Evaluation of respiratory and cardiac motion correction schemes in dual gated PET/CT cardiac imaging.

PURPOSE: Cardiac imaging suffers from both respiratory and cardiac motion. One of the proposed solutions involves double gated acquisitions. Although such an approach may lead to both respiratory and cardiac motion compensation there are issues associated with (a) the combination of data from cardiac and respiratory motion bins, and (b) poor statistical quality images as a result of using only part of the acquired data. The main objective of this work was to evaluate different schemes of combining binned data in order to identify the best strategy to reconstruct motion free cardiac images from dual gated positron emission tomography (PET) acquisitions. METHODS: A digital phantom study as well as seven human studies were used in this evaluation. PET data were acquired in list mode (LM). A real-time position management system and an electrocardiogram device were used to provide the respiratory and cardiac motion triggers registered within the LM file. Acquired data were subsequently binned considering four and six cardiac gates, or the diastole only in combination with eight respiratory amplitude gates. PET images were corrected for attenuation, but no randoms nor scatter corrections were included. Reconstructed images from each of the bins considered above were subsequently used in combination with an affine or an elastic registration algorithm to derive transformation parameters allowing the combination of all acquired data in a particular position in the cardiac and respiratory cycles. Images were assessed in terms of signal-to-noise ratio (SNR), contrast, image profile, coefficient-of-variation (COV), and relative difference of the recovered activity concentration. RESULTS: Regardless of the considered motion compensation strategy, the nonrigid motion model performed better than the affine model, leading to higher SNR and contrast combined with a lower COV. Nevertheless, when compensating for respiration only, no statistically significant differences were observed in the performance of the two motion models considered. Superior image SNR and contrast were seen using the affine respiratory motion model in combination with the diastole cardiac bin in comparison to the use of the whole cardiac cycle. In contrast, when simultaneously correcting for cardiac beating and respiration, the elastic respiratory motion model outperformed the affine model. In this context, four cardiac bins associated with eight respiratory amplitude bins seemed to be adequate. CONCLUSIONS: Considering the compensation of respiratory motion effects only, both affine and elastic based approaches led to an accurate resizing and positioning of the myocardium. The use of the diastolic phase combined with an affine model based respiratory motion correction may therefore be a simple approach leading to significant quality improvements in cardiac PET imaging. However, the best performance was obtained with the combined correction for both cardiac and respiratory movements considering all the dual-gated bins independently through the use of an elastic model based motion compensation.

Evaluation of clinical IMRT treatment planning using the GATE Monte Carlo simulation platform for absolute and relative dose calculations.

PURPOSE: The objective of this study was to evaluate and validate the use of the Geant4 application for emission tomography (GATE) Monte Carlo simulation platform for clinical intensity modulated radiotherapy (IMRT) dosimetry studies. METHODS: The first step consisted of modeling a 6 MV photon beam linear accelerator (LINAC), with its corresponding validation carried out using percent depth dose evaluation, transverse profiles, tissue phantom ratio, and output factor on water phantom. The IMRT evaluation was performed by comparing simulation and measurements in terms of absolute and relative doses using IMRT dedicated quality assurance phantoms considering seven different patient datasets. RESULTS: Concerning the LINAC simulated model validation tissue phantom ratios at 20 and 10 cm in water TPR(10) (20) obtained from GATE and measurements were 0.672 ± 0.063 and 0.675, respectively. In terms of percent depth dose and transverse profiles, error ranges were, respectively: 1.472% ± 0.285% and 4.827% ± 1.323% for field size of 4 × 4, 5 × 5, 10 × 10, 15 × 15, 20 × 20, 25 × 25, 30 × 30, and 40 × 40 cm(2). Most errors were observed at the edge of radiation fields because of higher dose gradient in these areas. Output factors showed good agreement between simulation and measurements with a maximum error of 1.22%. Finally, for IMRT simulations considering seven patient datasets, GATE provided good results with a relative error of 0.43% ± 0.25% on absolute dose between simulated and measured beams (measurements at the isocenter, volume 0.125 cm(3)). Planar dose comparisons were also performed using gamma-index analysis. For the whole set of beams considered the mean gamma-index value was 0.497 ± 0.152 and 90.8% ± 3.6% of the evaluated dose points satisfied the 5% ∕ 4 mm criterion. CONCLUSIONS: These results show that GATE allows reliable simulation of complex beams in radiotherapy after an accurate LINAC modeling is validated. A simple cross-calibration procedure proposed in this work allows obtaining absolute dose values even in complex fields.

[Image-guided and adaptive radiotherapy]. / Radiothérapie guidée par l'image et adaptative.

Image-guided radiotherapy (IGRT) aims to take into account anatomical variations occurring during irradiation by visualization of anatomical structures. It may consist of a rigid registration of the tumour by moving the patient, in case of prostatic irradiation for example. IGRT associated with intensity-modulated radiotherapy (IMRT) is strongly recommended when high-dose is delivered in the prostate, where it seems to reduce rectal and bladder toxicity. In case of significant anatomical deformations, as in head and neck tumours (tumour shrinking and decrease in volume of the salivary glands), replanning appears to be necessary, corresponding to the adaptive radiotherapy. This should ideally be "monitored" and possibly triggered based on a calculation of cumulative dose, session after session, compared to the initial planning dose, corresponding to the concept of dose-guided adaptive radiotherapy. The creation of "planning libraries" based on predictable organ positions (as in cervical cancer) is another way of adaptive radiotherapy. All of these strategies still appear very complex and expensive and therefore require stringent validation before being routinely applied.

Pharmacogenetic analysis of BR.21, a placebo-controlled randomized phase III clinical trial of erlotinib in advanced non-small cell lung cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

SU-E-I-88: Realistic Pathological Simulations of the NCAT and Zubal Anthropomorphic Models, Based on Clinical PET/CT Data.

PURPOSE: In the present study a patient-specific dataset of realistic PET simulations was created, taking into account the variability of clinical oncology data. Tumor variability was tested in the simulated results. A comparison of the produced simulated data was performed to clinical PET/CT data, for the validation and the evaluation of the procedure. METHODS: Clinical PET/CT data of oncology patients were used as the basis of the simulated variability inserting patient-specific characteristics in the NCAT and the Zubal anthropomorphic phantoms. GATE Monte Carlo toolkit was used for simulating a commercial PET scanner. The standard computational anthropomorphic phantoms were adapted to the CT data (organ shapes), using a fitting algorithm. The activity map was derived from PET images. Patient tumors were segmented and inserted in the phantom, using different activity distributions. RESULTS: The produced simulated data were reconstructed using the STIR opensource software and compared to the original clinical ones. The accuracy of the procedure was tested in four different oncology cases. Each pathological situation was illustrated simulating a) a healthy body, b) insertion of the clinical tumor with homogenous activity, and c) insertion of the clinical tumor with variable activity (voxel-by-voxel) based on the clinical PET data. The accuracy of the presented dataset was compared to the original PET/CT data. Partial Volume Correction (PVC) was also applied in the simulated data. CONCLUSIONS: In this study patient-specific characteristics were used in computational anthropomorphic models for simulating realistic pathological patients. Voxel-by-voxel activity distribution with PVC within the tumor gives the most accurate results. Radiotherapy applications can utilize the benefits of the accurate realistic imaging simulations, using the anatomicaland biological information of each patient. Further work will incorporate the development of analytical anthropomorphic models with motion and cardiac correction, combined with pathological patients to achieve high accuracy in tumor imaging. This research was supported by the Joint Research and Technology Program between Greece and France; 2009-2011 (protocol ID: 09FR103).

Elevated plasma ferritin and busulfan pharmacodynamics during high-dose chemotherapy regimens in children with malignant solid tumors.

Hepatic veno-occlusive disease (HVOD) is a frequent complication during hematopoietic stem-cell transplantation (HSCT). A strong relationship has been demonstrated between busulfan exposure and HVOD for busulfan-cyclophosphamide and allogeneic HSCT in adults. Busulfan disposition after the first intake was studied in 77 children treated for solid malignancies with high-dose busulfan-containing regimens and autologous HSCT. Busulfan was combined with cyclophosphamide and melphalan (n=30), melphalan (n=27), and thiotepa (n=20). No relationship was observed between busulfan exposure and HVOD. In contrast, plasma ferritin at baseline was higher in patients with HVOD (750 ng/ml (20-3,110)) compared with those without HVOD (189 ng/ml (8-3,967), P=0.012). Multivariate analysis showed that a ferritin level exceeding 300 ng/ml was the only risk factor for HVOD with an odds ratio of 4.0 (confidence interval 95% (1.5-11.2), P=0.0071). A high ferritin level at baseline was explained by the diagnosis of neuroblastoma, related treatments and transfusions.

Falciparum malaria treated with a chloroquine suspension administered rectally in Trinidad.

A new mode of administering malaria chemotherapy to patients unable to tolerate oral medication is described. A patient with Plasmodium falciparum malaria, severe hyponatremia and hypokalaemia who regurgitated oral treatment of chloroquine phosphate and pyrimethamine and sulfadoxine (Fansidar) is presented. But neither chloroquine nor quinine intravenous formulations were available locally. As the patient was deteriorating, a suspension of chloroquine phosphate was prepared and administered rectally, resulting in a decline in the level of parasitaemia from ++++ to ++ within 48 hours. The patient improved, and further clinical management was uncomplicated.

An outbreak of Plasmodium vivax malaria in Trinidad, W.I.

An outbreak of Plasmodium vivax malaria occurred in Trinidad some 25 years after a successful eradication programme. The 'index case' was infected while visiting Perdaneles, Venezuela, and was responsible for the renewal of malaria transmission by indigenous Anopheles aquasalis mosquitoes in Icacos, Trinidad, W.I. Nine cases (four females and five males) of P. vivax malaria were locally transmitted in Icacos. Most of the cases (70%) were in the 15-24 or 25-44 year age groups. In Granville/Chatham, another, unrelated case of locally transmitted P. vivax malaria was discovered through active surveillance. The intervention measures adopted, which successfully eradicated P. vivax malaria from Trinidad, are described. The need to maintain malaria surveillance is emphasized.

Serum cholinesterase levels of vector control workers in Trinidad, West Indies (1979-1987).

During 1979-1987 studies were carried out in vitro on the serum cholinesterase levels of 46 vector control workers exposed to insecticides on a daily basis but without clinical manifestations of insecticide poisoning. The results were compared with those of a control group of workers who had not been exposed to insecticides at home or at work. Cholinesterase levels of both groups were determined by a standard colorimetric method. Suppressed serum cholinesterase levels were detected in all 46 workers exposed to insecticides, 25 of whom were aged 30-39 years. Four persons from the control group showed suppressed levels of enzyme; one of these had a genetically low level, and the other three were on medication when the low levels were recorded.

Serum cholinesterase levels of vector control workers in Trinidad, West Indies 1979-1982

During the period 1979-1982, serum cholinesterase levels were determined in blood samples collectedfrom workers employed at the Insect Vector Control Division, Trinidad, W.I. A total of 1,162 blood samples were collected, of which 116 showed suppressed cholinesterase levels. Those workers with low serum cholinesterase levels included 46 residual spraymen, 66 Aedes aegypti operators and 4 controls. The difference in number of spraymen and Aedes operations with low cholinesterase levels was significant (p<.001). No significant differences were found in the number of Aedes operators with low cholinesterase levels from North and South Trinidad. Similarly, no differences were found in the number of residual spraymen from North and South Trinidad with low cholinesterase levels. A total of 7 Aedes operators and 4 residual spraymen had persistently low serum cholinesterase levels. It is likely that the main areas of absorption were the hands and forearms, with further absorption occurin via respiration. The need for continuous monitoring and supervision of vector contro workers who handle insecticides is stressed