An assessment of the impact of incorporating time-of-flight information into clinical PET/CT imaging.

The introduction of fast scintillators with good stopping power for 511-keV photons has renewed interest in time-of-flight (TOF) PET. The ability to measure the difference between the arrival times of a pair of photons originating from positron annihilation improves the image signal-to-noise ratio (SNR). The level of improvement depends upon the extent and distribution of the positron activity and the time resolution of the PET scanner. While specific estimates can be made for phantom imaging, the impact of TOF PET is more difficult to quantify in clinical situations. The results presented here quantify the benefit of TOF in a challenging phantom experiment and then assess both qualitatively and quantitatively the impact of incorporating TOF information into the reconstruction of clinical studies. A clear correlation between patient body mass index and gain in SNR was observed in this study involving 100 oncology patient studies, with a gain due to TOF ranging from 1.1 to 1.8, which is consistent with the 590-ps time resolution of the TOF PET scanner. The visual comparison of TOF and non-TOF images performed by two nuclear medicine physicians confirmed the advantages of incorporating TOF into the reconstruction, advantages that include better definition of small lesions and image details, improved uniformity, and noise reduction.

Abnormal connectivity in the posterior cingulate and hippocampus in early Alzheimer's disease and mild cognitive impairment.

BACKGROUND: Brain imaging studies of early Alzheimer's disease (AD) have shown decreased metabolism predominantly in the posterior cingulate cortex (PCC), medial temporal lobe, and inferior parietal lobe. This study investigated functional connectivity between these regions, as well as connectivity between these regions and the whole brain. METHODS: Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) studies were performed in subjects with early AD, mild cognitive impairment (MCI), and normal controls. RESULTS: The data indicate both decreased fiber connections and disrupted connectivity between the hippocampus and PCC in early AD. The MCI group showed reduced fiber numbers derived from PCC and hippocampus to the whole brain. CONCLUSIONS: The fMRI and DTI results confirmed decreased connectivity from both the PCC and hippocampus to the whole brain in MCI and AD and reduction in connectivity between these two regions, which plausibly represents an early imaging biomarker for AD.

Positron emission tomography/computerized tomography (PET/CT) scanning for preoperative staging of patients with oral/head and neck cancer.

PURPOSE: To investigate the role of 18-fluorine-fluorodeoxyglucose positron emission tomography/computerized tomography ((18)F-FDG PET/CT) in the preoperative prediction of the presence and extent of neck disease in patients with oral/head and neck cancer. PATIENTS AND METHODS: Seventy patients were enrolled in the study, 47 of whom had a clinically negative neck (N0), 19 of whom had a clinically positive unilateral neck (N+), and 4 of whom were negative on 1 side of the neck and positive on the other. Each patient underwent a PET/CT study before undergoing selective neck dissection for N0 disease or modified radical neck dissection for N+ disease. Tissues were submitted for histopathologic examination and were oriented for the pathologist as to the oncologic levels so as to permit correlation between histopathologic findings and the imaging results. RESULTS: The sensitivity and specificity of the PET/CT procedure were 79% and 82% for the N0 neck, and 95% and 25% for the N+ neck. One hundred ninety-two (11.4%) of the 1,678 nodes identified at histopathology were positive for metastases. The overall nodal sensitivity and specificity were 48% and 99%, respectively. CONCLUSION: In patients with clinically negative necks, a negative test would not help the surgeon in the management strategy of the patient because of the rate of false-negative results, but a positive test can diagnose metastatic deposits with a high positive predictive value. In patients with clinically positive necks, a positive test will confirm the presence of disease, although false-negative lymph nodes were additionally identified in these clinically positive necks. With respect to nodes, the sensitivity of the imaging procedure is such that the results could not help the surgeon in deciding which level to dissect and which to spare. In the final analysis, the head and neck oncologic surgeon should not depend on the results of the PET/CT scan to determine which patients will benefit from neck dissection. Rather, time-honored principles of neck surgery should be followed, particularly with regard to the liberal execution of prophylactic neck dissections in patients with clinically N0 necks.

Time course of early response to chemotherapy in non-small cell lung cancer patients with 18F-FDG PET/CT.

UNLABELLED: PET and (18)F-FDG have the potential to follow the early metabolic response to chemotherapy in patients with non-small cell lung cancer and to predict success or failure of the therapy. METHODS: We studied 16 patients with non-small cell lung cancer as they followed 2 courses of docetaxel and carboplatin. Each patient was studied weekly for 7 wk, and tissue activity was assessed by the amount of radioactivity retained 90 min after the intravenous injection of (18)F-FDG. In a prospective analysis, the linear least-squares method was used to evaluate the time course of metabolic activity in tumor and liver, bone marrow, and unaffected lung tissues; a metabolic response was defined as a response in which the slope of the regression was negative and significantly different from zero. Our hypothesis was that patients who exhibited a tumor metabolic response would survive longer than those who did not. In a retrospective examination of our data, we grouped our patients into those who survived <6 mo and those who survived longer and calculated the difference in the standardized uptake value (SUV) between day 7 and subsequent time points to determine the most appropriate timing of 2 PET studies in predicting response to therapy. RESULTS: Fifteen of 16 patients completed the study. In the prospective study, 8 patients were classified as nonresponders as the slope of the regression of tumor SUV versus time was not different from zero; they all died within 35 wk of the end of their study. Seven patients were classified as responders; 5 survived and 2 died, one at 25 wk and the other at 76 wk. In the retrospective study, a decrease of 0.5 SUV between studies performed at 1 and 3 wk after the initiation of chemotherapy was predictive of those patients who survived >6 mo and in whom chemotherapy was presumably successful. CONCLUSION: Patients with non-small cell lung cancer who had a positive outcome, as exhibited by prolonged survival, were those who showed a tumor metabolic response assessed using weekly (18)F-FDG PET studies. (18)F-FDG PET studies performed at 1 and 3 wk after the initiation of chemotherapy allowed prediction of the response to therapy.

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.

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.