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Biomedical subjects

I J Cox

Publications and source records attributed to I J Cox.

At least 19 recordsLinked to original sources
PubMed1995

MRI assessment of the blood-brain barrier in a hamster model of scrapie.

Magnetic resonance (MR) imaging in combination with gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) enhancement was used to investigate the integrity of the blood-brain barrier in a hamster model of scrapie (263K) during the clinical phase of the disease. The post Gd-DTPA images of the infected hamster brain showed marked enhancement, which was not present in control animals. These results suggest that blood-brain barrier function is disrupted in the clinically-affected animal.

Animals↗
PubMed1995

Effect of functional grade and etiology on in vivo hepatic phosphorus-31 magnetic resonance spectroscopy in cirrhosis: biochemical basis of spectral appearances.

Hepatic phosphorus-31 magnetic resonance spectroscopy (31P MRS) was undertaken in 85 patients with histologically proven cirrhosis of varying etiologies and functional severity. Reference data were acquired from 16 healthy volunteers who had no history or evidence of liver disease or alcohol abuse. In vivo hepatic 31P MR spectra were acquired with pulse angle 45 degrees and repetition times (TR) of 5 and 0.5 seconds. Peak area ratios of phosphomonoesters (PME), inorganic phosphate (Pi), and phosphodiesters (PDE) relative to beta ATP, and of PME relative to PDE were calculated from spectra acquired at TR 5 seconds. Estimates of saturation effects for individual resonances were obtained by dividing the peak height at TR 5 seconds by that at TR 0.5 seconds to yield a T1-related signal height ratio (SHR). When compared with reference values, the patients with liver disease showed a significantly higher PME/ATP (P < .0001), PME/PDE (P < .0001), PME SHR (P < .001), and Pi SHR (P < .02), and a lower PDE/ATP (P < .001) and PDE SHR (P < .001). The magnitude of these changes increased significantly and progressively with increasing functional impairment. In patients with compensated cirrhosis spectral appearances varied with etiology; thus, patients with postviral cirrhosis showed a significantly higher Pi/ATP; those with alcoholic cirrhosis, a significantly lower PDE/ATP; and those with cirrhosis secondary to primary sclerosing cholangitis, a significantly lower Pi/ATP than the healthy volunteers or other etiological groups. However, spectral appearances did not vary with etiology in patients with decompensated disease. In vitro 31P MRS of perchloric extracts of samples of liver tissue obtained from 10 patients with cirrhosis at transplant hepatectomy showed increases in levels of the soluble PME metabolites, phosphorylcholine and phosphorylethanolamine, and reductions in the levels of the soluble PDE metabolites, glycerophosphorylcholine and glycerophosphorylethanolamine. These changes suggest regenerative activity in cirrhotic livers. The increases in soluble phosphomonoesters in the aqueous extracts accounted for the increased PME/ATP ratio seen in the in vivo spectra, and might account for the increase in PME SHR. The reduction in soluble phosphodiesters in the aqueous extracts did not entirely account for the reduction PDE/ATP ratio seen in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1992

Phosphorus-31 magnetic resonance spectroscopy of the human liver using chemical shift imaging techniques.

Phosphorus-31 magnetic resonance spectroscopy of the human liver was undertaken in 28 healthy adult individuals and in 49 patients with liver disease of varying aetiology. Data localised to the liver were obtained using chemical shift imaging techniques. The mean (+/- 1 S.D.) of the peak area ratio phosphomonoesters (PME)/phosphodiesters (PDE) in healthy adult individuals, from spectra obtained with pulse angle 45 degrees and repetition time 1 s, was 0.24 +/- 0.07. The intra-examination variability of this ratio was 20%, the intra-subject variability 27% and the inter-subject variability 32%. An increase in the PME/PDE was observed in the 31P hepatic MR spectrum from primary or secondary tumours in all 17 patients studied, which invariably represented an increase in PME/ATP and, in some cases, a reduction in PDE/ATP. The spectra did not show aetiological characteristics. A non-specific elevation in PME/PDE was also observed in the 31P hepatic MR spectra of 10 (40%) of 25 patients studied who had diffuse liver diseases, such as cirrhosis and infiltrating malignancies. The spectral pattern did not distinguish between diseases of varying aetiologies, but there was a linear correlation between increasing PME/PDE and a reduction in plasma albumin concentrations (p = 0.03). In three patients with hepatic malignancy and abnormal hepatic 31P-MRS, marked spectral changes were observed after successful treatment to debulk the tumour. Only minor changes were observed in the abnormal spectrum of a fourth patient in whom treatment was unsuccessful. Hepatic 31P-MR spectroscopy may prove useful for monitoring disease processes and treatment effects in well characterised patient populations.

Adenocarcinoma↗
PubMed1992

Effect of L-alanine infusion on 31P nuclear magnetic resonance spectra of normal human liver: towards biochemical pathology in vivo.

1. 31P n.m.r. spectroscopy in vivo was used to study the effect of L-alanine infusion on the concentrations of gluconeogenic intermediates in normal human liver. Studies were performed in six healthy male subjects (34-44 years, fasted overnight) using a chemical shift imaging pulse sequence on a whole-body n.m.r. system operating at 1.6T. Hepatic 31P n.m.r. spectra were obtained from 10 min before to 70 min after intravenous administration of 0.70 (n = 2), 1.40 (n = 3) or 2.80 (n = 5) nmol of L-alanine/kg body weight over 4.5 min. Concentrations of phosphomonoesters, Pi and phosphodiesters relative to ATP were calculated from peak areas in the n.m.r. spectra, using the beta-ATP peak as a reference. 2. Dose-dependent spectral changes were observed for [phosphomonoesters]/[ATP] and [Pi]/[ATP]. At the highest dose given, maximal changes in [phosphomonoesters]/[ATP] (mean +/- SEM: 98 +/- 12%, P < 0.005) and [Pi]/[ATP] (-33 +/- 3%, P < 0.001) were observed approximately 45 min after the L-alanine infusion. [Phosphodiesters]/[ATP] showed a maximal increase of 24 +/- 6% (P < 0.05), which was independent of the L-alanine dose. Hepatic ATP levels and pH did not change. 3. To identify the metabolites responsible for the changes observed in vivo, male Wistar rats were infused with 11.2 mmol of L-alanine/kg body weight. After 15 min, livers were freeze-clamped and were extracted according to standard procedures. In vitro, 31P n.m.r. spectra obtained at 8.4 or 11.7 T revealed sharp increases in the concentrations of 3-phosphoglycerate and phosphoenolpyruvate after L-alanine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
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

In vivo detection of metabolic changes in a mouse model of scrapie using nuclear magnetic resonance spectroscopy.

In vivo proton nuclear magnetic resonance (NMR) spectroscopy studies of scrapie in a mouse model have shown the appearance of an abnormal peak in the brain early in the incubation period. This abnormal peak was detected weeks before the detection of a protease-resistant form of a membrane protein and vacuolar histopathology in vitro, and several months before clinical signs, and the signal increased in intensity as the disease progressed. In the chronic stage of the disease, a reduction in N-acetyl aspartate levels was observed using in vivo and in vitro proton NMR spectroscopy.

Animals↗
PubMed1990

31P magnetic resonance spectroscopy of the human paediatric liver.

Localized 31P NMR spectroscopy was used to study the developing human liver in three neonates and one infant, all with neonatal intracranial problems, but normal liver function. A prominent resonance was present in the phosphomonoester (PME) region of the spectrum of the neonates; the PME/ATP ratio was 1.0 +/- 0.4 (repetition time 1 s), compared to the mean adult liver value of 0.2 +/- 0.1. The saturation factor of PME in the neonates was large, indicating that the increase in PME/ATP reflected an increase in relative PME concentration. The chemical shift of the PME peak in the neonatal liver (6.8 +/- 0.1) was similar to that found in neonatal brain, suggesting that phosphorylethanolamine may be a major constituent. The phosphodiester (PDE)/ATP ratio in these patients (0.4 +/- 0.1) was decreased compared with the mean adult value (1.3 +/- 0.2), and the saturation factor of PDE was small. The results from the infant were different from both the neonates and adults; PME/ATP was decreased compared to the neonates, but increased compared to adults. The saturation factor of PDE was increased compared to neonates. The biochemical implications of the observed changes in PME and PDE in paediatric liver are discussed in relation to membrane turnover.

Brain Diseases↗
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

Some considerations concerning susceptibility, longitudinal relaxation time constants and motion artifacts in vivo human spectroscopy.

Artifacts due to localized susceptibility effects, variations in the spin-lattice relaxation time constants of signals and a mixing of signals arising from tissue motions can contaminate otherwise credible results. The sources and magnitude of some of these are discussed and their likely impact assessed, so that the necessity of incorporating additional measurements in an individual study can be demonstrated.

Diagnostic Errors↗
PubMed1988

Four-dimensional phosphorus-31 chemical shift imaging of carcinoid metastases in the liver.

Four-dimensional chemical shift imaging was used to map spatial variations in phosphorus metabolites in a patient with carcinoid metastases in the liver. The results were compared to those from an age and sex matched volunteer, with no known previous history of liver disease. In the patient local abnormalities were observed. These included elevated phosphomonoester and decreased phosphodiester concentrations relative to adenosine triphosphate. The regions of abnormality corresponded to regions containing metastases identified with x-ray computed tomography and magnetic resonance imaging.

Adult↗
PubMed1987

Osteosarcoma and other neoplasms of bone. Magnetic resonance spectroscopy to monitor therapy.

Fourteen patients with malignant tumors of bone (ten osteogenic sarcomas, one Ewing's tumor, one giant-cell tumor, two non-Hodgkin's lymphomas), plus one patient with a synovial cell sarcoma, who had been treated by standard extremity-conserving chemotherapy regimens, were examined before treatment by means of localized phosphorus 31 magnetic resonance spectroscopy. Thirteen (86%) of 15 examinations were successful, and 100% of successful examinations showed metabolic abnormality in the tumor. Tumors contained excess adenosine triphosphate and inorganic phosphate, an unusual peak of phosphomonoester, consistent with excessive glycolysis in tumors. The intratumor pH was normal in the 12 bone tumors, but acidic in the single soft-tissue sarcoma (pH 6.8). Metabolic response was observed in all seven patients monitored during chemotherapy, with the earliest examinations being performed two days after first treatment. An increase in the inorganic phosphate level, loss of adenosine triphosphate, and loss of phosphomonoester indicated tumor response; loss of all abnormal metabolites (two of seven patients) indicated regression of the tumor. Tumor relapse was accompanied by reappearance of abnormalities in the magnetic resonance spectrum. Phosphorus 31 magnetic resonance spectroscopy offers a unique means of determining the early response of these malignant tumors to therapy as well as predicting their relapse.

Adenosine Triphosphate↗
PubMed1987

Spectral resolution in clinical magnetic resonance spectroscopy.

We observe linewidths of 0.1-0.4 ppm in 31P spectra of human muscle, liver, and brain. T2 measurements of muscle phosphocreatine, together with previous brain studies, indicate that further improvements in linewidth to 0.02-0.05 ppm might often be achieved, but in some lesions magnetic susceptibility variations may limit spectral resolution.

Brain↗
PubMed1984

Scanning optical fluorescence microscopy.

A scanning optical fluorescence microscope is described which possesses several advantages over a conventional fluorescence microscope. These include improved resolution, a reduction in background- and auto-fluorescence, an increase in the available fluorescence spectrum and simple modification for automated fluorescence studies. Experimental results are included.

Animals↗
PubMedDate not supplied

In vivo and in vitro 31P magnetic resonance spectroscopy of focal hepatic malignancies.

In vivo 31P magnetic resonance spectroscopy (MRS) was undertaken in 28 healthy adult individuals and 32 patients with hepatic malignancies of varying histology, using chemical shift imaging techniques. The mean peak area ratio (total range) of phosphomonoester (PME) to phosphodiester (PDE) in the health adult group was 0.23 (0.15-0.41). The mean (total range) PME/PDE ratio of the total patient group was 0.68 (0.15-2.38), which was significantly elevated (P less than 0.001) compared to the mean of the healthy adult group. Liver biopsies, obtained at operation, were analysed using high-field in vitro MRS techniques in order to identify the contributions of aqueous-soluble metabolites to the multicomponent PME and PDE in vivo signals. Concentrations of phosphorylethanolamine (PE), phosphorylcholine (PC), glycerophosphorylethanolamine (GPE) and glycerophosphorylcholine (GPC) were measured. The in vitro spectrum of six samples of liver of normal histological appearance all showed a similar pattern of PE, PC, GPE and GPC. The in vitro spectrum of seven liver tumours of differing histology all showed an increase in PE and PC signals and a decrease in GPC and GPE signals. The in vitro results were compared with in vivo findings in five patients. The increase in PME/PDE observed in vivo represented, in part, an increase in PE and PC in the PME region and a decrease in GPE and GPC in the PDE region.

Adenocarcinoma↗
PubMedDate not supplied

The benefits of increasing spatial resolution as a means of reducing artifacts due to field inhomogeneities.

All users of NMR equipment are familiar with the desirability of achieving as high a quality of field as possible. On the other hand, it is easy to forget that the field quality of relevance in both imaging and spectroscopy is that over individual voxels, and not the whole volume. This note demonstrates in practice how performance in poor fields is improved substantially by reducing voxel size (or increasing spatial resolution), offering a potential alternative to additional shimming under appropriate circumstances. It argues that the best criterion for assessing magnet quality in spatially localized systems is the maximum field error gradient in the volume of usable field, rather than the maximum deviation in the field.

Humans↗
PubMedDate not supplied

Clinical magnetic susceptibility mapping of the brain.

A field mapping technique was used to detect changes in the local magnetic field in 14 tumors, five hematomas, one lacunar infarct, and two cases of multiple sclerosis. These changes were attributed to variations in the tissue susceptibility. A partial or complete rim of changed susceptibility was detected at the margin of five of the tumors and localized changes were seen within two of the tumors. All five hematomas displayed susceptibility effects. These were seen at the rim of the hematoma in all cases but central effects were also seen in four cases. One area of probable lacunar infarction also displayed susceptibility effects. The effects described may be due to the paramagnetic contribution of species such as deoxyhemoglobin, methemoglobin, free ferric iron, hemosiderin, and other breakdown products of blood. Local field inhomogeneities due to changes in tissue susceptibility have implications for magnetic resonance (MR) image interpretation and the performance of MR spectroscopy.

Brain Diseases↗
PubMedDate not supplied

Clinical use of rapid T2 weighted partial saturation sequences in MR imaging.

Rapid T2 dependent field echo [partial saturation (PS)] sequences were used in 38 patients with brain tumors, intracerebral hematomas, and cerebral infarction as well as other neurological and abdominal disease. Reduction in the radiofrequency excitation angle (alpha) from 90 to 30 degrees produced an increase in lesion contrast as did change of echo time (TE) from 33 to 59 or 120 ms using repetition time (TR) values in the range of 120-500 ms. The PS sequence showing most lesion contrast was compared with conventional spin echo (SE 1,500/80 and SE 1,500/120) and inversion recovery (IR 1,500/500/44 and IR 1,500/100/44) sequences. Although PS sequences with TE = 39 ms were usually inferior to conventional SE sequences, those with TE = 59 or 120 ms were comparable and in some cases (particularly hematomas) superior. The PS sequences with alpha of approximately 30 degrees, TR of 80-250 ms, and TE of 60-120 ms offer considerable savings in time compared with conventional sequences although more work will be required to explore the limits of this approach and to optimize sequences at different field strengths.

Brain Diseases↗