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

Comparison of breath-hold, respiratory navigated and free-breathing MR elastography of the liver

$\textit{Purpose:}$ Hepatic magnetic resonance elastography (MRE) is currently a breath-hold imaging technique. Patients with chronic liver disease can have comorbidities that limit their ability to breath-hold (BH) for the required acquisition time. Our aim was to evaluate whether stiffness measurements obtained from a navigator-triggered MRE acquisition are comparable to standard expiratory breath-hold, inspiratory breath-hold or free-breathing in healthy participants. $\textit{Materials and methods:}$ Twelve healthy participants were imaged using the four methods on a clinical 1.5 T MR system equipped with a product MRE system. Mean liver stiffness, and measurable area of stiffness (with a confidence threshold >95%) were compared between sequences using the concordance correlation coefficient. Repeatability of each sequence between two acquisitions was also assessed. $\textit{Results:}$ The standard BH expiratory technique had high concordance with the navigated technique (r = 0.716), and low concordance with the BH inspiration (r = 0.165) and free-breathing (r = 0.105) techniques. The navigator-triggered technique showed no statistical difference in measurable area of liver or in repeatability compared with the standard expiratory acquisition (p = 0.997 and p = 0.407 respectively). The free-breathing technique produced less measurable liver area and was less repeatable than the alternative techniques. The increase in acquisition time for navigator techniques was 3 min 6 s compared to standard expiratory breath-hold. $\textit{Conclusion:}$ Navigator-based hepatic MRE measurements are comparable to the reference standard expiratory breath-hold acquisition in healthy participants.This work was supported by the Addenbrooke's Charitable Trust and the NIHR Comprehensive Biomedical Research Centre award to Cambridge University Hospitals NHS Foundation Trust in partnership with the University of Cambridge

Amniotic fluid volume: Rapid MR-based assessment at 28-32 weeks gestation.

OBJECTIVES: This work evaluates rapid magnetic resonance projection hydrography (PH) based amniotic fluid volume (AFV) estimates against established routine ultrasound single deepest vertical pocket (SDVP) and amniotic fluid index (AFI) measurements, in utero at 28-32 weeks gestation. Manual multi-section planimetry (MSP) based measurement of AFV is used as a proxy reference standard. METHODS: Thirty-five women with a healthy singleton pregnancy (20-41 years) attending routine antenatal ultrasound were recruited. SDVP and AFI were measured using ultrasound, with same day MRI assessing AFV with PH and MSP. The relationships between the respective techniques were assessed using linear regression analysis and Bland-Altman method comparison statistics. RESULTS: When comparing estimated AFV, a highly significant relationship was observed between PH and the reference standard MSP (R(2) = 0.802, p < 0.001). For the US measurements, SDVP measurement related most closely to amniotic fluid volume, (R(2) = 0.470, p < 0.001), with AFI demonstrating a weaker relationship (R(2) = 0.208, p = 0.007). CONCLUSION: This study shows that rapid MRI based PH measurement is a better predictor of AFV, relating more closely to our proxy standard than established US techniques. Although larger validation studies across a range of gestational ages are required this approach could form part of MR fetal assessment, particularly where poly- or oligohydramnios is suspected. KEY POINTS: • MR projection hydrography can be used to estimate amniotic fluid volume. • MR projection hydrography relies on the T2w signal from amniotic fluid. • Amniotic fluid volume (AFV) is more accurately assessed than with ultrasound.This study was supported by the National Institute of Health Research, Cambridge Biomedical Research Centre. The authors also acknowledge the support of Addenbrooke’s Charitable Trust and thank the participants for their contribution to the study.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s00330-015-4179-

Combined MR direct thrombus imaging and non-contrast magnetic resonance venography reveal the evolution of deep vein thrombosis: a feasibility study.

OBJECTIVES: Lower limb deep venous thrombosis (DVT) is a common condition with high morbidity and mortality. The aim of the study was to investigate the temporal evolution of the acute thrombus by magnetic resonance imaging (MRI) and its relationship to venous recanalization in patients with recurrent DVTs. METHODS: Thirteen patients with newly diagnosed lower limb DVTs underwent MRI with non-contrast MR venography (NC-MRV) and MR direct thrombus imaging (MR-DTI), an inversion-recovery water-selective fast gradient-echo acquisition. Imaging was performed within 7 days of the acute thrombotic event, then at 3 and 6 months. RESULTS: By 3 months from the thrombotic event a third of the thrombi had resolved and by 6 months about half of the cases had resolved on the basis of vein recanalisation using NC-MRV. On the initial MR-DTI acute thrombus was clearly depicted by hyperintense signal, while the remaining thrombi were predominantly low signal at 3 and 6 months. Some residual thrombi contained small and fragmented persisting hyperintense areas at 3 months, clearing almost completely by 6 months. CONCLUSIONS: Our study suggests that synergistic venous assessment with combined NC-MRV and MR-DTI is able to distinguish acute venous thrombosis from the established (old) or evolving DVT detected by ultrasound. KEY POINTS: • MRI can distinguish between acute and evolving or chronic lower limb DVT • Two advanced MRI techniques can follow the evolution of lower limb DVT • MRI could be used to avoid an incorrect diagnosis of recurrent DVT • MRI could help avoid the risks and complications of lifelong anticoagulation therapy.National Institute for Health Research, Addenbrooke’s Charitable TrustThis is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00330-016-4555-

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 $6960 per site) and 2$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

Uterine artery pulsatility and resistivity indices in pregnancy: Comparison of MRI and Doppler US.

OBJECTIVE: The aim of this work was to evaluate whether the uterine arteries (UtA) could be identified and their flow profiles measured during a fetal MRI examination. A comparison was performed against same day sonographic Doppler assessment. METHODS: 35 normal, healthy, singleton pregnancies at 28-32 weeks gestation underwent routine Doppler examination, followed by MRI examination. The resistivity index (RI) and pulsatility index (PI) of the left and right UtA were measured using phase contrast MRI. Bland Altman statistics were used to compare MRI and ultrasound results. RESULTS: Sixty-nine comparable vessels were analysed. Six vessels were excluded due to artefact or technical error. Bland-Altman analysis demonstrated the ultrasound indices were comparable, although systematically lower than the MRI indices; Right UtA RI bias -0.03 (95% limits of agreement (LOA) -0.27 to +0.20), and left UtA RI bias -0.06 (95% LOA -0.26 to +0.14); Right UtA PI bias -0.06 (95% LOA -0.50 to +0.38), Left UtA PI bias -0.11 (95% LOA -0.54 to +0.32). The inter-rater agreement for the MRI derived PI and RI analysis was good. CONCLUSION: This study demonstrates that in the majority of early third trimester pregnancies, the uterine arteries can be identified, and their flow profiles measured using MRI, and that the derived PI and RI values are comparable with Doppler ultrasound values.This study was supported by The National Institute for Health Research, Cambridge Biomedical Research Centre. We are grateful for support from the Addenbrooke’s Charitable Trust and the help of the Rosie Ultrasound Department and MRI Radiographers.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.placenta.2016.04.00

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

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