Fractional calculus tracer kinetic compartment model for quantification of microvascular perfusion

2021 ◽  
Author(s):  
Stefan Hindel ◽  
Lena Heuchel ◽  
Lutz Lüdemann
Keyword(s):  
Fractional Calculus ◽  
Compartment Model ◽  
Microvascular Perfusion ◽  
Tracer Kinetic

scholarly journals Tracer-Kinetic Models for Measuring Cerebral Blood Flow Using Externally Detected Radiotracers

1987 ◽  
Vol 7 (4) ◽  
pp. 443-463 ◽  
Author(s):  
Kenneth B. Larson ◽  
Joanne Markham ◽  
Marcus E. Raichle
Keyword(s):  
Kinetic Models ◽  
Counting Rate ◽  
Compartment Model ◽  
Distributed Parameter ◽  
High Temporal Resolution ◽  
Yield Model ◽  
Residue Detection ◽  
Positron Emission ◽  
Tracer Kinetic ◽  
Tissue Systems

All tracer-kinetic models currently employed with positron-emission tomography (PET) are based on compartmental assumptions. Our first indication that a compartmental model might suffer from severe limitations in certain circumstances when used with PET occurred when we implemented the Kety tissue-autoradiography technique for measuring CBF and observed that the resulting CBF estimates, rather than remaining constant (to within predictable statistical uncertainty) as expected, fell with increasing scan duration T when T > 1 min. After ruling out other explanations, we concluded that a one-compartment model does not possess sufficient realism for adequately describing the movement of labeled water in brain. This article recounts our search for more realistic substitute models. We give our derivations and results for the residue-detection impulse responses for unit capillary-tissue systems of our two candidate distributed-parameter models. In a sequence of trials beginning with the simplest, we tested four progressively more detailed candidate models against data from appropriate residue-detection experiments. In these, we generated high-temporal-resolution counting-rate data reflecting the history of radiolabeled-water uptake and washout in the brains of rhesus monkeys. We describe our treatment of the data to yield model-independent empirical values of CBF and of other parameters. By substituting these into our trial-model functions, we were able to make direct comparisons of the model predictions with the experimental dynamic counting-rate histories, confirming that our reservations concerning the one-compartment model were well founded and obliging us to reject two others. We conclude that a two-barrier distributed-parameter has the potential of serving as a substitute for the Kety model in PET measurements of CBF in patients, especially when scan durations for T > 1 min are desired.

scholarly journals Differentiation of Radioligand Delivery and Binding in the Brain: Validation of a Two-Compartment Model for [11C]Flumazenil

1991 ◽  
Vol 11 (5) ◽  
pp. 745-752 ◽  
Author(s):  
Vjera A. Holthoff ◽  
Robert A. Koeppe ◽  
Kirk A. Frey ◽  
Avram H. Paradise ◽  
David E. Kuhl
Keyword(s):  
Benzodiazepine Receptor ◽  
Occipital Cortex ◽  
Compartment Model ◽  
Stable Measure ◽  
Intravenous Injections ◽  
Audiovisual Stimulation ◽  
Positron Emission ◽  
Two Compartment Model ◽  
Tracer Kinetic

We recently developed a two-compartment, two-parameter tracer kinetic model to estimate the in vivo ligand transport rate ( K1) and distribution volume (DV) for the benzodiazepine antagonist [11C]flumazenil (FMZ) as measured by positron emission tomography (PET). The aim of the present study was to validate that this simplified model provides a stable measure of regional benzodiazepine receptor availability even when ligand delivery is altered. Six young normal volunteers underwent two PET studies subsequent to intravenous injections of [11C]FMZ. Each FMZ study was immediately preceded by measurements of CBF following injection of [15O]water. One set of scans (water/FMZ) was acquired under resting conditions and the other set during audiovisual stimulation. Six additional volunteers underwent two FMZ studies under identical resting conditions. Parametric images were analyzed and a comparison of test-retest studies in the stimulation group revealed a significant increase of CBF and K1 of FMZ in the occipital cortex evoked by visual activation, whereas no regional changes were noted for the DV of FMZ. No significant changes were noted for either K1 or DV of FMZ when comparing studies in the rest-rest setting. The results indicate that the use of a simple two-compartment model for the tracer kinetic analysis of [11C]FMZ makes it possible to separate high-affinity binding from altered radioligand delivery to the human brain.

scholarly journals Development of a Tracer Kinetic Plasma Input Model for (R)-[11C]PK11195 Brain Studies

2005 ◽  
Vol 25 (7) ◽  
pp. 842-851 ◽  
Author(s):  
Marc A Kropholler ◽  
Ronald Boellaard ◽  
Alie Schuitemaker ◽  
Bart NM van Berckel ◽  
Gert Luurtsema ◽  
...  
Keyword(s):  
Monte Carlo ◽  
Monte Carlo Simulations ◽  
Benzodiazepine Receptor ◽  
Compartment Model ◽  
Input Function ◽  
Volume Of Distribution ◽  
Binding Potential ◽  
Arterial Blood ◽  
Tracer Kinetic ◽  
Input Model

(R)-[11C]PK11195 ([1-(2-chlorophenyl)- N-methyl- N-(1-methylpropyl]-3-isoquinoline carboxamide) is a ligand for the peripheral benzodiazepine receptor, which, in the brain, is mainly expressed on activated microglia. Using both clinical studies and Monte Carlo simulations, the aim of this study was to determine which tracer kinetic plasma input model best describes (R)-[11C]PK11195 kinetics. Dynamic positron emission tomography (PET) scans were performed on 13 subjects while radioactivity in arterial blood was monitored online. Discrete blood samples were taken to generate a metabolite corrected plasma input function. One-tissue, two-tissue irreversible, and two-tissue reversible compartment models, with and without fixing K1/ k2 ratio, k4 or blood volume to whole cortex values, were fitted to the data. The effects of fixing parameters to incorrect values were investigated by varying them over a physiologic range and determining accuracy and reproducibility of binding potential and volume of distribution using Monte Carlo simulations. Clinical data showed that a two-tissue reversible compartment model was optimal for analyzing (R)-[11C]PK11195 PET brain studies. Simulations showed that fixing the K1/ k2 ratio of this model provided the optimal trade-off between accuracy and reproducibility. It was concluded that a two-tissue reversible compartment model with K1/ k2 fixed to whole cortex value is optimal for analyzing (R)-[11C]PK11195 PET brain studies.

scholarly journals Head-to-head comparison of (R)-[11C]verapamil and [18F]MC225 in non-human primates, tracers for measuring P-glycoprotein function

2021 ◽  
Author(s):  
Lara García-Varela ◽  
David Vállez García ◽  
Pablo Aguiar ◽  
Takeharu Kakiuchi ◽  
Hiroyuki Ohba ◽  
...  
Keyword(s):  
Regional Differences ◽  
Compartment Model ◽  
Input Function ◽  
Positive Slope ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Tracer Kinetic ◽  
Best Parameter ◽  
Pet Scans

Abstract Purpose P-glycoprotein (P-gp) function is altered in several brain disorders; thus, it is of interest to monitor the P-gp function in vivo using PET. (R)-[11C]verapamil is considered the gold standard tracer to measure the P-gp function; however, it presents some drawbacks that limit its use. New P-gp tracers have been developed with improved properties, such as [18F]MC225. This study compares the characteristics of (R)-[11C]verapamil and [18F]MC225 in the same subjects. Methods Three non-human primates underwent 4 PET scans: 2 with (R)-[11C]verapamil and 2 with [18F]MC225, at baseline and after P-gp inhibition. The 30-min PET data were analyzed using 1-Tissue Compartment Model (1-TCM) and metabolite-corrected plasma as input function. Tracer kinetic parameters at baseline and after inhibition were compared. Regional differences and simplified methods to quantify the P-gp function were also assessed. Results At baseline, [18F]MC225 VT values were higher, and k2 values were lower than those of (R)-[11C]verapamil, whereas K1 values were not significantly different. After inhibition, VT values of the 2 tracers were similar; however, (R)-[11C]verapamil K1 and k2 values were higher than those of [18F]MC225. Significant regional differences between tracers were found at baseline, which disappeared after inhibition. The positive slope of the SUV-TAC was positively correlated to the K1 and VT of both tracers. Conclusion [18F]MC225 and (R)-[11C]verapamil show comparable sensitivity to measure the P-gp function in non-human primates. Moreover, this study highlights the 30-min VT as the best parameter to measure decreases in the P-gp function with both tracers. [18F]MC225 may become the first radiofluorinated tracer able to measure decreases and increases in the P-gp function due to its higher baseline VT.

scholarly journals A Comparative Study of Two-Compartment Exchange Models for Dynamic Contrast-Enhanced MRI in Characterizing Uterine Cervical Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Xue Wang ◽  
Wenxiao Lin ◽  
Yiting Mao ◽  
Wenwen Peng ◽  
Jiao Song ◽  
...  
Keyword(s):  
Compartment Model ◽  
Cervix Cancer ◽  
Tissue Blood Flow ◽  
Distributed Parameter ◽  
Cervix Carcinoma ◽  
Dynamic Contrast Enhanced ◽  
Two Compartment Model ◽  
Contrast Enhanced ◽  
Tracer Kinetic ◽  
Highly Correlated

A variety of tracer kinetic methods have been employed to assess tumor angiogenesis. The Standard two-Compartment model (SC) used in cervix carcinoma was less frequent, and Adiabatic Approximation to the Tissue Homogeneity (AATH) and Distributed Parameter (DP) model are lacking. This study compares two-compartment exchange models (2CXM) (AATH, SC, and DP) for determining dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters in cervical cancer, with the aim of investigating the potential of various parameters derived from 2CXM for tumor diagnosis and exploring the possible relationship between these parameters in patients with cervix cancer. Parameters (tissue blood flow, Fp; tissue blood volume, Vp; interstitial volume, Ve; and vascular permeability, PS) for regions of interest (ROI) of cervix lesions and normal cervix tissue were estimated by AATH, SC, and DP models in 36 patients with cervix cancer and 17 healthy subjects. All parameters showed significant differences between lesions and normal tissue with a P value less than 0.05, except for PS from the AATH model, Fp from the SC model, and Vp from the DP model. Parameter Ve from the AATH model had the largest AUC (r = 0.85). Parameters Fp and Vp from SC and DP models and Ve and PS from AATH and DP models were highly correlated, respectively, (r > 0.8) in cervix lesions. Cervix cancer was found to have a very unusual microcirculation pattern, with over-growth of cancer cells but without evident development of angiogenesis. Ve has the best performance in identifying cervix cancer. Most physiological parameters derived from AATH, SC, and DP models are linearly correlated in cervix cancer.

Disposal and distribution of rT3 in humans: a new double-tracer kinetic study

1993 ◽  
Vol 264 (2) ◽  
pp. E239-E249 ◽  
Author(s):  
A. Pilo ◽  
G. Iervasi ◽  
F. Vitek ◽  
S. Turchi ◽  
R. Bianchi
Keyword(s):  
Experimental Data ◽  
Compartment Model ◽  
Normal Subjects ◽  
Peripheral Tissues ◽  
Experimental Base ◽  
Tracer Kinetic ◽  
Disappearance Curve ◽  
Definition Of ◽  
Plasma Disappearance Curve

A satisfactory definition of reverse 3,3',5'-triiodothyronine (rT3) kinetics in humans cannot be obtained if the plasma disappearance curve of the injected labeled hormone is the only experimental data available; most of the kinetic parameters can only be bounded within ranges showing unacceptable variabilities. To gain additional experimental data a double-tracer approach is proposed. After simultaneous injection of [125I]rT3 and 131I the following three experimental curves were determined in plasma: 1) the disappearance of [125I]rT3, 2) the disappearance of 131I, and 3) the appearance of 125I generated in vivo from labeled rT3 degradation. Combined analysis of these three curves, based on a complex six-compartment model, was developed and applied to data obtained in a group of normal subjects. Through this new analysis, fractional disposal rates and fractional exchange rates between the plasma compartment and the periphery are uniquely determined. The main physiologically interesting information on the degradation of the hormone that emerges from these studies are 1) all degradative pathways of rT3 generate iodide, being in all cases the [125I]rT3 dose completely recovered as 125I in plasma; and 2) most rT3 is degraded (65–90%) in peripheral tissues rapidly exchanging with the plasma pool. The extended experimental base is not yet sufficient to compute unique values for production rate (PR) and body mass (Qt); the validity of estimates of PR and Qt is based on the assumption that injected [125I]rT3 is able to trace all rT3 peripherally produced (from thyroxine). The new approach yields ranges for PR and Qt (1.12–2.15 micrograms/h and 2.88–8.24 micrograms) much narrower than those computable from the [125I]rT3 disappearance curve only (1.12–5.07 micrograms/h for PR and 2.88-23.7 micrograms for Qt).

Influence of stable iodine on the uptake of the thyroid – model vs. experiment

2001 ◽  
Vol 40 (01) ◽  
pp. 31-37 ◽  
Author(s):  
U. Wellner ◽  
E. Voth ◽  
H. Schicha ◽  
K. Weber
Keyword(s):  
Time Course ◽  
Compartment Model ◽  
The Body ◽  
Iodine Uptake ◽  
Model Calculations ◽  
Physiological Conditions ◽  
Iodine Supply ◽  
Predicted Values ◽  
The Individual ◽  
Stable Iodine

Summary Aim: The influence of physiological and pharmacological amounts of iodine on the uptake of radioiodine in the thyroid was examined in a 4-compartment model. This model allows equations to be derived describing the distribution of tracer iodine as a function of time. The aim of the study was to compare the predictions of the model with experimental data. Methods: Five euthyroid persons received stable iodine (200 μg, 10 mg). 1-123-uptake into the thyroid was measured with the Nal (Tl)-detector of a body counter under physiological conditions and after application of each dose of additional iodine. Actual measurements and predicted values were compared, taking into account the individual iodine supply as estimated from the thyroid uptake under physiological conditions and data from the literature. Results: Thyroid iodine uptake decreased from 80% under physiological conditions to 50% in individuals with very low iodine supply (15 μg/d) (n = 2). The uptake calculated from the model was 36%. Iodine uptake into the thyroid did not decrease in individuals with typical iodine supply, i.e. for Cologne 65-85 μg/d (n = 3). After application of 10 mg of stable iodine, uptake into the thyroid decreased in all individuals to about 5%, in accordance with the model calculations. Conclusion: Comparison of theoretical predictions with the measured values demonstrated that the model tested is well suited for describing the time course of iodine distribution and uptake within the body. It can now be used to study aspects of iodine metabolism relevant to the pharmacological administration of iodine which cannot be investigated experimentally in humans for ethical and technical reasons.

An approach for comparative quantification of myocardial blood flow (0-15-H2O-PET), perfusion (Tc-99m-tetrofosmin-SPECT), and metabolism (F 18-FDG-PET)

2001 ◽  
Vol 40 (05) ◽  
pp. 164-171 ◽  
Author(s):  
B. Nowak ◽  
H.-J. Kaiser ◽  
S. Block ◽  
K.-C. Koch ◽  
J. vom Dahl ◽  
...  
Keyword(s):  
Blood Flow ◽  
Myocardial Blood Flow ◽  
Fdg Pet ◽  
Model Fitting ◽  
Compartment Model ◽  
Left Ventricular ◽  
Short Axis ◽  
New Approach ◽  
Single Compartment Model ◽  
Tissue Fraction

Summary Aim: In the present study a new approach has been developed for comparative quantification of absolute myocardial blood flow (MBF), myocardial perfusion, and myocardial metabolism in short-axis slices. Methods: 42 patients with severe CAD, referred for myocardial viability diagnostics, were studied consecutively with 0-15-H2O PET (H2O-PET) (twice), Tc-99m-Tetrofosmin 5PECT (TT-SPECT) and F-18-FDG PET (FDG-PET). All dato sets were reconstructed using attenuation correction and reoriented into short axis slices. Each heart was divided into three representative slices (base, rnidventricular, apex) and 18 ROIs were defined on the FDG PET images and transferred to the corresponding H2O-PET and TT-SPECT slices. TT-SPECT and FDG-PET data were normalized to the ROI showing maximum perfusion. MBF was calculated for all left-ventricular ROIs using a single-compartment-model fitting the dynamic H2O-PET studies. Microsphere equivalent MBF (MBF_micr) was calculated by multiplying MBF and tissue-fraction, a parameter which was obtained by fitting the dynamic H2O-PET studies. To reduce influence of viability only well perfused areas (>70% TT-SPECT) were used for comparative quantification. Results: First and second mean global MBF values were 0.85 ml × min-1 × g-1 and 0.84 ml × min-1 × g1, respectively, with a repeatability coefficient of 0.30 ml ÷ min-1 × gl. After sectorization mean MBF_micr was between 0.58 ml × min1 ÷ ml"1 and 0.68 ml × min-1 × ml"1 in well perfused areas. Corresponding TT-SPECT values ranged from 83 % to 91 %, and FDG-PET values from 91 % to 103%. All procedures yielded higher values for the lateral than the septal regions. Conclusion: Comparative quantification of MBF, MBF_micr, TT-SPECT perfusion and FDG-PET metabolism can be done with the introduced method in short axis slices. The obtained values agree well with experimentally validated values of MBF and MBF_micr.

Pharmacokinetics and Effects on Fibrinolytic and Coagulation Parameters of Two Doses of Recombinant Tissue-Type Plasminogen Activator in Healthy Volunteers

1986 ◽  
Vol 56 (01) ◽  
pp. 001-005 ◽  
Author(s):  
M Verstraete ◽  
C A P F Su ◽  
P Tanswell ◽  
W Feuerer ◽  
D Collen
Keyword(s):  
Healthy Volunteers ◽  
Plasminogen Activator ◽  
Degradation Products ◽  
Plasma Concentrations ◽  
State Level ◽  
Compartment Model ◽  
Tissue Type ◽  
Maximum Plasma ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator

SummaryPharmacokinetics and pharmacological effects of two intravenous doses of recombinant tissue-type plasminogen activator (rt-PA) (40 and 60 mg over 90 min) were determined in healthy volunteers. Mean maximum plasma concentrations were 1080 and 1560 ng/ml respectively. The steady state level during subsequent maintenance infusion of 30 mg over 6 h was 250 ng/ml. The pharmacokinetics of rt-PA showed a bi-exponential disappearance from plasma consistent with a 2-compartment model of t½α = 5.7 min, a t½β = 1.3 h and a total clearance of 380 ml/min.Mean fibrinogen levels at the end of the infusions of 40 mg or 60 mg rt-PA over 90 min, measured in thawed plasma samples collected on citrate/aprotinin, decreased to 74% and 57% of the preinfusion values respectively. Plasminogen fell to 55% and 48%, and α2-antiplasmin to 28% and 18% of initial values. No further decrease of these parameters was observed during the infusion of 30 mg rt-PA over 6 h. Only 2% of the preinfusion fibrinogen levels could be recovered as fibrinogen-fibrin degradation products. This moderate extent of systemic fibrinogenolysis is much less than that reported for therapeutic i.v. infusions of streptokinase.

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