Probing human sperm metabolism using 13C-magnetic resonance spectroscopy.

STUDY QUESTION: Can 13C-Magnetic Resonance Spectroscopy (MRS) of selected metabolites provide useful information about human sperm metabolism and how glycolysis or oxidative phosphorylation are used by different sperm populations? SUMMARY ANSWER: Sperm populations, prepared by density gradient centrifugation (DGC) and incubated with either 13Cu-glucose, 13Cu-fructose or 13C1-pyruvate, showed consistent evidence of metabolism generating principally lactate and more intermittently bicarbonate, and significantly more lactate was produced from 13Cu-glucose by vital or motile sperm recovered from the 40/80% interface compared to those from the pellet, which could not be accounted for by differences in the non-sperm cells present. WHAT IS KNOWN ALREADY: Previous studies have focused on CO2 or other specific metabolite production by human sperm and there remains considerable debate about whether glycolysis and/or oxidative phosphorylation is the more important pathway for ATP production in sperm. STUDY DESIGN, SIZE, DURATION: Sperm populations were prepared by DGC and subjected to 13C-MRS to answer the following questions. (i) Is it possible to detect human sperm metabolism of 13C substrates implicated in energy generation? (ii) What are the kinetics of such reactions? (iii) Do different sperm populations (e.g. '80%' pellet sperm and '40%' interface sperm) utilise substrates in the same way? Semen samples from 97 men were used in these experiments; 52 were used in parallel for aims (i) and (ii) and 45 were used for aim (iii). PARTICIPANTS/MATERIALS, SETTING, METHODS: Sperm populations were prepared from ejaculates of healthy men using a Percoll/Phosphate Buffered Saline (PBS) DGC and then incubated with a range of 13C-labelled substrates (13Cu-glucose, 13Cu-fructose, 13C1-pyruvate, 13C1-butyrate, 13C3-lactate, 13C2,4-D-3-hydroxybutyrate, 13C5-l-glutamate, 13C1,2-glycine or 13Cu-galactose) along with penicillin/streptomycin antibiotic at 37°C for 4 h, 24 h or over 48 h for an estimated rate constant. Sperm concentration, vitality and motility were measured and, for a subset of experiments, non-sperm cell concentration was determined. A 9.4 T magnetic resonance spectrometer was used to acquire 1D 13C, inverse gated 1H decoupled, MRS spectra. Spectrum processing was carried out using spectrometer software and Matlab scripts to determine peak integrals for each spectrum. MAIN RESULTS AND THE ROLE OF CHANCE: 13Cu-glucose, 13Cu-fructose and 13C1-pyruvate were consistently converted into lactate and, to a lesser extent, bicarbonate. There was a significant correlation between sperm concentration and lactate peak size for 13Cu-glucose and 13Cu-fructose, which was not observed for 13C1-pyruvate. The lactate peak did not correlate with the non-sperm cell concentration up to 6.9 × 106/ml. The concentration of 13Cu-glucose, 13Cu-fructose or 13C1-pyruvate (1.8, 3.6, 7.2 or 14.4 mM) had no influence on the size of the observed lactate peak over a 4 h incubation. The rate of conversion of 13C1-pyruvate to lactate was approximately three times faster than for 13Cu-glucose or 13Cu-fructose which were not significantly different from each other. After incubating for 4 h, the utilisation of 13Cu-glucose, 13Cu-fructose or 13C1-pyruvate by sperm from the '40%' interface of the DGC was no different from those from the pellet when normalised to total sperm concentration. However, after normalising by either the vital or motile sperm concentration, there was a significant increase in conversion of 13Cu-glucose to lactate by '40%' interface sperm compared to pellet sperm (Vital = 3.3 ± 0.30 × 106 vs 2.0 ± 0.21 × 106; P = 0.0049; Motile = 7.0 ± 0.75 × 106 vs 4.8 ± 0.13 × 106; P = 0.0032. Mann-Whitney test P < 0.0055 taken as statistically significant). No significant differences were observed for 13Cu-fructose or 13C1-pyruvate. LARGE SCALE DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION: Only 13C labelled metabolites that accumulate to a sufficiently high concentration can be observed by 13C MRS. For this reason, intermediary molecules in the metabolic chain are difficult to observe without trapping the molecule at a particular step using inhibitors. Non-sperm cell concentration was typical of the general population and no link was found between these cells and the magnitude of the 13C-lactate peak. However, it is possible that higher concentrations than the maximum observed (6.9 × 106/ml) may contribute to exogenous substrate metabolism in other experiments. WIDER IMPLICATIONS OF THE FINDINGS: 13C-MRS can provide information on the underlying metabolism of multiple pathways in live sperm. Dysfunction in sperm metabolism, as a result of either impaired enzymes of lack of metabolisable substrate, could be detected in sperm by a non-destructive assay, potentially offering new treatment options to improve overall sperm quality and outcomes for reproduction. STUDY FUNDING AND COMPETING INTERESTS: This work was supported by the Medical Research Council Grant MR/M010473/1. The authors declare no conflicts of interest.

1H Magnetic Resonance Spectroscopy of live human sperm.

STUDY QUESTION: Can 1H Magnetic Resonance Spectroscopy (MRS) be used to obtain information about the molecules and metabolites in live human spermatozoa? SUMMARY ANSWER: Percoll-based density gradient centrifugation (DGC) followed by a further two washing steps, yielded enough sperm with minimal contamination (<0.01%) from seminal fluid to permit effective MRS which detected significant differences (P < 0.05) in the choline/glycerophosphocholine (GPC), lipid and lactate regions of the 1H MRS spectrum between sperm in the pellet and those from the 40%/80% interface. WHAT IS KNOWN ALREADY: Current methods to examine sperm are either limited in their value (e.g. semen analysis) or are destructive (e.g. immunohistochemistry, sperm DNA testing). A few studies have previously used MRS to examine sperm, but these have either looked at seminal plasma from men with different ejaculate qualities or at the molecules present in pooled samples of lyophilized sperm. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Sperm suspended in phosphate buffered saline (PBS) at 37°C were examined by 1H MRS scanning using a 1H excitation-sculpting solvent suppression sequence after recovery from fresh ejaculates by one of three different methods: (i) simple centrifugation; (ii) DGC with one wash; or (iii) DGC with two washes. In the case of DGC, sperm were collected both from the pellet ('80%' sperm) and the 40/80 interface ('40%' sperm). Spectrum processing was carried out using custom Matlab scripts to determine; the degree of seminal plasma/Percoll contamination, the minimum sperm concentration for 1H MRS detection and differences between the 1H MRS spectra of '40%' and '80%' sperm. MAIN RESULTS AND THE ROLE OF CHANCE: DGC with two washes minimized the 1H MRS peak intensity for both seminal plasma and Percoll/PBS solution contamination while retaining sperm specific peaks. For the MRS scanner used in this study, the minimum sperm concentration required to produce a choline/GPC 1H MRS peak greater than 3:1 signal to noise ratio (SNR) was estimated at ~3 × 106/ml. The choline/GPC and lactate/lipid regions of the 1H spectrum were significantly different by two-way ANOVA analysis (P < 0.0001; n = 20). ROC curve analysis of these region showed significant ability to distinguish between the two sperm populations: choline/GPC ROC AUC = 0.65-0.67, lactate/lipid ROC AUC = 0.86-0.87. LIMITATIONS, REASONS FOR CAUTION: Only 3-4 semen samples were used to assess the efficacy of each sperm washing protocol that were examined. The estimated minimum sperm concentration required for MRS is specific to the hardware used in our study and may be different in other spectrometers. Spectrum binning is a low resolution analysis method that sums MRS peaks within a chemical shift range. This can obscure the identity of which metabolite(s) are responsible for differences between sperm populations. Further work is required to determine the relative contribution of somatic cells to the MRS spectrum from the '40%' and '80%' sperm. WIDER IMPLICATIONS OF THE FINDINGS: 1H MRS can provide information about the molecules present in live human sperm and may therefore permit the study of the underlying functional biology or metabolomics of live sperm. Given the relatively low concentration of sperm required to obtain a suitable MRS signal (~3 × 106/ml), this could be carried out on sperm from men with oligo-, astheno- or teratozoospermia. This may lead to the development of new diagnostic tests or ultimately novel treatments for male factor infertility. STUDY FUNDING AND COMPETING INTEREST(S): This work was supported by the Medical Research Council Grant MR/M010473/1. The authors declare no conflicts of interest.

Diffusion-weighted imaging and magnetic resonance proton spectroscopy following preterm birth.

AIM: To study the associations between magnetic resonance proton spectroscopy (MRS) data and apparent diffusion coefficients (ADC) from the preterm brain with developmental outcome at 18 months corrected age and clinical variables. MATERIALS AND METHODS: A prospective observational cohort study of 67 infants born before 35 weeks gestational age who received both magnetic resonance imaging of the brain between 37 and 44 weeks corrected gestational age and developmental assessment around 18 months corrected age. RESULTS: No relationships were found between ADC values and MRS results or outcome. MRS ratios involving N-acetyl aspartate (NAA) from the posterior white matter were associated with "severe" and "moderate to severe" difficulties, and fine motor scores were significantly lower in participants with a visible lactate doublet in the posterior white matter. The presence of a patent ductus arteriosus (PDA) was the only clinical factor related to NAA ratios. CONCLUSION: Altered NAA levels in the posterior white matter may reflect subtle white matter injury associated with neuro-developmental difficulties, which may be related to a PDA. Further work is needed to assess the longer-term neuro-developmental implications of these findings, and to study the effect of PDAs on developmental outcome in later childhood/adolescence.

Brain structure and function in patients after metal-on-metal hip resurfacing.

BACKGROUND AND PURPOSE: Hip prostheses that use a metal-on-metal articulation expose the brain to elevated metal concentrations that, in acute excess due to prosthesis malfunction, is associated with neurologic damage, including visual and hearing loss and motor deficits. Here, we examined whether chronic exposure to lower elevated metal levels, typical of well-functioning prostheses, also affects brain structure and function. MATERIALS AND METHODS: We compared brain volumes, metal deposition, and gray matter attenuation by MR imaging and clinical neurologic function in patients 8 years after receiving a metal-on-metal hip resurfacing versus a matched group of patients with the same duration exposure to a conventional hip prosthesis. RESULTS: Twenty-nine patients (25 men; mean, age 59±7 years) after metal-on-metal hip resurfacing and 29 patients (25 men; 59±8 years) after total hip arthroplasty were compared. Whole blood cobalt and chromium concentrations were 5-10 times higher in the metal-on-metal hip resurfacing group (P<.0001). Occipital cortex gray matter attenuation tended to be lower (P<.005 uncorrected, P>.05 corrected), and the optic chiasm area tended to be lower (mean difference, -2.7 mm2; P=.076) in the metal-on-metal hip resurfacing group. Subgroup analyses in 34 patients (17 per group), after exclusion of primary ocular pathology, showed the same trend in gray matter attenuation in the occipital cortex and basal ganglia and a smaller optic chiasm in the metal-on-metal hip resurfacing group (mean difference, -3.9 mm2; P=.048). No other structural or functional differences were found between the groups. CONCLUSIONS: Chronic exposure to metal-on-metal hip resurfacing is associated with subtle structural change in the visual pathways and the basal ganglia in asymptomatic patients.

Kinetic modeling of hyperpolarized (13)C pyruvate metabolism in tumors using a measured arterial input function.

Mathematical models are required to estimate kinetic parameters of [1-(13)C] pyruvate-lactate interconversion from magnetic resonance spectroscopy data. One- or two-way exchange models utilizing a hypothetical approximation to the true arterial input function (AIF), (e.g. an ideal 'box-car' function) have been used previously. We present a method for direct measurement of the AIF in the rat. The hyperpolarized [1-(13)C] pyruvate signal was measured in arterial blood as it was continuously withdrawn through a small chamber. The measured signal was corrected for T1 relaxation of pyruvate, RF pulses and dispersion of blood in the chamber to allow for the estimation of the direct AIF. Using direct AIF, rather than the commonly used box-car AIF, provided realistic estimates of the rate constant of conversion of pyruvate to lactate, kpl, the rate constant of conversion of lactate to pyruvate klp, the clearance rate constant of pyruvate from blood to tissue, Kip, and the relaxation rate of lactate T1la. Since no lactate signal was present in blood, it was possible to use a simple precursor-product relationship, with the tumor tissue pyruvate time-course as the input for the lactate time-course. This provided a robust estimate of kpl, similar to that obtained using a directly measured AIF.

An MR-compatible neonatal incubator.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: The incubator provides a safe, quiet environment for neonates during transport and imaging, at low cost.

Fetuses with ventriculomegaly diagnosed in the second trimester of pregnancy by in utero MR imaging: what happens in the third trimester?

BACKGROUND AND PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A prospective study of fetuses with isolated ventriculomegaly investigated by antenatal sonography and in utero MR imaging.

BACKGROUND AND PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The value of in-utero magnetic resonance imaging in ultrasound diagnosed foetal isolated cerebral ventriculomegaly.

AIM: To assess whether magnetic resonance imaging (MRI) is a useful adjunct to ultrasound (US) when imaging cases of foetal isolated cerebral ventriculomegaly. To assess whether, in such cases, ventricular morphology is a useful indicator for the underlying pathology, as has recently been suggested. MATERIALS AND METHODS: A retrospective analysis was undertaken of 30 cases of isolated ventriculomegaly diagnosed using US and referred for in utero MRI. The gestational age of each case was noted and the MRI report. Both ventricles were measured and each case was categorized according to severity and morphology. The MRI report was compared to the final diagnosis. RESULTS: Of the 30 cases evaluated 18 had mild ventriculomegaly (<15 mm; gestational age range 20-31 weeks, mean 22.8, median 22) and 12 had severe ventriculomegaly (>15 mm; gestational age range 21-37 weeks, mean 28, median 28.5). Additional abnormalities were found in 50% of cases overall (44% mild, 58% severe) using MRI. CONCLUSIONS: Using MRI additional abnormalities were identified in 50% of the foetuses. The morphology of the cases did not suggest underlying pathology in this group. In utero MRI is a useful adjunct to US in cases of foetal cerebral ventriculomegaly referred after initial diagnosis using US.

Post-mortem MRI of the foetal spine and spinal cord.

AIMS: To compare the findings of post-mortem magnetic resonance imaging (MRI) of the foetal spine with autopsy with a view to using post-mortem MRI as an alternative or adjunct to autopsy, particularly in foetal and neonatal cases. MATERIALS AND METHODS: The brains and spines of 41 foetuses, with a gestational age range of 14-41 weeks, underwent post-mortem MRI before autopsy. Post-mortem MRI of the brain consisted of T2-weighted sequences in three orthogonal planes and MRI of the spine consisted of T2-weighted sequence in the sagittal and axial planes in all cases and coronal planes in selected cases. RESULTS: Thirty of 41 (78%) foetal spines were found to be normal at autopsy and on post-mortem MRI. Eleven of 41 (22%) foetal spines were abnormal: eight foetuses had myelomeningocoeles and Chiari 2 deformities, one foetus had limited dorsal myeloschisis, one foetus had caudal regression syndrome, and one had diastematomyelia. The post-mortem MRI findings concurred with the autopsy findings in 10/11 of the abnormal cases, the disagreement being the case of diastematomyelia that was shown on post-mortem MRI but was not diagnosed at autopsy. CONCLUSIONS: In this series, post-mortem MRI findings agreed with the autopsy findings in 40/41(98%) cases and in one case the post-mortem MRI demonstrated an abnormality not demonstrated at autopsy.

Combined simulated annealing and Shinnar-Le Roux pulse design of slice-multiplexed RF pulses for multi-slice imaging.

Slice-multiplexed RF pulses have recently been introduced for simultaneous multi-slice imaging. Their novel aspect is that each slice is given a different linear phase profile, and hence a different slice-rephasing requirement, by the pulse. During readout, extra slice gradients are applied such that when one slice is rephased, the others are dephased to prevent aliasing. In this paper, an improved method of designing slice-multiplexed RF pulses is presented: component pulses which are optimized with simulated annealing for a specific rephasing are combined using Shinnar-Le Roux methods. In this way, non-linearities at higher flip angles are taken into account and more slices can be excited. Bloch simulations show the phase and amplitude profile of component pulses are faithfully preserved in the multiplexed pulse. Three- and four-slice multiplex pulses are demonstrated in gradient- and spin-echo in-vivo imaging.

Normal fetal lumbar spine on postmortem MR imaging.

BACKGROUND AND PURPOSE: There is an increasing interest in use of postmortem MR imaging as an adjunct or alternative to autopsy. Before evaluating spinal pathology on postmortem MR imaging, it is important to have knowledge of the normal appearance of the fetal spine at different gestational ages. The aim of this study is to describe the MR imaging appearances of normal development of the fetal spine at different gestational ages. METHODS: Postmortem MR imaging was performed on 30 fetuses ranging from 14 to 41 gestational weeks. There was no structural abnormality of the spine in these fetuses on MR imaging or at autopsy. Fast spin-echo T2-weighted MR imaging of the lumbar spine was performed in the coronal plane in all cases and supplemented by sagittal and/or axial imaging. The following parameters were measured: height of the L1/2 disk and L2 vertebral body and area of ossification center in L2 vertebral body as well as area of vertebral body. The signal intensity of the disk space and the vertebral level of conus termination were also assessed. RESULTS: The height and area of the vertebral body increased linearly with gestational age (P <.01). The increase in disk space was proportionally greater than the increase in vertebral body height as gestational age increased (P <.01). The disk space appeared as a linear low-signal-intensity area in fetuses < or = 21 weeks gestation but increasingly developed high signal intensity in the disk after 21 weeks. The size of the ossification center increased with gestational age (P <.01), and the ratio of ossification center to the overall size of the vertebral body also increased with gestational age (P <.01). In fetuses less than 35 weeks of age, the conus lay between L2 and L5 level, whereas in fetuses more than 35 weeks of age, the conus lay between L1/2 and L2/3 level. CONCLUSION: Understanding the normal growth and signal-intensity characteristics of the fetal spine on postmortem MR imaging is essential before studying abnormal fetal spine.

Post-mortem fetal MRI: what do we learn from it?

Post-mortem magnetic resonance (MR) imaging is of increasing interest not only as an alternative to autopsy but as a research tool to aid the interpretation and diagnosis of in utero MR images. The information from the post-mortem MR has allowed the development of imaging sequences applicable to in utero imaging and neonatal imaging. It has established brain development during gestation and has provided data on this to which in utero MR can be compared. The detail available from the post-mortem images is such that brain development can be studied in a non-invasive manner, a permanent record on the normal and abnormal areas is available and a greater understanding of developmental abnormalities is possible.

Simultaneous multislice imaging with slice-multiplexed RF pulses.

A method for simultaneous multislice imaging is presented that uses a multislice RF pulse that imparts a different linear phase profile to each slice. During readout, slices are unaliased by using extra slice-select gradient lobes, which rephase and dephase individual slices one at a time. Compared to other simultaneous slice methods, this method avoids distortion by slice-select gradients, and does not require extra views or additional hardware. However, because one echo per slice is required, the method requires a longer read period. This can cause non-ideal rephasing of the individual slices due to susceptibility gradients, which manifests itself as crosstalk between slices. There is also a concomitant increase in the minimum TR of the sequence. The method is demonstrated with phantom and in vivo images using gradient-echo and spin-echo versions.

Method of generalized projections algorithm for image-based reduction of artifacts in radial imaging.

This work describes the method of generalized projections (MGP) as an image-based, postprocessing method to correct for phase inconsistencies caused by echo misalignments in radial imaging. Computer simulations show that MGP can correct for echo shifts, constant phase, and amplitude errors, but the accuracy of the correction is limited, and this accuracy is reduced by the addition of more degrees of freedom. In phantom experiments, MGP performed better than magnitude filtered backprojection and anti-parallel projections correction.

Post-mortem MRI as an adjunct to fetal or neonatal autopsy.

CONTEXT: Understanding what was wrong with a dead fetus or why a newborn child died can help the parents to grieve, while any findings can be used to inform the parents if there is a risk to future pregnancies and the level of risk. This information is mainly obtained from autopsies, but the number of parents agreeing to autopsy has dropped, which has prompted the search for adjuncts to autopsy. STARTING POINT: The UK's Chief Medical Officer outlined the rationale for exploring alternatives to autopsy in 2000 and 2001. After wide consultation, MRI was deemed to offer the most realistic chance of making a contribution. Results so far are promising, but of insufficient depth and quality to make firm recommendations about providing a service in the future. In 2004, the UK Department of Health therefore tendered for this research to be done in fetal and neonatal (and adult) cases, and this work is due to start in 2005. WHERE NEXT? High-quality anatomical information about the brain and spine of fetuses and neonates can be easily obtained with standard MRI scanners. Most developmental and acquired abnormalities can be seen on post-mortem MRI. More work needs to be done on organs not in the central nervous system, and heart malformations, in particular, might present diagnostic problems. A possible outcome could be whole-body MRI plus targeted biopsies of abnormalities taken under image guidance as an adjunct to formal autopsy.

Diffusion tensor imaging for the assessment of upper motor neuron integrity in ALS.

BACKGROUND: High angular resolution diffusion tensor imaging (HARD) is an MRI technique that exploits the mobility of water molecules to yield maps of structural order and directionality of white matter tracts with greater precision than six-direction diffusion tensor imaging (DTI) schemes. OBJECTIVE: To assess whether HARD is more sensitive than conventional MRI or neurologic assessment in detecting the upper motor neuron (UMN) pathology of patients with ALS. METHODS: Twenty-five patients with definite UMN clinical signs and 23 healthy volunteers underwent conventional MRI. HARD datasets were collected from a subset of these participants plus four patients with isolated lower motor neuron (LMN) signs. ALS symptom severity was assessed by a neurologist, the conventional MR images were reviewed by neuroradiologists, and the DTI maps were subject to quantitative region of interest analysis. RESULTS: Motor cortex hypointensity on T2-weighted images and corona radiata hyperintensity on proton density-weighted images distinguished patients with UMN involvement from volunteers with 100% specificity, but only 20% sensitivity. Fractional anisotropy (FA) was reduced in the posterior limb of the internal capsule in patients with UMN involvement compared to volunteers. A FA threshold value with a sensitivity of 95% to detect patients with ALS (including those with isolated LMN signs) had a specificity of 71%. CONCLUSIONS: High angular resolution diffusion tensor imaging may be more sensitive than conventional MRI or neurologic assessment to the upper motor neuron (UMN) pathology of ALS, but it lacks the specificity required of a diagnostic marker. Instead, it is potentially useful as a quantitative tool for monitoring the progression of UMN pathology.

Corroboration of in utero MRI using post-mortem MRI and autopsy in foetuses with CNS abnormalities.

AIMS: To corroborate the findings of in utero magnetic resonance imaging (MRI) with autopsy and post-mortem MRI in cases of known or suspected central nervous system (CNS) abnormalities on ultrasound and to compare the diagnostic accuracy of ante-natal ultrasound and in utero MRI. METHODS: Twelve pregnant women, whose foetuses had suspected central nervous system abnormalities underwent in utero MRI. The foetuses were imaged using MRi before autopsy. The data were used to evaluate the diagnostic accuracy of in utero MRI when compared with a reference standard of autopsy and post-mortem MRI in 10 cases and post-mortem MRI alone in two cases. RESULTS: The diagnostic accuracy of antenatal ultrasound and in utero MRI in correctly characterizing brain and spine abnormalities were 42 and 100%, respectively. CONCLUSION: In utero MRI provides a useful adjuvant to antenatal ultrasound when assessing CNS abnormalities by providing more accurate anatomical information. Post-mortem MRI assists the diagnosis of macroscopic structural abnormalities.

Comparison of ultrasound and magnetic resonance imaging in 100 singleton pregnancies with suspected brain abnormalities.

OBJECTIVE: To compare the diagnostic accuracy of the current reference standard-ultrasound with in utero magnetic resonance imaging, in a selected group of patients. DESIGN: Prospective study. SETTING: Five fetal maternal tertiary referral centres and an academic radiology unit. SAMPLE: One hundred cases of fetuses with central nervous system abnormalities where there has been diagnostic difficulties on ultrasound. In 48 cases the women were less than 24 weeks of gestation and in 52 cases later in pregnancy. METHODS: All women were imaged on a 1.5 T clinical system using a single shot fast spin echo technique. The results of antenatal ultrasound and in utero magnetic resonance were compared. MAIN OUTCOME MEASURES: The definitive diagnosis was made either at autopsy or by postmortem magnetic resonance imaging, in cases that went to termination of pregnancy, or a combination of postnatal imaging and clinical follow up in the others. RESULTS: In 52 of cases, ultrasound and magnetic resonance gave identical results and in a further 12, magnetic resonance provided extra information that was judged not to have had direct effects on management. In 35 of cases, magnetic resonance either changed the diagnosis (29) or gave extra information that could have altered management (6). In 11 of the 30 cases where magnetic resonance changed the diagnosis, the brain was described as normal on magnetic resonance. CONCLUSIONS: In utero magnetic resonance imaging is a powerful tool in investigating fetal brain abnormalities. Our results suggest that in selected cases of brain abnormalities, detected by ultrasound, antenatal magnetic resonance may provide additional, clinically useful information that may alter management.

A method of generalized projections (MGP) ghost correction algorithm for interleaved EPI.

Investigations into the method of generalized projections (MGP) as a ghost correction method for interleaved EPI are described. The technique is image-based and does not require additional reference scans. The algorithm was found to be more effective if a priori knowledge was incorporated to reduce the degrees of freedom, by modeling the ghosting as arising from a small number of phase offsets. In simulations with phase variation between consecutive shots for n-interleaved echo planar imaging (EPI), ghost reduction was achieved for n = 2 only. With no phase variation between shots, ghost reduction was obtained with n up to 16. Incorporating a relaxation parameter was found to improve convergence. Dependence of convergence on the region of support was also investigated. A fully automatic version of the method was developed, using results from the simulations. When tested on in vivo 2-, 16-, and 32-interleaved spin-echo EPI data, the method achieved deghosting and image restoration close to that obtained by both reference scan and odd/even filter correction, although some residual artifacts remained.