Sadek A. Nehmeh

Effect of respiratory gating on reducing lung motion artifacts in PET imaging of lung cancer

Positron emission tomography (PET) has shown an increase in both sensitivity and specificity over computed tomography (CT) in lung cancer. However, motion artifacts in the 18F fluorodioxydoglucose (FDG) PET images caused by respiration persists to be an important factor in degrading PET image quality and quantification. Motion artifacts lead to two major effects: First, it affects the accuracy of quantitation, producing a reduction of the measured standard uptake value (SUV). Second, the apparent lesion volume is overestimated. Both impact upon the usage of PET images for radiation treatment planning. The first affects the visibility, or contrast, of the lesion. The second results in an increase in the planning target volume, and consequently a greater radiation dose to the normal tissues. One way to compensate for this effect is by applying a multiple-frame capture technique. The PET data are then acquired in synchronization with the respiratory motion. Reduction in smearing due to gating was investigated in both phantoms and patient studies. Phantom studies showed a dependence of the reduction in smearing on the lesion size, the motion amplitude, and the number of bins used for data acquisition. These studies also showed an improvement in the target-to-background ratio, and a more accurate measurement of the SUV. When applied to one patient, respiratory gating showed a 28% reduction in the total lesion volume, and a 56.5% increase in the SUV. This study was conducted as a proof of principle that a gating technique can effectively reduce motion artifacts in PET image acquisition.

Respiratory Motion in Positron Emission Tomography/Computed Tomography: A Review

The development of positron emission tomography/computed tomography (PET/CT) scanners has allowed not only straightforward but also synergistic fusion of anatomical and functional information. Combined PET/CT imaging yields an increased sensitivity and specificity beyond that which either of the 2 modalities possesses separately and therefore provides improved diagnostic accuracy. Because attenuation correction in PET is performed with the use of CT images, with CT used in the localization of disease, accurate spatial registration of PET and CT image sets is required. Correcting for the spatial mismatch caused by respiratory motion represents a particular challenge for the requisite registration accuracy as a result of differences in temporal resolution between the 2 modalities. This review provides a brief summary of the materials, methods, and results involved in multiple investigations of the correction for respiratory motion in PET/CT imaging of the thorax, with the goal of improving image quality and quantitation. Although some schemes use respiratory-phase data selection to exclude motion artifacts, others have adopted sophisticated software techniques. The various image artifacts associated with breathing motion are also described.

Quantitation of respiratory motion during 4D-PET/CT acquisition

We report on the variability of the respiratory motion during 4D-PET/CT acquisition. The respiratory motion for five lung cancer patients was monitored by tracking external markers placed on the abdomen. CT data were acquired over an entire respiratory cycle at each couch position. The x-ray tube status was recorded by the tracking system, for retrospective sorting of the CT data as a function of respiration phase. Each respiratory cycle was sampled in ten equal bins. 4D-PET data were acquired in gated mode, where each breathing cycle was divided into ten 500 ms bins. For both CT and PET acquisition, patients received audio prompting to regularize breathing. The 4D-CT and 4D-PET data were then correlated according to their respiratory phases. The respiratory periods, and average amplitude within each phase bin, acquired in both modality sessions were then analyzed. The average respiratory motion period during 4D-CT was within 18% from that in the 4D-PET sessions. This would reflect up to 1.8% fluctuation in the duration of each 4D-CT bin. This small uncertainty enabled good correlation between CT and PET data, on a phase-to-phase basis. Comparison of the average-amplitude within the respiration trace, between 4D-CT and 4D- PET, on a bin-by-bin basis show a maximum deviation of approximately 15%. This study has proved the feasibility of performing 4D-PET/CT acquisition. Respiratory motion was in most cases consistent between PET and CT sessions, thereby improving both the attenuation correction of PET images, and co-registration of PET and CT images. On the other hand, in two patients, there was an increased partial irregularity in their breathing motion, which would prevent accurately correlating the corresponding PET and CT images.

The Influence of Changes in Tumor Hypoxia on Dose-Painting Treatment Plans Based on 18F-FMISO Positron Emission Tomography

PURPOSE To evaluate how changes in tumor hypoxia, according to serial fluorine-18-labeled fluoro-misonidazole (18F-FMISO) positron emission tomography (PET) imaging, affect the efficacy of intensity-modulated radiotherapy (IMRT) dose painting. METHODS AND MATERIALS Seven patients with head and neck cancers were imaged twice with FMISO PET, separated by 3 days, before radiotherapy. Intensity-modulated radiotherapy plans were designed, on the basis of the first FMISO scan, to deliver a boost dose of 14 Gy to the hypoxic volume, in addition to the 70-Gy prescription dose. The same plans were then applied to hypoxic volumes from the second FMISO scan, and the efficacy of dose painting evaluated by assessing coverage of the hypoxic volumes using Dmax, Dmin, Dmean, D95, and equivalent uniform dose (EUD). RESULTS Similar hypoxic volumes were observed in the serial scans for 3 patients but dissimilar ones for the other 4. There was reduced coverage of hypoxic volumes of the second FMISO scan relative to that of the first scan (e.g., the average EUD decreased from 87 Gy to 80 Gy). The decrease was dependent on the similarity of the hypoxic volumes of the two scans (e.g., the average EUD decrease was approximately 4 Gy for patients with similar hypoxic volumes and approximately 12 Gy for patients with dissimilar ones). CONCLUSIONS The changes in spatial distribution of tumor hypoxia, as detected in serial FMISO PET imaging, compromised the coverage of hypoxic tumor volumes achievable by dose-painting IMRT. However, dose painting always increased the EUD of the hypoxic volumes.

Validation of GATE Monte Carlo simulations of the GE Advance/Discovery LS PET scanners

The recently developed GATE (GEANT4 application for tomographic emission) Monte Carlo package, designed to simulate positron emission tomography (PET) and single photon emission computed tomography (SPECT) scanners, provides the ability to model and account for the effects of photon noncollinearity, off-axis detector penetration, detector size and response, positron range, photon scatter, and patient motion on the resolution and quality of PET images. The objective of this study is to validate a model within GATE of the General Electric (GE) Advance/Discovery Light Speed (LS) PET scanner. Our three-dimensional PET simulation model of the scanner consists of 12 096 detectors grouped into blocks, which are grouped into modules as per the vendors specifications. The GATE results are compared to experimental data obtained in accordance with the National Electrical Manufactures Association/Society of Nuclear Medicine (NEMA/SNM), NEMA NU 2-1994, and NEMA NU 2-2001 protocols. The respective phantoms are also accurately modeled thus allowing us to simulate the sensitivity, scatter fraction, count rate performance, and spatial resolution. In-house software was developed to produce and analyze sinograms from the simulated data. With our model of the GE Advance/Discovery LS PET scanner, the ratio of the sensitivities with sources radially offset 0 and 10 cm from the scanners main axis are reproduced to within 1% of measurements. Similarly, the simulated scatter fraction for the NEMA NU 2-2001 phantom agrees to within less than 3% of measured values (the measured scatter fractions are 44.8% and 40.9 +/- 1.4% and the simulated scatter fraction is 43.5 +/- 0.3%). The simulated count rate curves were made to match the experimental curves by using deadtimes as fit parameters. This resulted in deadtime values of 625 and 332 ns at the Block and Coincidence levels, respectively. The experimental peak true count rate of 139.0 kcps and the peak activity concentration of 21.5 kBq/cc were matched by the simulated results to within 0.5% and 0.1% respectively. The simulated count rate curves also resulted in a peak NECR of 35.2 kcps at 10.8 kBq/cc compared to 37.6 kcps at 10.0 kBq/cc from averaged experimental values. The spatial resolution of the simulated scanner matched the experimental results to within 0.2 mm.

Prospective trial incorporating pre-/mid-treatment [18F]-misonidazole positron emission tomography for head-and-neck cancer patients undergoing concurrent chemoradiotherapy.

PURPOSE To report the results from a prospective study of a series of locoregionally advanced head-and-neck cancer patients treated with platinum-based chemotherapy and intensity-modulated radiotherapy and to discuss the findings of their pre-/mid-treatment [(18)F]-misonidazole ((18)F-FMISO) positron emission tomography (PET) scans. METHODS AND MATERIALS A total of 28 patients agreed to participate in this study. Of these 28 patients, 20 (90% with an oropharyngeal primary cancer) were able to undergo the requirements of the protocol. Each patient underwent four PET scans: one pretreatment fluorodeoxyglucose PET/computed tomography scan, two pretreatment (18)F-FMISO PET/computed tomography scans, and a third (18)F-FMISO PET (mid-treatment) scan performed 4 weeks after the start of chemoradiotherapy. The (18)F-FMISO PET scans were acquired 2-3 h after tracer administration. Patients were treated with 2-3 cycles of platinum-based chemotherapy concurrent with definitive intensity-modulated radiotherapy. RESULTS A heterogeneous distribution of (18)F-FMISO was noted in the primary and/or nodal disease in 90% of the patients. Two patients had persistent detectable hypoxia on their third mid-treatment (18)F-FMISO PET scan. One patient experienced regional/distant failure but had no detectable residual hypoxia on the mid-treatment (18)F-FMISO PET scan. CONCLUSION Excellent locoregional control was observed in this series of head-and-neck cancer patients treated with concurrent platinum-based chemotherapy and intensity-modulated radiotherapy despite evidence of detectable hypoxia on the pretreatment (18)F-FMISO PET/computed tomography scans of 18 of 20 patients. In this prospective study, neither the presence nor the absence of hypoxia, as defined by positive (18)F-FMISO findings on the mid-treatment PET scan, correlated with patient outcome. The results of this study have confirmed similar results reported previously.

Deep-Inspiration Breath-Hold PET/CT: Clinical Findings with a New Technique for Detection and Characterization of Thoracic Lesions

Respiratory motion during PET/CT acquisition can cause misregistration and inaccuracies in calculation of standardized uptake values (SUVs). Our aim was to compare the detection and characterization of thoracic lesions on PET/CT with and without a deep-inspiration protocol. Methods: We studied 15 patients with suspected pulmonary lesions who underwent clinical PET/CT, followed by deep-inspiration breath-hold (BH) PET/CT. In BH CT, the whole chest of the patient was scanned in 15 s at the end of deep inspiration. For BH PET, patients were asked to hold their breath 9 times for 20-s intervals. One radiologist reviewed images, aiming to detect and characterize pulmonary, nodal, and skeletal abnormalities. Clinical CT and BH CT were compared for number, size, and location of lesions. Lesion SUVs were compared between clinical PET and BH PET. Images were also visually assessed for accuracy of fusion and registration. Results: All patients had lesions on clinical CT and BH CT. Pulmonary BH CT detected more lesions than clinical CT in 13 of 15 patients (86.7%). The total number of lung lesions detected increased from 53 with clinical CT to 82 with BH CT (P < 0.001). Eleven patients showed a total of 31 lesions with abnormal 18F-FDG uptake. BH PET/CT had the advantage of reducing misregistration and permitted a better localization of sites with 18F-FDG uptake. A higher SUV was noted in 22 of 31 lesions on BH PET compared with clinical PET, with an average increase in SUV of 14%. Conclusion: BH PET/CT enabled an increased detection and better characterization of thoracic lesions compared with a standard PET/CT protocol, in addition to more precise localization and quantification of the findings. The technique is easy to implement in clinical practice and requires only a minor increase in the examination time.

Effect of motion on tracer activity determination in CT attenuation corrected PET images: A lung phantom study

Respiratory motion is known to affect the quantitation of FDG18 uptake in lung lesions. The aim of the study was to investigate the magnitude of errors in tracer activity determination due to motion, and its dependence upon CT attenuation at different phases of the motion cycle. To estimate these errors we have compared maximum activity concentrations determined from PET/CT images of a lung phantom at rest and under simulated respiratory motion. The NEMA 2001 IEC body phantom, containing six hollow spheres with diameters 37, 28, 22, 17, 13, and 10 mm, was used in this study. To mimic lung tissue density, the phantom (excluding spheres) was filled with low density polystyrene beads and water. The phantom spheres were filled with FDG18 solution setting the target-to-background activity concentration ratio at 8:1. PET/CT data were acquired with the phantom at rest, and while it was undergoing periodic motion along the longitudinal axis of the scanner with a range of displacement being 2 cm, and a period of 5 s. The phantom at rest and in motion was scanned using manufacturer provided standard helical/clinical protocol, a helical CT scan followed by a PET emission scan. The moving phantom was also scanned using a 4D-CT protocol that provides volume image sets at different phases of the motion cycle. To estimate the effect of motion on quantitation of activities in six spheres, we have examined the activity concentration data for (a) the stationary phantom, (b) the phantom undergoing simulated respiratory motion, and (c) a moving phantom acquired with PET/4D-CT protocol in which attenuation correction was performed with CT images acquired at different phases of motion cycle. The data for the phantom at rest and in motion acquired with the standard helical/clinical protocol showed that the activity concentration in the spheres can be underestimated by as much as 75%, depending on the sphere diameter. We have also demonstrated that fluctuations in spheres activity concentration from one PET/CT scan to another acquired with standard helical/clinical protocol can arise as a consequence of spatial mismatch between the spheres location in PET emission and the CT data.

Evaluation of an automated deformable image matching method for quantifying lung motion in respiration‐correlated CT images

We have evaluated an automated registration procedure for predicting tumor and lung deformation based on CT images of the thorax obtained at different respiration phases. The method uses a viscous fluid model of tissue deformation to map voxels from one CT dataset to another. To validate the deformable matching algorithm we used a respiration-correlated CT protocol to acquire images at different phases of the respiratory cycle for six patients with nonsmall cell lung carcinoma. The position and shape of the deformable gross tumor volumes (GTV) at the end-inhale (EI) phase predicted by the algorithm was compared to those drawn by four observers. To minimize interobserver differences, all observers used the contours drawn by a single observer at end-exhale (EE) phase as a guideline to outline GTV contours at EI. The differences between model-predicted and observer-drawn GTV surfaces at EI, as well as differences between structures delineated by observers at EI (interobserver variations) were evaluated using a contour comparison algorithm written for this purpose, which determined the distance between the two surfaces along different directions. The mean and 90% confidence interval for model-predicted versus observer-drawn GTV surface differences over all patients and all directions were 2.6 and 5.1 mm, respectively, whereas the mean and 90% confidence interval for interobserver differences were 2.1 and 3.7 mm. We have also evaluated the algorithms ability to predict normal tissue deformations by examining the three-dimensional (3-D) vector displacement of 41 landmarks placed by each observer at bronchial and vascular branch points in the lung between the EE and EI image sets (mean and 90% confidence interval displacements of 11.7 and 25.1 mm, respectively). The mean and 90% confidence interval discrepancy between model-predicted and observer-determined landmark displacements over all patients were 2.9 and 7.3 mm, whereas interobserver discrepancies were 2.8 and 6.0 mm. Paired t tests indicate no significant statistical differences between model predicted and observer drawn structures. We conclude that the accuracy of the algorithm to map lung anatomy in CT images at different respiratory phases is comparable to the variability in manual delineation. This method has therefore the potential for predicting and quantifying respiration-induced tumor motion in the lung.

Evaluation of a compartmental model for estimating tumor hypoxia via FMISO dynamic PET imaging.

This paper systematically evaluates a pharmacokinetic compartmental model for identifying tumor hypoxia using dynamic positron emission tomography (PET) imaging with 18F-fluoromisonidazole (FMISO). A generic irreversible one-plasma two-tissue compartmental model was used. A dynamic PET image dataset was simulated with three tumor regions-normoxic, hypoxic and necrotic-embedded in a normal-tissue background, and with an image-based arterial input function. Each voxelized tissues time activity curve (TAC) was simulated with typical values of kinetic parameters, as deduced from FMISO-PET data from nine head-and-neck cancer patients. The dynamic dataset was first produced without any statistical noise to ensure that correct kinetic parameters were reproducible. Next, to investigate the stability of kinetic parameter estimation in the presence of noise, 1000 noisy samples of the dynamic dataset were generated, from which 1000 noisy estimates of kinetic parameters were calculated and used to estimate the sample mean and covariance matrix. It is found that a more peaked input function gave less variation in various kinetic parameters, and the variation of kinetic parameters could also be reduced by two region-of-interest averaging techniques. To further investigate how bias in the arterial input function affected the kinetic parameter estimation, a shift error was introduced in the peak amplitude and peak location of the input TAC, and the bias of various kinetic parameters calculated. In summary, mathematical phantom studies have been used to determine the statistical accuracy and precision of model-based kinetic analysis, which helps to validate this analysis and provides guidance in planning clinical dynamic FMISO-PET studies.