Matsutaro Murakami

Error Analysis of a Quantitative Cerebral Blood Flow Measurement Using H215O Autoradiography and Positron Emission Tomography, with Respect to the Dispersion of the Input Function

The effect of the inaccuracy of the input function on CBF measured by the H152O autoradiographic method was investigated. In H152O autoradiography the measured input function usually includes a larger dispersion than the true input function, as well as the absolute time axis having been already lost. The time constant of the external dispersion that occurred in our continuous sampling system was evaluated as 10–12 s when the dispersion function was approximated by a monoexponential function. The internal dispersion occurring in arterial lines in a human body was evaluated as 4–6 s. Such dispersion, indispensable in a patient study, was found to produce large errors in calculating CBF, e.g., 5(10) s of the dispersion caused + 15(33) and + 10(20)% systematic overestimations for the 40- and 60-s accumulation time, respectively. An analytical correction employing an inverse Laplace transform was applied to clinical CBF studies, and the results were compared with those from the C15O2 steady-state inhalation method. Correction by 10 s in time constant, corresponding to the external dispersion, reduced the overestimation significantly from 70–100% to ∼20%. Further correction by 5 s, corresponding to the internal dispersion, resulted in a negligible difference (less than a few percent) from the steady-state method.

Measurement of absolute myocardial blood flow with H215O and dynamic positron-emission tomography. Strategy for quantification in relation to the partial-volume effect.

An in vivo technique was developed for measuring the absolute myocardial blood flow with H215O and dynamic positron-emission tomography. This technique was based on a new model involving the concept of the tissue fraction, which was defined as the fraction of the tissue mass in the volume of the region of interest. The myocardium was imaged dynamically by positron-emission tomography, starting at the time of intravenous bolus injection of H215O. The arterial input function was measured continuously with a beta-ray detector. A separate image after C15O inhalation was also obtained for correction of the H215O radioactivity in the blood. The absolute myocardial blood flow and the tissue fraction were calculated for 15 subjects with a kinetic technique under region-of-interest analysis. These results seem consistent with their coronary angiographic findings. The mean value of the measured absolute myocardial blood flows in normal subjects was 0.95 +/- 0.09 ml/min/g. This technique detected a diffuse decrease of myocardial blood flow in patients with triple-vessel disease.

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).

A Determination of the Regional Brain/Blood Partition Coefficient of Water Using Dynamic Positron Emission Tomography

In order to investigate the validity of the single compartment model in measuring CBF with the use of 15O-labeled water (H215O), dynamic positron emission tomography (PET) was performed following bolus injection of H215O. Careful attention was paid to accuracy in the measurement system (especially for the input function). In the region of the putamen, which includes the smallest mixture of gray and white matters in addition to the smallest contamination of cerebrospinal fluid (CSF) spaces, the partition coefficient obtained was 0.88 ± 0.06 (ml/g). The discrepancy from the prediction estimated from the brain/blood water content ratio was only 7%. This finding suggests that there is no more complicated model than the usual single compartment one to describe the physiological behaviour of 15O water. On the other hand, in the other cortical regions, the discrepancy was larger (e.g., about 12% for the insular cortex and 26% for the frontal cortex) than in the region of the putamen, and a significant fit–interval dependence was observed in the calculated parameters. These observations suggest a significant effect of tissue heterogeneity and/or contamination with nonperfusable spaces in actual clinical PET data.

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.

Design and evaluation of a positron emission tomograph: HEADTOME III.

A high performance positron emission tomograph, HEADTOME III, with 480 bismuth germanate oxide detectors (13.4 X 25.0 X 40.0 mm), arranged in three rings of 750 mm diameter, with independent shadow masks and septa, is described. Image plane resolution at the center of the field of view (FOV) is 7.9 and 6.5 mm full width at half maximum (FWHM) in low resolution (LR) and high resolution (HR) mode, respectively. Axial resolution is 13.1, 11.3, and 9.1 mm FWHM at the center of FOV for direct planes of low quantitation (LQ), cross planes of LQ, and high quantitation (HQ) mode, respectively. Sensitivities evaluated by true events for a 68Ga 20 cm diameter cyclindrical pool were 34.5 (56.7), 16.4 (27.5), 19.4 and 9.5 kcps (muCi/ml)-1 with the direct (cross) planes of LQLR, direct (cross) planes of LQHR, and direct planes of HQLR and HQHR, respectively. The fraction of scattered coincidence in a cold spot phantom after software correction is 2.5% in LRLQ mode. Count rate linearity after software correction is within 1% up to 50 X 10(3) true events per second per plane with LRLQ mode.

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.

A Simulation Study of a Method to Reduce Positron Annihilation Spread Distributions Using a Strong Magnetic Field in Positron Emission Tomography

The positron trajectories have been three-dimensionally simulated using a Monte-Carlo method under various strength of the magnetic field. More than 5 tesla of the field confined the positrons effectively, resulting in increase of the probability of the annihilation within a limited small region, hence the higher spatial resolution in positron emission tomography.