Regarding the tissue elemental composition calculation from "Dynamic PET/CT measurements of induced positron activity in a prostate cancer patient after 50-MV photon radiation therapy" osama Mawlawi, MD Anderson Cancer Center 21 November 2013 Jongmin Cho1,2, Geoffrey Ibbott2, and Osama Mawlawi3 1The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA 2Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA 3Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA Corresponding author email: email@example.com Abstract We describe limitations of the approach used by Janek et al to determine tissue elemental composition from radioisotope count rate measurements following photon therapy. The approach used by Janek et al lacked three correction factors that are essential to convert the count rate to the elemental composition. We describe these factors here. Correspondence Dear Editor, We read with interest the original research work of Janek et al  that was recently published in the European Journal of Nuclear Medicine and Molecular Imaging (2013, 3:6). Janek et al evaluated the feasibility of determining patient tissue elemental composition following photo-nuclear activation by positron emission tomography. The authors compared the initial count rate of each radioisotope from activated tissue with the International Commission on Radiation Units and Measurements (ICRU) elemental composition data to determine the accuracy of their elemental tissue composition calculation. The method they used was: ρ C12 ~ S1 , ρ O16 ~ S2 , ρ N14 ~ S3 , (1) where ρ C12 , ρ O16 , and ρ N14 are the percentage composition (number of atoms/cm3 ) of 12 C, 16 O, and 14 N, respectively and S1 , S2 , and S3 are the initial count rates of 11 C, 15 O, and 13 N, respectively following activation. For the volume of interest (VOI) containing adipose tissue only, the authors calculated an S1 and an S2 of 32% and 65% while the published ICRU values are 67.7% and 31.5%, respectively. The difference in the elemental compositions between the approach used by the authors and the ICRU data is more than 100%, which can hardly be interpreted as ‘in moderate agreement,’ as indicated by Janek et al. We believe the main reason for the discrepancy between the two measurements in the adipose tissue VOI is the omission of two fundamental factors. The first is the build-up factor 1– e-λI tR , where λ I and tR are the decay constant of radioisotope I and irradiation time, respectively. This factor accounts for the amount of radioactivity generated during the time of its creation. The second factor accounts for the activation rate and is expressed as ∫σ TI Φ E dE, where σ TI is the photo-nuclear cross-section of an atom T converting to a radioisotope I and Φ E is the photon flux. This factor accounts for the amount of radioisotope created due to the product of the cross-section and photon flux. When these two factors are included in the model, the count rate for each element can be calculated by: ST ~ ρ T (1– e-λ I tR ) ∫σ TI Φ E dE (2) and the percentage composition of an element T can be obtained by: ρ T ~ ST / ((1– e- λ I tR ) ∫σ TI Φ E dE) (3) Using the suggested model, the elemental composition for the adipose VOI used by Janek et al. result in a percentage composition of 67.1% carbon, 31.5% oxygen, and 1.4% nitrogen which are in excellent agreement with the published ICRU data (67.7% carbon, 31.5% oxygen, and 0.58% nitrogen). For this calculation, a continuous irradiation time of tR = 6 min 52 s (the total irradiation time, including rotation of the gantry as described by Janek et al) and ∫σ C12C11 Φ E dE = ∫σ O16O15 Φ E dE = 0.4 × ∫σ N14N13 Φ E dE were assumed because ∫σ C12C11 dE and ∫σ O16O15 dE are somewhat similar over the photon energy range of 0 ~ 50 MeV, whereas ∫σ N14N13 dE are two to three times greater than ∫σ C12C11 dE, according to the Experimental Nuclear Reaction Data Database  and Fuller . In addition to the above two factors, there is a third factor that should also be taken into consideration –the perfusion-driven activity, wash-in/out factor. This factor accounts for the accumulation or removal of activity in a VOI due to wash in/out effects during scan time. For the adipose VOI, this factor is negligible because perfusion-driven wash in/out in the adipose tissue is slow . However, for the bladder VOI used by Janek et al, this factor has a much bigger impact. For example, if the wash in/out factor is ignored when using our suggested model, the carbon and oxygen fractions in the bladder VOI will be 27.4% and 72.8%, respectively, which are much worse than the values reported by Janek et al (8% and 92%) compared to the ICRU data (4% and 96%). Modeling the exact amount of new radioisotopes added (wash in) to the bladder VOI is very difficult. However, when such a component is included in the model, the carbon and oxygen fractions are expected to be closer to the published ICRU values. This is primarily due to correcting the overestimation of the slowly decaying 11C (reducing the 12C fraction) from the continuous radioisotope influx to the bladder. Recently, our group published the results of using PET/CT measurements to calculate patient tissue elemental composition after proton radiation therapy . We calculated patients’ soft tissue elemental composition (C and O) for the entire activated region and compared seven regions of interest with the ICRU data. We used a previously published perfusion driven wash-out model [4,6,7], and the calculated C and O compositions in all of these regions were on average within 10% (range 3% ~ 15%) of the ICRU values. The omission of a wash-out model increased the differences between our calculations and ICRU data by as much as 30%. We think that the mathematical approach described by Cho et al , which includes all factors described above, should be used to improve the approach used by Janek et al to determine C, O, and N compositions after photon radiation therapy. Authors’ contributions Jongmin Cho first read the article by Janek et al and found the limitations of their approach. Jongmin Cho was then assisted by Geoffrey Ibbott and Osama Mawlawi in developing a methodology to improve the approach of Janek et al. All authors read and approved the final manuscript. Acknowledgement The authors thank Carlos Gonzalez-Lepera, Michael Gillin, and Frances Stingo at the University of Texas MD Anderson Cancer Center and Harald Paganetti at Massachusetts General Hospital and Harvard Medical School for valuable comments. This research was supported in part by the National Institutes of Health through MD Anderson’s Cancer Center Support Grant (CA016672). References 1. Janek Straat S, Jacobsson H, Noz ME, Andreassen B, Naslund I, Jonsson C: Dynamic PET/CT measurements of induced positron activity in a prostate cancer patient after 50-MV photon radiation therapy. EJNMMI Res 2013, 3:6. 2. Experimental Nuclear Reaction Data (EXFOR) Database. [http://www.nndc.bnl.gov/exfor/exfor00.htm]. Accessed May 2013. 3. Fuller EG: Photonuclear reaction cross sections for 12C, 14N and 16O. Phys Rep 1985, 127:185–231. 4. 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