K Karki

Apparent diffusion coefficient (ADC) change on repeated diffusion-weighted magnetic resonance imaging during radiochemotherapy for non-small cell lung cancer: A pilot study

OBJECTIVES Serial diffusion-weighted magnetic resonance imaging (DW-MRI) during radiochemotherapy of non-small cell lung cancer (NSCLC) is analyzed to investigate the apparent diffusion coefficient (ADC) as a potential biomarker for tumor response. METHODS Ten patients underwent DW-MRI prior to and at three and six weeks during radiochemotherapy. Three methods of contouring primary tumors (PT) were performed to evaluate the impact of tumor heterogeneity on ADC values: PTT: whole tumor volume; PTT-N: PTT-necrosis; PTL: small volume of presumed active tumor with low ADC value. Pretreatment and during-treatment absolute ADC values and ADC value changes were analyzed for PT and involved lymph nodes (LN). RESULTS ADC values for PTT, PTT-N, PTL and LN increased by 8-14% (PT) and 15% (LN) at three weeks, and 19-26% and 23% at 6 weeks post initial treatment (p=0.04-0.002). Average percent ADC value increase was smaller than tumor volume regression (p=0.06-0.0005). Patients with overall survival <12 months had a lower increase of ADC values compared to longer surviving patients (p=0.008 for PTT). CONCLUSIONS Significant ADC value increases during radiochemotherapy for non-small cell lung cancer were observed. ADC value change during treatment appears to be an independent marker of patient outcome and warrants further investigation.

Estimation of optimal b-value sets for obtaining apparent diffusion coefficient free from perfusion in non-small cell lung cancer

The purpose of this study was to determine optimal sets of b-values in diffusion-weighted MRI (DW-MRI) for obtaining monoexponential apparent diffusion coefficient (ADC) close to perfusion-insensitive intravoxel incoherent motion (IVIM) model ADC (ADCIVIM) in non-small cell lung cancer. Ten subjects had 40 DW-MRI scans before and during radiotherapy in a 1.5 T MRI scanner. Respiratory triggering was applied to the echo-planar DW-MRI with TR ≈ 4500 ms, TE  =  74 ms, eight b-values of 0-1000 μs μm(-2), pixel size  =  1.98 × 1.98 mm(2), slice thickness  =  6 mm, interslice gap  =  1.2 mm, 7 axial slices and total acquisition time ≈6 min. One or more DW-MRI scans together covered the whole tumour volume. Monoexponential model ADC values using various b-value sets were compared to reference-standard ADCIVIM values using all eight b-values. Intra-scan coefficient of variation (CV) of active tumour volumes was computed to compare the relative noise in ADC maps. ADC values for one pre-treatment DW-MRI scan of each of the 10 subjects were computed using b-value pairs from DW-MRI images synthesized for b-values of 0-2000 μs μm(-2) from the estimated IVIM parametric maps and corrupted by various Rician noise levels. The square root of mean of squared error percentage (RMSE) of the ADC value relative to the corresponding ADCIVIM for the tumour volume of the scan was computed. Monoexponential ADC values for the b-value sets of 250 and 1000; 250, 500 and 1000; 250, 650 and 1000; 250, 800 and 1000; and 250-1000 μs μm(-2) were not significantly different from ADCIVIM values (p > 0.05, paired t-test). Mean error in ADC values for these sets relative to ADCIVIM were within 3.5%. Intra-scan CVs for these sets were comparable to that for ADCIVIM. The monoexponential ADC values for other sets-0-1000; 50-1000; 100-1000; 500-1000; and 250 and 800 μs μm(-2) were significantly different from the ADCIVIM values. From Rician noise simulation using b-value pairs, there was a wide range of acceptable b-value pairs giving small RMSE of ADC values relative to ADCIVIM. The pairs for small RMSE had lower b-values as the noise level increased. ADC values of a two b-value set-250 and 1000 μs μm(-2), and all three b-value sets with 250, 1000 μs μm(-2) and an intermediate value approached ADCIVIM, with relative noise comparable to that of ADCIVIM. These sets may be used in lung tumours using comparatively short scan and post-processing times. Rician noise simulation suggested that the b-values in the vicinity of these experimental best b-values can be used with error within an acceptable limit. It also suggested that the optimal sets will have lower b-values as the noise level becomes higher.

SU-F-R-35: Repeatability of Texture Features in T1- and T2-Weighted MR Images

PURPOSE To evaluate repeatability of lung tumor texture features from inspiration/expiration MR image pairs for potential use in patient specific care models and applications. Repeatability is a desirable and necessary characteristic of features included in such models. METHODS T1-weighted Volumetric Interpolation Breath-Hold Examination (VIBE) and/or T2-weighted MRI scans were acquired for 15 patients with non-small cell lung cancer before and during radiotherapy for a total of 32 and 34 same session inspiration-expiration breath-hold image pairs respectively. Bias correction was applied to the VIBE (VIBE_BC) and T2-weighted (T2_BC) images. Fifty-nine texture features at five wavelet decomposition ratios were extracted from the delineated primary tumor including: histogram(HIST), gray level co-occurrence matrix(GLCM), gray level run length matrix(GLRLM), gray level size zone matrix(GLSZM), and neighborhood gray tone different matrix (NGTDM) based features. Repeatability of the texture features for VIBE, VIBE_BC, T2-weighted, and T2_BC image pairs was evaluated by the concordance correlation coefficient (CCC) between corresponding image pairs, with a value greater than 0.90 indicating repeatability. RESULTS For the VIBE image pairs, the percentage of repeatable texture features by wavelet ratio was between 20% and 24% of the 59 extracted features; the T2-weighted image pairs exhibited repeatability in the range of 44-49%. The percentage dropped to 10-20% for the VIBE_BC images, and 12-14% for the T2_BC images. In addition, five texture features were found to be repeatable in all four image sets including two GLRLM, two GLZSM, and one NGTDN features. No single texture feature category was repeatable among all three image types; however, certain categories performed more consistently on a per image type basis. CONCLUSION We identified repeatable texture features on T1- and T2-weighted MRI scans. These texture features should be further investigated for use in specific applications such as tissue classification and changes during radiation therapy utilizing a standard imaging protocol. Authors have the following disclosures: a research agreement with Philips Medical systems (Hugo, Weiss), a license agreement with Varian Medical Systems (Hugo, Weiss), research grants from the National Institute of Health (Hugo, Weiss), UpToDate royalties (Weiss), and none(Mahon, Ford, Karki). Authors have no potential conflicts of interest to disclose.

Clinically relevant investigation of flattening filter-free skin dose

As flattening filter-free (FFF) photon beams become readily available for treatment delivery in techniques such as SBRT, thorough investigation of skin dose from FFF photon beams is necessary under clinically relevant conditions. Using a parallel-plate PTW Markus chamber placed in a custom water-equivalent phantom, surface-dose measurements were taken at 2×2,3×3,4×4,6×6,8×8,10×10,20×20, and 30×30 cm2 field sizes, at 80, 90, and 100 cm source-to-surface distances (SSDs), and with fields defined by jaws and multileaf collimator (MLC) using multiple beam energies (6X, 6XFFF, 10X, and 10XFFF). The same set of measurements was repeated with the chamber at a reference depth of 10 cm. Each surface measurement was normalized by its corresponding reference depth measurement for analysis. The FFF surface doses at 100 cm SSD were higher than flattened surface doses by 45% at 2×2 cm2 to 13% at 20×20 cm2 for 6 MV energy. These surface dose differences varied to a greater degree as energy increased, ranging from +63% at 2×2 cm2 to -2% at 20×20 cm2 for 10 MV. At small field sizes, higher energy increased FFF surface dose relative to flattened surface dose; while at larger field sizes, relative FFF surface dose was higher for lower energies. At both energies investigated, decreasing SSD caused a decrease in the ratios of FFF-to-flattened surface dose. Variability with SSD of FFF-to-flattened surface dose differences increased with field size and ranged from 0% to 6%. The field size at which FFF and flattened beams gave the same skin dose increased with decreasing beam energy. Surface dose was higher with MLC fields compared to jaw fields under most conditions, with the difference reaching its maximum at a field size between 4×4 cm2 and 6×6 cm2 for a given energy and SSD. This study conveyed the magnitude of surface dose in a clinically meaningful manner by reporting results normalized to 10 cm depth dose instead of depth of dose maximum. PACS number(s): 87.53.Bn, 87.53.Ly, 87.55.-x, 87.55.N-, 87.56.N.As flattening filter‐free (FFF) photon beams become readily available for treatment delivery in techniques such as SBRT, thorough investigation of skin dose from FFF photon beams is necessary under clinically relevant conditions. Using a parallel‐plate PTW Markus chamber placed in a custom water‐equivalent phantom, surface‐dose measurements were taken at 2×2,3×3,4×4,6×6,8×8,10×10,20×20, and 30×30 cm2 field sizes, at 80, 90, and 100 cm source‐to‐surface distances (SSDs), and with fields defined by jaws and multileaf collimator (MLC) using multiple beam energies (6X, 6XFFF, 10X, and 10XFFF). The same set of measurements was repeated with the chamber at a reference depth of 10 cm. Each surface measurement was normalized by its corresponding reference depth measurement for analysis. The FFF surface doses at 100 cm SSD were higher than flattened surface doses by 45% at 2×2 cm2 to 13% at 20×20 cm2 for 6 MV energy. These surface dose differences varied to a greater degree as energy increased, ranging from +63% at 2×2 cm2 to −2% at 20×20 cm2 for 10 MV. At small field sizes, higher energy increased FFF surface dose relative to flattened surface dose; while at larger field sizes, relative FFF surface dose was higher for lower energies. At both energies investigated, decreasing SSD caused a decrease in the ratios of FFF‐to‐flattened surface dose. Variability with SSD of FFF‐to‐flattened surface dose differences increased with field size and ranged from 0% to 6%. The field size at which FFF and flattened beams gave the same skin dose increased with decreasing beam energy. Surface dose was higher with MLC fields compared to jaw fields under most conditions, with the difference reaching its maximum at a field size between 4×4 cm2 and 6×6 cm2 for a given energy and SSD. This study conveyed the magnitude of surface dose in a clinically meaningful manner by reporting results normalized to 10 cm depth dose instead of depth of dose maximum. PACS number(s): 87.53.Bn, 87.53.Ly, 87.55.‐x, 87.55.N‐, 87.56.N‐

TH-CD-204-02: Longitudinal Assessment of Radiation Treatment Response in Non-Small Cell Lung Cancer Using Intravoxel Incoherent Motion Model Diffusion-Weighted MRI

Purpose: Perfusion-insensitive apparent diffusion coefficient (ADC) is obtained using intravoxel incoherent motion (IVIM) model by separating perfusion compartment. The purpose of this study is to assess the longitudinal changes in the reference-standard IVIM model ADC (ADCIVIM) values of lung tumor volumes due to treatment response and to compare the relative longitudinal changes of the monoexponential model ADC values with that of ADCIVIM. Methods: Ten subjects had diffusion-weighted MRI (DW-MRI) scans at 0 week (pre-treatment), and 3 and 6 weeks during radiotherapy in 1.5T MRI scanner. Respiratory triggering was applied to the echo-planar DW-MRI with TR=∼4500 ms, TE=74 ms, eight b-values of 0–1000 µs/µm 2 , pixel size=1.98×1.98 mm 2 , slice thickness/gap=6 mm/1.2 mm and 7 axial slices. The ADCIVIM values and volumes of active tumors were compared longitudinally using paired t-test. Changes in monoexponential model ADC values using the sets-0–1000; 50–1000; 100–1000; 250–1000; 500–1000; 250, 500 and 1000; 250, 650 and 1000; 250, 800 and 1000; 250 and 800; and 250 and 1000 µs/µm 2 at 3 and 6 weeks relative to their corresponding baseline values at 0 week were also compared with that of ADCIVIM using all b-values. Results: The ADCIVIM values increased significantly from 0 to 3 weeks, and from 3 to 6 weeks (p 0.05) except for 0–1000, and 50–1000 µs/µm 2 sets at 3 weeks. The active tumor volume decreased significantly from 0 to 6 weeks. Conclusion: Active tumor ADCIVIM value increased and volume decreased during radiotherapy. No significant differences between the longitudinal changes of monoexponential ADC and ADCIVIM values were generally observed. DW-MRI is efficient in showing active tumor functional and volume changes due to radiation treatment in lung cancer. This work was supported by Virginia Commonwealth University Massey Cancer Center pilot project A35242 (EW). There are no conflicts of interest.

TH‐CD‐207‐10: Effect of Noise On the Optimal B‐Value Pairs for Obtaining Perfusion‐Insensitive Apparent Diffusion Coefficient in Diffusion‐Weighted MRI

Purpose: Monoexponential model using typically two or three b-values is used in clinical diffusion-weighted MRI (DW-MRI) to compute the apparent diffusion coefficient (ADC) due to computational simplicity and reduced post-processing times compared to the intravoxel incoherent motion (IVIM) model. The purpose of this study is to find the effect of noise level on the optimal b-values to obtain monoexponential ADC values close to the perfusion-insensitive IVIM model ADC (ADCIVIM). Methods: Respiratory triggering was applied to the echo-planar DW-MRI in 1.5T scanner with TR=∼4500 ms, TE=74 ms, eight b-values of 0–1000 µs/µm 2 , pixel size=1.98×1.98 mm 2 , slice thickness/gap=6 mm/1.2 mm and 7 axial slices. For one pre-treatment DW-MRI scan of each of ten subjects, DW-MRI signal intensity images with b-values of 0–2000 µs/µm 2 were synthesized on a voxel-by-voxel basis from the estimated IVIM parameters. The images were corrupted by Rician noise distribution with σ=0, 5, 10 and 15. Monoexponential ADC value was computed using b-value pairs with low b-value (blow) of 0–500 µs/µm 2 and high b-value (bhigh) of 650–2000 µs/µm 2 . The square root of the mean of squared error percentage (RMSE) of the ADC value relative to the corresponding reference-standard ADCIVIM for the tumor volumes of the scans was computed. Results: There were wide bands of b-value sets giving small RMSE of ADC value relative to the ground-truth ADCIVIM value. The band of sets with small errors moved from high values of both blow and b high for the lowest noise level towards the lower values with the increase of the noise levels. The minimum error corresponding to the optimal sets increased with the noise level. The range of RMSE for σ=5 was approximately 5–30% whereas that for σ=15 was approximately 10–50%. Conclusion: The optimal b-value pairs for obtaining ADC values close to reference-standard values depended on the noise level and hence SNR. This work was supported by Virginia Commonwealth University Massey Cancer Center pilot project A35242 (EW). There are no conflicts of interest.

SU-E-T-185: Clinically-Relevant Investigation of Flattening Filter Free Skin Dose

Purpose: Flattening-filter-free (FFF) beams are increasingly used for small-field treatments due to inherent advantages like higher MU efficiency and reduced treatment time and scatter dose. Removal of the flattening-filter increases the electron contamination and low-energy x-rays. As such, surface-dose characteristics are different from traditional flattened (FF) beams. The goal of this work is to investigate surface dose of 6/10 MV FFF and FF beams under conditions representative of emerging complex techniques like small-field stereotactic treatments which use small fields formed with multi-leaf-collimators (MLCs) at closer SSDs. Methods: A parallel-plate PTW Markus-chamber (N23343) placed in custom air- and water-equivalent phantoms was used to measure surface-dose at 2/3/4/6/8/10/20/30 cm2 field sizes, at 80/90/100 cm source-to-surface distances, and at fields defined by jaws and MLCs. The effect of dose rate (600 and 1400/2400 MU/min) was also investigated at 100 cm SSD. Measurements were performed on TrueBeam linac (Varian Medical Systems, Palo Alto, CA) for 6X/6XFFF/10X/10XFFF beam energies. Results: No dose-rate dependence was seen for FFF skin-dose. Air-phantom measurements were, on average, 5±3% larger than for water-phantom measurements. With SSD increase from 80 to 100 cm, skin-dose decreased by an average of 3.9±2.5%. FFF beams were found to be more sensitive to SSD changes in comparison to FF beams. The difference in skin dose between MLC- and jaw-fields was less variable with field size for FFF compared to FF beams. 10 MV beams showed greater difference in FFF-to-FF ratio, 50% (jaws) and 22% (MLC), between the largest and smallest field sizes compared to 6 MV beams, 30% (jaws) and 9% (MLC). Conclusion: Under clinically-relevant conditions, surface dose for FFF beams was higher at small field size (<10 cm), lower at largest field size (30 cm), more sensitive to SSD changes, and had less variation with field size compared to dose for FF beams.

WE-G-18C-02: Estimation of Optimal B-Value Set for Obtaining Apparent Diffusion Coefficient Free From Perfusion in Non-Small Cell Lung Cancer

PURPOSE Diffusion-weighted MRI (DW-MRI) is increasingly being investigated for radiotherapy planning and response assessment. Selection of a limited number of b-values in DW-MRI is important to keep geometrical variations low and imaging time short. We investigated various b-value sets to determine an optimal set for obtaining monoexponential apparent diffusion coefficient (ADC) close to perfusion-insensitive intravoxel incoherent motion (IVIM) model ADC (ADCIVIM) in nonsmall cell lung cancer. METHODS Seven patients had 27 DW-MRI scans before and during radiotherapy in a 1.5T scanner. Respiratory triggering was applied to the echo-planar DW-MRI with TR=4500ms approximately, TE=74ms, pixel size=1.98×1.98mm2 , slice thickness=4-6mm and 7 axial slices. Diffusion gradients were applied to all three axes producing traceweighted images with eight b-values of 0-1000μs/μm2 . Monoexponential model ADC values using various b-value sets were compared to ADCIVIM using all b-values. To compare the relative noise in ADC maps, intra-scan coefficient of variation (CV) of active tumor volumes was computed. RESULTS ADCIVIM, perfusion coefficient and perfusion fraction for tumor volumes were in the range of 880-1622 μm2 /s, 8119-33834 μm2 /s and 0.104-0.349, respectively. ADC values using sets of 250, 800 and 1000; 250, 650 and 1000; and 250-1000μs/μm2 only were not significantly different from ADCIVIM(p>0.05, paired t-test). Error in ADC values for 0-1000, 50-1000, 100-1000, 250-1000, 500-1000, and three b-value sets- 250, 500 and 1000; 250, 650 and 1000; and 250, 800 and 1000μs/μm2 were 15.0, 9.4, 5.6, 1.4, 11.7, 3.7, 2.0 and 0.2% relative to the reference-standard ADCIVIM, respectively. Mean intrascan CV was 20.2, 20.9, 21.9, 24.9, 32.6, 25.8, 25.4 and 24.8%, respectively, whereas that for ADCIVIM was 23.3%. CONCLUSION ADC values of two 3 b-value sets (250, 650 and 1000; and 250, 800 and 1000μs/μm2 ) approached ADCIVIM, with relative noise comparable to that of ADCIVIM. These sets may be used to obtain perfusion-insensitive ADC values in lung tumors. E. Weiss: Funding through Varian Medical Systems and Philips Oncology Systems, UpToDate royalties. G. Hugo: NIH R01CA166119, P01 CA116602, NHMRC Project Grant.