1,147 research outputs found
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Impact of physiological noise correction on detecting blood oxygenation level-dependent contrast in the breast.
Physiological fluctuations are expected to be a dominant source of noise in blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) experiments to assess tumour oxygenation and angiogenesis. This work investigates the impact of various physiological noise regressors: retrospective image correction (RETROICOR), heart rate (HR) and respiratory volume per unit time (RVT), on signal variance and the detection of BOLD contrast in the breast in response to a modulated respiratory stimulus. BOLD MRI was performed at 3 T in ten volunteers at rest and during cycles of oxygen and carbogen gas breathing. RETROICOR was optimized using F-tests to determine which cardiac and respiratory phase terms accounted for a significant amount of signal variance. A nested regression analysis was performed to assess the effect of RETROICOR, HR and RVT on the model fit residuals, temporal signal-to-noise ratio, and BOLD activation parameters. The optimized RETROICOR model accounted for the largest amount of signal variance ([Formula: see text] = 3.3 ± 2.1%) and improved the detection of BOLD activation (P = 0.002). Inclusion of HR and RVT regressors explained additional signal variance, but had a negative impact on activation parameter estimation (P < 0.001). Fluctuations in HR and RVT appeared to be correlated with the stimulus and may contribute to apparent BOLD signal reactivity.This work was supported by the NIHR Cambridge Biomedical Research Centre, the Cambridge Experimental Cancer Medicine Centre and the CRUK-EPSRC Cancer Imaging Centre in Cambridge and Manchester (C197/A16465 and C8742/A18097)
Imaging Carotid Atherosclerosis Plaque Ulceration: Comparison of Advanced Imaging Modalities and Recent Developments.
Atherosclerosis remains the leading cause of long-term mortality and morbidity worldwide, despite remarkable advancement in its management. Vulnerable atherosclerotic plaques are principally responsible for thromboembolic events in various arterial territories such as carotid, coronary, and lower limb vessels. Carotid plaque ulceration is one of the key features associated with plaque vulnerability and is considered a notable indicator of previous plaque rupture and possible future cerebrovascular events. Multiple imaging modalities have been used to assess the degree of carotid plaque ulceration for diagnostic and research purposes. Early diagnosis and management of carotid artery disease could prevent further cerebrovascular events. In this review, we highlight the merits and limitations of various imaging techniques for identifying plaque ulceration
The high costs of getting ethical and site-specific approvals for multi-centre research.
BACKGROUND: Multi-centre studies generally cost more than single-centre studies because of larger sample sizes and the need for multiple ethical approvals. Multi-centre studies include clinical trials, clinical quality registries, observational studies and implementation studies. We examined the costs of two large Australian multi-centre studies in obtaining ethical and site-specific approvals. METHODS: We collected data on staff time spent on approvals and expressed the overall cost as a percent of the total budget. RESULTS: The total costs of gaining approval were 38 % of the budget for a study of 50 centres (mean cost AUD 2300 per site). Seventy-five and 90 % of time was spent on repeated tasks, respectively, and many time-consuming tasks, such as reformatting documents, did nothing to improve the study design or participant safety. CONCLUSIONS: Improvements have been made to the ethical approval application system, but more gains could be made without increasing risks of harm to research participants. We propose that ethical review bodies and individual sites publish statistics on how long they take to process approvals which could then be nationally benchmarked
Dynamic contrast-enhanced MRI of synovitis in knee osteoarthritis: repeatability, discrimination and sensitivity to change in a prospective experimental study
OBJECTIVES: Evaluate test-retest repeatability, ability to discriminate between osteoarthritic and healthy participants, and sensitivity to change over 6 months, of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) biomarkers in knee OA. METHODS: Fourteen individuals aged 40-60 with mild-moderate knee OA and 6 age-matched healthy volunteers (HV) underwent DCE-MRI at 3 T at baseline, 1 month and 6 months. Voxelwise pharmacokinetic modelling of dynamic data was used to calculate DCE-MRI biomarkers including Ktrans and IAUC60. Median DCE-MRI biomarker values were extracted for each participant at each study visit. Synovial segmentation was performed using both manual and semiautomatic methods with calculation of an additional biomarker, the volume of enhancing pannus (VEP). Test-retest repeatability was assessed using intraclass correlation coefficients (ICC). Smallest detectable differences (SDDs) were calculated from test-retest data. Discrimination between OA and HV was assessed via calculation of between-group standardised mean differences (SMD). Responsiveness was assessed via the number of OA participants with changes greater than the SDD at 6 months. RESULTS: Ktrans demonstrated the best test-retest repeatability (Ktrans/IAUC60/VEP ICCs 0.90/0.84/0.40, SDDs as % of OA mean 33/71/76%), discrimination between OA and HV (SMDs 0.94/0.54/0.50) and responsiveness (5/1/1 out of 12 OA participants with 6-month change > SDD) when compared to IAUC60 and VEP. Biomarkers derived from semiautomatic segmentation outperformed those derived from manual segmentation across all domains. CONCLUSIONS: Ktrans demonstrated the best repeatability, discrimination and sensitivity to change suggesting that it is the optimal DCE-MRI biomarker for use in experimental medicine studies. KEY POINTS: • Dynamic contrast-enhanced MRI (DCE-MRI) provides quantitative measures of synovitis in knee osteoarthritis which may permit early assessment of efficacy in experimental medicine studies. • This prospective observational study compared DCE-MRI biomarkers across domains relevant to experimental medicine: test-retest repeatability, discriminative validity and sensitivity to change. • The DCE-MRI biomarker Ktrans demonstrated the best performance across all three domains, suggesting that it is the optimal biomarker for use in future interventional studies
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Feasibility of metabolic imaging of hyperpolarized 13C-pyruvate in human breast cancer
Introduction
Imaging of the breast with hyperpolarized 13C yields new challenges compared to imaging the prostate [1]. E.g. large anteroposterior B0 gradients [2] require correction and the anatomy and patient positioning need a new, highly optimized RF coil array for achieving sufficient SNR/spatial resolution. As a first step, we have investigated single-breast imaging in the coronal plane.
Methods
A BRCA gene carrier with a 38-mm diameter grade 3 triple-negative invasive ductal carcinoma was studied on a 3T MRI (GE Healthcare) using a prototype 8-channel 13C breast coil (Rapid Biomedical), containing 2 transmit/receive coils and 6 receive-only covering both breasts in a prone position. 1H imaging was performed with the body coil. Following injection of 40ml of 250mM 13C-pyruvate, polarized to c. 25%, a 1-minute time series of spirals with IDEAL encoding (3) was collected (flip angle 10°, TR=260ms, 8-step cycle, time resolution 2.08s, 3 x 3-cm thick slices, 3mm gap, 40-pt spiral, 24cm coronal FOV, real pixel size 12 x 12 x 30mm). IDEAL reconstruction of images was optimized separately for each slice to enable independent frequency offsets to be applied. Kinetic modelling was performed in MATLAB, with automated tumour segmentation.
Results
Tumour pixels were identified by the segmentation algorithm only in the tumour-containing slice 2, and the average estimated flux from pyruvate to lactate kPL within this ROI was 0.022 s-1 (Fig. 1). The frequency shift of pyruvate relative to slice 2 was +6 Hz in slice 3 and -34 Hz in slice 1, confirming a sharp gradient in B0 approaching the nipple, which was corrected by optimizing slices separately (Fig 2). Images of lactate and pyruvate summed over the time course (Fig 3) showed strong signal of both metabolites over the tumour in slice 2, lower pyruvate in the slice toward the chest wall, and no consistent signal in slice 1.
Conclusion
This first-in-Europe study in breast cancer established the feasibility of obtaining metabolite images with high temporal and moderate spatial resolution in humans in vivo following administration of hyperpolarized 13C-pyruvate. Coronal image orientation allowed application of significant corrections for a known limitation, the anteroposterior B0 gradient, as well as a small FOV to improve spatial resolution. Kinetic rate constants within the tumour were found to be consistent with previous reports in human prostate cancer (1).
References
1) Nelson SJ et al. Sci Transl Med 5, 198ra108 (2013). 2) Maril N, et al. Magn. Reson. Med. 2005; 54:1139-1145. 3) Wiesinger F, et al. Magn Reson Med 2012; 68:8-16
Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive Motivation
FUNDING AND DISCLOSURE The research was funded by Wellcome Trust (WT098012) to LKH; and National Institute of Health (DK056731) and the Marilyn H. Vincent Foundation to MGM. The University of Michigan Transgenic Core facility is partially supported by the NIH-funded University of Michigan Center for Gastrointestinal Research (DK034933). The remaining authors declare no conflict of interest. ACKNOWLEDGMENTS We thank Dr Celine Cansell, Ms Raffaella Chianese and the staff of the Medical Research Facility for technical assistance. We thank Dr Vladimir Orduña for the scientific advice and technical assistance.Peer reviewedPublisher PD
The Status of Dosage Compensation in the Multiple X Chromosomes of the Platypus
Dosage compensation has been thought to be a ubiquitous property of sex chromosomes that are represented differently in males and females. The expression of most X-borne genes is equalized between XX females and XY males in therian mammals (marsupials and “placentals”) by inactivating one X chromosome in female somatic cells. However, compensation seems not to be strictly required to equalize the expression of most Z-borne genes between ZZ male and ZW female birds. Whether dosage compensation operates in the third mammal lineage, the egg-laying monotremes, is of considerable interest, since the platypus has a complex sex chromosome system in which five X and five Y chromosomes share considerable genetic homology with the chicken ZW sex chromosome pair, but not with therian XY chromosomes. The assignment of genes to four platypus X chromosomes allowed us to examine X dosage compensation in this unique species. Quantitative PCR showed a range of compensation, but SNP analysis of several X-borne genes showed that both alleles are transcribed in a heterozygous female. Transcription of 14 BACs representing 19 X-borne genes was examined by RNA-FISH in female and male fibroblasts. An autosomal control gene was expressed from both alleles in nearly all nuclei, and four pseudoautosomal BACs were usually expressed from both alleles in male as well as female nuclei, showing that their Y loci are active. However, nine X-specific BACs were usually transcribed from only one allele. This suggests that while some genes on the platypus X are not dosage compensated, other genes do show some form of compensation via stochastic transcriptional inhibition, perhaps representing an ancestral system that evolved to be more tightly controlled in placental mammals such as human and mouse
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