Local Cerebral Metabolic Rates For Glucose Research Articles

Using the rPatlak plot and dynamic FDG-PET to generate parametric images of relative local cerebral metabolic rate of glucose

Local cerebral metabolic rate of glucose (LCMRGlc) is an important index for the description of neural function. Dynamic 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) has been used for quantitative imaging of LCMRGlc in humans, but is seldom used routinely because of the difficulty in obtaining the input function noninvasively. A reference tissue-based Patlak plot model (rPatlak) was proposed to generate parametric images of LCMRGlc in a quantitative dynamic FDG-PET study without requiring blood sampling. Dynamic emission scans (4×0.5, 4×2 and 10×5 min) were acquired simultaneously with an IV bolus injection of 155 MBq of FDG. Arterial blood samples were collected during the scans via a catheter placed in the radial artery. Simulation data were also generated using the same scan sequence. The last ten scan data sets were used in a graphical analysis using the Patlak plot. The ratio of LCMRGlc estimated from the original Patlak (oPatlak, using plasma input) was used as the gold standard, and the standardized uptake value ratio (SUVR) was also calculated for comparison. Eight different tissues including white matter, gray matter, and whole brain were chosen as reference tissues for evaluation. Regardless of the reference region used, the slopes in the linear regression between oPatlak and rPatlak were closer to unity than the regression slopes between oPatlak and SUVR. The intercepts for the former were also closer to 0 than those for the latter case. The squared correlation coefficients were close to 1.0 for both cases. This showed that the results of rPatlak were in good agreement with those of oPatlak, however, SUVR exhibited more deviation. The simulation study also showed that the relative variance and bias for rPatlak were less than those for SUVR. The images obtained with rPatlak were very similar to those obtained with oPatlak, while there were differences in the relative spatial distribution between the images of SUVR and oPatlak. This study validates that the rPatlak method is better than the SUVR method and is a good approximation to the oPatlak method. The new method is suitable for generating LCMRGlc parametric images noninvasively.

Whiskers Area as Extracerebral Reference Tissue for Quantification of Rat Brain Metabolism Using 18F-FDG PET: Application to Focal Cerebral Ischemia

Diseases and dysfunction of the central nervous system are often associated with regional changes in cerebral glucose metabolism, which can be measured in vivo by PET using (18)F-FDG as the tracer. For quantification, the arterial tracer input function must be determined. For rodents in particular, direct measurement of blood radioactivity concentration is scarcely feasible for follow-up of individual animals because of the invasiveness of blood sampling. We show that the whiskers area of the rat's muzzle serves as an extracerebral reference region. The derived model also takes into account local variations of the lumped constant, which is crucial in pathologic tissue. In 11 rats, the reference tissue kinetic parameters were determined from PET data and measured whole blood radioactivity concentration. Parametric images of cerebral kinetic rate constants were calculated using the directly measured input function, the reference tissue time-activity curve with individually fitted reference kinetic parameters, and the reference time-activity curve with fixed reference kinetic parameters calculated from the fitted parameters averaged over all animals. The need for kinetic modeling in disease models is demonstrated in 5 rats subjected to acute focal cerebral ischemia. (18)F-FDG metabolism and transport rate constants and local cerebral glucose metabolic rates were calculated. Cerebral kinetic constants derived from the 3 methods corresponded closely. The maximum difference in whole-brain kinetic parameters observed between the directly measured input function and the reference tissue time-activity curve with individually fitted reference kinetic parameters was less than 5%. Taking fixed reference parameters (the reference time-activity curve with fixed reference kinetic parameters calculated from the fitted parameters averaged over all animals) still provided whole-brain kinetic parameters with an accuracy of approximately 90%. In the rats subjected to focal cerebral ischemia, (18)F-FDG kinetic parameters in healthy tissue were not significantly different from whole-brain kinetic parameters in naive rats. The ischemic region was characterized by preserved glucose metabolism, although (18)F-FDG uptake was elevated significantly-that is, the lumped constant in the ischemic region was different from that of healthy brain tissue. The method presented here allows for the quantitative noninvasive determination of cerebral glucose consumption in rats, takes into account local variations of the lumped constant, and is suitable for follow-up measurements of individuals.

Treatment for Late-Onset Obsessive-Compulsive Disorder with Parkinsonism

Treatment for Late-Onset Obsessive-Compulsive Disorder with Parkinsonism

Noninvasive Quantification of Local Cerebral Metabolic Rate of Glucose for Clinical Application Using Positron Emission Tomography and 18F-Fluoro-2-Deoxy-d-Glucose

Until now, input function is still required in quantification of local cerebral metabolic rate of glucose (LCMRGlc) using positron emission tomography (PET) and (18)F-fluoro-2-deoxy-D-glucose (FDG). Some image-derived methods were developed to get input function noninvasively instead of the arterial blood sampling method, but they needed to make complicated corrections manually, so they cannot always be applied in clinic directly. Here, we propose a simple method based on the Patlak approach by using a reference tissue region and without using any information of input function. This simulation study revealed that the present method was in good agreement with Patlak method; the difference between two methods was less than 5%. The statistical errors with two methods were also obtained, and the results showed the accuracy of LCMRGlc estimated with present method was better than that with Patlak method slightly. The simulation results indicated that the calculation of LCMRGlc with present method was quite stable and independent of the choosing of reference tissue region. All of these show that the present method is a good approximation to Patlak method. The calculation with this method is very simple and easy to perform voxel by voxel; therefore, it can be widely used not only in laboratory studies but also in clinical applications although it only provides the relative rates.

Reduced Cerebral Blood Flow but Elevated Cerebral Glucose Metabolic Rate in Erythropoietin Overexpressing Transgenic Mice with Excessive Erythrocytosis

To examine the impact of excessive erythrocytosis on local cerebral blood flow (CBF) and cerebral glucose metabolic rate (CMR(glc)), we made use of our constitutively erythropoietin (Epo)-overexpressing transgenic mouse line (tg-6) that reach a mean hematocrit of 0.87. Compared with wild-type (wt) control siblings, CBF decreased by 44% in tg-6 mice, while upon hemodilution (tg-6-HD) to a physiologic hematocrit (e.g., 0.44) tg-6-HD mice returned the CBF to wt levels. Cerebral blood flow was determined in another transgenic mouse line that overexpresses human Epo in the brain only (tg-21): CBF increased by 17% compared with wt controls. However, oxygen delivery was similar in all four mouse groups tested (wt, tg-6, tg-6-HD and tg-21). Mean CMR(glc) was higher in tg-6 (+72%), tg-6-HD mice (+43%) and tg-21 (+22%) than in wt mice. Local CMR(glc) was higher in all 40 brain regions in tg-6 but only in 15 and 8 regions in tg-6-HD and tg-21 mice. These results show that prolonged increases in hematocrit did not alter cerebral oxygen delivery at a decreased CBF and increased CMR(glc). Hemodilution suggests that high blood viscosity is a cause of the decrease in CBF and partly of the increase in CMR(glc). Cerebral glucose metabolic rate may also be increased by a direct effect of Epo in the brain (tg-21 mice).

Nimodipine does not affect the flow-metabolism couple in permanent cerebral ischemia.

Despite widespread investigational and clinical usage of the calcium channel blocker nimodipine, its effects on cerebral physiology in normal and ischemic brain remain poorly understood. In order to gain insight into this subject we examined the effects of nimodipine on glucose metabolism and cerebral blood flow-metabolism coupling in the rat during conditions of reproducible focal ischemia. Nimodipine-treated animals were then matched with vehicle-treated controls for both study conditions. Animals were subjected to permanent occlusion of the middle cerebral artery (MCA) along with occlusion of the common carotid arteries. Five minutes into ischemia, an intravenous infusion of nimodipine (1 micro g/kg per min, n=9) or vehicle ( n=9) was initiated and continued until the end of the study. Seventy-five minutes after the occlusion, [14C]2-deoxyglucose was injected into the venous catheter for the measurement of the local cerebral metabolic rate for glucose (LCMRgl), followed 25 min later by the injection of N-isopropyl-[123I] p-iodoamphetamine for the measurement of local cerebral blood flow (LCBF). The animals were killed at the end of 2 h of ischemia, and the brains were processed for double-labeled autoradiography. In all animals, permanent MCA occlusion produced significant decrements in LCBF, LCMRgl, and LCBF/LCMRgl ratio in both the core of the ischemia as well as regions peripheral to the ischemia within the same cerebral hemisphere when compared with non-ischemic brain. There were no significant differences between the nimodipine-treated and vehicle-treated groups. In conclusion, nimodipine does not appear to alter cerebral blood flow or cerebral metabolism in ischemic brain.

Cytopathology, Abstract 293–298, Study Group

McGeer, Patrick L., Edith G. McGeer, Hisaki Kamo and Kathy Wong: Positron emission tomography and the possible origins of cytopathology in Alzheimer's disease. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1986, 10 (3–5): 501–518. 1.1. The local cerebral metabolic rate for glucose (LCMRgl), as determined by positron emission tomography (PET), declines in the cerebral cortex in Alzheimer's disease; the severity of the decline parallels the severity of the dementia and correlates with regional cortical neuronal loss and glial proliferation.2.2. The cholinergic cells of the medial basal forebrain show a pathological dropout in Alzheimer's disease which accounts for the decline in choline acetyltransferase in the cerebral cortex and hippocampus.3.3. It is proposed that these cholinergic cells serve both as an acquisition and readout device for memory; reconstruction of real time events can thus be created in the areas of neocortex where consciousness resides.4.4. Alzheimer's disease may have a toxic, genetic or infectious origin; electron microscopic evidence is presented for the possible presence of viral particles of the double stranded DNA type in Alzheimer's brain tissue.

Dr. Wu and Colleagues Reply

Back to table of contents Previous article Next article Letter to the EditorFull AccessDr. Wu and Colleagues ReplyJOSEPH C. WU, M.D., J. CHRISTIAN GILLIN, M.D., MONTE S. BUCHSBAUM, M.D., and WILLIAM E. BUNNEY JR., M.D., JOSEPH C. WUSearch for more papers by this author, M.D., J. CHRISTIAN GILLINSearch for more papers by this author, M.D., MONTE S. BUCHSBAUMSearch for more papers by this author, M.D., and WILLIAM E. BUNNEY JR.Search for more papers by this author, M.D., Irvine, Calif.Published Online:1 Oct 2000https://doi.org/10.1176/appi.ajp.157.10.1704-bAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: We appreciate the suggestion that 1) “a deficient adenosinergic inhibitory tone” at baseline accounts for the higher local metabolic rates in responders than in nonresponders and comparison subjects and 2) “increases in extracellular adenosine” account for the reduced metabolic rates observed in responders after sleep deprivation. Whether this interesting adenosine hypothesis will weather the tests of time remains to be seen.If adenosine inhibits the local cerebral glucose metabolic rate, then the present patterns of relative local cerebral glucose metabolic rates could possibly fit a model of 1) loss of adenosinergic tone at baseline in depressed responders or 2) augmentation of adenosinergic function with sleep deprivation in responders. However, insofar as the administration of caffeine mimics “deficient adenosinergic inhibitory tone,” its effects on functional brain imaging are complex and not necessarily consistent with the baseline patterns of local cerebral glucose metabolic rates in responders and nonresponders to sleep deprivation. Caffeine increases the local cerebral glucose metabolic rate throughout the brain but decreases cerebral blood flow at the same time, inducing a relative brain hypoperfusion (1–3). Administration of caffeine to normal volunteers does reduce slow-wave activity during non-REM sleep and prolongs sleep latency (4), both of which are characteristic of the sleep of depressed patients, suggesting that some depressed patients might have deficient adenosinergic tone.In addition, adenosine is only one of many proposed “endogenous sleep-promoting substances,” including prostaglandin D2, interleukin-1, or muramyl peptides, which may accumulate during sleep deprivation and promote sleep (5–7). Any of these other substances could also theoretically act in the fashion proposed for adenosine.We welcome speculation about the mechanisms of the antidepressant effects of sleep deprivation, particularly neurochemical changes or gene expression, which may lead to new antidepressant medications. Sleep deprivation is one of the easiest and most well-documented experimental antidepressant treatments known.

Oral18F-fluoro-2-deoxyglucose for primate PET studies without behavioral restraint: Demonstration of principle

We describe a method of orally administering 18F-fluoro-2-deoxyglucose (FDG) for positron emission tomography (PET) scans to determine local cerebral metabolic rates for glucose (LCMRGlc), normalized to that of whole brain, in fully conscious, non-restrained primates. Oral FDG-PET studies were performed in both non-restrained and chaired monkeys, and in one human where results could be compared with traditional intravenous FDG administration. The oral route of FDG administration gave images and whole brain-normalized PET LCMRGlc results comparable to those obtained by the intravenous route. This oral FDG-PET method may provide a useful means by which to obtain measures of LCMRGlcs for brain structures, relative to each other, in non-restrained, non-drugged primates in field and laboratory studies. This method might also have clinical applications for PET studies of children.

A technique for extracting physiological parameters and the required input function simultaneously from PET image measurements: theory and simulation study.

Positron emission tomography (PET) is an important tool for enabling quantification of human brain function. However, quantitative studies using tracer kinetic modeling require the measurement of the tracer time-activity curve in plasma (PTAC) as the model input function. It is widely believed that the insertion of arterial lines and the subsequent collection and processing of the biomedical signal sampled from the arterial blood are not compatible with the practice of clinical PET, as it is invasive and exposes personnel to the risks associated with the handling of patient blood and radiation dose. Therefore, it is of interest to develop practical noninvasive measurement techniques for tracer kinetic modeling with PET. In this paper, a technique is proposed to extract the input function together with the physiological parameters from the brain dynamic images alone. The identifiability of this method is tested rigorously by using Monte Carlo simulation. The results show that the proposed method is able to quantify all the required parameters by using the information obtained from two or more regions of interest (ROI's) with very different dynamics in the PET dynamic images. There is no significant improvement in parameter estimation for the local cerebral metabolic rate of glucose (LCMRGlc) if the number of ROI's are more than three. The proposed method can provide very reliable estimation of LCMRGlc, which is our primary interest in this study.

Optimal image sampling schedule: a new effective way to reduce dynamic image storage space and functional image processing time

An optimal image sampling schedule for tracer dynamic studies with positron emission tomography (PET) is proposed. This schedule incorporates the characteristics of PET measurement and uses a new cost function and the D-optimal criterion. A detailed case study of the estimation of the local cerebral metabolic rate of glucose (LCMRGLc) using the tracer fluorodeoxyglucose (FDG) and the four-parameter FDG model is presented. As the sampling schedule designed requires only four dynamic images, the storage space and data processing time are greatly reduced, while the precision of the parameter estimates is almost the same as that achieved with a commonly used schedule. The effects of intersubject and intrasubject parameter variations on parameter estimation with the use of this optimal sampling schedule are investigated by computer simulation. The simulation results show that the estimation of parameters is sufficiently robust with respect to these intersubject and intrasubject variations. The optimal sampling schedule is quite suitable therefore for PET regional parameter estimation, as well as for image-wide parameter estimation, for different subjects.

Cerebral metabolic rate for glucose during the first six months of life: an FDG positron emission tomography study.

To measure the local cerebral metabolic rate for glucose (LCMRGlc) in neonatal brains during maturation using positron emission tomography (PET) and 2-[18F]fluoro-2-deoxy-D-glucose (FDG). Twenty infants were studied using PET during the neonatal period. The postconceptional age ranged from 32.7 to 60.3 weeks. All infants had normal neurodevelopment and were normoglycaemic. The development of the infants was carefully evaluated (follow up 12-36 months) clinically, and by using a method based on Gesell Amatruda's developmental diagnosis. LCMRGlc was quantitated using PET derived from FDG kinetics and calculated in the whole brain and for regional brain structures. LCMRGlc for various cortical brain regions and the basal ganglia was low at birth (from 4 to 16 mumol/100 g/minute). In infants 2 months of age and younger LCMRGlc was highest in the sensorimotor cortex, thalamus, and brain stem. By 5 months, LCMRGlc had increased in the frontal, parietal, temporal, occipital and cerebellar cortical regions. In general, the whole brain LCMRGlc correlated with postconceptional age (r = 0.90; P < 0.001). The change in the glucose metabolic pattern observed in the neonatal brain reflects the functional maturation of these brain regions. These findings show that LCMRGlc in infants increases with maturation. Accordingly, when LCMRGlc is measured during infancy, the postconceptional age has to be taken into account when interpretating the results.

Interictal metabolism and blood flow are uncoupled in temporal lobe cortex of patients with complex partial epilepsy.

We used positron emission tomography (PET) with 18F-2-deoxyglucose (FDG) and 15O water in 20 patients with complex partial seizures to compare glucose metabolism and blood flow in temporal lobe epileptic foci identified by ictal scalp-sphenoidal video-EEG telemetry. Glucose metabolism was measured 20 minutes after blood flow without moving the patient from the scanner. We also studied 11 patients with 99mTc-HMPAO single-photon emission computed tomography (SPECT). Both local cerebral metabolic rate of glucose (LCMRGlc) and regional cerebral blood flow (rCBF) were significantly decreased in temporal cortex ipsilateral to the EEG focus. However, LCMRGlc was reduced by 11.2% in inferior lateral and 11.1% in inferior mesial temporal cortex and rCBF by only 3.2% and 6.1%. The ratio of LCMRGlc to rCBF was significantly reduced in inferior lateral temporal cortex ipsilateral to the ictal focus (p < 0.009). Moreover, using standardized criteria, blinded raters found that 16 of 20 patients had focal FDG-PET hypometabolism, all in the epileptogenic region; 10 of 20 had focal 15O water PET hypoperfusion, but it was falsely lateralized in two of these 10; and five of 11 had focal 99mTc-HMPAO SPECT hypoperfusion, but it was falsely lateralized in two of these five. Our data suggest that interictal glucose metabolism and blood flow may be uncoupled in epileptogenic cortex.

An evaluation of the algorithms for determining local cerebral metabolic rates of glucose using positron emission tomography dynamic data

Measurement of the local cerebral metabolic rate of glucose (LCMRGlc) and the individual rate constant parameters of the [(18 )F]2-fluoro-2-deoxy-D-glucose (FDG) model can provide a clearer understanding and insight to the physiological processes in the human brain, and a quicker and more accurate means of diagnosis in clinical applications. A systematic study using simulated and clinical tissue time activity data is presented to evaluate several existing and newly developed major algorithms used for determining LCMRGlc and the individual rate constants from positron emission tomography dynamic data. The computational and statistical properties of the autoradiographic approach, weighted and unweighted nonlinear least squares methods, Patlak graphic approach, weighted integration method, linear least squares and generalized linear least squares methods are investigated and discussed in this paper.

A computer simulation study on the input function sampling schedules in tracer kinetic modeling with positron emission tomography (PET)

Tracer kinetic modeling with positron emission tomography (PET) requires measurements of the time-activity curves in both plasma (PTAC) and tissue (TTAC) to estimate physiological parameters, i.e. to fit the parameters of certain compartmental models using PTAC and TTAC as the model input and output functions, respectively. In this paper, we first explored the optimal blood sampling schedule (OBSS) for the input function, based on the tracer [ 18F]2-fluoro-2-deoxy- d-glucose (FDG) blood sample experimental data. Then using a 5-parameter FDG model we investigated the effects of the plasma sampling schedule, as well as PTAC measurement noise, on the estimation accuracy and reliability of FDG model macro- and micro-parameters and the physiological parameter local cerebral metabolic rates of glucose (LCMRGlc), using computer simulation. Three different methods were used: (a) estimation of the FDG model parameters ignoring PTAC noise using the traditional PTAC schedule (non-OBSS); (b) estimation of the PTAC model parameters and FDG model parameters simultaneously using both non-OBSS and OBSS; (c) estimation of the PTAC model parameters first, then the FDG model parameters using both non-OBSS and OBSS. The results show that OBSS can provide more reliable estimates and largely simplifies the experiment operations.

Regional Metabolie Dependency in Obstructive Sleep Apnea

Abnormalities of oxygen use occur in obstructive sleep apnea, as do impaired cerebral perfusion and alterations of cerebral function. In this case study, the authors quantitated the local cerebral glucose metabolic rate in two patients with obstructive sleep apnea (one with and one without oxygen supply dependency) and assessed cerebral glucose use by increasing oxygen delivery through passive leg elevation. Obstructive sleep apnea was confirmed by visual analysis of nocturnal pulse oximetry traces in two patients and its severity assessed from the respiratory disturbance index and minimum oxygen saturation. Awake local cerebral glucose metabolic rate (microM/min/100 g) was determined by positron-emission tomography using [18F]-2-Fluoro-2-Deoxy-D-Glucose at baseline and on the following day during passive leg elevation. Conditions otherwise were unchanged. The patient with global oxygen supply dependency exhibited a significant increase in the local cerebral glucose metabolic rate. In contrast, the patient without global supply dependency had no change in the local cerebral glucose metabolic rate. These case studies demonstrate the first evidence of improvement in regional metabolic consumption in response to increased oxygen delivery and in the presence of global oxygen supply dependency.

The central effect of electro-acupuncture analgesia on visceral pain of rats: a study using the [3H] 2-deoxyglucose method.

This study had the objective to understand the central effect of electro-acupuncture analgesia (EAA) on visceral pain of rats. We used the method of Sokoloff's 2-deoxyglucose (2-DG) auto-radiographic quantitative analysis to observe the changes of local cerebral metabolic rate of glucose (LCMRG) in rats given electrical stimulation of greater splanchnic nerve (GSN) followed by electro-acupuncture. From the results of this study, we found that the LCMRG had a significant difference between EAA group and pain group at some structures, such as the spinal thoracic and lumbar dorsal horns (segments T6-T8, L1-L3), locus coeruleus (lc), nucleus raphe magnus (rm), nucleus reticular gigantocellularis (rgi), periaqueductal gray (PAG) and habenulae lateralis (hl) of thalanum. The results combining reports by other investigators, suggest that these local cerebral structures might be the key nuclei in EAA on visceral pain.

Human brain metabolic responses to familiarity during lexical decision

Local cerebral glucose metabolic rate was measured using F18-DG/PET in 11 normal righthanded male volunteers performing two versions of a visual lexical decision task differing only with respect to whether the stimuli were all novel and shown only once, or whether they were all repeated many times. Each subject was also scanned in a resting state (eyes open and ears unplugged). Scalp recordings of cognitive evoked potentials in the same subjects and tasks confirmed that the effects of familiarity were present during the entire 30 min FDG uptake period. The N4 (a left temporoparietal negativity 400 ms after stimulus onset) decreased with repetition, and the P3b (a 600 ms latency parietal positivity) increased. The pattern of metabolic activation was also significantly different between the three experimental conditions. Planned comparisons of the tasks with the resting condition revealed significant relative activations of visual and motor areas. Novel words evoked significantly greater activation in the left and right anterior cingulate gyri and right hippocampal formation than did repeated words in the same task. Relative glucose metabolism in the left angular gyrus was significantly greater to novel words than to resting. Thus, two tasks equated in sensory, motor, and decision processes, but differing in the familiarity of the stimuli, evoke significantly different patterns of brain activation. The patterns observed provided evidence that recent episodic memory for words engages a system that includes the bilateral anterior cingulate gyri, the medial temporal lobe, and the left angular gyrus. © 1994 Wiley-Liss, Inc.

Models for computer simulation studies of input functions for tracer kinetic modeling with positron emission tomography

In tracer kinetic modeling with Positron Emission Tomography (PET), the direct measurement (piecewise linear approximation) of plasma time-activity curve of tracer (PTAC) is often used as the input function to estimate regional physiological parameters. However, no explicit general model is available for PTAC itself, which limits the further study of the effects of PTAC, such as PTAC measurement noise or PTAC sampling schedules, on the physiological parameters estimation. A PTAC model is proposed in this paper and compared with other four possible candidates. Eight sets of [ 18F]-fluoro-2-deoxy- d-glucose (FDG) experimental data were used to test the models and several statistical criteria were used to validate their adequacy. An application of the model to improve the estimation of local cerebral metabolic rate of glucose (LCMRGlc) is presented. This model is also expected to be useful for generating realistic PTAC curves in computer simulation studies of other tracers and their kinetic modeling characteristics.

A computer simulation study on the effects of input function measurement noise in tracer kinetic modeling with positron emission tomography (PET)

Tracer kinetic modeling with positron emission tomography (PET) requires measurements of the time-activity curves in both plasma (PTAC) and tissue (TTAC) to estimate physiological parameters, i.e. to fit the parameters of certain compartmental models using PTAC and TTAC as the model input and output functions, respectively. However, the estimation usually ignores the measurement noise in plasma tracer activity curves. The accuracy and reliability of the physiological parameters estimated by ignoring such noise are not well understood. In this paper, effects of noise in [ 18F] 2-fluoro-2-deoxy- d-glucose (FDG) tracer plasma concentration measurements on estimation of local cerebral metabolic rates of glucose (LCMRGlc) with PET is investigated systematically. The PTAC modeling approach used in this paper also provides a realistic means to filter out the noise and to improve the physiological parameter accuracy, which can be potentially used in model-based non-invasive measurements of PTAC.