Search PubMed⌕ Search

Biomedical subjects

C Thomsen

Publications and source records attributed to C Thomsen.

At least 19 recordsLinked to original sources

Muscarinic receptor agonists decrease cocaine self-administration rates in drug-naive mice.

(5R,6R)-6-(3-Propylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[ 3.2.1]octane (PTAC) is a selective muscarinic receptor ligand. The compound exhibits high affinity for central muscarinic receptors with partial agonist mode of action at muscarinic M(2) and M(4) and antagonist mode of action at muscarinic M(1), M(3) and M(5) receptor subtypes. The compound was earlier reported to exhibit functional dopamine receptor antagonism in rodents despite its lack of affinity for dopamine receptors. In the present study, we report that PTAC, as well as the muscarinic receptor agonists pilocarpine and oxotremorine, dose-dependently decreased rates of intravenous self-administration (fixed ratio 1) of the indirect dopamine receptor agonist cocaine in drug naive mice. Similar decreases in cocaine self-administration rates were obtained with the dopamine receptor antagonists olanzapine, clozapine, risperidone, fluphenazine and haloperidol. These findings suggest that compounds with partial muscarinic receptor agonist mode of action may be used in the medical treatment of cocaine abuse.

Animals↗

Determination of fenpyroximate in apples by supercritical fluid extraction and packed capillary liquid chromatography with UV detection.

A method using off-line supercritical fluid extraction (SFE) and micro liquid chromatography (microLC) with UV detection at 260 nm, was developed for selective determination of fenpyroximate in apple samples. The packed capillary liquid chromatography method utilises 20 microl injection volumes with on-column focusing. A 350x0.32 mm capillary column packed with Kromasil 100-C18 of 5 microm particle size was used with a mobile phase of acetonitrile-10 mM ammonium acetate (85:15, v/v) at a flow of 5 microl/min. A two-step SFE procedure was used to extract fenpyroximate selectively in 2 g apple samples, with Hydromatrix (HMX) added as a water absorbent at a 1:1 (w:w) ratio. Fenpyroximate was extracted at 200 bar and 90 degrees C for 15 min using carbon dioxide at a flow of 2 ml/min, and solvent trapping collection in 10 ml acetonitrile. The volume of the acetonitrile extract was reduced by evaporation and water was added to a final composition of acetonitrile-water (40:60, v/v). The resulting 2.0 ml solution was filtered using a 0.45 microm poly(vinylidene difluoride) syringe filter before microLC analysis. Validation of the method was accomplished with apple samples spiked with fenpyroximate, covering the range of 0.1 to 1.0 microg/kg. The within-day and between-day repeatabilities were in the range 4-18% relative standard deviation. Accuracy, measured as recovery, was found to be approximately 60%. Apple samples from a field treated with fenpyroximate were analysed. None of the samples contained fenpyroximate above the quantification level.

Benzoates↗

Vasodilatation with felodipine in chronic asymptomatic aortic regurgitation.

BACKGROUND: Afterload reduction decreases volume overload on the left ventricle and may thereby delay the need for valve replacement in chronic asymptomatic aortic regurgitation. The aims of this randomized double-blind, placebo-controlled trial were to examine short- and long-term hemodynamic effects of felodipine in chronic asymptomatic aortic regurgitation. METHODS: Sixteen patients were randomly assigned to an intravenous infusion of either felodipine 0. 3 mg or placebo followed by 3 months' treatment with felodipine 10 mg or placebo orally once daily. Magnetic resonance imaging was performed at baseline, immediately after intravenous treatment, and after 3 months of oral treatment. RESULTS: Intravenous felodipine caused a statistically significant reduction in the systemic vascular resistance from (mean +/- SD) 1160 +/- 400 to 970 +/- 320 dynes. s. cm(-5) (P <.05), in the regurgitant volume index from 1.5 +/- 0.8 to 1.3 +/- 0.8 L. min(-1). m(-2) (P <.05), and in the regurgitant fraction from 0.31 +/- 0.15 to 0.26 +/- 0.14 (P <.05). The forward cardiac output index increased significantly from 3.2 +/- 0.9 to 3.5 +/- 0.7 L. min(-1). m(-2) (P <.05). Three months of oral treatment with felodipine caused a corresponding but more pronounced decrease in systemic vascular resistance of 880 +/- 330 dynes. s. cm(-5) (P <.05), regurgitant volume index of 1.2 +/- 0.7 L. min(-1). m(-2) (P <.05), and regurgitant fraction 0.25 +/- 0.11 (P <.05), whereas the forward cardiac output index increased to 3.6 +/- 0.7 L. min(-1). m(-2) (P <.05). No significant changes were found in the placebo group. Left ventricular volumes and ejection fraction remained unaffected by treatment, but compared with the placebo group left ventricular myocardial mass decreased significantly from 137 +/- 24 to 132 +/- 21 g. m(-2) (P <.01). CONCLUSION: In chronic asymptomatic aortic regurgitation, felodipine causes beneficial hemodynamic effects that may postpone the need for valve replacement.

Adult↗

High-resolution diffusion imaging using phase-corrected segmented echo-planar imaging.

Diffusion magnetic resonance imaging (MRI) was performed with a high-resolution segmented echo-planar imaging technique, which provided images with substantially less susceptibility artifacts than images obtained with single-shot echo-planar imaging (EPI). Diffusion imaging performed with any multishot pulse sequence is inherently sensitive to motion artifacts and in order to reduce motion artifacts, the presented method utilizes navigator echo phase corrections, performed after a one-dimensional Fourier transform along the frequency-encoding direction. Navigator echo phases were fitted to a straight line prior to phase correction to avoid errors from internal motion. In vivo imaging was performed using electro cardiographic (ECG) triggering. Apparent diffusion coefficient (ADC) maps were calculated on a pixel-by-pixel basis using up to seven diffusion sensitivities, ranging from b = 0 to 1129 x 10(6) s/m(2).

Adult↗

Quantitation of regional cerebral blood flow corrected for partial volume effect using O-15 water and PET: I. Theory, error analysis, and stereologic comparison.

Limited spatial resolution of positron emission tomography (PET) can cause significant underestimation in the observed regional radioactivity concentration (so-called partial volume effect or PVE) resulting in systematic errors in estimating quantitative physiologic parameters. The authors have formulated four mathematical models that describe the dynamic behavior of a freely diffusible tracer (H215O) in a region of interest (ROI) incorporating estimates of regional tissue flow that are independent of PVE. The current study was intended to evaluate the feasibility of these models and to establish a methodology to accurately quantify regional cerebral blood flow (CBF) corrected for PVE in cortical gray matter regions. Five monkeys were studied with PET after IV H2(15)O two times (n = 3) or three times (n = 2) in a row. Two ROIs were drawn on structural magnetic resonance imaging (MRI) scans and projected onto the PET images in which regional CBF values and the water perfusable tissue fraction for the cortical gray matter tissue (hence the volume of gray matter) were estimated. After the PET study, the animals were killed and stereologic analysis was performed to assess the gray matter mass in the corresponding ROIs. Reproducibility of the estimated parameters and sensitivity to various error sources were also evaluated. All models tested in the current study yielded PVE-corrected regional CBF values (approximately 0.8 mL x min(-1) x g(-1) for models with a term for gray matter tissue and 0.5 mL x min(-1) x g(-1) for models with a term for a mixture of gray matter and white matter tissues). These values were greater than those obtained from ROIs tracing the gray matter cortex using conventional H2(15)O autoradiography (approximately 0.40 mL x min(-1) x g(-1)). Among the four models, configurations that included two parallel tissue compartments demonstrated better results with regards to the agreement of tissue time-activity curve and the Akaike's Information Criteria. Error sensitivity analysis suggested the model that fits three parameters of the gray matter CBF, the gray matter fraction, and the white matter fraction with fixed white matter CBF as the most reliable and suitable for estimating the gray matter CBF. Reproducibility with this model was 11% for estimating the gray matter CBF. The volume of gray matter tissue can also be estimated using this model and was significantly correlated with the results from the stereologic analysis. However, values were significantly smaller compared with those measured by stereologic analysis by 40%, which can not be explained by the methodologic errors. In conclusion, the partial volume correction was essential in quantitation of regional CBF. The method presented in this article provided the PVE-corrected regional CBF in the cortical gray matter tissue. This study also suggests that further studies are required before using MRI derived anatomic information for PVE correction in PET.

Animals↗

Probing the ligand-binding domain of the mGluR4 subtype of metabotropic glutamate receptor.

Metabotropic glutamate receptors (mGluRs) are G-protein-coupled glutamate receptors that subserve a number of diverse functions in the central nervous system. The large extracellular amino-terminal domains (ATDs) of mGluRs are homologous to the periplasmic binding proteins in bacteria. In this study, a region in the ATD of the mGluR4 subtype of mGluR postulated to contain the ligand-binding pocket was explored by site-directed mutagenesis using a molecular model of the tertiary structure of the ATD as a guiding tool. Although the conversion of Arg(78), Ser(159), or Thr(182) to Ala did not affect the level of protein expression or cell-surface expression, all three mutations severely impaired the ability of the receptor to bind the agonist L-[(3)H]amino-4-phosphonobutyric acid. Mutation of other residues within or in close proximity to the proposed binding pocket produced either no effect (Ser(157) and Ser(160)) or a relatively modest effect (Ser(181)) on ligand affinity compared with the Arg(78), Ser(159), and Thr(182) mutations. Based on these experimental findings, together with information obtained from the model in which the glutamate analog L-serine O-phosphate (L-SOP) was "docked" into the binding pocket, we suggest that the hydroxyl groups on the side chains of Ser(159) and Thr(182) of mGluR4 form hydrogen bonds with the alpha-carboxyl and alpha-amino groups on L-SOP, respectively, whereas Arg(78) forms an electrostatic interaction with the acidic side chains of L-SOP or glutamate. The conservation of Arg(78), Ser(159), and Thr(182) in all members of the mGluR family indicates that these amino acids may be fundamental recognition motifs for the binding of agonists to this class of receptors.

Amino Acid Sequence↗

N-substituted adenosines as novel neuroprotective A(1) agonists with diminished hypotensive effects.

The synthesis and pharmacological profile of a series of neuroprotective adenosine agonists are described. Novel A(1) agonists with potent central nervous system effects and diminished influence on the cardiovascular system are reported and compared to selected reference adenosine agonists. The novel compounds featured are derived structurally from two key lead structures: 2-chloro-N-(1-phenoxy-2-propyl)adenosine (NNC 21-0041, 9) and 2-chloro-N-(1-piperidinyl)adenosine (NNC 90-1515, 4). The agonists are characterized in terms of their in vitro profiles, both binding and functional, and in vivo activity in relevant animal models. Neuroprotective properties assessed after postischemic dosing in a Mongolian gerbil severe temporary forebrain ischemia paradigm, using hippocampal CA1 damage endpoints, and the efficacy of these agonists in an A(1) functional assay show similarities to some reference adenosine agonists. However, the new compounds we describe exhibit diminished cardiovascular effects in both anesthetized and awake rats when compared to reference A(1) agonists such as (R)-phenylisopropyladenosine (R-PIA, 5), N-cyclopentyladenosine (CPA, 2), 4, N-[(1S,trans)-2-hydroxycyclopentyl]adenosine (GR 79236, 26), N-cyclohexyl-2'-O-methyladenosine (SDZ WAG 994, 27), and N-[(2-methylphenyl)methyl]adenosine (Metrifudil, 28). In mouse permanent middle cerebral artery occlusion focal ischemia, 2-chloro-N-[(R)-[(2-benzothiazolyl)thio]-2-propyl]adenosine (NNC 21-0136, 12) exhibited significant neuroprotection at the remarkably low total intraperitoneal dose of 0.1 mg/kg, a dose at which no cardiovascular effects are observed in conscious rats. The novel agonists described inhibit 6, 7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate-induced seizures, and in mouse locomotor activity higher doses are required to reach ED(50) values than for reference A(1) agonists. We conclude that two of the novel adenosine derivatives revealed herein, 12 and 5'-deoxy-5'-chloro-N-[4-(phenylthio)-1-piperidinyl]adenosine (NNC 21-0147, 13), representatives of a new series of P(1) ligands, reinforce the fact that novel selective adenosine A(1) agonists have potential in the treatment of cerebral ischemia in humans.

Adenosine↗

Synthesis of novel GABA uptake inhibitors. 3. Diaryloxime and diarylvinyl ether derivatives of nipecotic acid and guvacine as anticonvulsant agents.

(3R)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylic acid 1 (tiagabine, Gabitril) is a potent and selective gamma-aminobutyric acid (GABA) uptake inhibitor with proven anticonvulsant efficacy in humans. This drug, which has a unique mechanism of action among marketed anticonvulsant agents, has been launched for add-on treatment of partial seizures with or without secondary generalization in patients >12 years of age. Using this new agent as a benchmark, we have designed two series of novel GABA uptake inhibitors of remarkable potency, using a putative new model of ligand interaction at the GABA transporter type 1 (GAT-1) uptake site. This model involves the postulated interaction of an electronegative region in the GABA uptake inhibitor with a positively charged domain in the protein structure of the GAT-1 site. These two novel series of anticonvulsant agents contain diaryloxime or diarylvinyl ether functionalities linked to cyclic amino acid moieties and were derived utilizing the new model, via a series of design steps from the known 4,4-diarylbutenyl GABA uptake inhibitors. The new compounds are potent inhibitors of [(3)H]-GABA uptake in rat brain synaptosomes in vitro, and their antiepileptic potential was demonstrated in vivo by their ability to protect against seizures induced by the benzodiazepine receptor inverse agonist methyl 4-ethyl-6,7-dimethoxy-beta-carboline-3-carboxylate (DMCM) in mice. From structure-activity studies of these new GABA uptake inhibitors, we have shown that insertion of an ether oxygen in conjugation with the double bond in tiagabine (K(i) = 67 nM) improves in vitro potency by 5-fold to 14 nM.

Animals↗

1-(1,2,5-Thiadiazol-4-yl)-4-azatricyclo[2.2.1.0(2,6)]heptanes as new potent muscarinic M1 agonists: structure-activity relationship for 3-aryl-2-propyn-1-yloxy and 3-aryl-2-propyn-1-ylthio derivatives.

Two new series of 1-(1,2,5-thiadiazol-4-yl)-4-azatricyclo[2.2.1.0(2, 6)]heptanes were synthesized and evaluated for their in vitro activity in cell lines transfected with either the human M1 or M2 receptor. 3-Phenyl-2-propyn-1-yloxy and -1-ylthio analogues substituted with halogen in the meta position showed high functional potency, efficacy, and selectivity toward the M1 receptor subtype. A quite unique functional M1 receptor selectivity was observed for compounds 8b, 8d, 8f, 9b, 9d, and 9f. Bioavailability studies in rats indicated an oral bioavailability of about 20-30%, with the N-oxide as the only detected metabolite.

Animals↗

Pentylenetetrazol-induced seizures increase [3H]L-2-amino-4-phosphonobutyrate binding in discrete regions of the rat brain.

Convulsions were induced in rats by a single injection of pentylenetetrazol (PTZ) and [3H]L-2-amino-4-phosphonobutyrate ([3H]L-AP4) in vitro receptor autoradiography was used to evaluate the effects on the expression of group III metabotropic glutamate receptors. Significant increases by 60-80% in [3H]L-AP4 binding was observed in the frontal parts of cortex (sensory, motor and cingulate cortex) and by 28% in the molecular layer of the cerebellar cortex 24 h after PTZ-induced seizures. Since group III metabotropic glutamate receptors has an inhibitory effect on glutamatergic transmission, the observed increases in binding may indicate that these receptors serve as a mechanism for preventing further seizure activity.

Aminobutyrates↗

Magnetic resonance imaging of valvular heart disease.

The optimum management of patients with valvular heart diseases requires accurate and reproducible assessment of the valvular lesion and its hemodynamic consequences. Magnetic resonance imaging (MRI) techniques, such as volume measurements, signal-void phenomena, and velocity mapping, can be used in an integrated approach to gain qualitative and quantitative information on valvular heart disease as well as ventricular dimensions and functions. Thus, MRI may be advantageous to the established diagnostic tools in assessing the severity of valvular heart disease as well as monitoring the lesion and predicting the optimal timing for valvular surgery. This paper reviews the validation of these MRI techniques in assessing valvular heart disease and discusses some typical pitfalls of the techniques, including suggestions for solutions.J. Magn. Reson. Imaging 1999;10:627-638.

Blood Flow Velocity↗

Comparison of the effects of a monounsaturated fat diet and a high carbohydrate diet on cardiovascular risk factors in first degree relatives to type-2 diabetic subjects.

OBJECTIVE: Recent studies have demonstrated beneficial metabolic effects of dietary monounsaturated fatty acids (MUFA) in Type-2 diabetes mellitus (Type-2 DM). The question arises if dietary MUFA also has desirable effects on risk markers in subjects with high risk of developing Type-2 DM. SETTING: University department of endocrinology. SUBJECTS: Sixteen healthy, first-degree relatives (six men, 10 women, age (mean+/-s.d.): 35+/-2 years) with normal oral glucose tolerance tests. INTERVENTIONS: Randomised study with two 4-week treatment periods with either a carbohydrate-rich (CHO) diet (55 E% carbohydrate, 30 E% fat, 15 E% protein) or a diet rich in olive oil [MUFA 40 E% fat (25 E% as MUFA), 45 E% carbohydrate, 15 E% protein]. The periods were divided by a 4-week wash-out period. RESULTS: Similar lowering effects on total cholesterol, low density lipoprotein (LDL)-cholesterol, triglyceride and apoB levels were seen after the two diets. Slightly higher levels of high-density lipoprotein (HDL)-cholesterol (1.4+/-0.4 vs 1.3+/-0.4 mmol/l, P<0. 0001) and apoA-1 (1.2+/-0.3 vs 1.1+/-0.3 mmol/l, P<0.05) were found in the MUFA-diet. Furthermore, the insulin sensitivity, as assessed by Bergman's minimal model, and the first response insulin areas were similar, as were the 24-h blood pressures and the von Willebrand Factor (vWF) levels. CONCLUSIONS: Isocaloric diets rich in MUFA or rich in carbohydrate, respectively, seem to have similar effects on cardiovascular risk factors in persons at high risk of developing Type-2 DM. A potential risk, however, on body weight of high-fat diets should be kept in mind. SPONSORSHIP: This study was supported by grants from the Danish Diabetes Association, Institute of Clinical Experimental Research, Aarhus University, The Danish Heart Foundation, The Danish Medical Research Council, Velux Foundation, Poul and Erna Sehested Hansens Foundation, Mogens Svarre Mogensens Foundation.

Adult↗

Contribution of metabotropic glutamate receptor mGluR4 to L-2-[3H]amino-4-phosphonobutyrate binding in mouse brain.

The binding of L-2-[3H]amino-4-phosphonobutyrate ([3H]L-AP4) was examined in brain sections of wild-type mice and mice lacking the mGluR4 subtype of metabotropic glutamate receptors (mGluRs). Very high relative densities of [3H]L-AP4 binding were observed in the molecular layer of the cerebellar cortex, the nucleus basalis, the outer layer of the superior colliculus, and the substantia nigra. In mGluR4 knock-out mice, very low levels of binding were observed in these regions. The moderate levels of binding observed with wild-type mice in the molecular layer of the hippocampal dentate gyrus and in the thalamus were absent in mGluR4 knock-out mice. In contrast, the moderate levels observed in most of the cerebral cortex, caudate putamen, and globus pallidus were not different in mGluR4 knock-out mice compared with wild-type. In these regions, mGluR8 is likely to be labeled by [3H]L-AP4 because mGluR8 is expressed in such brain regions and, like mGluR4, has high affinity for L-AP4. We conclude that mGluR4 contributes substantially to the high-affinity binding site for [3H]L-AP4 in several regions of mouse brain, including cerebellar cortex, nucleus basalis, thalamus, superior colliculus, substantia nigra, and hippocampal dentate gyrus.

Aminobutyrates↗

Astroglia contain a specific transport mechanism for N-acetyl-L-aspartate.

N-Acetylaspartate (NAA) is the second most abundant amino acid in the adult brain. It is located and synthesized in neurons and probably degraded in the glia compartment, but the transport mechanisms are unknown. Rat primary neuron and astrocyte cell cultures were exposed to the L isomer of [3H]NAA and demonstrated concentration-dependent uptake of [3H]NAA with a Km approximately 80 microM. However, Vmax was 23+/-6.4 pmol/mg of protein/min in astrocytes but only 1.13+/-0.4 pmol/mg of protein/min in neurons. The fact that neuron cultures contain 3-5% astrocytes suggests that the uptake mechanism is expressed only in glial cells. The astrocyte uptake was temperature and sodium chloride dependent and specific for L-NAA. The affinity for structural analogues was (IC50 in mM) as follows: L-NAA (0.12) > N-acetylaspartylglutamate (0.4) > N-acetylglutamate (0.42) > L-aspartate (>1) > L-glutamate (>1) > or = DL-threo-beta-hydroxyaspartate > N-acetyl-L-histidine. The naturally occurring amino acids showed no inhibitory effect at 1 mM. The glutamate transport blocker trans-pyrrolidine-2,4-dicarboxylate exhibited an IC50 of 0.57 mM, whereas another specific glutamate transport inhibitor, DL-threo-beta-hydroxyaspartate, had an IC50 of >1 mM. The experiments suggest that NAA transport in brain parenchyma occurs by a novel type of sodium-dependent carrier that is present only in glial cells.

Animals↗

Differential effects of saturated and monounsaturated fatty acids on postprandial lipemia and incretin responses in healthy subjects.

BACKGROUND: Elevations of postprandial triacylglycerol-rich plasma lipoproteins and suppressions of HDL-cholesterol concentrations are considered potentially atherogenic. Long-term studies have shown beneficial effects of monounsaturated fatty acids (eg, oleic acid) on fasting lipid and lipoprotein concentrations in humans. A direct stimulatory effect of oleic acid on the secretion of glucagon-like peptide 1 (GLP-1) was shown in animal studies. OBJECTIVE: We compared the postprandial responses of glucose, insulin, fatty acids, triacylglycerol, gastric inhibitory polypeptide (GIP), and GLP-1 to test meals rich in saturated and monounsaturated fatty acids. DESIGN: Ten young, lean, healthy persons ingested 3 meals: an energy-free soup consumed with 50 g carbohydrate (control meal), the control meal plus 100 g butter, and the control meal plus 80 g olive oil. Triacylglycerol and retinyl palmitate responses were measured in total plasma, in a chylomicron-rich fraction, and in a chylomicron-poor fraction. RESULTS: No significant differences in glucose, insulin, or fatty acid responses to the 2 fat-rich meals were seen. Plasma triacylglycerol responses were highest after the butter meal, with chylomicron triacylglycerol rising 2.5-5-fold. Retinyl palmitate responses were higher and more prolonged after the butter meal than after the control and olive oil meals, whereas both postprandial HDL-cholesterol concentrations and GLP-1 and GIP responses were higher after the olive oil meal than after the butter meal. CONCLUSIONS: Olive oil induced lower triacylglycerol concentrations and higher HDL-cholesterol concentrations than butter, without eliciting differences in concentrations of glucose, insulin, or fatty acids. Furthermore, olive oil induced higher concentrations of GLP-1 and GIP than did butter, which may point to a relation between fatty acid composition, incretin responses, and triacylglycerol metabolism in the postprandial phase.

Adult↗

Increased insulin secretion and normalization of glucose tolerance by cholinergic agonism in high fat-fed mice.

Increased insulinotropic activity by the cholinergic agonist carbachol exists in insulin-resistant high fat-fed C57BL/6J mice. We examined the efficiency and potency of carbachol to potentiate glucose-stimulated insulin secretion and to improve glucose tolerance in these animals. Intravenous administration of carbachol (at 15 and 50 nmol/kg) markedly potentiated glucose (1 g/kg)-stimulated insulin secretion in mice fed both a control and a high-fat diet (for 12 wk), with a higher relative potentiation in high fat-fed mice measured as increased (1-5 min) acute insulin response and area under the 50-min insulin curve. Concomitantly, glucose tolerance was improved by carbachol. In fact, carbachol normalized glucose-stimulated insulin secretion and glucose tolerance in mice subjected to a high-fat diet. Carbachol (>100 nmol/l) also potentiated glucose-stimulated insulin secretion from isolated islets with higher efficiency in high fat-fed mice. In contrast, binding of the muscarinic receptor antagonist [N-methyl-(3)H]scopolamine to islet muscarinic receptors and the contractile action of carbachol on ileum muscle strips were not different between the two groups. We conclude that carbachol normalizes glucose tolerance in insulin resistance.

Animals↗

Triggering in quantitative diffusion imaging with single-shot EPI.

PURPOSE: The aim of this study was to evaluate any possible effects of brain motion, CSF pulsations and other possible sources of physiological motion in electrocardiographic (ECG) triggered and non-triggered single-shot echo-planar imaging (EPI) measurements of diffusion. MATERIAL AND METHODS: Three different triggering protocols were evaluated in 6 healthy volunteers: 1) ECG triggering with time delay (TD) 100 ms; 2) ECG triggering with TD 400 ms; and 3) no triggering at all. RESULTS: The results obtained showed that white matter mean apparent diffusion coefficient (ADC) values were similar for all triggering protocols and that the reproducibility in ADC measurements using diffusion-weighted (DW) EPI was good. The average standard deviation of the ADC values was, however, higher for ADC maps obtained without ECG triggering. CONCLUSION: The use of prospective diastolic ECG triggering significantly improves the accuracy of quantitative diffusion measurements but for routine clinical diffusion imaging, where quantitative data is of less importance, the accuracy obtained without ECG triggering can be considered adequate.

Adult↗