Low-dose CT imaging of a total hip arthroplasty phantom using model-based iterative reconstruction and orthopedic metal artifact reduction.

OBJECTIVE: To compare quantitative measures of image quality, in terms of CT number accuracy, noise, signal-to-noise-ratios (SNRs), and contrast-to-noise ratios (CNRs), at different dose levels with filtered-back-projection (FBP), iterative reconstruction (IR), and model-based iterative reconstruction (MBIR) alone and in combination with orthopedic metal artifact reduction (O-MAR) in a total hip arthroplasty (THA) phantom. MATERIALS AND METHODS: Scans were acquired from high- to low-dose (CTDIvol: 40.0, 32.0, 24.0, 16.0, 8.0, and 4.0 mGy) at 120- and 140- kVp. Images were reconstructed using FBP, IR (iDose4 level 2, 4, and 6) and MBIR (IMR, level 1, 2, and 3) with and without O-MAR. CT number accuracy in Hounsfield Units (HU), noise or standard deviation, SNRs, and CNRs were analyzed. RESULTS: The IMR technique showed lower noise levels (p < 0.01), higher SNRs (p < 0.001) and CNRs (p < 0.001) compared with FBP and iDose4 in all acquisitions from high- to low-dose with constant CT numbers. O-MAR reduced noise (p < 0.01) and improved SNRs (p < 0.01) and CNRs (p < 0.001) while improving CT number accuracy only at a low dose. At the low dose of 4.0 mGy, IMR level 1, 2, and 3 showed 83%, 89%, and 95% lower noise values, a factor 6.0, 9.2, and 17.9 higher SNRs, and 5.7, 8.8, and 18.2 higher CNRs compared with FBP respectively. CONCLUSIONS: Based on quantitative analysis of CT number accuracy, noise values, SNRs, and CNRs, we conclude that the combined use of IMR and O-MAR enables a reduction in radiation dose of 83% compared with FBP and iDose4 in the CT imaging of a THA phantom.

Quantifying metal artefact reduction using virtual monochromatic dual-layer detector spectral CT imaging in unilateral and bilateral total hip prostheses.

PURPOSE: To quantify the impact of prosthesis material and design on the reduction of metal artefacts in total hip arthroplasties using virtual monochromatic dual-layer detector Spectral CT imaging. METHODS: The water-filled total hip arthroplasty phantom was scanned on a novel 128-slice Philips IQon dual-layer detector Spectral CT scanner at 120-kVp and 140-kVp at a standard computed tomography dose index of 20.0mGy. Several unilateral and bilateral hip prostheses consisting of different metal alloys were inserted and combined which were surrounded by 18 hydroxyapatite calcium carbonate pellets representing bone. Images were reconstructed with iterative reconstruction and analysed at monochromatic energies ranging from 40 to 200keV. CT numbers in Hounsfield Units (HU), noise measured as the standard deviation in HU, signal-to-noise-ratios (SNRs) and contrast-to-noise-ratios (CNRs) were analysed within fixed regions-of-interests placed in and around the pellets. RESULTS: In 70 and 74keV virtual monochromatic images the CT numbers of the pellets were similar to 120-kVp and 140-kVp polychromatic results, therefore serving as reference. A separation into three categories of metal artefacts was made (no, mild/moderate and severe) where pellets were categorized based on HU deviations. At high keV values overall image contrast was reduced. For mild/moderate artefacts, the highest average CNRs were attained with virtual monochromatic 130keV images, acquired at 140-kVp. Severe metal artefacts were not reduced. In 130keV images, only mild/moderate metal artefacts were significantly reduced compared to 70 and 74keV images. Deviations in CT numbers, noise, SNRs and CNRs due to metal artefacts were decreased with respectively 64%, 57%, 62% and 63% (p<0.001) compared to unaffected pellets. Optimal keVs, based on CNRs, for different unilateral and bilateral metal hip prostheses consisting of different metal alloys varied from 74 to 150keV. The Titanium alloy resulted in less severe artefacts and were reduced more effectively compared to the Cobalt alloy. CONCLUSIONS: Virtual monochromatic dual-layer Spectral CT imaging results in a significant reduction of streak artefacts produced by beam-hardening in mild and moderate artefacts by improving CT number accuracy, SNRs and CNRs, while decreasing noise values in a total hip arthroplasty phantom. An optimal monochromatic energy of 130keV was found ranging from 74keV to 150keV for different unilateral and bilateral hip prostheses consisting of different metal alloys.

Quantitative MRI and strength measurements in the assessment of muscle quality in Duchenne muscular dystrophy.

The purpose of this study was to assess leg muscle quality and give a detailed description of leg muscle involvement in a series of Duchenne muscular dystrophy patients using quantitative MRI and strength measurements. Fatty infiltration, as well as total and contractile (not fatty infiltrated) cross sectional areas of various leg muscles were determined in 16 Duchenne patients and 11 controls (aged 8-15). To determine specific muscle strength, four leg muscle groups (quadriceps femoris, hamstrings, anterior tibialis and triceps surae) were measured and related to the amount of contractile tissue. In patients, the quadriceps femoris showed decreased total and contractile cross sectional area, attributable to muscle atrophy. The total, but not the contractile, cross sectional area of the triceps surae was increased in patients, corresponding to hypertrophy. Specific strength decreased in all four muscle groups of Duchenne patients, indicating reduced muscle quality. This suggests that muscle hypertrophy and fatty infiltration are two distinct pathological processes, differing between muscle groups. Additionally, the quality of remaining muscle fibers is severely reduced in the legs of Duchenne patients. The combination of quantitative MRI and quantitative muscle testing could be a valuable outcome parameter in longitudinal studies and in the follow-up of therapeutic effects.

Convergence of HbA1c values towards target in 272 primary care patients following nine years of target-driven care.

BACKGROUND: We wished to determine the effect of a target-driven incentivised programme on haemoglobin A1c (HbA1c ) values in a UK diabetic population. METHODS: An audit was carried out in 1999-2000, which included an estimation of glycaemic control in a randomly selected diabetic cohort from ten primary care practices in Sutton Coldfield, serving a population of 90 000 patients. Each practice was given a randomised list of patients and asked to complete detailed questionnaires on patients with confirmed diabetes. We collected data on 516 patients, 425 of whom had their HbA1c measured in 1999-2000 (Audit 2000). A re-audit of HbA1c was carried out in 2007-08 (Audit 2008) determining the changes in HbA1c since the original audit. Of the original cohort, 272 patients had an audit of HbA1c carried out in Audit 2008. RESULTS: Overall, a small increase in median and mean HbA1c values was observed. We estimated that the proportion of patients with HbA1c achieving the lower Quality and Outcomes Framework HbA1c target of < 7.5%; 173 of the 272 patients met this target in Audit 2000, whereas the number was 162 in Audit 2008. To understand the changes observed, patients were stratified as quintiles based on the HbA1c in Audit 2000 and changes in HbA1c after 8 years for each quintile were estimated. The mean changes for the different quintiles are: quintile 1 (HbA1c < 6.1%), +1.49%; quintile 2 (HbA1c 6.1- 6.6%), +0.8%; quintile 3 (HbA1c 6.7-7.3%), +0.3%; quintile 4 (HbA1c 7.4-8.5%), -0.18%; and quintile 5 (HbA1c > 8.5%), -1.55%. CONCLUSION: Our results suggest that, eight years on, patients with poor glycaemic control in 2000 saw an overall decrease in HbA1c by 2008, with the reverse seen in patients with good control.

Magnetization transfer imaging in premanifest and manifest huntington disease: a 2-year follow-up.

BACKGROUND AND PURPOSE: MTI is a quantitative MR imaging technique that has recently demonstrated structural integrity differences between controls and patients with HD. Potentially, MTI can be used as a biomarker for monitoring disease progression. To establish the value of MTI as a biomarker, we aimed to examine the change in these measures during the course of HD. MATERIALS AND METHODS: From the Leiden TRACK-HD study, 25 controls, 21 premanifest gene carriers, and 21 patients with manifest HD participated at baseline and during a 2-year follow-up visit. Brain segmentation of the cortical gray matter, white matter, caudate nucleus, putamen, pallidum, thalamus, amygdala, and hippocampus was performed by using the automated tools FAST and FIRST in FSL. Individual MTR values were calculated from these regions, and MTR histograms were constructed. RESULTS: In the premanifest HD group stage "far from disease onset," a significant increase in MTR peak height of the putamen was observed with time. During the manifest HD stage, neither the mean MTR nor the MTR peak height showed a significant change during a 2-year follow-up. CONCLUSIONS: MTI-derived measures are not suitable for monitoring in Huntington disease during a 2-year period because there was no decrease in structural integrity detected in any of the manifest HD groups longitudinally. The finding of increased putaminal MTR peak height in the premanifest far from disease onset group could relate to a predegenerative process, compensatory mechanisms, or aberrant development but should be interpreted with caution until future studies confirm this finding.

Magnetization transfer imaging in premanifest and manifest Huntington disease.

BACKGROUND AND PURPOSE: MTI has the potential to detect abnormalities in normal-appearing white and gray matter on conventional MR imaging. Early detection methods and disease progression markers are needed in HD research. Therefore, we investigated MTI parameters and their clinical correlates in premanifest and manifest HD. MATERIALS AND METHODS: From the Leiden TRACK-HD study, 78 participants (28 controls, 25 PMGC, 25 MHD) were included. Brain segmentation of cortical gray matter, white matter, caudate nucleus, putamen, pallidum, thalamus, amygdala, and hippocampus was performed using FSL's automated tools FAST and FIRST. Individual MTR values were calculated from these regions and MTR histograms constructed. Regression analysis of MTR measures from all gene carriers with clinical measures was performed. RESULTS: MTR peak height was reduced in both cortical gray (P = .01) and white matter (P = .006) in manifest HD compared with controls. Mean MTR was also reduced in cortical gray matter (P = .01) and showed a trend in white matter (P = .052). Deep gray matter structures showed a uniform pattern of reduced MTR values (P < .05). No differences between premanifest gene carriers and controls were found. MTR values correlated with disease burden and motor and cognitive impairment. CONCLUSIONS: Throughout the brain, disturbances in MTI parameters are apparent in early HD and are homogeneous across white and gray matter. The correlation of MTI with clinical measures indicates the potential to act as a disease monitor in clinical trials. However, our study does not provide evidence for MTI as a marker in premanifest HD.

Shape analysis of subcortical nuclei in Huntington's disease, global versus local atrophy--results from the TRACK-HD study.

Huntington's disease (HD) is characterized by brain atrophy. Localized atrophy of a specific structure could potentially be a more sensitive biomarker reflecting neuropathologic changes rather than global volume variation. We examined 90 TRACK-HD participants of which 30 were premanifest HD, 30 were manifest HD and 30 were controls. Using FMRIB's Integrated Registration and Segmentation Tool, segmentations were obtained for the pallidum, caudate nucleus, putamen, thalamus, accumbens nucleus, amygdala, and hippocampus and overall volumes were calculated. A point distribution model of each structure was obtained using Growing and Adaptive Meshes. Permutation testing between groups was performed to detect local displacement in shape between groups. In premanifest HD overall volume loss occurred in the putamen, accumbens and caudate nucleus. Overall volume reductions in manifest HD were found in all subcortical structures, except the amygdala, as compared to controls. In premanifest HD shape analysis showed small areas of displacement in the putamen, pallidum, accumbens and caudate nucleus. When the premanifest group was split into two groups according to predicted disease onset, the premanifest HD group close to expected disease onset showed more pronounced displacements in caudate nucleus and putamen compared to premanifest HD far from disease onset or the total premanifest group. Analysis of shape in manifest HD showed widespread shape differences, most prominently in the caudal part of the accumbens nucleus, body of the caudate nucleus, putamen and dorsal part of the pallidum. We conclude that shape analysis provides new insights in localized intrastructural atrophy patterns in HD, but can also potentially serve as specific target areas for disease tracking.

Non-parametric model selection for subject-specific topological organization of resting-state functional connectivity.

In recent years, graph theory has been successfully applied to study functional and anatomical connectivity networks in the human brain. Most of these networks have shown small-world topological characteristics: high efficiency in long distance communication between nodes, combined with highly interconnected local clusters of nodes. Moreover, functional studies performed at high resolutions have presented convincing evidence that resting-state functional connectivity networks exhibits (exponentially truncated) scale-free behavior. Such evidence, however, was mostly presented qualitatively, in terms of linear regressions of the degree distributions on log-log plots. Even when quantitative measures were given, these were usually limited to the r(2) correlation coefficient. However, the r(2) statistic is not an optimal estimator of explained variance, when dealing with (truncated) power-law models. Recent developments in statistics have introduced new non-parametric approaches, based on the Kolmogorov-Smirnov test, for the problem of model selection. In this work, we have built on this idea to statistically tackle the issue of model selection for the degree distribution of functional connectivity at rest. The analysis, performed at voxel level and in a subject-specific fashion, confirmed the superiority of a truncated power-law model, showing high consistency across subjects. Moreover, the most highly connected voxels were found to be consistently part of the default mode network. Our results provide statistically sound support to the evidence previously presented in literature for a truncated power-law model of resting-state functional connectivity.

A circadian rhythm sleep disorder: melatonin resets the biological clock.

Circadian rhythm sleep disorders are poorly understood and often misdiagnosed. They are all related to the timing of sleep within the 24-hour day. This paper describes a patient with a long history of sleep disturbance whom we diagnosed as having delayed sleep phase syndrome by history and measurement of urinary melatonin metabolite excretion. Literature on the characteristics, diagnosis and management of this syndrome are briefly reviewed. In addition, the relation of the neurohormone melatonin to circadian rhythm and its other physiological roles are described.

Mapping displacement and deformation of the heart with local sine-wave modeling.

The new SinMod method extracts motion from magnetic resonance imaging (MRI)-tagged (MRIT) image sequences. Image intensity in the environment of each pixel is modeled as a moving sine wavefront. Displacement is estimated at subpixel accuracy. Performance is compared with the harmonic-phase analysis (HARP) method, which is currently the most common method used to detect motion in MRIT images. SinMod can handle line tags, as well as speckle patterns. In artificial images (tag distance six pixels), SinMod detects displacements accurately (error < 0.02 pixels). Effects of noise are suppressed effectively. Sharp transitions in motion at the boundary of an object are smeared out over a width of 0.6 tag distance. For MRIT images of the heart, SinMod appears less sensitive to artifacts, especially later in the cardiac cycle when image quality deteriorates. For each pixel, the quality of the sine-wave model in describing local image intensity is quantified objectively. If local quality is low, artifacts are avoided by averaging motion over a larger environment. Summarizing, SinMod is just as fast as HARP, but it performs better with respect to accuracy of displacement detection, noise reduction, and avoidance of artifacts.

Fully automated registration of first-pass myocardial perfusion MRI using independent component analysis.

This paper presents a novel method for registration of cardiac perfusion MRI. The presented method successfully corrects for breathing motion without any manual interaction using Independent Component Analysis to extract physiologically relevant features together with their time-intensity behavior. A time-varying reference image mimicking intensity changes in the data of interest is computed based on the results of ICA, and used to compute the displacement caused by breathing for each frame. Qualitative and quantitative validation of the method is carried out using 46 clinical quality, short-axis, perfusion MR datasets comprising 100 images each. Validation experiments showed a reduction of the average LV motion from 1.26+/-0.87 to 0.64+/-0.46 pixels. Time-intensity curves are also improved after registration with an average error reduced from 2.65+/-7.89% to 0.87+/-3.88% between registered data and manual gold standard. We conclude that this fully automatic ICA-based method shows an excellent accuracy, robustness and computation speed, adequate for use in a clinical environment.

Paradoxical HDL-C reduction during rosiglitazone and fibrate treatment.

AIMS: Dyslipidaemia in Type 2 diabetes mellitus (T2DM) is one of the major contributors in the pathogenesis of atherosclerosis. Thiazolidinediones (TZD), a class of drugs used in the treatment of T2DM, also modify lipids, especially lowering serum triglycerides and raising high-density lipoprotein cholesterol (HDL-C). METHODS: We describe five patients taking rosiglitazone and a fibrate who showed a paradoxical fall in HDL-C, which would have been missed if HDL-C had not been routinely monitored. This could have had a major impact in increasing the cardiovascular risk in these patients. RESULTS: Our five patients showed marked variation in both the decrease in serum HDL-C (50-89%) and also in the time taken for recovery of HDL-C after withdrawal of rosiglitazone (between 5 and 20 weeks). Apolipoprotein A1 mirrored the drop in HDL-C in four of the five patients but in one subject this was not seen, suggesting the possibility of multiple mechanisms leading to the phenomenon described, perhaps involving HDL metabolism. Improvements in glycaemic control with rosiglitazone (absolute HbA(1c) reduction between 0.6 and 3.0%) were seen in four of our patients. This suggests that the peroxisomal proliferator-activated receptor gamma signalling pathways relevant to glucose homeostasis were intact. CONCLUSION: As atherosclerosis is associated with a decrease in the HDL-C level, our observations reinforce the message that HDL-C should be measured before and after the commencement of rosiglitazone and also on increasing the dosage

Development of a proteomic approach to monitor protein synthesis in mycotoxin producing moulds.

In general, proteome studies compare different states of metabolism to investigate external or internal influences on protein expression. In the context of mycotoxin production the method could open another view on this complex and could be helpful to gain knowledge about proteins which are involved in metabolism (enzymes, transporters). In this short technical report, we describe a new protocol suitable for protein preparation for whole proteome analysis ofFusarium graminearum. Cell lysis was performed by grinding the mycelium with liquid nitrogen. Proteins were extracted with TCA/acetone and then cleaned; the isolated proteins were separated in a 2D-gel electrophoresis system (BioRad) using different pH gradients. The protocol established seems also generally applicable for other mycotoxin producing fungi.

Simple and efficient cell disruption of extremely small quantities of mycelium of phytopathogenic mycotoxin-producing moulds for quantitative extraction of genomic DNA.

DNA was efficiently and quantitatively isolated from extremely small quantities of mycelia (0.1-10 mg) of different phytopathogenic moulds by grinding freeze-dried mycelia with glass beads and then using a commercial DNA extraction kit. The efficiency of disruption of the mycelia and the quantitative DNA extraction was proved by microscopy and the quantification of isolated DNA by real time PCR.

Development of a thyroid function strategy for general practice.

A study was carried out to investigate a thyroid stimulating hormone (TSH) frontline strategy that could potentially result in a more straightforward interpretation of thyroid function tests, a reduction in the number of inappropriate referrals to medical outpatients, an improvement in the 'turnaround time' of results, and a reduction in the number of unnecessary tests carried out, thereby reducing costs.

Lipoprotein subfraction composition in non-insulin-dependent diabetes treated by diet, sulphonylurea, and insulin.

Lipoprotein abnormalities may predispose to an increased risk of coronary heart disease in type II (non-insulin-dependent) diabetes mellitus. To investigate the effects of different treatment modalities, the composition and concentrations of fasting plasma lipoproteins were determined in a cross-sectional study of patients with type II diabetes at diagnosis, treated by diet alone, treated by diet + glibenclamide (2.5 to 15 mg/d for 6 to 48 months), and treated by diet + insulin (25 to 65 U/d for 8 to 144 months). Compared with normal subjects matched for sex, age, body mass index, exercise, alcohol consumption and smoking, type II patients at diagnosis showed increased concentrations of nonesterified and esterified cholesterol, triglyceride, phospholipid, and protein in the very low density lipoprotein (VLDL) fraction. However, the only alteration in VLDL composition was a small decrease in the relative proportion of phospholipid. Apolipoprotein-B and low density lipoprotein (LDL) cholesterol concentrations were also raised in type II patients at diagnosis. Plasma concentrations of high density lipoprotein (HDL) nonesterified and esterified cholesterol, phospholipid, and apo-AI were lower in type II patients at diagnosis. This was largely accounted for by reduced concentrations of these components in the HDL2 subfraction, which retained a normal composition. Type II patients treated by diet alone and diet + glibenclamide exhibited similar abnormalities of plasma lipoprotein concentrations, which are associated with premature coronary disease, to the type II patients at diagnosis. However, in type II patients treated with insulin, plasma lipoprotein concentrations and composition were normal, except LDL cholesterol, which was lower than normal in insulin-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein assays: methodological considerations and studies in non-insulin-dependent diabetes treated by diet, glibenclamide and insulin.

The effect of sample pre-treatment as a source of variability of apolipoprotein (apo) AI, AII and B assays was demonstrated with lipid dissociating agents. The average mean percentage change ranged from -58 to +133% compared with untreated samples. The apolipoprotein method selected was validated by comparing their concentrations with their corresponding lipoprotein lipid or protein in normal controls and Type 2 (non-insulin-dependent) diabetic patients. The coefficient of variation was maintained below 3.5% for apo AI, AII, B and HDL2-apo AI. The apolipoprotein concentrations of fasting plasma lipoproteins were determined in a cross-sectional study of non-obese (body-mass index less than or equal to 30) patients with Type 2 diabetes mellitus. Compared with normal subjects matched for sex, age, body-mass index, exercise, alcohol consumption and smoking. Type 2 patients at diagnosis showed reduced apo AI and HDL2-apo AI concentrations, lowered apo AI:B ratio and increased concentrations of apo B. Type 2 patients treated by diet alone (for 6-72 months) and diet plus glibenclamide (2.5-15 mg/day for 6-48 months) exhibited similar abnormalities of plasma apolipoprotein concentration to Type 2 patients at diagnosis. However, in Type 2 patients treated with insulin (25-65 U/day for 8-144 months) concentrations of apo AI and HDL2-apo AI, and the apo AI:B ratio were normal. Apo B concentrations were generally lower compared with all groups of non-insulin treated patients. These abnormalities of apolipoprotein metabolism, which are associated with premature coronary disease, are still evident in patients treated by diet and diet plus glibenclamide, but are not seen in Type 2 patients treated with insulin.