[show abstract][hide abstract] ABSTRACT: We have developed a Magnetic Resonance Imaging (MRI)-compatible system to enable gating of a scanner to the heartbeat of a foetus for cardiac, umbilical cord flow and other possible imaging applications. We performed radiofrequency safety testing prior to a fetal electrocardiogram (fECG) gated imaging study in pregnant volunteers (n = 3). A compact monitoring device with advanced software capable of reliably detecting both the maternal electrocardiogram (mECG) and fECG simultaneously was modified by the manufacturer (Monica Healthcare, Nottingham, UK) to provide an external TTL trigger signal from the detected fECG which could be used to trigger a standard 1.5 T MR (GE Healthcare, Milwaukee, WI, USA) gating system with suitable attenuation. The MR scanner was tested by triggering rapidly during image acquisition at a typical fetal heart rate (123 beats per minute) using a simulated fECG waveform fed into the gating system. Gated MR images were also acquired from volunteers who were attending for a repeat fetal Central Nervous System (CNS) examination using an additional rapid cardiac imaging sequence triggered from the measured fECG. No adverse safety effects were encountered. This is the first time fECG gating has been used with MRI and opens up a range of new possibilities to study a developing foetus.
[show abstract][hide abstract] ABSTRACT: Over recent years hyperpolarization by dissolution dynamic nuclear polarization has become an established technique for studying metabolism in vivo in animal models. Temporal signal plots obtained from the injected metabolite and daughter products, e.g. pyruvate and lactate, can be fitted to compartmental models to estimate kinetic rate constants. Modelling and physiological parameter estimation can be made more robust by consistent and reproducible injections through automation. An injection system previously developed by us was limited in the injectable volume to between 0.6 and 2.4 ml and injection was delayed due to a required syringe filling step. An improved MR-compatible injector system has been developed that measures the pH of injected substrate, uses flow control to reduce dead volume within the injection cannula and can be operated over a larger volume range. The delay time to injection has been minimised by removing the syringe filling step by use of a peristaltic pump. For 100 ul to 10.000 ml, the volume range typically used for mice to rabbits, the average delivered volume was 97.8% of the demand volume. The standard deviation of delivered volumes was & ul for 100 ul and 200 ul for 10.000 ml demand volumes (mean S.D. was 9 ul in this range). In three repeat injections through a fixed 0.96 mm O.D tube the coefficient of variation for the area under the curve was 2%. For in vivo injections of hyperpolarized pyruvate in tumor-bearing rats, signal was first detected in the input femoral vein cannula at 3-4 s post injection trigger signal and at 9-12 s in tumor tissue. The pH of the injected pyruvate was 7.1± 0.3 (mean ± S.D., n=10). For small injection volumes, e.g. less than 100 ul, the internal diameter of the tubing contained within the peristaltic pump could be reduced to improve accuracy. Larger injection volumes are limited only by the size of the receiving vessel connected to the pump.
Journal of Magnetic Resonance 01/2013; · 2.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: To develop a neonatal MR-compatible incubator for transporting babies between a neonatal intensive care unit and an MRI unit that is within the same hospital but geographically separate.
The system was strapped to a standard MR-compatible patient trolley, which provides space for resuscitation outside the incubator. A constant-temperature exothermic heat pad was used to maintain temperature together with a logging fluoro-optic temperature monitor and alarm system. The system has been designed to accommodate standard knee-sized coils from the major MR manufacturers. The original incubator was constructed from carbon fibre, but this required modification to prevent radiofrequency shading artefacts due to the conducting properties of the carbon fibre. A high-tensile polyester material was used, which combined light weight with high impact strength. The system could be moved onto the patient bed with the coils and infant in place by one technologist.
Studies in eight neonatal patients produced high quality 1.5 T MR images with low motion artefacts. The incubator should also be compatible with imaging in 3 T MR systems, although further work is required to establish this. Images were acquired using both rapid and high-resolution sequences, including three-dimensional volumes, proton spectra and diffusion weighting.
The incubator provides a safe, quiet environment for neonates during transport and imaging, at low cost.
The British journal of radiology 12/2011; 85(1015):952-8. · 2.11 Impact Factor
[show abstract][hide abstract] ABSTRACT: Diffuse excessive high signal intensity (DEHSI) may represent damage to the white matter in preterm infants, but may be best studied alongside quantitative markers. Limited published data exists on its neuro-developmental implications.
The purpose of this study was to assess whether preterm children with DEHSI at term-corrected age have abnormal neuro-developmental outcome.
This was a prospective observational study of 67 preterm infants with MRI of the brain around term-equivalent age, including diffusion-weighted imaging (DWI). Images were reported as being normal, overtly abnormal or to show DEHSI. A single observer placed six regions of interest in the periventricular white matter and calculated the apparent diffusion coefficients (ADC). DEHSI was defined as (1) high signal on T2-weighted images alone, (2) high signal with raised ADC values or (3) raised ADC values independent of visual appearances. The neuro-development was assessed around 18 months' corrected age using the Bayley Scales of Infant and Toddler Development (3rd Edition). Standard t tests compared outcome scores between imaging groups.
No statistically significant difference in neuro-developmental outcome scores was seen between participants with normal MRI and DEHSI, regardless of which definition was used.
Preterm children with DEHSI have similar neuro-developmental outcome to those with normal brain MRI, even if the definition includes objective markers alongside visual appearances.
[show abstract][hide abstract] ABSTRACT: Characterising the protein signatures in tumours following vascular-targeted therapy will help determine both treatment response and resistance mechanisms. Here, mass spectrometry imaging and MS/MS with and without ion mobility separation have been used for this purpose in a mouse fibrosarcoma model following treatment with the tubulin-binding tumour vascular disrupting agent, combretastatin A-4-phosphate (CA-4-P). Characterisation of peptides after in situ tissue tryptic digestion was carried out using Matrix-Assisted Laser Desorption/Ionisation-Mass Spectrometry (MALDI-MS) and Matrix-Assisted Laser Desorption/Ionisation-Ion Mobility Separation-Mass Spectrometry Imaging (MALDI IMS-MSI) to observe the spatial distribution of peptides. Matrix-Assisted Laser Desorption/Ionisation-Ion Mobility Separation-Tandem Mass Spectrometry (MALDI-IMS-MS/MS) of peaks was performed to elucidate any pharmacological responses and potential biomarkers. By taking tumour samples at a number of time points after treatment gross changes in the tissue were indicated by changes in the signal levels of certain peptides. These were identified as arising from haemoglobin and indicated the disruption of the tumour vasculature. It was hoped that the use of PCA-DA would reveal more subtle changes taking place in the tumour samples however these are masked by the dominance of the changes in the haemoglobin signals.
[show abstract][hide abstract] ABSTRACT: The aim of this study is to computationally estimate local magnetic fields from evoked axons to support previously reported experimental evidence of direct neuronal detection (DND) of axonal firing using magnetic resonance imaging (MRI). The hypothesis tested is that the fields resulting from the electrical activity of axons can perturb the main field of the scanner, thereby producing visible image artefacts so that direct imaging of brain functioning may be possible. In this work magnetic fields are calculated for multiple axons using a hybrid model of the electro-physiological parameters of the human optic nerve and a complete 3 dimensional solution of the differential form of Poisson's equation.
[show abstract][hide abstract] ABSTRACT: Although MR imaging of the fetal brain has been shown to provide additional diagnostic information, the optimal timing of the study and the value of repeat studies remain unclear. The primary purpose of this study was to look for structural abnormalities of the fetal brain shown at 30-32 weeks' gestational age but not on the 20-24 weeks' study in fetuses originally referred with isolated VM. In particular, we wished to study the hypothesis that third-trimester fetal MR imaging studies would not show extra brain abnormalities compared with the second-trimester studies in this group.
Ninety-nine women were admitted for a fetal MR study between 20-24 weeks' gestational age, and 46 of these women agreed to return for a second MR imaging examination at 30-32 weeks' gestational age. The other women were either lost to follow-up or declined the invitation to return. Two experienced observers measured the width of the trigones, and the results were compared, to test reliability. Changes in the degree of VM are reported along with changes in the diagnosis of structural brain abnormalities.
There was excellent reproducibility of trigone measurements between the 2 observers, with a mean absolute difference of <1 mm in the 40 fetuses that were ultimately shown to have isolated VM. Twenty-eight of 40 fetuses studied had mild VM on the first iuMR imaging examination, but in just more than half, the category of VM changed between the studies (5 had become normal-sized, 7 had progressed to moderate, 3 had become severe, and 13 remained mild). In 1 case, hypogenesis of the corpus callosum was recognized at 30-32 weeks but had not been reported on the 20-24 weeks' examination; the other 5 fetuses had brain pathology recognized on both fetal MR studies.
Trigone measurements can be made in a highly repeatable fashion on iuMR imaging. We have not shown any major advantage in repeating iuMR imaging at 30-32 weeks' gestation in terms of improved diagnosis of other structural brain abnormalities. With the converse of that argument, however, our data suggest that there is no advantage in delaying iuMR imaging studies to 30-32 weeks in the hope of improving detection rates.
American Journal of Neuroradiology 12/2010; 32(3):474-80. · 3.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: To establish whether fetal exposure to the operating noise of 1.5-T magnetic resonance (MR) imaging is associated with cochlear injury and subsequent hearing loss in neonates.
The study was performed with local research ethics committee approval and written informed parental consent. Neonatal hearing test results, including otoacoustic emission (OAE) data, were sought for all neonates delivered in Sheffield who had previously undergone in utero MR imaging between August 1999 and September 2007. The prevalence of hearing impairment in these neonates was determined, with corresponding 95% confidence intervals calculated by using the binomial exact method, and mean OAE measurements were compared with anonymized local audiometric reference data by using the t test.
One hundred three neonates who had undergone in utero MR imaging were identified; 96 of them had completed hearing screening assessment. Thirty-four of these babies were admitted to the neonatal intensive care unit (NICU), and one of them had bilateral hearing impairment. The prevalence of hearing impairment was 1% (one of 96; 95% confidence interval: 0.03%, 5.67%), which is in accordance with the prevalence expected, given the high proportion of babies in this study who had been in the NICU (ie, NICU graduates). In addition, for the well babies, there was no significant difference in mean OAE cochlear response compared with that for a reference data set of more than 16,000 OAE results. When NICU graduates were included in the comparison, a significant difference (P = .002) was found in one of four frequency bands used to analyze the cochlear response; however, this difference was small compared with the normal variation in OAE measurements.
The findings in this study provide some evidence that exposure of the fetus to 1.5-T MR imaging during the second and third trimesters of pregnancy is not associated with an increased risk of substantial neonatal hearing impairment.
[show abstract][hide abstract] ABSTRACT: The aim of this study was to determine if apparent diffusion coefficients (ADCs) generated with diffusion-weighted imaging of cerebral white matter and the cerebellum are affected by white matter damage.
Seventy-two preterm infants (32 males, 40 females; mean gestational age at birth 30.3 wks, SD 3.0 wks; mean birthweight 1458g, SD 534g) underwent magnetic resonance imaging of the brain around term-equivalent age and were categorized into three groups: normal, overt abnormality, and diffuse excessive high signal intensity (DEHSI). ADC values were calculated from cerebral white matter, cerebellar hemispheres, and cerebellar midline, and were compared between groups. Regression analysis identified clinical parameters correlated with ADC values.
Imaging was normal in 27 infants, and revealed overt abnormalities in 14 and DEHSI in 31. ADC values did not differ between groups. ADC values from cerebral white matter were negatively correlated with the number of episodes of postnatal sepsis (p=0.002). ADC values from cerebellar hemispheres (p=0.007) and cerebellar midline (p=0.036) correlated with gestational age at birth.
ADC values from white matter are not altered in preterm infants with DEHSI but are negatively correlated with the number of episodes of postnatal sepsis. ADC values in the cerebellum are not altered by white matter damage, but are affected by preterm birth itself.
[show abstract][hide abstract] ABSTRACT: Medical imaging has seen great advances over the last twenty years since the introduction of Magnetic Resonance Imaging (MRI). MRI has proved to be a very powerful technique providing the opportunity to observe very detailed body images which has taken the field of body and neuro-imaging to a new level. In addition MRI is widely used for functional imaging with a high spatial resolution. Functional imaging of the brain for the purpose of medical diagnosis and research has relied previously on the hemodynamic response based technique BOLD (Blood Oxygen Level Dependent) fMRI (functional Magnetic Resonance Imaging). Although this is a very powerful and informative imaging method the temporal resolution can be improved by exploiting other information that might be present when imaging the brain. The hypothesis tested here is that the weak neuronal magnetic fields that result from the local neuronal currents cause scanner field perturbations strong enough to appear as contrast on MR images. Such Direct Neuronal Detection (DND) of neuronal currents would allow real time imaging of the electrical activity of detailed regions of the brain, potentially leading to a better understanding of brain functionality.
[show abstract][hide abstract] ABSTRACT: Fetal ventriculomegaly (VM) is important because of its high prevalence and high risk of association with other brain abnormalities. The purpose of this article was to investigate the hypotheses that including in utero MR imaging (iuMR) in the diagnostic pathway for fetuses with isolated VM on antenatal imaging will show other brain abnormalities in a high proportion of cases and that these will have a significant effect on clinical management.
One hundred forty-seven pregnant women were recruited prospectively from 8 fetomaternal centers in Britain. All of the fetuses had VM diagnosed on sonography but no other abnormality. iuMR was performed, and the results of the examinations were compared with those of sonography. Two fetomaternal experts made independent assessments of the effects of any new diagnoses on clinical management.
Categoric assessments of ventricular size were the same in approximately 90% of fetuses. Other abnormalities were shown in 17% of fetuses. The most frequent additional brain abnormality shown on iuMR was agenesis of the corpus callosum. Severe VM was associated with an approximately 10-fold increase in the risk of another brain abnormality being present when compared with fetuses with mild VM. The most profound effects on clinical management, however, were found in cases of mild VM.
This work supports our hypotheses by showing a high detection rate of other brain pathology when iuMR was used to supplement antenatal sonography (17%). In a high proportion of cases, the detection of the extra pathology would have led to significant changes in clinical management.
American Journal of Neuroradiology 09/2009; 31(1):106-11. · 3.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: Summary Aim - To correlate the magnetic resonance imaging signal changes observed during interstitial laser photocoagulation (ILP) therapy with histopatho-logical analysis of tissue necrosis. A 1.5T MR system was used. Lesions were produced with a diode laser (805 nm) in the liver of normal Wistar rats at laparotomy under general anaesthesia and imaged during treatment. Seventeen lesions were monitored with a T1-weighted spin echo (T1WSE) sequence, and 15 with a FLASH sequence. Treated tissue was removed and stained for NADPH-diaphorase to determine the extent of devitalization. Per-procedural T1WSE showed an expanding area of low signal which developed a high signal rim as ILP progressed. FLASH imaging showed an expanding area of low intensity which was replaced by a complex region of signal change as treatment progressed. Good imaging-histopathological correlation was shown: for T1WSE, r2=0.88 (P < 0.001) and for FLASH, r2=0.95 (P < 0.001). MR imaging during hepatic ILP accurately shows the extent of tissue necrosis and therefore may become clinically useful in the control of interstitial thermal treatments to liver lesions.
[show abstract][hide abstract] ABSTRACT: Summary Interstitial laser photocoagulation (ILP) is currently limited by deficient per-procedural monitoring. The purpose of this study was to evaluate MR control of ILP of hepatic metastases. Twenty-two laser activations were used to treat eight metastases in seven patients under local anaesthesia and sedation. Laser energy was delivered via optical fibres positioned in the tumour under ultrasound guidance. T1-weighted FLASH and spin-echo sequences were used to monitor the procedure. Enhanced CT was performed at 24 h to assess thermal necrosis. FLASH imaging showed an enlarging area of signal change during ILP. The final extent of this correlated closely with the extent of tissue necrosis on CT. Spin-echo imaging was disappointing because of poor contrast between the treated tissue and normal liver/untreated tumour. Per-procedural MR imaging accurately and reliably depicts ILP-induced necrosis. MR control may permit more widespread application of ILP to the treatment of hepatic tumours.
[show abstract][hide abstract] ABSTRACT: This study aimed (1) to image clinically normal newborn infants to detect the presence of any intracranial bleed and (2) to establish the natural history of the bleed. Newborn babies were imaged within 48 hours of delivery and all details of the labour and delivery were recorded. MR imaging was carried out on a dedicated 0.2T Niche MR system on the special care baby unit. Images were obtained in axial and coronal planes using T1, T2 plus gradient echo weighted images; similarly for the follow-up imaging. χ2 test was used for analysis. One hundred and two newborn infants were scanned. Forty-five had a normal vaginal delivery, 10 were ventouse (three metal cup, seven silastic), 10 were emergency sections, 15 were elective sections, 22 were forceps (19 Neville Barnes, three Keillands). Five had subdural collections that were clinically silent throughout their duration and had resolved fully within 4 weeks.All five babies with subdural collections had been delivered by forceps following an attempt at a ventouse delivery. In total 15 babies were delivered by forceps following a ventouse delivery and one by emergency caesarian section following an attempted ventouse delivery. The method of delivery was the only statistically significant factor in these babies (duration of labour, fetal blood pH, etc. were not statistically significant) for the presence of a subdural collection, using the χ2 test (P < 0.001).
[show abstract][hide abstract] ABSTRACT: A number of studies have now shown that direct detection of neuronal firing by MRI may be possible. The optic nerve carries all visual information from the eye to the brain and is a particularly promising target for these measurements. However, it has been assumed that the effects of axonal firing may not be detectable, as a single firing event produces a bipolar waveform of around 1 ms duration whose effects should cancel on MR. A simulation of the magnetic modulation which could feasibly be produced by the optic nerve over an extended period and with different firing rates has been developed. The Hodgkin–Huxley equations were calculated for an array of model ganglion cell axons which were assumed to act as voltage to pulse frequency converters. Dependence of the modulating waveform on relative action potential firing start time was investigated. Although the simulated waveforms were bipolar at the beginning, during the period of MR acquisition the different frequencies combine to produce a largely positive waveform. The simulation included only contrast luminance changes and not color, spatial correlations or other more sophisticated processing in the retina. A gradient echo sequence was used at 3 T to create images for analysis by the ghost reconstructed alternating current estimation (GRACE) method from phantoms subject to current modulation by the actual modelled axonal waveforms. The optic nerve was also imaged using the same method during visual stimulus by a strobe light in adult human volunteers at 3 T. Analysis of digitized video recordings of eye locations during strobe stimulation outside the magnet showed no correlation with the applied strobe frequency over the short duration of the scans. Images of the optic nerves at an echo time of TE = 39 ms had weak but significant first harmonic ghosts in locations consistent with the applied stimulus as calculated from GRACE theory in just two out of thirteen studies on 10 volunteers and a detection rate of only 15% providing no clear evidence for direct detection in these experiments.
[show abstract][hide abstract] ABSTRACT: Direct-MR neuronal detection (DND) of transient magnetic fields has recently been investigated as a novel imaging alternative to the conventional BOLD functional MRI (fMRI) technique. However, there remain controversial issues and debate surrounding this methodology, and this study attempts clarification by comparing BOLD responses in the human visual system with those of DND. BOLD relies on indirectly measuring blood oxygenation and flow changes as a result of neuronal activity, whereas the putative DND method is based on the hypothesis that the components of the in vivo neuronal magnetic fields, which lie parallel to the B(0) field, can potentially modulate the MR signal, thus providing a means of direct detection of nerve impulses. Block paradigms of checkerboard patterns were used for visual stimulation in both DND and BOLD experiments, allowing detection based on different frequency responses. This study shows colocalization of some voxels with slow BOLD responses and putative fast DND responses using General Linear Model (GLM) analysis. Frequency spectra for the activated voxel cluster are also shown for both stimulated and control data. The mean percentage signal change for the DND responses is 0.2%, corresponding to a predicted neuronal field of 0.14 nT.
Magnetic Resonance in Medicine 12/2008; 60(5):1147-54. · 3.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: To estimate the levels of basal ganglia iron levels in Parkinson's disease (PD) using the PRIME MR sequence at 3.0 Tesla, in relation to patients' motor symptom severity.
Seventy patients with PD and 10 healthy controls underwent assessment of movement and MR imaging. Mean R2' relaxation rates were recorded in the substantia nigra, frontal white matter and in the rostral, mid, and caudal putamen.
R2' relaxation rates were significantly higher in patients with PD than in healthy controls. R2' in the most affected substantia nigra correlated with PD patients' motor symptom severity, but not with disease duration. Neuroradiological observation revealed a rostral to caudal "gradient" of putaminal hypointensity. This was substantiated by the finding that the mid and caudal putamen showed significantly higher R2' relaxation rates, consistent with higher iron levels in PD relative to the healthy controls.
MRI at 3.0 Tesla suggests that substantia nigra iron levels are increased and linked to the severity of motor symptoms experienced in PD. Findings consistent with increased iron levels in the PD putamen are shown, in a region-specific rostral to caudal gradient.
Journal of Magnetic Resonance Imaging 12/2008; 28(5):1061-7. · 2.57 Impact Factor