Biomedical subjects
Publications and source records attributed to N J Patronas.
Enhanced contrast of transplanted human colon carcinoma in athymic mice is seen in magnetic resonance images upon iv injection of the complexes of Mn(III) with two water-soluble porphyrins, tetra (4-sulfonatophenyl) porphyrin and tetra (N-methyl-4-pyridyl) porphyrin.
Thirty-three patients with either primary spinal cord tumors (n = 18), intradural tumors excavating into the cord (n = 9), or spinal arteriovenous malformations (AVM) (n = 6) were studied with magnetic resonance (MR) imaging. In 25 of 38 examinations (66%) (five patients were studied twice), MR provided more information than that provided by other neuroradiologic procedures. In several cases, MR affected patient management decisions. Advantages of MR, in addition to the absence of ionizing radiation and its noninvasive nature, include good spinal cord-CSF-theca contrast, lack of bone-derived artifacts, ease of multiplanar imaging, improved discrimination between intra- and extramedullary lesions, better definition of tumoral cavities and possible distinction from true syringes, ability to help one recognize thrombus formation within an AVM, and ease of follow-up of cord lesions for possible size changes. Apart from factors precluding the study in several patients (life support systems, pacemakers, claustrophobia, neurovascular clips), disadvantages of MR imaging include motion artifacts (prevalent in thoracolumbar area), poor capability of typing and grading of tumors, potential of false-positive results, poor detection of calcification, and poor delineation of feeders and drainers of AVM.
To enhance the contrast between cerebrospinal fluid (CSF), brain, spinal cord, and surrounding meninges and bone on magnetic resonance (MR) images, as well as to study CSF flow, gadolinium-DTPA was injected in the subarachnoid space of eight monkeys. Six doses of progressively higher concentrations (from .125 mmol to 250 mmol) were injected every 30-40 minutes. Images of head and spine were obtained at .26 T or .5 T in sagittal and axial planes, using both spin-echo and inversion-recovery sequences in 13 imaging experiments. Marked, consistent changes of signal intensity in the CSF cavities were observed following the injections. These changes were dose related and occurred at different times in the areas close to the injection site versus those distant, a disparity that obviously was related to CSF flow. Gd-DTPA cisternography and myelography may be valuable in MR imaging of central nervous system disease, such as tumors adjacent to the CSF cavities, abnormal CSF collections (e.g., arachnoidal cysts), CSF rhinorrhea and otorrhea, syringohydromyelia, and studies of hydrocephalus and CSF flow dynamics.
The central auditory (dichotic) function of 38 patients with Alzheimer's disease was found to be significantly impaired when compared with a control group. Significant relationships were observed between dichotic scores and intelligence quotient, cortical atrophy in the temporal lobes, and cerebral glucose metabolism in the left temporal lobe. Comparing atrophy and glucose metabolism in the temporal lobes, we observed contralateral ear effects in dichotic performance as well as an interaction of asymmetry of atrophy with dichotic performance, consistent with previous models of dichotic listening in other forms of temporal lobe pathology.
The aim of this study was to determine whether positron emission tomography (PET) with fluorine-18 (18F)-2-deoxyglucose (FDG) can be used as a prognostic test in patients with high-grade cerebral gliomas, regardless of the treatment given. Forty-five patients with astrocytoma Grade III or IV were included in this analysis. The mean survival time of patients with tumors exhibiting high glucose utilization as determined by PET-FDG was 5 months, whereas patients with gliomas showing lower glucose utilization had a mean survival period of 19 months. It is postulated that PET-FDG scans reflect the biological behavior of high-grade astrocytomas and may be used to predict the survival time of patients harboring such neoplasms.
Fifty-four patients with supratentorial tumor and one with brainstem tumor were examined with positron emission tomography (PET) using [18F]fluoro-deoxyglucose (FDG). Twenty-one of these cases had satisfactory studies of the cerebellum. Of these, 12 showed significant metabolic asymmetry between the two cerebellar hemispheres, with the rate of glucose utilization in the hemisphere contralateral to the cerebral tumor being 8-34% lower than on the ipsilateral side, as compared with a right-left asymmetry of only--1.6% +/- 2.1% standard deviation for a group of 5 normal subjects. In these 12 cases the tumor involved the sensorimotor cortex and/or the thalamus with varying degrees of hemiparesis being present. For the remaining 9 patients with no significant cerebellar metabolic asymmetry, the tumor involved regions other than the sensorimotor cortex, and unilateral motor dysfunction was not a prominent clinical feature. The correlation between cerebellar metabolic suppression and unilateral motor dysfunction observed in our cases appears to be due to impairment or interruption of the cortico-thalamo-ponto-olivo-cerebellar circuitry by either the tumor itself or by edema. These results illustrate the ability of FDG-PET scans to detect metabolic changes, not apparent on CT scans, in areas of the brain remote from the primary lesion.
Over 150 cases of central nervous system tumors have been studied with positron emission tomography using fluorine-18-labeled fluorodeoxyglucose (18FDG) as a tracer. From this material 100 consecutive cases of cerebral glioma have been reviewed and analyzed. The results show a strong correlation of tumor grade with glycolytic rate, with visual "hot spots" present in all high-grade neoplasms and in only four low-grade tumors. The quantitative accuracy is limited by three basic factors. First, the measurement of tissue uptake, as compared with the parent technique, autoradiography, is more difficult because detection must be done outside the body. Effects such as scattered radiation and self-attenuation introduce errors unless properly corrected. A more serious problem when measuring small structures, such as a rim-shaped high-grade glioma, is the limited spatial resolution. The most advanced scanner, the Neuro-PET, has a resolution of 6 to 7 mm. Second, corrections are needed for backflow, including free tracer at the time of the scan that will return to the blood and "trapped" tracer that will backflow because of the presence of phosphatase. These corrections are calculated from the blood activity using nominal rate constants for 18FDG. Our study found no significant alteration in rate constants between normal and tumoral tissue. Finally, a lumped constant is needed to correct for kinetic differences between 18FDG and glucose. If there is a change in the mechanism of either membrane transport or the hexokinase reaction, the lumped constant may change. However, measurements of actual glucose utilization in tissue culture lines from six patients support the 18FDG results.
Regional cerebral glucose metabolism, an index of neuronal activity, was compared in 20 patients with Alzheimer's disease and 8 age-matched normal volunteers by positron emission tomography following [18F]2-fluoro-2-deoxy-D-glucose administration. Overall cortical glucose utilization in the Alzheimer's group was 10 to 49% below that of control individuals. The posterior parietal cortex and contiguous portions of posterior temporal and anterior occipital lobes were most severely affected; frontal cortex was relatively spared. This pattern of cortical involvement is consistent with the major clinical features of Alzheimer's disease. Comparison of patients with early and more advanced dementia suggested that a substantial decline in glucose metabolism occurs before cognitive impairment becomes evident; once the patient is symptomatic, however, small additional metabolic decrements are associated with a marked deterioration in intellectual function.
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A new high resolution positron emission scanner (Neuro-PET) has made possible clear visualization and quantitation of glucose metabolism in the brain stem and upper cervical cord (above C4) using 18F-2-deoxyglucose. The following mean measurements of the glucose utilization rate are based on studies of 34 normal volunteers and patients with no apparent pathology in the brain stem or cord: 5.0 +/- 1.0 (SD) mg Glu/100 g/min for the mesencephalon-upper pons, 3.2 +/- 1.0 for the pons-medulla, and 1.7 +/- 0.6 for the upper cervical cord. (The first value also includes studies done with the ECAT-II scanner.) Resolution of white-gray matter within these structures was not possible. Whenever possible, a correlation was made with autoradiographic data in monkeys, and good agreement was found. The glucose utilization in cases showing brain stem and cord pathology was altered, with marked elevation (as high as 8.2 mg/100 g/min) in cases of high-grade gliomas, and reduction in cases of low-grade gliomas and one pontine hematoma.
Local rates of cortical glucose metabolism were estimated by positron emission tomography in 13 right-handed patients with Alzheimer's disease. Individuals with disproportionate failure of language function had markedly diminished metabolism in the left frontal, temporal, and parietal regions. Patients with predominant visuo-constructive dysfunction evidenced a hypometabolic focus in the right parietal cortex. Patients with memory failure as the most apparent feature had no significant metabolic asymmetry in cortical regions. In all subjects, verbal competency generally correlated with metabolic activity in the left frontal and temporal areas, while visuo-constructive test performance was linked to glucose utilization in the right parietal lobe.
Partially purified protein from washed and artificially hemolyzed erythrocytes, known to cause significant contractions of isolated canine cerebral vessels in vitro, was injected into the cisterna magna of intact anesthetized dogs. Cerebral blood flow, measured by the xenon-133 washout technique, decreased from a control value of 49.5 +/- 1.17 ml/100 gm/min to an experimental value of 34.1 +/- 1.65 ml/100 gm/min at 2 hours. Cerebral vascular resistance rose from a control value of 2.05 +/- 0.17 PRU (peripheral resistance units) to an experimental value of 2.91 +/- 0.25 PRU at 2 hours. Mean arterial blood pressure, heart rate, intracranial pressure, and cerebral perfusion pressure remained stable. Cardiac output also fell significantly (in 2-hour control animals it was 2.89 +/- 0.37 liter/min, and in 2-hour experimental animals 1.43 +/- 0.13 liter/min) and peripheral vascular resistance rose. These changes were evident by 10 minutes after the cisternal injection of the hemolysate protein, and remained for the duration of the 2-hour monitoring period. Serial vertebrobasilar angiograms demonstrated marked narrowing of the intracranial basilar artery when compared to control values. The narrowing persisted for several days in most animals, and tended to increase with time. Relaxation occurred by the 10th through the 14th day. The authors conclude that this experimental preparation may be a useful model for both in vitro and in vivo investigation of chronic cerebral vasospasm.
Perfluorocarbon, a new tumor-seeking x-ray contrast agent, was injected into three rats with experimental brain tumors. After 1 to 3 days the rats were sacrificed, and the brains were removed and subjected to x-ray study. All showed dense radiopaque areas which correlated with the size and shape of the corresponding brain tumors. Conversely, none of the radiograms taken of the brain tumor in five rats receiving no perfluorocarbon (control animals) showed similar increased density. These findings suggest that perfluorocarbon may serve a useful role as a contrast medium for computerized tomography studies of brain tumors in man.
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Five patients who had undergone radiation therapy for cerebral tumors and whose conditions were deteriorating were examined by means of positron emission tomography (PET) with [18F] fluorodeoxyglucose. All five cases had similar clinical and computed tomographic findings. Using the PET technique the two cases of radiation necrosis were distinguished from the three recurrent tumors. In the two cases of radiation necrosis the rate of glucose utilization in the lesion was markedly reduced compared with the normal brain parenchyma. In the recurrent gliomas, however, the glucose metabolic rate was elevated. All five diagnoses were confirmed by biopsy or autopsy.
Positron emission tomography was used to measure local cerebral glucose utilization by the 1-[18F]fluoro-2-deoxy-D-glucose technique in 23 patients with cerebral gliomas. All 10 high-grade (III and IV) astrocytomas demonstrated a region of high activity with a glucose consumption of 7.4 +/- 3.5 (SD) mg/100 gm per minute. The 13 low-grade (I and II) gliomas had a glucose metabolic rate of 4.0 +/- 1.8 mg/100 gm per minute, with no distinctly visible hot spot. Thus, we found a correlation between rate of glycolysis and malignancy in primary cerebral tumors. Cerebral cortical glucose utilization was often depressed in areas adjacent to or neurally connected to the tumor site, and there was focal irregular delta wave EEG activity in these areas.
Ectopic origin of the ophthalmic artery from the middle meningeal artery was found in a patient with amaurosis fugax. The origin of the external carotid artery on the symptomatic side was markedly stenotic. The patient's symptoms disappeared after external carotid endarterectomy. We review the ectopic sites of the ophthalmic artery and discuss atheromatous disease of the external carotid system as a cause of transient ischemic attacks.
Superior sagittal sinus thrombosis is an often unrecognized clinical condition. This is due to its variable clinical presentation and its association with other serious disease states. The following cases demonstrate that, in the infant, thrombosis of the superior sagittal sinus can be diagnosed quickly and noninvasively by computed tomography (CT). In those clinical situations in which thrombosis of the superior sagittal sinus may occur and neurological changes exist, axial and coronal CT scans may be quite specific in detecting its occurrence.