A total of five hundred and five mice were exposed to different X-ray doses in the range of 500 to 40, 000 R. at 200 kVp, 20 mA, 1.15 mm Cu, HVL (0.5 mm Cu + 0.5 mm Al), as a single dose for the whole head. Mean life span (LD50-time) of these mice exposed to 2, 000 R. was 11.04 days and that of those exposed to 30, 000 R. was 0.87 days.
The LD50 (5 days) was 19, 700 R.. High incidences of gastrointestinal bleeding, intracranial bleeding, and brain edema were found after head exposure to 2, 000 and 20, 000 R.. None of the mice exposed to 500 and 1, 000 R. died within 300 days.
Fifty-six mice were exposed to 2, 000 or 20, 000 R. by the same method. All the mice were sacrificed at some postirradiation period, and pathological examinations were performed. The degree of the brain tissue damage was microscopically classified into four grades of scoring with respect to severity. These microscopic evaluations were made in at least, three mice at 18 locations in the cerebellum, 36 locations in the brain stem, and six locations in the hypothalamus under 400-fold magnification. Brain tissue damage appearing before the mean life span (LD50time) at each irradiation dosage was observed in the cerebellum and the brain stem at the higher dosage, and in the hypothalamus at the lower dosage.
It was suggested that the damage in the brain stem, cerebellum, and hypothalamus caused death after the high dose of 20, 000 R., and that the hypothalamic damage caused death after the low dose of 2, 000 R., In addition, the intracranial bleeding may have affected their life spans.

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The cytoplasmic fibrillar system, microtubules and microfilaments (MT & MF), has been known to control several aspects of cell functions, such as motility, configuration and various membrane activities. The author utilized the cell motility and configuration as the indicator for the evaluation of MT & MF functions in cultured benign and malignant brain tumors. The cellular motility was studied by continuous monitoring of the cultured cell locomotion through a computerized autotracking microscope. The data were analysed by a computer using electric address signals obtained 60 times per second from a television camera. Morphological investigation of the cell configuration consisted of serial photography of the TV monitor and electron microscopy of the fixed cells. These observations were performed before, during and after perfusion of the cultured cells with a normal culture media and various chemical solutions which affect MT & MF functions. Motility of the cell was expressed as the mean motility which is a sum of distances (X and Y components) in an unit time.
When RG-C6 (mouse glioma) cells and cultured human brain tumor cells were exposed to cytochalasin B (an inhibitor of microfilaments), the cell shape and locomotion were affected significantly. The motility of the cells increased remarkably as much as 2, 000% in malignant astrocytomas and 300% in benign astrocytomas. Morphologically, ruffling of the mean cytoplasmic membrane disappeared, and the leading edge then retracted. These changes associated with the cytochalasin B perfusion were dose dependent, occurred promptly and were fully reversible. However, these changes were not observed with colchicine (an inhibitor of the microtubular function) treatment of the cell.
A significant difference was observed in the degree of the rate of motility increase between the cultured human malignant astrocytoma cells and the benign astrocytoma cells. The author postulated that the difference between benign and malignant type cells is probably related to a difference in the quality of the microfilament rather than quantity, since the difference is calculated as a ratio between pre and post perfusion values. Functions of microfilaments and microtubules in the brain tumor cells and the relation of these functions to the clinical malignancy of the brain tumor were discussed.

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Comparative anti-tumor effects of ACNU and MCNU were studied on 20-methylcholanthrene-induced C₅₇ black mouse malignant gliomas (MG-cells) and rat glial tumors (C₆-cells) in vitro and in vivo.
The inhibitory effects of ACNU and MCNU in vitro were dependent on dose and time. The concentration showing inhibitory effect was more than 10 μg/ml. ACNU was a slightly more effective than MCNU. ACNU significantly inhibited DNA synthesis at concentrations higher than 10 μg/ml, but had no such effect on RNA and protein syntheses. MCNU also inhibited DNA synthesis similar to but less than that of ACNU.
By a single intraperitoneal administration on day 5, an increased life span (ILS) was observed with ACNU (120.3 % increase) and with MCNU (100.4%). The optimal dosis was 25 mg/kg/day for both drugs. The therapeutic ratio, or optimal dose divided by the dose producing an increased life span of 30% over controls, of ACNU was 4.17 and that of MCNU was 6.67. When 25 mg/kg/day of ACNU was administered intraperitoneally on day 5, two out of 10 mice survived over 60 days. In case of MCNU, one out of 10 mice survived. A single administration of ACNU or MCNU was more effective for the increased life span compared with intermittent administration.
From these results, it is suggested that the new water soluble nitrosourea, MCNU, can be utilized as a chemotherapeutic agent against brain tumors as in the case of ACNU.

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Adjuvant immunochemotherapy and irradiation therapy were applied following surgery for gliomas from 1975 to 1978. It is the authors' principle to remove the tumor extensively. About one week after the operation, irradiation was started. Along with the irradiation, adjuvant immunochemotherapy was also started. For supratentorial gliomas, initially, adriamycin was given in three divided dosis of 0.5 mg/kg, up to 30 mg, on every other day. After a rest of 6 weeks, methyl-CCNU was given in a single dose of 3 mg/kg orally. This course of treatment was repeated after another 6 weeks. Along with the chemotherapy, OK-432 was given as an immunopotentiator. For medulloblastomas, methyl-CCNU was given at first, in a single dose of 3 mg/kg. After a rest of 6 weeks, methotrexate was given intrathecally via an Ommaya reservoir on five successive days in a single dose of 0.25 mg/kg. After another 6 weeks methyl-CCNU was repeated every 6 weeks. Methotrexate was also given during the spring, summer and winter vacations. OK-432 was also administered. This combined therapy was applied to 14 cases of supratentorial malignant gliomas, seven cases of supratentorial low grade gliomas, and 10 cases of medulloblastomas. In addition, nine low grade gliomas in the brain stem without surgery received this therapy.
The survival rate ofsupratentorial malignant gliomas was 79% for one year, 50% for two years and 46% for three years. The survival rate of medulloblastomas was 80% for one year, 67% for two years, and 57% for three years. All the survivors among medulloblastoma cases could go to school or kindergarden.
Toxicity was examined by white blood cell count, liver function, renal function and lymphocyte count. The difference of mean white blood cell counts between the first postoperative year and thereafter was not significant. GOT and GPT were elevated in the early postoperative period, but returned to normal values in the late postoperative period. ALP increased in the late postoperative period. Throughout the course of immunotherapy, it is necessary to measure immunoparameters. Lymphocyte count and PPD skin test were measured. Difference of lymphocyte counts between the first postoperative year and thereafter was not significant. Although the lymphocyte count was said to be depressed in glioma cases, and especially during chemotherapy, this series showed no apparent immunosuppression. Because some toxicity, such as elevating ALP, was noted, it seems better to discontinue the combined therapy at the end of the second postoperative year.

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Results of the treatment of multiple modalities on 74 cases with metastatic brain tumors were reported. Hospital patients with malignant diseases were surveyed by the authors even before being refered, and the majority of the cases was detected in this way. Bronchogenic carcinoma was the most frequent primary tumor, and was found in 62% of the cases. In four cases, no neurological symptoms were manifested when CT scans disclosed the brain metastasis. The treatment consisted of removal of the brain metastasis through a craniotomy (nine cases), shunt operation (17 cases), radiotherapy (41 cases; whole brain and local, Linac), chemotherapy (46 cases), endocrine therapy (a few cases) and immunotherapy (a few cases). Adequate treatment was completed under betamethazone administration in 52 cases, but it was interrupted in another 14 cases, and no treatment was given in the remaining eight, mainly because of the deteriorated systemic dissemination. Out of 52 cases adequately treated, 43 (82%) showed a satisfactory remission in the neurological examination and/or CT scan following the treatment. Among them, 23 were discharged, but the others remained hospitalized for the metastases disseminated outside the central nervous system. The remaining nine still showed a progressive disease. Eventually, 49 expired 2 to 39 months after the onset of brain metastasis, while all of the insufficiently treated and untreated cases died within 5 months. Brain metastasis was the cause of death in 32.6% of the adequately treated, and 55.8% of the insufficiently treated and untreated cases. There are three surviving cases. The longest survivors were a female with breast cancer (removal, radiotherapy, endocrine therapy and chemotherapy), and a male with seminoma (radiotherapy), both remaining alive for more than 40 months. Calculated according to Kaplan and Meier, the 50% survival time was 6.8 months in the removal cases, 5.3 months in the non-surgically treated cases (p>0.5), and 0.9 months in the insufficiently treated and untreated cases (p<0.001). Autopsy was performed in 24 cases adequately treated, and revealed disappearance of the metastatic foci in the brain in seven cases, regressive changes of the tumor cells in the brain metastasis in nine, and proliferative tumors in six cases. In seven cases, meningeal carcinomatosis was complicated.

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Mediobasal skull fractures which encroach through or near the sella turcica are often associated with injury of the midline structures. The purpose of this study is to clarify the correlation between clinical symptoms and fractures. Experimental studies such as the stress coat, a strain gage method and free drop impacts allowed assessement of mediobasal skull fractures.
Patterns of the fractures in autopsy cases were classified into four types from the impact site as follows. Type 1 : frontal blow. Type 2 : frontolateral blow. Type 3 : temporal blow. Type 4: occipital blow. Patterns of the fractures in clinical cases analysed by skull x-rays were almost consistent with the autopsied cases except for the absence of Type 4.
In experimental cases of midfrontal loading related to Type 1, the stress was concentrated in the midline on the anterior cranial base and lateral to the sella turcica on the middle cranial base.
CSF rhinorrhea, impariment of the optic chiasma, and the III and V cranial nerves were closely associated with Type 1 and 2 fractures. In Type 3 fractures, CSF otorrhea, VI and VII cranial nerve injuries and damage of the internal carotid artery were prominent findings. Structural derangement through or near the superior orbital fissure on the middle cranial fossa might impair small branches of the internal carotid artery distributed to the hypothalamus and pituitary stalk or optic chiasma, thus causing diabetes insipidus and bitemporal hemianopsia, respectively.

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A completely implantable intracranial pressure sensor was designed for chronic measurement of intraventricular pressure (IVP) in hydrocephalic patients. It is a passive-resonant circuit transducer and the implantable sensor does not contain an active element such as an electric battery. The size and shape of the sensor are nearly those of Pudenz's single flushing device, so that the transducer can be used in place of a traditional flushing device in the ventriculo-peritoneal shunt system. The IVP meter is sensitive to 1 mmH²O of pressure and it has a linear pressure range from -500 to + 1, 000 mmH²O. The zero drift of the sensor was negligible during a 10⁴ hour running test. The errors induced by changes in external atmospheric pressure were automatically corrected by placing a accurate barometer in the line of pressure-calculation.
The intraventricular pressure of hydrocephalic dogs was measured by this new IVP meter and by the LADD transducer simultaneously, and the reliability of this IVP sensor was confirmed.
These sensors were applied to eight hydrocephalic patients, and chronic and continuous measurements of the ventricular pressure were performed. These preliminary clinical experiences disclosed; (1) this IVP meter offers a method almost ideal for simple, safe and accurate, recording of the intraventricular pressure of hydrocephalic patients, (2) patency of the ventricular tube can be easily demonstrated by a steep rise of intracranial pressure at the time of jugular compression, and (3) abnormal pressure waves with obstructed shunt and their disappearance when the shunt is working are easily recognized.

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Platelet aggregability and coagulation and fibrinolytic activities were determined statistically in all cases of ruptured intracranial aneurysms in the acute stage during the waiting period for intentionally delayed operations. The following items were measured: platelet aggregability by screen filtration pressure (SFP), fibrinogen, antithrombin-III, partial thromboplastin time, prothrombin time, platelet count, plasminogen, streptokinase euglobulin lysis time and fibrin/fibrinogen degradation products (FDP).
It was revealed that in the acute stage of ruptured intracranial aneurysms, systemic coagulation abnormalities similar to the intravascular coagulation syndrome (DIC), which was said to cause abnormal exasperation in the coagulation and fibrinolytic activities, were observed fairly frequently, and further that it had a serious relation to the outcome of the case. Thirteen patients out of 38 cases of ruptured intracranial aneurysms died during the waiting period. Except for one patient who died from a fatal rebleeding, all other 12 patients died from marked brain swelling caused by cerebral vasospasms. In eight patients out of the 12 dead cases, coagulation abnormalities which might be called DIC appeared immediately after bleeding and later marked cerebral vasospasms occurred.
DIC following intracranial diseases was reported in serious head injury cases. It was made clear that DIC could also appear in ruptured intracranial aneurysms so that it should be counted as one of the risk factors in the acute stage of ruptured intracranial aneurysms.

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This prospective study was undertaken to objectively assess the feasibility of prevention of vasospasm by removal of subarachnoid blood in early operations by means of pre and postoperative CT scans.
During the past 3 years, 181 patients with ruptured aneurysms were operated on. Among these, 64 cases with a single rupture and without intracerebral hematoma (except one case of temporal lobe hematoma) underwent direct operations within 4 days after hemorrhage. CT scans were performed on the day and the day following the operation. Localization and grading system of CT-visualized subarachnoid blood followed Fisher's classification. The clinical condition of the patients was graded according to Hunt and Hess's classification. All aneurysms were approached through a frontobasal lateral route and the side of approach was determined based on CT findings to remove the subarachnoid clot as much as possible when high density (HD) (which indicates a collection of blood) in the subarachnoid space was visualized on preoperative CT. Postoperative angiography was performed between day 6 and day 15 (the day of hemorrhage was day 0) because the symptomatic vasospasm usually occur between day 6 and day 15 after hemorrhage. Bilateral carotid system was studied. Only motor weakness associated with angiographic vasospasm was considered as ischemic symptoms due to vasospasm. It was possible to remove the subarachnoid clot in 90% of cisterns as follows: basal frontal interhemispheric fissure, bilateral Sylvian stems, Sylvian cisterns and the anterior part of insular cisterns, but it was impossible in frontal interhemispheric fissures and the posterior part of insular cisterns. Angiography revealed no spasm or mild spasm in the site where the clot was successfully removed and no ischemic symptoms or transient ischemic symptoms developed. Permanent symptoms due to vasospasm occurred in 8 patients in whom the subarachnoid clot remained on postoperative CT scans, mostly in the frontal inter hemispheric fissure, contralateral insular cistern and ipsilateral posterior part of the insular cistern where clots could not be romoved. Only one patient in Grade IV died due to vasospasm and excellent results(which indicates those who were able to return to their usual social life) were obtained in 100% in Grade I, 84% in Grade II, 85% in Grade III, and 15.5% in Grade IV.
Our experience discloses that early surgery affords an opportunity to remove much of the blood from the subarachnoid space and that it perhaps minimizes the development of vasospasm.

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Compared with single photon emission CT, positron emission CT posesses several dominant features which are dependent on the properties of positron emitters. The superiority of positron emission CT from a practical point of view is consisted as follows: (1) improvement of the spatial resolution, (2) potential ability of the quantification, and (3) availability of the isotopes of the life-constituent elements such as carbon-11, nitrogen-13, oxygen-15, and fluorine-18; in other words, availability of in vivo autoradiography using these tracers.
The National Institute of Radiological Science developed a newly designed positron CT, named POSITOLOGICA. This device has unique and outstanding features in systems with unequally spaced 64 BGO detectors arranged in a circle and a continuously rotating detector ring. PUSITOLOGICA has been applied for neurosurgical patients. The radioparmaceuticals administered are N-13-ammonia, C-11-CO, and F-18-fluorodeoxyglucose, which are produced and synthesized in the Institute using the cyclotron. N-13-ammonia and F-18fluorodeoxyglucose are administered by intravenous injection but C-11-CO is administered by inhaling. N-13ammonia acts as a diffusible tracer and is readily metabolized to glutamine in the brain tissue, but the extraction fraction of the glutamine is so slow that the N-13-ammonia imaging reflects the distribution of the cerebral perfusion.C-11-CO is combined with the hemoglobin and undiffusible in behavior. This makes the C-11CO images conduct the cerebral blood pooling distribution. F-18-fluorodeoxyglucose is an analogous substance of glucose and is transported within the brain tissue competitively. Then, fluorodeoxyglucose is metabolized to fluorodeoxyglucose-6-phosphate but no further. This characteristic property of fluorodeoxyglucose let F-18fluorodeoxyglucose images convey the local cerebral metabolic rate of glucose.
In normal volunteer subjects, the distribution of N-13-ammonia and F-18-fluorodeoxyglucose appeared in a similar fashion, and was in accordance with the brain tissue. Both tracers were accumulated in particularly high concentrations in the gray matter and the basal ganglia. C-11-CO activity was prominently accumulated in various dural sinuses and the vascular areas. In stroke patients, old lesions showed a lack of perfusion but fresh lesions showed hyperperfusion surrounded by a decreased perfused area. F-18-fluorodeoxyglucose activity was decreased in the lesion in spite of the hyperperfusion. Even in a TIA case in which X-ray CT images appeared normal, decreased perfusion and the lowered glucose metabolism were recognized in the area matching the neurological signs.
Positron CT's will flourish in the near future because of their ability to obtain the physiological and biochemical information of the brain.

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