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Purpose To compare mono- and bi-exponential relaxation model equations to discriminate between normal and fatty liver disease. Materials and Methods Six rats on a choline deficient amino acid modified (CDAA) diet and six on normal chow were studied. Multiple spin echo images with increasing echo times (TEs) were collected at 9.4T. Pixel-wise T2 maps were generated using mono-exponential decay function to calculate T2M, and a bi-exponential to calculate, short T2 component (T2S), long T2 component (T2L), and fractions of these components (ρS, ρL), respectively. Statistical F-tests and Akaike's information criterion (AIC) were used to assess the relative performance of the two models. Results F-test and AIC showed that in the CDAA group, T2 bi-exponential model described the signal of T2 weighted imaging of the liver better than the mono-exponential model. Controls were best described by the mono-exponential model. Mean values for T2M, T2L, T2S, ρS, ρL were 31.2 ± 0.7 ms, 72.8 ± 3.3 ms, 8.2 ± 0.6 ms,71.2 ± 2.1%, 30.4 ± 1.3%, respectively, in CDAA rats, compared with 18.8 ± 0.5 ms, 32.3 ± 0.7 ms, 9.2 ± 1.8 ms, 79 ± 2%, 21.0 ± 1.1% in controls. Conclusion In the fatty liver of CDAA rats we have shown that T2 weighted images fit the bi-exponential model better than mono-exponential decays thus providing a better description of the data. Level of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:468–476.

Background Atorvastatin and metformin are known energy restricting mimetic agents that act synergistically to produce molecular and metabolic changes in advanced prostate cancer (PCa). This trial seeks to determine whether these drugs favourably alter selected parameters in men with clinically-localized, aggressive PCa. Methods/design This prospective phase II randomized, controlled window trial is recruiting men with clinically significant PCa, confirmed by biopsy following multiparametric MRI and intending to undergo radical prostatectomy. Ethical approval was granted by the Royal Brisbane and Women's Hospital Human and The University of Queensland Medical Research Ethics Committees. Participants are being randomized into four groups: metformin with placebo; atorvastatin with placebo; metformin with atorvastatin; or placebo alone. Capsules are consumed for 8 weeks, a duration selected as the most appropriate period in which histological and biochemical changes may be observed while allowing prompt treatment with curative intent of clinically significant PCa. At recruitment and prior to RP, participants provide blood, urine and seminal fluid. A subset of participants will undergo 7Tesla magnetic resonance spectroscopy to compare metabolites in-vivo with those in seminal fluid and biopsied tissue. The primary end point is biochemical evolution, defined using biomarkers (serum prostate specific antigen; PCA3 and citrate in seminal fluid and prostatic tissue). Standard pathological assessment will be undertaken. Discussion This study is designed to assess the potential synergistic action of metformin and atorvastatin on PCa tumour biology. The results may determine simple methods of tumour modulation to reduce disease progression.

We present a combined PET/7 T MR imaging and 16.4 T microscopic MR imaging dual-modality imaging approach enabling quantification of the amyloid load at high sensitivity and high resolution, and of regional cerebral blood flow (rCBF) in the brain of transgenic APP23 mice. Moreover, we demonstrate a novel, voxel-based correlative data analysis method for in-depth evaluation of amyloid PET and rCBF data. Methods: We injected C-11-Pittsburgh compound B (PIB) intravenously in transgenic and control APP23 mice and performed dynamic PET measurements. rCBF data were recorded with a flow-sensitive alternating inversion recovery approach at 7 T. Subsequently, the animals were sacrificed and their brains harvested for ex vivo microscopic MR imaging at 16.4 T with a T-2*-weighted gradient-echo sequence at 30-mu m spatial resolution. Additionally, correlative amyloid histology was performed. The C-11-PIB PET data were quantified to nondisplaceable binding potentials (BPND) using the Logan graphical analysis; flow-sensitive alternating inversion recovery data were quantified with a simplified version of the Bloch equation. Results: Amyloid load assessed by both C-11-PIB PET and amyloid histology was highest in the frontal cortex of transgenic mice (C-11-PIB BPND: 0.93 +/- 0.08; amyloid histology: 15.1% +/- 1.5%), followed by the temporoparietal cortex (C-11-PIB BPND: 0.75 +/- 0.08; amyloid histology: 13.9% +/- 0.7%) and the hippocampus (C-11-PIB BPND: 0.71 +/- 0.09; amyloid histology: 9.2% +/- 0.9%), and was lowest in the thalamus (C-11-PIB BPND: 0.40 +/- 0.07; amyloid histology: 6.6% +/- 0.6%). However, C-11-PIB BPND and amyloid histology linearly correlated (R-2 = 0.82, P < 0.05) and were significantly higher in transgenic animals (P < 0.01). Similarly, microscopic MR imaging allowed quantifying the amyloid load, in addition to the detection of substructures within single amyloid plaques correlating with amyloid deposition density and the measurement of hippocampal atrophy. Finally, we found an inverse relationship between C-11-PIB BPND and rCBF MR imaging in the voxel-based analysis that was absent in control mice (slope(tg): -0.11 +/- 0.03; slope.: 0.004 +/-. 0.005; P = 0.014). Conclusion: Our dual-modality imaging approach using C-11-PIB PET/7 T MR imaging and 16.4 T microscopic MR imaging allowed amyloid-load quantification with high sensitivity and high resolution, the identification of substructures within single amyloid plaques, and the quantification of rCBF.

Bruising of the mesocarp in avocado fruit is an important postharvest issue for the industry. Proton magnetic resonance imaging (H-1-MRI) was used as a non-destructive tool to monitor bruise expression over time in avocado cv. Hass fruit. H-1-MRI clearly identified fruit morphological features and bruised mesocarp tissue. The pixel intensity value of T-2 weighted spin echo H-1-MRI images of avocado fruit pericarp changed over time with fruit softening. Bruised mesocarp tissue in impacted fruit appeared relatively hyperintense (brighter) in T-2 weighted H-1-MRI images. For firm ripe fruit impacted from 25 cm drop height (0.38 J +/- 0.004) and for firm ripe fruit impacted from 50 cm drop height (0.81 J +/- 0.011), hyper-intensity in the mesocarp beneath the impact point was evident immediately after impact. However, visible symptoms of bruising in the form of flesh browning did not appear in parallel serial destructive assessments until after day 1 following impact on day 0. The brown, bruised mesocarp volume in ripe fruit increased progressively over the assessment period of 3 days. This trend was evident in destructive assessments as well as in H-1-MRI images. In hard green mature fruit impacted from 100 cm drop height (1.68 J +/- 0.020), contrast between mesocarp tissue beneath the impact site and surrounding sound mesocarp was evident in T-2 weighted H-1-MRI images from day 0. However, no bruise symptoms were evident as flesh browning upon serial destructive assessments of fruit over the 3 days assessment period. The average pixel intensity values at the impact site in T-2 weighted H-1-MRI images for both firm ripe and hard green mature fruit decreased over the period of assessment. In contrast, the pixel intensities in the T-2 weighted H-1-MRI images of diseased flesh increased over time. (C) 2014 Elsevier B.V. All rights reserved.

ABSTRACT: MRI is a key radiological imaging technique that plays an important role in the diagnosis and characterization of heterogeneous multiple sclerosis (MS) lesions. Various MRI methodologies such as conventional T 1/T 2 contrast, contrast agent enhancement, diffusion-weighted imaging, magnetization transfer imaging and susceptibility weighted imaging have been developed to determine the severity of MS pathology, including demyelination/remyelination and brain connectivity impairment from axonal loss. The broad spectrum of MS pathology manifests in diverse patient MRI presentations and affects the accuracy of patient diagnosis. To study specific pathological aspects of the disease, rodent models such as experimental autoimmune encephalomyelitis, virus-induced and toxin-induced demyelination have been developed. This review aims to present key developments in MRI methodology for better characterization of rodent models of MS.

To report guide-wire fragment embolisation of paediatric peripherally inserted central catheter (PICC) devices and explore the safety profile of four commonly used devices.Clinical incidents involving paediatric PICC devices in Queensland public hospitals were reviewed. A PICC user-experience survey was conducted at five public hospitals with 32 clinicians. A device design evaluation was undertaken, and magnetic resonance imaging (MRI) safety was tested by a simulation study.Embolisation events; technical mistakes, multiple attempts and breakages during insertion; willingness to use the device; failure modes and risk priority rating; movement and/or temperature change on exposure to MRI.Six clinical incidents of silent guide-wire embolisation, and four near misses were identified; all were associated with one type of device. The survey found that this device had a reported broken-wire embolisation rate of 0.9/100 insertions with no events in other devices; two of the four devices had a higher all-cause embolisation rate (3.3/100 insertions v 0.4/100 insertions) and lower clinician acceptance (68%-71% v 91%-100%). All devices had 6-17 identified failure modes; the two devices that allowed removal of a guide wire through a septum had the highest overall risk rating. Guide-wire exposure to MRI was rated a potential safety risk due to movement.There is marked variation in the safety profile of 3 Fr PICC devices in clinical use, and safety performance can be linked to design factors. Pre-MRI screening of all children who have previously had a PICC device inserted is recommended. We advocate a decision-making model for evaluation of device safety.

Principal component analysis of 1H NMR spectra of dichloromethane extracts taken from grapevine leaves reveals that phylloxera infestation of the root system causes metabolic changes in the leaves of infested grapevines, both in the field and in the glasshouse. A number of potential markers of phylloxera infestation were detected but their presence is transient and varies with the stage of the growing season. The changes in the metabolic profile caused by phylloxera infestation more closely resemble those caused by nitrogen deficiency than those induced by water stress. A reduction in the ratio of linoleic acid to linolenic acid in the triglyceride component of the leaf extract may provide an indicator of phylloxera infestation.

Magnetic Resonance Imaging (MRI) of the rodent brain at ultra-high magnetic fields (> 9.4 Tesla) offers a higher signal-to-noise ratio that can be exploited to reduce image acquisition time or provide higher spatial resolution. However, significant challenges are presented due to a combination of longer T 1 and shorter T 2/T2* relaxation times and increased sensitivity to magnetic susceptibility resulting in severe local-field inhomogeneity artefacts from air pockets and bone/brain interfaces. The Stejskal-Tanner spin echo diffusion-weighted imaging (DWI) sequence is often used in high-field rodent brain MRI due to its immunity to these artefacts. To accurately determine diffusion-tensor or fibre-orientation distribution, high angular resolution diffusion imaging (HARDI) with strong diffusion weighting (b >3000 s/mm2) and at least 30 diffusion-encoding directions are required. However, this results in long image acquisition times unsuitable for live animal imaging. In this study, we describe the optimization of HARDI acquisition parameters at 16.4T using a Stejskal-Tanner sequence with echo-planar imaging (EPI) readout. EPI segmentation and partial Fourier encoding acceleration were applied to reduce the echo time (TE), thereby minimizing signal decay and distortion artefacts while maintaining a reasonably short acquisition time. The final HARDI acquisition protocol was achieved with the following parameters: 4 shot EPI, b = 3000 s/mm2, 64 diffusion-encoding directions, 125×150 μm2 in-plane resolution, 0.6 mm slice thickness, and 2h acquisition time. This protocol was used to image a cohort of adult C57BL/6 male mice, whereby the quality of the acquired data was assessed and diffusion tensor imaging (DTI) derived parameters were measured. High-quality images with high spatial and angular resolution, low distortion and low variability in DTI-derived parameters were obtained, indicating that EPI-DWI is feasible at 16.4T to study animal models of white matter (WM) diseases.

Renal osmolyte concentrations are reduced during reflow following ischemia. Osmolyte decreases may follow oxygen depletion or loss of extracellular osmolality in the medulla. Image-guided volume-localized magnetic resonance (MR) microspectroscopy was used to monitor regional osmolytes during hyposmotic shock and hypoxia in the intact rat kidney. Alternate spectra were acquired from 24-μl voxels in cortex and medulla of the isolated perfused kidney. There was a progressive decrease in the combined betaine-glycerophosphorylcholine (GPC) peak intensity of 21% in cortex and 35% in medulla of normoxic kidneys between 60 and 160 min after commencing perfusion. Hypoxia had no significant effect on the betaine-GPC peak intensity in cortex or medulla, despite a dramatic reduction in tubular sodium, potassium, and water reabsorption. The results suggest that cortical and medullary intracellular osmolyte concentrations depend on osmotically regulated channels that are insensitive to oxygen and dissociated from the oxygen-dependent parameters of renal function, the fractional excretion of sodium, the fractional excretion of potassium, and urine-to-plasma inulin concentration ratio.

The aim of this work is to develop 3-acyl prodrugs of the potent analgesic morphine-6-sulfate (M6S). These are expected to have higher potency and/or exhibit longer duration of analgesic action than the parent compound. M6S and the prodrugs were synthesized, then purified either by recrystallization or by semi-preparative HPLC and the structures confirmed by mass spectrometry, IR spectrophotometry and by detailed 1- and 2-D NMR studies. The lipophilicities of the compounds were assessed by a combination of shake-flask, group contribution and HPLC retention methods. The octanol-buffer partition coefficient could only be obtained directly for 3-heptanoylmorphine-6-sulfate, using the shake-flask method. The partition coefficients (P) for the remaining prodrugs were estimated from known methylene group contributions. A good linear relationship between log P and the HPLC log capacity factors was demonstrated. Hydrolysis of the 3-acetyl prodrug, as a representative of the group, was found to occur relatively slowly in buffers (pH range 6.15-8.01), with a small buffer catalysis contribution. The rates of enzymatic hydrolysis of the 3-acyl group in 10% rat blood and in 10% rat brain homogenate were investigated. The prodrugs followed apparent first order hydrolysis kinetics, with a significantly faster hydrolysis rate found in 10% rat brain homogenate than in 10% rat blood for all compounds. (C) 1998 Elsevier Science B.V. All rights reserved.

The structures of haliclonacyclamines A (1) and B (2), and their methiodide salts (3) and (4), were investigated by 1D- and 2D-NMR experiments, notably DQFCOSY, HMBC, HMQC-HOHAHA, and HOHAHA. The relative stereochemistry and position of alkene substituents were determined by single crystal x-ray study at low temperature. The parent haliclonacyclamines show pronounced cytotoxic, antibacterial and antifungal activity.

A movable, actively decoupled surface coil has been employed to obtain a localized 1H NMR spectrum from the lumbosacral spinal cord of a live Lewis rat. A volume selective 'VOSY' normally spelled out as 'volume selective spectroscopy' spectroscopy pulse sequence that incorporates 'phase ramped' selective RF pulses, has been used to minimize random phase jitter in the NMR signal as a result of the large frequency shifts required to locate the voxel in the center of the cord while using intense gradient pulses. Spectra from 13-microliters voxels in healthy rats and in rats inoculated with guinea pig spinal cord and complete Freund's adjuvant, resulting in experimental autoimmune encephalomyelitis, are shown.

Medical image registration is generally faced with the confounding effect of spatially dependent intensity variations. This can be the case when images have been acquired using the same imaging modality, for example, in magnetic resonance imaging and also when using various histology and staining processes. We propose the application of an intensity-invariant dense feature extraction method through the use of phase Fourier transforms. The approach allows medical images containing intensity in homogeneities to be aligned and warped as part of a feature-based registration technique. Registration performance was evaluated on mono-modality and multi-modality data, namely magnetic resonance and histology images. Qualitative and quantitative validation was conducted with respect to two established image intensity correction methods.

A method for the acquisition of localized 2D shift-correlated spectra, based on the combination of the stimulated-echo volume-selection and gradient-enhanced COSY experiments, is described. The sequence can be modified to perform a number of localized experiments including HOHAHA and DQF-COSY. The method is demonstrated in vivo by presentation of localized COSY and HOHAHA spectra of human tibia marrow, and a localized COSY spectrum of human brain acquired at a field strength of 2 Tesla. Cross peaks corresponding to correlations between coupled groups along the acyl chains of triglycerides are observed in the spectra of marrow. The major cerebral metabolites are represented in the in vivo COSY brain spectrum, including N-acetylaspartate, glutamate/glutamine, total creatine, aspartate, and myo-inositol. Difficulties in the implementation of localized shift-correlation spectroscopy, including water suppression and T2 relaxation, are discussed.

Proton magnetic resonance imaging (MRI) was used to observe disinfestation heat treatment-induced injury in the mesocarp of ripening mango cv. Kensington Pride. Injured areas were characterised by relatively low water levels (low signal intensity) corresponding to air filled cavities and “islands” of starchy mesocarp. Heat treatment-induced lesions started to develop on the day of treatment (day 0) and were maximally evident in fruit held at 22°C by day 4. Nondestructive proton MRI was shown to be a sensitive method for detecting and monitoring the progress of heat treatment-induced injury in mango fruit.

Caribbean ciguatoxins (C-CTXs) are responsible for the widespread occurrence of ciguatera in the Caribbean Sea. The structure and configuration of C-CTX-1 (1), the major ciguatoxin isolated from the horse-eye jack (Caranx latus), has been determined from DQF-COSY, E-COSY, TOCSY, NOESY, POESY, ge-HSQC. and HMQC experiments performed at 750 MHz and 500 MHz on a 0.13 pmol sample. C-CTX-1 ([M + H](+) m/z 1141.6 Da, molecular formula C62H92O19) has a ciguatoxin/breveroxin ladder structure comprising 14 trans-fused, ether-linked rings (7/6/6/7/8/9/7/6/8/6/7/6/7/6) assembled fi um 6 protonated fragments. The relative stereochemistry and ring configuration of 1 was determined from an analysis of coupling constant and NOE data. Like ciguatoxins in the Pacific Ocean (P-CTX), C-CTX-1 possesses a flexible nine-membered ring which may be a conserved feature among ciguatoxins. However, C-CTX-1 has a longer contiguous carbon backbone (57 vs 55 carbons for P-CTX-1), one extra ring, and a hemiketal in ring N but no spiroketal as found in P-CTX. C-CTX-1 possesses a primary hydroxyl which may allow selective derivatization. A minor analogue, C-CTX-2, was also isolated from fish and assigned the structure 56 epi-C-CTX-1 (2). since it slowly rearranged to C-CTX-1 in solution. Given the structural similarities between Caribbean and Pacific ciguatoxins, we propose that C-CTX-1 and C-CTX-2 arise from a Caribbean strain of the benthic dinoflagellate, Gambierdiscus toxicus.

Different folivorous marsupials select their food from different subgenera of Eucalyptus, but the choices cannot be explained by known antifeedants, such as formylated phloroglucinol compounds or tannins, or by nutritional quality. Eucalypts contain a wide variety of plant secondary metabolites so it is difficult to use traditional methods to identify the chemicals that determine food selection. Therefore, we used a metabolomic approach in which we employed (1)H nuclear magnetic resonance spectroscopy to compare chemical structures of representatives from the two subgenera and to identify chemicals that consistently differ between them. We found that dichloromethane extracts of leaves from most species in the subgenus Eucalyptus differ from those in Symphyomyrtus by the presence of free flavanones, having no substitution in Ring B. Although flavanoids are known to deter feeding by certain insects, their effects on marsupials have not been established and must be tested with controlled feeding studies.

Theoretical and experimental results are presented demonstrating that the slice intensity resulting from a self‐refocusing 270° Gaussian pulse (L. Elmsley and G. Bodenhausen, Magn. Reson. in Med. 10, 273, 1989) is approximately 60% of that following an appropriately refocused 90° Gaussian pulse.

MRI of the lung using hyperpolarized helium as an inhaled contrast agent has important research applications and clinical potential. Owing to the limited availability of hyperpolarized helium, this type of imaging has not been performed in the human lung outside of North America or Europe. The objective of this study was to test the feasibility of imaging human lungs in Australia using hyperpolarized helium gas imported from Germany.A Bruker 2-Tesla whole-body magnetic resonance scanner located in Brisbane, Australia was adapted with a helium-3 radiofrequency transceiver coil. Helium-3 was hyperpolarized to 72% in Mainz, Germany and airfreighted to Brisbane. The time taken for the journey was 32 h and scanning was performed 36-40 h after departure from Mainz, with an estimated polarization level of 44%. Procedures were developed to transfer 300 mL of the hyperpolarized helium to Tedlar bags filled with 700 mL of nitrogen. Healthy volunteers inhaled the 1 L helium/nitrogen mixture from FRC, and imaging was performed with a 10 s breathhold.Imaging showed very detailed and even ventilation of all regions of the lung with a good signal-to-noise ratio. No adverse effects of inhaling the gas mixture were noted.This report of MRI of the human lung using hyperpolarized helium demonstrates the feasibility of long distance gas transport from Germany to Australia. This will help to facilitate research and clinical application of this innovative functional lung imaging technique.

Chemical synthesis was used to prepare the HIV-1 protease specifically 13C-labelled in the catalytically essential Asp 25 in each monomer. The NMR chemical shift of the 13C-enriched homodimeric enzyme was measured in the presence of the inhibitor pepstatin, a mimic of the tetrahedral intermediate formed in enzyme catalysis. In this complex, the catalytic carboxyls do not titrate in the pH range where the enzyme is active; throughout the range pH 2.5-6.5, one Asp 25 side chain is protonated and the other deprotonated. By contrast, in the absence of inhibitor the two Asp side chains are chemically equivalent and both deprotonated at pH 6, the optimum for enzymatic activity. These direct observations of the chemical properties of the catalytic apparatus of the enzyme provide concrete information on which to base the design of improved HIV-1 protease inhibitors.

In vivo, volume-selected H-1 NMR spectroscopy employing the SPACE technique was used to monitor biochemical changes in the thiamin deficient rat brain in response to glucose loading. The concentrations of brain N-acetylaspartate, glutamate/glutamine/gamma-aminobutyric acid, lactate and glucose differed significantly from those of control animals. The results are consistent with a metabolic block at the reaction catalyzed by the thiamin dependent enzyme alpha-keto glutarate dehydrogenase soon after the onset of neurological symptoms of thiamin deficiency, and a further block at pyruvate dehydrogenase arising late in the course of thiamin deficiency.

Induction of iron overload in mice using 1% (w/w) dietary carbonyl iron resulted in marked decreases in 1H and 31P NMR relaxation times. Natural-abundance deuterium (2H) NMR spectroscopy has been used to measure 2H T1 values in vivo in the presence of body paramagnetic iron. This procedure offers a method for noninvasive determination of body iron stores.

A single slice of z-magnetization is used to generate high-speed images. The slice selection step is achieved using two sin-sinc pulses. This procedure eliminates the need for continual slice gradient reversal, a requirement for the FLASH technique. The RAPID imaging method has less inherent T1 and/or T2 dependence than current fast imaging methods and is more sensitive.

Volume-localized proton nuclear magnetic resonance spectroscopy was used as an assay of regional biochemistry in the isolated perfused rat kidney. This model eliminated artifacts caused by respiratory and cardiac motion experienced in vivo. Immersion of the kidney under its venous effluent reduced the susceptibility artifacts evoked by tissue-air interfaces. The rapid acquisition with relaxation enhancement imaging sequence was used for scout imaging. This gave excellent spatial resolution of the cortex, outer medulla, and inner medulla. Spectra were then acquired in 10 minutes using the volume-selective multipulse spectroscopy sequence from voxels with a volume of approximately 24 microL located within the cortical or medullary regions. Spectral peaks were assigned by the addition of known compounds to the perfusion medium and by comparison with spectra of protein-free extracts of cortex and medulla. The medullary region spectra were characterized by signals from the osmolytes betaine, glycerophosphorylcholine, and inositol. The spectra from the cortex were more complex and contained lesser contributions from osmolytes.