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Biomedical subjects

I J Cox

Publications and source records attributed to I J Cox.

52 records · Page 3Linked to original sources

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↗

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↗

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↗

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↗

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↗

Effects of fish oil on phospholipid metabolism in human and rat liver studied by 31P NMR spectroscopy in vivo and in vitro.

The effect of omega 3 fatty acids on the metabolism of the normal liver was studied using 31P NMR spectroscopy. Human subjects were examined before and after 1, 3 and 7 days of supplementation with 50 mL fish oil per day (12 g omega 3 fatty acids). 31P NMR spectra (1.6 T) revealed a significant increase in phosphodiester (PDE) to ATP ratios after 1 and 3 days of fish oil. After 7 days, [PDE]/[ATP] ratios at a TR of 1 s had returned to baseline levels, but [PDE]/[ATP] at a TR of 5 s appeared to remain high. Rats were fed diets containing 50% of the energy from fish oil or normal rat chow (controls) for 14 days. 31P NMR liver spectra in vivo (4.7 T) confirmed increased [PDE]/[ATP] in rats fed fish oil compared to controls, although the difference was only statistically significant at a TR of 1.5 s but not at a TR of 8 s. 31P NMR spectra of rat liver extracts (8.7 T) suggested that increased concentrations of glycerophosphocholine and possibly glycerophosphoethanolamine were responsible for rising PDE levels in vivo. Phosphocholine (PC) concentrations were markedly reduced in rat liver after fish oil. The combined rise in glycerophosphocholine and reduction in PC would be consistent with a shift from the phospholipase C to the phospholipase A1/A2 pathway of phosphatidylcholine breakdown after fish oil consumption.

Adult↗

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↗

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↗

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↗

Use of phosphorus-31 MR spectroscopy to monitor response to chemotherapy in non-Hodgkin lymphoma.

Two patients with non-Hodgkin lymphoma of the femur were examined with 31P magnetic resonance spectroscopy (MRS) and proton magnetic resonance imaging before and during treatment with chemotherapy. Prior to treatment, 31P MRS of the tumor showed that in comparison to normal skeletal muscle, phosphocreatine was reduced, and phosphomonoesters (PME) and phosphodiesters were elevated. The 31P spectrum became similar to that of normal muscle after 40 days of treatment in both cases. Following the initial dose of chemotherapy, an increase in PME relative to adenosine triphosphate was observed within 48 h in one patient. Magnetic resonance showed a change in the soft tissue component of both tumors and 6-12 months later there was no clinical evidence of any recurrence. Magnetic resonance spectroscopy with 31P may prove to be a sensitive technique for monitoring therapeutic response of tumors.

Adult↗

Proton MR spectroscopy in herpes simplex encephalitis: assessment of neuronal loss.

We present here the case of an 11-year-old boy with herpes simplex encephalitis diagnosed on the basis of clinical features, serology, and response to acyclovir, who relapsed after 3 weeks of therapy. In vivo proton magnetic resonance spectroscopy (1H MRS) of the brain, at 8 and 16 weeks after the onset of symptoms, showed abnormalities, most prominently a reduction in the N-acetylaspartate/choline ratio. The role of 1H MRS in assessing disease activity is discussed.

Aspartic Acid↗

Proton MR spectroscopy of intracranial tumours: in vivo and in vitro studies.

Proton magnetic resonance spectroscopy (1H MRS) was used to investigate intracranial tumours in vitro and in vivo. Biopsy specimens were studied from 47 patients, 11 of whom were also examined in vivo. Analysis was based on the signals from N-acetylaspartate (NAA), phosphocreatine plus creatine (Cr), choline-containing compounds (Cho), alanine (Ala), and lactate. Biopsy data from 26 astrocytomas showed that the NAA/Cr ratio differs significantly in all grades from its value in normal white matter and that the Cho/Cr ratio differs significantly in grade IV tumours from its value in the other grades. Meningiomas have an unusually high Ala/Cr ratio. Spectra obtained in vivo are consistent with in vitro results from the same patients, and their lactate signal provides additional information about abnormal metabolism. We conclude that 1H MRS has a clear role in the diagnosis and biochemical assessment of intracranial tumours and in the evaluation and monitoring of therapy.

Adult↗

Proton MR spectroscopy of the brain in infants.

Proton magnetic resonance spectroscopy (MRS) was used to study the brain of 2 normal and 15 abnormal infants aged from 33 weeks postmenstrual age (PMA) to 14 months postnatal age. Eleven of the infants were examined on at least two occasions. The principal clinical diagnoses in the abnormal infants were perinatal ischemic and hemorrhagic brain injury. All proton spectra demonstrated peaks that were assigned to N-acetylaspartate (NAA), choline containing compounds (Cho), and creatine plus phosphocreatine (Cr). The NAA/Cho and NAA/Cr ratios increased with age, while the Cho/Cr ratio decreased with age in the majority of infants. The NAA/Cho ratio was generally lower in abnormal infants, but the difference was not apparent before 40 weeks (PMA). This ratio was lowest in infants with the severest degree of neurological abnormality. Proton and phosphorus MRS was compared in seven infants. In those with severe brain lesions, early phosphorus spectra were abnormal. On follow-up the phosphorus spectra became normal, but the proton spectra showed persistently low NAA/Cho and NAA/Cr ratios. Proton MRS provides new information that may be complementary to phosphorus MRS in the diagnosis and monitoring of brain development in normal and neurologically damaged infants.

Asphyxia Neonatorum↗

Proton MR spectroscopy of the brain in AIDS dementia complex.

Proton MR spectroscopy of the brain has been undertaken in 8 healthy volunteers and in 11 patients with human immunodeficiency virus infection and varying stages of AIDS dementia complex (ADC). Spectral appearances in patients with no ADC or early ADC were not significantly different from normal volunteers. Spectra from patients with moderate to severe ADC exhibited significant reductions in levels of N-acetyl aspartate (NAA) relative to creatine (Cr) and also showed elevations in choline containing compounds (relative to Cr). Because NAA is though to be a metabolic marker for normally functioning neurons, these findings suggest the presence of neuronal injury or loss in moderate to severe ADC. The significance of these findings is discussed.

AIDS Dementia Complex↗