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The "brain work" is characterized by an input which is the processing of sensory information and by an output consisting in the production of ideo-motor activities. This work is performed through electrochemical mechanisms. These biologic mechanisms are strictly dependent on the continuous arrival at regional level of sufficient amounts of glucose and oxygen through blood flow. In fact the regional level of function determines the amount of blood flow and therefore of substrates to that region. This close relationship, function-blood flow-metabolism, permits the study of the cerebral function at any of these three levels. Neurophysiologists recording neuronal firing and clinicians assessing regional levels of blood flow and metabolism activities are seeing very specular aspects of cerebral physiology. The application to the human being of the techniques for regional quantitation of blood flow and of glucose (or oxygen) consumption offers to physiologists and clinicians a new possibility for understanding cerebral functioning both in health and disease.

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.

The feasibility of assessing regional cerebral perfusion using the new brain imaging agent N,N,N'-trimethyl-N'-(2)-hydroxy-3-methyl-5-(123I) iodobenzyl)-1,3-propanediamine 2 HCl (I-123 HIPDM) and single photon emission computed tomography (SPECT) was evaluated in normal subjects and patients with cerebrovascular disorders. Following intravenous injection, I-123 HIPDM was rapidly extracted from the circulating blood by the brain (6.7%) and other organs. Its intracerebral distribution, as tomographically assessed by SPECT with a rotating gamma camera, reflected the distribution of blood flow within brain structures (gray and white matter, basal ganglia, etc.). Asymptomatic patients with history of transient ischemic attacks or minor stroke and angiographic evidence of internal carotid artery occlusion showed large cortical areas of reduced I-123 HIPDM distribution with normal or slightly positive CT. After extracranial-intracranial bypass surgery, reperfusion could be shown in previously ischemic areas. This study indicates the clinical usefulness of using I-123 HIPDM and gamma camera SPECT for the functional evaluation of brain disorders.

Eighty patients were studied by angiography within 6 h of an ischaemic stroke. Angiography was carried out with digital equipment and was usually limited to the vascular territory responsible for the neurological deficits. In 12 of 19 patients with internal carotid occlusion, the contralateral side was also studied. The angiographic abnormalities were classified as extracranial, intracranial, and combined extra and intracranial. The data show a high incidence (66%) of occlusive pathology of intracranial arteries, either isolated or associated with a significant presence of a potential embolic source (85%), and a high incidence of carotid occlusions located at the cervical segment (8 of 19). These observations suggest that most strokes are occlusive in origin.

Sixty-three patients (115 carotid arteries) have been examined first by Dopplersonography, then by echotomography and finally by angiography using the Seldinger technique. The comparison between echotomography and angiography showed a sensitivity of 0.9, a specificity of 0.7 and a accuracy of 0.8. There have been 15 false positive results; in 14 of them the lesions were lower than 10% of lumen reduction and in one case there was a 10-45% stenosis. It seems that echotomography can better estimate lower degree lesions. It was difficult for echotomography to detect correctly the presence of an occlusion and to evaluate the surface aspect mainly in the presence of ulcerations.

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.

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.

Regional cerebral and cerebellar blood flows were studied by N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-[123I]iodobenzyl)-1,3- propanediamine 2 HCl (I-123 HIPDM) and single-photon emission computerized tomography (SPECT) in a patient with an ischemic lesion of the pons. An asymmetry of perfusion of the cerebellar hemispheres, normal on transmission computerized tomography scan, was demonstrated by SPECT studies in the early acute phase and confirmed 15 days after. This finding may be related to the interruption of the corticopontocerebellar pathways.

1. The differential block of cutaneous nerve fibres has been achieved with a simple method of electrical stimulation, employing a single pair of active electrodes. 2. The method allows the selective activation of 95% of small myelinated (delta) axons, without activation of the larger (beta) ones; and activation of unmyelinated (C) fibres, without A fibre activation. Asynchronous firing of myelinated axons was absent in the majority of the experiments. 3. The method employs triangularly shaped electrical pulses, with a steep rise front and a slow exponential decay. The outward flow of current at the cathode fires conducted impulses in both larger and smaller axons, and the inward flow inactivates differentially the conduction in the smaller ones. 4. The differential effect of anodal currents rests upon the greater internal conductance and greater conduction velocity of larger fibres. 5. The method has the advantage over the conventional polarization block of simpler surgical preparation, longer nerve survival and minimal latency distortion. However, it cannot be applied in experiments requiring physiological stimulation of peripheral receptors.

The present study has been devoted to the analysis of 120 patients presenting with reversible focal cerebral ischemia without conventional signs of cardiopathy and/or relevant atherosclerotic disease. In 77% of the patients vascular risk factors, such as hypertension or hyperlipemia, were present. In 23% of the patients, no abnormal finding was discovered at clinical, hematochemical and cardiological examinations. In these patients a further cardiological evaluation was performed with echocardiography. Dynamic electrocardiography was performed in 52 patients. Echocardiography and dynamic electrocardiography revealed the occurrence of 6 cases of mitral valve prolapse (MVP), 2 cases of frequent premature ventricular beats, and 1 proximal atrial arrhythmia. All 6 cases of MVP were detected in the subgroups of patients without vascular risk factors. In our patients younger than 45 years, the relative frequency of MVP attains 21.5%. This study confirms that MVP has to be regarded as a risk factor for focal cerebral ischemia in young patients.

Methods of diagnosis and anatomical localization of cerebral neoplasms have reached a high level of efficiency. A new method of studying cerebral circulation and metabolism by a simple noninvasive technique of steady-state imaging during the inhalation of radioactive oxygen and radioactive oxygen-labelled CO2 is described. The results of preliminary studies of a group of cerebral neoplasms of various histological types are presented and the implications discussed.

The current neurological indications for calcium entry blockers list a potential usefulness in tissue protection against the effects of cerebral anoxia and ischemia. Experimental data support these indications. Clinical data are preliminary so far and suggest designs for larger trials. A possible alternative strategy is the study of particular subgroups of patients such as the patients at excessive risk of stroke.

Clinical, anatomical and functional findings in two cases of previous caudate nucleus hemorrhage, with good recovery, are presented. CBF data obtained with SPECT and 123 I-HIPDM well correlate with functional residual deficit, despite normal TCT examinations. These observations are suggestive of a partial "wallerian" diaschisis.

The impact of computerized neuroimaging in the neurologic sciences has been so dramatic that it has completely changed our approach to the individual patient. Further changes may be expected from the newborn positron emission tomography (PET) and nuclear magnetic resonance (NMR) in order to help the reader digest a large bulk of data and fully realize the present state of the art of PET, the authors have shaped this review mainly on results rather than on methods and on published reports rather than on future potential.

The rCBF was evaluated using I-123 HIPDM and single photon emission computed tomography (SPECT) on 14 patients undergoing extracranial-intracranial (EC-IC) bypass surgery because of internal carotid artery (ICA) occlusion. Before surgery, all patients showed cortical areas of hypoperfusion over the affected cerebral hemisphere. Shortly after EC-IC bypass a rCBF increase was observed in six patients. However, at the 6 and 12 month follow-ups, with angiographic control of bypass patency, rCBF studies did not show any significant rCBF change. Long-term noninvasive tomographic monitoring of perfusion changes occurring after EC-IC bypass surgery failed to show a long-lasting improvement in perfusion.

A new technique for assessing regional oxygen use and blood flow has been applied to a wide range of neurological patients. The method couples the brain's high metabolic demand for oxygen with a shortlived radioactive form of this metabolite, namely oxygen-15 (half life: 2.1 min). This combination produces during the continuous inhalation of either molecular oxygen-15 or labelled carbon dioxide, steady state functional images of the brain which are relatively free of contribution from extracerebral tissues. These are complementary images in that they relate to regional oxygen uptake and blood flow and hence offer a direct insight to the regional demand-to-supply relationships within the brain in physiological and pathological conditions. In the clinical groups studied, metabolic and circulatory defects were observed and instances of cerebrovascular insufficiency and relative luxury perfusion were defined which hitherto have been deduced from indirect methods. The clinical acceptability of this non-invasive approach allowed us to study those categories of patients which normally do not warrant invasive examination.

The development of fibrinolytic agents such as streptokinase and recombinant tissue type plasminogen activator (r-TPA) and other modalities of treatment in acute ischemic stroke, has raised the need for a more precise knowledge of the pathophysiology of the acute phases of ischemic stroke as it pertains to prediction of clinical outcome. In a prospective analysis, 80 patients were studied within less than 6 h from the onset of symptoms by means of a detailed protocol including clinical evaluation, cerebral computed tomography, digital angiography and ultrasound transcranial Doppler sonography. Early angiography revealed a complete arterial occlusion in 76% of cases, the majority of which were intracranial (66%). Seventy percent of the occlusions that were retested were removed within 1 week. Potential embolic sources were found in more than 80% of cases. Patients with documented intracranial occlusion and scarce or absent collateral filling at early angiography, had the worst clinical outcome (P less than 0.05), based on mortality data and the Canadian Neurological Scale. The 30-day mortality rate was 25%. Survival was significantly better (P less than 0.01) in patients with a Canadian Neurological Score on entry of greater than or equal to 6.5 than in patients with a less than 6.5 value. Our data indicate that early pathophysiological studies augment the clinical information and should be taken into account in the design and analysis of therapeutic trials of acute ischemic stroke.

Positron emission tomography (PET) has opened new fields of investigation on clinicometabolic correlations in subcortical infarcts. Functional changes occurring in structurally unaffected brain regions represent one of the most interesting aspects of PET application. So far, the only one PET study on lacunar infarcts has not shown any significant cortical metabolic abnormality. Correlations between distribution and severity of cortical metabolic depression, the size and site of lesion and clinical symptoms still have to be better elucidated.

We compared digital intra-arterial angiography and transcranial Doppler sonography in acute cerebral ischemia as part of a wider study on a continuous series of 48 patients with acute focal cerebral ischemia in the carotid territory, observed within 4 hours of the onset of symptoms. The most significant Doppler findings of the middle cerebral artery included no detection of the artery when occlusion of the carotid siphon or the middle cerebral artery at its origin was shown by angiography and reduced flow velocities and asymmetry (symptomatic less than asymptomatic) when the occlusion was located in the terminal tract of the middle cerebral artery mainstem or in numerous terminal branches. Higher flow velocities in the anterior cerebral artery or posterior cerebral artery, mostly in the symptomatic hemisphere, often accompanied middle cerebral artery pathology, probably indicating collateral compensatory pathways.

Cortical regional cerebral perfusion was assessed by N, N, N1-trimethyl-N1-(2)-hydroxy-3-methyl-5-(I-123) iodobenzyl-1, 3-propanediamine 2 HCl I-123 (HIPDM) and single photon emission computerised tomography (SPECT) in six aphasic and two neglect patients with unilateral subcortical vascular lesions. Assessments were carried out both in the acute phase and after a period ranging from 1 to 6 months after stroke onset. In all patients an almost complete spontaneous recovery occurred and was associated with a significant improvement of cortical perfusion. A relationship between severity of aphasia and degree of cortical hypoperfusion was found, in both the acute and the follow up assessments, in the aphasic subgroup.