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ABSTRACT: Purpose: Longitudinal measurements of pulmonary function must account for subject variation when assessing radiation-induced changes. Previously, we reported intra-subject reproducibility of Jacobian-based measures of lung tissue expansion using repeat 4DCT scans prior to radiation therapy without correcting for differences in respiratory effort. In this study, we present two normalization schemes that correct ventilation images for variations in respiratory effort. Methods: Two repeat 4DCT image acquisitions were collected before treatment from seven patients. Using a tissue volume preserving deformable image registration algorithm, two Jacobian ventilation maps were computed from separate acquisitions. Two effort normalization strategies were investigated using intermediated inspiration phases upon the principles of equivalent tidal volume (ETV) and equivalent lung volume (ELV). Additional experiments were performed to verify the effectiveness of the ETV method. Scatter plots of two ventilation maps and statistical parameters of Jacobian ratio were compared before and after each effort correction approach. Results: The scatter plots of the ventilation maps show improvement in measurement reproducibility using either the ETV or ELV effort correction for all but one case. The one case that did not show improvement had a very similar lung volumes and tidal volumes in the two studies, so effort correction was unnecessary. The coefficient of variation (CV) of Jacobian ratio improved by 21±11 percent (mean±standard deviation) after ETV, and improved by 20±17 percent after ELV. Our experimental results on ETV show the decrease of tidal volume difference in two acquisitions improves reproducibility of lung expansion measures. Conclusions: ETV and ELV correction methods improve the reproducibility of pulmonary function measurements in subjects that have differences in respiratory effort in the baseline and followup scans. Additional work is needed to investigate whether ETV or ELV is more effective, and to develop alternate regional normalization schemes that can account for difference in lung expansion rates.
Medical Physics 06/2012; 39(6):3671. · 2.83 Impact Factor
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ABSTRACT: Purpose: Radiation Therapy (RT) induced pulmonary function change may depend on the location, underlying function of that lung prior to radiations, radiation dose/fractionation and other factors. We propose to evaluate the radiation induced pulmonary function change using static breath-hold MRI scans with vascular information and 3D deformable image registration which can provide pulmonary function relative to RT dose on a regional basis. Methods: A MRI scan pair near the end of inhale and near the end of exhale with breath hold were acquired for one lung cancer patient before RT and 6 months after RT. The patient was treated with SBRT with 55 Gy to PTVs in the right and the left lung respectively. B-spline based vesselness preserving image registration algorithm was applied to register the MRI pair for the calculation of local lung expansion as a measurement of regional pulmonary function (PF). The PF maps before RT and after RT were then mapped to the planning CT using the same algorithm tuned for MRI-CT registration. The pulmonary function change was calculated via the PF ratio between two MRI pairs. Results: Strong spatial correlation was found between the irradiated lung region and the region with greatly decreased PF. Based on dose and PFC distribution, no strong determinant factor was found for PF lost in the left lung while the right lung shows that all the lung tissue receiving dose larger than 28 Gy will have a decreased PF. Conclusions: We demonstrated a method that uses static breath-hold MRI based lung imaging to evaluate radiation induced pulmonary function change which can be applied to study the dose and the pulmonary function change in a regional basis. This work is supported by NIH grant support 1R21CA144063.
Medical Physics 06/2012; 39(6):3697. · 2.83 Impact Factor
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K Ding,
J Deng,
K Du,
K Cao,
G Christensen,
J Reinhardt,
K Sheng,
B Libby,
S Benedict,
J Lamer,
Q Chen
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ABSTRACT: Purpose: Recent clinical trials and animal studies have indicated that the tissue sensitivity to radiation induced lung injury (RILI) may be region- specific. In this study, we propose a new 4D cone beam CT (CBCT) basedcompliance imaging method to measure regional pulmonary function change in precisely irradiated small animal under CBCT guidance on small animal radiation research platform (SARRP) to facilitate our understanding of region-specific tissue sensitivity to RILI. Methods: Four Sprague-Dawley rats underwent prospective pressure gated 4D CBCT on SARRP. Three animals were selected as control group which underwent a second 4D CBCT scan. The fourth animal was irradiated in the central lung (24 Gy) using 3 × 3 mm collimating cone 2 months prior to the scan. The specific compliance (Csp) was calculated via the real time pressure measurement from the ventilator and displacement field from 3D B-spline image registration between the end of inhale and end of exhale phases from the 4D CBCT scan. The 3D Csp maps from the control animal group were mapped to the irradiated animal as a Csp functional atlas for statistical analysis. We alsoevaluated the repeatability of the Csp measurement on a voxel-by-voxel basis. Results: No significant Csp difference is found after two month of radiation between the irradiated rat (0.22±0.05) and the functional atlas (0.21±0.07). The observation is consistent with previous publications. The averaged linear correlation coefficient between the voxel-by-voxel Csp measurements from initial and repeat scans in control group is 0.98.Conclusions: We proposed a method that uses 4D CBCT based compliance imaging to measure region-specific tissue sensitivity of RILI. We compared the irradiated animal two months after radiation with the control group. Our study shows an excellent robustness of the proposed method for regional lung tissue specific compliance measurement. This work was supported in part by UVa George Amorino Pilot Grant.
Medical Physics 06/2012; 39(6):3615. · 2.83 Impact Factor
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ABSTRACT: BR.21 is a double-blind, placebo-controlled trial of second-/third-line erlotinib in stage IIIB/IV non-small cell lung cancer patients. Predictive and prognostic analyses of epidermal growth factor receptor (EGFR), ABCG2, and AKT1 genetic polymorphisms were performed.
Two hundred forty-two patients were genotyped for EGFR-216G>T (EGFR216), EGFR-191C>A (EGFR191), EGFR intron 1 CA-dinucleotide-repeat (CADR), ABCG2+421C>A (ABCG2), and AKT1-SNP4G>A (AKT1). Cox proportional hazard and logistic regression models compared genotypes with overall survival (OS), progression-free survival (PFS), and presence/absence of skin toxicity.
Prognostic evaluation was based on the placebo arm: patients carrying at least one CADR long allele (>16 repeats) had a trend toward worse PFS: the adjusted hazard ratio was 1.7 (95% confidence interval [CI]: 1.0-3.0; p = 0.07). EGFR216, EGFR191, ABCG2, and AKT1 were not prognostic. Polymorphisms were not predictive for erlotinib effect (OS/PFS): no treatment-polymorphism interactions were demonstrated. Individuals carrying the rare T/T genotype of EGFR216 had an adjusted odds ratio of 8.8 (95% CI: 1.1-72; p = 0.04) of developing skin toxicity; no other significant polymorphic relationships with skin toxicity were found.
In contrast to previous publications, carrying shorter alleles of the EGFR CADR polymorphism was not predictive of OS or PFS. EGFR216 homozygous variants were associated with greater skin toxicity from erlotinib.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 02/2012; 7(2):316-22. · 4.55 Impact Factor
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K Murphy,
B Ginneken,
Joseph M Reinhardt,
S Kabus, K Ding,
X Deng,
K Cao,
K Du,
G E Christensen,
V Garcia, [......],
J C Gee,
M Staring,
S Klein,
B C Stoel,
M Urschler,
M Werlberger,
J Vandemeulebroucke,
S Rit,
D Sarrut,
J P Pluim
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ABSTRACT: EMPIRE10 (Evaluation of Methods for Pulmonary Image REgistration 2010) is a public platform for fair and meaningful comparison of registration algorithms which are applied to a database of intrapatient thoracic CT image pairs. Evaluation of nonrigid registration techniques is a nontrivial task. This is compounded by the fact that researchers typically test only on their own data, which varies widely. For this reason, reliable assessment and comparison of different registration algorithms has been virtually impossible in the past. In this work we present the results of the launch phase of EMPIRE10, which comprised the comprehensive evaluation and comparison of 20 individual algorithms from leading academic and industrial research groups. All algorithms are applied to the same set of 30 thoracic CT pairs. Algorithm settings and parameters are chosen by researchers expert in the configuration of their own method and the evaluation is independent, using the same criteria for all participants. All results are published on the EMPIRE10 website (http://empire10.isi.uu.nl). The challenge remains ongoing and open to new participants. Full results from 24 algorithms have been published at the time of writing. This paper details the organization of the challenge, the data and evaluation methods and the outcome of the initial launch with 20 algorithms. The gain in knowledge and future work are discussed.
IEEE Transactions on Medical Imaging 11/2011; 30:1901-1920. · 3.64 Impact Factor
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Keelin Murphy,
Bram van Ginneken,
Joseph M Reinhardt,
Sven Kabus, Kai Ding,
Xiang Deng,
Kunlin Cao,
Kaifang Du,
Gary E Christensen,
Vincent Garcia, [......],
James C Gee,
Marius Staring,
Stefan Klein,
Berend C Stoel,
Martin Urschler,
Manuel Werlberger,
Jef Vandemeulebroucke,
Simon Rit,
David Sarrut,
Josien P W Pluim
[show abstract]
[hide abstract]
ABSTRACT: EMPIRE10 (Evaluation of Methods for Pulmonary Image REgistration 2010) is a public platform for fair and meaningful comparison of registration algorithms which are applied to a database of intrapatient thoracic CT image pairs. Evaluation of nonrigid registration techniques is a nontrivial task. This is compounded by the fact that researchers typically test only on their own data, which varies widely. For this reason, reliable assessment and comparison of different registration algorithms has been virtually impossible in the past. In this work we present the results of the launch phase of EMPIRE10, which comprised the comprehensive evaluation and comparison of 20 individual algorithms from leading academic and industrial research groups. All algorithms are applied to the same set of 30 thoracic CT pairs. Algorithm settings and parameters are chosen by researchers expert in the configuration of their own method and the evaluation is independent, using the same criteria for all participants. All results are published on the EMPIRE10 website (http://empire10.isi.uu.nl). The challenge remains ongoing and open to new participants. Full results from 24 algorithms have been published at the time of writing. This paper details the organization of the challenge, the data and evaluation methods and the outcome of the initial launch with 20 algorithms. The gain in knowledge and future work are discussed.
IEEE Transactions on Medical Imaging 05/2011; 30(11):1901-20. · 3.64 Impact Factor
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K Murphy,
B Ginneken,
J Reinhardt,
S Kabus, K Ding,
X Deng,
K Cao,
K Du,
G Christensen,
V Garcia, [......],
J Gee,
M Staring,
S Klein,
B Stoel,
M Urschler,
M Werlberger,
J Vandemeulebroucke,
S Rit,
D Sarrut,
J Pluim
[show abstract]
[hide abstract]
ABSTRACT: EMPIRE10 (Evaluation of Methods for Pulmonary Image REgistration 2010) is a public platform for fair and meaningful comparison of registration algorithms which are applied to a database of intra-patient thoracic CT image pairs. Evaluation of non-rigid registration techniques is a non trivial task. This is compounded by the fact that researchers typically test only on their own data, which varies widely. For this reason, reliable assessment and comparison of different registration algorithms has been virtually impossible in the past. In this work we present the results of the launch phase of EMPIRE10, which comprised the comprehensive evaluation and comparison of 20 individual algorithms from leading academic and industrial research groups. All algorithms are applied to the same set of 30 thoracic CT pairs. Algorithm settings and parameters are chosen by researchers expert in the configuration of their own method and the evaluation is independent, using the same criteria for all participants. All results are published on the EMPIRE10 website (http://empire10.isi.uu.nl). The challenge remains ongoing and open to new participants. Full results from 24 algorithms have been published at the time of writing. This article details the organisation of the challenge, the data and evaluation methods and the outcome of the initial launch with 20 algorithms. The gain in knowledge and future work are discussed.
TMI.
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CQ Zhu,
G da Cunha Santos, K Ding,
A Sakurada,
JC Cutz,
N Liu,
T Zhang,
P Marrano,
M Whitehead,
JA Squire,
S Kamel-Reid,
L Seymour,
FA Shepherd,
MS Tsao
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ABSTRACT: PURPOSE: To evaluate the effect of KRAS and epidermal growth factor receptor (EGFR) genotype on the response to erlotinib treatment in the BR.21, placebo-controlled trial. PATIENTS AND METHODS: We analyzed 206 tumors for KRAS mutation, 204 tumors for EGFR mutation, and 159 tumors for EGFR gene copy by fluorescent in situ hybridization (FISH). We reanalyzed EGFR deletion/mutation using two highly sensitive techniques that detect abnormalities in samples with 5% to 10% tumor cellularity. KRAS mutation was analyzed by direct sequencing. RESULTS: Thirty patients (15%) had KRAS mutations, 34 (17%) had EGFR exon 19 deletion or exon 21 L858R mutations, and 61 (38%) had high EGFR gene copy (FISH positive). Response rates were 10% for wild-type and 5% for mutant KRAS (P = .69), 7% for wild-type and 27% for mutant EGFR (P = .03), and 5% for EGFR FISH-negative and 21% for FISH-positive patients (P = .02). Significant survival benefit from erlotinib therapy was observed for patients with wild-type KRAS (hazard rat
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