Fractal analysis improves tumour size measurement on computed tomography in pancreatic ductal adenocarcinoma. Comparison with gross pathology and multi-parametric MRI

Tumour size measurement is pivotal for staging and stratifying patients with pancreatic ductal adenocarcinoma (PDA). However, computed tomography (CT) frequently underestimates tumour size due to insufficient depiction of the tumour rim. CT-derived fractal dimension (FD) maps might help to visualise perfusion chaos, thus allowing more realistic size measurement. In 46 patients with histology-proven PDA, we compared tumour size measurements in routine multiphasic CT scans, CT-derived FD maps, multi-parametric magnetic resonance imaging (mpMRI), and, where available, gross pathology of resected specimens. Gross pathology was available as reference for diameter measurement in a discovery cohort of 10 patients. The remaining 36 patients constituted a separate validation cohort with mpMRI as reference for diameter and volume. Median RECIST diameter of all included tumours was 40 mm (range: 18-82 mm). In the discovery cohort, we found significant (p = 0.03) underestimation of tumour diameter on CT compared with gross pathology (Δdiameter${}_{3D}$ = -5.7 mm), while realistic diameter measurements were obtained from FD maps (Δdiameter${}_{3D}$ = 0.6 mm) and mpMRI (Δdiameter${}_{3D}$ = -0.9 mm), with excellent correlation between the two (R${}^2$ = 0.88). In the validation cohort, CT also systematically underestimated tumour size in comparison to mpMRI (Δdiameter${}_{3D}$ = -10.6 mm, Δvolume = -10.2 mL), especially in larger tumours. In contrast, FD map measurements agreed excellently with mpMRI (Δdiameter${}_{3D}$ = +1.5 mm, Δvolume = -0.6 mL). Quantitative perfusion chaos was significantly (p = 0.001) higher in the tumour rim (FD${}_{rim}$ = 4.43) compared to the core (FD${}_{core}$ = 4.37) and remote pancreas (FD${}_{pancreas}$ = 4.28). In PDA, fractal analysis visualises perfusion chaos in the tumour rim and improves size measurement on CT in comparison to gross pathology and mpMRI, thus compensating for size underestimation from routine CT. CT-based measurement of tumour size in pancreatic adenocarcinoma systematically underestimates both tumour diameter (Δdiameter = -10.6 mm) and volume (Δvolume = -10.2 mL), especially in larger tumours. Fractal analysis provides maps of the fractal dimension (FD), which enable a more reliable and size-independent measurement using gross pathology or multi-parametric MRI as reference standards. FD quantifies perfusion chaos---the underlying pathophysiological principle---and can separate the more chaotic tumour rim from the tumour core and adjacent non-tumourous pancreas tissue.