Volume-normalized uptake rates with robust transportability from PET dual-time and Patlak analyses.

PURPOSE: The intention here is to enhance the usefulness of the Gjedde-Patlak plot of dynamic positron emission tomography (PET) tracer uptake. Two additional parameters closely related to the physiologically significant and diagnostically useful phosphorylation rate k (3) are therefore studied. Additionally, their inter-institutional transportability is examined. METHODS: The two traditional parameters obtained from a Patlak plot are its slope Ki and its usually ignored tissue/plasma (=Q/Cp) axis intercept V. As a useful result, a normalized uptake rate may be defined as k=Ki /V. This is can be theoretically close to k (3). Similar to this an alternative normalized uptake rate is defined as k (3)' =Ki /V '. Here, V ' would be a composite of model rate constants, reasonably known a priori, and the measured V so as to depend less on errors in the latter. Parameter determination demonstrations utilize data from the 2-deoxy-2-[F-18]fluoro-D-glucose(FDG)-PET literature. RESULTS: Using median k (i) values from 24 FDG dynamic studies and algebraic relationships, on average: k=1.07 k (3)(r=0.97), and k (3)' =0.95k (3) (r=0.91). A skeletal muscle case also demonstrates agreements with k (3). For liver malignancies k and k (3)' can be diagnostically slightly superior to Ki. Unaffected by institutionally dependent Q and Cp calibrations and methods, these can be more robust than Ki in a number of circumstances. CONCLUSION: Two studied physiologically meaningful parameters, close to the diagnostically important k (3), can supplement Ki and enhance Patlak analysis by appropriately utilizing normally ignored information. Hitherto, k (3) was obtainable only by complex nonlinear least squares compartmental model analysis. The additional parameters can have more robust inter-institutional transportability than Ki.

Optimizing dual-time and serial positron emission tomography and single photon emission computed tomography scans for diagnoses and therapy monitoring.

INTRODUCTION: A region's early and late tracer uptake activities, QE and QL, within a dual-time scan (i.e. using two frames) or in serial scans (as for monitoring therapeutic response), are popular quantitative diagnostic aids, especially in oncology. In this paper, maximum performance is sought from their joint use. METHODS: QL/QnE is introduced as a tumor marker with an empirical n. This generalizes traditional data weighting having n=1 for QL/QE, the retention index (RI), with its associated % difference. Using patient data, iterative guessing finds an optimal n that maximizes a measure of diagnostic performance: D=(difference of normal and abnormal marker means)/(their combined SD), which may be computed from values of QL/QnE, as well as of QL, QE, and RI each used alone. For 2-deoxy-2-[F-18]fluoro-D-glucose(FDG)-positron emission tomography (PET) dual-time protocols, another approach to optimization-selection of scan times-is investigated by simulations using the Sokolov model. RESULTS: A meta-analysis of 12 PET and single photon emission computed tomography (SPECT) studies with various tracers, cancers, and scan classes (dual-time or serial) finds ns from 0.5 to 1.1. The optimal D necessarily exceeds the best (or any) computed using QE, QL, or RI: negligibly to by as much as 0.6 (or 1.5). The increases in optimal receiver operating curve area (Az) over the best (or any) traditional marker range from negligible to 0.07 (or 0.4). QE alone usually has the lowest D and Az. Statistically significant performance improvement of QL/QnE over QE and QL is shown for most studies. Contrasting with an optimal n, another value n0 can also be found where D=0. Occasionally, n0 can be close to 1, and RI then will have a small D and poor performance. Simulation with kinetic modeling of FDG dual-time scans for liver and liver metastases demonstrates worst and best scan times. Indicated for these imaging protocols are QE at very early cellular transport associated times and QL rather late when phosphorylation/dephosphorylation dominate. Benefits from choosing optimal times in dual-time protocols, especially in combination with choosing optimal ns, can be significant. CONCLUSION: A protocol-dependent optimizing parameter n in an improved classification marker can easily be identified in a learning set of scans having normals and abnormals. Finding this parameter below 1.0 in most all studies suggests that a popularly used QL/QE may often overweight early activities. Additionally, QL/QE may sometimes be a poor marker choice and underestimate a protocol's diagnostic capability. Subsequent use of the proposed QL/QnE in settings similar to that of the learning set gives improved diagnostic performance over traditional approaches, although by widely varying amounts. Additionally, a method of seeking optimal scan times is demonstrated and suggests significant gains in dual-time protocol performances are possible.

A weight index for the standardized uptake value in 2-deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography.

INTRODUCTION: Known errors in the standardized uptake value (SUV) caused by variations in subject weights W encountered can be corrected by lean body mass or body surface area (bsa) algorithms replacing W in calculations. However this is infrequently done. The aims of the work here are: quantify sensitivity to W, encourage SUV correction with an approach minimally differing from tradition, and show what improvements in the SUV coefficient of variation (cv) for a population can be expected. METHODS: Selected for analyses were 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) SUV data from positron emission tomography (PET) and PET/computed tomography (CT) scans at the University of Tennessee as well as from the literature. A weight sensitivity index was defined as -n=slope of ln(SUV/W) vs. lnW. The portion of the SUV variability due to this trend is removed by using the defined [formula: see text], or a virtually equal SUVm using [formula: see text], with Q and ID being tissue specific-activity and injected dose. [formula: see text] measures performance. Adapting to animal studies' tradition, [formula: see text] is preferred over the conventional [formula: see text]. RESULTS: For FDG in adults [formula: see text] from averaging over most tissues. In children, however, [formula: see text]. Tissues have the same index if their influx constants are independent of W. Suggested, therefore, is a very simplified [formula: see text], which is dimensionless and keeps the same population averages as traditional SUVs. It achieves [formula: see text]. Hence, for cv's of SUVs below approximately 1/3 improvements over tradition are possible, leading to F's<0.95. Accounting additionally for height, as in SUVbsa, gives very little improvement over the simplified approach here and gives essentially the same F's as SUVm. CONCLUSIONS: Introduced here is a weight index useful in reducing variability and further understanding the SUV. Addressing weight sensitivity is appropriate where the cv of the SUVs is below about 1/3. Proposed is the very simple approach of using an average of an adult patient's weight and approximately 70 kg for FDG SUV calculations. Unlike other approaches the dimensionless population average of SUVms is unchanged from tradition.

2-deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography sensitivity to serum glucose: a survey and diagnostic applications.

OBJECTIVE: The positron emission tomography (PET) clinical utility of the sensitivity (gamma) of uptake (Q) to a change in plasma glucose concentration (C) is investigated. METHODS: Gamma is obtained from data as [ln(Q (2)/Q (1))] / [ln(C(2)/C(1))], using previously published intrapatient studies varying C within a single patient and some interpatient ones. It can be theoretically related to the half-saturation constant in the Michaelis-Menten quantification of competitive uptake. One of its uses is making uptake corrections for desired vs. actual C using Q(2) = Q(1) (C(2)/C(1))(gamma). RESULTS: Intrapatient studies proved to be preferable to interpatient ones, and a 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-PET survey with analyses for gamma yielded the following result: usually the gamma values of tumors and brain tissues were near -1, whereas those of other noncerebral tissues were near 0. Regarding correcting uptakes for C, instead of a universally assumed and applied gamma = -1, corrections should be for a single tissue using its known gamma. An advantageous use of gamma is predicting how C affects image contrast, including where glucose loading is sometimes preferable to fasting. CONCLUSIONS: A potentially useful quantifier of uptake sensitivity to plasma glucose has been defined and values obtained. Correcting uptakes to some standard C requires special care. gamma can help PET clinicians select fasting or loading to achieve glucose levels for optimum contrast.

Degree of fractal behavior as a diagnostic aid in quantitative image analyses.

PURPOSE: Multiple strategies in diagnoses of different diseases from images can include their histogram analyses. Any fractal behavior in the latter is to be quantified as to extent here, with a view toward contributing to a diagnostic process. PROCEDURE: One tool in quantitative image analyses is the fractal dimension D of the pixel histogram, a measure of self-similarity over various scales in a fitted power-law behavior of pixel intensity cumulative probability distribution. Proposed and developed here as diagnostic markers are features of its determination process that indicate to what extent there is fractal behavior. One of these is the curvature c that exists in log-log plots used for extracting the fractal exponent D of power-law behavior. RESULTS: Specific implementations are given both for a general lognormal pixel intensity distribution and for lung images. Both Ds and cs are determined for: normals, pulmonary embolism, cystic fibrosis, as well as a theoretical lognormal distribution. It is shown that D and heterogeneity described by a standard deviation are reciprocally related and not typically independent markers. The added independent information from c has possibilities of assisting in discrimination of normal and pathologic conditions, such as in lung diseases. CONCLUSION: In addition to a histogram's fractal dimension itself, there are indications that measures of the degree of fractal behavior may also hold promise in image diagnoses.

Optimizing imaging time for improved performance in oncology PET studies.

PURPOSE: The potential for improving the diagnostic performance of static positron imaging tomography (PET) by judiciously choosing optimum post-injection imaging times is investigated. PROCEDURES: Dynamic and whole-body scan data, from 2-deoxy-2-[18F]fluoro-D-glucose (FDG) oncological studies, are analyzed for changing standardized uptake value (SUV) behavior with increasing post-injection times at either single- or multiple-bed positions. Model-based interpretations address d(SUV)/dt, shown to correlate with SUV, and the contrast ratio for a tumor and its surroundings. A method for correcting measurements to a standardized time is given. RESULTS: Both data and model-based equations suggest that starting data acquisition later than the average 55 +/- 15 (SD) minutes post-injection reported in the FDG literature can improve contrast ratios. Considerations for choosing an optimum time from a clinical standpoint are listed. CONCLUSIONS: It is concluded that the appropriate time for each particular protocol can be found with the aid of the information presented here. True optimization, however, remains a complex issue.

Cost Analysis of FDG PET for Managing Patients with Ovarian Cancer.

Monte Carlo simulation analysis was used to compare the cost of managing recurrent ovarian cancer patients with and without the use of positron emission tomography (PET) scanning. Assumptions in the management pathway were: (1) a positive PET scan led to either laparoscopy or laparotomy, followed by chemotherapy (true positive PET) or follow-up (false positive PET); (2) a negative PET scan resulted in continued follow-up (true negative PET) or laparotomy (false negative PET); and, (3) a laparotomy led to chemotherapy or follow-up. In this simulation, sensitivity and specificity of FDG PET for recurrent ovarian cancer varied from 72-91% (mean 83%) and 69-95% (mean 85%), respectively, as defined by the ROC curve. Using a prevalence rate of 30% for recurrent ovarian cancer, the mean PET false negative rate was 5%. Thus, when using PET to manage the diagnostic evaluation, the number of unnecessary laparotomies was reduced from 70% to 5%, with 35% of patients undergoing laparoscopy for recurrent disease instead of laparotomy. If laparotomy is used in place of laparoscopy, unnecessary surgery can be avoided in 30% of patients. Costs for procedures were based both on hospital charges, and Medicare reimbursement rates. Cost savings per patient ranged from $1,941 to $11,766, assuming that follow-up evaluation was similar for both groups. Estimated cost savings were due to the need for fewer surgical procedures when using PET in the diagnostic evaluation, the reimbursement rate scheme employed, and whether laparotomy or laparoscopy was used in the management algorithm for PET positive patients. In conclusion, FDG PET can reduce unnecessary invasive staging procedures and save health care costs when used appropriately in the management of patients with recurrent ovarian cancer.

Model Interpretation and Clinical Implications.

Useful characterizing parameters have been derived from historical positron emission tomography (PET) standardized uptake values (SUV) and influx constants K. Meta-analysis was performed on 30 multipatient PET oncological studies providing same patient SUVs and K's. Averaged results for fluorine-18 fluorodeoxyglucose (FDG) and L-methionine respectively were: SUV vs. K correlation coefficients = 0.89 and 0.80; SUV/K ratios = 192 and 63 minutes as average tracer clearance times T in these populations. For cancers, coefficients of variation (CV) for K's were 0.61 and 0.46, notably larger than the CVs (0.50 and 0.40) for SUVs. A Monte Carlo simulation model, matching these results, represents 1/T as (an effective tracer clearance rate) x (its initial distribution volume). We conclude that T is a characteristic tracer clearance time that is independent of cancer type. A measurement model is introduced that might help improve protocols. The higher CVs of K's vs. SUVs is worth noting clinically when seeking an effective diagnostic marker. Also, SUV conversions to K can provide some quality assurance in K measurements.