Ramsey D. Badawi

Initial Characterization of a Dedicated Breast PET/CT Scanner During Human Imaging

We have constructed a dedicated breast PET/CT scanner capable of high-resolution functional and anatomic imaging. Here, we present an initial characterization of scanner performance during patient imaging. Methods: The system consisted of a lutetium oxyorthosilicate–based dual–planar head PET camera (crystal size, 3 × 3 × 20 mm) and 768-slice cone-beam CT. The position of the PET heads (separation and height) could be adjusted for varying breast dimensions. For scanning, the patient lay prone on a specialized bed and inserted a single pendent breast through an aperture in the table top. Compression of the breast as used in mammography is not required. PET and CT systems rotate in the coronal plane underneath the patient sequentially to collect fully tomographic datasets. PET images were reconstructed with the fully 3-dimensional maximum a posteriori method, and CT images were reconstructed with the Feldkamp algorithm, then spatially registered and fused for display. Phantom scans were obtained to assess the registration accuracy between PET and CT images and the influence of PET electronics and activity on CT image quality. We imaged 4 women with mammographic findings highly suggestive of breast cancer (breast imaging reporting and data system, category 5) in an ongoing clinical trial. Patients were injected with 18F-FDG and imaged for 12.5 min per breast. From patient data, noise-equivalent counting rates and the singles-to-trues ratio (a surrogate for the randoms fraction) were calculated. Results: The average registration error between PET and CT images was 0.18 mm. PET electronics and activity did not significantly affect CT image quality. For the patient trial, biopsy-confirmed cancers were visualized on dedicated breast PET/CT on all patient scans, including the detection of ductal carcinoma in situ in 1 case. The singles-to-trues ratio was found to be inversely correlated with breast volume in the field of view, suggesting that larger breasts trend toward increased noise-equivalent counting rates for all other things equal. Conclusion: Scanning of the uncompressed breast with dedicated breast PET/CT can accurately visualize suspected lesions in 3 dimensions.

Variations in PET/CT Methodology for Oncologic Imaging at U.S. Academic Medical Centers: An Imaging Response Assessment Team Survey

In 2005, 8 Imaging Response Assessment Teams (IRATs) were funded by the National Cancer Institute (NCI) as supplemental grants to existing NCI Cancer Centers. After discussion among the IRATs regarding the need for increased standardization of clinical and research PET/CT methodology, it became apparent that data acquisition and processing approaches differ considerably among centers. To determine the variability in detail, a survey of IRAT sites and IRAT affiliates was performed. Methods: A 34-question instrument evaluating patient preparation, scanner type, performance approach, display, and analysis was developed. Fifteen institutions, including the 8 original IRATs and 7 institutions that had developed affiliate IRATs, were surveyed. Results: The major areas of variation were 18F-FDG dose (259–740 MBq [7–20 mCi]) uptake time (45–90 min), sedation (never to frequently), handling of diabetic patients, imaging time (2–7 min/bed position), performance of diagnostic CT scans as a part of PET/CT, type of acquisition (2-dimensional vs. 3-dimensional), CT technique, duration of fasting (4 or 6 h), and (varying widely) acquisition, processing, display, and PACS software—with 4 sites stating that poor-quality images appear on PACS. Conclusion: There is considerable variability in the way PET/CT scans are performed at academic institutions that are part of the IRAT network. This variability likely makes it difficult to quantitatively compare studies performed at different centers. These data suggest that additional standardization in methodology will be required so that PET/CT studies, especially those performed quantitatively, are more comparable across sites.

Developments in component-based normalization for 3D PET

Normalization in positron emission tomography (PET) is the process of ensuring that all lines of response joining detectors in coincidence have the same effective sensitivity. In three-dimensional (3D) PET, normalization is complicated by the presence of a large proportion of scattered coincidences, and by the fact that cameras operating in 3D mode encounter a very wide range of count-rates. In this work a component-based normalization model is presented which separates the normalization of true and scattered coincidences and accounts for variations in normalization effects with count-rate. The effects of the individual components in the model on reconstructed images are investigated, and it is shown that only a subset of these components has a significant effect on reconstructed image quality.

Randoms variance reduction in 3D PET

In positron emission tomography (PET), random coincidence events must be removed from the measured signal in order to obtain quantitatively accurate data. The most widely implemented technique for estimating the number of random coincidences on a particular line of response is the delayed coincidence channel method. Estimates obtained in this way are subject to Poisson noise, which then propagates into the final image when the estimates are subtracted from the prompt signal. However, this noise may be reduced if variance reduction techniques similar to those used in normalization of PET detectors are applied to the randoms estimates prior to use. We have investigated the effects of randoms variance reduction on noise-equivalent count (NEC) rates on a whole-body PET camera operating in 3D mode. NEC rates were calculated using a range of phantoms representative of situations that might be encountered clinically. We have also investigated the properties of three randoms variance reduction methods (based on algorithms previously used for normalization) in terms of their systematic accuracy and their variance reduction efficacy, both in phantom studies and in vivo. Those algorithms investigated that do not make assumptions about the spatial distribution of random coincidences give the best estimates of the randoms distribution. With the camera used, which has a limited axial extent (10.8 cm) and a large ring diameter (102 cm), the gains in image signal-to-noise ratio obtained with this technique ranged from approximately 5% to approximately 15%, depending on object size, activity distribution and the amount of activity in the field of view. Larger gains would be expected if this technique were to be employed on cameras of greater axial extent and smaller ring diameter.

The effect of camera geometry on singles flux, scatter fraction and trues and randoms sensitivity for cylindrical 3D PET-a simulation study

Preliminary results of an assessment of the effects of changing the axial field of view (AFOV) and detector ring diameter (DRD) of a cylindrical PET tomograph on count rate performance are presented. The assessment was made using Monte Carlo simulations of an anthropomorphic phantom based on the Zubal phantom. This phantom was modified to include cylinders approximating arms and legs, and was sequentially stepped through the AFOV to simulate a whole-body scan covering an axial region of interest of 1 m. DRD was varied from /spl sim/60 cm to /spl sim/108 cm, and AFOV was varied from 10 cm to 60 cm. A simple activity distribution and dead time model was assumed to allow the calculation of noise-equivalent count (NEC) rates for a situation similar to that of a typical 18F-FDG study. Both the scatter fraction and singles flux were found to be strongly dependent on DRD, but only weakly dependent on AFOV when the latter was greater than /spl sim/25 cm. Trues and randoms sensitivity were strongly dependent on AFOV, and randoms sensitivity was also strongly dependent on DRD. Scatter and singles flux do not appear to be limiting factors for extended AFOV configurations, and randoms rates, while high, appear to be manageable with existing detector technology. This initial assessment suggests that for whole-body applications, substantial gains in NEC may be possible by extending the AFOV.

PET characteristics of a dedicated breast PET/CT scanner prototype

A dedicated breast PET/CT system has been constructed at our institution, with the goal of having increased spatial resolution and sensitivity compared to whole-body systems. The purpose of this work is to describe the design and the performance characteristics of the PET component of this device. Average spatial resolution of a line source in warm background using maximum a posteriori (MAP) reconstruction was 2.5 mm, while the average spatial resolution of a phantom containing point sources using filtered back projection (FBP) was 3.27 mm. A sensitivity profile was computed with a point source translated across the axial field of view (FOV) and a peak sensitivity of 1.64% was measured at the center of the FOV. The average energy resolution determined on a per-crystal basis was 25%. The characteristic dead time for the front-end electronics and data acquisition (DAQ) was determined to be 145 ns and 3.6 micros, respectively. With no activity outside the FOV, a peak noise-equivalent count rate of 18.6 kcps was achieved at 318 microCi (11.766 MBq) in a cylindrical phantom of diameter 75 mm. After the effects of exposing PET detectors to x-ray flux were evaluated and ameliorated, a combined PET/CT scan was performed. The percentage standard deviations of uniformity along axial and transaxial directions were 3.7% and 2.8%, respectively. The impact of the increased reconstructed spatial resolution compared to typical whole-body PET scanners is currently being assessed in a clinical trial.

Evaluation of Myocardial Perfusion Using Positron Emission Tomography in Infants Following a Neonatal Arterial Switch Operation

Abstract. This study was performed to examine the use of positron emission tomography (PET) as a method of evaluating myocardial perfusion after the arterial switch operation for correction of transposition of the great arteries. Eleven asymptomatic patients (median age 2.3 years, range 1.3–4.3 years) post successful neonatal arterial switch repair for transposition underwent cardiac PET scanning using N13 ammonia before and after dipyridamole infusion. Reconstructed data from static scans were analyzed for regional perfusion defects before and after pharmacological stress. Simultaneous assessment of coronary flow before and after stress was performed using a Patlak graphical analysis of data from dynamic scans. Results obtained from PET scanning were correlated with patterns of coronary artery anatomy, electrocardiogram (ECG) recordings, and echocardiographic evaluation. PET scanning demonstrated normal distribution of myocardial perfusion before and after stress in all but one patient, who was found to have a discrete inferior transmural perfusion defect. The defect was well correlated with perioperative ECG changes and a complicated postoperative course. Myocardial blood flow before dipyridamole (0.690 ml/min/g) was similar to reported adult rest values. There was a small but significant (p < 0.002) increase in myocardial blood flow after dipyridamole stress with a mean coronary flow reserve of 1.19 (±0.103). Echocardiographic evaluation failed to demonstrate significant wall motion abnormalities in any of the patients. Cardiac PET scanning is a reliable noninvasive method for evaluation of myocardial perfusion in small children. In this study, the incidence of myocardial perfusion defects after the arterial switch operation is lower than previously reported. The data obtained concerning coronary flow and coronary flow reserve after the arterial switch need to be interpreted with caution because normal data in children are not available.

High-resolution 18F-FDG PET with MRI for monitoring response to treatment in rheumatoid arthritis

Eur J Nucl Med Mol Imaging (2010) 37:1047 DOI 10.1007/s00259-009-1364-x IMAGE OF THE MONTH High-resolution 18 F-FDG PET with MRI for monitoring response to treatment in rheumatoid arthritis Abhijit J. Chaudhari & Spencer L. Bowen & George W. Burkett & Nathan J. Packard & Felipe Godinez & Anand A. Joshi & Stanley M. Naguwa & David K. Shelton & John C. Hunter & John M. Boone & Michael H. Buonocore & Ramsey D. Badawi Received: 20 November 2009 / Accepted: 10 December 2009 / Published online: 30 January 2010 # The Author(s) 2010. This article is published with open access at Springerlink.com Molecular imaging can potentially provide means for mon- itoring response to therapy in rheumatoid arthritis (RA) early in the course of disease [1].Quantitative measurements of RA disease activity made in the wrist by whole-body PET scanners, however, have inadequate accuracy because of limited spatial resolution [2]. A high-resolution PET/CT scanner for imaging extremities has been built at our insti- tution [3]. In conjunction with a clinical MRI scanner, high- resolution PET/MR images can be obtained for the wrist. The CT image is used for PET/MR image coregistration. A 57-year-old female with established RA was stable until a recent clinical flare-up in the right wrist. Clinical exami- nation revealed synovitis, swelling, and diminished range of motion. The patient also had a history of osteoarthritis (OA). An extremity 18 F-FDG PET/CT scan immediately following MRI at baseline was performed on this patient. Tumor necrosis factor alpha (TNF-α) inhibitor (etanercept) therapy was then initiated as a part of the patient’s standard of care. The patient was re-scanned 5 weeks after starting treatment. The figure shows high-resolution 18 F-FDG PET images (pseudocolor) overlaid on pre-contrast MRI images (gray This work was funded by the NIH grants UL1-RR024146, R01CA129561, R01EB002138 and the UC Davis Imaging Research Center. A. J. Chaudhari (*) : S. L. Bowen : G. W. Burkett : N. J. Packard : F. Godinez : D. K. Shelton : J. C. Hunter : J. M. Boone : M. H. Buonocore : R. D. Badawi Department of Radiology, UC Davis Medical Center, Sacramento, CA, USA e-mail: ajchaudhari@ucdavis.edu A. A. Joshi Department of Neurology, UCLA School of Medicine, Los Angeles, CA, USA S. M. Naguwa Department of Internal Medicine, UC Davis Medical Center, Sacramento, CA, USA scale) at baseline (left column) and 5 weeks (right column). Significant reduction in PET signal (suggesting reduced inflammation) in the synovium and at sites of erosions (white arrows) is visible. The green arrow shows inflammation due to OA. Physician examination at 3 months confirmed that this patient responded positively to etanercept. This case illustrates the potential of high-resolution PET with MRI for quantitative visualization of early response to therapy in RA. Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which per- mits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. References 1. Brenner W. 18F-FDG PET in rheumatoid arthritis: there still is a long way to go. J Nucl Med. 2004;45(6):927–9. 2. Beckers C, Ribbens C, Andre B, Marcelis S, Kaye O, Mathy L, et al. Assessment of disease activity in rheumatoid arthritis with (18)F-FDG PET. J Nucl Med. 2004;45(6):956–64. 3. Bowen SL, Wu Y, Chaudhari AJ, Fu L, Packard NJ, Burkett GW, et al. Initial characterization of a dedicated breast PET/CT scanner during human imaging. J Nucl Med. 2009;50(9):1401–8.

Semiautomated Segmentation for Volumetric Analysis of Intratumoral Ethiodol Uptake and Subsequent Tumor Necrosis After Chemoembolization

OBJECTIVE Linear measurements, such as those described by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, may be limited for assessment of response after transarterial chemoembolization (TACE). The purpose of this pilot study was to show intra- and interobserver reproducibility of volumetric measurements of Ethiodol (ethiodized oil) seen within tumor 24 hours after TACE and of necrotic and viable tumor 1 month after treatment. Volumetric measurements are compared with linear measurements and survival outcomes. MATERIALS AND METHODS Between 2006 and 2009, 37 consecutive TACE procedures were performed in 27 patients with hepatic malignancies. CT images obtained 24 hours and 1 month after TACE were retrospectively analyzed. Three observers measured volumes twice. Intraoperator reproducibility was determined using Wilcoxons signed rank test to assess whether the difference in each volumetric measurement approaches zero. The intraclass correlation coefficient (ICC) and Bland-Altman plots were used to determine interoperator reproducibility. Survival data were retrospectively obtained from the electronic medical record. RESULTS Good intraobserver reproducibility and interobserver reproducibility (p > 0.05, ICC > 0.9, respectively) were shown for Ethiodol, whole tumor, and necrotic tumor volumes. The volume of Ethiodol correlated with subsequent necrotic tumor volume (p = 0.009), reduction in whole tumor volume (p = 0.004), and patient survival (p = 0.029). Kaplan-Meier curves suggest that Ethiodol accumulation in more than 50% of the tumor and a 10% or greater increase in the volume of necrotic tumor correlated with survival (p = 0.028 and 0.047, respectively). CONCLUSION Semiautomated volumetric analysis can be performed with good intra- and interobserver reproducibility. The volume of Ethiodol accumulated in the tumor after TACE correlates with subsequent necrosis. These early measurements may predict survival outcomes.

Excitation spectroscopy in multispectral optical fluorescence tomography: methodology, feasibility and computer simulation studies

Molecular probes used for in vivo optical fluorescence tomography (OFT) studies in small animals are typically chosen such that their emission spectra lie in the 680-850 nm wavelength range. This is because tissue attenuation in this spectral band is relatively low, allowing optical photons even from deep sites in tissue to reach the animal surface and consequently be detected by a CCD camera. The wavelength dependence of tissue optical properties within the 680-850 nm band can be exploited for emitted light by measuring fluorescent data via multispectral approaches and incorporating the spectral dependence of these optical properties into the OFT inverse problem-that of reconstructing underlying 3D fluorescent probe distributions from optical data collected on the animal surface. However, in the aforementioned spectral band, due to only small variations in the tissue optical properties, multispectral emission data, though superior for image reconstruction compared to achromatic data, tend to be somewhat redundant. A different spectral approach for OFT is to capitalize on the larger variations in the optical properties of tissue for excitation photons than for the emission photons by using excitation at multiple wavelengths as a means of decoding source depth in tissue. The full potential of spectral approaches in OFT can be realized by a synergistic combination of these two approaches, that is, exciting the underlying fluorescent probe at multiple wavelengths and measuring emission data multispectrally. In this paper, we describe a method that incorporates both excitation and emission spectral information into the OFT inverse problem. We describe a linear algebraic formulation of the multiple wavelength illumination-multispectral detection forward model for OFT and compare it to models that use only excitation at multiple wavelengths or those that use only multispectral detection techniques. This study is carried out in a realistic inhomogeneous mouse atlas using singular value decomposition and analysis of reconstructed spatial resolution versus noise. For simplicity, quantitative results have been shown for one representative fluorescent probe (Alexa 700) and effects due to tissue autofluorescence have not been taken into account. We also demonstrate the performance of our method for 3D reconstruction of tumors in a simulated mouse model of metastatic human hepatocellular carcinoma.