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D G Gadian

Publications and source records attributed to D G Gadian.

At least 19 recordsLinked to original sources
PubMed1992

Perfusion and diffusion MR imaging.

Diffusion-weighted images of the rat brain were obtained using the pulsed-gradient spin-echo method. An attempt was made to extract perfusion-related parameters from signal intensity data taken from the caudate-putamen region of the images, by using a nonlinear least-squares calculation to fit the Le Bihan biexponential expression (Le Bihan et al., Radiology, 168, 497 (1988)) to the data. The perfusion-related parameters could not be obtained with sufficient accuracy to be useful, although the perfusion-weighted images appear to contain meaningful qualitative information. An analysis of the perfusion model is presented and shows why the Le Bihan pseudo-diffusion coefficient is particularly difficult to measure with reasonable accuracy.

Animals↗
PubMed1992

Cell and tissue responses of a murine tumour to phthalocyanine-mediated photodynamic therapy.

Mice bearing a subcutaneously growing tumour (Colo 26) were injected intravenously with the photosensitiser chloroaluminum sulphonated phthalocyanine (5 mg/kg) 24 h prior to irradiating the tumour with laser light (675 nm; 50mW, 100 J/tumour). Energy status of the tumour, as assessed by the loss of high energy phosphates in the 31P-nuclear magnetic resonance spectra, was altered dramatically following treatment, such that the ATP fell to undetectable levels within 1 h of light irradiation. However, assessment of the clonogenic capacity of neoplastic cells isolated from dissociated tumours showed that these rapid changes in cellular metabolism were not reflected in similar rapid changes in cell viability. Reductions in clonogenic capacity, which fell to less than 0.1% of control values at 24h postirradiation, closely mirrored those resulting from the cessation of vascular perfusion. Evaluation of tumour blood flow, using the technique of hydrogen washout, showed that the treatment protocol evoked a gradual and selective reduction in flow within the tumour resulting in complete vascular stasis by approximately 5 h after treatment. The results indicate that while chloroaluminum sulphonated phthalocyanine-mediated photodynamic therapy caused early metabolic damage in neoplastic cells, loss of viability paralleled the induction of complete inhibition of vascular flow in the tumour.

Animals↗
PubMed1992

Specific expression of N-acetylaspartate in neurons, oligodendrocyte-type-2 astrocyte progenitors, and immature oligodendrocytes in vitro.

To test the specificity of N-acetylaspartate (NAA) as a neuronal marker for proton nuclear magnetic resonance (1H NMR) spectroscopy, purified and characterized cultured cells were analyzed for their NAA content using both 1H NMR and HPLC. Cell types studied included cerebellar granule neurons, type-1 astrocytes, meningeal cells, oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells, and oligodendrocytes. A high concentration of NAA was found in extracts of cerebellar granule neurons (approximately 12 nmol/mg of protein), whereas NAA remained undetectable in purified type-1 astrocytes, meningeal cells, and mature oligodendrocytes. However, twice the neuronal level of NAA was found in O-2A progenitors grown in vitro. In addition significant levels of NAA were also detected in cultures of immature oligodendrocytes. Our data partly support previous suggestions that NAA may be a useful neuronal marker for 1H NMR spectroscopic examination of the adult brain. However, they also raise the further possibility that alterations of NAA associated with some specific brain disorders, particularly disorders seen in newborn and young children, may reflect abnormalities in the development of oligodendroglia or their precursors.

Animals↗
PubMed1992

Diffusion-weighted imaging studies of cerebral ischemia in gerbils. Potential relevance to energy failure.

BACKGROUND AND PURPOSE: Diffusion-weighted magnetic resonance imaging has been shown to be particularly suited to the study of the acute phase of cerebral ischemia in animal models. The studies reported in this paper were undertaken to determine whether this technique is sensitive to the known ischemic thresholds for cerebral tissue energy failure and disturbance of membrane ion gradients. METHODS: Diffusion-weighted images of the gerbil brain were acquired under two sets of experimental conditions: as a function of cerebral blood flow after controlled graded occlusion of the common carotid arteries (partial ischemia), as a function of time following complete bilateral carotid artery occlusion (severe global ischemia), and on deocclusion after 60 minutes of ischemia. RESULTS: During partial cerebral ischemia, the diffusion-weighted images remained unchanged until the cerebral blood flow was reduced to 15-20 ml.100 g-1.min-1 and below, when image intensity increased as the cerebral blood flow was lowered further. This is similar to the critical flow threshold for maintenance of tissue high-energy metabolites and ion homeostasis. After the onset of severe global cerebral ischemia, diffusion-weighted image intensity increased gradually after a delay of approximately 2.5 minutes, consistent with complete loss of tissue adenosine triphosphate and with the time course of increase in extracellular potassium. This hyperintensity decreased on deocclusion following 60 minutes of ischemia. CONCLUSIONS: The data suggest that diffusion-weighted imaging is sensitive to the disruption of tissue energy metabolism or a consequence of this disruption. This raises the possibility of imaging energy failure noninvasively. In humans, this could have potential in visualizing brain regions where energy metabolism is impaired, particularly during the acute phase following stroke.

Animals↗
PubMed1992

T2- and diffusion-weighted magnetic resonance imaging of a focal ischemic lesion in rat brain.

BACKGROUND AND PURPOSE: We sought to evaluate the application of T2-weighted and diffusion-weighted magnetic resonance imaging techniques in the study of a focal ischemic lesion in the rat brain. METHODS: Unilateral cortical infarcts were induced using the photosensitive dye rose bengal and 560 nm light irradiation. Magnetic resonance images were recorded from a total of 11 rats at selected intervals from 1.5 hours to several days after induction of the lesion. Parallel experiments were performed in which Evans blue dye was injected into the lesioned animals either immediately after lesion induction (n = 11) or 1 hour before the animals were killed (n = 11). The second procedure was designed to show regions of blood-brain barrier permeability to plasma proteins at the time of sacrifice, whereas the first procedure showed the accumulation and subsequent dispersion of plasma protein following disruption of the blood-brain barrier. RESULTS: Regions of the cortex highlighted by the T2-weighted images corresponded well to the pattern of dye staining seen from the first procedure while the diffusion-weighted images showed visual correspondence with the staining pattern obtained using the second procedure. CONCLUSIONS: These results illustrate the complementary use of T2-weighted and diffusion-weighted magnetic resonance imaging in discerning the pathophysiology of developing lesions.

Animals↗
PubMed1991

Saturation effects in phosphorus-31 magnetic resonance spectra of the human liver.

Phosphorus-31 liver spectra were recorded from 6 controls and 12 patients with liver disease using TR values of 0.5 and 5 s and a pulse angle of 45 degrees. One of the control subjects was also examined at seven TR values ranging from 0.5 to 20 s. Spectra from one additional patient were collected at TRs of 0.5, 1, and 2 s only. There was a significant increase in the mean ratio of peak areas phosphomonoesters (PME)/beta-ATP in 9 of the 13 patients and a decrease in phosphodiesters (PDE)/beta-ATP in 3 of the patients, compared with controls, at the longer TR values. The saturation factors for PME and PDE were greater than those for Pi and beta-ATP, and spectral abnormalities in disease were often more evident as the TR value was increased from 0.5 to 5 s. Acquisition parameters need to be chosen with a knowledge of the impact that saturation effects have on metabolite quantification and spectral contrast.

Adenosine Triphosphate↗
PubMed1991

Localized 1H NMR spectroscopy in Canavan's disease: a report of two cases.

Two children with Canavan's Disease, an autosomal recessive leukodystrophy, were studied by localized 1H spectroscopy. The N-acetylaspartate (NAA) signal intensity was high relative to other metabolite signals, and the signal intensity from choline-containing compounds was low. These findings are discussed in relation to a possible role for NAA in normal myelination.

Aspartic Acid↗
PubMed1991

Approaches to editing, assignment and interpretation of proton spectra.

Clinical 1H spectroscopy of the brain is complemented by parallel analyses of biopsy specimens and by studies of animal models of disease. 1H spectroscopy has been carried out on perchloric acid extracts of biopsy specimens from patients with intracranial tumours. The data suggest that clinical spectroscopy may be useful in the identification and grading of these tumours. In addition, the spectra from extracts derived from normal white matter add weight to the possibility that acetyl-containing compounds other than N-acetylaspartate may make a significant contribution to the signal at 2.0 ppm in vivo. Edited 1H spectra of brain metabolites in rats with acute liver failure demonstrate an elevation of glutamine and of lactate, suggesting a role for 1H spectroscopy in clinical investigations of metabolic encephalopathies. However, the observation and resolution of signals from glutamate and glutamine is more difficult at the lower fields that are available for clinical spectroscopy. Finally, some studies of patients with inborn errors of metabolism are described. It is shown that in a disorder of oxidative metabolism, brain lactate can be detected without the need for complex spectral editing techniques. Investigations of the metabolic abnormalities associated with Canavan's disease have shed further light on a possible role for N-acetylaspartate.

Animals↗
PubMed1990

Restoration of energy metabolism and resolution of oedema following profound ischaemia.

Cerebral ischaemia was produced in 2 groups of gerbils by occlusion of the common carotid arteries for 30 minutes, resulting in cerebral oedema. In group 1 cerebral oedema was measured by specific gravity microgravimetry, and in group 2 brain metabolism and blood flow were measured by 31P and 1H NMR spectroscopy and hydrogen clearance respectively. In group 1 the brain water content did not return to control levels by 180 minutes of reperfusion. Energy metabolism, determined by 31P NMR spectroscopy returned to control by 12 minutes, intracellular pH (pHi) by 20 minutes, and lactate, determined by 1H NMR spectroscopy, by 50 minutes. There was a lag of about 10 minutes before lactate began to be cleared from the brain. We suggest that while pHi is low, Na+/H+ exchange will negate the Na+ extrusion driven by the Na+/K+ ATPase. When pHi approaches normal there will be a net extrusion of Na+, taking osmotic water with it, and presumably with passive washout of lactate. This may be the cause of the initial delay in lactate clearance.

Animals↗
PubMed1989

Phosphodiesters in the liver: the effect of field strength on the 31P signal.

31P NMR spectra of the rat liver were recorded in vivo at 2.35 and 8.5 T. There was a large peak in the phosphodiester region of spectra obtained at 2.35 T which was much reduced at 8.5 T. The peak at 2.35 T is unlikely to be primarily from free cytosolic phosphodiesters, which would not be expected to display such a marked field dependence.

Animals↗
PubMed1989

31P magnetic resonance spectroscopy of the normal human brain: approaches using four dimensional chemical shift imaging and phase mapping techniques.

The use of four-dimensional chemical shift imaging to monitor phosphorus metabolites within the human brain is illustrated. Saturation effects are described, and acquisition conditions are discussed in relation to quantification and sensitivity. The effects of magnetic field variations on spectral parameters are assessed and the use of a field mapping technique is illustrated.

Adult↗
PubMed1989

Brain metabolites as 1H NMR markers of neuronal and glial disorders.

1H NMR spectroscopy of human brain in vivo can be used to detect a number of cerebral metabolites including N-acetylaspartate, creatine + phosphocreatine and choline-containing compounds. We have used 1H NMR spectroscopy to analyse these signals in (i) biopsy material from both normal human brain and astrocytomas, and (ii) primary astrocyte cultures. On the basis of this analysis, we conclude that in vivo 1H NMR spectroscopy could play an important clinical role in the non-invasive assessment of neuronal degeneration and proliferation of non-neuronal cells.

Animals↗
PubMed1989

1H NMR study of cerebral development in the rat.

1H NMR spectroscopy of brain extracts was used to investigate the metabolic changes that take place during development of the neonatal rat brain. Data were obtained over the range 1-21 days. The concentration of N-acetylaspartate rose by a factor of 9 during this period, the most rapid rise occurring after day 9. The total creatine concentration rose from days 1-21, with a large increase between days 1 and 5. Taurine concentration rose until day 5, then fell from days 5-21. The concentration of choline-containing compounds fell during the 21 day period. The results are discussed in relation to brain development and conventional biochemical data. A major conclusion in relation to spectroscopy of children is that interpretation of changes seen in disease will require adequate data from age-matched controls.

Animals↗
PubMed1989

Ammonia causes a drop in intracellular pH in metabolizing cortical brain slices. A [31P]- and [1H]nuclear magnetic resonance study.

[31P]- and [1H]Nuclear magnetic resonance spectroscopy were used to study metabolism in cortical brain slices in the guinea-pig during acute exposure to pathophysiological concentrations of ammonia. Intracellular acidification, measured from the chemical shift of endogenous inorganic phosphate, was observed without any change in cellular energy status or concentrations of lactate, glutamate and glutamine. The initial acidification, which developed over a period of 9 min appeared to be heterogeneous, on the basis of a splitting of the inorganic phosphate resonance in a number of experiments, corresponding to pH changes of 0.07 and 0.27 pH units. Subsequently a homogeneous acidification, of 0.15 pH units, developed by 23 min following exposure to ammonia. Intracellular pH recovered within 6 min after discontinuation of the ammonia load. In the absence of external bicarbonate, intracellular pH was 0.12 units more acidic than in the bicarbonate buffer and ammonia caused a further acidification by 0.16 units. When glutamine synthase inhibitor, methionine sulphoximine, was added, there was a slow fall in intracellular pH. Under these conditions, subsequent addition of ammonia failed to cause acidification directly. Thus acute elevation of ammonia does not lead to a change in cerebral high-energy phosphate or lactate metabolism, but may be associated with a fall in cortical intracellular pH.

Acid-Base Equilibrium↗
PubMed1989

31P nuclear magnetic resonance of rat pancreatic grafts.

This study investigates whether phosphate metabolite concentrations and intracellular pH alter in early acute rejection of rat pancreatic allografts. In vitro biochemical assays, in vitro 31P nuclear magnetic resonance spectroscopy, and in vivo 31P NMR spectroscopy of the grafts were compared. Duct-ligated, vascularized rat pancreatic isografts and allografts were transplanted onto the infrarenal aorta of the recipients with inferior vena cava venous drainage. In order to obtain reproducible acute rejection, allografting was performed across a major histocompatibility barrier. For the in vitro experiments freeze-clamped graft extracts were prepared and analyzed for adenosine triphosphate concentration by fluorimetry, then placed in an 8.5 Tesla vertical bore magnet. 31P NMR spectra were recorded using a Bruker AM 360 spectrometer operating at 145.7 MHz for 31P. Spectra were acquired from nontransplanted controls; 3-day, 5-day, and 1-month posttransplant isografts, and 3-day and 5-day posttransplant allografts. All grafts examined were functioning satisfactorily. The ATP content of the extracts was significantly lower in the 3- and 5-day allografts than the respective isografts. Invasive in vivo 31P NMR spectra were recorded using surface coils adjacent to the grafts from functioning 5-day posttransplant isografts and allografts (i.e., 3 days prior to an expected elevation in blood sugar from acute rejection in the allografts). The ATP/inorganic phosphate ratios and pH from the in vivo spectra were significantly lower in the allografts than in the isografts. It is concluded that changes in intracellular metabolism occur early in the process of acute rejection and that 31P NMR spectroscopy may provide a means of diagnosing this before current methods.

Adenosine Triphosphate↗