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J K Saunders

Publications and source records attributed to J K Saunders.

At least 37 records · Page 2Linked to original sources
PubMed1995

Correlation between Gd-enhanced MR imaging and histopathology in treated and untreated 9L rat brain tumors.

Gadolinium-based MR imaging contrast agents cause signal enhancement of intracerebral tumors on T1-weighted MR images because they cross the compromised blood-brain barrier, increasing the T1 relaxation rate of extracellular water. Tumor extent measured by Gd-enhanced MR imaging often does not agree with T2-weighted MRI or biopsy measurements, due to possible peritumoral barrier defects or infiltration of tumor cells beyond the region of enhancement. In this study, the 9L rat brain tumor model was used to measure the correlation between tumor size measured by Gd-enhanced and unenhanced MRI and histological measurements. There was excellent agreement between Gd-enhanced MRI measurements and histology. Morphological features of untreated 9L intracranial tumors and those treated with radiation and/or cisplatin were compared with histological features. No significant change in intracranial tumor size was detected in the treated animals up to 7 days following treatment, despite substantial tumor necrosis evident on histological analysis.

Animals↗
PubMed1995

A 31p-magnetic resonance study of antegrade and retrograde cerebral perfusion during aortic arch surgery in pigs.

To evaluate the effect of hypothermic circulatory arrest on brain metabolism, we used 31P-magnetic resonance spectroscopy to monitor brain metabolites in pigs during 2 hours of ischemia and 1 hour of reperfusion. Twenty-eight pigs were divided into five groups. Anesthesia (n = 5) and hypothermic cardiopulmonary bypass groups (n = 5) served as controls. In the circulatory arrest (n = 6), antegrade perfusion (n = 6), and retrograde (n = 6) brain perfusion groups, the bypass flow rate was 60 to 100 ml.kg-1.min-1. In the antegrade group, the brain was perfused via the carotid arteries at a blood flow rate of 180 to 200 ml.min-1 during circulatory arrest at 15 degrees C. In the retrograde group, the brain was perfused through the superior vena cava at a flow rate of 300 to 500 ml.min-1 during circulatory arrest at 15 degrees C. The intracellular pH was 7.1 +/- 0.1 and 7.3 +/- 0.1 in the anesthesia and hypothermic cardiopulmonary bypass groups, respectively. In the circulatory arrest group, the intracellular pH decreased to 6.2 +/- 0.1 and did not recover to its initial value (7.0 +/- 0.1) during reperfusion (p < 0.05 compared with the value obtained from the control groups at the corresponding time). Inorganic phosphate did not return to its initial level during reperfusion. In three animals in this group, levels of high-energy phosphates, adenosine triphosphate and phosphocreatine, recovered partially but did not reach the levels observed before arrest. In the group receiving antegrade perfusion, cerebral metabolites and intracellular pH were unchanged throughout the protocol. During circulatory arrest in the retrograde perfusion group the intracellular pH decreased to 6.4 +/- 0.1 and recovered fully during reperfusion (7.1 +/- 0.1). High-energy phosphates also returned to their initial levels during reperfusion. These studies show that deep hypothermic circulatory arrest with antegrade brain perfusion provides the best brain protection of the options investigated.

Adenosine Triphosphate↗
PubMed1995

Classification of brain tumors by ex vivo 1H NMR spectroscopy.

Ex vivo biopsy samples (n = 42) from human brain tumors and normal brain have been examined by high-resolution proton magnetic resonance spectroscopy. Parameters from one-dimensional 1H spectra, two-dimensional COSY spectra, and transverse relaxation time (T2) data were used to classify the tumors according to the histopathological diagnoses. The ratio of the area between 3.4 and 3.1 ppm to that between 1.5 and 1.1 ppm distinguished glioblastomas from astrocytomas and normal brain, and appeared to be indicative of malignant potential. In support of the one-dimensional data, cross-peaks in the COSY spectra of brain specimens classified glioblastomas and metastases into one group and the more benign tumors, meningiomas, astrocytomas, and normal brain into a second group. The transverse relaxation of the resonance at 1.3 ppm was fitted by a model with two T2 values. The longer T2 value could be used to distinguish glioblastomas from normal brain, the latter having a much longer long T2 value. Astrocytomas showed a continuum of T2 values between glioblastomas and normal brain, with the grade of the astrocytoma correlating roughly with the value of the long T2 component.

Astrocytoma↗
PubMed1995

One-dimensional phosphorus-31 chemical shift imaging of human brain tumors.

RATIONALE AND OBJECTIVES: Phosphorus magnetic resonance spectroscopy has been used noninvasively to determine characteristic spectral parameters for untreated human brain tumors as a prelude to its use in clinical diagnosis. METHODS: The spectra, which reflect the relative amounts of phosphorus-containing compounds, and the pH within and surrounding the tumors, were obtained in vivo using the localization technique of one-dimensional chemical shift imaging applied with a surface coil. Phosphorus-31 chemical shift imaging was performed successfully in vivo on 9 volunteers and 27 patients with untreated brain tumors, including 7 with astrocytoma, 4 with glioblastoma, 3 with meningioma, and 11 with metastases. This study provides spectra from within and surrounding the brain tumors, and allows accountability for the heterogeneity of brain tumors by the selection of the maximum data point for each parameter. RESULTS: The ratios of resonance areas, phosphodiesters over nucleoside triphosphate (NTP), and phosphomonoesters over NTP, were found to be higher in glioblastomas (2.55 +/- 0.22, 1.06 +/- 0.09) and astrocytomas (3.04 +/- 0.36, 1.28 +/- 0.36) than in normal brain (2.00 +/- 0.32, 0.79 +/- 0.22). The ratios of areas due to inorganic phosphate and NTP, and phosphocreatine and NTP, also were higher in astrocytomas (1.16 +/- 0.40, 1.17 +/- 0.41) compared with glioblastomas (0.68 +/- 0.01, 0.88 +/- 0.19) and normal brain (0.61 +/- 0.03, 0.77 +/- 0.03). The pH of brain tumors ranged from alkaline to neutral, with meningiomas consistently having alkaline pH. CONCLUSIONS: These data show that there are statistically significant differences in the magnetic resonance parameters of the affected brain hemispheres of patients with astrocytomas, glioblastomas, meningiomas, and normal brain tissue, and underline the need for a multisite clinical trial to establish clinical criteria for diagnosis.

Adenosine Triphosphate↗
PubMed1993

Double inversion recovery improves water suppression in vivo.

It is shown that double inversion recovery used for water suppression can be made much less sensitive to pulse imperfections and to the variations in the relaxation times than a single inversion recovery. This insensitivity results in up to 10-fold improvement in the water suppression in vivo. The excellent water suppression by double inversion recovery is demonstrated experimentally by the in vivo proton spectra obtained from a rat brain.

Animals↗
PubMed1993

Simultaneous measurement of both lipid and lactate in isolated rat hearts by 1H NMR spectroscopy.

Myocardial lipid and lactate levels are sensitive indicators of biochemical status: lipid levels have been shown to increase in response to high fat diets, disease or metabolic stress and elevated lactate levels are indicative of reduced oxygen supply. Selective measurement of lactate or lipid levels by 1H NMR is not straightforward since both the lactate methyl group and lipid methylene groups resonate at 1.3 ppm. We have overcome this difficulty by employing spectral editing techniques to observe both lipid methylene and lactate methyl resonances, and have measured lipid and lactate levels in perfused rat hearts during control perfusion and in response to metabolic stress. Lactate increased during ischemia and decreased during reperfusion, and the ischemia-induced increase is inhibited by iodoacetate, as expected. In contrast, lipid levels increased during ischemia and remained elevated during reperfusion. Hearts from rats fed high fat diet show elevated lipid levels during control perfusion. Data obtained by 1H NMR are consistent with biochemical data, validating the technique.

Animals↗
PubMed1992

Chronic cerebrovascular insufficiency induces dementia-like deficits in aged rats.

Young and aged rats were subjected to cerebrovascular insufficiency (CVI) for 3 and 9 weeks. At the end of each time period, local cerebral blood flow (lCBF), spatial memory function, 31P- and 1H-NMR spectroscopy and imaging of the brains were evaluated in vivo. Morphometric counts of CA1 hippocampal neuron damage and staining for glial fibrillary acidic protein (GFAP) were done post-mortem. Results show that after 3 weeks of CVI, cortical and hippocampal lCBF was significantly reduced in young and aged animals respectively. In addition, young and aged rats at 3 weeks following CVI showed spatial memory deficits in the Morris water maze and elevation of 31P-phosphomonoester as measured by non-invasive NMR spectroscopy. At the same time period, in vivo 1H-microimaging (MRI) of brains showed areas of high signal intensity (suggesting local edema) localized asymmetrically to the right hippocampal region in young and aged CVI rats. Morphometry of the hippocampal CA1 sector at post-mortem confirmed the in vivo MRI changes and demonstrated that a significant percentage of the CA1 pyramidal cells were damaged after CVI. Nine weeks after CVI, hippocampal CBF reductions, spatial memory impairment, spectroscopic-microimaging changes and CA1 sector cell damage continued to be observed in the aged animals but were resolved in the young rat brains. In addition, GFAP immunoreaction progressively increased in the hippocampus of aged rats subjected to CVI for 9 weeks. It is concluded that cognitive, metabolic and morphologic damage was significantly more severe and longer lasting in aged than young rat brain after chronic CVI. The deficits observed in this rat model appear to mimic the early pathology reported in Alzheimer's disease and suggest that the present model could provide fundamental clues relative to the etiology and possible management of this dementia.

Aging↗
PubMed1992

Shielded gradient coils and radio frequency probes for high-resolution imaging of rat brains.

A shielded gradient system and radio frequency probes for a 4.7-T/30-cm horizontal bore magnet are described. The systems were designed principally to obtain images and localized spectra from rat brains. The gradients can operate in either a shielded or non-shielded mode. The rf probe, which combines both highest sensitivity and highest resolution, consists of a large modified saddle type transmitter and a small surface reception coil, actively decoupled using diodes. The system performance is demonstrated on phantoms and on a rat brain, where an image with in plane resolution of 80 microns and a slice thickness of 150 microns is obtained.

Animals↗
PubMed1992

A simple procedure for obtaining high-quality NMR spectra of semiquantitative value from small tissue specimens: cervical biopsies.

The handling of small tissue biopsy samples (< 100 microliters) for NMR investigations poses special problems. Optimal and stable positioning of the samples within the sensitive volume of the radiofrequency coil can be achieved by inserting the sample in a capillary. Methods for quantitation of the spectral information from samples requiring histological evaluation after the NMR experiment are discussed, in particular with respect to cervical biopsies.

Biopsy↗
PubMed1992

The no-reflow phenomenon is a post-mortem artifact.

Post-ischemic reperfusion impairment, ("no-reflow phenomenon"), was studied in rats subjected to 8-30 minutes of global brain ischemia. During ischemia, rapid and complete loss of cerebral blood flow, EEG and 31P-high energy phosphates (ATP/PCr) was observed. Brain intravascular perfusion defects were examined by injecting carbon black intravenously in a group of rats with stable cardiopulmonary function and in another group subjected to rapid thoracotomy and intraarterial infusion of the carbon marker. Results indicate that global brain ischemic or non-ischemic control rats given intraarterial carbon black after thoracotomy had varying degrees of vessel filling defects in brain resulting in "pale tissue areas" suggestive of impaired perfusion (no-reflow). All rats given carbon black intravenously whether global brain ischemic or not, showed normal cerebrovascular filling of the carbon black and absence of "pale tissue areas". In addition, post-ischemic cerebral reperfusion following 8-30 minutes global brain ischemia can reverse neuroelectric, energy metabolite and cerebral blood flow loss in rats whose cardiopulmonary function is not compromised. These findings indicate that the "no-reflow phenomenon" is an agonal or post-mortem artifact observed in the presence of cardiopulmonary failure.

Adenosine Triphosphate↗
PubMed1992

Forebrain ischemia in diabetic and nondiabetic BB rats studied with 31P magnetic resonance spectroscopy.

In spontaneously diabetic BB rats, the effect of chronically maintained blood glucose levels on the degree of energy failure and brain pH change during an ischemic insult, and on subsequent recovery after reperfusion, was studied with in vivo 31P magnetic resonance spectroscopy. Short duration forebrain ischemia (10-min carotid occlusion plus hypotension of 50 mmHg) was induced in diabetic and nondiabetic male BB rats whose blood glucose levels were maintained with insulin. Spectra were obtained in 1-min blocks before, during, and for 1 h after ischemia. Before ischemia, hypoglycemic (blood glucose less than 3 mM) diabetic rats had an increased Pi peak intensity, with no significant pH change, compared with other groups. During ischemia, the rate and extent of hydrolysis of high-energy phosphate metabolites (as measured by an increase in Pi) decreased, and the severity of tissue acidosis increased as preischemia blood glucose concentration increased. Among hyperglycemic BB rats, similar ischemia-induced changes were found for subgroups with blood glucose levels of 13.7 +/- 1.2 and 20.3 +/- 0.6 mM, in keeping with the known decrease in hexose binding sites associated with chronic hyperglycemia. Decline in PCr level during ischemia was not significantly different between groups. With reperfusion, both Pi and pH values rapidly returned to preischemia values. PCr levels, however, did not recover in hyperglycemic diabetic animals, with the degree of residual impairment dependent on the preischemia glucose level. Results suggest that optimal management of diabetes may lessen the degree of injury within the ischemic penumbra in diabetic patients who suffer a stroke.

Analysis of Variance↗
PubMed1992

Magnetic resonance imaging and 31P magnetic resonance spectroscopy study of the effect of temperature on ischemic brain injury.

Transient forebrain ischemia was induced in rats whose brain temperature was 31, 33, 35, 38, or 40 degrees C. The development of regional injury was followed using magnetic resonance (MR) imaging, with the ultimate extent of neuronal injury quantified histopathologically. Animals in the hypothermic groups showed minimal changes in MR images over 4 days; normothermic animals showed intensity enhancement attributed to progressive edema developing in the striatum and, later, in the hippocampus. Ischemia at 40 degrees C resulted in widespread edema formation by 1 day post-ischemia; animals in this group did not survive beyond 30 hours. Histopathological analysis at 4 days (1 day for the hyperthermic group) post-ischemia showed that neuronal damage in the normothermic group was confined to the hippocampus and striatum. Minimal damage was found in the hypothermic groups; damage in the hyperthermic group was severe throughout the forebrain. There were no differences in the pre-ischemia 31P MR spectra for the different groups. During ischemia, the increase in intensity of the Pi peak and the fall in tissue pH increased with temperature in the order hypothermic less than normothermic less than hyperthermic group of animals. Post-ischemia energy recovery was similar in all groups, while pH recovered more rapidly in hypothermic animals.

Animals↗
PubMed1991

Evaluation of a simple line width test involving magnetic resonance spectroscopy of plasma in carcinoma of the ovary.

Magnetic resonance spectroscopic (MRS) measurement of human plasma has been reported as a generally applicable marker for malignancy: patients with malignancy had a MRS line width significantly different from patients with benign diseases or healthy controls. The authors investigated the value of this test in 213 women with ovarian carcinoma, benign pelvic masses, benign nongynecologic diseases, and healthy controls. The MRS measurements were performed on plasma samples at 21 degrees C or 27 degrees C. The line width parameters were obtained by averaging the width at half the height of the methyl and methylene peaks on the resonance spectra. At 27 degrees C using 33 Hz as the threshold for an abnormal result, there was a significant correlation between the result of the test and the presence or absence of malignancy. However, the study demonstrates that the specificity (0.44) and positive predictive value (0.42) are too low for the test to be useful in the management of patients with carcinoma of the ovary. At 21 degrees C no correlation between the results of the test and the clinical status of women with carcinoma of the ovary were observed. In 47 patients the test did not predict preoperatively the benign or malignant nature of a pelvic mass.

Carcinoma↗
PubMed1991

Hexagonal surface gradient coil for localized MRS of the heart.

A surface gradient coil designed to obtain localized magnetic resonance spectroscopy of the heart in vivo is described. Images and 31P spectra from phantoms and both pig and dog hearts in vivo are shown. The coil was used in conjunction with a rf surface coil to obtain 31P spectra from transmural sections of the left ventricular wall of a dog heart in vivo to demonstrate differences between normal and ischemic tissue.

Animals↗