Comparison of two threshold detection criteria methodologies for determination of probe positivity for intraoperative in situ identification of presumed abnormal 18F-FDG-avid tissue sites during radioguided oncologic surgery

Abstract

Background: Intraoperative in situ identification of (18)F-FDG-avid tissue sites during radioguided oncologic surgery remains a significant challenge for surgeons. The purpose of our study was to evaluate the 1.5-to-1 ratiometric threshold criteria method versus the three-sigma statistical threshold criteria method for determination of gamma detection probe positivity for intraoperative in situ identification of presumed abnormal (18)F-FDG-avid tissue sites in a manner that was independent of the specific type of gamma detection probe used.

Methods: From among 52 patients undergoing appropriate in situ evaluation of presumed abnormal (18)F-FDG-avid tissue sites during (18)F-FDG-directed surgery using 6 available gamma detection probe systems, a total of 401 intraoperative gamma detection probe measurement sets of in situ counts per second measurements were cumulatively taken.

Results: For the 401 intraoperative gamma detection probe measurement sets, probe positivity was successfully met by the 1.5-to-1 ratiometric threshold criteria method in 150/401 instances (37.4%) and by the three-sigma statistical threshold criteria method in 259/401 instances (64.6%) (P < 0.001). Likewise, the three-sigma statistical threshold criteria method detected true positive results at target-to-background ratios much lower than the 1.5-to-1 target-to-background ratio of the 1.5-to-1 ratiometric threshold criteria method.

Conclusions: The three-sigma statistical threshold criteria method was significantly better than the 1.5-to-1 ratiometric threshold criteria method for determination of gamma detection probe positivity for intraoperative in situ detection of presumed abnormal (18)F-FDG-avid tissue sites during radioguided oncologic surgery. This finding may be extremely important for reshaping the ongoing and future research and development of gamma detection probe systems that are necessary for optimizing the in situ detection of radioisotopes of higher-energy gamma photon emissions used during radioguided oncologic surgery.

Figure 1

Illustration of the probability distribution for the background count measurement and the target count measurement. The target count measurement (T) represents the summation of source count measurement (S) plus the background count measurement (B). Probabilities (P) for true positive, true negative, false positive, and false negative are shown for target count rates at three standard deviations above the mean background count.

Figure 2

Plot of the target-to-background ratio and mean background count rate for those 291 of the 401 gamma detection probe measurement data sets that were limited to a mean background count rate range of less than 1250 counts per second. Malignant ¹⁸F-FDG-avid tissue sites are shown as (o) and benign¹⁸F-FDG-avid tissue sites are shown as (x). The thresholds for probe positivity, expressed as target-to-background ratios, are graphed as a function of the mean background count rate. The ratiometric threshold criteria of 1.5-to-1 is shown as a dashed line and the three-sigma threshold criteria is shown as a solid line curve.

Figure 3

The receiver operating characteristic (ROC) curve for various statistical threshold criteria values for probe positivity from the entire group of 401 gamma detection probe measurement sets is illustrated. The data curve is labeled with the specific numbers of standard deviations indicated. The dashed line indicates a hypothesis test of no diagnostic discrimination. The ROC curve ranges from −46 to 74 standard deviations above the mean background count rate. The operating point on the data curve for three standard deviations above the mean background count rate is indicated as three-sigma threshold criteria (*), and corresponds to a true positive rate of 71% and false positive rate of 40%. Two-sigma operating point is indicated by (●). The optimal operating point is indicated by (+). The area under the ROC curve is 0.6728 (67.3%).

Figure 4

The receiver operating characteristic (ROC) curve for various ratiometric threshold criteria values for probe positivity from the entire group of 401 gamma detection probe measurement sets is illustrated. The ROC curve ranges from target-to-background ratios of −1-to-1 to 9-to-1 above the mean background count rate. The 1.5-to-1 ratiometric operating point is indicated by (*). The 1.33-to-1 (optimal) ratiometric operating point is indicated by (+). The area under the ROC curve is 0.7150 (71.5%).