Marcelo Mamede

Evaluation of the combined effects of target size, respiratory motion and background activity on 3D and 4D PET/CT images

Gated (4D) PET/CT has the potential to greatly improve the accuracy of radiotherapy at treatment sites where internal organ motion is significant. However, the best methodology for applying 4D-PET/CT to target definition is not currently well established. With the goal of better understanding how to best apply 4D information to radiotherapy, initial studies were performed to investigate the effect of target size, respiratory motion and target-to-background activity concentration ratio (TBR) on 3D (ungated) and 4D PET images. Using a PET/CT scanner with 4D or gating capability, a full 3D-PET scan corrected with a 3D attenuation map from 3D-CT scan and a respiratory gated (4D) PET scan corrected with corresponding attenuation maps from 4D-CT were performed by imaging spherical targets (0.5-26.5 mL) filled with (18)F-FDG in a dynamic thorax phantom and NEMA IEC body phantom at different TBRs (infinite, 8 and 4). To simulate respiratory motion, the phantoms were driven sinusoidally in the superior-inferior direction with amplitudes of 0, 1 and 2 cm and a period of 4.5 s. Recovery coefficients were determined on PET images. In addition, gating methods using different numbers of gating bins (1-20 bins) were evaluated with image noise and temporal resolution. For evaluation, volume recovery coefficient, signal-to-noise ratio and contrast-to-noise ratio were calculated as a function of the number of gating bins. Moreover, the optimum thresholds which give accurate moving target volumes were obtained for 3D and 4D images. The partial volume effect and signal loss in the 3D-PET images due to the limited PET resolution and the respiratory motion, respectively were measured. The results show that signal loss depends on both the amplitude and pattern of respiratory motion. However, the 4D-PET successfully recovers most of the loss induced by the respiratory motion. The 5-bin gating method gives the best temporal resolution with acceptable image noise. The results based on the 4D scan protocols can be used to improve the accuracy of determining the gross tumor volume for tumors in the lung and abdomen.

FDG-PET/CT tumor segmentation-derived indices of metabolic activity to assess response to neoadjuvant therapy and progression-free survival in esophageal cancer: correlation with histopathology results.

Purpose:To evaluate the diagnostic and prognostic abilities of PET tumor segmentation-derived indices of metabolic activity for the assessment of response to neoadjuvant chemoradiotherapy and progression-free survival in patients with esophageal cancer. Methods:Twenty-five patients with histologically confirmed esophageal cancer were retrospectively evaluated. The patients underwent PET-CT imaging before and after completion of neoadjuvant therapy. Images were evaluated visually and quantitatively with a three-dimensional threshold-based region-growing program, which calculates SUVm, SUVa of the entire tumor, metabolic tumor length (Lm) and volume (Vm) before and after therapy (SUVm1, SUVm2, SUVa1, SUVa2, Lm1, Lm2, Vm1, and Vm2, respectively). Percentage changes in these metabolic variables before and after therapy were also calculated (%SUVm, %SUVa, %Lm, %Vm, respectively). Results:SUVm1 (P = 0.018), SUVa1 (P = 0.019), Lm1 (P = 0.016), and Vm1 (P = 0.016) correlated with T-status. Advanced stage tumors (T3 + T4) had significantly higher glucose metabolism, metabolic length, and volume. Moreover, Lm1 >47.4 mm and Vm1 >29 cm3 were the best predictors of the level of tumor invasiveness. SUVm1 >12.7 and SUVa1 >5.9 could differentiate patients with positive lymph nodes from those without at presentation. %SUVa >32.3% and the SUVa1 >5.5 proved to be reliable predictors of pathologic response. SUVa2 >3.55 and SUVm2 >4.35 were the best predictors of disease progression during follow-up, with the latter having the best prognostic value. Conclusions:This study showed that FDG-PET tumor segmentation-derived indices of metabolic activity play a definite role in the evaluation of response to neoadjuvant chemoradiotherapy and progression-free survival in patients with esophageal cancer.

Abdominal Masses Sampled at PET/CT-guided Percutaneous Biopsy: Initial Experience with Registration of Prior PET/CT Images

PURPOSEnTo establish the feasibility of performing combined positron emission tomography (PET)/computed tomography (CT)-guided biopsy of abdominal masses by using previously acquired PET/CT images registered with intraprocedural CT images.nnnMATERIALS AND METHODSnIn this HIPAA-compliant institutional review board-approved study, 14 patients underwent clinically indicated percutaneous biopsy of abdominal masses (mean size, 3.3 cm; range, 1.2-5.0 cm) in the liver (n = 6), presacral soft tissue (n = 3), retroperitoneal lymph nodes (n = 2), spleen (n = 2), and pancreas (n = 1). PET/CT images obtained no more than 62 days (mean, 18.3 days) before the biopsy procedure were registered with intraprocedural CT images by using image registration software. The registered images were used to plan the procedure and help target the masses.nnnRESULTSnThe image registrations were technically successful in all but one patient, who had severe scoliosis. The remaining 13 biopsy procedures yielded diagnostic results, which were positive for malignancy in 10 cases and negative in three cases.nnnCONCLUSIONnPET/CT-guided abdominal biopsy with use of prior PET/CT images registered with intraprocedural CT scans is feasible and may be helpful when fluorine 18 fluorodeoxyglucose-avid masses that are not seen sufficiently with nonenhanced CT are sampled at biopsy.

FDG PET/CT patterns of treatment failure of malignant pleural mesothelioma: relationship to histologic type, treatment algorithm, and survival

PurposeThis study investigated the diagnostic performance and prognostic value of fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in suspected malignant pleural mesothelioma (MPM) recurrence, in the context of patterns and intensity of FDG uptake, histologic type, and treatment algorithm.MethodsFifty patients with MPM underwent FDG PET/CT for restaging 11u2009±u20096xa0months after therapy. Tumor relapse was confirmed by histopathology, and by clinical evolution and subsequent imaging. Progression-free survival was defined as the time between treatment and the earliest clinical evidence of recurrence. Survival after FDG PET/CT was defined as the time between the scan and death or last follow-up. Overall survival was defined as the time between initial treatment and death or last follow-up date.ResultsTreatment failure was confirmed in 42 patients (30 epithelial and 12 non-epithelial MPM). Sensitivity, specificity, accuracy, negative predictive value, and positive predictive value for FDG PET/CT were 97.6, 75, 94, 86, and 95.3%, respectively. FDG PET/CT evidence of single site of recurrence was observed in the ipsilateral hemithorax in 18 patients (44%), contralaterally in 2 (5%), and in the abdomen in 1 patient (2%). Bilateral thoracic relapse was detected in three patients (7%). Simultaneous recurrence in the ipsilateral hemithorax and abdomen was observed in ten (24%) patients and in seven (17%) in all three cavities. Unsuspected distant metastases were detected in 11 patients (26%). Four patterns of uptake were observed in recurrent disease: focal, linear, mixed (focal/linear), and encasing, with a significant difference between the intensity of uptake in malignant lesions compared to benign post-therapeutic changes. Lesion uptake was lower in patients previously treated with more aggressive therapy and higher in intrathoracic lesions of patients with distant metastases. FDG PET/CT helped in the selection of 12 patients (29%) who benefited from additional previously unplanned treatment at the time of failure. Multivariate analysis showed that histologic type remained the only independent predictor of progression-free survival. Survival after relapse was independently predicted by the pattern of FDG uptake and PET nodal status, and overall survival by the maximum standard uptake value.ConclusionFDG PET/CT is an accurate modality to diagnose and to estimate the extent of locoregional and distant MPM recurrence, and it carries independent prognostic value. Once the disease recurs, survival outcomes seem to be independent of histologic type and highly dependent on the intensity of lesion uptake and on the pattern of metabolically active disease in FDG PET/CT. Our observations should be considered limited to patients treated surgically with or without perioperative therapies and should not be extrapolated to those unresectable cases treated with chemotherapy alone.

Impact of Manual and Automated Interpretation of Fused PET/CT Data on Esophageal Target Definitions in Radiation Planning

PURPOSEnWe compare CT-only based esophageal tumor definition with two PET/CT based methods: (1) manual contouring and (2) a semiautomated method based on specific thresholds.nnnMETHODS AND MATERIALSnPatients with esophageal cancer treated at Brigham and Womens Hospital from 2003 to 2006 were identified. CT-based tumor volumes were compared with manual PET/CT-based volumes and semiautomated PET-based tumor volumes. Differences were scored as (1) minor if the superior or inferior extent of the primary tumor (or both) differed by 1-2 cm and (2) major if the difference was > 2 cm or if different noncontiguous nodal regions were identified as being grossly involved.nnnRESULTSnComparing CT-based gross tumor volumes (GTVs) to manually defined PET/CT-based GTVs, use of PET changed volumes for 21 of 25 (84%) patients: 12 patients (48%) exhibited minor differences, whereas for 9 patients (36%), the differences were major. For 4 (16%) patients, the major difference was due to discrepancy in celiac or distant mediastinal lymph node involvement. Use of automated PET volumes changed the manual PET length in 14 patients (56%): 8 minor and 6 major.nnnCONCLUSIONSnThe use of PET/CT in treatment planning for esophageal cancer can affect target definition. Two PET-based techniques can also produce significantly different tumor volumes in a large percentage of patients. Further investigations to clarify the optimal use of PET/CT data in treatment planning are warranted.

Motion artifacts occurring at the lung/diaphragm interface using 4D CT attenuation correction of 4D PET scans

For PET/CT, fast CT acquisition time can lead to errors in attenuation correction, particularly at the lung/diaphragm interface. Gated 4D PET can reduce motion artifacts, though residual artifacts may persist depending on the CT dataset used for attenuation correction. We performed phantom studies to evaluate 4D PET images of targets near a density interface using three different methods for attenuation correction: a single 3D CT (3D CTAC), an averaged 4D CT (CINE CTAC), and a fully phase matched 4D CT (4D CTAC). A phantom was designed with two density regions corresponding to diaphragm and lung. An 8 mL sphere phantom loaded with 18F‐FDG was used to represent a lung tumor and background FDG included at an 8:1 ratio. Motion patterns of sin(x) and sin4(x) were used for dynamic studies. Image data was acquired using a GE Discovery DVCT‐PET/CT scanner. Attenuation correction methods were compared based on normalized recovery coefficient (NRC), as well as a novel quantity “fixed activity volume” (FAV) introduced in our report. Image metrics were compared to those determined from a 3D PET scan with no motion present (3D STATIC). Values of FAV and NRC showed significant variation over the motion cycle when corrected by 3D CTAC images. 4D CTAC‐ and CINE CTAC–corrected PET images reduced these motion artifacts. The amount of artifact reduction is greater when the target is surrounded by lower density material and when motion was based on sin4(x). 4D CTAC reduced artifacts more than CINE CTAC for most scenarios. For a target surrounded by water equivalent material, there was no advantage to 4D CTAC over CINE CTAC when using the sin(x) motion pattern. Attenuation correction using both 4D CTAC or CINE CTAC can reduce motion artifacts in regions that include a tissue interface such as the lung/diaphragm border. 4D CTAC is more effective than CINE CTAC at reducing artifacts in some, but not all, scenarios. PACS numbers: 87.57.qp, 87.57.cp

SU‐GG‐I‐141: Automatic Segmentation of Static and Moving Target Volumes Using Respiratory Ungated (3D) and Gated (4D) PET/CT Images

Purpose: Thresholding methods are commonly used to segment lesion volumes in PETimages. However, the presence of motion makes it difficult to determine the optimum threshold. To measure the threshold needed to produce the true volume of a moving target, we have investigated the effect of respiratory motion on the threshold at varying target‐to‐background activity concentration ratios (TBRs) using gated (4D) and ungated (3D) PETimages.Method and Materials: Using a PET/CT scanner with gating capability, spherical targets (0.5–26.5 mL) filled with 18 F ‐ FDG in a NEMA IEC body phantom were imaged with both a 3D‐PET scan corrected with a 3D‐CT attenuation map and a 4D‐PET scan corrected with phase‐matched 4D‐CT maps. . The phantom was either at rest or moving sinusoidally in the superior‐inferior direction with an amplitude of 2 cm and a period of 4.5 s to simulate respiratory motion. The optimum threshold values which give the true volumes of the spheres were derived from the 3D and 4D‐PET images at TBR = 4, 8, and infinite. For the 4D‐PET images, 5‐bin gating data were used in this analysis.Results: The TBR‐threshold‐volume curves show that the optimum threshold exponentially decreases as the volume increases. In addition, the threshold increases as the TBR decreases. The results also illustrate that the threshold values applied to the 4D‐PET images for the moving targets are well correlated with the optimum threshold values applied to the 3D‐PET images for the targets at rest. However, the same thresholds significantly over‐estimate the target volume if applied to the 3D‐PET images of moving targets. Conclusion: The TBR‐threshold‐volume curves clearly demonstrate the advantage of gating for detecting the true volume of moving target. Therefore, respiratory‐gated PET acquisition should be performed in the presence of relatively large organ movement to accurately determine the gross tumor volume for clinical applications.

TU‐C‐332‐10: Evaluation of Combined Effects of Target Size, Background Activity, and Respiratory Motion On 3D and 4D PET/CT Images

Purpose: In recent years, quantitative analysis of gated (4D) PET/CT images has been introduced for diagnosis, staging, and prediction of tumor response where internal organ motion is significant. However, the best methodology for applying 4D information to radiotherapy target definition is not currently well established. In order to accurately determine moving target volume, we have investigated the combined effects of target size, respiratory motion, target‐to‐background activity concentration ratio (TBR) on ungated (3D) and 4D PETimages as well as gating methods. Method and Materials: Using a GE Discovery PET/CT scanner, a 3D‐PET scan corrected with a 3D attenuation map from 3D‐CT scan and a 4D‐PET scan corrected with matching attenuation maps from 4D‐CT were performed using spherical targets (0.5–26.5 mL) filled with 18 F ‐ FDG in a NEMA IEC body phantom at different TBRs (infinite, 8, and 4). To simulate respiratory motion, the phantoms were driven sinusoidally in the superior‐inferior direction with amplitudes of 0, 1, and 2 cm and a period of 4.5 s. Recovery coefficients were determined on PETimages. In addition, gating methods using different numbers of gating bins (1–20 bins) were evaluated by determining imagenoise and temporal resolution. Results: Signal loss in 3D‐PET images was measured from both the partial volume effect, due to the limited PET resolution, as well as respiratory motion. The results show that signal loss depends on both the amplitude and shape of respiratory motion. However, 4D‐PET successfully recovers most of the loss induced by respiratory motion. The 5‐bin gating method gives the best temporal resolution with acceptable imagenoise.Conclusion: The results based on the 4D scan protocols can be used to improve the accuracy of gross tumor volume definition in the lung and abdomen.

SU‐GG‐J‐166: Reduction of Motion Artifacts Occurring at the Lung/diaphragm Interface Using 4D‐CT Attenuation Correction On 4D‐PET Scans: Implications for Radiation Therapy Planning

Purpose: For PET/CT the fast CT acquisition time can lead to errors in attenuation correction, particularly at the lung/diaphragm interface. Gated 4D‐PET can reduce motion artifacts, though it is not always attenuation corrected with a similarly acquired 4D‐CT. We performed phantom studies specifically designed to evaluate 4D‐PET images using three different methods for attenuation correction: a single 3D‐CT (3D‐CTAC), an averaged 4D‐CT (CINE‐CTAC), and a fully phase matched 4D‐CT (4D‐CTAC). Method and Materials: A phantom was designed with two density regions corresponding to diaphragm and lung. An 8ml vial loaded with FDG was used to represent a lungtumor and background FDG was also added with an 8:1 ratio. Imaging was performed with a GE Discovery DVCT‐PET/CT scanner. Periodic motion of 2 cm amplitude was used and the image data was reconstructed into 10 phase bins over the motion cycle. Image data was analyzed using a GEimage processing workstation and in‐house developed software. Values of activity within the target for each relative phase were corrected for decay and compared to those derived from a 3D PET scan with no motion present (3D‐STATIC). Results: Activity values derived from 4D‐CTAC corrected PETimages are generally closer to 3D‐STATIC images with no motion present. Mean activity over the known target volume over the motion cycle, normalized to the activity for 3D‐STATIC, was 93%, 101% and 98% for 3D‐CTAC, CINE‐CTAC and 4D‐CTAC images respectively with corresponding standard deviations of 6%, 10% and 3%. Conclusion: Compared to other attenuation correction methods, 4D‐CTAC corrected 4D‐PET images correspond more closely on average to similar 3D‐STATIC images. Using CINE‐CTAC for correction resulted in mean activity values slightly closer to 3D‐STATIC, but with much greater variation over the motion cycle. We believe these results have implications for the use of 4D‐PET imaging for radiation therapy target definition.

SU‐FF‐I‐100: Experimental Evaluation of Motion Effects by Integration of the 4DCT/4DPET Hybrid GE Discovery VCT Scanner with the CIRS Dynamic Lung Phantom

Purpose: The integrated 4DPET/CT scanner has the advantage of accurate body position correspondence between the PET and CT scans as well as 4D acquisition capabilities for both modalities. The former reduces possible errors from misalignment when fusing PET and CT scans taken on different machines, while the latter improves our capability to account for anatomical changes due to respiratory motion. However, owing to the fundamental differences between the scanning techniques, artifacts may differ between the modalities. Materials and Methods: In our investigation we have expanded the advantage of the integrated scanner single reference frame by the improvement of a lung dynamic phantom that can be monitored by both the PET and CT 4D scanning procedures. This was achieved by the development of custom made inserts for the dynamic phantom that can accommodate different sized FDG‐filled spheres. The motion of the dynamic phantom was preprogrammed for trajectories of sine, sine6 and prerecorded traces of lung implanted fiducials from a previous study. In the case of the analytical curves, periods between 3.5 and 8.5 seconds were used along with amplitudes varying from 0.5 to 3cm. Spheres of various sizes filled with FDG of various activities were used. Results: Gated PET and CTimages of the same moving target were obtained within the same frame of reference for various amplitudes and periods of motion and for various sizes and activities of FDG‐filled spheres. Comparison of the images from the two modalities shows differences in the motion artifacts, which should be taken into account in radiotherapy planning. Conclusion: We have successfully developed a phantom system for obtaining highly correlated data sets for PET and CT with and without gated (4D) acquisition. Our preliminary results suggest that motions do have significant impact on the images. Further studies will investigate the clinical implications of this work.