In this study, we tested a method to automatically delineate lung functional volumes with 68Ga-V/Q PET/CT consisting in applying a fixed threshold value expressed as a percentage of the maximal value. The most appropriate cutoff was 15%max for both ventilation and perfusion images. However, using this unique threshold systematically provided unacceptable difference compared to the reference volume in most individual patients and relatively poor correlation with PFT parameters.
In an initial approach, we looked at global parameters such as Pearson’s coefficients, mean volume difference, and similarity indexes. For both ventilation and perfusion volumes, we found a threshold value (15%max) that provided promising results according to these global parameters. For example, we found with the 15%max threshold for perfusion functional volumes a mean volume difference of − 3.3%, a Pearson’s coefficient of 0.81, and a median Dice similarity coefficient of 0.93.
However, on an individual patient basis, these optimal cutoffs provided, in some patients, wide difference as compared to the visual method. The limits of agreement between the “optimal” automatic volume and the manual volume were large, − 31.0 and 30.2% for ventilation images and − 21.1 and 27.8% for perfusion images, respectively. In addition, the range of volume difference was up to 40.4% for ventilation images and 35.5% of WL for perfusion images. This appears unacceptably wide for a quantitative imaging tool of regional lung function. This was confirmed by assessing correlation with PFT parameters. Indeed, correlation was only observed with FEV1/FVC and was much lower as compared with the manual segmentation. Using an automatic method of delineation consisting in applying the same threshold for all patients is therefore inaccurate and inappropriate for the determination of lung functional volumes with 68Ga-V/Q PET/CT.
On the other hand, applying a threshold value expressed as a percentage of the maximal value retains several advantages as compared with the manual method. First, it allows a much more rapid delineation of contours. Second, it may allow a more accurate delineation of small areas of lung dysfunction, especially in patients with heterogeneous disease. Finally, it allows an objective and reproducible description of how the contours were obtained. Accordingly, a threshold expressed as a percentage of the maximal value but visually adapted to an individual patient may be an interesting compromise. The delineation process should start with the 15%max threshold. Based on a visual analysis, lower (e.g., 10%max, 5%max, …) or higher (20%max, 25%max, …) thresholds could then be tried to determine which one provides the most representative of functional volumes. Of note, the range of threshold values was relatively small in our series, from 5%max to 30%max, limiting the number of thresholds needing to be tested.
The main limitation of our delineation method is that it essentially relies on the determination of the maximal value, which then determines the cutoff value. Especially for ventilation images, the presence of focal tracer accumulation due to airway deposition may hamper the determination of the maximal value . In our study, the maximal value was determined excluding such foci, but this process may be somewhat difficult in patients with very heterogeneous lung disease. Future research may focus on other reference value to determine the cutoff. An approach based on an absolute quantification, especially for perfusion image, may also become a reality with PET technology. Finally, the automatic delineation was applied to the whole lung volumes. In scans with an important physiological anterior-posterior gradient, an automatic segmentation may exclude the anterior part of the lungs while it appears to be functional. In that respect, a delineation based on a segmental approach may be of interest.
Another possible limitation of our study is the choice of the visual delineation as the reference standard. Although we have demonstrated this to be correlated with pulmonary function test parameters, the variability in manual delineation may have added to the variability. In addition, we performed gated acquisition, which may limit the generalization of the results to non-gated 68Ga-V/Q PET/CT. However, the mid-time expiratory phase of the breathing cycle that was chosen for most of patients is the phase that is usually imaged without gated acquisition.
PET technology offers many additional advantages. It is a noninvasive modality that does not rely on patient effort, except the need to breathe the radioactive gas for a few seconds and to lie relatively still on the PET/CT camera bed during the acquisition time. The acquisition time is low, about 15–20 min with our protocol, and could be reduced due to the high sensitivity of PET technology. There are no known contraindications or acute side effects associated with the radiotracers. The majority of nuclear medicine physicians are now familiar with tomographic images for V/Q scan interpretation , enabling rapid familiarization with this new technique. The effective radiation dose of the scan is low, approximately 2 mSv for the PET acquisition plus an additional 1–2 mSv for the low-dose CT component, equivalent to the dose of V/Q SPECT/CT. Finally, 68Ga is produced by an on-site generator enabling on-demand availability similar to 99mTc but with a longer shelf life of 9–12 months versus 1–2 weeks for 99mTc generator. The 68Ga generator is increasingly available owing to its use for neuroendocrine and prostate cancer imaging [18, 19]. With PET/CT and 68Ga becoming increasingly available, we envisage that widespread adoption of V/Q PET/CT could become a reality.