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.

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.

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.

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.

Frequency and natural history of subdural haemorrhages in babies and relation to obstetric factors.

BACKGROUND: Subdural haematomas are thought to be uncommon in babies born at term. This view is mainly based on findings in symptomatic neonates and babies in whom subdural haemorrhages are detected fortuitously. We aimed to establish the frequency of subdural haemorrhages in asymptomatic term neonates; to study the natural history of such subdural haematomas; and to ascertain which obstetric factors, if any, are associated with presence of subdural haematoma. METHODS: We did a prospective study in babies who were born in the Jessop wing of the Central Sheffield University Hospitals between March, 2001, and November, 2002. We scanned neonates with a 0.2 T magnetic resonance machine. FINDINGS: 111 babies underwent MRI in this study. 49 were born by normal vertex delivery without instrumentation, 25 by caesarean section, four with forceps, 13 ventouse, 18 failed ventouse leading to forceps, one failed ventouse leading to caesarean section, and one failed forceps leading to caesarean section. Nine babies had subdural haemorrhages: three were normal vaginal deliveries (risk 6.1%), five were delivered by forceps after an attempted ventouse delivery (27.8%), and one had a traumatic ventouse delivery (7.7%). All babies with subdural haemorrhage were assessed clinically but no intervention was needed. All were rescanned at 4 weeks and haematomas had completely resolved. INTERPRETATION: Presence of unilateral and bilateral subdural haemorrhage is not necessarily indicative of excessive birth trauma.

Cerebral proton magnetic resonance spectroscopy in asymptomatic HIV infection.

OBJECTIVE: To determine whether proton magnetic resonance spectroscopy (MRS) demonstrates central nervous system abnormalities in asymptomatic HIV-1-infected individuals. DESIGN: Both prospective and retrospective cross-sectional analyses of MRS in asymptomatic HIV-infected individuals. SETTING: Two specialists HIV/AIDS outpatient facilities in London. PARTICIPANTS: Eighty-four HIV-1 seropositive asymptomatic men; 29 HIV-1 antibody-negative homosexual men at high-risk for HIV infection and 48 HIV-1 antibody-negative men at low-risk for HIV infection as controls. MAIN OUTCOME MEASURES: Single voxel, gradient-localized proton MRS performed at 1.5 T with 135 msec echo-time and 1,600 msec repeat-time in an 8 ml volume of interest positioned in the parieto-occipital white matter. Spectroscopic results were expressed as ratios between the areas under the N-acetyl (NA), creatine (Cr) and choline (Cho) resonance peaks. RESULTS: There were no differences between those controls at high and those at low-risk for HIV infection. Comparing the combined control groups with the asymptomatic seropositive patients there were statistically significant differences in NA/Cho, NA/Cr (both P < 0.05) and NA/(NA + Cho + Cr) (P < 0.01). CONCLUSION: Abnormalities in cerebral biochemistry may be demonstrated by proton MRS during asymptomatic HIV-1 infection.

Multimodality MR imaging depiction of hemodynamic changes and cerebral ischemia in subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) is a common and serious neurologic emergent condition. We tested the hypothesis that multimodality MR imaging depicts changes in cerebral blood flow SAH, before any surgical or endovascular intervention, and that the frequency of these changes increases with time after ictus. METHODS: We prospectively examined 37 patients with suspected SAH and three with symptoms of acute stroke but who subsequently had SAH. Routine CT and multimodality MR imaging were performed within 18 h of presentation. Standard MR imaging, diffusion-weighted MR imaging, time-of-flight MR angiography, and dynamic first-pass gadolinium-enhanced MR perfusion imaging were performed. Images were reviewed for abnormalities in cerebral blood flow, ischemia, and infarction. Nine patients did not have SAH at CT and CSF investigations. Of 31 patients with proved SAH, 13 were examined during the acute stage (within 4 d of ictus) and 18, during the subacute stage (4-14 d after ictus). RESULTS: MR imaging showed alteration in cerebral blood flow parameters in 16 of 31 patients before surgery or endovascular treatment. The frequency of blood flow changes and associated complications increased with worsening clinical grade and increasing time after ictus. CONCLUSION: Multimodality MR imaging provides information not available from CT in patients with SAH. MR imaging shows oligemic and ischemic areas in SAH before surgery or endovascular treatment. MR imaging is a simple noninvasive method of assessing cerebral blood flow and its complications in SAH. It can be performed in a clinical environment.

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.

MR imaging of the lungs with hyperpolarized helium-3 gas transported by air.

Hyperpolarized noble gas MRI shows promise in the functional imaging of the pulmonary air spaces. The production of hyperpolarized (HP) gas requires specialized laser optical pumping apparatus, which is not likely to be home built in the majority of clinical MRI radiology centres. There are two routes through which HP gas will be made available to hospitals for clinical use: either the apparatus will be installed locally at a considerable expense to the centre, or a central facility will produce the gas and then deliver it to remote MRI sites as and when required. In this study, the feasibility of transporting large quantities of HP gas for in vivo MR imaging from a remote production facility in Mainz, Germany, by airfreight to Sheffield, UK, was successfully demonstrated.

Low field strength magnetic resonance imaging of the neonatal brain.

BACKGROUND: Magnetic resonance (MR) imaging of the neonate has been restricted by the need to transport the sick baby to the large magnetic resonance scanners and often the need for sedation or anaesthesia in order to obtain good quality images. Ultrasound is the reference standard for neonatal imaging. OBJECTIVE: To establish a dedicated neonatal MR system and compare the clinical usefulness of MR imaging with ultrasound imaging. DESIGN: Prospective double blind trial. SETTING: Neonatal intensive care unit, Sheffield. MAIN OUTCOME MEASURES: Imaging reports. PATIENTS: 134 premature and term babies. RESULTS: In 56% of infants with pathology suspected on clinical grounds, MR provided additional useful clinical information over and above that obtained with ultrasound. CONCLUSION: Infants can be safely imaged by dedicated low field magnetic resonance on the neonatal intensive care unit without the need for sedation at a cost equivalent to ultrasound.

Magnetic resonance imaging with stepped B(0) fields.

This paper introduces the concept of imaging with stepped magnetic fields within the main B(0) field. The resonance frequency within each step is separated from the next by an amount greater than the imaging bandwidth. Each step thus gives rise to a separate imaging region enabling simultaneous imaging over multiple slices without aliasing. The auxiliary magnetic field regions are produced by coil inserts. The principle is illustrated using simple coil designs which introduce up to two steps into the main B(0) field. Phantoms placed in each uniform region were successfully imaged simultaneously with no aliasing.

Fast two-dimensional MR imaging by multiple acquisition with micro B(0) array (MAMBA).

A new method for acquiring MR data in two dimensions is described. This is achieved by combining coils into an array so as to produce a unique local magnetic field within each coil when placed within the B(0) field of a standard MRI scanner. In this way each known location of a coil is associated with a unique resonant frequency. Each coil now represents a location of a pixel in the plane, and after Fourier transformation of the signal the resulting frequency spectrum gives immediately the spin distribution in the plane of the array. In effect, the two-dimensional spatial distribution is frequency encoded without the use of switched gradients or phase encoding. As only static fields are used, this technique offers the potential of fast imaging. Furthermore, signals from different locations would also be inherently time-registered. Initial experiments to demonstrate the principle are described, using a square array of 5 by 5 coils. The currents in the coils were determined by using a genetic algorithm. Echoes from pellet phantoms placed in the array were acquired using standard spin-echo sequences with gradients switched off. The results are promising, with the spectra showing generally good resolution between peaks, enabling localisation in up to half the pixels. Technical difficulties are discussed and possible applications are outlined.

Cerebral volumes and spectroscopic proton metabolites on MR: is sex important?

One of the factors that may influence the selection of appropriate controls for MR studies of the brain is gender. This study compared calculated intracranial volumes and proton spectroscopic metabolite ratios obtained from male and female volunteers. Thirty-two males (mean age = 36; range = 30-53 yr) and 19 females (mean age = 39; range = 26-53 yr) underwent investigation at 1.5T. Brain, cerebrospinal fluid (CSF), and intracranial (ICV = brain + CSF) volumes were measured by the CLASS technique on data acquired using an axial dual spin-echo imaging sequence (TE = 20/90 ms, TR = 3500 ms). Proton spectra (TE = 135 ms, TR = 1600 ms) were acquired from an 8 ml cubic region placed in parieto-occipital white matter. The mean male and female brain, CSF and ICV were significantly different (p < .005). However, the mean CSF/ICV ratios of the two groups were not significantly different. The N-acetyl/choline and choline/creatine metabolite ratios of the two groups were significantly different (p < .05). When comparing proton metabolite ratios and absolute brain volumes between groups, gender is an important factor. CSF/ ICV ratios do not appear to depend on gender.

The measurement of R2, R2* and R2' in HIV-infected patients using the prime sequence as a measure of brain iron deposition.

Brain iron deposition was assessed at 1.5 T in the caudate nucleus, globus pallidus and frontal and parieto-occipital white matter in 28 human immunodeficiency virus (HIV)-infected patients and 15 control subjects with a new Partially Refocussed Interleaved Multi-Echo sequence by measuring 1/T2, 1/T2* and 1/T2' (i.e., R2, R2* and R2'). There were significant differences in the R2 and R2* of the caudate nucleus (p < 0.0001 and p < 0.05) and the R2, R2* and R2' of the globus pallidus (p < 0.01, p < 0.005 and p < 0.05) in HIV-infected patients compared to control subjects. There was a trend for higher values of R2, R2* and R2' in the globus pallidus and caudate nucleus in HIV-infected patients with later stage HIV disease. These results suggest that there is greater iron deposition in the basal ganglia of HIV-infected patients compared with control subjects, with a predilection for the globus pallidus. The relationship between iron deposition in the brain and various parameters of severity of HIV infection remains uncertain.

Cerebral magnetic resonance relaxometry in HIV infection.

A prospective, cross-sectional study was designed to determine the magnetic resonance relaxation times of cerebral white matter in human immunodeficiency virus (HIV) infected individuals. T1 and T2 were estimated at 1.5 T using four-point methods. Seventy-five HIV-1 seropositive subjects, 48 seronegative blood donors, and 17 seronegative homosexual men were studied. Associations between relaxometry and clinical classification, neurological status, immunological status, and qualitative MRI were investigated. Statistically significant differences in white matter T1 relaxation time were found comparing low-risk control and AIDS groups (p < .005), seropositive subjects with neurological signs and those without (p < .005), and subjects with low (CD4 < or = 200 x 10(6)/l) and high (CD4 > 200 x 10(6)/1) CD4 cell counts (p < .05). These findings add to the body of information that reveals no HIV-related change in the brain before the onset of symptomatic immunosuppression and go someway to validating the previous visually rated, qualitative findings. Statistically significant difference in white matter T2 relaxation time were also found comparing the two control groups (p < .005) highlighting the need for appropriate controls.

MR imaging of the fetal brain and spine: a maturing technology.

INTRODUCTION: We describe the background and refinements to a 3-year research study designed to evaluate the role of magnetic resonance (MR) imaging in detecting and defining abnormalities of the fetal central nervous system in utero. METHODS: We describe our experience of using ultra-fast MR imaging methods (specifically single-shot fast spin echo) in 250 fetuses at various gestational ages. All fetuses had known or suspected brain or spine abnormalities based on antenatal ultrasound imaging. We describe the ethical issues raised by this type of work and the differences in diagnostic accuracy between ultrasound and MR imaging. RESULTS: We show that MR imaging can be performed in a clinical environment with a high degree of success: only 2 women out of 250 could not be examined (1 was claustrophobic and the other was too large for our scanner). In the 100 cases of singleton pregnancies, where detailed follow-up is available, there is a > 40% improvement in diagnostic accuracy when MR imaging is included in the fetal assessment compared to ultrasound alone. CONCLUSION: We conclude that in utero MR imaging is a powerful tool in the assessment of fetal brain and spine abnormalities, and suggest that further work be undertaken to provide a widely available clinical service.