Asphericity of tumor FDG uptake in non-small cell lung cancer: reproducibility and implications for harmonization in multicenter studies

Abstract

Background: Asphericity (ASP) of the primary tumor's metabolic tumor volume (MTV) in FDG-PET/CT is independently predictive for survival in patients with non-small cell lung cancer (NSCLC). However, comparability between PET systems may be limited. Therefore, reproducibility of ASP was evaluated at varying image reconstruction and acquisition times to assess feasibility of ASP assessment in multicenter studies.

Methods: This is a retrospective study of 50 patients with NSCLC (female 20; median age 69 years) undergoing pretherapeutic FDG-PET/CT (median 3.7 MBq/kg; 180 s/bed position). Reconstruction used OSEM with TOF_4/16 (iterations 4; subsets 16; in-plane filter 2.0, 6.4 or 9.5 mm), TOF_4/8 (4 it; 8 ss; filter 2.0/6.0/9.5 mm), PSF + TOF_2/17 (2 it; 17 ss; filter 2.0/7.0/10.0 mm) or Bayesian-penalized likelihood (Q.Clear; beta, 600/1750/4000). Resulting reconstructed spatial resolution (FWHM) was determined from hot sphere inserts of a NEMA IEC phantom. Data with approx. 5-mm FWHM were retrospectively smoothed to achieve 7-mm FWHM. List mode data were rebinned for acquisition times of 120/90/60 s. Threshold-based delineation of primary tumor MTV was followed by evaluation of relative ASP/SUVmax/MTV differences between datasets and resulting proportions of discordantly classified cases.

Results: Reconstructed resolution for narrow/medium/wide in-plane filter (or low/medium/high beta) was approx. 5/7/9 mm FWHM. Comparing different pairs of reconstructed resolution between TOF_4/8, PSF + TOF_2/17, Q.Clear and the reference algorithm TOF_4/16, ASP differences was lowest at FWHM of 7 versus 7 mm. Proportions of discordant cases (ASP > 19.5% vs. ≤ 19.5%) were also lowest at 7 mm (TOF_4/8, 2%; PSF + TOF_2/17, 4%; Q.Clear, 10%). Smoothing of 5-mm data to 7-mm FWHM significantly reduced discordant cases (TOF_4/8, 38% reduced to 2%; PSF + TOF_2/17, 12% to 4%; Q.Clear, 10% to 6%), resulting in proportions comparable to original 7-mm data. Shorter acquisition time only increased proportions of discordant cases at < 90 s.

Conclusions: ASP differences were mainly determined by reconstructed spatial resolution, and multicenter studies should aim at comparable FWHM (e.g., 7 mm; determined by in-plane filter width). This reduces discordant cases (high vs. low ASP) to an acceptable proportion for TOF and PSF + TOF of < 5% (Q.Clear: 10%). Data with better resolution (i.e., lower FWHM) could be retrospectively smoothed to the desired FWHM, resulting in a comparable number of discordant cases.

Keywords: Asphericity; FDG-PET; Image reconstruction; Non-small cell lung cancer; Prognosis; Reproducibility; Spatial resolution.

Fig. 1

Sphere activity profiles. a Radial activity profiles of the 37-mm sphere for the reference algorithm with different in-plane filter widths to achieve different levels of reconstructed spatial resolution (FWHM). Acquisition time was 180 s. Substantial noise propagation can be observed at FWHM of approx. 5 mm. b Corresponding profiles for 6.4-mm in-plane filter width at shorter acquisition times. Noise especially increases between 90 and 60 s acquisition time, while reconstructed spatial resolution remains similar

Fig. 2

Patient example. Coronar FDG-PET images of the thorax for a patient are displayed for all 12 reconstruction algorithms (body mass index 22.5 kg/m²; injected activity 3.5 MBq/kg; acquisition time 180 s per bed position). The given noise level is the median of all 50 patients. Data are separated by reconstructed spatial resolution of approx. 5 mm (left column), 7 mm (middle column) or 9 mm FWHM (right column), respectively. The reference algorithm is highlighted in green. At 7 mm FWHM spatial resolution, ASP of the primary tumor (red arrow) was concordantly high (> 19.5%) with all algorithms except for Q.Clear

Fig. 3

Distribution of ASP values with the reference algorithm. ASP values at reconstructed spatial resolution of 7.0-mm FWHM and acquisition time of 180 s are displayed for each of the 50 patients for TOF_4/8/6, PSF + TOF_2/17/7 and Q.Clear₁₇₅₀. The cutoff at 19.5% is highlighted at each axis. Several tumors feature ASP in proximity to this cutoff. Data points that are located either in the left upper section or in the right lower section of the diagram represent discordantly classified cases when compared to the reference algorithm TOF_4/16/6.4 (TOF_4/8/6, n = 1; PSF + TOF_2/17/7, n = 2; Q.Clear₁₇₅₀, n = 5 discordant cases)

Fig. 4

Correlation plots for ASP and MTV. Correlation plots for ASP and MTV for the three TOF_4/16 algorithms. a shows plots for all patients. Correlation was moderate with TOF_4/16/2 and moderate to high with TOF_4/16/6.4 and TOF_4/16/9.5. b Correlation was negligible (r < 0.3) in lesions with MTV ≤ 15 ml for TOF_4/16/2, while the threshold was lower for TOF_4/16/6.4 (MTV ≤ 2.5 ml) and TOF_4/16/9.5 (MTV ≤ 5.0 ml). The generally lower correlation of ASP and MTV in smaller lesions results from the limited spatial resolution. With TOF_4/16/2, high noise level contributes to the high MTV threshold for correlation. With TOF_4/16/9.5, the poorer reconstructed spatial resolution may contribute to the higher MTV threshold compared to TOF_4/16/6.4