title: PET quantification with a histogram derived total activity metric: superior quantitative consistency compared to total lesion glycolysis with absolute or relative SUV thresholds in phantoms and lung cancer patients.
abstract: BACKGROUND
  The increasing use of molecular imaging probes as biomarkers in oncology emphasizes the need for robust and stable methods for quantifying tracer uptake in PET imaging. The primary motivation for this research was to find an accurate method to quantify the total tumor uptake. Therefore we developed a histogram-based method to calculate the background subtracted lesion (BSL) activity and validated BSL by comparing the quantitative consistency with the total lesion glycolysis (TLG) in phantom and patient studies.
  
  
  METHODS
  A thorax phantom and a PET-ACR quality assurance phantom were scanned with increasing FDG concentrations. Volumes of interest (VOIs) were placed over each chamber. TLG was calculated with a fixed threshold at SUV 2.5 (TLG2.5) and a relative threshold at 42% of SUVmax (TLG42%). The histogram for each VOI was built and BSL was calculated. Comparison with the total injected FDG activity (TIA) was performed using concordance correlation coefficients (CCC) and the slope (a). Fifty consecutive patients with FDG-avid lung tumors were selected under an IRB waiver. TLG42%, TLG2.5 and BSL were compared to the reference standard calculating CCC and the slope.
  
  
  RESULTS
  In both phantoms, the CCC for lesions with a TIA ≤50ml*SUV between TIA and BSL was higher and the slope closer to 1 (CCC=0.933, a=1.189), than for TLG42% (CCC=0.350, a=0.731) or TLG2.5 (CCC=0.761, a=0.727). In 50 lung lesions BSL had a slope closer to 1 compared to the reference activity than TLG42% (a=1.084 vs 0.618 - for high activity lesions) and also closer to 1 than TLG2.5 (a=1.117 vs 0.548 - for low activity lesions).
  
  
  CONCLUSIONS
  The histogram based BSL correlated better with TIA in both phantom studies than TLG2.5 or TLG42%. Also in lung tumors, the BSL activity is overall more accurate in quantifying the lesion activity compared to the two most commonly applied TLG quantification methods.
authors.affiliation: Department of Radiology and Nuclear Medicine, University Hospital Zurich, Ramistrasse 100, 8091 Zurich, Switzerland. Electronic address: Irene.burger@usz.ch.
authors.forename: Irene A
authors.initials: IA
authors.lastname: Burger
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065.
authors.forename: Hebert Alberto
authors.initials: HA
authors.lastname: Vargas
authors.affiliation: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065.
authors.forename: Aditya
authors.initials: A
authors.lastname: Apte
authors.affiliation: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Beattie
authors.affiliation: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065.
authors.forename: John L
authors.initials: JL
authors.lastname: Humm
authors.affiliation: Department of Epidemiology-Biostatistics, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065.
authors.forename: Mithat
authors.initials: M
authors.lastname: Gonen
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Larson
authors.affiliation: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065.
authors.forename: C
authors.initials: C
authors.lastname: Ross Schmidtlein
mesh_terms: D001692:Biological Transport; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D019047:Phantoms, Imaging; D049268:Positron-Emission Tomography / Q000295:instrumentation*; D013382:Subtraction Technique / Q000295:instrumentation*
chemical_list: D019788:Fluorodeoxyglucose F18
keywords: Histogram; PET quantification; Phantom; Total lesion glycolysis; Tumor uptake