title: FDG uptake heterogeneity evaluated by fractal analysis improves the differential diagnosis of pulmonary nodules.
abstract: OBJECTIVE
  The present study aimed to determine whether fractal analysis of morphological complexity and intratumoral heterogeneity of FDG uptake can help to differentiate malignant from benign pulmonary nodules.
  
  
  METHODS
  We retrospectively analyzed data from 54 patients with suspected non-small cell lung cancer (NSCLC) who were examined by FDG PET/CT. Pathological assessments of biopsy specimens confirmed 35 and 19 nodules as NSCLC and inflammatory lesions, respectively. The morphological fractal dimension (m-FD), maximum standardized uptake value (SUV(max)) and density fractal dimension (d-FD) of target nodules were calculated from CT and PET images. Fractal dimension is a quantitative index of morphological complexity and tracer uptake heterogeneity; higher values indicate increased complexity and heterogeneity.
  
  
  RESULTS
  The m-FD, SUV(max) and d-FD significantly differed between malignant and benign pulmonary nodules (p<0.05). Although the diagnostic ability was better for d-FD than m-FD and SUV(max), the difference did not reach statistical significance. Tumor size correlated significantly with SUV(max) (r=0.51, p<0.05), but not with either m-FD or d-FD. Furthermore, m-FD combined with either SUV(max) or d-FD improved diagnostic accuracy to 92.6% and 94.4%, respectively.
  
  
  CONCLUSIONS
  The d-FD of intratumoral heterogeneity of FDG uptake can help to differentially diagnose malignant and benign pulmonary nodules. The SUV(max) and d-FD obtained from FDG-PET images provide different types of information that are equally useful for differential diagnoses. Furthermore, the morphological complexity determined by CT combined with heterogeneous FDG uptake determined by PET improved diagnostic accuracy.
authors.affiliation: Department of Nuclear Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan; Division of Medical Quantum Science, Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: kenta5710@gmail.com.
authors.forename: Kenta
authors.initials: K
authors.lastname: Miwa
authors.affiliation: Department of Nuclear Medicine, Kawasaki Medical School, 577 Matsushima Kurashiki, Okayama 701-0192, Japan. Electronic address: inubushi@med.kawasaki-m.ac.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Inubushi
authors.affiliation: Department of Nuclear Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan. Electronic address: kei1192@hotmail.co.jp.
authors.forename: Kei
authors.initials: K
authors.lastname: Wagatsuma
authors.affiliation: Department of Molecular Imaging and Diagnosis, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: minagao@radiol.med.kyushu-u.ac.jp.
authors.forename: Michinobu
authors.initials: M
authors.lastname: Nagao
authors.affiliation: Department of Nuclear Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan. Electronic address: taisuke113@gmail.com.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Murata
authors.affiliation: Department of Nuclear Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan. Electronic address: masamichi.koyama@jfcr.or.jp.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Koyama
authors.affiliation: Department of Nuclear Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan. Electronic address: mitsuru@jfcr.or.jp.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Koizumi
authors.affiliation: Division of Medical Quantum Science, Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: msasaki@hs.med.kyushu-u.ac.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sasaki
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D003074:Solitary Pulmonary Nodule / Q000175:diagnosis* / Q000378:metabolism*; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: (18)F-FDG PET/CT; Diagnostic accuracy; Non-small cell lung cancer; Texture analysis