Patlak Analysis Research Articles

Inflammation and White Matter Damage in Vascular Cognitive Impairment

Vascular cognitive impairment is a term used to describe a heterogeneous group of diseases, including large vessel disease with strategic single and multiple strokes and small vessel disease with progressive damage to the deep white matter. Identification of patients with the progressive form of vascular cognitive impairment, referred to by some investigators as Binswanger disease, is important for treatment trials. Pathologically, Binswanger disease is associated with small vessel disease, extensive regions of demyelination, inflammatory cells around damaged blood vessels, and lacunar infarcts. Clinically, patients with Binswanger disease have impairments of gait and balance, focal neurological findings, and executive dysfunction on neuropsychological tests. White matter changes on MRI are thought to be due to hypoxic episodes related to hypoperfusion of the vulnerable deep white matter secondary to hypertension, diabetes, and other vessel diseases. Disruption of the blood-brain barrier suggests an inflammatory response. Matrix metalloproteinases are present in the brain of patients with vascular cognitive impairment and can be measured in the cerebrospinal fluid of some patients. Preliminary studies with quantification of the blood-brain barrier, using the multiple time graphical method (Patlak plots), supports disruption of the blood-brain barrier. Because no single clinical feature or diagnostic test is sufficient to identify patients with the small vessel form of vascular cognitive impairment, we propose that a multimodal approach will be needed to select patients for treatment trials.

ISSLS Prize Winner: Positron Emission Tomography and Magnetic Resonance Imaging for Monitoring Interbody Fusion With Equine Bone Protein Extract, Recombinant Human Bone Morphogenetic Protein-2, and Autograft

Prospective and randomized experimental study with anterior lumbar interbody fusion in a porcine model. To assess the early time-course of spinal fusion with equine bone protein extract (COLLOSS E), recombinant human bone morphogenetic protein-2 (rhBMP-2), and autograft using quantitative methods of positron emission tomography (PET)/computed tomography and magnetic resonance imaging (MRI). Different growth and differentiation factors are currently being used for inducing bone formation in spinal fusion. However, the mechanisms and time-course of bone formation using these graft substitutes remain less known. Eighteen female Danish landrace pigs underwent a 3-level anterior lumbar interbody fusion procedure from L3-L6. A PEEK cage, packed with COLLOSS E, rhBMP-2, or autograft, was randomly placed. Each group of 6 pigs was observed for 2, 4, or 8 weeks, respectively. F PET/computed tomography and MRI examinations were performed, and data were correlated with histomorphometry. PET data were analyzed using a Gjedde-Patlak plot. K-values from the plot correspond to the metabolic rate. T2-values were calculated by T2 mapping. rhBMP-2 presented the highest bone formation on histologic sections at 25.6% at 4 weeks after surgery. Eight weeks after surgery, autograft had the highest bone formation with 37.3%, which was significantly higher than rhBMP-2 at 30.5% (P < 0.05), and higher than COLLOSS E at 27.0% (P = 0.06). COLLOSS E and rhBMP-2 had significantly higher K-values than autograft (P < 0.05) at 2 weeks after surgery. There were no differences in K-values between COLLOSS E and autograft at 4 and 8 weeks. However, rhBMP-2 was significantly higher at 4 weeks and lower at 8 weeks than these 2 (P < 0.05). Linear correlation, R = 0.8275, was observed for intertrabecular volume/total volume and T2-values. PET and MRI are valid tools for monitoring the process of interbody fusion in vivo. Osteogenic mechanisms using COLLOSS E resembles that of autograft by the process of endochondral ossification. rhBMP-2 deposits osteoid directly on the collagen network.

Dynamic Contrast-enhanced CT of Head and Neck Tumors: Comparison of First-pass and Permeability Perfusion Measurements Using Two Different Commercially Available Tracer Kinetics Models

To evaluate the interchangeability of perfusion parameters between two software packages for the postprocessing of dynamic contrast-enhanced (DCE) computed tomographic images of head and neck tumors. DCE computed tomographic images of 75 patients with head and neck tumors were postprocessed using a software package based on the maximum-slope approach and Patlak analysis, as well as a software package with deconvolution-based analysis incorporating an adiabatic approximation of tissue homogeneity (ATH) model. The evaluated perfusion parameters included blood flow (F), blood volume (v), and permeability-surface area product (PS). Region-of-interest (ROI) analysis of the tumors and the metastatic lymph nodes was performed. The perfusion parameters were compared using the Wilcoxon matched-pairs test and Bland-Altman plots. One hundred fifty-two ROIs of tumors and nodes were outlined and analyzed. Moderate to good correlations were demonstrated between the various perfusion values (r = 0.56-0.72, P < .0001). The Wilcoxon test revealed a significant difference between the two methods (P < .001), with the F, v, and PS values obtained using the maximum-slope approach and Patlak analysis higher than those obtained using deconvolution-based analysis with the assumptions of the ATH model. The Bland-Altman plots for F and v values revealed a proportionality trend with outliers, which were strongly associated with the magnitudes of the parameters. Analysis of the PS values did not show any systematic bias. There were significant differences in the perfusion parameters obtained using the two software packages, and thus, these parameters are not directly interchangeable.

Determination of glomerular filtration rate in anesthetized pigs by use of three-phase whole-kidney computed tomography and Patlak plot analysis

To develop a whole-kidney computed tomography (CT) technique that would allow 3-point Patlak plot determination of glomular filtration rate (GFR) and assess the correlation of GFR determined via CT (CT-GFR) with GFR determined via renal plasma clearance of inulin (Inu-GFR) in pigs. 6 healthy anesthetized pigs. Each pig underwent 3-phase whole-kidney helical CT (arterial, early, and late parenchymal phases) before and after contrast medium administration. After contrast medium administration, corrected Hounsfield unit values were determined for each kidney and the aorta. A 3-point Patlak plot for each kidney was generated, and plasma clearance per unit volume was multiplied by renal volume to obtain whole-animal CT-GFR. Correlations of mean Inu-GFR for the left and right kidneys (and combined [total] values) with the corresponding CT-GFRs were assessed via linear regression and Bland-Altman analyses. Left kidney, right kidney, and total CT-GFRs were good predictors of the respective Inu-GFR values (r(2) = 92.3%, r(2) = 85.5%, and r(2) = 93.7%, respectively). For the left kidney, no significant bias between Inu-GFR and CT-GFR was detected. Right kidney and total CT-GFRs underestimated the corresponding Inu-GFRs (mean underestimation, -8.4 mL*min(1) and -12.6 mL*min(1), respectively). Three-phase whole-kidney CT with Patlak plot analysis of GFR may underestimate right kidney and total Inu-GFRs in pigs. The Patlak plot generated may be sensitive to nonlinearity caused by temporal variation in GFR. Nonetheless, the 3-phase CT approach offers some practical advantages for simultaneous evaluation of renal morphology and measurement of GFR.

Abstract 4175: Quantitative Assessment of Myocardial Blood Flow Using Adenosine Triphosphate Stress Multidetector-row Computed Tomography in Coronary Artery Disease

Introduction: The purpose of this study was to test the hypothesis that cardiac multidetector-row computed tomography (MDCT) technology can assess myocardial perfusion quantitatively using adenosine triphosphate (ATP) load technique. Methods: Ten patients (median age 71 (range 65–79) years) who were scheduled for surgical revascularization, underwent cardiac electrocardiography-gated MDCT using ATP-load technique. The patients with unstable angina and myocardial infraction were excluded. Myocardial infarction was detected by late gadolinium enhancement MRI which was assessed before MDCT. Myocardial blood flow (MBF) was estimated from the slope of the linear regression equation with Patlak plots analysis. MBF results were compared to the presence of stenoses more than 75% on coronary angiography (CAG) and moderate to severe myocardium ischemia on stress thallium-201 myocardial perfusion scintigraphy (MPS). Results: The overall mean MBF was 1.64±0.61 ml/g/min. Mean MBF in territories with stenosis on CAG was 0.81±0.49 ml/g/min, while mean MBF in territories without stenosis was 1.83±0.64 ml/g/min (p&lt;0.01). Mean MBF in territories with moderate to severe ischemia on MPS was 0.76±0.49 ml/g/min, while mean MBF in territories without ischemia was 2.15±0.66ml/g/min (p&lt;0.01). When the cut off value of MBF was set at 1.5 ml/g/min, there was good correlation between MBF vs CAG, and MBF and MPS. MBF vs CAG: sensitivity=71.4%, specificity=82.6%; MBF vs MPS: sensitivity=85.7%, specificity=87.0%. Conclusions: This study proposed the possibility of MDCT to quantify myocardial blood flow using ATP in coronary artery disease. Our data suggested that the ATP stress MDCT has an advantage in the assessment of CAD to evaluate both coronary artery stenoses and myocardial perfusion information in one modality.

Abstract 4177: Quantitative Evaluation of Regional Myocardial Blood Flow Using Multi-detector Row Computed Tomography in Pre- and Post- Coronary Artery Bypass Grafting Patients; Assessment with Regional Left Ventricular Function

Introduction: The advent of high resolution multidetector computed tomography (MDCT) created the potential to quantify myocardial blood flow (MBF) reduction. The effect in regional MBF produced by coronary artery bypass grafting has not been quantitatively evaluated. The purpose of this study was to test the hypothesis that adenosine stress/rest MDCT can detect ischemia by measuring MBF differences in pre- versus post-CABG patients. Methods: Ninety regional areas in 10 patients (median age 71; 65–79, 7 males), scheduled for CABG at our institution, were studied. Each patient underwent adenosine stress 64-slice MDCT perfusion imaging in both pre- and postoperative period. Myocardial blood flow was calculated with Patlak plots analysis. Regional left ventricular function (LVF) was assessed by Echocardiography. Results: Preoperative mean MBF in ischemic and non-ischemic areas was 0.76±0.49 (ml/g/min) and 2.15±0.66, respectively (p&lt;0.05). Postoperative MBF increased to 1.40±0.77 (ml/g/min) in ischemic areas (p&lt;0.05), though the non-ischemic area showed no differences. The degree of ischemia on MDCT was correlated to change in regional LVF. Postoperative assessment revealed the improved regional LVF that was correlated with the increase in regional MBF. Conclusions: The regional MBF can be quantitatively assessed by adenosine stress 64-slice MDCT perfusion imaging. This technique provides quantitative information about regional MBF in pre- and post- CABG patients, which may predict the regional LVF recovery after CABG.

Accuracy and Anatomical Coverage of Perfusion CT Assessment of the Blood-Brain Barrier Permeability: One Bolus versus Two Boluses

Purpose: To assess whether blood-brain barrier permeability (BBBP) values, extracted with the Patlak model from the second perfusion CT (PCT) contrast bolus, are significantly lower than the values extracted from the first bolus in the same patient. Materials and Methods: 125 consecutive patients (29 with acute hemispheric stroke and 96 without stroke) who underwent a PCT study using a prolonged acquisition time up to 3 min were retrospectively identified. The Patlak model was applied to calculate the rate of contrast leakage out of the vascular compartment. Patlak plots were created from the arterial and parenchymal time enhancement curves obtained in multiple regions of interest drawn in ischemic brain tissue and in nonischemic brain tissue. The slope of a regression line fit to the Patlak plot was used as an indicator of BBBP. Square roots of the mean squared errors and correlation coefficients were used to describe the quality of the linear regression model. This was performed separately for the first and the second PCT bolus. Results from the first and the second bolus were compared in terms of BBBP values and the quality of the linear model fitted to the Patlak plot, using generalized estimating equations with robust variance estimation. Results: BBBP values from the second bolus were not lower than BBBP values from the first bolus in either nonischemic brain tissue [estimated mean with 95% confidence interval: 1.42 (1.10–1.82) ml·100 g^–1·min^–1 for the first bolus versus 1.64 (1.31–2.05) ml·100 g^–1·min^–1 for the second bolus, p = 1.00] or in ischemic tissue [1.04 (0.97–1.12) ml·100 g^–1·min^–1 for the first bolus versus 1.19 (1.11–1.28) ml·100 g^–1·min^–1 for the second bolus, p = 0.79]. Compared to regression models from the first bolus, the Patlak regression models obtained from the second bolus were of similar or slightly better quality. This was true both in nonischemic and ischemic brain tissue. Conclusion: The contrast material from the first bolus of contrast for PCT does not negatively influence measurements of BBBP values from the second bolus. The second bolus can thus be used to increase anatomical coverage of BBBP assessment using PCT.

Dynamic Perfusion CT Assessment of the Blood-Brain Barrier Permeability: First Pass versus Delayed Acquisition

The Patlak model has been applied to first-pass perfusion CT (PCT) data to extract information on blood-brain barrier permeability (BBBP) to predict hemorrhagic transformation in patients with acute stroke. However, the Patlak model was originally described for the delayed steady-state phase of contrast circulation. The goal of this study was to assess whether the first pass or the delayed phase of a contrast bolus injection better respects the assumptions of the Patlak model for the assessment of BBBP in patients with acute stroke by using PCT. We retrospectively identified 125 consecutive patients (29 with acute hemispheric stroke and 96 without) who underwent a PCT study by using a prolonged acquisition time up to 3 minutes. The Patlak model was applied to calculate BBBP in ischemic and nonischemic brain tissue. Linear regression of the Patlak plot was performed separately for the first pass and for the delayed phase of the contrast bolus injection. Patlak linear regression models for the first pass and the delayed phase were compared in terms of their respective square root mean squared errors (square root MSE) and correlation coefficients (R) by using generalized estimating equations with robust variance estimation. BBBP values calculated from the first pass were significantly higher than those from the delayed phase, both in nonischemic brain tissue (2.81 mL x 100 g(-1) x min(-1) for the first pass versus 1.05 mL x 100 g(-1) x min(-1) for the delayed phase, P < .001) and in ischemic tissue (7.63 mL x 100 g(-1) x min(-1) for the first pass versus 1.31 mL x 100 g(-1) x min(-1) for the delayed phase, P < .001). Compared with regression models from the first pass, Patlak regression models obtained from the delayed data were of better quality, showing significantly lower square root MSE and higher R. Only the delayed phase of PCT acquisition respects the assumptions of linearity of the Patlak model in patients with and without stroke.

The Effects of Anesthetic Agent and Carrier Gas on Blood Glucose and Tissue Uptake in Mice Undergoing Dynamic FDG-PET Imaging: Sevoflurane and Isoflurane Compared in Air and in Oxygen

We sought to identify an anesthetic regime that, unlike isoflurane in air, would maintain glucose homeostasis in mice undergoing Positron emission tomography (PET) imaging with 2-deoxy-2-[18F]fluoro-D: -glucose (FDG). FDG uptake was also measured in normal and tumor tissues. Athymic and Balb/c nude mice were studied. Blood glucose levels were measured before and after 30 min of FDG PET imaging under isoflurane or sevoflurane carried in air or oxygen. FDG uptake was quantified as a percentage of the injected dose and using Patlak analysis yielding Ki values. Blood glucose levels were more stable under sevoflurane than under isoflurane, especially in the athymic nude mice. Under isoflurane, FDG uptake into myocardium was higher than under sevoflurane and was strongly correlated with the intrascan change in blood glucose. Sevoflurane should be preferred for physiologic imaging in mice, minimizing changes in glucose and, for FDG PET, reducing signal spillover from the myocardium.

Volumetric perfusion CT assessment of concurrent combretastatin-A4-phosphate (CA4P) and radiotherapy (RT) in non-small cell lung cancer

14584 Background: Preclinical studies demonstrated enhanced growth delay with concurrent CA4P and RT (Chaplin, D.J et al. Anticancer Res. 1999; 19: 189–195). In human advanced non-small cell lung carcinoma (NSCLC) this has been explored in a Phase 1B study where a volumetric helical Perfusion CT technique has been developed to assess the acute and late vascular effects throughout the entire tumour. Methods: Eligible patients had histologically confirmed inoperable NSCLC,unsuitable for radical radiotherapy, ECOG PS ≤ 2. All patients received RT, 27 Gray in 6 fractions over 3 weeks. 18 patients (3 cohorts of 6 patients) were treated prospectively. Intravenous CA4P (50mg/m2) was given in an escalation schedule: Cohort 1 single dose CA4P after 2 fractions RT, Cohort 2 weekly CA4P after 2, 4 + 6 fractions RT and Cohort 3 twice weekly CA4P after every fraction RT. Up to 8 volumetric Perfusion CT were performed in 14 patients using a 16-MDCT scanner (Sensation 16, Siemens Medical Solutions, Germany): 2 baseline, post RT (2,4+6 fractions) then 4 hours post CA4P. Whole tumour blood volume (BV) and extraction fraction (EF) were determined on a pixel by pixel basis for each patient using software based on Patlak analysis (FuncCT, Siemens). Changes in vascularity were compared using t testing; statistical significance was at 5%. Results: See Table. Cohorts 1+2 had significant group decrease in BV 4h post CA4P (p=0.029) not seen in Cohort 3. No other significant group effects were observed. Conclusion: Demonstrated changes in tumour vascularity may indicate a schedule dependant synergistic interaction between CA4P and RT in NSCLC. Changes in group mean from baseline (%) 2# RT 4h CA4P 4# RT 4h CA4P 6# RT 4h CA4P BV (mL/100 mL) Cohorts 1+2 12.92 − 5.39 0.60 −7.77 −12.26 −20.38 Cohort 3 45.00 15.71 6.32 11.26 0.39 23.46 EF (mL/100 mL/min) Cohorts 1+2 14.55 5.22 7.80 20.74 14.26 22.69 Cohort 3 16.34 8.51 10.16 16.79 4.94 13.43 No significant financial relationships to disclose.

Comparison of Tumor Volumes Derived from Glucose Metabolic Rate Maps and SUV Maps in Dynamic 18F-FDG PET

Tumor delineation using noninvasive medical imaging modalities is important to determine the target volume in radiation treatment planning and to evaluate treatment response. It is expected that combined use of CT and functional information from 18F-FDG PET will improve tumor delineation. However, until now, tumor delineation using PET has been based on static images of 18F-FDG standardized uptake values (SUVs). 18F-FDG uptake depends not only on tumor physiology but also on blood supply, distribution volume, and competitive uptake processes in other tissues. Moreover, 18F-FDG uptake in tumor tissue and in surrounding healthy tissue depends on the time after injection. Therefore, it is expected that the glucose metabolic rate (MRglu) derived from dynamic PET scans gives a better representation of the tumor activity than does SUV. The aim of this study was to determine tumor volumes in MRglu maps and to compare them with the values from SUV maps. Twenty-nine lesions in 16 dynamic 18F-FDG PET scans in 13 patients with non-small cell lung carcinoma were analyzed. MRglu values were calculated on a voxel-by-voxel basis using the standard 2-compartment 18F-FDG model with trapping in the linear approximation (Patlak analysis). The blood input function was obtained by arterial sampling. Tumor volumes were determined in SUV maps of the last time frame and in MRglu maps using 3-dimensional isocontours at 50% of the maximum SUV and the maximum MRglu, respectively. Tumor volumes based on SUV contouring ranged from 1.31 to 52.16 cm3, with a median of 8.57 cm3. Volumes based on MRglu ranged from 0.95 to 37.29 cm3, with a median of 3.14 cm3. For all lesions, the MRglu volumes were significantly smaller than the SUV volumes. The percentage differences (defined as 100% x (V MRglu - V SUV)/V SUV, where V is volume) ranged from -12.8% to -84.8%, with a median of -32.8%. Tumor volumes from MRglu maps were significantly smaller than SUV-based volumes. These findings can be of importance for PET-based radiotherapy planning and therapy response monitoring.

Perfusion CT measurements in healthy cervical spinal cord: feasibility and repeatability of the study as well as interchangeability of the perfusion estimates using two commercially available software packages

Our purpose was to examine the feasibility and reproducibility of perfusion CT studies in the cervical spinal cord and the interchangeability of the values obtained by two post-processing methods. The perfusion CT studies of 40 patients with neck tumours were post-processed using two software packages (Software-1: deconvolution-based analysis with adiabatic tissue homogeneity approach and Software-2: maximum-slope-model with Patlak analysis). Eight patients were examined twice for assessing the reproducibility of the technique. Two neuroradiologists separately post-processed the images with two arterial input functions (AIFs): (1) the internal carotid artery (ICA) and (2) the vertebral artery (VA). Maps of blood flow (F) in ml/min/100 g, blood volume (V) in ml/100 g, mean transit time (MTT) in seconds (s) and permeability (PS) in ml/min/100 g were generated. The mean F, V, MTT and PS (Software-1) with VA-AIF and ICA-AIF were 8.93, 1.12, 16.3, 1.88 and 8.57, 1.19, 16.85 and 1.94, respectively. The reproducibility of the techniques was satisfactory, while the V and MTT values (in Software-1) and the F and V values (in Software-2) were dependent on the site of the AIF (p >or= 0.03 and p=0.02, respectively). The interobserver agreement was very good. The significant differences in measurements for a single patient (%) using Software-1/Software-2 were +/-120%/110%, 90%/80%, 180% and 250%/130% for F, V, MTT and PS, respectively. Only F and PS values in the healthy tissue seemed to be interchangeable. Our results were in essential agreement with those derived by invasive measurements in animals. The cervical spine perfusion CT studies are feasible and reproducible. The present knowledge has to be validated with studies in spinal cord tumours in order to decide the usefulness of the perfusion CT in this field.

Long-Term Precision of 18F-Fluoride PET Skeletal Kinetic Studies in the Assessment of Bone Metabolism

(18)F-Fluoride PET allows noninvasive evaluation of regional bone metabolism and has the potential to become a useful tool for assessing patients with metabolic bone disease and evaluating novel drugs being developed for these diseases. The main PET parameter of interest, termed K(i), reflects regional bone metabolism. The aim of this study was to compare the long-term precision of (18)F-fluoride PET with that of biochemical markers of bone turnover assessed over 6 mo. Sixteen postmenopausal women with osteoporosis or significant osteopenia and a mean age of 64 y underwent (18)F-fluoride PET of the lumbar spine and measurements of biochemical markers of bone formation (bone-specific alkaline phosphatase and osteocalcin) and bone resorption (urinary deoxypyridinoline) at baseline and 6 mo later. Four different methods for analyzing the (18)F-fluoride PET data were compared: a 4k 3-compartmental model using nonlinear regression analysis (K(i-4k)), a 3k 3-compartmental model using nonlinear regression analysis (K(i-3k)), Patlak analysis (K(i-PAT)), and standardized uptake values. With the exception of a small but significant decrease in K(i-3k) at 6 mo, there were no significant differences between the baseline and 6-mo values for the PET parameters or biochemical markers. The long-term precision, expressed as the coefficient of variation (with 95% confidence interval in parentheses), was 12.2% (9%-19%), 13.8% (10%-22%), 14.4% (11%-22%), and 26.6% (19%-40%) for K(i-3k), K(i-PAT), mean standardized uptake value, and K(i-4k), respectively. For comparison, the precision of the biochemical markers was 10% (7%-15%), 18% (13%-27%), and 14% (10%-21%) for bone-specific alkaline phosphatase, osteocalcin, and urinary deoxypyridinoline, respectively. Intraclass correlation between the baseline and 6-mo values ranged from 0.44 for K(i-4k) to 0.85 for K(i-3k). No significant correlation was found between the repeated mean standardized uptake value measurements. The precision and intraclass correlation observed for K(i-3k) and K(i-PAT) was equivalent to that observed for biochemical markers. This study provided initial data on the long-term precision of (18)F-fluoride PET measured at the lumbar spine, which will aid in the accurate interpretation of changes in regional bone metabolism in response to treatment.

Study of direct and indirect parametric estimation methods of linear models in dynamic positron emission tomography

In dynamic positron emission tomography (PET) studies, the time changing activity of the radiotracer is measured through multiple consecutive frames. Subsequent pixel-by-pixel application of the appropriate kinetic model provides quantitative information in terms of images of the distribution of the physiological parameter of interest. In this context, iterative reconstruction methods may be used to reconstruct for each time frame a static image of appreciable higher quality than the analytical algorithms, especially in low-count cases. Furthermore, if the reconstruction algorithm also models the kinetics of the measured counts, the parametric image is expected to be of even higher quality. In this work, we investigate the methodology to directly reconstruct parametric images in three-dimensional PET when the kinetic model is linear in its parameters (Patlak plot) and compare with indirectly estimated parametric maps, where the radioactivity distribution was estimated by the filtered back projection and ordered subsets expectation maximization algorithms. Both real and simulated data for tracers with irreversible kinetics in brain studies are included. The results demonstrate appreciable smaller standard deviation and mean squared error characteristics for the direct reconstruction. However, some regions may converge slowly. The FBP and ordered subsets expectation maximization (OSEM) indirect estimations have a similar level of bias after matching their resolutions, but OSEM has smaller standard deviation.

Chemotherapy response evaluation with FDG–PET in patients with colorectal cancer

BackgroundThe aim of this prospective study was to evaluate the value of F-18-fluorodeoxyglucose–positron emission tomography (FDG–PET) for early assessment of chemotherapy response in patients with advanced colorectal cancer. MethodsDynamic FDG–PET was carried out before and at 2 (n=50) and 6 months (n=19) after the start of treatment. Quantitative Patlak analysis [metabolic rate of glucose (MRGlu)] and a simplified method to measure glucose metabolism [standardized uptake value (SUV)] were evaluated. The predictive value of changes in glucose metabolism was assessed with Cox proportional regression analysis. Overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan–Meier estimates. ResultsThere was an increase in the rates of death (P=0.049 for ΔMRGlu PET1–2; P=0.017 for ΔSUV PET1–2; P=0.032 for ΔMRGlu PET1–3; P=0.048 for ΔSUV PET1–3) and progression (P=0.026 for ΔMRGlu PET1–2; P=0.035 for ΔSUV PET1–2; P=0.041 for ΔMRGlu PET1–3; P=0.081 for ΔSUV PET1–3) associated with worse response as assessed by PET on Cox proportional regression analysis. The OS and PFS analysis showed a significant predictive value at broad ranges of ΔMRGlu and ΔSUV cut-off levels. ConclusionThe degree of chemotherapy-induced changes in tumor glucose metabolism is highly predictive for patient outcome. The use of FDG–PET for therapy monitoring seems clinically feasible since simplified methods (SUV) are sufficiently reliable.

Maximum a posteriori reconstruction of the Patlak parametric image from sinograms in dynamic PET

Parametric imaging using the Patlak graphical method has been widely used to analyze dynamic PET data. Conventionally a Patlak parametric image is generated by reconstructing a sequence of dynamic images first and then performing Patlak graphical analysis on the time–activity curves pixel-by-pixel. However, because it is rather difficult to model the noise distribution in reconstructed images, the spatially variant noise correlation is simply ignored in the Patlak analysis, which leads to sub-optimal results. In this paper we present a Bayesian method for reconstructing Patlak parametric images directly from raw sinogram data by incorporating the Patlak plot model into the image reconstruction procedure. A preconditioned conjugate gradient algorithm is used to find the maximum a posteriori solution. The proposed direct method is statistically more efficient than the conventional indirect approach because the Poisson noise distribution in PET data can be accurately modeled in the direct reconstruction. The computation cost of the direct method is similar to reconstruction time of two dynamic frames. Therefore, when more than two dynamic frames are used in the Patlak analysis, the direct method is faster than the conventional indirect approach. We conduct computer simulations to validate the proposed direct method. Comparisons with the conventional indirect approach show that the proposed method results in a more accurate estimate of the parametric image. The proposed method has been applied to dynamic fully 3D PET data from a microPET scanner

Determination of blood-brain barrier permeability in brain-injured patients by Patlak plot analysis

Determination of blood-brain barrier permeability in brain-injured patients by Patlak plot analysis

Patlak Plot Analysis for Assessment of Single-Kidney Glomerular Filtration Rate with Dynamic CT

Patlak Plot Analysis for Assessment of Single-Kidney Glomerular Filtration Rate with Dynamic CT

Quantification of Regional Myocardial Blood Flow Using First-Pass Multidetector-Row Computed Tomography and Adenosine Triphosphate in Coronary Artery Disease

The feasibility of using cardiac multidetector-row computed tomography (MDCT) technology in the quantitative assessment of myocardial blood flow (MBF) using the adenosine triphosphate (ATP) load technique was investigated in the present study. The study group comprised 14 patients (11 men, 3 women, age range 52-79 years, mean age 69.2 years) who underwent cardiac cine MDCT using the ATP-load technique. MBF was estimated from the slope of the linear regression equation with Patlak plots analysis. The overall average MBF was 1.83+/-0.62 ml . g(-1) . min(-1). Mean MBF in territories with stenosis on coronary angiography was 1.19+/-0.36 ml . g(-1) . min(-1) and 2.06+/-0.54 ml . g(-1) . min(-1) (p<0.01) in territories without stenosis. The average MBF in territories with moderate to severe ischemia on myocardial perfusion scintigraphy was 1.32+/-0.14 ml .g(-1 ). min(-1 )and 1.95+/-0.64 ml . g(-1) . min(-1) (p<0.01) in territories without ischemia. MDCT can be used to quantify MBF using first-pass dynamic data.

In vivo measurement of cell proliferation in canine brain tumor using C-11-labeled FMAU and PET

Noncatabolized thymidine analogs are being developed for use in imaging DNA synthesis. We sought to relate a labeling index measured by immunohistochemical staining bromodeoxyuridine (BUdR) technique to the uptake of (11)C 2'-fluoro-5-methyl-1-beta-d-arabinofuranosyluracil (FMAU) measured with positron emission tomography (PET) in a brain tumor model. Adult beagles (n=8) with implanted brain tumors received [(11)C]FMAU and dynamic imaging with arterial sampling. Six dogs were then infused with BUdR (200 mg/m(2)) and sacrificed. Tumor time-activity curves (TACs) obtained from computed-tomography-defined regions of interest were corrected for partial volume effects and crosstalk from brain tissue. Tissue was analyzed for the percentage of tumor volume occupied by viable cells and by viable cells in S-phase as identified by BUdR staining. PET/[(11)C]FMAU and BUdR were compared by linear regression analysis and analysis of variance, as well as by a nonparametric rank correlation test. Tumor standardized uptake values (SUVs) and tumor-to-contralateral-brain uptake ratios at 50 min were 1.6+/-0.4 and 5.5+/-1.2 (n=8; mean+/-S.E.M.), respectively. No (11)C-labeled metabolites were observed in the blood through 60 min. Tumor TACs were well described with a three-compartment/four-parameter model (k(4)=0) and by Patlak analysis. Parametric statistical analysis showed that FMAU clearance from plasma into tumor Compartment 3 (K(FMAU)) was significantly correlated with S-phase percent volume (P=.03), while tumor SUV was significantly correlated with both S-phase percent volume and cell percent volume (P=.02 and .03, respectively). Patlak slope, K(FMAU) and tumor SUV were equivalent with regard to rank correlation analysis, which showed that tumor uptake and trapping of FMAU were correlated with the volume density of dividing cells (P=.0003) rather than nondividing cells (P=.3). Trapping of [(11)C]FMAU correlated with tumor growth rate, as measured by direct tissue analysis with BUdR in a canine brain tumor model, suggesting that [(11)C]FMAU is useful for the imaging of cell proliferation in cancers.