Emission computed tomography in strokes.
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Biomedical subjects
Publications and source records attributed to C Pozzilli.
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Peripheral white blood cell (WBC) count was determined in 95 patients with ischemic cerebral infarction 3 days after the onset of the stroke. At this time, higher WBC counts were found in patients with more severe neurological impairment and larger infarct size. A relationship between increase of WBC count and poor clinical outcome was also demonstrated. The elevation of peripheral WBC count observed soon after cerebral infarction reflects the degree of the inflammatory response in the acute hase and seems to have a direct relationship with the extent of the local cerebral damage.
The purpose of this study was to compare the effect of indium oxine and indium-tropolone complexes (nonradiolabeled) on the function of isolated human lymphocytes. peripheral lymphocytes were obtained from 15 normal volunteers and incubated with indium oxine or indium tropolone according to the standard techniques currently used when cells are radiolabeled for subsequent in vivo studies. The phytohemagglutinin-induced (PHA) lymphocyte transformation and a more specific lymphocyte functional test (the mixed lymphocyte reaction) were performed following incubation with the indium complexes. The results indicate that PHA transformation is not affected by either indium oxine or indium tropolone, whereas both chelates reduced the mixed lymphocyte reaction. This suggests that these substances have a selective toxic effect only on a functionally distinct lymphocyte subset (i.e., the cytotoxic T cells) and indicates that there is no significant difference between the two indium chelates in terms of their effect on lymphocyte function.
The history of a patient with a suspected ischemic brain infarct undergoing an indium-111-tropolone white cell labelled test is reported. The patient, who died 12 h after injection of the labelled cells, suffered of a brain haemorrhage. The post-mortem examination has allowed for the first time the measurement of radioactivity in different organs following the injection of indium-111-labelled leucocytes. High radioactivity was found only in tissues affected by inflammatory processes and in the lymphonodes draining the corresponding areas. This report clearly indicates the importance of this method for the study of white cell localization and circulation to the sites of infections.
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Peripheral lymphocytes (approximately 10(8)) from 4 subjects affected by autoimmune thyroid disease (2 Hashimoto's thyroiditis, 1 primary myxoedema, 1 Graves' disease) and 4 normal subjects were labelled in vitro with 40 microCi of indium-111-oxine and, following autologous injection, the distribution of the cells in the body was investigated by gamma camera imaging. Lymphocytes in the thyroid were observed 24 h after injection in both patients with Hashimoto's thyroiditis and in the patient with primary myxoedema, but not in the patient with Graves' disease or in any of the controls. To our knowledge, this is the first report using this method to try and demonstrate lymphocytes in the thyroid gland, and supports the concept that cell-mediated immunity may be playing an important role in the pathogenesis of Hashimoto's thyroiditis and primary myxoedema.
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Experimental support for the steady state 15O inhalation technique, as used to measure cerebral blood flow (CBF) and oxygen utilisation (CMRO2), was obtained by describing the response of the cerebral vasculature to variations in arterial PCO2 in 6 anaesthetised dogs. Measurements were made using a positron emission tomography (ECAT II) and arterial blood sampling, during the sequential constant inhalation of C15O2 and 15O2. Values of CBF and CMRO2 were calculated for a mixture of white and grey matter, using the steady state tracer equations derived by Jones et al. (1976). The mean CMRO2 was 3.58 +/- 0.81 ml O2 . 100 ml-1 . min-1, whilst the mean CBF and OER (oxygen extraction ratio) values (for an arterial PCO2 of 40 mm Hg) were 39.9 ml . 100 ml-1 and 0.50 +/- 0.06, respectively. Arterial PCO2 was varied between 20 and 150 mm Hg. CBF was found to correlate closely with arterial PCO2, resulting in a mean slope (specific reactivity) of 1.52 +/- 0.38 ml . 10 ml-1. mm Hg-1. Pooling the flow data resulted in a linear relationship between CBF (% change) and arterial PCO2 in the range 20-70 mm Hg, with a slope (% reactivity) of 3.2% mm Hg-1 (2 P less than 0.001). The oxygen extraction ratio (OER) fell with increasing values of arterial PCO2 resulting in a stable CMRO2 throughout each study. There was no correlation between CMRO2 and artificially increased CBF. These results support and give confidence in the use of the 15O inhalation technique for measuring CBF, OER and CMRO2.
The cerebral blood flow, oxygen extraction and oxygen utilization has been measured regionally in 22 dements, and 14 aged normal volunteers. Ten demented patients were studied twice at a six-month interval from initial measurements. The use of a steady-state 15O technique and positron tomography for measuring regional cerebral blood flow, regional oxygen extraction fraction and mean cerebral oxygen utilization is discussed. The limitations of measurements are reviewed in the light of the present results and the current state of technological development in positron emission tomography is discussed. A decline in cerebral blood flow and mean cerebral oxygen utilization was correlated with increasing severity of dementia in both degenerative and vascular dements. The decline was coupled, both for the cerebral hemisphere as a whole and regionally. There was no increase in oxygen extraction ratio globally, and therefore no evidence to support the existence of a chronic ischaemic brain syndrome. Focal abnormalities in oxygen utilization were observed for both vascular and degenerative groups. In the vascular group, parietal defects were the most pronounced. Individual derangements of the regional pattern varied, reflecting the different unique patterns of ischaemic damage in these patients. In the degenerative group, parietal and temporal defects were seen in the less severe group, but a profound depression in the frontal regions with relative sparing of occipital area characterized the severe degenerative dements.
The oxygen-15 inhalation technique has been applied to the quantitation of regional CBF, CMRO2 and OER with positron emission tomography. The introduction of corrections for gamma-ray attenuation, and for recirculation, has allowed us to obtain values for CBF, CMRO2 and OER in close agreement with values obtained using other techniques. In 27 normal volunteers mean CMRO2 shows values ranging from 4.98 to 3.79 ml/100/min, depending on the region evaluated. Mean CBF values range from 55.3 to 38.8 ml/100ml/min. Mean OER is more constant, ranging from 0.56 to 0.49, with a mean of 0.53 +/- 0.04, thus reflecting the close matching between metabolism and blood supply. We have further identified corrections for cerebral blood volume, which is measurable, and for water partition coefficient, which remains uncertain. In preliminary studies these corrections decrease the OER over the physiological range of flow by 10%, with a 15% lower CMRO2. The reproducibility of the results and the effects of aging have been studied. A series of 27 studies on acute ischaemic CVD are reported. The course of the clinical condition has been correlated with the quantitation of oxygen utilization and blood flow performed at different intervals from the onset of symptoms.
Blood-brain barrier (BBB) permeability to [68Ga]EDTA was measured by positron emission tomography (PET) in four normal volunteers and in 11 patients with brain tumors. A unidirectional transfer constant, Ki, was calculated applying multiple-time graphical analysis (MTGA). This method allows the detection of backflux from brain to blood and, by generalization, the measurement of the constant Kb (brain to blood). Furthermore, the need for an independent measurement of the intravascular tracer is obviated: MTGA itself provides an estimate of the cerebral plasma volume (Vp). In the four normal volunteers the Ki was 3.0 +/- 0.8 X 10(-4) ml g-1 min-1 (mean +/- SD) and the Vp 0.034 +/- 0.007 ml g-1. A net increase in Ki up to a maximum of 121.0 X 10(-4) ml g-1 min-1 (correspondent value of Kb = 0.025 min-1) as well as an increase of Vp was observed in malignant tumors. The input function was calculated using both the [68Ga]EDTA concentration in sequential arterial blood samples and, noninvasively, the activity derived from the superior sagittal sinus image. The values of Ki and Vp from these two calculations were in good agreement. The application of MTGA to PET permits the evaluation of passage of substances across the BBB without making assumptions about the compartments in which the tracer distributes.
The circulating white blood cells of patients with brain infarction were labelled in vitro with Indium-111 tropolonate; the cells were reinjected to study the inflammatory process by gamma camera imaging. Eight patients with acute cerebral ischemic infarct were studied during the first two weeks after the onset of neurological symptoms. In seven cases a well defined area of increased radioactivity was revealed in the infarcted hemisphere indicating active migration and tracking of labelled leukocytes in cerebral infarct. This method allows monitoring of the cellular inflammatory response in human cerebral infarcts and adds another imaging technique.
We studied 70 consecutive patients with definite multiple sclerosis (MS) to examine the relationship between magnetic resonance imaging (MRI) cerebral findings and urinary disturbances. Thirty-two subjects (46%) had urinary symptoms and 38 (54%) were asymptomatic. Patients with urinary symptoms exhibited greater overall functional disability. A significant correlation between the presence of midbrain lesions and urinary dysfunctions was found which may indicate an important role of the mesencephalic formation to preserve continence.
Central pontine myelinolysis (CPM), a disorder occurring for the most part in alcohol abusers, is characterized by the symmetric and selective destruction of medullated sheaths in the central pontine region. Detection of CPM in the pre-symptomatic phase may improve the outcome, which is usually serious. We describe a case of CPM in a 48-year-old female alcohol abuser who was seen at our out-patient clinic for a history of generalized seizures. Neurological examination was normal while magnetic resonance imaging revealed a pontine lesion consistent with CPM. On the basis of this report we hypothesize that the possibility to detect CPM in the pre-symptomatic phase will lead to increased diffusion of magnetic resonance imaging, and in turn to improved therapeutic strategies, such as the use of greater caution when correcting plasma electrolyte imbalance in alcoholics.
BACKGROUND AND PURPOSES: New strategies have been developed to improve the sensitivity of contrast-enhanced MR imaging in quantifying disease activity in patients with multiple sclerosis (MS). The goal of the present study was to evaluate the sensitivity of T1-weighted images after injection of a triple dose of contrast material and application of a magnetization transfer (MT) pulse in the detection of enhancing lesions as compared with the conventional approach. METHODS: Monthly MR images were obtained in 13 patients with relapsing-remitting MS for a period of 3 months. The MR studies were performed on two separate occasions with single- and triple-dose contrast material. In each session, T1- and T2-weighted spin-echo images with and without the MT pulse were obtained before and after contrast administration. All images were evaluated in a blinded fashion and scored in random order and consensually by two readers. The number of total and new enhancing lesions and active images was counted. RESULTS: Eighty-six percent more enhancing lesions and 54% more new enhancing lesions were detected with triple-dose as compared with single-dose non-MT sequences, whereas single-dose MT images depicted 33% more enhancing lesions and 18% more new enhancing lesions than the single-dose non-MT images. Twenty-nine percent more lesions were detected on triple-dose non-MT images than on single-dose MT images. The combination of a triple dose of contrast material and MT did not produce any significant change in detection of enhancing lesions as compared with a triple dose of contrast without MT. CONCLUSION: The use of a triple dose of contrast material is the best approach to maximize the sensitivity of enhanced MR imaging.