John J. Totman

Task-Related Default Mode Network Modulation and Inhibitory Control in ADHD: Effects of Motivation and Methylphenidate.

BACKGROUND Deficits characteristic of attention deficit/hyperactivity disorder (ADHD), including poor attention and inhibitory control, are at least partially alleviated by factors that increase engagement of attention, suggesting a hypodopaminergic reward deficit. Lapses of attention are associated with attenuated deactivation of the default mode network (DMN), a distributed brain system normally deactivated during tasks requiring attention to the external world. Task-related DMN deactivation has been shown to be attenuated in ADHD relative to controls. We hypothesised that motivational incentives to balance speed against restraint would increase task engagement during an inhibitory control task, enhancing DMN deactivation in ADHD. We also hypothesised that methylphenidate, an indirect dopamine agonist, would tend to normalise abnormal patterns of DMN deactivation. METHOD We obtained functional magnetic resonance images from 18 methylphenidate-responsive children with ADHD (DSM-IV combined subtype) and 18 pairwise-matched typically developing children aged 9-15 years while they performed a paced Go/No-go task. We manipulated motivational incentive to balance response speed against inhibitory control, and tested children with ADHD both on and off methylphenidate. RESULTS When children with ADHD were off-methylphenidate and task incentive was low, event-related DMN deactivation was significantly attenuated compared to controls, but the two groups did not differ under high motivational incentives. The modulation of DMN deactivation by incentive in the children with ADHD, off-methylphenidate, was statistically significant, and significantly greater than in typically developing children. When children with ADHD were on-methylphenidate, motivational modulation of event-related DMN deactivation was abolished, and no attenuation relative to their typically developing peers was apparent in either motivational condition. CONCLUSIONS During an inhibitory control task, children with ADHD exhibit a raised motivational threshold at which task-relevant stimuli become sufficiently salient to deactivate the DMN. Treatment with methylphenidate normalises this threshold, rendering their pattern of task-related DMN deactivation indistinguishable from that of typically developing children.

Gastric emptying of three liquid oral preoperative metabolic preconditioning regimens measured by magnetic resonance imaging in healthy adult volunteers: a randomised double-blind, crossover study.

BACKGROUND & AIMS Preoperative starvation has many undesirable effects but the minimum length of fasting is limited by gastric emptying, which may be dependent on nutrient content, viscosity and osmolarity of the feed. We compared the gastric emptying of two types of preoperative metabolic preconditioning drinks [Oral Nutritional Supplement (ONS) (Fresenius Kabi, Germany) and preOp (Nutricia Clinical Care, UK)] in healthy volunteers. METHODS Twenty (10 male, 10 female) healthy adult volunteers were studied on 3 separate occasions in a randomised crossover manner. Volunteers ingested 400 ml preOp, which is a clear carbohydrate drink (CCD) (50 g carbohydrate, 0 g protein), 70 g ONS (50 g carbohydrate and 15 g glutamine) dissolved in water to a total volume of 400 ml (ONS400) and 300 ml (ONS300). Gastric emptying time was measured using magnetic resonance imaging. RESULTS Mean (95% CI) T(50) and T(100) gastric emptying times for CCD were significantly lower (p<0.001) compared with ONS400 and ONS300. T(50) was 47 (39-55), 78 (69-87) and 81 (70-92)min for CCD, ONS400 and ONS300 respectively. Correspondingly T(100) was 94 (79-110), 156 (138-173) and 162 (140-184)min. Residual gastric volumes returned to baseline 120 min after CCD and 180 min after ONS400 and ONS300. CONCLUSIONS The faster gastric emptying for CCD compared to ONS400 and ONS300 signifies that gastric emptying may be more dependent on nutrient load than volume or viscosity in healthy volunteers. While it is safe to give CCD 2h preoperatively, ONS400 and ONS300 should be given at least 3h preoperatively.

Non-invasive quantification of small bowel water content by MRI: a validation study

Substantial water fluxes across the small intestine occur during digestion of food, but so far measuring these has required invasive intubation techniques. This paper describes a non-invasive magnetic resonance imaging (MRI) technique for measuring small bowel water content which has been validated using naso-duodenal infusion. Eighteen healthy volunteers were intubated, with the tube position being verified by MRI. After a baseline MRI scan, each volunteer had eight 40 ml boluses of a non-absorbable mannitol and saline solution infused into their proximal small bowel with an MRI scan being acquired after each bolus. The MRI sequence used was an adapted magnetic resonance cholangiopancreatography sequence. The image data were thresholded to allow for intra- and inter-subject signal variations. The MRI measured volumes were then compared to the known infused volumes. This MRI technique gave excellent images of the small bowel, which closely resemble those obtained using conventional radiology with barium contrast. The mean difference between the measured MRI volumes and infused volumes was 2% with a standard deviation of 10%. The maximum 95% limits of agreement between observers were -15% to +17% while measurements by the same operator on separate occasions differed by only 4%. This new technique can now be applied to study alterations in small bowel fluid absorption and secretion due to gastrointestinal disease or drug intervention.

Simultaneous PET–MR acquisition and MR-derived motion fields for correction of non-rigid motion in PET

ObjectivePositron emission tomography (PET) provides an accurate measurement of radiotracer concentration in vivo, but performance can be limited by subject motion which degrades spatial resolution and quantitative accuracy. This effect may become a limiting factor for PET studies in the body as PET scanner technology improves. In this work, we propose a new approach to address this problem by employing motion information from images measured simultaneously using a magnetic resonance (MR) scanner.MethodsThe approach is demonstrated using an MR-compatible PET scanner and PET–MR acquisition with a purpose-designed phantom capable of non-rigid deformations. Measured, simultaneously acquired MR data were used to correct for motion in PET, and results were compared with those obtained using motion information from PET images alone.ResultsMotion artefacts were significantly reduced and the PET image quality and quantification was significantly improved by the use of MR motion fields, whilst the use of PET-only motion information was less successful.ConclusionsCombined PET–MR acquisitions potentially allow PET motion compensation in whole-body acquisitions without prolonging PET acquisition time or increasing radiation dose. This, to the best of our knowledge, is the first study to demonstrate that simultaneously acquired MR data can be used to estimate and correct for the effects of non-rigid motion in PET.

Sequence optimization to reduce velocity offsets in cardiovascular magnetic resonance volume flow quantification - A multi-vendor study

PurposeEddy current induced velocity offsets are of concern for accuracy in cardiovascular magnetic resonance (CMR) volume flow quantification. However, currently known theoretical aspects of eddy current behavior have not led to effective guidelines for the optimization of flow quantification sequences. This study is aimed at identifying correlations between protocol parameters and the resulting velocity error in clinical CMR flow measurements in a multi-vendor study.MethodsNine 1.5T scanners of three different types/vendors were studied. Measurements were performed on a large stationary phantom. Starting from a clinical breath-hold flow protocol, several protocol parameters were varied. Acquisitions were made in three clinically relevant orientations. Additionally, a time delay between the bipolar gradient and read-out, asymmetric versus symmetric velocity encoding, and gradient amplitude and slew rate were studied in adapted sequences as exploratory measurements beyond the protocol. Image analysis determined the worst-case offset for a typical great-vessel flow measurement.ResultsThe results showed a great variation in offset behavior among scanners (standard deviation among samples of 0.3, 0.4, and 0.9 cm/s for the three different scanner types), even for small changes in the protocol. Considering the absolute values, none of the tested protocol settings consistently reduced the velocity offsets below the critical level of 0.6 cm/s neither for all three orientations nor for all three scanner types. Using multilevel linear model analysis, oblique aortic and pulmonary slices showed systematic higher offsets than the transverse aortic slices (oblique aortic 0.6 cm/s, and pulmonary 1.8 cm/s higher than transverse aortic). The exploratory measurements beyond the protocol yielded some new leads for further sequence development towards reduction of velocity offsets; however those protocols were not always compatible with the time-constraints of breath-hold imaging and flow-related artefacts.ConclusionsThis study showed that with current systems there was no generic protocol which resulted into acceptable flow offset values. Protocol optimization would have to be performed on a per scanner and per protocol basis. Proper optimization might make accurate (transverse) aortic flow quantification possible for most scanners. Pulmonary flow quantification would still need further (offline) correction.

Performance Evaluation of an MRI-Compatible Pre-Clinical PET System Using Long Optical Fibers

We have designed and constructed an MR-compatible PET system for fully simultaneous PET/MR studies of small animals. The scanner uses long optical fibers to distance the magnetic field sensitive PET PMTs from the high magnetic field at the center of an MR scanner. It is a single slice system with an inner diameter of 7 cm. A full evaluation of the performance of the PET system and the results of an MR compatibility assessment in a Philips Achieva whole body 3 T MRI scanner are presented. The reconstructed resolution of the PET scanner is 1.5 mm at the center falling to 2.5 mm at the edge of the field of view; the system sensitivity is 0.95%; the count rate is linear up to an activity of 6 MBq (~4 kcps) and the scatter fraction is 42% which can be reduced to 26% using MR-compatible gamma shields. Simultaneous PET/MR images of phantoms and a mouse have been acquired. The system is highly MR compatible, as demonstrated here, showing no degradation in performance of either the MR or PET system in the presence of the other modality. The system will be used to demonstrate novel pre-clinical applications of simultaneous PET/MR.

Effects of various food ingredients on gall bladder emptying

Background/objectives:The emptying of the gall bladder in response to feeding is pivotal for the digestion of fat, but the role of various food ingredients in contracting the gall bladder postprandially is not well understood. We hypothesized that different food ingredients, when consumed, will have a different effect on stimulating gall bladder emptying. To investigate this we designed two randomized, investigator-blind, cross-over studies in healthy subjects using magnetic resonance imaging (MRI) to measure gall bladder volumes serially and non-invasively.Subjects/methods:Study 1: exploratory study evaluating the effects of 10 different food ingredients on gall bladder emptying in eight healthy subjects. The choice of ingredients varied from common items like coffee, tea and milk to actives like curcumin and potato protease inhibitor. Study 2: mechanistic study investigating the cholecystokinin (CCK) dose response to the best performer ingredient from Study 1 in 21 healthy subjects four ways.Results:The largest gall bladder volume change in Study 1 was observed with fat, which therefore became the dose-response ingredient in Study 2, where the maximum % gall bladder volume change correlated well with CCK.Conclusions:These serial test-retest studies showed that the fasted gall bladder volume varied remarkably between individuals and that individual day-to-day variability had wide coefficients of variation. Improved knowledge of how to stimulate bile release using food ingredients will be useful to improve in vitro–in vivo correlation of bioavailability testing of hydrophobic drugs. It could improve performance of cholesterol-lowering plant stanol and sterol products and possibly aid understanding of some cholesterol gallstone disease.

Effects of a 5‐HT3 antagonist, ondansetron, on fasting and postprandial small bowel water content assessed by magnetic resonance imaging

Aliment Pharmacol Ther 2010; 32: 655–663

Realtime fusion of cardiac magnetic resonance imaging and computed tomography venography with X-ray fluoroscopy to aid cardiac resynchronisation therapy implantation in patients with persistent left superior vena cava.

Persistent left superior vena cava can lead to significant technical difficulties when implanting a left ventricular (LV) lead for cardiac resynchronisation therapy. We present two cases in which coronary sinus anatomy was reconstructed with computed tomography and magnetic resonance imaging and fused with live fluoroscopy to facilitate LV lead implantation.

Performance evaluation and MR compatibility assessment of an optical fibre based pre-clinical MR-compatible PET scanner

We have designed and constructed a small animal MR-compatible PET system for fully simultaneous MR/PET acquisitions. The scanner uses long optical fibres to distance the field sensitive PET PMTs from the high magnetic field at the centre of an MR scanner. The system has been designed to operate inside a number of different high field MRI scanners. We present a detailed performance evaluation and high field MR compatibility assessment of the PET system. The PET-only performance results are encouraging. We report a reconstructed transaxial resolution of 1.49mm at the centre of the field of view which falls off gradually to 2.52mm at 26.5mm from the centre. The average axial resolution is 2.7mm. The slice sensitivity to a point source is 0.95%, when corrected for both scatter and randoms. The count rate is linear up to an activity of 6 MBq (∼ 5kcps). The scatter fraction was 42% which could be reduced to 26% using MR compatible gamma shields. We have produced images of various hotspot phantoms that demonstrate good image quality. We assessed the MR compatibility of the PET system in a Philips Achieva human 3T scanner. We found there were no artefacts or distortions imposed on either the PET 2D flood position histograms of the PET PMTs or the PET images when the PET system was operated inside the MRI scanner. We have demonstrated that the MRI scanner did not pick up any significant levels of RF interference from the PET electronics by acquiring data across the entire frequency range of the RF head coil whilst the PET was inside the MRI scanner acquiring data. We have characterised the effects of the PET scanner materials on the main magnetic field of the MR scanner using a field map of a large uniform phantom with the PET scanner in the MRI scanner. We found that there were no significant distortions seen in MR images when the PET was located in the MR FOV. We acquired simultaneous MR and PET images of a mouse brain using a dedicated small animal coil in the 3T human system, which demonstrated good image quality. We now plan to use the system to demonstrate novel pre-clinical applications of simultaneous PET/MR.