A Method for Accurate Reconstructions of the Upper Airway Using Magnetic Resonance Images

Objective

The purpose of this study is to provide an optimized method to reconstruct the structure of the upper airway (UA) based on magnetic resonance imaging (MRI) that can faithfully show the anatomical structure with a smooth surface without artificial modifications.

Methods

MRI was performed on the head and neck of a healthy young male participant in the axial, coronal and sagittal planes to acquire images of the UA. The level set method was used to segment the boundary of the UA. The boundaries in the three scanning planes were registered according to the positions of crossing points and anatomical characteristics using a Matlab program. Finally, the three-dimensional (3D) NURBS (Non-Uniform Rational B-Splines) surface of the UA was constructed using the registered boundaries in all three different planes.

Results

A smooth 3D structure of the UA was constructed, which captured the anatomical features from the three anatomical planes, particularly the location of the anterior wall of the nasopharynx. The volume and area of every cross section of the UA can be calculated from the constructed 3D model of UA.

Conclusions

A complete scheme of reconstruction of the UA was proposed, which can be used to measure and evaluate the 3D upper airway accurately.     

Infrequent Breakfast Consumption Is Associated with Higher Body Adiposity and Abdominal Obesity in Malaysian School-Aged Adolescents

Unhealthy dietary pattern increases the risk of obesity and metabolic disorders in growing children and adolescents. However, the way the habitual pattern of breakfast consumption influences body composition and risk of obesity in adolescents is not well defined. Thus, the aim of the present study was to assess any associations between breakfast consumption practices and body composition profiles in 236 apparently healthy adolescents aged 12 to 19 years. A self-administered questionnaire on dietary behaviour and lifestyle practices and a dietary food frequency questionnaire were used. Body composition and adiposity indices were determined using standard anthropometric measurement protocols and dual energy χ-ray absorptiometry (DXA). Mean age of the participants was 15.3±1.9 years. The majority of participants (71.2%) fell in the normal body mass index (BMI) ranges. Breakfast consumption patterns showed that only half of the participants (50%) were consuming breakfast daily. Gender-specific multivariate analyses (ANCOVA) showed that in both boys and girls, those eating breakfast at least 5 times a week had significantly lower body weight, body mass index (BMI), BMI z-scores, waist circumference, body fat mass and percent body fat (%BF) compared to infrequent breakfast eaters, after adjustment for age, household income, pubertal status, eating-out and snacking practices, daily energy intakes, and daily physical activity levels. The present findings indicate that infrequent breakfast consumption is associated with higher body adiposity and abdominal obesity. Therefore, daily breakfast consumption with healthy food choices should be encouraged in growing children and adolescents to prevent adiposity during these critical years of growth.     

Novel Gd Nanoparticles Enhance Vascular Contrast for High-Resolution Magnetic Resonance Imaging

Background

Gadolinium (Gd), with its 7 unpaired electrons in 4f orbitals that provide a very large magnetic moment, is proven to be among the best agents for contrast enhanced MRI. Unfortunately, the most potent MR contrast agent based on Gd requires relatively high doses of Gd. The Gd-chelated to diethylene-triamine-penta-acetic acid (DTPA), or other derivatives (at 0.1 mmole/kg recommended dose), distribute broadly into tissues and clear through the kidney. These contrast agents carry the risk of Nephrogenic Systemic Fibrosis (NSF), particularly in kidney impaired subjects. Thus, Gd contrast agents that produce higher resolution images using a much lower Gd dose could address both imaging sensitivity and Gd safety.

Methodology/Principal Findings

To determine whether a biocompatible lipid nanoparticle with surface bound Gd can improve MRI contrast sensitivity, we constructed Gd-lipid nanoparticles (Gd-LNP) containing lipid bound DTPA and Gd. The Gd-LNP were intravenously administered to rats and MR images collected. We found that Gd in Gd-LNP produced a greater than 33-fold higher longitudinal (T₁) relaxivity, r₁, constant than the current FDA approved Gd-chelated contrast agents. Intravenous administration of these Gd-LNP at only 3% of the recommended clinical Gd dose produced MRI signal-to-noise ratios of greater than 300 in all vasculatures. Unlike current Gd contrast agents, these Gd-LNP stably retained Gd in normal vasculature, and are eliminated predominately through the biliary, instead of the renal system. Gd-LNP did not appear to accumulate in the liver or kidney, and was eliminated completely within 24 hrs.

Conclusions/Significance

The novel Gd-nanoparticles provide high quality contrast enhanced vascular MRI at 97% reduced dose of Gd and do not rely on renal clearance. This new agent is likely to be suitable for patients exhibiting varying degrees of renal impairment. The simple and adaptive nanoparticle design could accommodate ligand or receptor coating for drug delivery optimization and in vivo drug-target definition in system biology profiling, increasing the margin of safety in treatment of cancers and other diseases.     

Evaluation of a Quantitative Magnetic Resonance Method for Mouse Whole Body Composition Analysis

Objective: To evaluate applicability, precision, and accuracy of a new quantitative magnetic resonance (QMR) analysis for whole body composition of conscious live mice. Research Methods and Procedures: Repeated measures of body composition were made by QMR, DXA, and classic chemical analysis of carcass using live and dead mice with different body compositions. Caloric lean and dense diets were used to produce changes in body composition. In addition, different strains of mice representing widely diverse populations were analyzed. Results: Precision was found to be better for QMR than for DXA. The coefficient of variation for fat ranged from 0.34% to 0.71% compared with 3.06% to 12.60% for DXA. Changes in body composition in response to dietary manipulation were easily detected using QMR. An increase in fat mass of 0.6 gram after 1 week (p < 0.01) was demonstrated in the absence of hyperphagia or a change in mean body weight. Discussion: QMR and DXA detected similar fat content, but the improved precision afforded by QMR compared with DXA and chemical analysis allowed detection of a significant difference in body fat after 7 days of consuming a diet rich in fat even though average body weight did not significantly change. QMR provides a very precise, accurate, fast, and easy‐to‐use method for determining fat and lean tissue of mice without the need for anesthesia. Its ability to detect differences with great precision should be of value when characterizing phenotype and studying regulation of body composition brought about by pharmacological and dietary interventions in energy homeostasis.     

Prediction of Depression in Individuals at High Familial Risk of Mood Disorders Using Functional Magnetic Resonance Imaging

Objective

Bipolar disorder is a highly heritable condition. First-degree relatives of affected individuals have a more than a ten-fold increased risk of developing bipolar disorder (BD), and a three-fold risk of developing major depressive disorder (MDD) than the general population. It is unclear however whether differences in brain activation reported in BD and MDD are present before the onset of illness.

Methods

We studied 98 young unaffected individuals at high familial risk of BD and 58 healthy controls using functional Magnetic Resonance Imaging (fMRI) scans and a task involving executive and language processing. Twenty of the high-risk subjects subsequently developed MDD after the baseline fMRI scan.

Results

At baseline the high-risk subjects who later developed MDD demonstrated relatively increased activation in the insula cortex, compared to controls and high risk subjects who remained well. In the healthy controls and high-risk group who remained well, this region demonstrated reduced engagement with increasing task difficulty. The high risk subjects who subsequently developed MDD did not demonstrate this normal disengagement. Activation in this region correlated positively with measures of cyclothymia and neuroticism at baseline, but not with measures of depression.

Conclusions

These results suggest that increased activation of the insula can differentiate individuals at high-risk of bipolar disorder who later develop MDD from healthy controls and those at familial risk who remain well. These findings offer the potential of future risk stratification in individuals at risk of mood disorder for familial reasons.     

Changes in Visceral Adiposity and Serum Cholesterol with a Novel Viscous Polysaccharide in Japanese Adults with Abdominal Obesity

Objective: Evidence supports the role of dietary fiber in improving metabolic health. PolyGlycopleX^® (PGX^®), a viscous functional polysaccharide improves lipidemia and glycemia in healthy adults. Our objective was to examine the effects of PGX^® on risk factors associated with the metabolic syndrome in Japanese adults with abdominal obesity. Design and Methods: Sixty four subjects assigned to 14 weeks of 15 g day^?1 of PGX^® or placebo were assessed in a randomized, double‐blind, placebo‐controlled, parallel group trial. At week 0 and 14, primary outcome measures were serum lipids, abdominal adiposity, glucose tolerance and blood pressure. Results: Total and LDL cholesterol were reduced at week 14 with PGX^® but not placebo (P < 0.05). The reduction in waist circumference at week 14 was greater with PGX^® versus placebo (P < 0.05). In females, abdominal visceral fat was decreased to a greater extent with PGX^® versus placebo (P < 0.05). While glucose tolerance worsened with placebo over time, PGX^® reduced glucose total area under the curve from week 0 to 6 (P = 0.039). Serum concentrations of resistin and IL6 increased slightly in placebo and decreased slightly with PGX^®. Conclusions: PGX^® is a functional fiber that shows promise in reducing risk factors related to the metabolic syndrome in Japanese adults with abdominal obesity.     

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.     

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.     

Evaluation of Multiparametric Magnetic Resonance Imaging in Detection and Prediction of Prostate Cancer

Background

Although European Society of Urogenital Radiology proposed the potential of multiparametric magnetic resonance imaging (MP-MRI) as a tool in the diagnostic pathway for prostate cancer (PCa) and published a unified scoring system named Prostate Imaging Reporting and Data System (PI-RADS version 1), these still need to be validated by real-life studies.

Objective

To evaluate the role of MP-MRI in detection and prediction of PCa.

Methods

Patients with clinical suspicion of PCa who underwent prebiopsy MP-MRI from 2002 to 2009 were recruited. MP-MRI results were retrospectively assigned as overall scores using PI-RADS by two radiologists. Patients were followed and the end point was the diagnosis of PCa. Receiver operating characteristics (ROC) curve was performed to test diagnostic efficacy of MP-MRI, under results of biopsy within three months. The cox proportional hazards model was used to identify independent variables for the detection of PCa.

Results

Finally, 1113 of the 1806 enrolled patients were included for analysis. The median follow-up was 56.0 months (1–137 mo). For 582 patients biopsied within three months, area under the curve for the detection of PCa with MP-MRI was 0.88 (95% confidence interval [CI], 0.75–1.00) in group of baseline prostate specific antigen (PSA) 0.01–4.00 ng/ml (n = 31), 0.90 (95% CI, 0.84–0.95) in PSA 4.01–10.00 ng/ml (n = 142), and 0.91 (95% CI, 0.87–0.94) in PSA >10.00 ng/ml (n = 409), respectively. In the cox model adjusted for age and baseline PSA level, for the detection rate of PCa, compared with PI-RADS 1–2 (reference), the hazard ratio was 6.43 (95% CI, 4.29–9.65) for PI-RADS 3, 18.58 (95% CI, 13.36–25.84) for PI-RADS 4–5 (p < 0.001).

Conclusions

Prebiopsy MP-MRI with PI-RADS is demonstrated as a valuable diagnostic and predictive tool for PCa.     

Quantitative Study of Liver Magnetic Resonance Spectroscopy Quality at 3T Using Body and Phased Array Coils with Physical Analysis and Clinical Evaluation

This study aims to investigate the quality difference of short echo time (TE) breathhold 1H magnetic resonance spectroscopy (MRS) of the liver at 3.0T using the body and phased array coils, respectively. In total, 20 pairs of single-voxel proton spectra of the liver were acquired at 3.0T using the phased array and body coils as receivers. Consecutive stacks of breathhold spectra were acquired using the point resolved spectroscopy (PRESS) technique at a short TE of 30 ms and a repetition time (TR) of 1500 ms. The first spectroscopy sequence was “copied” for the second acquisition to ensure identical voxel positioning. The MRS prescan adjustments of shimming and water suppression, signal-to noise ratio (SNR), and major liver quantitative information were compared between paired spectra. Theoretical calculation of the SNR and homogeneity of the region of interest (ROI, 2 cm×2 cm×2 cm) using different coils loaded with 3D liver electromagnetic model of real human body was implemented in the theoretical analysis. The theoretical analysis showed that, inside the ROI, the SNR of the phase array coil was 2.8387 times larger than that of body coil and the homogeneity of the phase array coil and body coil was 80.10% and 93.86%, respectively. The experimental results showed excellent correlations between the paired data (all r > 0.86). Compared with the body coil group, the phased array group had slightly worse shimming effect and better SNR (all P values < .01). The discrepancy of the line width because of the different coils was approximately 0.8 Hz (0.00625 ppm). No significant differences of the major liver quantitative information of Cho/Lip2 height, Cho/Lip2 area, and lipid content were observed (all P values >0.05). The theoretical analysis and clinical experiment showed that the phased array coil was superior to the body coil with respect to 3.0T breathhold hepatic proton MRS.     

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.     

A Novel Method for Prediction of Protein Domain Using Distance-Based Maximal Entropy

Detecting the boundaries of protein domains is an important and challenging task in both experimental and computational structural biology. In this paper, a promising method for detecting the domain structure of a protein from sequence information alone is presented. The method is based on analyzing multiple sequence alignments derived from a database search. Multiple measures are defined to quantify the domain information content of each position along the sequence. Then they are combined into a single predictor using support vector machine. What is more important, the domain detection is first taken as an imbal- anced data learning problem. A novel undersampling method is proposed on distance-based maximal entropy in the feature space of Support Vector Machine （SVM）. The overall precision is about 80%. Simulation results demonstrate that the method can help not only in predicting the complete 3D structure of a protein but also in the machine learning system on general im- balanced datasets.     

Development and Evaluation of an Algorithm for the Computer-Assisted Segmentation of the Human Hypothalamus on 7-Tesla Magnetic Resonance Images

Post mortem studies have shown volume changes of the hypothalamus in psychiatric patients. With 7T magnetic resonance imaging this effect can now be investigated in vivo in detail. To benefit from the sub-millimeter resolution requires an improved segmentation procedure. The traditional anatomical landmarks of the hypothalamus were refined using 7T T1-weighted magnetic resonance images. A detailed segmentation algorithm (unilateral hypothalamus) was developed for colour-coded, histogram-matched images, and evaluated in a sample of 10 subjects. Test-retest and inter-rater reliabilities were estimated in terms of intraclass-correlation coefficients (ICC) and Dice''s coefficient (DC). The computer-assisted segmentation algorithm ensured test-retest reliabilities of ICC≥.97 (DC≥96.8) and inter-rater reliabilities of ICC≥.94 (DC = 95.2). There were no significant volume differences between the segmentation runs, raters, and hemispheres. The estimated volumes of the hypothalamus lie within the range of previous histological and neuroimaging results. We present a computer-assisted algorithm for the manual segmentation of the human hypothalamus using T1-weighted 7T magnetic resonance imaging. Providing very high test-retest and inter-rater reliabilities, it outperforms former procedures established at 1.5T and 3T magnetic resonance images and thus can serve as a gold standard for future automated procedures.     

Accuracy and Reproducibility of Adipose Tissue Measurements in Young Infants by Whole Body Magnetic Resonance Imaging

PurposeMR might be well suited to obtain reproducible and accurate measures of fat tissues in infants. This study evaluates MR-measurements of adipose tissue in young infants in vitro and in vivo.ResultsIn vitro accuracy errors depended on the chosen segmentation procedure, ranging from 5.4% to 76%, while the sequence showed no significant influence. Artificial breathing increased the minimal accuracy error to 9.1%. In vivo reproducibility errors for total fat volume of the sleeping infants ranged from 2.6% to 3.4%. Neither segmentation nor sequence significantly influenced reproducibility.ConclusionWith both cartesian and PROPELLER sequences an accurate and reproducible measure of body fat was achieved. Adequate segmentation was mandatory for high accuracy.     

Quantitation and Localization of Regional Body Fat Distribution - A Comparison Between Magnetic Resonance Imaging and Somatometry

The emerging concept that various fat compartments are metabolically active and play separate and decisive roles in the pathogenesis of coronary atherosclerosis, hypertension, insulin resistance, diabetes and stroke, has given obesity research a new direction. Of particular interest is the relative amount of intra-abdominal fat thought to be responsible for the metabolic complications. We studied the precise fat distribution and its correlations with the metabolic parameters in 44 non-human primates (Macaca fascicularis). Intra-abdominal, subcutaneous, and total abdominal fat (IAF, SAF, TAF) were assessed by magnetic resonance imaging (MRI) and somatometry. Quantitative computer analyses of abdominal MRI scans revealed predominant IAF distribution. Box plot analysis of IAF and SAF revealed wide diversity in the amounts of fat, especially in monkeys with body mass index (BMI) <30 kg/m². Primates with similar BMI in each quartile revealed an extensive heterogeneity in IAF as well as SAF. Numerous significant correlations within site-specific somatometric measurements as well as within the MRI determinants of abdominal fat were seen. However, only body weight correlated with IAF and skinfolds could predict SAF. After adjusting for body weight, partial correlation analysis showed a significant correlation (P<0.05) between total cholesterol and IAF. Conclusion: MRI revealed considerable heterogeneity of IAF, SAF and TAF in a cohort of primates believed to be homogeneous by somatometric definition. Male cynomolgus monkeys appear to be a valuable model for a systematic evaluation of fat. Individuals with identical body weight and height may show a diverse pattern of fat distribution.