Quantitative positron emission tomography requires the determination of the tracer concentration ... more Quantitative positron emission tomography requires the determination of the tracer concentration in arterial plasma or full blood as a function of time. This defines the experimental input function. The model prediction, with which the positron camera regional time-activity curves are compared, is given by the experimental input function convoluted with the model. This paper reviews different strategies for determining the input function, invasive techniques, such as manual blood sampling and the use of automated blood sampling systems, and non-invasive techniques. The importance of corrections is discussed, such as accurate cross-calibrations of the different detectors used in quantitative PET and corrections for differences in time phase between the regional PET time-activity curves and the input function. We also report on the use of a PET system in non-invasive determinations of the input function. By imaging the neck region the time-activity curve of the carotid arteries can be obtained. The PET time-activity curves of the carotid arteries are in good agreement with a conventional experimental input function determined from the radial artery with an automated blood sampling system. However, PET time-activity curves of the radial arteries can not be used without a deconvolution since the resistance in the intact radial artery causes dispersion compared to the input function obtained by invasive methods.
Quantitative positron emission tomography requires the determination of the tracer concentration ... more Quantitative positron emission tomography requires the determination of the tracer concentration in arterial plasma or full blood as a function of time. This defines the experimental input function. The model prediction, with which the positron camera regional time-activity curves are compared, is given by the experimental input function convoluted with the model. This paper reviews different strategies for determining the input function, invasive techniques, such as manual blood sampling and the use of automated blood sampling systems, and non-invasive techniques. The importance of corrections is discussed, such as accurate cross-calibrations of the different detectors used in quantitative PET and corrections for differences in time phase between the regional PET time-activity curves and the input function. We also report on the use of a PET system in non-invasive determinations of the input function. By imaging the neck region the time-activity curve of the carotid arteries can be...
Measurement of the arterial input function is essential for quantitative assessment of physiologi... more Measurement of the arterial input function is essential for quantitative assessment of physiological function in vivo using PET. However, frequent arterial blood sampling is invasive and labor intensive. Recently, a PET system has been developed that consists of two independent PET tomographs for simultaneously scanning the brain and heart, which should avoid the need for arterial blood sampling. The aim of this study was to validate noninvasive quantitation with this system for 15O-labeled compounds. Methods: Twelve healthy volunteers underwent a series of PET studies after C15O inhalation and intravenous H2(15)O administration using a Headtome-V-Dual tomograph (Shimadzu Corp., Kyoto, Japan). The C15O study provided gated blood-pool images of the heart simultaneously with quantitative static blood-volume images of both the brain and heart. Weighted-integrated H2(15)O sinograms were acquired for estimating rate constant (K1) and distribution-volume (Vd) images in the brain, in addition to single-frame sinograms for estimating autoradiographic cerebral blood flow images. Noninvasive arterial input functions were determined from the heart scanner (left ventricular chamber) according to a previously developed model and compared directly to invasive input functions measured with an on-line beta probe in six subjects. Results: The noninvasive input functions derived from this PET system were in good agreement with those obtained by continuous arterial blood sampling in all six subjects. There was good agreement between quantitative values obtained noninvasively and those using the invasive input function: average autoradiographic regional cerebral blood flow was 0.412 +/- 0.058 and 0.426 +/- 0.062 ml/min/g, K1 of H2(15)O was 0.416 +/- 0.073 and 0.420 +/- 0.067 ml/min/ml and Vd of H2(15)O was 0.800 +/- 0.080 and 0.830 +/- 0.070 ml/ml for the noninvasive and invasive input functions, respectively. In addition to the brain functional parameters, the system also simultaneously provided cardiac function such as regional myocardial blood flow (0.84 +/- 0.19 ml/min/g), left ventricular volume (132 +/- 22 mm at end diastole and 45 +/- 14 ml at end systole) and ejection fraction (66% +/- 5%). Conclusion: This PET system allows noninvasive quantitation in both the brain and heart simultaneously without arterial cannulation, and may prove useful in clinical research.
European Journal of Nuclear Medicine and Molecular Imaging, May 1, 2004
Measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction... more Measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO(2)) by positron emission tomography (PET) with oxygen-15 labelled carbon dioxide (C(15)O(2)) or (15)O-labelled water (H(2)(15)O), (15)O-labelled carbon monoxide (C(15)O) and (15)O-labelled oxygen ((15)O(2)) is useful for diagnosis and treatment planning in cases of cerebrovascular disease. The measured values theoretically depend on various factors, which may differ between PET centres. This study explored the applicability of a database of (15)O-PET by examining between-centre and within-centre variation in values. Eleven PET centres participated in this multicentre study; seven used the steady-state inhalation method, one used build-up inhalation and three used bolus administration of C(15)O(2) (or H(2)(15)O) and (15)O(2). All used C(15)O for measurement of CBV. Subjects comprised 70 healthy volunteers (43 men and 27 women; mean age 51.8+/-15.1 years). Overall mean+/-SD values for cerebral cortical regions were: CBF=44.4+/-6.5 ml 100 ml(-1) min(-1); CBV=3.8+/-0.7 ml 100 ml(-1); OEF=0.44+/-0.06; CMRO(2)=3.3+/-0.5 ml 100 ml(-1) min(-1). Significant between-centre variation was observed in CBV, OEF and CMRO(2) by one-way analysis of variance. However, the overall inter-individual variation in CBF, CBV, OEF and CMRO(2) was acceptably small. Building a database of normal cerebral haemodynamics obtained by the(15)O-PET methods may be practicable.
Since Roy and Sherrington (1890) described that neural activity would regulate blood supply to th... more Since Roy and Sherrington (1890) described that neural activity would regulate blood supply to the brain, it has been widely accepted that neural activation will increase cerebral blood flow (CBF). Lassen and Munck (1955) first demonstrated the regional change of CBF at the cortical areas using radioisotopes. The recent development of technology, e.g. positron emission tomography (PET), has allowed us to measure quantitative CBF at every cubic centimeter of the brain. However, most of psychophysiological brain mapping studies mainly utilize the topographic information to delineate CBF change by canceling out quantitative information of CBF in the process of the statistical analysis to evaluate regional CBF change relating to the neural activity (Friston et al. 1990).
Electroencephalography and Clinical Neurophysiology, Sep 1, 1997
To determine the relationship between EEG slowing and cerebral hypometabolism in dementia, 10 pat... more To determine the relationship between EEG slowing and cerebral hypometabolism in dementia, 10 patients with dementia of Alzheimer's type (DAT) were evaluated with quantitative topographic EEG and positron emission tomography (PET). Power in each 1-Hz frequency band from 2-20 Hz, power ratio index, and normalised PET data from corresponding cortical sites were compared to data obtained from 20 normal volunteers. PET revealed significant parieto-temporal hypometabolism, and topographic EEG mapping and power spectrum analysis revealed a slowing of the background EEG that was most pronounced in the parietal-temporal areas. Correlation analysis between EEG power spectrum data and CMRO2 revealed significant negative correlations for frequencies below 8 Hz and significant positive correlations above 8 Hz in the parieto-temporal regions, which have previously been identified as the areas most severely affected by pathological changes associated with DAT. Correlation coefficients plotted as functions of frequency illustrated the relationships between EEG changes and reduced CMRO2, supporting previous views that EEG slowing in DAT may be related to hypometabolism in cortical regions most affected by the disease.
In a positron emission tomography activation analysis with task replications within subject, a nu... more In a positron emission tomography activation analysis with task replications within subject, a number of analysis of variance (ANOVA) designs are applicable with different definitions of t and error. The characteristics of t (and z) maps and error images and how they depend on the ANOVA design and on the anatomical standardization method have been investigated. Six subjects underwent measurement of regional cerebral blood flow with [15O]water under resting and while thinking of verbs associated with auditorily presented nouns, three times for each. The images were anatomically standardized with LINear, SPM95, or HBA. ANOVA was performed pixel by pixel to compute t statistics for the task main effect (verb vs rest) in four different ANOVA designs: (i) two way (subject and task) (2W), (ii) two way with interaction (2WI), (iii) two way with interaction, except that the “subject” was considered a random factor (2WI-RF), and (iv) three way (subject, task, and replication). The left frontal cortex extending from Broca's area to the premotor cortex was activated by the verb generation. The foci localization in the z images depended both on the anatomical standardization method and on the ANOVA design, and the variation ranged from 1 to 3 cm. SPM tended to present a higher peak z than LIN and HBA. The z images of 2W and 2WI looked alike, but 2WI-RF and 3W each presented a different z map within the activated area. The peak z score by 2WI-RF was lower than the others. The error images for 2W, 2WI, and 3W were heterogeneous, being high in gray and low in white.
Quantification of the receptor binding potential (BP) in human brain has been performed with posi... more Quantification of the receptor binding potential (BP) in human brain has been performed with positron emission tomography. In this quantitative analysis, the uncertainty in estimated kinetic parameters depends on the SNR. Evaluation of the reliability of parameter estimates is important for the optimization of scan protocol and quantitative analysis methods. However, estimating the reliability is not easy for human data
Quantitative positron emission tomography requires the determination of the tracer concentration ... more Quantitative positron emission tomography requires the determination of the tracer concentration in arterial plasma or full blood as a function of time. This defines the experimental input function. The model prediction, with which the positron camera regional time-activity curves are compared, is given by the experimental input function convoluted with the model. This paper reviews different strategies for determining the input function, invasive techniques, such as manual blood sampling and the use of automated blood sampling systems, and non-invasive techniques. The importance of corrections is discussed, such as accurate cross-calibrations of the different detectors used in quantitative PET and corrections for differences in time phase between the regional PET time-activity curves and the input function. We also report on the use of a PET system in non-invasive determinations of the input function. By imaging the neck region the time-activity curve of the carotid arteries can be obtained. The PET time-activity curves of the carotid arteries are in good agreement with a conventional experimental input function determined from the radial artery with an automated blood sampling system. However, PET time-activity curves of the radial arteries can not be used without a deconvolution since the resistance in the intact radial artery causes dispersion compared to the input function obtained by invasive methods.
Quantitative positron emission tomography requires the determination of the tracer concentration ... more Quantitative positron emission tomography requires the determination of the tracer concentration in arterial plasma or full blood as a function of time. This defines the experimental input function. The model prediction, with which the positron camera regional time-activity curves are compared, is given by the experimental input function convoluted with the model. This paper reviews different strategies for determining the input function, invasive techniques, such as manual blood sampling and the use of automated blood sampling systems, and non-invasive techniques. The importance of corrections is discussed, such as accurate cross-calibrations of the different detectors used in quantitative PET and corrections for differences in time phase between the regional PET time-activity curves and the input function. We also report on the use of a PET system in non-invasive determinations of the input function. By imaging the neck region the time-activity curve of the carotid arteries can be...
Measurement of the arterial input function is essential for quantitative assessment of physiologi... more Measurement of the arterial input function is essential for quantitative assessment of physiological function in vivo using PET. However, frequent arterial blood sampling is invasive and labor intensive. Recently, a PET system has been developed that consists of two independent PET tomographs for simultaneously scanning the brain and heart, which should avoid the need for arterial blood sampling. The aim of this study was to validate noninvasive quantitation with this system for 15O-labeled compounds. Methods: Twelve healthy volunteers underwent a series of PET studies after C15O inhalation and intravenous H2(15)O administration using a Headtome-V-Dual tomograph (Shimadzu Corp., Kyoto, Japan). The C15O study provided gated blood-pool images of the heart simultaneously with quantitative static blood-volume images of both the brain and heart. Weighted-integrated H2(15)O sinograms were acquired for estimating rate constant (K1) and distribution-volume (Vd) images in the brain, in addition to single-frame sinograms for estimating autoradiographic cerebral blood flow images. Noninvasive arterial input functions were determined from the heart scanner (left ventricular chamber) according to a previously developed model and compared directly to invasive input functions measured with an on-line beta probe in six subjects. Results: The noninvasive input functions derived from this PET system were in good agreement with those obtained by continuous arterial blood sampling in all six subjects. There was good agreement between quantitative values obtained noninvasively and those using the invasive input function: average autoradiographic regional cerebral blood flow was 0.412 +/- 0.058 and 0.426 +/- 0.062 ml/min/g, K1 of H2(15)O was 0.416 +/- 0.073 and 0.420 +/- 0.067 ml/min/ml and Vd of H2(15)O was 0.800 +/- 0.080 and 0.830 +/- 0.070 ml/ml for the noninvasive and invasive input functions, respectively. In addition to the brain functional parameters, the system also simultaneously provided cardiac function such as regional myocardial blood flow (0.84 +/- 0.19 ml/min/g), left ventricular volume (132 +/- 22 mm at end diastole and 45 +/- 14 ml at end systole) and ejection fraction (66% +/- 5%). Conclusion: This PET system allows noninvasive quantitation in both the brain and heart simultaneously without arterial cannulation, and may prove useful in clinical research.
European Journal of Nuclear Medicine and Molecular Imaging, May 1, 2004
Measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction... more Measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO(2)) by positron emission tomography (PET) with oxygen-15 labelled carbon dioxide (C(15)O(2)) or (15)O-labelled water (H(2)(15)O), (15)O-labelled carbon monoxide (C(15)O) and (15)O-labelled oxygen ((15)O(2)) is useful for diagnosis and treatment planning in cases of cerebrovascular disease. The measured values theoretically depend on various factors, which may differ between PET centres. This study explored the applicability of a database of (15)O-PET by examining between-centre and within-centre variation in values. Eleven PET centres participated in this multicentre study; seven used the steady-state inhalation method, one used build-up inhalation and three used bolus administration of C(15)O(2) (or H(2)(15)O) and (15)O(2). All used C(15)O for measurement of CBV. Subjects comprised 70 healthy volunteers (43 men and 27 women; mean age 51.8+/-15.1 years). Overall mean+/-SD values for cerebral cortical regions were: CBF=44.4+/-6.5 ml 100 ml(-1) min(-1); CBV=3.8+/-0.7 ml 100 ml(-1); OEF=0.44+/-0.06; CMRO(2)=3.3+/-0.5 ml 100 ml(-1) min(-1). Significant between-centre variation was observed in CBV, OEF and CMRO(2) by one-way analysis of variance. However, the overall inter-individual variation in CBF, CBV, OEF and CMRO(2) was acceptably small. Building a database of normal cerebral haemodynamics obtained by the(15)O-PET methods may be practicable.
Since Roy and Sherrington (1890) described that neural activity would regulate blood supply to th... more Since Roy and Sherrington (1890) described that neural activity would regulate blood supply to the brain, it has been widely accepted that neural activation will increase cerebral blood flow (CBF). Lassen and Munck (1955) first demonstrated the regional change of CBF at the cortical areas using radioisotopes. The recent development of technology, e.g. positron emission tomography (PET), has allowed us to measure quantitative CBF at every cubic centimeter of the brain. However, most of psychophysiological brain mapping studies mainly utilize the topographic information to delineate CBF change by canceling out quantitative information of CBF in the process of the statistical analysis to evaluate regional CBF change relating to the neural activity (Friston et al. 1990).
Electroencephalography and Clinical Neurophysiology, Sep 1, 1997
To determine the relationship between EEG slowing and cerebral hypometabolism in dementia, 10 pat... more To determine the relationship between EEG slowing and cerebral hypometabolism in dementia, 10 patients with dementia of Alzheimer's type (DAT) were evaluated with quantitative topographic EEG and positron emission tomography (PET). Power in each 1-Hz frequency band from 2-20 Hz, power ratio index, and normalised PET data from corresponding cortical sites were compared to data obtained from 20 normal volunteers. PET revealed significant parieto-temporal hypometabolism, and topographic EEG mapping and power spectrum analysis revealed a slowing of the background EEG that was most pronounced in the parietal-temporal areas. Correlation analysis between EEG power spectrum data and CMRO2 revealed significant negative correlations for frequencies below 8 Hz and significant positive correlations above 8 Hz in the parieto-temporal regions, which have previously been identified as the areas most severely affected by pathological changes associated with DAT. Correlation coefficients plotted as functions of frequency illustrated the relationships between EEG changes and reduced CMRO2, supporting previous views that EEG slowing in DAT may be related to hypometabolism in cortical regions most affected by the disease.
In a positron emission tomography activation analysis with task replications within subject, a nu... more In a positron emission tomography activation analysis with task replications within subject, a number of analysis of variance (ANOVA) designs are applicable with different definitions of t and error. The characteristics of t (and z) maps and error images and how they depend on the ANOVA design and on the anatomical standardization method have been investigated. Six subjects underwent measurement of regional cerebral blood flow with [15O]water under resting and while thinking of verbs associated with auditorily presented nouns, three times for each. The images were anatomically standardized with LINear, SPM95, or HBA. ANOVA was performed pixel by pixel to compute t statistics for the task main effect (verb vs rest) in four different ANOVA designs: (i) two way (subject and task) (2W), (ii) two way with interaction (2WI), (iii) two way with interaction, except that the “subject” was considered a random factor (2WI-RF), and (iv) three way (subject, task, and replication). The left frontal cortex extending from Broca's area to the premotor cortex was activated by the verb generation. The foci localization in the z images depended both on the anatomical standardization method and on the ANOVA design, and the variation ranged from 1 to 3 cm. SPM tended to present a higher peak z than LIN and HBA. The z images of 2W and 2WI looked alike, but 2WI-RF and 3W each presented a different z map within the activated area. The peak z score by 2WI-RF was lower than the others. The error images for 2W, 2WI, and 3W were heterogeneous, being high in gray and low in white.
Quantification of the receptor binding potential (BP) in human brain has been performed with posi... more Quantification of the receptor binding potential (BP) in human brain has been performed with positron emission tomography. In this quantitative analysis, the uncertainty in estimated kinetic parameters depends on the SNR. Evaluation of the reliability of parameter estimates is important for the optimization of scan protocol and quantitative analysis methods. However, estimating the reliability is not easy for human data
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