Kinetic modelling of dissolution dynamic nuclear polarisation 13 C magnetic resonance spectroscopy data for analysis of pyruvate delivery and fate in tumours.

Dissolution dynamic nuclear polarisation (dDNP) of 13 C-labelled pyruvate in magnetic resonance spectroscopy/imaging (MRS/MRSI) has the potential for monitoring tumour progression and treatment response. Pyruvate delivery, its metabolism to lactate and efflux were investigated in rat P22 sarcomas following simultaneous intravenous administration of hyperpolarised 13 C-labelled pyruvate (13 C1 -pyruvate) and urea (13 C-urea), a nonmetabolised marker. A general mathematical model of pyruvate-lactate exchange, incorporating an arterial input function (AIF), enabled the losses of pyruvate and lactate from tumour to be estimated, in addition to the clearance rate of pyruvate signal from blood into tumour, Kip , and the forward and reverse fractional rate constants for pyruvate-lactate signal exchange, kpl and klp . An analogous model was developed for urea, enabling estimation of urea tumour losses and the blood clearance parameter, Kiu . A spectral fitting procedure to blood time-course data proved superior to assuming a gamma-variate form for the AIFs. Mean arterial blood pressure marginally correlated with clearance rates. Kiu equalled Kip , indicating equivalent permeability of the tumour vasculature to urea and pyruvate. Fractional loss rate constants due to effluxes of pyruvate, lactate and urea from tumour tissue into blood (kpo , klo and kuo , respectively) indicated that T1 s and the average flip angle, θ, obtained from arterial blood were poor surrogates for these parameters in tumour tissue. A precursor-product model, using the tumour pyruvate signal time-course as the input for the corresponding lactate signal time-course, was modified to account for the observed delay between them. The corresponding fractional rate constant, kavail , most likely reflected heterogeneous tumour microcirculation. Loss parameters, estimated from this model with different TRs, provided a lower limit on the estimates of tumour T1 for lactate and urea. The results do not support use of hyperpolarised urea for providing information on the tumour microcirculation over and above what can be obtained from pyruvate alone. The results also highlight the need for rigorous processes controlling signal quantitation, if absolute estimations of biological parameters are required.

Initial experience of an investigational 3T MR scanner designed for use on neonatal wards.

OBJECTIVES: MR imaging of neonates is difficult for many reasons and a major factor is safe transport to the MR facilities. In this article we describe the use of a small, investigational 3-T MR customised for brain imaging and sited on a neonatal unit of a tertiary centre in the UK, which is in contrast to a 300-m journey to the whole-body MR scanner used at present for clinical cases. METHODS: We describe our methods for preparing babies for safe transport and scanning on an investigational 3-T MR scanner on a neonatal unit and the development of appropriate MR sequences. The MR scanner does not have CE marking at present so this early development work was undertaken on normal neonates whose parents consented to a research examination. RESULTS: Fifty-two babies were scanned and there were no serious adverse events. The MR examinations were considered to be diagnostically evaluable in all 52 cases and in 90% the imaging was considered to be at least as good as the quality obtained on the 1.5-T scanner currently used for clinical cases. CONCLUSION: We have shown that this investigational 3-T MR scanner can be used safely on a neonatal unit and we have refined the MR sequences to a point that they are clinically usable. KEY POINTS: • Access to neonatal MR imaging is limited. • We describe an investigational 3-T MR scanner site on a neonatal unit. • The scanner produces images suitable for clinical practice.

Direct arterial injection of hyperpolarized 13 C-labeled substrates into rat tumors for rapid MR detection of metabolism with minimal substrate dilution.

PURPOSE: A rat model was developed to enable direct administration of hyperpolarized 13 C-labeled molecules into a tumor-supplying artery for magnetic resonance spectroscopy (MRS) studies of tumor metabolism. METHODS: Rat P22 sarcomas were implanted into the right inguinal fat pad of BDIX rats such that the developing tumors received their principle blood supply directly from the right superior epigastric artery. Hyperpolarized 13 C-molecules were either infused directly to the tumor through the epigastric artery or systemically through the contralateral femoral vein. Spectroscopic data were obtained on a 7 Tesla preclinical scanner. RESULTS: Intra-arterial infusion of hyperpolarized 13 C-pyruvate increased the pyruvate tumor signal by a factor of 4.6, compared with intravenous infusion, despite an approximately 7 times smaller total dose to the rat. Hyperpolarized glucose signal was detected at near-physiological systemic blood concentration. Pyruvate to lactate but not glucose to lactate metabolism was detected in the tumor. Hyperpolarized 13 C-labeled combretastatin A1 diphosphate, a tumor vascular disrupting agent, showed an in vivo signal in the tumor. CONCLUSIONS: The model maximizes tumor substrate/drug delivery and minimizes T1 relaxation signal losses in addition to systemic toxicity. Therefore, it permits metabolic studies of hyperpolarized substrates with relatively short T1 and opens up the possibility for preclinical studies of hyperpolarized drug molecules. Magn Reson Med 78:2116-2126, 2017. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

MALDI-MSI and label-free LC-ESI-MS/MS shotgun proteomics to investigate protein induction in a murine fibrosarcoma model following treatment with a vascular disrupting agent.

Tumour vasculature is notoriously sinusoidal and leaky, and is hence susceptible to vascular disruption. Microtubule destabilising drugs such as the combretastatins form the largest group of tumour vascular disrupting agents and cause selective shutdown of tumour blood flow within minutes to hours, leading to secondary tumour cell death. Targeting the tumour vasculature is a proven anticancer strategy but early treatment response biomarkers are required for personalising treatment planning. Protein induction following treatment with combretastatin A4-phosphate was examined in a mouse fibrosarcoma model (fs188), where tumour cells express only the matrix-bound isoform of vascular endothelial growth factor A (VEGF188). These tumours are relatively resistant to vascular disruption by combretastatin A4-phosphate and hence a study of protein induction following treatment could yield insights into resistance mechanisms. The distribution of a number of proteins induced following treatment were visualised by MALDI-mass spectrometry imaging. Responses identified were validated by LC-ESI-MS/MS and immunohistochemical staining. Significant changes in proteins connected with necrosis, cell structure, cell survival and stress-induced molecular chaperones were identified. Protein-protein interactions were identified using STRING 9.0 proteomic network software. These relationship pathways provided an insight into the activity of the active tumour milieu and a means of linking the identified proteins to their functional partners.

Fetal electrocardiogram (fECG) gated MRI.

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.

Targeted magnetic resonance imaging (tMRI) of small changes in the T1 and spatial properties of normal or near normal appearing white and gray matter in disease of the brain using divided subtracted inversion recovery (dSIR) and divided reverse subtracted inversion recovery (drSIR) sequences.

This review describes targeted magnetic resonance imaging (tMRI) of small changes in the T1 and the spatial properties of normal or near normal appearing white or gray matter in disease of the brain. It employs divided subtracted inversion recovery (dSIR) and divided reverse subtracted inversion recovery (drSIR) sequences to increase the contrast produced by small changes in T1 by up to 15 times compared to conventional T1-weighted inversion recovery (IR) sequences such as magnetization prepared-rapid acquisition gradient echo (MP-RAGE). This increase in contrast can be used to reveal disease with only small changes in T1 in normal appearing white or gray matter that is not apparent on conventional MP-RAGE, T2-weighted spin echo (T2-wSE) and/or fluid attenuated inversion recovery (T2-FLAIR) images. The small changes in T1 or T2 in disease are insufficient to produce useful contrast with conventional sequences. To produce high contrast dSIR and drSIR sequences typically need to be targeted for the nulling TI of normal white or gray matter, as well as for the sign and size of the change in T1 in these tissues in disease. The dSIR sequence also shows high signal boundaries between white and gray matter. dSIR and drSIR are essentially T1 maps. There is a nearly linear relationship between signal and T1 in the middle domain (mD) of the two sequences which includes T1s between the nulling T1s of the two acquired IR sequences. The drSIR sequence is also very sensitive to reductions in T1 produced by Gadolinium based contrast agents (GBCAs), and when used with rigid body registration to align three-dimensional (3D) isotropic pre and post GBCA images may be of considerable value in showing subtle GBCA enhancement. In serial MRI studies performed at different times, the high signal boundaries generated by dSIR and drSIR sequences can be used with rigid body registration of 3D isotropic images to demonstrate contrast arising from small changes in T1 (without or with GBCA enhancement) as well as small changes in the spatial properties of normal tissues and lesions, such as their site, shape, size and surface. Applications of the sequences in cases of multiple sclerosis (MS) and methamphetamine dependency are illustrated. Using targeted narrow mD dSIR sequences, widespread abnormalities were seen in areas of normal appearing white matter shown with conventional T2-wSE and T2-FLAIR sequences. Understanding of the features of dSIR and drSIR images is facilitated by the use of their T1-bipolar filters; to explain their targeting, signal, contrast, boundaries, T1 mapping and GBCA enhancement. Targeted MRI (tMRI) using dSIR and drSIR sequences may substantially improve clinical MRI of the brain by providing unequivocal demonstration of abnormalities that are not seen with conventional sequences.

NMR spectroscopy of live human asthenozoospermic and normozoospermic sperm metabolism.

Sperm motility varies between ejaculates from different men and from individual men. We studied normozoospermic and asthenozoospermic ejaculates after density-gradient centrifugation washing (DCG, 80/40%) and compared high- (80%) and low (40%)-motility sperm populations within the same sample. Our objective was to identify differences in endogenous metabolomes and energy metabolism in relation to sperm motility. 1H-Nuclear Magnetic Resonance spectroscopy (NMR) measured the endogenous metabolome of live human sperm. Incubating sperm with 13C-labelled substrates detected energy metabolism by 13C-NMR. The study examined 850 ejaculates and diagnosed asthenozoospermia in 6.1%. DGC was used to wash 160 normozoospermic (N) and 52 asthenozoospermic (A) ejaculates to recover high-motility sperm from the pellet (80N/80A) and low motility from the interface (40N/40A). 1H-NMR spectra, 45(N) and 15(A), were binned and the integrals normalised by sperm concentration. Sperm from 126(N) and 36(A) ejaculates were incubated with either 13C-glucose, 13C-fructose or 13C-pyruvate. 13C-NMR lactate and bicarbonate integrals were normalised by motile or vital sperm concentrations. 1H-NMR spectra choline integrals from the 80A population were significantly lower than the 80N, P < 0.0001. 13C-substrate conversion to lactate was significantly higher for 40A sperm than 80A sperm when normalised by motile sperm concentration. Bicarbonate integrals were sporadically observed. Sperm from asthenozoospermic ejaculates had similar glycolytic requirements to normozoospermic ones, with larger differences observed between 40 and 80% sperm populations. Higher lactate levels produced by 40% sperm may indicate that impaired sperm motility is due to dysregulated energy metabolism. The alteration in choline metabolism provides opportunities to understand the aetiology of asthenozoospermia. Lay summary: How well sperm swim (motility) varies between ejaculates from different men? Normal sperm motility is beneficial to conception and some men diagnosed with infertility have low sperm motility. Sperm metabolise molecules to produce the energy required for motility. We measured concentrations of molecules within sperm and metabolism of molecules given to sperm and related these to the proportion of motile sperm. The study examined 850 sperm samples and found low motility in 6.1%. Metabolism of molecules given to sperm was similar between low and normal motility sperm samples. However, when the most motile sperm were separated from the rest, they were more efficient in metabolising these molecules to achieve motility. Lower concentrations of a molecule called choline were found in low-motility sperm samples compared to normal samples. Choline is associated with cell membranes, energy metabolism and oxidative stress, which may give opportunities to understand the causes of low motility.

Recent advances on optic nerve magnetic resonance imaging and post-processing.

The optic nerve is known to be one of the largest nerve bundles in the human central nervous system. There have been many studies of optic nerve imaging and post-processing that have provided insights into pathophysiology of optic neuritis related to multiple sclerosis and neuromyelitis optica spectrum disorder, glaucoma, and Leber's hereditary optic neuropathy. There are many challenges in optic nerve imaging, due to the morphology of the nerve through its course to the optic chiasm, its mobility due to eye movements and the high signal from cerebrospinal fluid and orbital fat surrounding the optic nerve. Recently, many advanced and fast imaging sequences have been used with post-processing techniques in attempts to produce higher resolution images of the optic nerve for evaluating various diseases. Magnetic resonance imaging (MRI) is one of the most common imaging methodologies for the optic nerve. This review paper will focus on recent MRI advances in optic nerve imaging and explain several post-processing techniques being used for analysis of optic nerve images. Finally, some challenges and potential for future optic nerve studies will be discussed.

Neonatal cochlear function: measurement after exposure to acoustic noise during in utero MR imaging.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Diffusion-weighted imaging of cerebral white matter and the cerebellum following preterm birth.

AIM: 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. METHOD: 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. RESULTS: 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. INTERPRETATION: 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.

Comparison of BOLD and direct-MR neuronal detection (DND) in the human visual cortex at 3T.

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.

SNR phase order k-space encoding (SPOKE).

A method of determining the phase-encode order for MR Fourier-encoded imaging is described, which provides an additional option for optimizing images from samples with signals that change during data acquisition. Examples are in hyperpolarized helium gas imaging of the lungs where polarization is lost with each RF pulse or the signal changes observed in rapid dynamic studies with T(1) or T(2)* contrast agents when mixing is taking place. The method uses a single frequency-encoded projection in the proposed phase-encoding direction. The projection is subsequently sorted into signal-to-noise ratio (SNR) order. The indices of the sorted array are then used to create the phase-encode table to be used for the scan. This phase table is sorted in descending SNR order for signals that decrease during data acquisition and in ascending order for signals that increase during data acquisition. Simulations suggest that this technique can produce higher resolution than centric-ordered phase encoding at the expense of increased modulation (ghosting) artifact for dynamically changing signals. Initial practical implementation of the technique has been carried out on a dedicated 0.2-T Niche MR system, and the test object results agree well with simulations. Hyperpolarized 3-He lung images have also been acquired and postprocessed using the SNR phase order k-space encoding (SPOKE) methodology and show potential for improved imaging with high flip angles where polarization is rapidly lost. Applications may also be found for 3D volumetric acquisitions where two dimensions can be SPOKE encoded.

Evidence for Rapid Oxidative Phosphorylation and Lactate Fermentation in Motile Human Sperm by Hyperpolarized 13C Magnetic Resonance Spectroscopy.

Poor sperm motility is a common cause of male infertility for which there are no empirical therapies. Sperm motility is powered by adenosine triphosphate but the relative importance of lactate fermentation and Oxidative Phosphorylation (OxPhos) is debated. To study the relationship between energy metabolism and sperm motility we used dissolution Dynamic Nuclear Polarization (dDNP) for the first time to show the rapid conversion of 13C1-pyruvate to lactate and bicarbonate, indicating active glycolytic and OxPhos metabolism in sperm. The magnitude of both lactate and bicarbonate signals were positively correlated with the concentration of progressively motile sperm. After controlling for sperm concentration, increased progressive sperm motility generated more pyruvate conversion to lactate and bicarbonate. The technique of dDNP allows 'snapshots' of sperm metabolism to be tracked over the different stages of their life. This may provide help to uncover the causes of poor sperm motility and suggest new approaches for novel treatments or therapies.

Steady-state free precession with hyperpolarized 3He: experiments and theory.

The magnetization response of hyperpolarized 3He gas to a steady-state free precession (SSFP) sequence was simulated using matrix product operators. The simulations included the effects of flip angle (alpha), sequence timings, resonant frequency, gas diffusion coefficient, imaging gradients, T1 and T2. Experiments performed at 1.5 T, on gas phantoms and with healthy human subjects, confirm the predicted theory, and indicate increased SNR with SSFP through use of higher flip angles when compared to optimized spoiled gradient echo (SPGR). Simulations and experiments show some compromise to the SNR and some point spread function broadening at high alpha due to the incomplete refocusing of transverse magnetization, caused by diffusion dephasing from the readout gradient. Mixing of gas polarization levels by diffusion between slices is also identified as a source of signal loss in SSFP at higher alpha through incomplete refocusing. Nevertheless, in the sample experiments, a SSFP sequence with an optimized flip angle of alpha=20 degrees, and 128 sequential phase encoding views, showed a higher SNR when compared to SPGR (alpha=7.2 degrees) with the same bandwidth. Some of the gas sample experiments demonstrated a transient signal response that deviates from theory in the initial phase. This was identified as being caused by radiation damping interactions between the large initial transverse magnetization and the high quality factor (Q=250) birdcage resonator. In 3He NMR experiments, performed without imaging gradients, diffusion dephasing can be mitigated, and the effective T2 is relatively long (1 s). Under these circumstances the SSFP sequence behaves like a CPMG sequence with sinalpha/2 weighting of SNR. Experiments and simulations were also performed to characterize the off-resonance behaviour of the SSFP HP 3He signal. Characteristic banding artifacts due to off-resonance harmonic beating were observed in some of the in vivo SSFP images, for instance in axial slices close to the diaphragm where B0 inhomogeneity is highest. Despite these artifacts, a higher SNR was observed with SSFP in vivo when compared to the SPGR sequence. The trends predicted by theory of increasing SSFP SNR with increasing flip angle were observed in the range alpha=10-20 degrees without compromise to image quality through blurring caused by excessive k-space filtering.

Investigation of MR signal modulation due to magnetic fields from neuronal currents in the adult human optic nerve and visual cortex.

Neuronal currents produce weak transient magnetic fields, and the hypothesis being investigated here is that the components of these parallel to the B0 field can potentially modulate the MR signal, thus providing a means of direct detection of nerve impulses. A theory for the phase and amplitude changes of the MR signal over time due to an external magnetic field has been developed to predict this modulation. Experimentally, a fast gradient-echo EPI sequence (TR = 158 ms, TE = 32.4 ms) was employed in an attempt to directly detect these neuronal currents in the adult human optic nerve and visual cortex using a 280-mm quadrature head coil at 1.5 T. A symmetrical intravoxel field distribution, which can be plausibly hypothesized for the axonal fields in the optic nerve and visual cortex, would result in phase cancellation within a voxel, and hence, only amplitude changes would be expected. On the other hand, an asymmetrical intravoxel field distribution would produce both phase and amplitude changes. The in vivo magnitude image data sets show a significant nerve firing detection rate of 56%, with zero detection using the phase image data sets. The percentage magnitude signal changes relative to the fully relaxed equilibrium signal fall within a predicted RMS field range of 1.2-2.1 nT in the optic nerve and 0.4-0.6 nT in the visual cortex, according to the hypothesis that the axonal fields create a symmetrical Lorentzian field distribution within the voxel.

Simultaneous parallel inclined readout image technique.

Sensitivity-encoded phase undersampling has been combined with simultaneous slice excitation to produce a parallel MRI method with a high volumetric acquisition acceleration factor without the need for auxiliary stepped field coils. Dual-slice excitation was produced by modulating both spin and gradient echo sequences at +/-6 kHz. Frequency aliasing of simultaneously excited slices was prevented by using an additional gradient applied along the slice axis during data acquisition. Data were acquired using a four-channel receiver array and x4 sensitivity encoding on a 1.5 T MR system. The simultaneous parallel inclined readout image technique has been successfully demonstrated in both phantoms and volunteers. A multiplicative image acquisition acceleration factor of up to x8 was achieved. Image SNR and resolution was dependent on the ratio of the readout gradient to the additional slice gradient. A ratio of approximately 2:1 produced acceptable image quality. Use of RF pulses with additional excitation bands should enable the technique to be extended to volumetric acquisition acceleration factors in the range of x16-24 without the SNR limitations of pure partially parallel phase reduction methods.

Identifying metabolite markers for preterm birth in cervicovaginal fluid by magnetic resonance spectroscopy.

INTRODUCTION: Preterm birth (PTB) may be preceded by changes in the vaginal microflora and metabolite profiles. OBJECTIVES: We sought to characterise the metabolite profile of cervicovaginal fluid (CVF) of pregnant women by 1H NMR spectroscopy, and assess their predictive value for PTB. METHODS: A pair of high-vaginal swabs was obtained from pregnant women with no evidence of clinical infection and grouped as follows: asymptomatic low risk (ALR) women with no previous history of PTB, assessed at 20-22 gestational weeks, g.w., n = 83; asymptomatic high risk (AHR) women with a previous history of PTB, assessed at both 20-22 g.w., n = 71, and 26-28 g.w., n = 58; and women presenting with symptoms of preterm labor (PTL) (SYM), assessed at 24-36 g.w., n = 65. Vaginal secretions were dissolved in phosphate buffered saline and scanned with a 9.4 T NMR spectrometer. RESULTS: Six metabolites (lactate, alanine, acetate, glutamine/glutamate, succinate and glucose) were analysed. In all study cohorts vaginal pH correlated with lactate integral (r = -0.62, p < 0.0001). Lactate integrals were higher in the term ALR compared to the AHR (20-22 g.w.) women (p = 0.003). Acetate integrals were higher in the preterm versus term women for the AHR (20-22 g.w.) (p = 0.048) and SYM (p = 0.003) groups; and was predictive of PTB < 37 g.w. (AUC 0.78; 95 % CI 0.61-0.95), and delivery within 2 weeks of the index assessment (AUC 0.84; 95 % CI 0.64-1) in the SYM women, whilst other metabolites were not. CONCLUSION: High CVF acetate integral of women with symptoms of PTL appears predictive of preterm delivery, as well as delivery within 2 weeks of presentation.

Measurements and modeling of long range 3He diffusion in the lung using a "slice-washout" method.

In healthy lung tissue, pulsed-gradient-spin-echo (PGSE) methods reveal apparent diffusion coefficients (ADC) of the order 0.20 cm2 s(-1); for diffusion times of approximately 2 ms. For these short diffusion times the ADC is only sensitive to structures approximately (2Dt)1/2 approximately 0.6mm in size. Recent work, using magnetic tagging of the longitudinal magnetization has revealed much smaller ADC values for longer length scales. In this work, the in vivo ADC from within the air-spaces, was measured using a new technique. The signal from a series of images was analyzed from a slice that was repeatedly imaged. Diffusion tends to "top-up" the non-renewable polarization within the slice, which leads to a non-exponential decay in image signal. Image data were compared to 1D finite-difference simulations of diffusion to calculate a long range ADC value. The results yield values of the order 0.034 cm2 s(-1), which are nearly an order of magnitude smaller than those reported by PGSE measurements at shorter diffusion times.

Postmortem MR imaging of the fetus: an adjunct or a replacement for conventional autopsy?

Fetal and perinatal autopsy provides essential diagnostic information not only for parents but also for medical audit and clinical trials. The autopsy rate is decreasing throughout the world for numerous reasons. Medical imaging has always been part of the autopsy process, but in the last decade there has been increased interest in imaging as additional to or a replacement for autopsy. This is especially so with the wider availability of magnetic resonance (MR) scanners that are able to provide detailed anatomy of all body structures as well as having the potential to provide information about histopathological patterns of injury. Postmortem MR imaging (MRI) provides similar information to autopsy for gross pathology of most organ systems. It often provides more information in cases of central nervous system abnormalities, but is less accurate for cardiac abnormalities. Targeted, image-guided biopsy may allow histological diagnosis following postmortem MRI.

Emphysematous changes and normal variation in smokers and COPD patients using diffusion 3He MRI.

INTRODUCTION: This study aims to quantify global and regional changes of diffusive motion of 3He gas within the lung, as determined by hyperpolarized 3He MR apparent diffusion coefficient (ADC) measurement, in non-smokers, smokers and chronic obstructive pulmonary disease (COPD) patients. METHODS: Age-matched groups of six healthy non-smokers, five healthy smokers and five patients with COPD. The experiments were performed with approval from the local Research Ethics Committee. Diffusion imaging was performed following hyperpolarized 3He gas inhalation, producing ADC maps. Mean and standard deviation of the ADCs were used to compare the subject groups and assess regional variations within individuals. RESULTS: The intra-individual standard deviation of ADC in the healthy smokers was significantly larger than that of the non-smoking group (P < 0.02). Compared to the non-smoking group, COPD patients had significantly higher mean and standard deviation of ADC (P < 0.01). The mean ADC in the anterior half of the chest was systematically higher than in the posterior half in the healthy non-smoking subject group. DISCUSSION: This study suggests that there are regional trends in the ADC values of healthy volunteers that may have implications for the clinical interpretation of ADC values. Less homogeneous ADC values have been detected in asymptomatic smokers, indicative of damage to the distal air spaces.