Evaluation of a Quantitative Magnetic Resonance Imaging System for Whole Body Composition Analysis in Rodents

We evaluated the EchoMRI‐900 combination rat and mouse quantitative magnetic resonance (QMR) body composition method in comparison to traditional whole‐body chemical carcass composition analysis (CCA) for measurements of fat and fat‐free mass in rodents. Live and postmortem (PM) QMR fat and lean mass measurements were obtained for lean, obese and outbred strains of rats and mice, and compared with measurements obtained using CCA. A second group of rats was measured before and after 18 h food or water deprivation. Significant positive correlations between QMR and CCA fat and lean mass measurements were shown for rats and mice. Although all live QMR fat and lean measurements were more precise than CCA for rats, values obtained for mice significantly differed from CCA for lean mass only. QMR performed PM slightly overestimated fat and lean values relative to live QMR but did not show lower precision than live QMR. Food deprivation reduced values for both fat and lean mass; water deprivation reduced estimates of lean mass only. In summary, all measurements using this QMR system were comparable to those obtained by CCA, but with higher overall precision, similar to previous reports for the murine QMR system. However, PM QMR measurements slightly overestimated live QMR values, and lean and fat mass measurements in this QMR system are influenced by hydration status and animal size, respectively. Despite these caveats, we conclude that the EchoMRI QMR system offers a fast in vivo method of body composition analysis, well correlated to but with greater overall precision than CCA.     

Quantitative Body Composition Analysis in Awake Mice and Rats by Magnetic Resonance Relaxometry

Objective: Magnetic resonance (MR) relaxometry has recently been introduced for noninvasive body composition analysis in awake mice. The purpose of the present study was to extend the method to rats and to introduce calibration procedures that render MR relaxometry fully quantitative. Research Methods and Procedures: Proton T₂ MR relaxometry at 4.7 Tesla was used for body composition analyses in 700 awake mice and 400 rats of different strains and conditions. Relaxograms calculated from the signal decays observed with multi‐spin‐echo acquisition provided well‐separated contributions of tissue water and fat. Analysis of fat composition was carried out in vivo using ¹³C‐MR spectroscopy. Evolution of body composition in rats was assessed during drug treatment. Results: MR relaxometry for noninvasive body composition analysis in laboratory rodents was implemented on a standard MR scanner, and a throughput of >30 animals per hour was achieved. Excellent linearity and reproducibility with coefficients of variance as low as 2.5% and 1.7% were obtained in mice and rats, respectively. The lean mass‐to‐water ratio (mice, 1.35 ± 0.03; rats, 1.39 ± 0.04) and the proton density of fat (mice, 8.1 ± 0.2; rats, 8.9 ± 0.2 g/mol) were determined from cross‐sectional data. Fat composition analysis by ¹³C‐MR spectroscopy corroborated these findings and yielded information on the average acyl chain length (16.3 ± 1.6) and contributions of saturated (27 ± 3%), monounsaturated (22 ± 2%), and polyunsaturated (51 ± 3%) fatty acids. Longitudinal assessments in rats treated with sibutramine and dexfenfluramine showed dose‐related changes in body composition. Discussion: T₂ MR relaxometry backed by solid calibration provides a powerful means for rapid quantitative body composition analysis in awake mice and rats that is suitable for serial investigations in pharmaceutical research.     

Body Composition and Hormonal Adaptations Associated with Forskolin Consumption in Overweight and Obese Men

Objective: This study examined the effect of forskolin on body composition, testosterone, metabolic rate, and blood pressure in overweight and obese (BMI ≥ 26 kg/m²) men. Research Methods and Procedure: Thirty subjects (forskolin, n = 15; placebo, n = 15) were studied in a randomized, double‐blind, placebo‐controlled study for 12 weeks. Results: Forskolin was shown to elicit favorable changes in body composition by significantly decreasing body fat percentage (BF%) and fat mass (FM) as determined by DXA compared with the placebo group (p ≤ 0.05). Additionally, forskolin administration resulted in a change in bone mass for the 12‐week trial compared with the placebo group (p ≤ 0.05). There was a trend toward a significant increase for lean body mass in the forskolin group compared with the placebo group (p = 0.097). Serum free testosterone levels were significantly increased in the forskolin group compared with the placebo group (p ≤ 0.05). The actual change in serum total testosterone concentration was not significantly different among groups, but it increased 16.77 ± 33.77% in the forskolin group compared with a decrease of 1.08 ± 18.35% in the placebo group. Discussion: Oral ingestion of forskolin (250 mg of 10% forskolin extract twice a day) for a 12‐week period was shown to favorably alter body composition while concurrently increasing bone mass and serum free testosterone levels in overweight and obese men. The results indicate that forskolin is a possible therapeutic agent for the management and treatment of obesity.     

Heritability of Body Composition Measured by DXA in the Diabetes Heart Study

Objective: The purpose of this study was to investigate the heritability of body composition measured by DXA in the Diabetes Heart Study (DHS). Research Methods and Procedures: Participants were 292 women and 262 men (age, 38 to 86 years; BMI, 17 to 57 kg/m²) from 244 families. There were 492 white and 49 African‐American sibling pairs. DXA measurements of percentage fat mass (FM), whole body FM, and lean mass (LM), as well as regional measurements of trunk fat mass (TFM) and appendicular lean mass (ALM), were obtained. Heritability of FM, LM, and BMI were estimated using Sequential Oligogenic Linkage Analysis Routines. Results: After adjusting for age, gender, ethnicity, and height, the heritability estimates of various compositional attributes were %FM = 0.64, whole body FM = 0.71, TFM = 0.63, whole body LM = 0.60, ALM = 0.66, and BMI = 0.64 (all p < 0.0001). Additional adjustment for diabetes status, smoking, dietary intake, and physical activity resulted in only minor changes in the heritability estimates (?² = 0.63 to 0.72, all p < 0.0001). Furthermore, heritability of TFM after additional adjustment for whole body FM was significant (?² = 0.55, p < 0.0001), and heritability of ALM after additional adjustment for whole body LM was also significant (?² = 0.51, p < 0.0001). Discussion: These data suggest that FM and LM measured by DXA are highly heritable and can be effectively used in designing linkage studies to locate genes governing body composition. In addition, regional distribution of FM and LM may be genetically determined.     

Quantitative Magnetic Resonance (QMR) for Longitudinal Evaluation of Body Composition Changes With Two Dietary Regimens

We have recently reported a validation study of a prototype low‐field strength quantitative magnetic resonance (QMR) instrument for measurement of human body composition (EchoMRI‐AH). QMR was very precise, but underreported fat mass (FM) by 2–4 kg when compared to a 4‐compartment (4C) model in this cross‐sectional study. Here, we report the performance of an updated instrument in two longitudinal studies where FM was decreasing. Healthy obese volunteers were given a modest energy deficit diet for 8 weeks (study A) and obese patients with heart failure and/or at high cardiovascular risk were prescribed a low energy liquid diet for 6 weeks (study B). FM was measured at the start and end of these periods by QMR, dual‐energy X‐ray absorptiometry (DXA) and 4C. A higher proportion of the weight lost came from fat in study A compared with study B, where loss of total body water (TBW) played a greater part. The intraclass correlation between QMR and 4C estimates of FM loss (ΔFat) was 0.95, but 20 of 22 estimates of ΔFat by QMR were lower than the corresponding estimate by the 4C model. Bland–Altman analysis demonstrated that estimates of FM loss by QMR were ～1.0 and 0.7 kg lower than those obtained with 4C (P = 0.0008) and DXA (P = 0.049), respectively. Measurement precision remained high. QMR measurement should prove valuable for quantifying modest changes of FM in small trials.     

Evaluation of Total Body Electrical Conductivity to Estimate Body Composition of a Small Mammal

ABSTRACT The ability to measure body composition is critical for studying the physiological ecology of animals. This is particularly true for small mammals that have a high metabolic rate. We evaluated a nondestructive method of body composition analysis that would allow accurate assessment of body fat, body water, and lean mass. We used total body electrical conductivity (TOBEC) to estimate body composition in the little brown myotis (Myotis lucifugus). In a sample of 46 individuals, TOBEC was both accurate and precise in estimating total body water and lean mass but was less effective at estimating total body fat. Mass-independent or whole-body compartments (i.e., total body water, total body fat, lean dry mass, and lean body mass) were more accurately estimated than mass-dependent or mass-specific body composition compartments (i.e., water content, fat index, and % lean dry mass). The TOBEC measurements we made using an SA-3000 analyzer were influenced by extremes in body temperature, as well as by aluminum and incoloy wing bands. Our study also presents a new method of restraint especially suited for small mammals and birds that increases precision of TOBEC measurements. This study shows that TOBEC is a potentially valuable tool for studying changes in body composition of small mammals and may provide insight into the physiological impacts of various life history stages such as postnatal growth, reproduction, and hibernation.     

基于低场核磁共振T1-T2谱技术定性和定量分析罗非鱼各组织的方法探究

形体指标的检测是鱼类常规营养评定的重要组成部分。目前,分析鱼类组织体重比的方法会对鱼体造成损伤,且取样过程复杂,迫切需要无损快速检测技术分析鱼体组织占比。低场核磁共振技术具有快速无损检测的特点,已有研究利用低场核磁共振T1谱技术检测小鼠内脂肪组织体积,但尚未有研究应用低场核磁共振T1-T2谱技术对鱼类各组织器官进行定性和定量分析。基于此,利用低场核磁共振T1-T2谱技术,将分离后的罗非鱼的肌肉组织、腹腔脂肪组织、肝脏组织、肠道组织单独以及混合后进行扫描分析,结果发现利用低场核磁共振T1-T2谱技术可以分离罗非鱼肌肉组织和腹腔脂肪组织,但是无法区分肝脏组织和肠道组织。进一步对能够实现分离的肌肉组织和脂肪组织建立定量分析的模型,分析罗非鱼组织信号强度与组织重量相关性,结果显示,肌肉组织相关性R2=0.974 3,腹腔脂肪组织相关性R2=0965 0。并利用罗非鱼活体验证了肌肉组织定量分析模型的可靠性,将活体扫描肌肉信号大小转换成肌肉组织重量并分析其与全鱼体重相关性,结果显示肌肉组织重量与体重相关性R2=0.806 9。研究表明,在鱼类营养代谢研究中,可以利用低场核磁共振T1-T2谱技术快速无损地定量分析鱼体内肌肉组织含量。     

Human Body Composition and the Epidemiology of Chronic Disease

Obesity and body fat distribution (FD) are established risk factors for chronic diseases. The body mass index (BMI) and the waist/hip circumference ratio (WHR) are used conventionally as indices of obesity and FD in epidemiological studies. Although some general limitations of these indices are recognized, others that affect their use in relative risks for disease are not well recognized. These include effects of sex, ethnicity, and especially age on the relationships between these indices and body composition, which can result in substantial misclassification of obesity and FD. There is considerable variability in body composition for any BMI, and some individuals with low BMIs have as much fat as those with high BMIs. This results in poor sensitivity for classifying levels of body fatness (e.g., too many “false negatives,” or overweight individuals classified as not overweight), and relative risks are attenuated across all categories of BMI. A more serious problem, however, is that at different ages the same levels of BMI correspond to different amounts of fat and fat-free mass. Data from the Rosetta Study and the New Mexico Aging Process Study show that older adults have, on average, more fat than younger adults at any BMI, due to the loss of muscle mass with age. As a result, the sensitivity of BMI cutpoints with respect to body fatness decreases with age, and the use of a fixed cutpoint for all ages results in “differential mis-classification bias.” Taken together, these issues sug- gest that the increases with age in the prevalences of overweight and obesity, and in the risks for chronic diseases, may be mis-estimated using BMI. Similar issues may affect the use of WHR for estimating prevalences and associated risks of FD. New field methods for estimating body composition are available that can be applied in large, epidemiologic follow-up studies of chronic diseases. These methods will allow epidemiologists to consider, for example, whether it is increased fat, or the replacement of fat-free mass with fat, with age that is associated with risk for chronic disease.     

Magnetic Resonance Neurography for Evaluation of Peripheral Nerves

Peripheral nerve injuries (PNIs) continue to present both diagnostic and treatment challenges. While nerve transections are typically a straightforward diagnosis, other types of PNIs, such as chronic or traumatic nerve compression, may be more difficult to evaluate due to their varied presentation and limitations of current diagnostic tools. As a result, diagnosis may be delayed, and these patients may go on to develop progressive symptoms, impeding normal activity. In the past, PNIs were diagnosed by history and clinical examination alone or techniques that raised concerns regarding accuracy, invasiveness, or operator dependency. Magnetic resonance neurography (MRN) has been increasingly utilized in clinical settings due to its ability to visualize complex nerve structures along their entire pathway and distinguish nerves from surrounding vasculature and tissue in a noninvasive manner. In this review, we discuss the clinical applications of MRN in the diagnosis, as well as pre- and postsurgical assessments of patients with peripheral neuropathies.     

Birth Weight,Adult Body Composition,and Subcutaneous Fat Distribution

Objectives: To investigate if birth weight is related to both body mass index (BMI) and distribution of subcutaneous fat at adult age. Research Methods and Procedures: A 9‐year longitudinal study was performed in 229 subjects (192 women) with ages ranging from 27 to 36 years. Birth weight was retrieved by a questionnaire, and adult weight, height, skinfold thicknesses, and waist‐to‐hip ratio (WHR) were repeatedly measured at mean ages 27, 29, 31, and 36 years. BMI, sum of four skinfolds (S4S), the ratio between two truncal skinfolds and S4S (SS/S4S), and the ratio between WHR and the cross‐sectional area of the left thigh were calculated with the available data. Results: The adjusted model showed that in women, birth weight was significantly negatively related to adult S4S [β = ?5.211; (?9.768 to ?0.654)], waist circumference [β = ?1.449; (?2.829 to ?0.069)], and SS/S4S ratio [β = ?3.579; (?5.296 to ?1.862)]. In men, a significant negative association was observed between birth weight and adult WHR [β = ?1.096; (?2.092 to ?0.100)] only. Other relationships showed, although not significantly, the same negative trend, namely that lower birth weight is related to higher adult body fat mass (S4S) and a more truncal subcutaneous fat distribution (SS/S4S). No associations were found between birth weight and either adult BMI or the cross‐sectional area of the thigh. Discussion: Lower birth weight is, in both adult men and women, related to a higher adult subcutaneous fat mass and a more truncal distribution of subcutaneous fat, indicating a higher risk for obesity.     

结构基因组学研究与核磁共振

各种生物的基因组DNA测序计划的完成,将结构生物学带入了结构基因组学时代.结构基因组学是对所有基因组产物结构的系统性测定,它运用高通量的选择、表达、纯化以及结构测定和计算分析手段,为基因组的每个蛋白质产物提供实验测定的结构或较好的理论模型,这将加速生命科学各个领域的研究.生物信息学、基因工程、结构测定技术等的发展为结构基因组学研究提供了保证.近年来核磁共振在技术方法上的进展,使其成为结构基因组学高通量结构分析中的一个关键方法.     

Fat and energy partitioning: longitudinal observations in leptin-treated adults homozygous for a Lep mutation

Objective: Partitioning of body energy content in the aleptinemic ob/ob mouse differs from that in wild‐type mice, but it is not known whether parallel differences exist between humans with leptin (Lep) gene mutations and healthy adults. The objective of this study was to evaluate body composition in three leptin‐treated Turkish adults homozygous for a missense mutation (C→T substitution at codon 105 resulting in Arg→Trp) of Lep. Research Methods and Procedures: Subjects, one male and two female Turkish family members, were evaluated at baseline and treated for 18 months with r‐MetHuLeptin. Patient data (fat mass, energy content) were compared with adult sex‐specific predicted values (adjusted for weight, height, and age) derived in healthy control subjects. Results: Weight loss with leptin treatment was substantial, ranging from 43.9% to 52.1%. At baseline and with leptin treatment, the two women had a fat mass and energy content similar (±12%) to predicted values. Baseline fat and energy content in the male patient was high compared with predicted values (e.g., fat +33%) but approached and reached normal values (e.g., fat, +2%) after 18 months of leptin therapy. Discussion: Adult women with Lep mutations had body composition similar to normal women at baseline and with leptin treatment. In contrast, the man with a Lep mutation had high body fat in the untreated state but a normal male phenotype with leptin administration, possibly secondary to androgenic fat partitioning effects. Fat and energy partitioning can, thus, be quantitatively assessed and linked with potential hormonal mechanisms in humans with inherited disturbances in energy regulation.     

核磁共振技术在蛋白质领域的应用

简要叙述了核磁共振技术(NMR)在蛋白质领域的研究及应用。NMR法通过测定蛋白质在稀溶液状态下反应位点的特定参数来计算蛋白质的三级结构,并可深入了解一定时间范围内化学反应和蛋白质构象转变的动力学过程。通过NMR对抗原决定簇和抗体CDR作图,可以分析其一级结构和三维构象;对抗原抗体动力学的分析,对于设计基因疫苗、检测细胞表面抗原提呈以及分析抗原抗体复合物的构象变化也有着重要意义。     

Adipose Tissue Quantification by Imaging Methods: A Proposed Classification

Recent advances in imaging techniques and understanding of differences in the molecular biology of adipose tissue has rendered classical anatomy obsolete, requiring a new classification of the topography of adipose tissue. Adipose tissue is one of the largest body compartments, yet a classification that defines specific adipose tissue depots based on their anatomic location and related functions is lacking. The absence of an accepted taxonomy poses problems for investigators studying adipose tissue topography and its functional correlates. The aim of this review was to critically examine the literature on imaging of whole body and regional adipose tissue and to create the first systematic classification of adipose tissue topography. Adipose tissue terminology was examined in over 100 original publications. Our analysis revealed inconsistencies in the use of specific definitions, especially for the compartment termed “visceral” adipose tissue. This analysis leads us to propose an updated classification of total body and regional adipose tissue, providing a well‐defined basis for correlating imaging studies of specific adipose tissue depots with molecular processes.     

二维核磁共振谱在多糖结构研究中的应用

二维核磁共振谱（2D NMR）是获取多糖结构信息,尤其是在多糖序列分析方面的有力工具。本文重点介绍了在多糖结构解析中常用的几种2D NMR谱以及2D NMR解析多糖结构的方法。     

High-Resolution Proton Magnetic Resonance Spectroscopy of Rabbit Brain: Regional Metabolite Levels and Postmortem Changes

The changes in 16 cerebral metabolites produced by cardiac arrest and subsequent room temperature autolysis were studied using high-resolution proton nuclear magnetic resonance spectroscopy. Biopsies of rabbit cerebral cortex, cerebral white matter, and cerebellum were quantitatively analyzed for acetate, alanine, gamma-aminobutyric acid, creatine, glutamate, glycine, inositol, lactate, N-acetylaspartate, phosphocreatine, succinate, taurine, and threonine. Of these, N-acetylaspartate and the total creatine pool are the best candidates for use as concentration reference standards linking in vitro to in vivo 1H nuclear magnetic resonance measurements. Both changed little immediately after death, and they varied in a distinctive way among cortex, white matter, and cerebellum.     

Anatomical patterning of visceral adipose tissue: race, sex, and age variation

Objective: We tested sex, race, and age differences in the patterning of visceral adipose tissue (VAT) and subcutaneous adipose tissue. Research Methods and Procedures: Contiguous 1‐cm‐thick magnetic resonance (MR) images of the abdomen were collected from 820 African‐American and white adults. Repeated‐measures ANOVA was used to examine the effects of image location, sex, race, and age (≥50 vs. <50 years) on adipose tissue areas. Maximum VAT area was identified for each subject from the raw data. Results: Compared to women, men had greater total VAT volume (p < 0.0001), and their maximum VAT area occurred higher in the abdomen (p < 0.0001). Among white men, maximim VAT area most frequently occurred 5 to 10 cm above L4‐L5, whereas in the other groups, maximim VAT area most frequently occurred 1 to 4 cm above L4‐L5 (p < 0.0001). African‐American men had greater total VAT volume than African‐American women (p < 0.01), but this sex difference was only significant using single images cranial to L4‐L5 + 2 cm. Age‐related increases in VAT tended to be greatest 5 to 10 cm above L4‐L5 in men and near L4‐L5 in women. Discussion: A single MR image 5 to 10 cm above L4‐L5 may allow more accurate conclusions than the L4‐L5 image regarding group differences in visceral adiposity.     

High-Resolution Proton Magnetic Resonance Analysis of Human Cerebrospinal Fluid

High-resolution proton magnetic resonance spectroscopy was used to analyze human cerebrospinal fluid obtained from patients with several neurological problems. The major metabolites measured included glucose, lactate, glutamine, citrate, inositol, acetate, creatine, creatinine, beta-hydroxybutyrate, alanine, and pyruvate. A drug vehicle, propylene glycol, was also measured. Alterations in the cerebrospinal fluid of these metabolites provided information concerning metabolism of the brain. Magnetic resonance spectroscopy offered a simple and rapid means of assessing these and other exogenous and endogenous compounds in diseases affecting the nervous system.     

Relationships between Insulin Sensitivity and Measures of Body Fat in Asymptomatic Men and Women

Objective: To assess whether measures of body fat by DXA scanning can improve prediction of insulin sensitivity (S_I) beyond what is possible with traditional measures, such as BMI, waist circumference, and waist‐to‐hip ratio (WHR). Research Methods and Procedures: Frequently sampled intravenous glucose tolerance tests were performed in 256 asymptomatic non‐Hispanic white subjects from Rochester, MN (age 19‐60 years; 123 men and 133 women) to determine the S_I index by Bergman's minimal model technique. Height, weight, and waist and hip circumferences were measured for calculation of BMI and WHR; DXA was used to determine fat in the head, upper body, abdomen, and lower body. Linear regression was used to assess their relationships with S_I after sex stratification and adjustment for age. Results: After controlling for age, increases in traditional and DXA measures of fat were consistently associated with smaller declines in S_I among women than among men. In men, after controlling for age, all of the predictive information of S_I was provided by waist circumference (additional R² = 0.39, p < 0.001); none of the DXA measures improved the ability to predict S_I. In women, after adjustment for age, BMI, and WHR, the only DXA measure that improved the prediction of S_I was percentage head fat (additional R² = 0.03, p < 0.001). Discussion: Equivalent increases in most measures of body fat had lesser impact on S_I in women than in men. In both sexes, the predictive information provided by DXA measures is approximately equal to, but not additive to, that provided by simpler, traditional measures.     

SD大鼠磁共振成像技术

目的：在常规磁共振成像仪（magnetic resonance imaging,MRI）上进行小型动物实验,探讨SD大鼠MRI最佳成像参数,为小型动物影像学实验研究提供参考.方法：采用西门子1.5T超导MR成像仪（Siemens Sonata, Erlangen, Germany）,膝关节专用线圈.选取雄性SD大鼠41只,体重250～400g,分5组依次进行T1加权（T1WI）、T2加权（T2WI）及质子密度加权成像,并比较5组参数成像的图像质量,确立Siemens Sonata 1.5T超导MR成像仪应用于大鼠的最佳成像参数.结果：T1WI采用SE序列、T2WI及质子密度加权采用TSE序列;T1WI、T2WI及质子密度加权的最佳成像参数分别为TR 350 ms/TE 12 ms、TR 2500 ms/TE 75 ms和TR 3000 ms/TE 15 ms.在MRI成像相关参数中,重复时间（TR）、回波时间（TE）主要影响对比度,决定权重;扫描野（FOV）、矩阵（Matrix）主要影响空间分辨率;层厚、激励次数（Nex）、带宽（Bandwidth）主要影响信噪比.结论：在常规MRI上进行小型动物实验切实可行,通过综合调节相应参数,不仅可以发现肝脏病变,证实了肝癌模型的成功建立,而且可以获得较理想的图像质量.