl) showed a lower minimum liver ATP/Pi ratio post-fructose challenge (4.5 vs. 7.0, p = 0.04). Conclusions High fructose consumption depletes hepatic ATP and impairs recovery from ATP depletion following an intravenous fructose challenge. Subjects with high UA show a greater nadir in hepatic ATP in response to fructose. Both high dietary fructose intake and elevated UA level may predict more severe hepatic ATP depletion in response to fructose and hence may be risk factors for the development and progression of NAFLD.

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Purpose: To quantify and examine the distribution of brain metabolites in normal young adults using single voxel MR spectroscopy at 3 Tesla (T). Materials and Methods:Short-echo time single-voxel PRESS technique was used to measure the apparent concentration of five metabolites at nine locations in the brains of young adults. Concentrations were estimated by means of an automated fitting method (LCModel) with reference to an unsuppressed water signal and were corrected for T 1 relaxation, T 2 relaxation, and cerebrospinal fluid partial volume. Analysis of variance with Tukey post hoc test was used to evaluate regional variations.Results: Statistically significant differences in regional concentrations were detected for each of the metabolites. The number of significant differences was greatest for total choline, whereas myo-inositol and the sum of glutamine and glutamate had the fewest. Magnitude of variation was greatest for total choline and least for the sum of N-acetyl aspartate and N-acetylaspartylglutamate. Conclusion:In agreement with previous studies at other field strengths, we found heterogeneous distribution of the major spectroscopically measurable brain metabolites. Although the most distinct differences are between tissue types, there is appreciable variation within a tissue type at different locations. The spectra and metabolite concentrations presented should provide a useful reference for both clinical and research MR spectroscopy studies performed at 3T. PROTON MR SPECTROSCOPY (MRS) of the brain is a useful technique for evaluating several neurological and psychiatric diseases (1). For clinicians interpreting spectra from individual patients, it is important to have knowledge of the normal range of spectral patterns from different brain regions, including how the spectra may depend on the patient's age, and on the spectroscopic technique used. While normal regional and age-related spectral variations have been reported previously at field strengths of 1T (2-5), 2T (6 -8), and 4T (9,10), to the best of our knowledge, there have been no reports using 3T scanners. Because use of 3T scanners is increasing for neuroimaging and spectroscopy in clinical practice, there is, therefore, a need for normative 3T data for comparison with patient studies. Also, even when results from all field strengths are taken together, there have been relatively few quantitative reports of normal values; therefore, expansion of coverage of different brain regions and confirmation of previously reported values is desirable.The purpose of this study was to establish normative spectroscopic data at 3T, from a variety of regions often involved in brain pathology, using commonly available methodology (single voxel PRESS localization at short echo time, with analysis using the LCModel software (11)). Because MRS-measurable metabolic asymmetry in the human brain is minimal (12), unilateral measurements from multiple different anatomical regions were measured, rather than bilateral measurements in fewer structures. Quantitative ...

Purpose: To quantify regional variations in metabolite levels in the developing brain using quantitative proton MR spectroscopic imaging (MRSI). Materials and Methods:Fifteen healthy subjects three to 19 years old were examined by in vivo multislice proton MRSI. Concentrations of N-acetyl aspartate (NAA), total choline (Cho), total creatine (Cr), and peak area ratios were determined in selected frontal and parietal gray and white matter regions, basal ganglia, and thalamus. Results:In cortical gray matter regions, the ratio of NAA/ Cho increased to a maximum at 10 years and decreased thereafter (P ϭ 0.010). In contrast, in white matter, average ratios NAA/Cho increased linearly with age (P ϭ 0.045). In individual brain regions, age-related changes in NAA/Cho were found in the putamen (P ϭ 0.044). No significant age-related changes in NAA, Cho, Cr, or other metabolite ratios could be determined. Conclusion:Consistent with recent studies using other structural and functional neuroimaging techniques, our data suggest that small but significant changes occur in regional cerebral metabolism during childhood and adolescence. Non-linear age related changes of NAA/Cho in frontal and parietal areas, resembling previously reported age related changes in rates of glucose utilization and cortical volumes, may be associated with dendritic and synaptic development and regression. Linear age-related changes of NAA/Cho in white matter are also in agreement with agerelated increases in white matter volumes, and may reflect progressive increases in axonal diameter and myelination. (2,3). However, the imaging-based study of functional changes during development, including physiological events and brain activation, has been more limited. Proton magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) are safe, noninvasive techniques that allow the study of brain metabolism in vivo. While proton MRS has been used quite extensively to study brain metabolism in the first few years of life (4 -13), there have been very few MRS (4,9,12,14,15) and MRSI (16) studies of normal brain metabolism during childhood and adolescence. Further, several of these previous reports either included subjects with possible neurological disorders, lacked quantitative analysis of metabolite concentrations, or were limited to the study of only a few different brain regions. This relative scarcity of normative MRS data not only limits the understanding of postnatal brain maturation, but also makes difficult the interpretation of abnormal metabolite concentrations in developmental disorders.Therefore, the aim of the present study was to examine the age-dependency of metabolite concentrations during postnatal brain development in normal, healthy subjects using quantitative multislice proton MRSI. Multiple, functionally-related cortical (frontal and parietal) and subcortical regions, in which significant agerelated volumetric differences have been previously

Objective: To examine five available software packages for the assessment of abdominal adipose tissue with magnetic resonance imaging, compare their features and assess the reliability of measurement results. Design: Feature evaluation and test-retest reliability of softwares (NIHImage, SliceOmatic, Analyze, HippoFat and EasyVision) used in manual, semi-automated or automated segmentation of abdominal adipose tissue. Subjects: A random sample of 15 obese adults with type 2 diabetes. Measurements: Axial T1-weighted spin echo images centered at vertebral bodies of L2-L3 were acquired at 1.5 T. Five software packages were evaluated (NIHImage, SliceOmatic, Analyze, HippoFat and EasyVision), comparing manual, semi-automated and automated segmentation approaches. Images were segmented into cross-sectional area (CSA), and the areas of visceral (VAT) and subcutaneous adipose tissue (SAT). Ease of learning and use and the design of the graphical user interface (GUI) were rated. Intra-observer accuracy and agreement between the software packages were calculated using intra-class correlation. Intra-class correlation coefficient was used to obtain test-retest reliability. Results: Three of the five evaluated programs offered a semi-automated technique to segment the images based on histogram values or a user-defined threshold. One software package allowed manual delineation only. One fully automated program demonstrated the drawbacks of uncritical automated processing. The semi-automated approaches reduced variability and measurement error, and improved reproducibility. There was no significant difference in the intra-observer agreement in SAT and CSA. The VAT measurements showed significantly lower test-retest reliability. There were some differences between the software packages in qualitative aspects, such as user friendliness. Conclusion: Four out of five packages provided essentially the same results with respect to the inter-and intra-rater reproducibility. Our results using SliceOmatic, Analyze or NIHImage were comparable and could be used interchangeably. Newly developed fully automated approaches should be compared to one of the examined software packages.