Victor H. Gerbaudo

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.

Low-dose oral propranolol could reduce brown adipose tissue F-18 FDG uptake in patients undergoing PET scans.

Fluorine-18 fluoro-2-deoxy-D-glucose (FDG) uptake in brown adipose tissue (BAT) may generate FDG-PET scan misinterpretation. Recent studies have shown reduced FDG uptake in BAT in rats treated with high doses of the beta-blocker propranolol. The aim of this observational study was to present a cohort of patients with high FDG uptake in BAT who underwent a second scan after receiving a low dose of propranolol, to determine whether the use of this premedication could improve the diagnostic confidence of FDG-PET scans by inhibition FDG uptake in BAT, and also whether administration of this drug affects tracer uptake in tumors. Methods: Twenty-six cancer patients, presenting with increased BAT FDG uptake, were selected prospectively. On a different day, patients were given propranolol 20 mg orally 60 minutes prior to FDG administration 185–277.5 MBq (5–7.5 mCi) and were scanned again. Basal and postpropranolol BAT SUVmax, and tumor SUVmax (when present) were measured. Results: Mean basal BAT SUVmax was 5.52 ± 2.3. Mean postpropranolol SUVmax was 1.39 ± 0.42 (P < 0.0001). In 11 patients, the basal mean tumor SUVmax was 8.07 ± 6.4, and 7.88 ± 5.9 in postpropranolol scans (P = 0.53). Nine patients showed mediastinal FDG uptake in the basal scan, affecting image interpretation. This was not observed in postpropranolol scans. No adverse effects due to propranolol were encountered. Conclusions: In this patient cohort, there was significant reduction of FDG uptake in BAT following propranolol administration, allowing for adequate interpretation of FDG-PET and software-fused FDG-PET with CT images, particularly in the mediastinal area, without affecting tumor tracer uptake.

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

PURPOSE To 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. MATERIALS AND METHODS In 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. RESULTS The 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. CONCLUSION PET/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.

PET/CT-guided Percutaneous Biopsy of Abdominal Masses: Initial Experience

PURPOSE To develop a technique for guiding percutaneous biopsies of abdominal masses in a positron emission tomography (PET)/computed tomography (CT) scanner, and test its feasibility and safety in patients. MATERIALS AND METHODS The authors conducted a prospective study in 12 patients who were in need of both a diagnostic (18)F-fluoro-deoxy-D-glucose (FDG) PET/CT scan and a percutaneous biopsy of an abdominal mass, located in the liver (n = 7), presacral soft tissue (n = 2), lymph node (n = 2), and kidney (n = 1). After completion of the PET/CT scan, with the patient remaining on the table, a one-table-position PET/CT scan was obtained with a radiopaque grid in place, and the biopsy procedure was planned. Then, a biopsy needle was placed into the mass using one-table-position CT scan registered to the planning PET scan. Masses were sampled after confirming accurate positioning of the needle tips with a final one-table-position PET/CT scan. Negative results were confirmed independently with follow-up imaging. RESULTS All biopsy procedures yielded diagnostic results; nine were positive for malignancy, and three were negative (fibrosis, steatosis, and Escherichia coli infection). One non-FDG-avid mass biopsy yielded a malignant result. Seven masses were either invisible or poorly depicted with unenhanced CT scan, and two masses contained FDG avidity in only a portion of the mass. There were no complications. CONCLUSIONS Although our data are preliminary, this initial experience suggests that abdominal masses can undergo successful biopsy in a PET/CT scanner. PET/CT guidance may be helpful when performing biopsy on FDG-avid masses that are either not visible with unenhanced CT or are FDG avid in only a portion.

Epithelial Malignant Pleural Mesothelioma After Extrapleural Pneumonectomy: Stratification of Survival With CT-Derived Tumor Volume

OBJECTIVE The purpose of this study was to assess the usefulness of CT-derived tumor volume, with control for other prognostic factors, for stratifying survival after surgery-based multimodality treatment of a large cohort of patients with epithelial malignant pleural mesothelioma. MATERIALS AND METHODS We retrospectively reviewed 338 patients with mesothelioma who underwent extrapleural pneumonectomy between 2001 and 2007. The study cohort comprised 88 patients with epithelial subtype tumors, DICOM-format CT scans, and data regarding neoadjuvant and adjuvant therapy. Tumor volume was calculated, and Kaplan-Meier survival and Cox regression analyses were performed to compare the estimated survival functions of patient subgroups based on volume and other covariates related to outcome (sex, age, preoperative platelet count, hemoglobin concentration, WBC count, clinical and pathologic TNM category, and administration of neoadjuvant and adjuvant therapy). A multivariate regression model was derived on the basis of the most significant univariate predictors. RESULTS The median estimated tumor volume was 319 cm(3) (range, 4-3256 cm(3)). In univariate analysis, tumor volume, hemoglobin concentration, platelet count, pathologic TNM category, and administration of adjuvant chemotherapy or radiation therapy met the criteria for inclusion in the reverse stepwise regression analysis. In the final model, tumor volume, hemoglobin concentration, and administration of adjuvant chemotherapy or radiotherapy were identified as independently associated with overall survival. CONCLUSION With control of prognostic covariates, CT-derived tumor volume can be used to stratify survival of patients with epithelial mesothelioma after extrapleural pneumonectomy and should be included in prognostic evaluation of patients for whom resection is being considered.

Metabolic significance of the pattern, intensity and kinetics of 18F-FDG uptake in malignant pleural mesothelioma.

Background: Malignant pleural mesothelioma is an aggressive neoplasm with a highly variable course. This pilot study evaluated the significance of the pattern, intensity and kinetics of 18F-FDG uptake in mesothelioma in the context of histopathology and surgical staging. Methods: Sixteen consecutive patients with pleural disease on CT scan underwent 18F-FDG imaging. Imaging was performed with a dual detector gamma camera operating in coincidence mode. Semiquantitative image analysis was performed by obtaining lesion-to-background ratios (18F-FDG uptake index) and calculating the increment of 18F-FDG lesion uptake over time (malignant metabolic potential index (MMPi)). Results: Twelve patients had histologically proven malignant mesotheliomas (10 epithelial, two sarcomatoid). Thirty two lesions were positive for tumour. Patterns of uptake matched the extent of pleural and parenchymal involvement observed on CT scanning and surgery. Mean (SD) 18F-FDG uptake index for malignant lesions was 3.99 (1.92), range 1.5–9.46. Extrathoracic spread and metastases had higher 18F-FDG uptake indices (5.17 (2)) than primary (3.42 (1.52)) or nodal lesions (2.99 (1)). No correlation was found between histological grade and stage. The intensity of lesion uptake had poor correlation with histological grade but good correlation with surgical stage. 18F-FDG lesion uptake increased over time at a higher rate in patients with more advanced disease. The MMPi was a better predictor of disease aggressiveness than the histological grade. Conclusions: This pilot study suggests that the pattern, intensity, and kinetics of 18F-FDG uptake in mesothelioma are good indicators of tumour aggressiveness and are superior to the histological grade in this regard.

Current Trends in Radiologic Management of Malignant Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is an aggressive pleural tumor with a complex growth pattern. Imaging plays a crucial role in diagnosis and management. Computed tomography (CT) has been the mainstay in the clinical evaluation of MPM; however it underestimates early chest wall invasion, peritoneal involvement, and has well-known limitations in nodal metastatic evaluation. Perfusion CT can evaluate the microvasculature of tumors; however its disadvantages, such as high radiation exposure and side effects from iodinated contrast, have limited its use to research settings. Magnetic resonance imaging (MRI) is superior to CT, both in the differentiation of malignant from benign pleural disease and in the assessment of chest wall and diaphragmatic involvement. Perfusion and diffusion MRI are promising new techniques for the assessment of tumor cellularity and microvasculature and can be used for quantitative and qualitative assessment of treatment response. Fluorodeoxyglucose positron emission tomography (FDG-PET) is useful for the differentiation of benign from malignant lesions, for staging, and for monitoring response to therapy. PET-CT is superior to other imaging modalities in detecting more extensive disease involvement and identifying unsuspected occult distant metastases. This review focuses on the practical aspects of the radiological assessment of MPM, highlighting the role of the radiologist in preoperative and postoperative evaluation with a multimodality approach.

Imaging characteristics of pathologically proven thymic hyperplasia: identifying features that can differentiate true from lymphoid hyperplasia.

OBJECTIVE The purpose of this article is to investigate the imaging characteristics of pathologically proven thymic hyperplasia and to identify features that can differentiate true hyperplasia from lymphoid hyperplasia. MATERIALS AND METHODS Thirty-one patients (nine men and 22 women; age range, 20-68 years) with pathologically confirmed thymic hyperplasia (18 true and 13 lymphoid) who underwent preoperative CT (n=27), PET/CT (n=5), or MRI (n=6) were studied. The length and thickness of each thymic lobe and the transverse and anterior-posterior diameters and attenuation of the thymus were measured on CT. Thymic morphologic features and heterogeneity on CT and chemical shift on MRI were evaluated. Maximum standardized uptake values were measured on PET. Imaging features between true and lymphoid hyperplasia were compared. RESULTS No significant differences were observed between true and lymphoid hyperplasia in terms of thymic length, thickness, diameters, morphologic features, and other qualitative features (p>0.16). The length, thickness, and diameters of thymic hyperplasia were significantly larger than the mean values of normal glands in the corresponding age group (p<0.001). CT attenuation of lymphoid hyperplasia was significantly higher than that of true hyperplasia among 15 patients with contrast-enhanced CT (median, 47.9 vs 31.4 HU; Wilcoxon p=0.03). The receiver operating characteristic analysis yielded greater than 41.2 HU as the optimal threshold for differentiating lymphoid hyperplasia from true hyperplasia, with 83% sensitivity and 89% specificity. A decrease of signal intensity on opposed-phase images was present in all four cases with in- and opposed-phase imaging. The mean maximum standardized uptake value was 2.66. CONCLUSION CT attenuation of the thymus was significantly higher in lymphoid hyperplasia than in true hyperplasia, with an optimal threshold of greater than 41.2 HU in this cohort of patients with pathologically confirmed thymic hyperplasia.

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