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F-18-Fluorodeoxyglucose positron emission tomography (FDG-PET) has been used to evaluate the metabolic response of metastatic brain tumors to treatment by comparing their tumor glucose metabolism before and after treatment. The standard analysis based on regions-of-interest has the advantage of simplicity. However, it is by definition restricted to those regions and is subject to observer variability. In addition, the observed changes in tumor metabolism are often confounded by normal changes in the tissue background, which can be heterogenous. We propose an analysis pipeline for automatically detecting the change at each voxel in the entire brain of a single subject, while adjusting for changes in the background. The complete analysis includes image registration, segmentation, a hierarchical model for background adjustment and voxelwise statistical comparisons. We demonstrate the method’s ability to identify areas of tumor response and/or progression in two subjects enrolled in a clinical trial using FDG-PET to evaluate lapatinib for the treatment of brain metastases in breast cancer patients.

Glioblastoma (GBM) is an incurable brain tumor characterized by the expression of pro-angiogenic cytokines. A recent phase II clinical trial studied VEGF Trap in adult patients with temozolomide-resistant GBM. We sought to explore changes in [18F]Fluorodeoxyglucose positron emission tomography (FDG-PET) or magnetic resonance imaging (MRI) in trial participants correlating these changes with disease response. FDG-PET and MRI images obtained before and after the first dose of VEGF Trap were spatially co-registered. Regions of interest on each image slice were combined to produce a volume of interest representative of the entire tumor. Percent and absolute changes in maximum FDG-avidity, mean apparent diffusion coefficient (ADC), Ktrans, and Ve were calculated per lesion. Among the 12 participants that underwent dynamic contrast enhanced MRI (DCE-MRI), there were large, statistically significant reductions in Ktrans and Ve (median difference = −41.8 %, p

Whole body (3D) and respiratory gated (4D) FDG-PET/CT scans performed pre-radiotherapy (pre-RT) and post-radiotherapy (post-RT) were analyzed to investigate the impact of 4D PET in evaluating 18F-fluorodeoxyglucose (FDG) uptake changes due to therapy, relative to traditional 3D PET.3D and 4D sequential FDG-PET/CT scans were acquired pre-RT and approximately one month post-RT for patients with non-small cell lung cancer (NSCLC). The lesions of high uptake targeted with radiotherapy were identified on the pre-RT scan of each patient. Each lesion on the 3D and each of the five phases of the 4D scan were analyzed using a region of interest (ROI). For each patient the ROIs of the pre-RT scans were used to locate the areas of initial FDG uptake on the post-RT scans following rigid registration. Post-RT ROIs were drawn and the FDG uptake was compared with that of the pre-RT scans.Sixteen distinct lesions from 12 patients were identified and analyzed. Standardized uptake value (SUV) maxima were significantly higher (p-value0.005) for the lesions as measured on the 4D compared to 3D PET. Comparison of serial pre and post-RT scans showed a mean 62% decrease in SUV with the 3D PET scan (range 36-89%), and a 67% decrease with the 4D PET scan (range 30-89%). The mean absolute difference in SUV change on 3D versus 4D scans was 4.9%, with a range 0-15% (p-value = 0.07).Signal recovery with 4D PET results in higher SUVs when compared to standard 3D PET. Consequently, differences in the evaluation of SUV changes between pre and post-RT plans were observed. Such difference can have a significant impact in PET-based response assessment.

To investigate the behavior of tumor subvolumes of high [18F]-fluorodeoxyglucose (FDG) uptake as seen on clinical four-dimensional (4D) FDG-positron emission tomography (PET) scans.Four-dimensional FDG-PET/computed tomography scans from 13 patients taken before radiotherapy were available. The analysis was focused on regions of high uptake that are potential dose-painting targets. A total of 17 lesions (primary tumors and lymph nodes) were analyzed. On each one of the five phases of the 4D scan a classification algorithm was applied to obtain the region of highest uptake and segment the tumor volume. We looked at the behavior of both the high-uptake subvolume, called "Boost," and the segmented tumor volume, called "Target." We measured several quantities that characterize the Target and Boost volumes and quantified correlations between them.The behavior of the Target could not always predict the behavior of the Boost. The shape deformation of the Boost regions was on average 133% higher than that of the Target. The gross to internal target volume expansion was on average 27.4% for the Target and 64% for the Boost, a statistically significant difference (p0.05). Finally, the inhale-to-exhale phase (20%) had the highest shape deformation for the Boost regions.A complex relationship between the measured quantities for the Boost and Target volumes is revealed. The results suggest that in cases in which advanced therapy techniques such as dose painting are being used, a close examination of the 4D PET scan should be performed.

microPETreg-Focus-F120 is the latest model of dedicated small animal PET scanners from CTI-Concorde Microsystems LLC, (Knoxville, TN). This scanner, based on the geometry of the microPET-R4, takes advantage of several detector modifications to the coincidence processing electronics that improve the image resolution, sensitivity, and counting rate performance as compared to the predecessor models. This work evaluates the performance of the Focus-F120 system and shows its improvement over the earlier models. In particular, the spatial resolution is shown to improve from 2.32 to 1.69 mm at 5 mm radial distance and the peak absolute sensitivity increases from 4.1% to 7.1% compared to the microPET-R4. The counting rate capability, expressed in noise equivalent counting rate (NEC-1R), was shown to peak at over 800 kcps at 88 MBq for both systems using a mouse phantom. For this small phantom, the NECR counting rate is limited by the data transmission bandwidth between the scanner and the acquisition console. The rat-like phantom showed peak NEC-1R value at 300 kcps at 140 MBq. Evaluation of image quality and quantitation accuracy was also performed using specially designed phantoms and animal experiments

Purpose: Clinical evaluation of novel agents that target tumor blood vessels requires pharmacodynamic end points that measure vascular damage. Positron emission tomography (PET) was used to measure the effects of the vascular targeting agent combretastatin A4 phosphate (CA4P) on tumor and normal tissue perfusion and blood volume. Patients and Methods: Patients with advanced solid tumors were enrolled onto part of a phase I, accelerated-titration, dose-escalation study. The effects of 5 to 114 mg/m2 CA4P on tumor, spleen, and kidney were investigated. Tissue perfusion was measured using oxygen-15 (15O)–labeled water and blood volume was measured using 15O-labeled carbon monoxide (C15O). Scans were performed immediately before, and 30 minutes and 24 hours after the first infusion of each dose level of CA4P. All statistical tests were two sided. Results: PET data were obtained for 13 patients with intrapatient dose escalation. Significant dose-dependent reductions were seen in tumor perfusion 30 minutes after CA4P administration (mean change, −49% at ≥ 52 mg/m2; P = .0010). Significant reductions were also seen in tumor blood volume (mean change, −15% at ≥ 52 mg/m2; P = .0070). Although by 24 hours there was tumor vascular recovery, for doses ≥ 52 mg/m2 the reduction in perfusion remained significant (P = .013). Thirty minutes after CA4P administration borderline significant changes were seen in spleen perfusion (mean change, −35%; P = .018), spleen blood volume (mean change, −18%; P = .022), kidney perfusion (mean change, −6%; P = .026), and kidney blood volume (mean change, −6%; P = .014). No significant changes were seen at 24 hours in spleen or kidney. Conclusion: CA4P produces rapid changes in the vasculature of human tumors that can be assessed using PET measurements of tumor perfusion.

Measurement of tumour and normal tissue perfusion in vivo in cancer patients will aid the clinical development of antiangiogenic and antivascular agents. We investigated the potential antiangiogenic effects of the drug razoxane by measuring the changes in parameters estimated from H(2)(15)O and C(15)O positron emission tomography (PET) to indicate alterations in vascular physiology. The study comprised 12 patients with primary or metastatic renal tumours >3 cm in diameter enrolled in a Phase II clinical trial of oral razoxane. Perfusion, fractional volume of distribution of water (VD) and blood volume (BV) were measured in tumour and normal tissue before and 4-8 weeks after treatment with 125 mg twice-daily razoxane. Renal tumour perfusion was variable but lower than normal tissue: mean 0.87 ml min(-1) ml(-1) (range 0.33-1.67) compared to renal parenchyma: mean 1.65 ml min(-1) ml(-1) (range 1.16-2.88). In eight patients, where parallel measurements were made during the same scan session, renal tumour perfusion was significantly lower than in normal kidney (P=0.0027). There was no statistically significant relationship between pretreatment perfusion and tumour size (r=0.32, n=13). In six patients scanned before and after razoxane administration, there was no statistically significant change in tumour perfusion: mean perfusion pretreatment was 0.81 ml min(-1) ml(-1) (range 0.46-1.26) and perfusion post-treatment was 0.72 ml min(-1) ml(-1) (range 0.51-1.15, P=0.15). Tumour VD and BV did not change significantly following treatment: mean pretreatment VD=0.66 (range 0.50-0.87), post-treatment VD=0.71 (range 0.63-0.82, P=0.22); pretreatment BV=0.18 ml ml(-1) (range 0.10-0.25), post-treatment BV=0.167 ml ml(-1) (range 0.091-0.24, P=0.55). Tumour perfusion, VD and BV did not change significantly with tumour progression. This study has shown that H(2)(15)O and C(15)O PET provide useful in vivo physiological measurements, that even highly angiogenic renal cancers have poor perfusion compared to surrounding normal tissue, and that PET can provide valuable information on the in vivo biology of angiogenesis in man and can assess the effects of antiangiogenic therapy.

An important challenge to using fluorodeoxyglucose-positron emission tomography (FDG-PET) in clinical trials of brain tumor patients is to identify malignant regions whose metabolic activity shows significant changes between pretreatment and a posttreatment scans in the presence of high normal brain background metabolism. This paper describes a semiautomated processing and analysis pipeline that is able to detect such changes objectively with a given false detection rate. Image registration and voxelwise comparison of the pre- and posttreatment images were performed. A key step is adjustment of the observed difference by the estimated background change at each voxel, thereby overcoming the confounding effect of spatially heterogeneous metabolic activity in the brain. Components of the proposed method were validated via phantom experiments and computer simulations. It achieves a false response volume accuracy of 0.4% at a significance threshold of 3 standard deviations. It is shown that the proposed methodology can detect lesion response with 100% accuracy with a tumor-to-background-ratio as low as 1.5, and it is not affected by the background brain glucose metabolism change. We also applied the method to FDG-PET patient images from a clinical trial to assess treatment effects of lapatinib, which demonstrated significant changes in metabolism corresponding to tumor regions.

Many image-reconstruction methods have been proposed to improve the spatial resolution of positron emission tomography (PET) images and, thus, to produce better quantification. However, these techniques, which are designed for static images, may be inadequate for good reconstruction from dynamic data. The authors present a simple, but effective, reconstruction approach intended specifically for dynamic studies. First, the level of noise in dynamic PET data is reduced by smoothing along the time axis using a low-order approximation. Next, the denoised sinograms are restored spatially by the method of projections onto convex sets. Finally, images are reconstructed from the restored sinograms by ordinary filtered backprojection. The authors present experimental results that demonstrate substantial improvements in region-of-interest quantification in actual and simulated dopamine D-2 neuroreceptor-imaging studies of a monkey brain.

The potential role of four-dimensional (4D) positron emission tomography (PET)/computed tomography (CT) in radiation treatment planning, relative to standard three-dimensional (3D) PET/CT, was examined.Ten patients with non-small-cell lung cancer had sequential 3D and 4D [(18)F]fluorodeoxyglucose PET/CT scans in the treatment position prior to radiation therapy. The gross tumor volume and involved lymph nodes were contoured on the PET scan by use of three different techniques: manual contouring by an experienced radiation oncologist using a predetermined protocol; a technique with a constant threshold of standardized uptake value (SUV) greater than 2.5; and an automatic segmentation technique. For each technique, the tumor volume was defined on the 3D scan (VOL3D) and on the 4D scan (VOL4D) by combining the volume defined on each of the five breathing phases individually. The range of tumor motion and the location of each lesion were also recorded, and their influence on the differences observed between VOL3D and VOL4D was investigated.We identified and analyzed 22 distinct lesions, including 9 primary tumors and 13 mediastinal lymph nodes. Mean VOL4D was larger than mean VOL3D with all three techniques, and the difference was statistically significant (p0.01). The range of tumor motion and the location of the tumor affected the magnitude of the difference. For one case, all three tumor definition techniques identified volume of moderate uptake of approximately 1 mL in the hilar region on the 4D scan (SUV maximum, 3.3) but not on the 3D scan (SUV maximum, 2.3).In comparison to 3D PET, 4D PET may better define the full physiologic extent of moving tumors and improve radiation treatment planning for lung tumors. In addition, reduction of blurring from free-breathing images may reveal additional information regarding regional disease.

The objective of this study was to determine the impact on image quality and risks in terms of artifacts and side effects of a low-density barium-based suspension as oral contrast material for CT during PET/CT examinations of an oncologic patient population.Eighty-five patients (51 men and 34 women; mean age, 53 years; age range, 21-87 years) were prospectively randomized to receive either 0.1% barium sulfate oral suspension or no oral contrast material during PET/CT. Patients in the oral contrast group were given 1,350 mL over 60-75 minutes. The (18)F-FDG PET component of each examination was reviewed for the presence of artifacts by two nuclear medicine physicians and was classified as adequate (no presence of artifactual focal FDG uptake attributed to attenuation-correction errors) or inadequate (focal uptake in attenuation-correction PET images with no corresponding uptake in non-attenuation-corrected PET images). Two radiologists reviewed the CT studies and scored the degree of bowel opacification using a 5-point scale, ranging from 0 for no opacification (i.e., not possible to delineate the bowel structures from the surrounding tissues) to 4 for excellent opacification (i.e., bowel structure identifiable and bowel wall clearly visible). The attenuation values (in Hounsfield units) were recorded in the stomach, duodenum, mid jejunum, and terminal ileum for quantitative analysis. Interobserver variability was assessed using kappa coefficients.None of the patients who received oral contrast material experienced side effects. All 85 PET examinations were considered adequate with no observable artifacts. The mean bowel opacification scores of the oral contrast group (2.59 and 2.93) as evaluated by radiologists 1 and 2, respectively, were significantly higher (p0.01) than those of the control group (1.55 and 1.59). The level of attenuation achieved in the contrast group was significantly higher than in the control group. The interobserver variability was moderate (kappa = 0.32).The use of low-density neutral oral contrast material for CT during combined FDG PET/CT studies significantly improves visualization of the bowel structures compared with no contrast material without causing side effects or clinically detectable errors in the attenuation correction of the FDG PET study.

Purpose: Osteonecrosis of the jaw (ONJ) has been reported in patients with a history of aminobisphosphonate use. This study was conducted in order to define ONJ clinically and radiographically and gain insights into its pathophysiology. Experimental Design: Eleven multiple myeloma (MM) patients with ONJ were included in the study. Patients underwent clinical, biochemical, radiographic, and molecular profiling. Ten MM patients on aminobisphosphonates without ONJ and five healthy volunteers were used as controls for biochemical and molecular studies. Results: MM patients with ONJ were treated with either pamidronate (n = 3), zoledronate (n = 4), or both agents sequentially (n = 4) for a mean of 38.7 months. Radiographic studies showed bone sclerosis and fragmentation on plain films and computerized tomography. Quantitative regional analysis of NaF-PET and FDG-PET scans confirmed an increased standardized uptake value (SUVmax) in areas of ONJ. The target to background ratio of SUVmax was significantly greater for NaF-PET compared with FDG-PET scan. Biochemical bone marker data and transcriptional profiling studies showed that genes and proteins involved in osteoblast and osteoclast signaling cascades were significantly down-regulated in patients with ONJ. Conclusions: ONJ was associated with a mean duration of 38.7 months of aminobisphosphonate exposure. Radiographic and functional imaging confirmed sites of clinically established ONJ. Gene and protein studies are consistent with altered bone remodeling, evidenced by suppression of both bone resorption and formation.

Standard whole-body PET/CT protocols collect PET emission data for a sequence of discrete, overlapping bed positions. An alternative acquisition mode in which the patient bed moves continuously through the scanner has some significant advantages, including uniform axial signal-to-noise, elimination of resolution artifacts by sampling continuously in the axial direction, and a reduction in both noise from detector normalization and artifacts from small patient movements. To validate this approach, continuous bed motion acquisition has been implemented on a high resolution, 16-slice LSO PET/CT scanner (CPS Innovations, Knoxville, TN). The emission data are acquired in list mode with the bed moving at a constant velocity in the range 0.3-0.7 mm/s for a total scan time in patients of around 20 minutes covering an axial extent of 36-84 cm. The absolute position of the bed is read and inserted directly into the list mode data stream. Following acquisition, the emission data are rebinned into a fully 3D data set and reconstructed using a 3D OSEM algorithm. Continuous movement of the patient bed yields uniform signal-to-noise throughout the axial imaging field. For short imaging times, the bed movement in the standard acquisition becomes a significant fraction of the total scan time and continuous bed motion acquisition offers a more efficient alternative. Results are presented for some representative patient studies with both step-and-shoot and continuous bed motion acquisition.

Recent advances in multi-detector CT design have enabled isotropic sub-millimeter spatial resolution. Although dedicated small animal CT scanners have been developed, the latest generation of high-performance clinical CT scanners may have sufficient spatial resolution for the purposes of small animal imaging. We have investigated the use of a clinical 16-slice PET/CT scanner in combination with the microPETreg scanner for rodent imaging. A method for co-registering PET/CT and microPET images was developed to improve the anatomical localization of PET uptake and perform attenuation and scatter correction. CT and PET visible fiducial markers containing a 68Ge point source are attached to a flat platform used in both the microPETreg and PET/CT imaging sessions to perform landmark based co-registration of the CT and microPETreg images. An automated registration method based on mutual information was also evaluated. The co-registered CT images were segmented into bone, soft tissue, and lungs and the respective attenuation coefficients at 511 keV were used to generate a transmission image for attenuation and scatter correction. Using this approach, high resolution co-registered CT and microPETreg images were obtained without the need for a dedicated small animal CT scanner or traditional PET transmission scanning. This improves the intreptation of microPET images and the correction for attenuation and scatter may be important when scanning larger species or multiple animals simultaneously

Evaluation and follow up of small pulmonary nodules has become commonplace with advancing PET and CT technology. Limits in system resolution, recovery coefficient estimations and transaxial ROI determinations often make obtaining useful SUV data difficult. We demonstrate a method which may be more accurate for making these determinations. It is assumed that the nodule can be distinguished clearly on CT and that it resides in a region of homogenous background PET uptake. By integrating the PET activity over a large region including the small nodule and determining the volume of the lesion (V/sub lesion/) from thin slice CT images the activity concentration in the lesion (AC/sub lesion/) can be determined if the background activity concentration (AC/sub background/) is determined away from the lesion. The total integrated activity (IA) in the ROI is: IA=AC/sub lesion//spl middot/V/sub lesion/+AC/sub background/$ 8SV/sub background/. Alternatively the ratio of the activity concentration in the lesion to the background is: [(IA/AC/sub background/)-V/sub background/]/V/sub l /e/sub sion/. Results for activity ratios using a hollow spheres phantom indicate this method gives the correct value for the smallest sphere (activity volume=0.6cc) whereas the ratio using usual SUV determinations is spuriously low by a factor of up to /spl sim/2. Clinical results for a 1cc volume SPN indicate a tumor to background ratio of /spl sim/20 compared with a ratio of 15 using the maximum SUV, similar to the behavior seen in phantom measurements.

In reconstructing PET data in PET/CT imaging the determination of attenuation correction factors (ACFs) involves the scaling and reprojecting of the CT images. However in the case of truncation it is possible to obtain a better estimate of the ACFs passing through the CT field-of-view, since the ACFs at the CT energy (-70 keV) are known directly from the CT raw data. A proposed method for estimating the correct ACFs at 511 keV is to calculate the ACFs from the reconstructed CT images in the usual way at 511 keV, but also calculate them at 70 keV (i.e. without scaling). The correction to ACF at 511 keV is taken as the difference between the measured and reprojected ACF at 70 keV, scaled to 511 keV assuming it scales like water. It is expected that this procedure may be useful in obtaining better quantification of lesions within the CT field-of-view in the case of very large patients where the adipose tissue outside the CT field-of-view accounts for much of the attenuation.

Purpose: Utilizing an automatic segmentation technique, the definition of tumor volume on clinical 4D (gated) and 3D (non‐gated) PET scans was compared and the potential benefits of gated PET/CT acquisition for lungcancer patients were explored. Method and Materials: Data from patients that underwent 3D and 4D PET/CT scans prior to radiation therapy were analyzed. A belt (Anzai Medical Systems Inc) was used to monitor patient breathing and gate the 4D acquisition. The raw data were then binned into five breathing phases. On the reconstructedPETimages, an automatic segmentation technique based on a Gaussian Mixture Model (GMM) was applied to each phase individually and five gross tumor volumes (4D‐GTVs) were defined. The individual 4D‐GTVs were grouped together to create an internal target volume (ITV). The GMM method was also applied to the 3D data and a 3D‐GTV was defined. The resulting ITV and GTVs were compared and the contours were superimposed on the CT portion of the PET/CT scan to visually assess tumor coverage. Results: The ITV was 8% to 148% greater than the 3D‐GTV with an average of 45%. Visual inspection of the ITV and 3D‐GTV contours superimposed on the CT revealed better coverage of the CT‐defined tumor with the ITV. This was especially apparent in the superior and inferior portions of tumors exhibiting respiratory motion close to 1cm and small lung nodules with moderate FDG uptake. Deformations in the FDG uptake between different breathing phases were observed, demonstrating the possibility of deformations in the tumor shape. Conclusion: This is one of the first studies comparing tumor volume definition on 4D and 3D PET/CT clinical data. The results suggest that ITV obtained from 4D PET/CT covers the full extent of moving tumors better than a 3D‐GTV obtained from 3D PET/CT.

We have developed a software package which combines the simulation and analysis of dynamic brain images acquired by positron emission tomography. In the spatial domain, standard digitized phantoms are used to create spatial maps which represent various structures in the brain. In the temporal domain, kinetic models are used to simulate the dynamics at the pixel level for each time-activity curve. Physical characteristics such as spatial resolution and noise are then modeled on individual image frames. This software has been used in the case of [18F]fluorodeoxyglucose studies to produce realistic simulations which were further analyzed to confirm previous findings based on real clinical data.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

The estimation of physiologic parameters from dynamic positron emission tomography is limited by the validity of the assumed kinetic model. Furthermore, the presence of noise introduces variability that can degrade the precision and accuracy of the parameter estimates. In the case of parametric imaging, the estimation can be especially inadequate because it is performed at the pixel level with much lower counts than averaged regions of interest. These limitations can be reduced or avoided by applying data-driven statistical techniques such as factor analysis to identify the relevant temporal signatures while removing the random variations due to noise. In the first case, principal component analysis (PCA) is used to condition the data prior to applying the conventional parameter estimation, thereby improving the noise limitations. In the second case, the PCA provides the initial solution for the factor analysis, which incorporates prior knowledge to generate factor images, and time factors, which themselves can be considered a form of parametric image, and their associated physiologic time functions. In this regard, data-driven parameter estimation can be performed that avoids the inconsistencies between the actual data and the assumed kinetic model. Factor analysis has already been applied to dynamic neuroreceptor and cerebral glucose metabolism positron emission tomography (PET) studies to generate meaningful factors that differentiate specific from nonspecific binding and normal from diseased tissue function, respectively. In the latter case, a simulated image sequence having a pathophysiologic disturbance is generated and analyzed by factor analysis to produce factors consistent with the clinical findings. Significant improvements can also be achieved in the estimation of the compartmental model rate constants using the PCA processed data as compared to the raw simulated sequence.

Purpose: To quantify PET treatment response using a novel image registration approach, and to investigate the impact of 4D PET/CT pre‐ radiotherapy scan for predicting residual high‐uptake areas toward dose‐ boosting in adaptive radiotherapy.Methods: 3D and 4D FDG‐PET/CT scans were obtained from ten patients with non‐small cell lungcancer(NSCLC) for approximately two weeks before radiotherapy (pre‐RT) and approximately one month after therapy (post‐RT). The 4D scan was taken immediately following a 3D PET scan. The areas of high uptake in the pre‐ RT scans were aligned with those in the post‐RT scans using a novel rigid‐ penalized deformable registration. The global lung bronchi and chest wall were non‐rigidly transformed to minimize the respiration effects while the target lesion is rigidly transformed to preserve the volume and SUV values. A region of interest (ROI) was defined by a threshold of 40% of the maximum SUV for both 3D and 4D PET scans. The maximal SUV within the ROI were measured. Volumetric overlap fraction (VOF) was calculated as the overlap volume of pre‐RT and post‐RT target volumes divided by the residual volume in the post‐RT scans. Results: The maximal SUVs for 4D pre and post PET have a 16.3% increase compared to those in 3D PET. The pre‐to‐post maximal SUV variations showed 57% lesions has nontrivial residual uptake (SUVmax>2.5) for 3D PET, and 64% for 4D PET. The results of the VOFs showed that the residual metabolic‐active areas are mainly located within the primary tumor volume, 92% for 3D and 89% for 4D. Conclusions: Residual metabolic‐active areas have strong physiological and geometric correspondence to the primary tumor. With better signal recovery than standard 3D PET, high uptake areas of 4D PET pre‐RT can predict areas where residual metabolic activity will be found after radiotherapy.

We have developed a knowledge-based approach to analyzing dynamic nuclear medicine data sets using factor analysis. Prior knowledge is used as constraints to produce factor images and their associated time functions which are physically and physiologically realistic. These methods have been applied to both planar and tomographic image sequences acquired using various single-photon emitting and positron emitting radiotracers. Computer-simulated data, non-human primate studies, and human clinical studies have been used to develop and evaluate the methodology. The organ systems studied include the kidneys, heart, brain, liver, and bone. The factors generated represent various isolated aspects of physiologic function, such as tissue perfusion and clearance. In some clinical studies, the factors have indicated the potential to isolate diseased tissue from normally functioning tissue. In addition, the factor analysis of data acquired using newly developed radioligands has shown the ability to differentiate the specific binding of the radioligand to the targeted receptors from the non-specific binding. This suggests the potential use of factor analysis in the development and evaluation of radiolabeled compounds as well as in the investigation of specific receptor systems and their role in diagnosing disease.© (1994) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Purpose: Imaging of lungcancer with 4D PET has recently received much attention in oncology diagnosis and staging. Independently studies have also shown the feasibility of dosimetric evaluation of delivery efficacy of lung stereotactic body radiotherapy(SBRT) using an EPID in cine mode. We propose a novel method to evaluate treatment delivery by quantifying dose deposited in the residual tumor using 4D PET and in‐treatment imaging. Methods: A two‐step dosimetric evaluation of treatment delivery for lungSBRT is proposed. First, delivered dose is calculated by motion‐corrected fluence. Megavoltage images are recorded throughout treatment delivery, and tumor positions are tracked using a multi‐template tracking algorithm for all fields and fractions. The delivered fluence is obtained by convolving the tracked tumor positions with the planned fluence. Utilizing the convolved fluence, the 3D delivered dose is obtained. Second, treatment delivery is evaluated utilizing a post‐therapy 4D PET scan. High FDG uptake regions are segmented as sites of residual disease at each phase of 4D PETimages. Residual structures are then fused with the planning CT using regional image registration. Relying on the pre‐computed delivered dose,dose volume histograms (DVHs) are obtained for the residual structures. Results: We validated the method using clinical data acquired from lungSBRT treatments. The planned and delivered DVHs were compared and verified on the target volume. The delivered dose to the residual tumor was calculated for each phase of 4D PET. For a patient with large tumor motion (1 cm), 10% deviation from prescription dose is observed at inhale phase of breathing. Conclusions: Dose delivered to residual disease provides critical evidence for evaluation of the efficacy of treatment delivery. 4D PET has a potential impact on dosimetric evaluation for lungcancer treatment.

Purpose: Gated (4D) PET/CT scans have been shown to be effective in recovering the signal lost due to respiratory motion. Ungated (3D) and 4D FDG‐PET scans obtained pre and post radiation therapy (RT) for lungcancer were compared to examine the role of 4D PET in assessing FDG uptake changes due to therapy. Methods: Sequential 3D and 4D FDG‐PET/CT scans were acquired approximately two weeks before (pre‐RT) and one month after (post‐RT) treatment for patients receiving definitive RT for lungcancer. Targeted lesions were identified for each patient, and a region of interest (ROI) was defined for each lesion on the 3D and each of the five phases of the 4D pre‐RT scans. The ROIs were generated using a 40% of the maximum standardized uptake value (SUV) threshold, and the maximum SUV for each lesion from the pre—RT scans was recorded. Pre‐RT ROIs were then used to locate the areas of the original FDG uptake on the post‐RT scans using rigid registration. A post‐RT ROI was generated, and the maximum post‐RT SUV was recorded. Results: Sixteen lesions were identified and analyzed for twelve patients. Comparison of pre‐RT to post‐RT 3D PET scans showed a median SUV decrease of 62% (range 36–89%), while comparison of pre‐RT to post‐RT 4D PET scans showed a median SUV decrease of 67% (range 30–89%). The mean difference between the SUV change on 3D versus 4D scans was 4.9% (range 0–15%, p=.07), and the highest quartile had an absolute difference greater than 9% in SUV change.Conclusion: When assessing SUV changes with PET scans done pre and post‐RT, a substantial proportion of lesions had showed differences of over 9% in measurement of SUV change when comparing 3D PET to 4D PET. Such differences could potentially influence classification of PET‐based response assessment.

Multi-modality image integration, in which functional positron emission tomography (PET) and single-photon emission computed tomography (SPECT) images are co-registered spatially with structural x-ray computed tomography (CT) and magnetic resonance (MR) images, can provide new knowledge of correlates of brain function and brain structure that was difficult to access previously. For visualization and analysis of brain function, we have used this concept in the following areas: (1) Image reconstruction: We have developed a Bayesian data augmentation method that uses Gibbs prior for incorporation of high-resolution structural information extracted from the correlated CT and MR images in reconstruction of functional PET images. (2) Image segmentation and visualization: We have developed multi-spectral approaches for segmenting brain images into entities of functional/structural importance based on the integrated PET, CT, and multiple MR images. These segmented regions can be displayed in both 2-D and 3-D by using various visualization techniques. (3) Brain function mapping: Brain activation using PET has become a powerful tool for mapping brain functions in health and disease. Image subtraction techniques applied to a pair of images acquired respectively under baseline and activated conditions form the basis for detecting subtle and localized brain functions. Image integration is useful in correction for possible shifts in subject position between two separate scans, in quantitative interpolation between slices for localizing small and subtle brain functional signals, and in overlaying of the detected brain function signals with structural MR or CT images for providing accurate localization of the physiology/anatomy correlates. These image integration approaches provide improvements in reconstruction accuracy and useful new tools for visualization, as well as powerful new techniques for brain mapping. When used in combination, understanding of certain brain functions that were difficult to assess previously becomes accessible.

Purpose: In lungcancerradiotherapy biologically image guided dose painting is a promising new technique. Correct localization of tumor sub‐volumes remains a major challenge. The purpose of this work was to investigate tumor deformations as observed with 4D PET.Method and Materials: A total of 17 lesions were identified on the 4D FDG‐PET/CT scans from 13 patients. The data were binned in five phase bins using the AZ‐733V gating system. On each one of the five phases of the 4D scan a classification algorithm was applied to obtain the region of highest uptake and segment the tumor volume. We looked at the shape deformation of both the high uptake sub‐volumes and the corresponding segmented tumor volumes. We examined the dependence of shape deformation on the amplitude of motion and the variation in the volume estimate. The effect of motion was minimized by registering the volumes of phases 20–80% with the 0% phase (inhale). The Overlap (O) of the volumes was measured and the shape deformation was defined as 1‐O. The variation in the volume estimate between the different phases was measured by the standard deviation of the % difference from the average volume.Results: The shape deformation of the high uptake sub‐volumes was on average 169% larger than that of the full tumor volumes; a statistically significant difference. The shape deformation of the high uptake sub‐volumes was moderately correlated with that of the tumor (0.75) and the amplitude of motion (0.55). The inhale‐to‐exhale phase (20%) resulted in the largest shape deformation.Conclusions: There is a complex relationship between the behavior of tumor volumes and high uptake sub‐volumes. In cases where advanced therapy techniques such as dose painting based on biological sub‐volumes, are being employed, a close examination of a 4D PET scan should be considered.

Context Individuals with Li-Fraumeni syndrome (LFS) have an inherited cancer predisposition to a diverse array of malignancies beginning early in life; survivors of one cancer have a markedly elevated risk of additional primary tumors. The underlying genetic defect in the majority of the families is a germline mutation in the TP53 tumor suppressor gene. The diversity of tumors and rarity of families have contributed to the difficulty in devising effective screening recommendations for members of LFS kindreds. Objective To gather preliminary data with which to evaluate F18-fluorodeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) imaging as a potential surveillance modality to detect early malignancies in asymptomatic members of LFS kindreds. Design, Setting, and Participants Members of LFS families with documented germline TP53 mutations or obligate carrier status, no history of cancer within 5 years of enrollment, and no symptoms of cancer or ill-health were offered FDG-PET/CT scanning as a screening test in a comprehensive US cancer center from 2006 to 2007. Scans were initially reviewed clinically, then centrally reviewed by an expert radiologist. Main Outcome Measure The primary outcome was the detection of new primary cancers using FDG-PET/CT scanning. Results Of 15 individuals, baseline FDG-PET/CT scan identified asymptomatic cancers in 3 (20%). Two individuals had papillary thyroid cancers (stage II and stage III) and one individual had stage II esophageal adenocarcinoma. Conclusions These preliminary data provide the first evidence for a potential cancer surveillance strategy that may be worthy of further investigation for patients with LFS. Concerns about radiation exposure and other challenges inherent in screening high-risk patients will require further consideration.

In PET/CT tomographs the PET emission data can be corrected for photon attenuation effects using the CT images which are scaled from the mean CT energy of /spl sim/70 keV to the PET photon energy of 511 keV. The standard scaling approach requires segmenting the CT image voxels into soft tissue or bone using a single threshold of 300 H.U. and then applying two separate scale factors. In practice oral contrast may be administered leading to enhanced CT values that are not correctly handled by the standard scaling algorithm, which then leads to a bias in the PET emission image corrected for attenuation. A modified algorithm is proposed which transforms the oral contrast enhanced CT values to the correct 511 keV value, leading to unbiased attenuation correction factors.

Background Metastatic renal cell carcinoma has a poor prognosis and an intrinsic resistance to standard treatment. Sunitinib is an oral receptor tyrosine kinase inhibitor that has been used as a first-line targeted therapy in metastatic renal cell carcinoma. While computed tomography (CT) is currently the gold standard for response assessment in oncological trials, numerous studies have shown that positron emission tomography (PET) imaging can provide information predictive of tumor response to treatment earlier than the typical interval for standard of care follow-up CT imaging. In this exploratory study we sought to characterize early tumor response in patients with metastatic renal cell carcinoma treated with continuous daily 37.5 mg sunitinib therapy. Methods Twenty patients underwent dynamic acquisition positron emission tomography (PET) imaging using 18 F-fluorodeoxyglucose (FDG) and 18 F-fluorothymidine (FLT) at baseline and early in treatment (after 1, 2, 3 or 4 weeks) with 37.5 mg continuous daily dosing of sunitinib. Semi-quantitative analyses were performed to characterize the tumor metabolic (FDG) and proliferative (FLT) responses to treatment. Results Proliferative responses were observed in 9/19 patients and occurred in 2 patients at one week (the earliest interval evaluated) after the initiation of therapy. A metabolic response was observed in 5/19 patients, however this was not observed until after two weeks of therapy were completed. Metabolic progression was observed in 2/19 patients and proliferative progression was observed in 1/19 patients. Baseline FDG-PET tumor maximum standardized uptake values correlated inversely with overall survival (p = 0.0036). Conversely, baseline 18 F-fluorothymidine PET imaging did not have prognostic value (p = 0.56) but showed a greater early response rate at 1–2 weeks after initiating therapy. Conclusions While preliminary in nature, these results show an immediate and sustained proliferative response followed by a delayed metabolic response beginning after two weeks in metastatic renal cell carcinoma treated with a continuous daily dose of 37.5 mg sunitinib. The results provide evidence of tumor response to lower-dose sunitinib while also supporting the inclusion of PET imaging as a tool for early assessment in oncological clinical trials. Trial registration ID: NCT00694096