Atsushi Inugami

A System for Cerebral Blood Flow Measurement Using an H215O Autoradiographic Method and Positron Emission Tomography

A system for CBF measurement using an H215O autoradiographic method and positron emission tomography (PET) has been designed and installed as a clinical tool. Following an intravenous injection of H215O, a radioactivity accumulation in the brain tissue for 60 s and a continuous record of radioactivity in arterial blood were measured by a high counting speed PET device and a beta-ray detector, respectively, and CBF was calculated by a table-lookup procedure. First, this method was compared with the C15O2 inhalation steady-state method on 17 cerebrovascular disease patients and four normal subjects. The two values for CBF agreed with each other when H215O autoradiographic method was applied by correction for the dispersion in the measured arterial radioactivity–time curve. However, without the correction, the CBF by the H215O autoradiographic method revealed substantial overestimation by 30.6 ± 17.5%. A reduced gray/white ratio of CBF was also observed in the H215O autoradiographic method. Second, simulation was performed in order to determine optimal accumulation time by PET scan; the result was that errors due to dispersion and time mismatch became critical as the accumulation time was shortened to <60 s.

Clinical Value of Pet with 18F-Fluorodeoxyglucose and L-Methyl-11C-Methionine for Diagnosis of Recurrent Brain Tumor and Radiation Injury

We studied 15 patients clinically suspected to have recurrent brain tumor or radiation injury, using positron emission tomography (PET) with 18F-fluorodeoxyglucose (18FDG) and L-methyl-11C-methionine (11C-Met). PET with 11C-Met (Met-PET) clearly delineated the extent of recurrent brain tumor as focal areas of increased accumulation of 11C-Met, and was useful for early detection of recurrent brain tumor. PET with 18FDG (FDG-PET) showed focal 18FDG-hypermetabolism in one patient with malignant transformation of low grade glioma, and demonstrated its usefulness for evaluation of malignant transformation. 18FDG-hypometabolism was observed in all patients with radiation injury, but was also found in one patient with recurrent malignant brain tumor. 11C-Met uptake in 3 patients with radiation injury was similar to that of the normal cortical tissue. FDG-PET can be used to initially exclude recurrent brain tumor which is seen as 18FDG-hypermetabolism. The combined use of Met-PET in addition to FDG-PET can improve the accuracy of differentiation of recurrent brain tumor with 18FDG-hypometabolism from radiation injury.

Regional cerebral blood flow, blood volume, oxygen extraction fraction, and oxygen utilization rate in normal volunteers measured by the autoradiographic technique and the single breath inhalation method

By means of a high resolution PET scanner, the regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen extraction fraction (rOEF), and metabolic rate of oxygen (rCMRO2) for major cerebral gyri and deep brain structures were studied in eleven normal volunteers during an eye-covered and ear-unplugged resting condition. Regional CBF was measured by the auto-radiographic method after intravenous administration of H215O. Regional OEF and rCMRO2 were measured by the single inhalation of15O2. With MR T1-weighted images as an anatomical reference, thirteen major cerebral gyri, caudate nucleus, lentiform nucleus, thalamus, midbrain, pons, cerebellum and vermis were defined on the CMRO2 images. Values were read by using circular regions of interest 16 mm in diameter. The posterior part of the cingulate gyri had the highest rCBF and rCMRO2 values among brain structures, followed by the lentiform nucleus, the cerebellum, the caudate nucleus, and the thalamus. Parahippocampal gyri had the lowest rCBF and rCMRO2 values amongthe cortical gyri.RegionalOEFforthepontinenuclei (0.34 ± 0.04), the midbrain (0.35 ± 0.05), the parahippocampal gyri (0.35 ± 0.04 for the right and 0.37 ± 0.05 for the left), and the thalami (0.37 ± 0.05 for the right and 0.36 ± 0.04 for the left) were significantly lower than the mean OEF for the cerebral cortices (0.42 ± 0.04) (p < 0.05 or less). The global CBF and CMRO2 were consistent with those obtained by the Kety-Schmidt method. Although several limitations to the quantification derived from an inadequate spacial resolution remain unsolved, the performance of the present PET scanner and the method for the quantification employed provide regional estimates of brain circulation and oxygen metabolism more acurately than the PET system and the steady state method previously used.

Oxygen Extraction Fraction at Maximally Vasodilated Tissue in the Ischemic Brain Estimated from the Regional CO2 Responsiveness Measured by Positron Emission Tomography

The oxygen extraction fraction (OEF) at maximally vasodilated tissue in patients with chronic cerebrovascular disease was evaluated using positron emission tomography. The vascular responsiveness to changes in PaCO2 was measured by the H215O autoradiographic method. It was correlated with the resting-state OEF, as estimated using the 15O steady-state method. The subjects comprised 15 patients with unilateral or bilateral occlusion and stenosis of the internal carotid artery or middle cerebral artery or moyamoya disease. In hypercapnia, the scattergram between the OEF and the vascular responsiveness to changes in PaCO2 revealed a significant negative correlation in 11 of 19 studies on these patients, and the OEF at the zero cross point of the regression line with a vascular responsiveness of 0 was 0.53 ± 0.08 (n = 11). This OEF in the resting state corresponds to exhaustion of the capacity for vasodilation. The vasodilatory capacity is discussed in relation to the lower limit of autoregulation.

A method to quantitate cerebral blood flow using a rotating gamma camera and iodine-123 iodoamphetamine with one blood sampling

A method has been developed to quantitate regional cerebral blood blow (rCBF) using iodine-123-labelled N-isopropyl-p-iodoamphetamine (IMP). This technique requires only two single-photon emission tomography (SPET) scans and one blood sample. Based on a two-compartment model, radioactivity concentrations in the brain for each scan time (early: te; delayed: td) aredescribed as: % MathType!MTEF!2!1!+-% feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-yqaqpepae9pg0FirpepeKkFr0xfr-x% fr-xb9adbaqaaeGaciGaaiaabeqaamaabaabaaGcbaGaam4qamaaBa% aaleaacaWG0baabeaakmaabmaabaGaamiDamaaBaaaleaacaWGLbaa% beaaaOGaayjkaiaawMcaaiabg2da9iaadAgacqWIpM+zcaWGdbWaaS% baaSqaaiaadggaaeqaaOWaaeWaaeaacaWG0bWaaSbaaSqaaiaadwga% aeqaaaGccaGLOaGaayzkaaGaey4LIqSaamyzamaalaaabaGaamOzaa% qaaiaadAfadaWgaaWcbaGaamizaaqabaaaaOGaamiDamaaBaaaleaa% caWGLbaabeaaaaa!4D64!\[C_t \left( {t_e } \right) = fC_a \left( {t_e } \right) \otimes e\frac{f}{{V_d }}t_e \] and % MathType!MTEF!2!1!+-% feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-yqaqpepae9pg0FirpepeKkFr0xfr-x% fr-xb9adbaqaaeGaciGaaiaabeqaamaabaabaaGcbaGaam4qamaaBa% aaleaacaWG0baabeaakmaabmaabaGaamiDamaaBaaaleaacaWGKbaa% beaaaOGaayjkaiaawMcaaiabg2da9iaadAgacqWIpM+zcaWGdbWaaS% baaSqaaiaadggaaeqaaOWaaeWaaeaacaWG0bWaaSbaaSqaaiaadsga% aeqaaaGccaGLOaGaayzkaaGaey4LIqSaamyzamaalaaabaGaamOzaa% qaaiaadAfadaWgaaWcbaGaamizaaqabaaaaOGaamiDamaaBaaaleaa% caWGKbaabeaaaaa!4D61!\[C_t \left( {t_d } \right) = fC_a \left( {t_d } \right) \otimes e\frac{f}{{V_d }}t_d \] respectively, where ⊗ denotes the convolution integral; Ca(t), the arterial input function; f rCBF; and Vd, the regional distribution volume of IMP. Calculation of the ratio of the above two equations and a “table look-up” procedure yield a unique pair of rCBF and Vd for each region of interest (ROI). A standard input function has been generated by combining the input functions from 12 independent studies prior to this work to avoid frequent arterial blood sampling, and one blood sample is taken at 10 min following IMP administration for calibration of the standard arterial input function. This calibration time was determined such that the integration of the first 40 min of the calibrated, combined input function agreed best with those from 12 individual input functions (the difference was 5.3% on average). This method was applied to eight subjects (two normals and six patients with cerebral infarction), and yielded rCBF values which agreed well with those obtained by a positron emission tomography H215O autoradiography method. This method was also found to provide rCBF values that were consistent with those obtained by the non-linear least squares fitting technique and those obtained by conventional microsphere model analysis. The optimum SPET scan times were found to be 40 and 180 min for the early and delayed scans, respectively. These scan times allow the use of a conventional rotating gamma camera for clinical purposes. Vd values ranged between 10 and 40 ml/g depending on the pathological condition, thereby suggesting the importance of measuring Vd for each ROI. In conclusion, optimization of the blood sampling time and the scanning time enabled quantitative measurement of rCBF with two SPET scans and one blood sample.

Changes of cerebral blood flow, and oxygen and glucose metabolism following radiochemotherapy of gliomas: a PET study.

The effects of radiochemotherapy on blood flow, blood volume, and consumption of oxygen and glucose in tumor tissue and normal brain were studied by positron emission tomography. Thirteen patients with cerebral gliomas were included, and they were examined before, during, and within approximately 1 month after the therapy. The 15O-labeled gas steady state inhalation and the 18F-fluorodeoxyglucose methods were used. After the therapy, glucose consumption and blood volume decreased (p less than 0.03) in the tumoral tissue. In the structurally (CT) normal gray matter, blood flow, blood volume, and oxygen consumption did not show any significant changes; oxygen extraction fraction, glucose consumption, and glucose extraction fraction, however, decreased significantly (p less than 0.05, less than 0.02, and less than 0.03, respectively).

Photic Stimulation Study of Changing the Arterial Partial Pressure Level of Carbon Dioxide

To investigate the effect of the level of baseline cerebral blood flow (CBF) on local CBF augmentation by activation, we have used positron emission tomography to measure regional CBF (rCBF) in 12 normal volunteers with and without photic stimulation during hypocapnia, normocapnia, and hypercapnia. The increase in rCBF in the primary visual cortex by photic stimulation was 10.8 ± 3.1, 18.6 ± 9.3, and 19.5 ± 6.1 ml 100 ml−1 min−1 in hypo-, normo-, and hypercapnia, respectively. The increase was significantly smaller in hypocapnia than in normocapnia (p < 0.005). The fractional CBF increase caused by the photic stimulation was the same in all breathing conditions. This result indicates that the magnitude of the CBF increase induced by neuronal activity correlates proportionally with the level of baseline CBF.

Age-related decline of cerebral oxygen metabolism in normal population detected with positron emission tomography

Using positron emission tomography (PET), cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were measured in 32 healthy volunteers aged from 27 to 67 years. In bilateral putamen, left supratemporal, left infrafrontal and left parietal cortices, CMRO2 showed a significant decline during aging. The age-related decline of CBF was seen only at the left superior temporal cortex. The mean CMRO2 was significantly lower in the elder group (over 51 years old) than in the younger group (under 50 years old), whereas no significant difference in mean CBF between the two groups. The poor correlation of CBF to the age could be explained partly by the fact that CBF is easily influenced by the physiological, psychological and/or environmental factors. The age-related changes of CMRO2 were more marked in the association cortices of the left hemisphere than in that of the right hemisphere.

Linearization Correction of 99mTc-Labeled Hexamethyl-Propylene Amine Oxime (HM-PAO) Image in Terms of Regional CBF Distribution: Comparison to C15O2 Inhalation Steady-State Method Measured by Positron Emission Tomography:

The radioisotope distribution following intravenous injection of 99mTc-labeled hexamethylpropyleneamine oxime (HM-PAO) in the brain was measured by single photon emission computed tomography (SPECT) and corrected for the nonlinearity caused by differences in net extraction. The “linearization” correction was based on a three compartment model, and it required a region of reference to normalize the SPECT image in terms of regional cerebral blood flow distribution. Two different regions of reference, the cerebellum and the whole brain, were tested. The uncorrected and corrected HM-PAO images were compared with cerebral blood flow (CBF) image measured by the C15O2 inhalation steady state method and positron emission tomography (PET). The relationship between uncorrected HM-PAO and PET–CBF showed a correlation coefficient of 0.85 but tended to saturate at high CBF values, whereas it was improved to 0.93 after the “linearization” correction. The whole-brain normalization worked just as well as normalization using the cerebellum. This study constitutes a validation of the “linearization” correction and it suggests that after linearization the HM-PAO image may be scaled to absolute CBF by employing a global hemispheric CBF value as measured by the nontomographic 133Xe clearance method.

Carotid artery resection for head and neck cancer

BACKGROUND Carotid artery resection has been shown to yield a chance of cure in patients with advanced head and neck carcinoma involving the carotid artery. However, the criteria for the identification of those who are vulnerable to neurologic injury after resection have not been established. Interposition grafting may minimize the risk of neurologic morbidity, although it is technically difficult when there is involvement of the internal carotid artery close to the skull base. METHODS We studied 24 patients with head and neck tumor involvement of the carotid artery. We performed carotid artery resection in 16 of them, including 10 in whom the carotid artery was reconstructed with interposition grafts covered with muscle flaps. When it was thought that the reconstruction would be difficult, positron emission tomography was performed during balloon test occlusion of the internal carotid artery to assess the adequacy of hemispheric collateral blood flow before carotid resection. In one patient with interposition graft, carotid rupture occurred as a result of wound infection, but none of the other patients experienced perioperative death, persistent hemiplegia, or delayed stroke. RESULTS Twelve patients have survived longer than 8 months, and seven (43.8%) were alive without disease at 12 months after resection, whereas all four patients who could not be treated operatively died within 8 months as a result of local primary tumors. CONCLUSIONS Carotid artery resection is the only therapy offering any potential for cure or palliation. Positron emission tomography is a rapid quantitative means of determining the cerebral blood flow, particularly when resection is planned without reconstruction.