Uemura K

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.

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.

Evaluation of regional differences of tracer appearance time in cerebral tissues using [15O] water and dynamic positron emission tomography.

The tracer appearance time relative to the radial artery–sampling site has been evaluated in six brain locations in five human subjects using dynamic positron emission tomography (PET) following the bolus injection of H215O. There was a maximum difference of ± 2 s from the average in each location. T o globally adjust the timing difference between the measured arterial curve and the PET scan, a correction method was developed based on a nonlinear least-squares fitting procedure. This new technique determined the global time delay with an accuracy of ± 0.5 s. On the other hand, the linear backward extrapolation method resulted in a systematic error of 4 s.

Design and evaluation of HEADTOME-IV, a whole-body positron emission tomograph

A whole-body positron emission tomograph called Headtome-IV has been developed, and its physical performance has been investigated. An in-plane spatial resolution of 4.5 mm was realized with stationary sampling at the center of the field of view. The axial slice thicknesses were 9.5 and 9.0 mm for direct and cross planes, respectively. By moving the gantry framework axially, transaxial images of 14 or 21 slices are obtained quasi-simultaneously. The real-time large-scale cache memory system allowed real-time corrections for deadtime and radionuclide decay and real-time weighted integration for the purpose of a rapid calculation of rate-constant images. >

A Multicenter Validation of Regional Cerebral Blood Flow Quantitation Using [123I]Iodoamphetamine and Single Photon Emission Computed Tomography

Recently, two methods have been proposed for regional cerebral blood flow (rCBF) quantitation using [123I]iodoamphetamine (IMP) and single-photon emission computed tomography (SPECT). The table look-up (TLU) method has been shown to provide both rCBF and volume of distribution, Vd, images from two SPECT scans, while a single-scan autoradiographic (ARG) technique provided rCBF using a fixed and assumed Vd. In both methods, a single blood sample was referred to calibrate the previously determined standard input function The present multicenter project was designed to evaluate the accuracy of both methods for use as clinical investigative tools. Ten independent institutions performed [123I]IMP-SPECT studies according to both methods in 76 subjects (10 normal volunteers, 32 patients with cerebrovascular disease, and 34 patients with other diseases). Calculated rCBF values were compared with those obtained by the following reference methods available in the participating institutions; [15O] H2O positron emission tomography (PET) (five institutions), [133Xe]SPECT (four institutions), and the [123I]IMP microsphere method (three institutions). Both ARG and TLU methods provided rCBF values that were significantly correlated with those measured by the [15O] H2O PET technique (p < 0.001 for all subjects; overall regression equation, y = 15.14 + 0.54×) and those measured by the [123I]IMP-microsphere method (p < 0.001 for all subjects; y = 2.0 + 0.80×). Significant correlation (p < 0.05) was observed in 18 of 24 subjects studied with the [133Xe] SPECT reference technique (overall regression equation, y = 15.0 + 0.55×). Mean cortical gray matter rCBF in a group of normal subject was 43.9 ± 3.3 and 43.4 ± 2.0 ml/min/100 g for the ARG and TLU methods, respectively. Regional Vd of [123I]IMP estimated by the TLU method was 45 ml/ml ± 20% in the normal cortical region. Close agreement between ARG and TLU rCBF values was observed (y = −3.21 + 1.07×, r = 0.97), confirming the validity of assuming a fixed Vd in the ARG method. Results of this study demonstrate that both the ARG and TLU methods accurately and reliably estimate rCBF in a variety of clinical settings.

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.

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.

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.

A Hybrid Emission CT - HEADTOME II

HEADTOME II for a hybrid emission computed tomography for brain has been developed. The system includes multislice capability of both positron emission tomography (PET) and single photon emission tomography (SET) in one system. It consists of three detector rings of 42cm in diameter on which 64 NaI crystals are arranged per ring, 192 as a total. Four kinds of collimators are prepared: high resolution (HR) collimator and high sensitivity (HS) collimator for both SET and PET. The tangential spatial resolution is 6.5mm-11mm for SET with the HR collimator and 10.5mm-20mm with the HS collimator measured with 99mTc line source. System sensitivity with the single photon HS collimator is 58.5 kcps/?Ci/ml for a 20cm diameter uniform solution of 99mTc. System sensitivity with the positron HS collimator is 25 kcps/?Ci/ml for 68Ga solution.

Effect of real-time weighted integration system for rapid calculation of functional images in clinical positron emission tomography

A system has been developed to rapidly calculate images of parametric rate constants, without acquiring dynamic frame data for clinical positron emission tomography (PET). This method is based on the weighted-integration algorithms for the two- and three-compartment models, and hardware developments (real-time operation and a large cache memory system) in HEADTOME-IV, which enables the acquisition of multiple sinograms with independent weight integration functions. Following the administration of the radio-tracer, the scan is initiated to collect multiple time-weighted, integrated sinograms with three weight functions. These sinograms are reconstructed and the images, with the arterial blood data, are inserted into the operational equations to provide parametric rate constant images. The implementation of this method has been tested in H/sub 2//sup 15/O and /sup 18/F-fluorophenylalanine (/sup 18/FPHE) studies based on a two-compartment model, and in a /sup 18/FDG study based on the three-compartment model. A volunteer study, completed for each compound, yielded results consistent with those produced by existing non-linear fitting methods. Thus, this system is capable of rapid generation of quantitative physiological functional images, without dynamic data acquisition, and will be of great advantage for clinical use of PET.<<ETX>>