Modelling approach for separating blood time activity curves in positron emission tomographic studies

Huang, Sung‐Cheng; Barrio, Jorge R.; Yu, Dan; Chen, B; Grafton, Scott T.; Melega, William P.; Hoffman, John M.; Satyamurthy, Nagichettiar; Mazziotta, John C.; Phelps, Michael E.

doi:10.1088/0031-9155/36/6/004

Cited by 38 publications

(34 citation statements)

References 11 publications

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“…We then subtracted it from the measured total arterial TAC in the second phase to obtain a TAC for the second tracer. Second, the metabolic product (recirculating water) following 15 O 2 administration was estimated using the plasma radioactivity measured during the phase of 15 O 2 Rapid quantitative measurement of CMRO 2 and CBF N Kudomi et al and a fitting procedure described previously (Huang et al, 1991;Iida et al, 1993 15 O 2 TAC from the first phase as described above, and then obtained A o and A w . The preliminary validation of this procedure is described elsewhere .…”

Section: Data Processingmentioning

confidence: 99%

Rapid Quantitative Measurement of CMRO₂ and CBF by Dual Administration of ¹⁵O-Labeled Oxygen and Water During a Single PET Scan—a Validation Study and Error Analysis in Anesthetized Monkeys

Kudomi

Hayashi

Teramoto

et al. 2005

J Cereb Blood Flow Metab

101

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Cerebral blood flow (CBF) and rate of oxygen metabolism (CMRO 2 ) may be quantified using positron emission tomography (PET) with 15 O-tracers, but the conventional three-step technique requires a relatively long study period, attributed to the need for separate acquisition for each of 15 O 2 , H 2 15 O, and C 15 O tracers, which makes the multiple measurements at different physiologic conditions difficult. In this study, we present a novel, faster technique that provides a pixel-by-pixel calculation of CBF and CMRO 2 from a single PET acquisition with a sequential administration of 15 O 2 and H 2 15 O. Experiments were performed on six anesthetized monkeys to validate this technique. The global CBF, oxygen extraction fraction (OEF), and CMRO 2 obtained by the present technique at rest were not significantly different from those obtained with three-step method. The global OEF (gOEF) also agreed with that determined by simultaneous arterio-sinus blood sampling (gOEF AÀV ) for a physiologically wide range when changing the arterial PaCO 2 (gOEF ¼ 1.03gOEF AÀV þ 0.01, Po0.001). The regional values, as well as the image quality were identical between the present technique and three-step method for CBF, OEF, and CMRO 2 . In addition, a simulation study showed that error sensitivity of the present technique to delay or dispersion of the input function, and the error in the partition coefficient was equivalent to that observed for three-step method. Error sensitivity to cerebral blood volume (CBV) was also identical to that in the three-step and reasonably small, suggesting that a single CBV assessment is sufficient for repeated measures of CBF/CMRO 2 . These results show that this fast technique has an ability for accurate assessment of CBF/CMRO 2 and also allows multiple assessment at different physiologic conditions.

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Section: Data Processingmentioning

confidence: 99%

Rapid Quantitative Measurement of CMRO₂ and CBF by Dual Administration of ¹⁵O-Labeled Oxygen and Water During a Single PET Scan—a Validation Study and Error Analysis in Anesthetized Monkeys

Kudomi

Hayashi

Teramoto

et al. 2005

J Cereb Blood Flow Metab

101

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“…To generate a continu ous curve from the 5-6 HPLC measurements, we used a method based on that of Huang et al (1991). Figure 1 shows the whole-body model used to describe raclopride metabolites.…”

Section: Blood Sampling and Metabolite Determinationmentioning

confidence: 99%

Quantification of Amphetamine-Induced Changes in [¹¹C]Raclopride Binding with Continuous Infusion

Carson

Breier

Bartolomeis

et al. 1997

J Cereb Blood Flow Metab

229

133

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Summar y : Positron emISSIOn tomography and single photon emission computer tomography receptor-binding ligands can be used to measure changes in neurotransmitter levels. In particular, amphetamine-induced dopamine re lease has been assessed with P lC)raclopride by paired bolus injections and with [l 23 I]iodobenzamide by using a single bolus plus infusion (B/I) study. Here, we measured the change in P lC)raclopride-specific binding in rhesus mon keys after 4v. administration of 0.4 mg/kg amphetamine by using both the bolus and B/I paradigms. Paired bolus studies (control and postamphetamine) were analyzed us ing compartment modeling and graphical analysis with a new plasma metabolite model to measure the total distribu tion volume (VT). Specific binding, calculated with threeThe tissue concentration of receptor-binding ra diopharmaceuticals depends on many physiological parameters. A wide variety of approaches have been developed to determine parameters of neuroreceptor binding that are ideally equal or at least linearly pro portional to the free receptor concentration. These techniques include full kinetic modeling with multi ple-parameter estimation, graphical approaches that estimate one or two combined model parameters such as the total volume of distribution (VT) and simple tissue concentration ratios. With such tech niques, within-subject changes in free receptor con centration-for example, caused by an intervention

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“…The kinetics of 18 F-FDOPA in the striatum and cerebellum of volunteers were investigated by Huang et al, and a model for the human brain was published (9). In the present study, we investigated the kinetics in brain gliomas, brain metastases, and benign lesions.…”

mentioning

confidence: 94%

18F-FDOPA Kinetics in Brain Tumors

Schiepers

Chen²,

Cloughesy³

et al. 2007

Journal of Nuclear Medicine

125

111

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L-3,4-Dihydroxy-6-18 F-fluoro-phenyl-alanine ( 18 F-FDOPA) is an amino acid analog used to evaluate presynaptic dopaminergic neuronal function. Evaluation of tumor recurrence in neurooncology is another application. Here, the kinetics of 18 F-FDOPA in brain tumors were investigated. Methods: A total of 37 patients underwent 45 studies; 10 had grade IV, 10 had grade III, and 13 had grade II brain tumors; 2 had metastases; and 2 had benign lesions. After 18 F-DOPA was administered at 1.5-5 MBq/kg, dynamic PET images were acquired for 75 min. Images were reconstructed with iterative algorithms, and corrections for attenuation and scatter were applied. Images representing venous structures, the striatum, and tumors were generated with factor analysis, and from these, input and output functions were derived with simple threshold techniques. Compartmental modeling was applied to estimate rate constants. Results: A 2-compartment model was able to describe 18 F-FDOPA kinetics in tumors and the cerebellum but not the striatum. A 3-compartment model with corrections for tissue blood volume, metabolites, and partial volume appeared to be superior for describing 18 F-FDOPA kinetics in tumors and the striatum. A significant correlation was found between influx rate constant K and late uptake (standardized uptake value from 65 to 75 min), whereas the correlation of K with early uptake was weak. High-grade tumors had significantly higher transport rate constant k 1 , equilibrium distribution volumes, and influx rate constant K than did low-grade tumors (P , 0.01). Tumor uptake showed a maximum at about 15 min, whereas the striatum typically showed a plateau-shaped curve. Patlak graphical analysis did not provide accurate parameter estimates. Logan graphical analysis yielded reliable estimates of the distribution volume and could separate newly diagnosed high-grade tumors from low-grade tumors. Conclusion: A 2-compartment model was able to describe 18 F-FDOPA kinetics in tumors in a first approximation. A 3-compartment model with corrections for metabolites and partial volume could adequately describe 18 F-FDOPA kinetics in tumors, the striatum, and the cerebellum. This model suggests that 18 F-FDOPA was transported but not trapped in tumors, unlike in the striatum. The shape of the uptake curve appeared to be related to tumor grade. After an early maximum, high-grade tumors had a steep descending branch, whereas low-grade tumors had a slowly declining curve, like that for the cerebellum but on a higher scale.

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Modelling approach for separating blood time activity curves in positron emission tomographic studies

Cited by 38 publications

References 11 publications

Rapid Quantitative Measurement of CMRO₂ and CBF by Dual Administration of ¹⁵O-Labeled Oxygen and Water During a Single PET Scan—a Validation Study and Error Analysis in Anesthetized Monkeys

Rapid Quantitative Measurement of CMRO₂ and CBF by Dual Administration of ¹⁵O-Labeled Oxygen and Water During a Single PET Scan—a Validation Study and Error Analysis in Anesthetized Monkeys

Quantification of Amphetamine-Induced Changes in [¹¹C]Raclopride Binding with Continuous Infusion

18F-FDOPA Kinetics in Brain Tumors

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Modelling approach for separating blood time activity curves in positron emission tomographic studies

Cited by 38 publications

References 11 publications

Rapid Quantitative Measurement of CMRO2 and CBF by Dual Administration of 15O-Labeled Oxygen and Water During a Single PET Scan—a Validation Study and Error Analysis in Anesthetized Monkeys

Rapid Quantitative Measurement of CMRO2 and CBF by Dual Administration of 15O-Labeled Oxygen and Water During a Single PET Scan—a Validation Study and Error Analysis in Anesthetized Monkeys

Quantification of Amphetamine-Induced Changes in [11C]Raclopride Binding with Continuous Infusion

18F-FDOPA Kinetics in Brain Tumors

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Rapid Quantitative Measurement of CMRO₂ and CBF by Dual Administration of ¹⁵O-Labeled Oxygen and Water During a Single PET Scan—a Validation Study and Error Analysis in Anesthetized Monkeys

Rapid Quantitative Measurement of CMRO₂ and CBF by Dual Administration of ¹⁵O-Labeled Oxygen and Water During a Single PET Scan—a Validation Study and Error Analysis in Anesthetized Monkeys

Quantification of Amphetamine-Induced Changes in [¹¹C]Raclopride Binding with Continuous Infusion