Toshio Sasajima

Indications for Differential Diagnosis of Nontumor Central Nervous System Diseases from Tumors

To accurately differentiate nontumor central nervous system (CNS) diseases from brain tumors, we retrospectively evaluated the cerebral circulation and metabolism in patients with nontumor CNS diseases using positron emission tomography (PET). Regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen extraction fraction (rOEF), the metabolic rates of oxygen (rCMR02), and of glucose (rCMRGI), and the uptake of 11C–methyl–L–methionine (11C–Met) were visually evaluated in lesions and compared with values for the contralateral white matter regions. PET findings were correlated with those of x–ray computed tomography (CT) and magnetic resonance imaging (MRI), and were analyzed for nontumor CNS diseases and cerebral gliomas. rCBF and rCBV were changeable from disease to disease or from stage to stage of disease progression. rOEF and rCMR02 remained low in 5 and 6, respectively, of 9 nontumor CNS diseases examined, whereas these parameters were increased in CNS infections such as brain abscess. Overall, noteworthy was the locally increased rOEF and rCMR02 in the patients with a brain abscess in contrast to the values for patients with gliomas. rCMRGI reflected biological characteristics of each disease, and correlated with cell density, whether reactive glial cells or inflammatory cells. 11C–Met was accumulated at a certain stage of nontumor CNS diseases, which implied uptake of the tracer as a result of disruption of the blood–brain barrier as well as metabolic incorporation.

Association of stem cell marker CD133 expression with dissemination of glioblastomas

Dissemination of glioblastoma was once considered rare but is now increasingly encountered with longer survival of glioblastoma patients. Despite the potential negative impact of dissemination on clinical outcome, however, molecular markers useful for prediction of dissemination risk still remains ill defined. We tested in this study for an association between the expression of stem cell marker CD133 and the risk of dissemination in 26 cases of glioblastoma (16 with dissemination and 10 without dissemination). The protein expression of CD133 was examined by western blot analysis of tumor specimens, and the CD133 expression levels were quantified by densitometry and normalized to β-actin. The results indicated that CD133 expression levels are significantly higher in glioblastomas with dissemination (mean 10.3, range 0.20-27.8) than in those without (mean 1.18, range 0.07-3.58). The results suggest that CD133 could be a molecular predictor of glioblastoma dissemination, and also give rise to an intriguing idea that CD133-positive cancer stem cells may be implicated in the initiation of disseminated lesions.

Quantitative evaluation of neutral amino acid transport in cerebral gliomas using positron emission tomography and fluorine-18 fluorophenylalanine

To elucidate the mechanism of large neutral amino acid (LNAA) transport in cerebral gliomas and to evaluate the clinical usefulness of positron emission tomography (PET) with fluorine-18 fluorophenylalanine (18F-Phe), we examined 18 patients with cerebral glioma using dynamic PET and18F-Phe. By employing two-compartment model analysis, the influx rateK1, the efflux ratek2 and the distribution volume (Vd) of18F-Phe were estimated in tumour tissue and contralateral normal grey matter.18F-Phe showed increased accumulation in tumour tissue regardless of the grade of malignancy in all patients. The rate of uptake of18F-Phe in high-grade glioma was significantly higher than in low-grade glioma (P <0.05). However, it was difficult to evaluate the tumour grade only from the18F-Phe accumulation in individual cases. Values ofK1 andVd were significantly increased in the tumour tissue. TheK1 value of the tumour tissue tended to decrease with increasing LNAA concentration in plasma. Therefore, influx of18F-Phe into tumour tissue is mainly related to the carrier-mediated active transport. It is concluded that PET with18F-Phe is of clinical value for tumour detection rather than assessment of tumour malignancy.

Spinal cord ependymoma: a positron emission tomographic study with (11C-methyl)-L-methionine.

An intramedullary spinal cord ependymoma was studied by positron emission tomography (PET) using (11C-methyl)-L-methionine (11C-Met). MRI showed a homogeneously enhancing tumour at C6-T2 with cysts at its rostral and caudal ends. Sagittal PET images demonstrated high11C-Met uptake in the solid portion of the tumour, particularly ventrally at C7-T2, where viable tumour cells proliferated in association with abundant perforating vessels. Met-PET would appear useful for delineating the viable protion of intramedullary ependymomas.

Trans-1-amino-3-18F-fluorocyclobutanecarboxylic acid (anti-18F-FACBC) is a feasible alternative to 11C-methyl-L-methionine and magnetic resonance imaging for monitoring treatment response in gliomas

INTRODUCTION Amino acid PET tracers are promising for visualizing gliomas and evaluating radiochemotherapeutic effects. We compared the glioma detection and early response assessment utility between trans-1-amino-3-fluoro-1-(14)C-cyclobutanecarboxylic acid (anti-(14)C-FACBC) and (3)H-methyl-l-methionine ((3)H-Met) by simultaneously analyzing their uptake by rat gliomas treated with and without temozolomide (TMZ) in vitro and in vivo. METHODS C6 rat gliomas were incubated with low-dose TMZ to induce chemoresistance. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay demonstrated a significantly greater surviving fraction in the TMZ-resistant subline (C6R) than in drug-naive cells (C6). The anti-(14)C-FACBC and (3)H-Met uptakes were quantified using a triple-label accumulation assay to examine the relationship between tracer uptake and proliferation ((3)H-thymidine (TdR) accumulation rate) in tumor cells. C6 and C6R cells were inoculated into the right and left basal ganglia, respectively, of rats. Efficacy of TMZ against the orthotopic gliomas was analyzed by MRI, Evans blue extravasation, anti-(14)C-FACBC and (3)H-Met autoradiography, and MIB-5 proliferation index. RESULTS The (3)H-TdR accumulation rate and amino acid tracer (anti-(14)C-FACBC and (3)H-Met) uptake significantly decreased 48 and 72 h, respectively, after TMZ treatment in C6 but not C6R cells. Anti-(14)C-FACBC uptake correlated significantly with (3)H-Met uptake and the (3)H-TdR accumulation rate. In the intracerebral glioma model, anti-(14)C-FACBC and (3)H-Met autoradiography clearly delineated the tumor extent, which spread well beyond the high-T2-intensity and enhancing lesions visible on MRI and Evans blue extravasation. TMZ significantly decreased anti-(14)C-FACBC and (3)H-Met uptake and the MIB-5 index of C6 but not C6R tumors. TMZ inhibited tracer uptake and tumor proliferation before morphological changes on MRI. CONCLUSIONS Anti-(14)C-FACBC, like (3)H-Met, was more sensitive than post-contrast T1-weighted MRI for detecting tumor extent and early tumor response to TMZ treatment. Anti-(18)F-FACBC should be a sensitive and precise imaging biomarker for tumor extent visualization and response assessment in glioma patients.

Extradural neuromas at the petrous apex: report of two cases.

OBJECTIVE AND IMPORTANCE Two rare cases of middle cranial fossa neuroma located in the epidural space at the petrous apex are reported. CLINICAL PRESENTATION Two women, aged 58 and 49 years, were admitted to our hospital with diagnoses of cavernous sinus tumor. Analysis of preoperative computed tomography scans showed bone erosion of the petrous apex, and magnetic resonance imaging demonstrated the presence of an extradural mass located along the course of the petrous internal carotid artery in both patients. INTERVENTION The tumor was completely removed in one patient and partially removed in the other by use of the epidural middle cranial fossa transpetrosal approach. In both patients, histological examination of tumor specimens revealed neuroma. CONCLUSION Because surgical exploration revealed that these epidural tumors adhered tightly to the internal carotid artery, and because they had no relationship to the trigeminal nerve, facial nerve, or proximal greater superficial petrosal nerve, in our opinion, these tumors originated from the distal portion of the greater superficial petrosal nerve or the deep petrosal nerve. These neuromas were mainly found in a site under the cavernous sinus at the petrous apex, a location not previously reported.

Primary central nervous system involvement of the so called 'peripheral T-cell lymphoma'. Report of a case and review of the literature.

Primary central nervous system (CNS) involvement of non-Hodgkins lymphoma is uncommon and a vast majority of reported cases are of B-cell origin. We present a 52-year-old woman with primary peripheral T-cell lymphoma of the brain. Immunostaining of paraffin-embedded sections proved tumor cells to be positive for T-cell markers MT1 and UCHL1, and negative for B-cell markers MB1, and 4KB5. Radiotherapy combined with steroid therapy rendered neurologic recovery and complete tumor remission confirmed by computed tomography and magnetic resonance imaging. From a review of documented 19 cases of primary CNS T-cell lymphoma including the present case, this disease is characterized by poor prognosis among CNS lymphomas.

Intracranial plasma cell granuloma evaluated by positron emission tomography

A 50-year-old farmer with plasma cell granuloma had PET scans showing marked accumulation of C-11 Met. The PET had superiority in imaging the existence and extent of the lesion and monitored therapeutic response as compared with CT and MR imaging. PET yields information on hemocirculatory and metabolic aspects of this rare disease.

Effects of radiotherapy determined by 11C-methyl-L-methionine positron emission tomography in patients with primary cerebral malignant lymphoma.

SummaryTwo cases of histologically proven primary cerebral malignant lymphoma were examined serially with positron emission tomography (PET) using11C-methyl-l-methionine (11C Met). Lesions delineated by11C Met accumulation extended beyond enhancing areas on either X-ray computed tomography (CT) or magnetic resonance imaging. High uptake of11C Met accurately showed biologically active and residual tumours, at a time when disappearance of a contrast-enhancing lesion on CT seemed to indicate involution. PET provides valuable information on the extent of tumour and assessment of radiotherapy in malignant lymphoma.

Sequential PET studies in neuro-behcet's syndrome

SummaryA case of neuro-Behcets syndrome is presented with sequential positron emission tomography (PET) studies. Regional cerebral blood flow (rCBF) and oxygen consumption (rCMRO2) were decreased in the brain lesion; however, on follow-up studies 3 months after steroid therapy rCBF and rCMRO2 had increased in the lesion, which demonstrated the reversibility of this disease. Such monitored improvement may accurately reflect the early stage of the disease and its response to steroid therapy.