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We acquire and compare three-dimensional tomographic breast images of three females with suspicious masses using diffuse optical tomography (DOT) and positron emission tomography (PET). Co-registration of DOT and PET images was facilitated by a mutual information maximization algorithm. We also compared DOT and whole-body PET images of 14 patients with breast abnormalities. Positive correlations were found between total hemoglobin concentration and tissue scattering measured by DOT, and fluorodeoxyglucose (18F-FDG) uptake. In light of these observations, we suggest potential benefits of combining both PET and DOT for characterization of breast lesions.

Objectives: Focal lesions in infants with congenital hyperinsulinism (HI) represent areas of adenomatosis that express a paternally derived ATP-sensitive potassium channel mutation due to embryonic loss of heterozygosity for the maternal 11p region. This study evaluated the accuracy of 18 F-fluoro-L-dihydroxyphenylalanine ([ 18 F]DOPA) positron emission tomography (PET) scans in diagnosing focal vs. diffuse disease and identifying the location of focal lesions. Design:Atotalof50infantswithHIunresponsivetomedicaltherapy were studied. Patients were injected iv with [ 18 F]DOPA, and PET scans were obtained for 50–60 min. Images were coregistered with abdominal computed tomography scans. PET scan interpretations were compared with histological diagnoses. Results: The diagnosis of focal or diffuse HI was correct in 44 of the 50 cases (88%). [ 18 F]DOPA PET identified focal areas of high uptake of radiopharmaceutical in 18 of 24 patients with focal disease. The locations of these lesions matched the areas of increased [ 18 F]DOPA uptake on the PET scans in all of the cases. PET scan correctly located five lesions that could not be visualized at surgery. The positive predictive value of [ 18 F]DOPA in diagnosing focal adenomatosis was 100%, and the negative predictive value was 81%. Conclusions: [ 18 F]DOPA PET scans correctly diagnosed 75% of focal cases and were 100% accurate in identifying the location of the lesion. These results suggest that [ 18 F]DOPA PET imaging provides a useful guide to surgical resection of focal adenomatosis and should be considered as a guide to surgery in all infants with congenital HI who have medically uncontrollable disease. (J Clin Endocrinol Metab 92: 4706–4711, 2007)

The PET Core Laboratory of the American College of Radiology Imaging Network (ACRIN) qualifies sites to participate in multicenter research trials by quantitatively reviewing submitted PET scans of uniform cylinders to verify the accuracy of scanner standardized uptake value (SUV) calibration and qualitatively reviewing clinical PET images from each site. To date, cylinder and patient data from 169 PET scanners have been reviewed, and 146 have been qualified. Methods: Each site is required to submit data from 1 uniform cylinder and 2 patient test cases. Submitted phantom data are analyzed by drawing a circular region of interest that encompasses approximately 90% of the diameter of the interior of the phantom and then recording the mean SUV and SD of each transverse slice. In addition, average SUVs are measured in the liver of submitted patient scans. These data illustrate variations of SUVs across PET scanners and across institutions, and comparison of results with values submitted by the site indicate the level of experience of PET camera operators in calculating SUVs. Results: Of 101 scanner applications for which detailed records of the qualification process were available, 12 (12%) failed because of incorrect SUV or normalization calibrations. For sites to pass, the average cylinder SUV is required to be 1.0 ± 0.1. The average SUVs for uniform cylinder images for the most common scanners evaluated—Siemens Biograph PET/CT (n = 43), GE Discovery LS PET/CT (n = 15), GE Discovery ST PET/CT (n = 34), Philips Allegro PET (n = 5), and Philips Gemini PET/CT (n = 11)—were 0.99, 1.01, 1.00, 0.98, and 0.95, respectively, and the average liver SUVs for submitted test cases were 2.34, 2.13, 2.27, 1.73, and 1.92, respectively. Conclusion: Minimizing errors in SUV measurement is critical to achieving accurate quantification in clinical trials. The experience of the ACRIN PET Core Laboratory shows that many sites are unable to maintain accurate SUV calibrations without additional training or supervision. This raises concerns about using SUVs to quantify patient data without verification.

11C-carfentanil is a radiopharmaceutical that selectively binds the mu-opiate receptor of the central nervous system. However, its dosimetry throughout the body and other organs has never been reported in the literature. The purpose of this study was to measure the radiation dosimetry of 11C-carfentanil in healthy human volunteers. The study was conducted within a regulatory framework that required its pharmacological safety to be assessed simultaneously.The sample included two male and three female participants ranging in age from 28 to 49 years. Three to four scans were obtained over approximately 2 h starting immediately after the intravenous administration of 0.03 microg/kg of [C]carfentanil injected as a slow bolus (mean activity injected was 280+/-68 MBq). The fraction of the administered dose in 10 regions of interest was quantified from the attenuation-corrected counts obtained on the axial images. Monoexponential functions were fit to each time-activity curve using a nonlinear, least-squares regression algorithm. These curves were numerically integrated to yield the number of disintegrations per unit activity administered in source organs. Sex-specific radiation doses were then estimated with the medical internal radiation dose technique.A few participants reported mild pharmacological effects of the radiotracer, primarily mild drowsiness, which is an expected side effect. The dose-limiting organ was the bladder wall, which received a mean of 3.65E-02 mGy/MBq. The mean effective dose equivalent and effective dose for 11C-carfentanil were 5.38E-03 and 4.59E-03 mSv/MBq, respectively.The observed dosimetry values for 11C-carfentanil indicate that it is safe for imaging micro-opiate receptors in the central nervous system and periphery.

Rebinning is used in PET to reduce three-dimensional (3D) data to a set of stacked two-dimensional (2D) slices that can be reconstructed using a conventional 2D algorithm. Rebinning is an attractive alternative to 3D reconstruction for time-of-flight PET data because the errors made by rebinning are much smaller while the data size is much larger than for conventional 3D PET. For rebinning algorithms that require consistent projection data, attenuation correction is performed prior to rebinning. However, statistical reconstruction algorithms assume Poisson-distributed data with uncorrected data as the input and incorporate attenuation effects in the system model. The usual assumption with rebinned data is that the attenuation factor for direct 2D lines of response (LORs) is close to that for the oblique LORs that contribute to the 2D LOR during rebinning. This approximation breaks down for objects with non-uniform attenuation distributions and sharp axial attenuation discontinuities, especially for large axial acceptance angles. Average 2D attenuation factors, calculated as the weighted average of attenuation factors for LORs contributing to each rebinned LOR, is a more accurate representation of attenuation effects seen by rebinned data. The weighted attenuation factors are easily determined from the ratio of rebinned data with and without prior attenuation correction. Using the weighted attenuation factors leads to a modest reduction in image noise near attenuation discontinuities.

Objectives To assess the accuracy of 18 F-fluoro-l-dihydroxyphenylalanine ([ 18 F]-DOPA) PET scans to diagnose focal versus diffuse disease and to localize focal lesions in infants with congenital hyperinsulinism. Study design Twenty-four infants with hyperinsulinism unresponsive to medical therapy were studied. Patients were injected intravenously with [ 18 F]-DOPA, and PET scans were obtained for 1 hour. Images were coregistered with abdominal CT scans. Results The diagnosis of focal or diffuse hyperinsulinism was correct in 23 of the 24 cases (96%) and equivocal in 1 case. [ 18 F]-DOPA PET identified focal areas of high uptake of radiopharmaceutical in 11 patients. Pathology results confirmed that all 11 had focal adenomatosis, and the locations of these lesions matched the areas of increased [ 18 F]-DOPA uptake on the PET scans in all of the cases. Conclusions [ 18 F]-DOPA PET scans were 96% accurate in diagnosing focal or diffuse disease and 100% accurate in localizing the focal lesion. These results suggest that [ 18 F]-DOPA PET imaging should be considered in all infants with congenital hyperinsulinism who need to have pancreatectomy.

We have acquired images of the breasts of four females with suspicious masses using Diffuse Optical Tomography and Positron Emission Tomography. The images are compared, and new types of contrast for cancer imaging are proposed.

A positron-sensitive surgical probe is being built based on a multi-anode PMT and a dual-layer detector, which consists of an 8/spl times/8 array of thin plastic scintillators and a matched GSO crystal array. Our probe uses three selection criteria to identify positrons and suppress background gammas, including annihilation 511 keV gammas. First an energy threshold was applied on the plastic signals; next a second energy threshold was applied on the PMT sum signal; finally, a coincidence technique between the positrons and the annihilation 511 keV gammas was applied. These selection criteria were individually tested and optimized, and have been implemented with 9 channels of electronics. Experiments were conducted using phantoms with /sup 18/F-FDG and /sup 99m/Tc, commonly used in sentinel lymph node (SLN) surgery. Measurements based on the 9-channel electronics indicate that the sensitivity of the 9-channel probe to positrons from /sup 18/F-FDG is /spl sim/69-152 cps/kBq (2.5-5.6 kcps//spl mu/LCi) at different signal selection criteria The final 64-channel probe is expected to have /spl sim/40% higher positron sensitivity. The pixel separation is /spl sim/3.2 in terms of the peak to valley ratio. The second layer of the detector gives superior rejection power for 140 keV gammas. The true to false positron count ratio in the presence of 511 keV and 140 keV background gammas is expected to be high (>10) at a tumor to background ratio of 10:1.

We present the first imaging results from phantom measurements of a dedicated, breast-only positron emission imager, BPET, using NaI(Tl) Curve Plate detectors. The scanner uses 19 mm thick NaI(Tl) detectors in a split-ring design which surrounds the breast as the woman lies prone and the breast hangs down from the body. Because the detectors are close to the breast and the scanner detects photons that do not pass through the body, system sensitivity and spatial resolution are both optimized. The split ring design provides for flexibility for needle aspirations of masses or alternate viewing orientations. We have measured energy resolution, spatial resolution, scatter fraction, and system sensitivity. We have compared the BPET scanner's performance to our clinical whole-body scanner using a breast phantom with hot spheres simulating lesions. The results show that for activity concentrations that correspond to clinical FDG doses, the dedicated scanner has better lesion detectability than the whole-body scanner for the 20 cm detector separation used.

The prototype 64-pixel positron-sensitive surgical probe has been repackaged in preparation for moving the probe into clinical surgical environment The probe detector front opening is covered with a 25 /spl mu/m thick aluminum foil, which makes the probe a both light-tight and sterilizable system. As previously reported, the probe consists of a dual-layer detector and a multi-anode PMT (Hamamatsu H7546). The first layer consists of an 8/spl times/8 array of thin plastic scintillators, which is 1:1 optically coupled to an 8/spl times/8 array of 2/spl times/2/spl times/10 mm/sup 3/ GSO crystals. Each pixel element is optically isolated using CaCO/sub 3/ sheet reflectors. With this dual-layer design and customized 64 channels of electronics (with FPGA), a valid event is a signal in the plastic layer characterized with an overshoot by the pulse-shaping circuit, in coincidence with an annihilation 511 keV gamma in the GSO layer, selected by an energy threshold on the PMT summed dynode signal. Operating this repackaged probe system outside of the black box, the new measurements show that the 64-pixel probe has a sensitivity of /spl sim/36 cps/pixel per /spl mu/Ci/cc using optimal signal selection criteria, which is 80% higher than the sensitivity of the previous system which did not have a foil covering. The repackaged probe system is also confirmed to have similar spatial resolution and good lesion identification ability as previous system. For example, it is able to identify in 10 seconds a /spl sim/2.8 mm lesion with a contrast of /spl sim/2.6 at the presence of both 511 keV gamma (tumor to background ratio: 7:1) and 140 keV gamma background (tumor to background ratio: 1:16).

Aim To determine whether there is stability of cerebral blood flow (CBF) measures using single photon emission computed tomography (SPECT) imaging in healthy controls in a test-retest split-dose paradigm. Such a paradigm is frequently used in the clinical and research setting to assess various brain states. Methods Five healthy volunteers underwent two brain SPECT scans after the administration of low and high doses of 9 9 m Tc-exametazime. The first SPECT scan was acquired approximately 30 min after the intravenous injection of approximately 259 MBq of 9 9 m Tc-exametazime. The second SPECT scan was acquired approximately 30 min after the intravenous injection of 925 MBq of 9 9 m Tc-exametazime. Both scans were acquired over approximately 30-45 min and the images were reconstructed using filtered backprojection, a low-pass filter and Chang's first-order attenuation correction. Values were obtained for regions of interest (ROIs) in major brain structures and normalized to whole brain activity. Counts on the second SPECT scan were also decay corrected for activity from the first scan. Results The results demonstrated a strong correlation between the low-dose and high-dose scans for all regions (r=0.86, P

We report on the performance of a completed 64-pixel positron-sensitive surgical probe using wall-less sphere sources in preparation for clinical testing. The method of making volumetric positron sources by uniformly mixing /sup 18/F with beeswax through a chemical procedure enables us to evaluate the performance of the probe in a more realistic environment. As previously reported, the probe consists of a dual-layer detector and a multianode PMT (Hamamatsu H7546). The first layer consists of an 8/spl times/8 array of thin plastic scintillators, which is 1:1 optically coupled to an 8/spl times/8 array of 2/spl times/ 2/spl times/10 mm/sup 3/ GSO crystals. Each pixel element is optically isolated using CaCO/sub 3/ reflectors. With this dual-layer design and customized 64 channels of electronics (with FPGA), a valid event is a signal in the plastic layer characterized with an overshoot by the pulse-shaping circuit, in coincidence with an annihilation 511 keV gamma in the GSO layer, selected by an energy threshold on the PMT summed dynode signal. Now using wall-less sphere sources we more completely characterize the probe's performance based on a more accurate simulation of the sentinel lymph node surgical environment. The new measurements show that the 64-pixel probe has a sensitivity of /spl sim/20 cps/pixel per /spl mu/Ci/cc using optimal signal selection criteria. The probe is able to identify in 10 seconds a /spl sim/4 mm lesion with a true-to-background ratio of /spl sim/3 at a tumor uptake ratio of /spl sim/8:1.

We report on the continued development of a 64-pixel positron-sensitive surgical probe with a dual-layer detector and a multi-anode PMT. An 8 /spl times/ 8 array of thin plastic scintillators in the first layer detects positrons and a matched GSO crystal array in the second layer detects annihilation 511 keV gammas, which are required to be in coincidence with the detected positrons. Also, the 64 PMT anode signals are differentiated and an overshoot threshold is applied to separate the fast decay plastic anode signals from the slower GSO anode signals. Finally, an energy threshold is applied to the summed anode signal to distinguish 511 keV gammas from the 140 keV gammas commonly used in sentinel lymph node (SLN) surgery. Previously we reported on how these signal selection criteria were individually tested and optimized based on 9 channels of prototype electronics. Currently the electronics have been upgraded to Xilinx/spl reg/ programmable components, allowing on-the-fly alteration of signal selection criteria, and all 64 channels are operational. Initial measurements of the complete 64-pixel probe were conducted using /sup 18/F-FDG positron sources and /sup 18/F-FDG and /sup 99m/Tc phantoms (background 511 keV and 140 keV gammas), simulating lesions in the SLN surgery environment. The average positron sensitivity is measured to be 3.0-7.0 kcps//spl mu/Ci at different signal selection criteria. The lower bound on sensitivity corresponds to settings optimized for high image resolution and high background rejection ability. The upper bound on sensitivity corresponds to settings optimized for high sensitivity at the cost of lower image resolution and lower background rejection ability. The measured true-to-background contrast in the presence of clinically observed levels of 511 keV and 140 keV background gammas is /spl sim/3:1 for a tumor-to-background uptake ratio of 5:1. Performance measurements of the complete 64-pixel probe including sensitivity, true-to-background ratio, and the pixel separation ability are presented.

The purpose of this study was to evaluate factors affecting the quality of the measured attenuation map and nonuniform attenuation compensation (AC) for SPECT myocardial perfusion imaging. Acquiring this map with low noise and accurate attenuation coefficients is important for simultaneous transmission-emission (STE) systems using fan beam geometry. The authors have investigated several factors affecting the measured attenuation map and AC using phantom and patient data. Myocardial uniformity decreased as extent of truncation increased. Finer sampling (128/spl times/128) in acquisition and reconstruction provided more accurate myocardial wall thickness and better contrast compared to 64/spl times/64 matrix. Downscatter correction improved accuracy of attenuation coefficients and myocardial uniformity. Reliable myocardial uniformity required scan durations of at least 14 minutes for myocardial activity of 350 /spl mu/Ci. Over a broad range of ML-EM iterations (20 to 50) in transmission (TCT) reconstruction measured attenuation coefficients for water were similar. Scatter correction improved normal myocardial wall contrast and moderate or severe defect contrast. In conclusion, methods to achieve accurate and low noise AC in myocardial imaging should use the best affordable sampling and scan duration, adequate activity of Gd-153 TCT source, proper positioning of patients and scatter correction.

Reports the design and performance of a portable positron-sensitive surgical probe. The probe is designed to be sensitive to positrons and insensitive to background gammas including 511 keV. The probe consists of a multi-mode PMT and an 8/spl times/8 array of thin 2 mm /spl times/2 mm plastic scintillators coupled 1:1 to GSO crystals. The probe uses three selection criteria to identify positrons. An energy threshold on the plastic signals reduces the false positron signals in the plastic due to background gammas: a second energy threshold on the PMT sum signal greatly reduces background gammas in the GSO. Finally, a timing window accepts only 511 keV gammas from the GSO that arrive within 15 ns of the plastic signals, reducing accidental coincidences to a negligible level. The first application being investigated is sentinel lymph node (SLN) surgery, to identify in real-time the location of SLNs in the axilla with /sup 18/F-FDG uptake, which may indicate metastasis. The authors' simulations and measurements suggest that the probe's signal to background ratio in this situation will be high. Preliminary results on the performance of the probe are presented.

In oncology,imaging studies play an increasingly important role in assessing patients' response to treatment. Serial CT scans of a patient are evaluated for changes in the number and size of tumors, while serial PET scans are assessed for changes in the metabolic activity of the lesions. The advent of combined CT and PET systems streamlines the fusion of these anatomic and functional images. However there are many confounding effects that complicate quantification in 3D PET/CT imaging. This lecture will review these sources of variability in the data, grouped into three broad categories: patient‐related factors (e.g. dose uptake time before imaging, blood glucose level, body habitus); instrument‐related factors (spatial and energy resolution, sensitivity, data acquisition mode (2D or 3D), attenuation and scatter correction method, image reconstruction algorithm, respiratory and cardiac motion‐correction method); and operator‐related factors such as acquisition and reconstruction protocols, instrument and imagequality control, instrument calibrations, and method of image analysis. The impact of these variables on quantification will be discussed, with particular emphasis on how to minimize those that are controllable. The presentation will conclude with a review of current efforts by government agencies, professional organizations, academic institutions, and sponsors of multicenter trials to grapple with the additional complexities that arise from combining data from multiple patients at multiple sites. Research partially supported by the American College of Radiology Imaging Network (ACRIN). Educational Objectives: 1. Understand the scope of the problems inherent in using PET/CT imaging to detect changes in patient response to treatment. 2. Understand the factors that affect the variability and accuracy of PET/CT quantification. 3. Understand the importance of minimizing variability in order to enhance the ability to identify non‐responders to treatment over ever‐shorter time intervals. 4. Understand the efforts currently underway to standardize acquisition and processing protocols and to monitor equipment performance through credentialing and periodic quality control checks.

In oncology,imaging studies play an increasingly important role in assessing patients' response to treatment. Serial CT scans of a patient are evaluated for changes in the number and size of tumors, while serial PET scans are assessed for changes in the metabolic activity of the lesions. The advent of combined CT and PET systems streamlines the fusion of these anatomic and functional images. However there are many confounding effects that complicate quantification in 3D PET/CT imaging. This lecture will review these sources of variability in the data, grouped into three broad categories: patient‐related factors (e.g. dose, uptake time before imaging, blood glucose level, body habitus); instrument‐related factors (spatial and energy resolution, sensitivity, data acquisition mode (2D or 3D), attenuation and scatter correction method, image reconstruction algorithm, respiratory and cardiac motion‐correction method); and operator‐related factors such as acquisition and reconstruction protocols, instrument and imagequality control, instrument calibrations, and method of image analysis. The impact of these variables on quantification will be discussed, with particular emphasis on how to minimize those that are controllable. The presentation will conclude with a review of current efforts by government agencies, professional organizations, academic institutions, and sponsors of multicenter trials to grapple with the additional complexities that arise from combining data from multiple patients at multiple sites. Research partially supported by the American College of Radiology Imaging Network (ACRIN). Educational Objectives: 1. Understand the scope of the problems inherent in using PET/CT imaging to detect changes in patient response to treatment. 2. Understand the factors that affect the variability and accuracy of PET/CT quantification. 3. Understand the importance of minimizing variability in order to enhance the ability to identify non‐responders to treatment over evershorter time intervals. 4. Understand the efforts currently underway to standardize acquisition and processing protocols and to monitor equipment performance through credentialing and periodic quality control checks.

The metabolic information provided by PET and SPECT has great potential for diagnosing and staging disease, customizing treatmentdoses for a particular patient, and tracking a patients' response to treatment. However, quantifying the information in these images remains challenging. This presentation will review the sources of variability in the data, grouped into three broad categories: patient — related factors (e.g. body habitus, medications); scanner‐related factors (spatial and energy resolution, sensitivity, data acquisition mode (2D or 3D), attenuation and scatter correction method, image reconstruction algorithm, respiratory and cardiac motion‐correction method); and operator‐related factors such as acquisition and reconstruction protocols, instrument and imagequality control, instrument calibrations, and method of image analysis. The impact of these variables on quantification will be discussed, along with methods for minimizing those that are controllable. The presentation will conclude with a review of current efforts by government agencies, professional organizations, academic institutions, and sponsors of multicenter trials to grapple with the additional complexities that arise from combining data from multiple patients at multiple sites. Particular emphasis will be placed on the author's experience as a member of the PETQuality Assurance Committee at the American College of Radiology Imaging Network (ACRIN) PET Core Lab, which has credentialed more than 100 PET scanners for participation in quantitative PET multicenter trials. Research partially supported by ACRIN. ACRIN is sponsored by the National Cancer Institute and receives additional support from industry partners, other governmental agencies and the ACRIN Fund for Imaging Innovation. NOTE: ACRIN is sponsored by the National Cancer Institute and receives additional support from industry partners, other governmental agencies and the ACRIN Fund for Imaging Innovation. Educational Objectives: 1. Understand the factors that affect the variability and accuracy of PET and SPECT biomarker quantification, with particular emphasis on scanner‐related parameters. 2. Understand the importance of minimizing variability in order to enhance the ability to distinguish signal from noise. 3. Understand the efforts currently underway to standardize acquisition and processing protocols and to monitor equipment performance through credentialing and periodic quality control checks.

Purpose: A technique is described to quantitatively evaluate several methods for coregistering PET and CTimages: 1) manual registration based on fiducial markers, and 2) automated registration using several commercial algorithms that maximize mutual information.Method and Materials:CT and PET scans of an Alderson Striatal head phantom were obtained with and without three rectangular fiducial markers (1 mm × 1 mm × 3 mm). Each marker contained 10 μCi of Na‐22 along with contrast agent so markers were visible on both CT and PET scans. Several CT scans were acquired with a pixel size of 0.7 mm × 0.7mm of the phantom rotated by known amounts along the principle axes. PET scans were obtained at two resolutions, 2 mm× 2 mm and 4 mm × 4 mm pixels, at a single orientation (supine, zero rotation). For these scans the main compartment of the phantom was filled with F‐18‐FDG at clinically‐observed concentrations. Transmission scans also were obtained. Results: The accuracy of both automatic and manual coregistration of the emission PET to the CT was evaluated by comparing the transformation matrices (TM) to the known displacements. Image fusion between different CT and the PET scans show TM within 2–4 degrees of the known rotation for manual fusions and 1–3 degrees for automated registration. A subjective qualitative evaluation of the results based on the structures in the phantom and intensity pattern showed agreement to within 2 mm for higher resolution PET scans. Results were similar for registration of the transmission PET to the CT. Because these results are based on rigid‐body motions, they establish an upper‐bound on the accuracy obtainable from these registration techniques. Conclusion: A method has been developed to assess and quantitatively evaluate image coregistration software for CT and PETimages.