Yoshio Ohmori

Chronological Positron Emission Tomographic Study of Severe Diffuse Brain Injury in the Chronic Stage

Cerebral blood flow and metabolism were investigated in five patients with severe diffuse brain injury in the chronic stage, using positron emission tomography (PET). Regional cerebral blood flow, regional oxygen extraction fraction, regional cerebral blood volume, regional cerebral metabolic rate for oxygen, and regional cerebral metabolic rate for glucose were measured bilaterally in the frontal, temporal, occipital, and parietal gray matter, as well as the white matter of the centrum semiovale. In 4 of 5 patients, a follow-up PET study was also performed. In three cases, below-normal regional cerebral blood flow and regional cerebral metabolic rate for oxygen values accompanied by above-normal regional oxygen extraction fraction values, as well as low metabolism, were demonstrated in the initial PET studies. In two of three cases, clinical improvements were observed, and follow-up PET data also improved. These findings suggest that chronological PET studies may be able to assess quantitatively clinical improvements in patients with diffuse brain injury.

Positron Emission Tomography and Boron Neutron Capture Therapy System to the Patient with Malignant Brain Tumor

We have conjugated a positron tracer F-18 to [10B]boronophenylalanine (10B-BPA) to synthesize [18F]fluoroboronophenylalanine (18F-10B-DL-BPA or 18F-10B-L-BPA), and analyzed 1013-BPA metabolism on 27 cases of the various brain tumors by positron emission tomography (PET). These PET data revealed that 18F-10B-BPA using the DL-form was actively incorporated to the malignant tumor cells, showing high B-10 concentration and T/N ratio, which was suggested of the sufficient effectiveness of boron neutron capture therapy (BNCT) on the malignant brain tumor. The experimental studies were undertaken with rat glioma model which showed that BNCT using 10B-L-BPA brought the good antitumor effect on rat glioma and no side effect on normal brain. Under this PET-BNCT system, the patient with malignant brain tumor was treated.

A Basic Concept for PET-BNCT System

[10B]Boronophenylalanine (10B-BPA) has been used as a tumor selective boron carrier for boron neutron capture therapy (BNCT) in the treatment of malignant melanoma1. In the same way, it is thought to be a potential boron carrier for the treatment of malignant glioma2–4. Glioma infiltrates peripheral brain tissue and we always fall into the dilemma between resection and preservation of the infiltrated brain. Thus the treatment will be effective in these infiltrative tumors. In our studies of malignant glioma using positron emission tomography (PET), accumulation of 10B-BPA analog, [18F]fluoroboronophenylalanine (18F-10B-FBPA), in tumor lesion was dramatically revealed3. The metabolic analysis of this positron-emitting analog demonstrated that enhancement of the amino acid transport is a primary factor for the high accumulation3,5. [18F]Fluoroboronophenylalanine has been recognized as a compound that is incorporated into tumor cell selectively.

Radioiodinated diacylglycerol analogue : a potential imaging agent for single-photon emission tomographic investigations of cerebral ischaemia

Phospholipid metabolism is closely related to membrane perturbation in cerebral ischaemia. We investigated in vivo topographical lipid metabolism using an iodine-123-labelled diacylglycerol analogue, (1-(15-(4-iodine-123-iodophenyl)-pentadecanoyl)-2-stearoyl-rac-glycerol) (123I-labelled DAG), in a middle cerebral artery (MCA) occlusion model with the aim of positive imaging of ischaemic insult. Sprague-Dawley rats underwent coagulation of the MCA to induce permanent occlusion. MCA occlusion times prior to injection of123I-labelled DAG ranged from 15 min to 14 days. Each rat was injected with 11–37 MBq of123I-labelled DAG via a tail vein. After 30 min, in vivo autoradiographs were reconstructed. Scanning of the living rat brain in this MCA occlusion model was performed using a gamma camera with a pinhole collimator. Cerebral infarctions were recognized in the frontal cortex, the parietal cortex and the lateral portion of the caudate-putamen by 2,3,5-triphenyltetrazolium hydrochloride staining. In infarcted regions (region 1),123I-labelled DAG incorporation showed a slight decrease up to 12 h; it then increased up to 6 days and decreased thereafter. In peri-infarcted regions (region 2), the incorporation showed almost no change up to 12 h, then increased up to 5–6 days and decreased thereafter. In other regions (region 3), the incorporation showed no change. Lipid analysis showed that123I-labelled DAG was metabolized to 15-(4-iodine-123-iodophenyl)-pentadecanoic acid by DAG lipase and to123I-labelled phosphatidylcholine. Scanning of the ischaemic region showed higher accumulation than on the non-lesioned side. We established a method to visualize ischaemic foci as positive images. The early changes in123I-labelled DAG incorporation were closely related to DAG lipase, which degraded the accumulated intrinsic DAG, and increased123I-labelled DAG incorporation in the chronic stage involves several aspects of neural destruction in the process of autolysis. It is concluded that the reported method could have a clinical future.

Cerebral Hemodynamics and Metabolism in Severe Diffuse Brain Injury in Chronic Stage: Positron Emission Tomography

The authors measured the cerebral hemodynamics and metabolism in patients with severe diffuse brain injury (SDBI) in the chronic stage using positron emission tomography (PET). In this study, regional cerebral blood flow (rCBF), oxygen extraction fraction (rOEF), cerebral blood volume (rCBV), cerebral metabolic rate for oxygen (rCMRO2), cerebral metabolic rate for glucose (rCMRGlu), and cerebral metabolic rate were measured in three patients with SDBI in the chronic stage. The patients were all male, and aged 17, 19 and 25 years. The Glasgow Coma Scale score on admission was 3,4 and 3, respectively. In all patients, the cause of injury had been a traffic accident, computed tomography and magnetic resonance imaging revealed findings of so-called diffuse axonal injury (DAI), and the clinical course was also typical of that of DAI. The PET studies were performed 2 to 16 months after injury. The clinical condition of the patients at that time was vegetative state in two and severely disabled in one. PET revealed misery perfusion and low metabolism in two and matched low perfusion and low metabolism in one. It is interesting that any slight difference in clinical state was correlated with a slight difference in PET findings in every patients. The authors stress the usefulness of PET study in the investigation of SDBI in the chronic stage and in the assessment of its prognosis.