Yoshiharu Horikawa

In vivo measurement of energy metabolism and the concomitant monitoring of electroencephalogram in experimental cerebral ischemia

The energy metabolites in rat brain in vivo were measured by using topical magnetic resonance (TMR) during the whole course of ischemia, in combination with the concomitant monitoring of electroencephalogram (EEG). Immediate loss of high energy phosphorus compounds, phosphocreatine (PCr) and ATP, resulted in the flattening of EEG after the induction of ischemia. PCr and ATP returned to almost normal level 30 min after recirculation of the ischemic brain, but EEG showed no recovery and the abnormality lasted for 12 h. The measurement of in vivo 31P-NMR is essential for the decision of the convalescence of cellular function in the brain.

Significance of proton relaxation time measurement in brain edema, cerebral infarction and brain tumors

We examined the proton relaxation times in vitro in various neurological diseases using experimental and clinical materials, and consequently obtained significant results for making a fundamental analysis of magnetic resonance imaging (MRI) as followings. 1) In the brain edema and cerebral infarction, T1 prolonged and T2 separated into two components, one fast and one slow. Prolongation of T1 referred to the volume of increased water in tissue. The slow component of T2 reflects both the volume and the content of increased edema fluid in tissue. 2) In the edematous brain tissue with the damaged Blood-Brain-Barrier (BBB), the slow component of T2 became shorter after the injection of Mn-EDTA. Paramagnetic ion could be used as an indicator to demonstrate the destruction of BBB in the brain. 3) After the i.v. injection of glycerol, the slow component of T2 became shorter in the edematous brain with the concomitant decrease of water content. The effects of therapeutic drug could be evaluated by the measurement of proton relaxation times. 4) Almost all tumor tissue showed a longer T1 and T2 values than the normal rat brain, and many of them showed two components in T2. It was difficult to determine the histology of tumor tissue by the relaxation time alone because of an overlap of T1 and T2 values occurred among various types of brain tumors. 5) In vivo T1 values of various brain tumor were calculated from the data of MRIs by zero-crossing method, and they were compared with the in vitro T1 values which were measured immediately after the surgical operation. Though the absolute value did not coincide with each other due to differences in magnetic field strength, the tendency of the changes was the same among all kinds of tumors. It is concluded that the fundamental analysis of proton relaxation times is essentially important not only for the study of pathophysiology in many diseases but also for the interpretation of clinical MRI.

In vivo studies of energy metabolism in experimental cerebral ischemia using topical magnetic resonance. Changes in 31P-nuclear magnetic resonance spectra compared with electroencephalograms and regional cerebral blood flow.

The energy state of the brain during and after transient cerebral ischemia was examined in rats by in vivo measurement of 31P-nuclear magnetic resonance (NMR) spectra using a topical magnetic resonance spectrometer. EEGs and regional CBF (rCBF) were monitored on the same ischemic models. Immediately after the induction of ischemia, the height of the ATP and phosphocreatine peaks in the spectrum began to decrease with a concurrent increase of the inorganic phosphate (Pi) peak. The calculated pH from the chemical shift of Pi decreased during ischemia. The EEG pattern became flat immediately after ischemic induction. The rCBF decreased below the sensitivity level of the measuring instrument. With 30-min ischemia, the 31P-NMR spectrum returned to a normal pattern rapidly after recirculation. However, recovery of the EEG was delayed. The rCBF after recirculation showed postischemic hyperemia followed by hypoperfusion. In cases of 120-min ischemia, none of the spectra showed recovery. Thus, we could investigate the dynamic process of pathophysiological changes occurring in the ischemic brain in vivo.

Effects of atrial natriuretic peptide on ischemic brain edema in rats evaluated by proton magnetic resonance method.

We examined the effect of atrial natriuretic peptide on cerebral edema in 96 rats. Forty-four rats were given 30 (n = 11), 120 (n = 26), or 150 (n = 7) micrograms/kg of the peptide intravenously over 24 hours after occlusion of the left middle cerebral artery to induce cerebral ischemia. We then measured the brain water content, the brain sodium and potassium contents, the in vitro proton nuclear magnetic resonance longitudinal (T1) and transverse (T2) relaxation times, and the area of the edematous regions. Compared with saline treatment (n = 39), peptide treatment decreased the brain water content in a dose-dependent manner and decreased the brain sodium content significantly (p less than 0.05). Peptide treatment also suppressed the lengthening of both T1 and T2 in edematous tissue (p less than 0.05 and p less than 0.01, respectively) and reduced the area of the edematous regions observed by magnetic resonance imaging (p less than 0.01). Atrial natriuretic peptide appears to have a pharmacological effect on ischemic brain edema, possibly by suppressing the elevation of water content through regulation of electrolyte transport in the brain.

Proton NMR relaxation times in ischemic brain edema.

The state of water in cerebral ischemia was studied by using the proton nuclear magnetic resonance (1H-NMR) method. Cerebral ischemia was induced experimentally in Mongolian gerbils by unilateral ligation of the common carotid artery. Longitudinal (T1) and transverse (T2) relaxation times of the ischemic brain were measured with a pulse FT-NMR spectrometer and the water content was determined by the wet/dry method. Quantitative analysis of the relaxation times was performed sequentially during the initial 7 hours following ligation and the data were compared with those of brain edema previously reported by S. Naruse in the rat. Characteristic findings in brain ischemia include prolongation of the slow component of T2 and increase in the water content. A quantitative comparison of relaxation rate and water content demonstrates that ischemic brain edema in Mongolian gerbils is different from cytotoxic and vasogenic types of brain edema. When R2 (1/T2) was plotted against the water content, the slope value of ischemia in the gerbil was between the slope values of the TET intoxication and cold injury induced edemas reported previously. From these results, it might be said that ischemic brain edema includes both the cytotoxic and vasogenic types of brain edema. Glycerol was demonstrated to affect brain ischemia by decreasing the water content and by shortening the slow component of T2. By analysis of the relaxation times and water content, we examined the pathophysiological characteristics of water molecules in ischemic brain tissue.

Observations of energy metabolism in neuroectodermal tumors using in vivo 31P-NMR

The energy metabolism of living tumors in rats and hamsters were investigated by obtaining in vivo 31P-NMR spectra, and the effects of chemotherapy on tumors were evaluated by observing the changes of these spectra. Tumor cells of rat glioma, human glioblastoma and human neuroblastoma were inoculated subcutaneously in the lumbar region of the animals. After the tumor grew to over 1.5 cm in diameter, in vivo 31P-NMR spectrum data was obtained selectively from the tumor with a TMR-32 spectrometer (Oxford Research Systems, U.K.). Several peaks (ATP, inorganic phosphate (Pi), phosphodiesters and phosphomonoesters (PME) were observed in the tumors. The heights of these peaks varied widely corresponding to the tumor growth. However, the spectrum pattern of each tumor in an active stage was found to be essentially the same regardless of histological type or tumor origin. The phosphocreatine (PCr) peak was small, ATP and PME peaks were large and tissue pH calculated from the chemical shift of Pi was low in each tumor group. After intravenous injection of a large dose of a chemotherapeutic agent, ATP peaks decreased and the Pi peak increased gradually, resulting in a dominant Pi peak pattern after several hours in all groups. With lower drug doses, spectrum changes were temporarily seen in the tumors. These findings indicated that drugs with a high dose have a selective and a direct action on the energy metabolism of tumor tissues. In vivo 31P-NMR spectra measurement is very valuable not only to investigate the energy metabolism in tumor tissue but also to evaluate the effects of chemotherapy on the tumor.

Proton nuclear magnetic resonance spectra of brain tumors

Proton nuclear magnetic resonance (NMR) spectra were successfully measured in human brain tumor tissues and experimental rat brain tumors. The investigation was performed on clinical materials which consisted of tissue from one normal brain and 36 brain tumors. Normal rat brain tissue and rat glioma implanted in the brain were also analysed. NMR measurements were carried out at the resonance frequency of 99.54 MHz. The proton NMR spectrum of the normal brain consisted of one broad component and eight superimposed sharp peaks. The sharp peaks obtained from the brain tumors varied from those of the normal brain. A decrease in the signal intensity from N-acetyl aspartate was the most common finding in all tumors. Spectral patterns were similar within the same histological types, but varied among the different types. Therefore, 1H-NMR spectra might indicate the metabolism characteristic of each tumor type which would be invaluable for clinical differential dagnosis of brain tumors.

Measurements of in vivo energy metabolism in experimental cerebral ischaemia using 31P-NMR for the evaluation of protective effects of perfluorochemicals and glycerol.

Effects of perfluorochemical (PFC) and glycerol on energy metabolism in cerebral ischaemia were examined by the sequential measurements of in vivo 31P-NMR spectrum using topical magnetic resonance (TMR). Experimental cerebral ischaemia was induced in forty-five Wistar rats by a four-vessel occlusion method. The 31P-NMR spectrum and the EEG were monitored during preischaemic and ischaemic periods and after circulation was restored for various periods up to 240 min. There were several peaks in the 31P-NMR spectrum of the preischaemic rat brain; beta-ATP, alpha-ATP, gamma-ATP, phosphocreatine (PCr), phosphodiesters, inorganic phosphate (Pi) and sugar phosphate. As soon as the ischaemia was induced, PCr and ATP decreased and Pi increased. The chemical shift of the increased Pi peak decreased, showing acidosis of the brain tissue. After circulation was restored following the 30 min ischaemia, recovery of the 31P-NMR spectrum occurred within 30 min in all sixteen untreated rats. Recovery of the 31P-NMR spectrum was induced by recirculation only in half of the six rats in the untreated 60 min ischaemia group. None of the six rats in the untreated group showed recovery of the spectrum after 120 min ischaemia. When 20% Fluosol-DA was administered at a dose of 20 ml/kg before the induction of ischaemia, all eight rats showed recovery of the spectrum after 120 min ischaemia. Moreover, four of six rats treated with both PFC and glycerol showed temporary recovery even after 240 min ischaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

MR angiography of intracranial aneurysms: a comparison of 0.5 T and 1.5 T.

The objective of this paper is to compare the diagnostic efficacy of 3 DFT time-of-flight MR angiography (MRA) at middle-field-strength and high-field-strength in diagnosis of intracranial aneurysms. Thirty-one patients, including 26 patients with angiographically confirmed intracranial aneurysms (n = 28), underwent MRA at 0.5 and 1.5 T. Images were interpreted by six trained observers who were blinded to diagnosis. Twelve projections of MRA of the circle of Willis, by maximum-intensity projection algorithm, were reviewed using continuous confidence-judgement scales. It was found that MRA at 1.5 T was more sensitive than that at 0.5 T in detection of aneurysms. The sensitivity of six observers ranged between 50 and 64% (mean 56%) at 0.5 T, and between 61 and 86 86% (mean 75%) at 1.5 T. In the smaller aneurysms less than 5 mm, the differences between the units became greater. The sensitivity for small aneurysms ranged from 23 to 54% (mean 32%) at 0.5 T, and from 31 to 69% (mean 58%) at 1.5 T. Our conclusion was that high field strength confers higher accuracy in the detection of intracranial aneurysms with MRA with current-generation MR imagers.

Value of high-resolution computed tomography in diagnosis of petrous bone fracture

High-resolution computed tomography (CT) was performed on 31 patients clinically suspected of having petrous bone fracture. The location of the fracture was demonstrated accurately in 28 patients (90.3%), whereas it could be diagnosed by plain skull film in only 17 patients (54.8%). The anatomic location of fractures demonstrated by high-resolution CT clearly corresponded to the clinical symptoms and signs. We have classified petrous bone fracture into five types according to the anatomic levels demonstrated on CT images. The findings indicate that high-resolution CT is extremely useful for diagnosing petrous bone fracture.