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Purpose Insulin, in typical use, undergoes multiple changes in temperature; from refrigerator, to room temperature, to body temperature. Although long-term storage temperature has been well-studied, the short term changes to insulin are yet to be determined. Insulin detemir (IDet) is a clinically available, slow-acting, synthetic analogue characterised by the conjugation of a C14 fatty acid. The function of this modification is to cause the insulin to form multi-hexameric species, thus retarding the pharmacokinetic rate of action. In this investigation, the temperature dependence properties of this synthetic analogue is probed, as well as expiration. Methods Dynamic light scattering (DLS) and viscometry were employed to assess the effect of temperature upon IDet. Mass spectrometry was also used to probe the impact of shelf-life and the presence of certain excipients. Results IDet was compared with eight other insulins, including human recombinant, three fast-acting analogues and two other slow-acting analogues. Of all nine insulins, IDet was the only analogue to show temperature dependent behaviour, between 20 °C and 37 °C, when probed with non-invasive backscatter dynamic light scattering. Upon further investigation, IDet observed significant changes in size related to temperature, direction of temperature (heated/cooled) and expiration with cross-correlation observed amongst all 4 parameters. Conclusions These findings are critical to our understanding of the behaviour of this particular clinically relevant drug, as it will allow the development of future generations of peptide-based therapies with greater clinical efficacy.

Urethane-based test objects are routinely used for ultrasound quality assurance because of their durability and robustness. The acoustic properties of these phantoms including speed of sound and attenuation, however, have a strong dependence on temperature. Reliable measurement of low-contrast penetration, which is widely used for ultrasound system quality assurance testing, with these phantoms is therefore problematic. To alleviate this, a correction method was proposed using speed of sound estimated by measuring filament target separation. The method was developed using a range of 17 transducer geometry and frequency combinations across 5 ultrasound systems and validated using a further 5 systems. This was found to reduce the uncertainty of low-contrast penetration measurement from an average 17.6 mm to 4.9 mm over the temperature range 8°C to 32°C. This represents a greater than threefold improvement in precision of low-contrast penetration measurement.

The purpose of the study was to survey MRI qualification and certification frameworks in the major English-speaking countries (Australia, New Zealand, US, Canada, UK, Ireland) with the aim of identifying elements of good practice. The intention is to incorporate these elements in a national framework that could be used in supporting an MRI specialist register. The study was conducted using document analysis of MRI qualification and certification documents from these states with data triangulated through a webbased questionnaire amongst an expert group of MRI radiographers (n = 59) from the same states. Based on the results of the study, recommendations have been put forward for those countries that are in the process of developing such frameworks. The main recommendations include that a professional or regulatory body externally accredits MRI programmes and that learning outcomes be based on an MRI competence profile that addresses current and forecasted needs of the particular country. The MRI competence profile should encompass a novice-to expert continuum and be referenced directly to a national qualification framework. Ideally each level of expertise should be assessed and evidenced by a portfolio of CPD activities, including clinical and management case studies appropriate to that level, peer-reviewed

Background Clinical imaging data are typically stored and transferred in the DICOM format, whereas the NIfTI format has been widely adopted by scientists in the neuroimaging community. Therefore, a vital initial step in processing the data is to convert images from the complicated DICOM format to the much simpler NIfTI format. While there are a number of tools that usually handle DICOM to NIfTI conversion seamlessly, some variations can disrupt this process. New method We provide some insight into the challenges faced with image conversion. First, different manufacturers implement the DICOM format differently which complicates the conversion. Second, different modalities and sub-modalities may need special treatment during conversion. Lastly, the image transferring and archiving can also impact the DICOM conversion. Results We present results in several error-prone domains, including the slice order for functional imaging, phase encoding direction for distortion correction, effect of diffusion gradient direction, and effect of gantry correction for some imaging modality. Comparison with existing methods Conversion tools are often designed for a specific manufacturer or modality. The tools and insight we present here are aimed at different manufacturers or modalities. Conclusions The imaging conversion is complicated by the variation of images. An understanding of the conversion basics can be helpful for identifying the source of the error. Here we provide users with simple methods for detecting and correcting problems. This also serves as an overview for developers who wish to either develop their own tools or adapt the open source tools created by the authors.

The locus coeruleus (LC) noradrenergic system regulates arousal and modulates attention through its extensive projections across the brain. LC dysfunction has been implicated in a broad range of neurodevelopmental, neurodegenerative and psychiatric disorders, as well as in the cognitive changes observed during normal aging. Magnetic resonance imaging (MRI) has been used to characterize the human LC (elevated contrast relative to surrounding structures), but there is limited understanding of the factors underlying putative LC contrast that are critical to successful biomarker development and confidence in localizing nucleus LC. We used ultra-high-field 7 T magnetic resonance imaging (MRI) to acquire T1-weighted microscopy resolution images (78 μm in-plane resolution) of the LC from post-mortem tissue samples. Histological analyses were performed to characterize the distribution of tyrosine hydroxylase (TH) and neuromelanin in the scanned tissue, which allowed for direct comparison with MR microscopy images. Our results indicate that LC-MRI contrast corresponds to the location of neuromelanin cells in LC; these also correspond to norepinephrine neurons. Thus, neuromelanin appears to serve as a natural contrast agent for nucleus LC that can be used to localize nucleus LC and may have the potential to characterize neurodegenerative disease.

Purpose: As high quality CPD courses become increasingly expensive and time off for radiographers progressively limited, it is important that CPD content be aligned to forecasted service portfolio development. When such a portfolio has not been developed locally the CPD planner should carry out an own forecasting exercise. The purpose of the study was to develop a 2020 MRI service portfolio using a Delphi study. MRI stakeholder experts participated in a first Delphi round based on semi structured interviews. The interviews were analysed thematically leading to a series of statements for a second Delphi round., peer-reviewed

The purpose of this study was to use interleaved transcranial magnetic stimulation/functional magnetic resonance imaging (TMS/fMRI) to investigate the effects of lamotrigine (LTG) and valproic acid (VPA) on effective connectivity within motor and corticolimbic circuits. In this randomized, double-blind, crossover trial, 30 healthy volunteers received either drug or placebo 3.5 h prior to interleaved TMS/fMRI. We utilized dynamic causal modeling (DCM) to assess changes in the endogenous effective connectivity of bidirectional networks in the motor-sensory system and corticolimbic circuit. Results indicate that both LTG and VPA have network-specific effects. When TMS was applied over the motor cortex, both LTG and VPA reduced TMS-specific effective connectivity between primary motor (M1) and pre-motor cortex (PMd), and between M1 and the supplementary area motor (SMA). When TMS was applied over prefrontal cortex, however, LTG alone increased TMS-specific effective connectivity between the left dorsolateral prefrontal cortex(DLPFC) and the anterior cingulate cortex (ACC). In summary, LTG and VPA inhibited effective connectivity in motor circuits, but LTG alone increased effective connectivity in prefrontal circuits. These results suggest that interleaved TMS/fMRI can assess region- and circuit-specific effects of medications or interventions.

Summary Children with neurological disorders may follow unique developmental trajectories whereby they undergo compensatory neuroplastic changes in brain structure and function that help them gain control over their symptoms [1–6]. We used behavioral and brain imaging techniques to investigate this conjecture in children with Tourette syndrome (TS). Using a behavioral task that induces high levels of intermanual conflict, we show that individuals with TS exhibit enhanced control of motor output. Then, using structural (diffusion-weighted imaging) brain imaging techniques, we demonstrate widespread differences in the white matter (WM) microstructure of the TS brain that include alterations in the corpus callosum and forceps minor (FM) WM that significantly predict tic severity in TS. Most importantly, we show that task performance for the TS group (but not for controls) is strongly predicted by the WM microstructure of the FM pathways that lead to the prefrontal cortex and by the functional magnetic resonance imaging blood oxygen level-dependent response in prefrontal areas connected by these tracts. These results provide evidence for compensatory brain reorganization that may underlie the increased self-regulation mechanisms that have been hypothesized to bring about the control of tics during adolescence., Highlights ► We combine behavioral studies with structural and functional neuroimaging ► We report enhanced cognitive control in children with Tourette syndrome ► Frontal lobe white-matter microstructure predicts tic severity in Tourette syndrome ► Frontal lobe white-matter and fMRI BOLD predict cognitive control in Tourette syndrome

Brain tractography techniques utilize a set of diffusion-weighted magnetic resonance images to reconstruct white matter tracts, non-invasively and in-vivo. Streamline tracking techniques propagate curves from a seed to imply connectivity to distal voxels. Alternative approaches have been developed that attempt to quantify connection strength between all voxels and the seed. Tractography based on graph theory is amongst them. Despite its potential, graph-based tracking through complex fibre configurations has not been extensively studied and existing methods have inherent limitations. Anatomically unlikely connections may be identified in fibre crossing regions, by assigning relatively high connection strengths to all crossing populations. In this study, we discuss these limitations and present a new approach for robustly propagating through fibre crossings, as described by the orientation distribution functions (ODFs) derived from Q-ball imaging. Each image voxel is treated as a graph node and graph arcs connect neighbouring voxels. Weights representative of both structural and diffusivity features are assigned to each arc. To account for the existence of crossing fibre populations within a voxel, complex ODFs are decomposed into components representative of single-fibre populations and an image multigraph is created. The multigraph is searched exhaustively, but efficiently, to find the strongest paths and assign connectivity strengths between a seed and all the other image voxels. A comparison with the existing graph-based tractography as well as Q-ball driven front evolution tractography is performed on simulated data, and on human Q-ball imaging data acquired from five healthy volunteers. The new approach improves the connection strengths through fibre crossing regions, reducing the strengths of paths that are less anatomically plausible.

The locus coeruleus (LC) is a brainstem structure that has widespread cortical and sub-cortical projections to modulate states of attention. Our understanding of the LC's role in both normal attention and clinical populations affected by disrupted attention would be advanced by having in vivo functional and structural markers of the human LC. Evidence for LC activation can be difficult to interpret because of uncertainty about whether brainstem activity can be accurately localized to the LC. High resolution T1-turbo spin echo (T1-TSE) magnetic resonance imaging (MRI) (in-plane resolution of 0.4 mm x 0.4 mm) was used in this study to characterize the location and distribution probability of the LC across 44 adults ranging in age from 19 to 79 years. Utilizing a study-specific brainstem template, the individual brainstems were aligned into standard space, while preserving variations in LC signal intensity. Elevated T1-TSE signal was observed in the rostral pons that was strongly correlated with the position and concentration of LC cells previously reported in a study of post-mortem brains (r=0.90). The elevated T1-TSE signal was used to produce a probabilistic map of the LC in standard Montreal Neurological Institute (MNI) coordinate space. This map can be used to test hypotheses about the LC in human structural and functional imaging studies. Such efforts will contribute to our understanding of attention systems in normal and clinical populations.

The increased blood oxygenation level-dependent contrast available at high field makes the implementation of combined EEG/fMRI experiments at 7 T highly worthwhile from the point of view of fMRI data quality, but the higher field poses greater technical challenges for achieving good quality EEG data. A study of the feasibility of recording EEG signals from human subjects at 7 T using a commercially available, MR-compatible EEG system has therefore been carried out. This involved systematic measurement of the sources of noise in EEG recordings made in the 7 T scanner and measurement of RF heating effects on a gel phantom in the presence of a 32-electrode EEG cap. Having found no significant safety concerns and identified a set-up (involving switching off the magnet's cryo-cooler pumps and mounting the EEG amplifier on a cantilever) that limited scanner-induced noise, combined EEG/fMRI experiments employing visual stimulation were then successfully carried out on two human subjects. With the use of beamformer-based analysis of the EEG data, driven responses and alpha-band, event-related desynchronisation were identified in both subjects.

Dopamine D1 receptors play an important role in memory and cognition in non-human primates. Dopamine D1 agonists have been shown to reverse performance deficits in both aged non-human primates and in primates with lesions to dopamine systems. This study explored whether a single dose of the first full D1 agonist dihydrexidine (DAR-0100) would cause changes in brain activity (perfusion) in dopamine-rich brain regions. We used a new gadolinium-contrast magnetic resonance perfusion scanning technique to measure brain activity. A within-subject cross-over double-blind randomized design was used in 20 adults with SCID-diagnosed schizophrenia. Each morning at 0800 h, they were scanned on a 3.0 T MRI scanner for perfusion. They then received either 20 mg of dihydrexidine, or placebo, subcutaneously over 15 min. Over the next 45 min, they had intermittent MRI scans. Two days later, they had a repeat of the Day 1 schedule, but received the opposite treatment from that given on the first day. Within-day, as well as between-day, comparisons were made to test for perfusion effects of dihydrexidine. Analysis revealed that dihydrexidine induced a significant increase in both prefrontal and non-prefrontal perfusion compared to placebo. The greatest increases occurred approximately 20 min after dihydrexidine infusion, consistent with the short pharmacokinetic half-life of dihydrexidine. These data are consistent with the hypothesis formulated from studies of non-human primates that dihydrexidine and other D1 agonists may be able to modulate prefrontal dopaminergic function.

The posterior parietal cortex (PPC) is thought to integrate different kinds of sensory information (e.g., visual, auditory, somatosensory) to produce multiple representations of space that are each associated with different types or combinations of action; such as saccadic eye movements and reaching or grasping movements of the upper limb. Lesion studies in monkeys and in humans have shown that reaching movements to visually defined and to posturally defined targets can be dissociated from one another; indicating that different regions of the parietal cortex may code the same movement in either extrinsic (visual) or intrinsic (postural) coordinates. These studies also suggest that regions within the posterior parietal cortex play an important role in maintaining an accurate and up-to-date representation of the current postural state of the body (the body schema). We used event-related functional magnetic resonance imaging (fMRI) to investigate those brain areas involved in maintaining and updating postural (i.e., non-visual) representations of the upper limb that participate in the accurate control of reaching movements. We show that a change in the posture of the upper-limb is associated with a significant increase in BOLD activation in only one brain region--the superior parietal cortex, particularly the medial aspect (precuneus). We note that this finding is consistent with the suggestion, based upon human neurological investigations and monkey electrophysiology, that this region of the PPC may participate in the dynamic representation of the body schema, and is the most likely location for damage leading to errors in visually guided reaching to non-foveated target locations. We also note that this brain area corresponds to a region of PPC recently identified as the human homologue of the Parietal Reach Region (PRR) observed in the monkey brain that has been thought to represent reaching movements in eye-centred coordinates.

Objectives. The aim of this study was to determine whether unstable carotid plaques, a known risk factor for cerebral emboli, are associated with cerebral white matter lesions. Methods. Seventy-one symptomatic patients undergoing magnetic resonance imaging prior to carotid endarterectomy for high grade carotid stenosis were included in this study. The number and volume of white matter hyperintense lesions (WMHL) on fluid attenuated inversion recovery brain scans were compared according to the morphology of carotid plaque based upon the American Heart Association (AHA) histological classification. Results. Of the 57 patients who had good quality brain scans and non-fragmented carotid plaques, 15 plaques were defined as stable (type V) and 42 as unstable (type VI). After adjustment for the major risk factors affecting WMHL, unstable carotid plaques were found to be associated with more WMHL in the ipsilateral cerebral hemisphere than stable plaques (transformed means 2.50G1.2 vs. 1.53G1.1, pZ0.016), however, there was only a trend towards larger WMHL volumes (pZ0.079). Conclusions. The observed association between unstable carotid plaques and the number of white matter lesions suggest that thromboembolic plaque activity may contribute to the development of leukoaraiosis, in particular smaller individual lesions. Larger studies are warranted to confirm this finding and explore the potential clinical impact for selecting candidates for carotid endarterectomy.

Specific neurological impairments in multiple sclerosis (MS) are dependent on the pathology in clinically eloquent areas of the central nervous system. We aimed to use diffusion tensor fiber tracking to identify the pyramidal tracts and corpus callosum in MS patients, measure the apparent diffusivity within the tracts, and evaluate whether this would correlate with relevant disability scores. Dual-echo and diffusion tensor magnetic resonance imaging (DT-MRI) brain scans were obtained from 29 patients with relapsing remitting MS, and 13 age and gender matched normal controls. Voxels from pyramidal tracts and corpus callosum were automatically identified using a tractography based algorithm. Mean apparent diffusion coefficient (ADC(av)) was measured for these tracts. Scores of Expanded Disability Status Scale (EDSS) and Paced Auditory Serial Addition Test (PASAT) were obtained. The median EDSS score was 2.5 (inter-quartile range 2-3.25). The ADC(av) in the pyramidal tracts (p=0.02) and corpus callosum (p=0.0004) in patients was significantly higher than in controls. Pyramidal tracts ADC(av) was correlated with pyramidal FSS (r=0.5, p=0.008). Corpus callosum ADC(av) was correlated with PASAT (r=-0.58, p=0.001). Global T2 lesion volume did not correlate with the EDSS, but correlated with ADC(av) of the pyramidal tracts (r=0.6, p=0.0007) and corpus callosum (r=0.8, p

Objectives Poor iliac vein recanalization has been associated with compression of the left common iliac vein by the right common iliac artery (RCIA/LCIV compression); however, this finding has been difficult to confirm. In a baseline study, RCIA/LCIV compression was detected with magnetic resonance imaging in patients with deep venous thrombosis. We compared recanalization of left femoropopliteal and iliac thrombosis with and without RCIA/LCIV compression. Methods This was a prospective blinded study carried out in a 1355-bed university hospital. Thirty-one patients were recruited from consecutive cohorts of patients with iliofemoral and femoropopliteal DVT who underwent direct thrombus magnetic resonance imaging, venous enhanced peak arterial magnetic resonance venography, and magnetic resonance arteriography as part of the baseline study relating RCIA/LCIV compression to extent of thrombosis. Magnetic resonance venography was performed 6 weeks, 6 months, and 1 year after diagnosis of deep venous thrombosis. Femoropopliteal and iliac venous segments that were occluded at diagnosis were classified as occluded, partially occluded, or patent on follow-up scans. Results At 6-week follow-up, recanalization of all segments was incomplete. At both 6-month and 1-year follow-up, recanalization of left iliac segments associated with RCIA/LCIV compression was poorer compared with recanalization of left iliac segments not associated with compression (6 of 6 occluded vs 1 of 6 occluded and 1 of 6 partially occluded at 6 months, P =.015; 6 of 6 occluded vs 5 of 5 patent at 1 year, P = .002). This was due to complete failure of recanalization of left common iliac veins associated with RCIA/LCIV compression in 6 of 6 cases. All other iliac and femoropopliteal segments including left external iliac veins associated with RCIA/LCIV compression had high rates of recanalization at both 6 months and 1 year. Conclusion RCIA/LCIV compression is associated with persistent occlusion of the left common iliac vein. The recanalization rate for all other femoropopliteal and iliac segments was high.

We have developed a new technique to measure the overall application accuracy of image-guided stereotactic systems. It has been used to measure the accuracy of the Pathfinder neurosurgical robot, which uses a robot-mounted camera to triangulate fiducial skin markers, virtually eliminating line-of-sight problems experienced by other optical localisation methods. A phantom consisting of plastic spheres on stalks was used. The targets are the centre of the spheres. Points on a sphere's surface were automatically selected on CT images, from which the centre of the sphere was calculated in image space to greater precision than the CT voxel dimensions. A depth gauge was attached to Pathfinder in place of a biopsy needle and driven to the target as defined on CT. Pathfinder then moved to several points over the sphere, moving perpendicular to the trajectory in a grid pattern. By considering the depth gauge reading, 3D points on the sphere's surface were measured in robot space and the centre of the sphere was found. The difference between the actual and planned targets yields the overall accuracy. Preliminary experiments show that the application accuracy of Pathfinder is 2.7 mm. Further calibrations of the robot are expected to improve this value significantly.

Background: Despite recent therapeutic advances, outcomes in pediatric high-grade glioma (HGG) remain poor. A phase 1 study (Glade-Bender et al., J Clin Oncol. 2008) indicated that bevacizumab (BEV) is well tolerated in children with refractory solid tumors and yielded pharmacokinetic data that support further studies of BEV in childhood cancer. Trial design: A total of 120 eligible patients aged 3 to 18 years with newly diagnosed, localized supratentorial or infratentorial cerebellar or peduncular, histologically confirmed World Health Organization grade 3 or 4 HGG (central independent histologic confirmation) will be randomized to 6 weeks of concomitant temozolomide (TMZ) and local radiotherapy, followed by a 4-week TMZ treatment break and 48 weeks of adjuvant TMZ ± BEV every other week. Children aged 6 months to 3 years with recurrent disease are eligible in a young patient cohort; at relapse, these patients will receive TMZ + BEV without radiotherapy. All patients/parents must provide written informed consent per the local institutional review boards. The primary end point is event-free survival, defined as the time to earliest occurrence of tumor progression/recurrence (by central independent assessment per Response Assessment in Neuro-Oncology criteria), secondary malignancy, or death. Secondary end points include overall survival, response rate, safety, feasibility, and tolerability. The usefulness of multimodal MRI will be explored with respect to the diagnosis of pseudoprogression and prognostication of tumor evolution. All randomized patients will be followed for ≥3 years. A futility analysis will be performed after the first 60 randomized patients have been followed for 1 year. The primary analysis will be performed after all patients have been followed for 1 year. Updated analyses will be performed 3 years after the last patient has been randomized. HERBY is being conducted at 87 clinical sites in 15 countries. The first patient was randomized in October 2011. Among 118 patients screened to date, 79 have been randomized, and 1 has been enrolled in the young patient cohort. Completion of the study is expected in 2016. Some content has been presented at ASCO 2012 (abs TPS9596), SNO 2013 (abs PC-007), and ISPN 2013 (abs P109). Disclosure: D. Hargrave: Advisory board: Roche; P. Varlet: Advisory board: Roche Other substantive relationships: Roche; T. Jaspan: Corporate sponsored research: Roche; C. Jones: Advisory board: Genentech Paediatric Oncology Advisory Board Corporate-sponsored research: Roche/Genentech - HERBY trial M. Massimino: Advisory board: Roche, present study; A.A. Azizi: Advisory board: Roche F. Saran: Advisory board: Roche; P. Morgan: Advisory board: Trial Steering Group for F Hoffmann‐La Roche sponsored HERBY study (BO25041) Corporate-sponsored research: Employing institution receives support for its role in the F Hoffmann‐La Roche sponsored HERBY study (BO25041); G. Zahlmann: Stock ownership: Roche employee program Corporate-sponsored research: Roche employee; M. Zheng: Stock ownership: Genentech/Roche; S. Fuerst-Recktenwald: Other substantive relationships: Roche employee C. Berger: Corporate sponsored research: Roche; E. Bouffet: Advisory board: Boehringer Ingelheim. All other authors have declared no conflicts of interest.

Background Despite an urgent need to develop biomarkers for Parkinson's disease, imaging strategies have been unable to directly mirror the pathological change in the substantia nigra. The dopaminergic neurons in the substantia nigra are concentrated in five structures called nigrosomes (NS) of which NS1 is the largest. Recent high-resolution T2*-weighted MRI (HR T2*-MRI) at ultra-high magnetic fields (7T) has shown NS1 as a comma-shaped high-signal-intensity region in the substantia nigra of healthy people with a corresponding absence of the NS1 signal in patients with Parkinson's disease. We investigated whether HR T2*-MRI at 3T could be used to image NS1 and serve as a diagnostic marker of Parkinson's disease in a routine clinical patient population. Methods In a prospective observational case-control study, patients with Parkinson's disease and healthy controls were recruited from movement disorder clinics. Two masked investigators (rater A and B) assessed HR T2*-MRI in 19 participants (ten Parkinson's disease, nine controls) for presence or absence of NS1. In an additional retrospective cross-sectional study, 105 consecutive routine clinical HR T2*-MRI studies (>50 years old, 44 women, nine Parkinson's disease) were retrospectively reviewed by the same investigators. Findings According to presence or absence of NS1, both raters independently correctly classified 16 of 19 participants of the prospective study (eight with Parkinson's disease) and 81 of 105 participants from the retrospective study (all nine Parkinson's disease). 14 of the 105 patients were excluded because of a non-definite clinical diagnosis or imaging artefacts. If results from the prospective and retrospective study were combined, 13 of 110 patients were misclassified by one or both raters. The sensitivity and specificity analysis for correctly classified cases for rater A was sensitivity 95%, specificity 91%, and accuracy 92%; and for rater B 89%, 91%, and 91%, respectively. Reproducibility analysis revealed a high level of absolute interobserver agreement (92%, kappa 0·79; p Interpretation Use of 3T MRI to image NS1 can help to distinguish patients with Parkinson's disease from those without the disease, even in a routine clinical population. The accuracy of this diagnostic test in our study population is comparable to that of more expensive nuclear medical techniques like DaTSCAN. In-vivo nigrosome imaging using 3T HR T2*-MRI is feasible and is a new, highly promising technique with potential to become an accessible and affordable MRI diagnostic technique in Parkinson's disease for clinicians. Funding Special Trustees for Nottingham University Hospital (Grant Ref: STR 82/04/N); Sarah Matheson Trust (now Multiple System Atrophy Trust founded by Sarah Matheson); Radiological Sciences Research Group; Division of Clinical Neuroscience, University of Nottingham. STS is funded by a National Institute for Health Research UK training grant.

Current magnetic resonance techniques generate high signal from venous blood and show thrombi as filling defects. Magnetic resonance direct thrombus imaging (MRDTI) directly visualizes acute thrombus.To determine the accuracy of MRDTI for diagnosis of acute symptomatic deep venous thrombosis (DVT) below and above the knee.Prospective, blinded study.A 1355-bed university hospital.101 patients with suspected DVT who had had routine venography. Participants were recruited from a cohort of patients with suspected DVT. All patients with a positive venogram and one quarter of patients with a negative venogram were selected by using a random sequence.MRDTI was performed within 48 hours of venography and was interpreted by two reviewers.Diagnosis of DVT overall; isolated calf, femoropopliteal, and ileofemoral DVT; and thrombus in the calf, femoropopliteal, and iliac segments.The reports from two readers had sensitivities of 96% and 94% and specificities of 90% and 92% for diagnosis of DVT. Sensitivities were 92% and 83% for isolated calf DVT, 97% and 97% for femoropopliteal DVT, and 100% and 100% for ileofemoral DVT. Specificities were 94% and 96% for isolated calf DVT and 100% and 100% for both femoropopliteal and ileofemoral DVT. Similarly, sensitivity and specificity within each of the venous segments ranged from 91% to 100%. Interobserver variability measured by using a weighted kappa statistic ranged from 0.89 to 0.98 for these measures.Magnetic resonance direct thrombus imaging is an accurate noninvasive test for diagnosis of DVT, and its accuracy is maintained below the knee. Comparison of individual venous segments showed that results of MRDTI agreed strongly with findings on venography. Scanning was well tolerated, and interpretation was highly reproducible.

Trials in acute stroke have recruited on the basis of clinical diagnosis. Using MRI we have shown that clinical diagnosis is more limited than previously appreciated, thus trials may have been underpowered or confounded.