Purpose: Raman scattering spectra can be thought of as the "fingerprints" of the investigated material. The purpose of this work was to link the absorbed doses of irradiated radiochromic film at the micrometer level with changes in their Raman spectra. Methods: Raman spectra of irradiated GAFCHROMIC EBT3 film with doses ranging from 0 to 40 Gy were acquired. The excitation wavelengths used in the experiments (457.9 and 647.1 nm) coincided with electronic transitions of the active layer of the film. The effect of resonance Raman scattering enhanced Raman peaks in the resonance region. Spectra were taken in the range of room temperature to around the temperature of liquid nitrogen (À190°C). Results: The Raman peak intensity redistribution is shown for films with different absorbed doses. The ratio of intensities of the 1445 cm À1 band with respect to the 1330 cm À1 band increases with the increase in absorbed dose. This allows building a dose calibration curve for the film. Conclusion: The dose distribution of the irradiated film can be identified based on the intensity ratio of the 1445 and 1330 cm À1 bands by means of Raman mapping. This is a noninvasive and computerized readout method which provides micrometer resolution results for the film surface. This is beneficial in the use of radiochromic films as dosimeters for high-precision radiotherapies.

Background Deriving individual tumor genomic characteristics from patient imaging analysis is desirable. We explore the predictive value of 2-[18F]FDG uptake with regard to the KRAS mutational status of colorectal adenocarcinoma liver metastases (CLM). Methods 2-[18F]FDG PET/CT images, surgical pathology and molecular diagnostic reports of 37 patients who underwent PET/CT-guided biopsy of CLM were reviewed under an IRB-approved retrospective research protocol. Sixty CLM in 39 interventional PET scans of the 37 patients were segmented using two different auto-segmentation tools implemented in different commercially available software packages. PET standard uptake values (SUV) were corrected for: (1) partial volume effect (PVE) using cold wall-corrected contrast recovery coefficients derived from phantom spheres with variable diameter and (2) variability of arterial tracer supply and variability of uptake time after injection until start of PET scan derived from the tumor-to-blood standard uptake ratio (SUR) approach. The correlations between the KRAS mutational status and the mean, peak and maximum SUV were investigated using Student’s t test, Wilcoxon rank sum test with continuity correction, logistic regression and receiver operation characteristic (ROC) analysis. These correlation analyses were also performed for the ratios of the mean, peak and maximum tumor uptake to the mean blood activity concentration at the time of scan: SURMEAN, SURPEAK and SURMAX, respectively. Results Fifteen patients harbored KRAS missense mutations (KRAS+), while another 3 harbored KRAS gene amplification. For 31 lesions, the mutational status was derived from the PET/CT-guided biopsy. The Student’s t test p values for separating KRAS mutant cases decreased after applying PVE correction to all uptake metrics of each lesion and when applying correction for uptake time variability to the SUR metrics. The observed correlations were strongest when both corrections were applied to SURMAX and when the patients harboring gene amplification were grouped with the wild type: p ≤ 0.001; ROC area under the curve = 0.77 and 0.75 for the two different segmentations, respectively, with a mean specificity of 0.69 and sensitivity of 0.85. Conclusion The correlations observed after applying the described corrections show potential for assigning probabilities for the KRAS missense mutation status in CLM using 2-[18F]FDG PET images.

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