Spatial Resolution Of PET Research Articles

WE‐H‐206‐01: Photoacoustic Tomography: Multiscale Imaging From Organelles to Patients by Ultrasonically Beating the Optical Diffusion Limit

Lihong V. Wang: Photoacoustic tomography (PAT), combining non‐ionizing optical and ultrasonic waves via the photoacoustic effect, provides in vivo multiscale functional, metabolic, and molecular imaging. Broad applications include imaging of the breast, brain, skin, esophagus, colon, vascular system, and lymphatic system in humans or animals. Light offers rich contrast but does not penetrate biological tissue in straight paths as x‐rays do. Consequently, high‐resolution pure optical imaging (e.g., confocal microscopy, two‐photon microscopy, and optical coherence tomography) is limited to penetration within the optical diffusion limit (∼1 mm in the skin). Ultrasonic imaging, on the contrary, provides fine spatial resolution but suffers from both poor contrast in early‐stage tumors and strong speckle artifacts. In PAT, pulsed laser light penetrates tissue and generates a small but rapid temperature rise, which induces emission of ultrasonic waves due to thermoelastic expansion. The ultrasonic waves, orders of magnitude less scattering than optical waves, are then detected to form high‐resolution images of optical absorption at depths up to 7 cm, conquering the optical diffusion limit. PAT is the only modality capable of imaging across the length scales of organelles, cells, tissues, and organs (up to whole‐body small animals) with consistent contrast. This rapidly growing technology promises to enable multiscale biological research and accelerate translation from microscopic laboratory discoveries to macroscopic clinical practice. PAT may also hold the key to label‐free early detection of cancer by in vivo quantification of hypermetabolism, the quintessential hallmark of malignancy. Learning Objectives: To understand the contrast mechanism of PAT To understand the multiscale applications of PATBenjamin M. W. Tsui: Multi‐modality molecular imaging instrumentation and techniques have been major developments in small animal imaging that has contributed significantly to biomedical research during the past decade. The initial development was an extension of clinical PET/CT and SPECT/CT from human to small animals and combine the unique functional information obtained from PET and SPECT with anatomical information provided by the CT in registered multi‐modality images. The requirements to image a mouse whose size is an order of magnitude smaller than that of a human have spurred advances in new radiation detector technologies, novel imaging system designs and special image reconstruction and processing techniques. Examples are new detector materials and designs with high intrinsic resolution, multi‐pinhole (MPH) collimator design for much improved resolution and detection efficiency compared to the conventional collimator designs in SPECT, 3D high‐resolution and artifact‐free MPH and sparse‐view image reconstruction techniques, and iterative image reconstruction methods with system response modeling for resolution recovery and image noise reduction for much improved image quality. The spatial resolution of PET and SPECT has improved from ∼6–12 mm to ∼1 mm a few years ago to sub‐millimeter today. A recent commercial small animal SPECT system has achieved a resolution of ∼0.25 mm which surpasses that of a state‐of‐art PET system whose resolution is limited by the positron range. More recently, multimodality SA PET/MRI and SPECT/MRI systems have been developed in research laboratories. Also, multi‐modality SA imaging systems that include other imaging modalities such as optical and ultrasound are being actively pursued. In this presentation, we will provide a review of the development, recent advances and future outlook of multi‐modality molecular imaging of small animals. Learning Objectives: To learn about the two major multi‐modality molecular imaging techniques of small animals. To learn about the spatial resolution achievable by the molecular imaging systems for small animal today. To learn about the new multi‐modality imaging instrumentation and techniques that are being developed.Sang Hyun Cho; X‐ray fluorescence (XRF) imaging, such as x‐ray fluorescence computed tomography (XFCT), offers unique capabilities for accurate identification and quantification of metals within the imaging objects. As a result, it has emerged as a promising quantitative imaging modality in recent years, especially in conjunction with metal‐based imaging probes. This talk will familiarize the audience with the basic principles of XRF/XFCT imaging. It will also cover the latest development of benchtop XFCT technology. Additionally, the use of metallic nanoparticles such as gold nanoparticles, in conjunction with benchtop XFCT, will be discussed within the context of preclinical multimodal multiplexed molecular imaging. Learning Objectives: To learn the basic principles of XRF/XFCT imaging To learn the latest advances in benchtop XFCT development for preclinical imagingFunding support received from NIH and DOD; Funding support received from GE Healthcare; Funding support received from Siemens AX; Patent royalties received from GE Healthcare; L. Wang, Funding Support: NIH; COI: Microphotoacoustics; S. Cho, Yes:;NIH/NCI grant R01CA155446 DOD/PCRP grant W81XWH‐12‐1‐0198

WE‐H‐206‐00: Advances in Preclinical Imaging

Lihong V. Wang: Photoacoustic tomography (PAT), combining non‐ionizing optical and ultrasonic waves via the photoacoustic effect, provides in vivo multiscale functional, metabolic, and molecular imaging. Broad applications include imaging of the breast, brain, skin, esophagus, colon, vascular system, and lymphatic system in humans or animals. Light offers rich contrast but does not penetrate biological tissue in straight paths as x‐rays do. Consequently, high‐resolution pure optical imaging (e.g., confocal microscopy, two‐photon microscopy, and optical coherence tomography) is limited to penetration within the optical diffusion limit (∼1 mm in the skin). Ultrasonic imaging, on the contrary, provides fine spatial resolution but suffers from both poor contrast in early‐stage tumors and strong speckle artifacts. In PAT, pulsed laser light penetrates tissue and generates a small but rapid temperature rise, which induces emission of ultrasonic waves due to thermoelastic expansion. The ultrasonic waves, orders of magnitude less scattering than optical waves, are then detected to form high‐resolution images of optical absorption at depths up to 7 cm, conquering the optical diffusion limit. PAT is the only modality capable of imaging across the length scales of organelles, cells, tissues, and organs (up to whole‐body small animals) with consistent contrast. This rapidly growing technology promises to enable multiscale biological research and accelerate translation from microscopic laboratory discoveries to macroscopic clinical practice. PAT may also hold the key to label‐free early detection of cancer by in vivo quantification of hypermetabolism, the quintessential hallmark of malignancy. Learning Objectives: To understand the contrast mechanism of PAT To understand the multiscale applications of PATBenjamin M. W. Tsui: Multi‐modality molecular imaging instrumentation and techniques have been major developments in small animal imaging that has contributed significantly to biomedical research during the past decade. The initial development was an extension of clinical PET/CT and SPECT/CT from human to small animals and combine the unique functional information obtained from PET and SPECT with anatomical information provided by the CT in registered multi‐modality images. The requirements to image a mouse whose size is an order of magnitude smaller than that of a human have spurred advances in new radiation detector technologies, novel imaging system designs and special image reconstruction and processing techniques. Examples are new detector materials and designs with high intrinsic resolution, multi‐pinhole (MPH) collimator design for much improved resolution and detection efficiency compared to the conventional collimator designs in SPECT, 3D high‐resolution and artifact‐free MPH and sparse‐view image reconstruction techniques, and iterative image reconstruction methods with system response modeling for resolution recovery and image noise reduction for much improved image quality. The spatial resolution of PET and SPECT has improved from ∼6–12 mm to ∼1 mm a few years ago to sub‐millimeter today. A recent commercial small animal SPECT system has achieved a resolution of ∼0.25 mm which surpasses that of a state‐of‐art PET system whose resolution is limited by the positron range. More recently, multimodality SA PET/MRI and SPECT/MRI systems have been developed in research laboratories. Also, multi‐modality SA imaging systems that include other imaging modalities such as optical and ultrasound are being actively pursued. In this presentation, we will provide a review of the development, recent advances and future outlook of multi‐modality molecular imaging of small animals. Learning Objectives: To learn about the two major multi‐modality molecular imaging techniques of small animals. To learn about the spatial resolution achievable by the molecular imaging systems for small animal today. To learn about the new multi‐modality imaging instrumentation and techniques that are being developed.Sang Hyun Cho; X‐ray fluorescence (XRF) imaging, such as x‐ray fluorescence computed tomography (XFCT), offers unique capabilities for accurate identification and quantification of metals within the imaging objects. As a result, it has emerged as a promising quantitative imaging modality in recent years, especially in conjunction with metal‐based imaging probes. This talk will familiarize the audience with the basic principles of XRF/XFCT imaging. It will also cover the latest development of benchtop XFCT technology. Additionally, the use of metallic nanoparticles such as gold nanoparticles, in conjunction with benchtop XFCT, will be discussed within the context of preclinical multimodal multiplexed molecular imaging. Learning Objectives: To learn the basic principles of XRF/XFCT imaging To learn the latest advances in benchtop XFCT development for preclinical imagingFunding support received from NIH and DOD; Funding support received from GE Healthcare; Funding support received from Siemens AX; Patent royalties received from GE Healthcare; L. Wang, Funding Support: NIH; COI: Microphotoacoustics; S. Cho, Yes:;NIH/NCI grant R01CA155446 DOD/PCRP grant W81XWH‐12‐1‐0198

WE‐H‐206‐02: Recent Advances in Multi‐Modality Molecular Imaging of Small Animals

Lihong V. Wang: Photoacoustic tomography (PAT), combining non‐ionizing optical and ultrasonic waves via the photoacoustic effect, provides in vivo multiscale functional, metabolic, and molecular imaging. Broad applications include imaging of the breast, brain, skin, esophagus, colon, vascular system, and lymphatic system in humans or animals. Light offers rich contrast but does not penetrate biological tissue in straight paths as x‐rays do. Consequently, high‐resolution pure optical imaging (e.g., confocal microscopy, two‐photon microscopy, and optical coherence tomography) is limited to penetration within the optical diffusion limit (∼1 mm in the skin). Ultrasonic imaging, on the contrary, provides fine spatial resolution but suffers from both poor contrast in early‐stage tumors and strong speckle artifacts. In PAT, pulsed laser light penetrates tissue and generates a small but rapid temperature rise, which induces emission of ultrasonic waves due to thermoelastic expansion. The ultrasonic waves, orders of magnitude less scattering than optical waves, are then detected to form high‐resolution images of optical absorption at depths up to 7 cm, conquering the optical diffusion limit. PAT is the only modality capable of imaging across the length scales of organelles, cells, tissues, and organs (up to whole‐body small animals) with consistent contrast. This rapidly growing technology promises to enable multiscale biological research and accelerate translation from microscopic laboratory discoveries to macroscopic clinical practice. PAT may also hold the key to label‐free early detection of cancer by in vivo quantification of hypermetabolism, the quintessential hallmark of malignancy. Learning Objectives: To understand the contrast mechanism of PAT To understand the multiscale applications of PATBenjamin M. W. Tsui: Multi‐modality molecular imaging instrumentation and techniques have been major developments in small animal imaging that has contributed significantly to biomedical research during the past decade. The initial development was an extension of clinical PET/CT and SPECT/CT from human to small animals and combine the unique functional information obtained from PET and SPECT with anatomical information provided by the CT in registered multi‐modality images. The requirements to image a mouse whose size is an order of magnitude smaller than that of a human have spurred advances in new radiation detector technologies, novel imaging system designs and special image reconstruction and processing techniques. Examples are new detector materials and designs with high intrinsic resolution, multi‐pinhole (MPH) collimator design for much improved resolution and detection efficiency compared to the conventional collimator designs in SPECT, 3D high‐resolution and artifact‐free MPH and sparse‐view image reconstruction techniques, and iterative image reconstruction methods with system response modeling for resolution recovery and image noise reduction for much improved image quality. The spatial resolution of PET and SPECT has improved from ∼6–12 mm to ∼1 mm a few years ago to sub‐millimeter today. A recent commercial small animal SPECT system has achieved a resolution of ∼0.25 mm which surpasses that of a state‐of‐art PET system whose resolution is limited by the positron range. More recently, multimodality SA PET/MRI and SPECT/MRI systems have been developed in research laboratories. Also, multi‐modality SA imaging systems that include other imaging modalities such as optical and ultrasound are being actively pursued. In this presentation, we will provide a review of the development, recent advances and future outlook of multi‐modality molecular imaging of small animals. Learning Objectives: To learn about the two major multi‐modality molecular imaging techniques of small animals. To learn about the spatial resolution achievable by the molecular imaging systems for small animal today. To learn about the new multi‐modality imaging instrumentation and techniques that are being developed.Sang Hyun Cho; X‐ray fluorescence (XRF) imaging, such as x‐ray fluorescence computed tomography (XFCT), offers unique capabilities for accurate identification and quantification of metals within the imaging objects. As a result, it has emerged as a promising quantitative imaging modality in recent years, especially in conjunction with metal‐based imaging probes. This talk will familiarize the audience with the basic principles of XRF/XFCT imaging. It will also cover the latest development of benchtop XFCT technology. Additionally, the use of metallic nanoparticles such as gold nanoparticles, in conjunction with benchtop XFCT, will be discussed within the context of preclinical multimodal multiplexed molecular imaging. Learning Objectives: To learn the basic principles of XRF/XFCT imaging To learn the latest advances in benchtop XFCT development for preclinical imagingFunding support received from NIH and DOD; Funding support received from GE Healthcare; Funding support received from Siemens AX; Patent royalties received from GE Healthcare; L. Wang, Funding Support: NIH; COI: Microphotoacoustics; S. Cho, Yes:;NIH/NCI grant R01CA155446 DOD/PCRP grant W81XWH‐12‐1‐0198

WE‐H‐206‐03: Promises and Challenges of Benchtop X‐Ray Fluorescence CT (XFCT) for Quantitative in Vivo Imaging

Lihong V. Wang: Photoacoustic tomography (PAT), combining non‐ionizing optical and ultrasonic waves via the photoacoustic effect, provides in vivo multiscale functional, metabolic, and molecular imaging. Broad applications include imaging of the breast, brain, skin, esophagus, colon, vascular system, and lymphatic system in humans or animals. Light offers rich contrast but does not penetrate biological tissue in straight paths as x‐rays do. Consequently, high‐resolution pure optical imaging (e.g., confocal microscopy, two‐photon microscopy, and optical coherence tomography) is limited to penetration within the optical diffusion limit (∼1 mm in the skin). Ultrasonic imaging, on the contrary, provides fine spatial resolution but suffers from both poor contrast in early‐stage tumors and strong speckle artifacts. In PAT, pulsed laser light penetrates tissue and generates a small but rapid temperature rise, which induces emission of ultrasonic waves due to thermoelastic expansion. The ultrasonic waves, orders of magnitude less scattering than optical waves, are then detected to form high‐resolution images of optical absorption at depths up to 7 cm, conquering the optical diffusion limit. PAT is the only modality capable of imaging across the length scales of organelles, cells, tissues, and organs (up to whole‐body small animals) with consistent contrast. This rapidly growing technology promises to enable multiscale biological research and accelerate translation from microscopic laboratory discoveries to macroscopic clinical practice. PAT may also hold the key to label‐free early detection of cancer by in vivo quantification of hypermetabolism, the quintessential hallmark of malignancy. Learning Objectives: To understand the contrast mechanism of PAT To understand the multiscale applications of PATBenjamin M. W. Tsui: Multi‐modality molecular imaging instrumentation and techniques have been major developments in small animal imaging that has contributed significantly to biomedical research during the past decade. The initial development was an extension of clinical PET/CT and SPECT/CT from human to small animals and combine the unique functional information obtained from PET and SPECT with anatomical information provided by the CT in registered multi‐modality images. The requirements to image a mouse whose size is an order of magnitude smaller than that of a human have spurred advances in new radiation detector technologies, novel imaging system designs and special image reconstruction and processing techniques. Examples are new detector materials and designs with high intrinsic resolution, multi‐pinhole (MPH) collimator design for much improved resolution and detection efficiency compared to the conventional collimator designs in SPECT, 3D high‐resolution and artifact‐free MPH and sparse‐view image reconstruction techniques, and iterative image reconstruction methods with system response modeling for resolution recovery and image noise reduction for much improved image quality. The spatial resolution of PET and SPECT has improved from ∼6–12 mm to ∼1 mm a few years ago to sub‐millimeter today. A recent commercial small animal SPECT system has achieved a resolution of ∼0.25 mm which surpasses that of a state‐of‐art PET system whose resolution is limited by the positron range. More recently, multimodality SA PET/MRI and SPECT/MRI systems have been developed in research laboratories. Also, multi‐modality SA imaging systems that include other imaging modalities such as optical and ultrasound are being actively pursued. In this presentation, we will provide a review of the development, recent advances and future outlook of multi‐modality molecular imaging of small animals. Learning Objectives: To learn about the two major multi‐modality molecular imaging techniques of small animals. To learn about the spatial resolution achievable by the molecular imaging systems for small animal today. To learn about the new multi‐modality imaging instrumentation and techniques that are being developed.Sang Hyun Cho; X‐ray fluorescence (XRF) imaging, such as x‐ray fluorescence computed tomography (XFCT), offers unique capabilities for accurate identification and quantification of metals within the imaging objects. As a result, it has emerged as a promising quantitative imaging modality in recent years, especially in conjunction with metal‐based imaging probes. This talk will familiarize the audience with the basic principles of XRF/XFCT imaging. It will also cover the latest development of benchtop XFCT technology. Additionally, the use of metallic nanoparticles such as gold nanoparticles, in conjunction with benchtop XFCT, will be discussed within the context of preclinical multimodal multiplexed molecular imaging. Learning Objectives: To learn the basic principles of XRF/XFCT imaging To learn the latest advances in benchtop XFCT development for preclinical imagingFunding support received from NIH and DOD; Funding support received from GE Healthcare; Funding support received from Siemens AX; Patent royalties received from GE Healthcare; L. Wang, Funding Support: NIH; COI: Microphotoacoustics; S. Cho, Yes:;NIH/NCI grant R01CA155446 DOD/PCRP grant W81XWH‐12‐1‐0198

SU‐F‐I‐55: Performance Evaluation of Digital PET/CT: Medical Physics Basis for the Clinical Applications

Purpose:Replacement of conventional PMT‐based detector with next generation digital photon counting (DPC) detector is a technology leap for PET imaging. This study evaluated the performance and characteristics of the DPC system and its stability within a 1 year time window following its installation focusing on the medical physics basis for clinical applications.Methods:A digital PET/CT scanner using 1:1 coupling of 23,040 crystal: detector elements was introduced and became operational at OSU. We tested and evaluated system performance and characteristics using NEMA NU2‐2012. System stabilities in timing resolution, energy resolution, detector temperature and humidity (T&H) were monitored over 1‐yr. Timing, energy and spatial resolution were characterized across clinically relevant count rate range. CQIE uniformity PET and NEMA IEC‐Body PET with hot spheres varying with sizes and contrasts were performed. PET reconstructed in standard(4mm), High(2mm) and Ultra‐High(1mm) definitions were evaluated.Results:NEMA results showed PET spatial resolution (mm‐FWHM) from 4.01&4.14 at 1cm to 5.82&6.17 at 20cm in transverse & axial. 322±3ps timing and 11.0% energy resolution were measured. 5.7kcps/MBq system sensitivity with 24kcps/MBq effective sensitivity was obtained. The peak‐NECR was ∼171kcps with the effective peak‐NECR >650kcps@50kBq/mL. Scatter fraction was ∼30%, and the maximum trues was >900kcps. NEMA IQ demonstrated hot sphere contrast ranging from ∼62%±2%(10mm) to ∼88%±2%(22mm), cold sphere contrast of ∼86%±2%(28mm) and ∼89%±3%(37mm) and excellent uniformity. Monitoring 1‐yr stability, it revealed ∼1% change in timing, ±0.4% change in energy resolution, and <10% variations in T&H. CQIE PET gave <3% SUV variances in axial. 60%–100% recovery coefficients across sphere sizes and contrast levels were achieved.Conclusion:Characteristics and stability of the next generation DPC PET detector system over an 1‐yr time window was excellent and better than prior experiences. It demonstrated improved and robust system characteristics and performance in spatial resolution, sensitivity, timing and energy resolution, count rate and image quality.Michael Miller is an employee of Philips Healthcare

124I PET Assessment of Response of Bone Metastases to Initial Radioiodine Treatment of Differentiated Thyroid Cancer.

Before and after initial radioiodine therapy, patients underwent serial PET/CT scanning after administration of 20-40 MBq of 124I. The pretherapy PET data were used to segment BM volumes and to predict the average ADs after administration of dosimetry-guided 131I activity. The lower volume limit of determinability of the applied segmentation method was a sphere volume of 0.16 mL. This volume limit classified the BMs into known-volume and fixed-volume groups with their respective average and minimum ADs. Follow-up 124I and 18F-FDG PET/CT data after treatment were analyzed to assess lesion-based therapy response. Response rates at different AD thresholds were calculated and were expressed as the percentage of completely responding BMs above the respective AD threshold. BMs with a maximum extent greater than twice the PET spatial resolution were visually scored for nonuniformity. In total, 61 BMs in 10 patients were included, of which 46 and 15 comprised the known-volume group and the fixed-volume group, respectively. The median follow-up time was 5.6 mo (range, 3.7-23.2 mo). The median average and median minimum ADs in therapy were 183 Gy (range, 39-3,600 Gy) and 270 Gy (range, 63-1,300 Gy), respectively. A range of response rate of 70%-80% was achieved at an AD threshold range of 350-650 Gy. There were 26 BMs that were amenable to visual assessment of nonuniformity, of which two thirds (17/26) were scored as clearly nonuniform, and the majority (11/17) of these nonuniform BMs responded incompletely. Both the high AD threshold associated with high response rates and the low median AD per unit of 131I activity elucidate the difficulty in achieving therapeutic efficacy for BMs when a single standard activity is administered. The relatively high AD threshold range is possibly a result of distinct levels of spatial nonuniformity in ADs.

Dose-Response Relationship in Differentiated Thyroid Cancer Patients Undergoing Radioiodine Treatment Assessed by Means of 124I PET/CT.

The dose-response relationship in a fixed-activity approach generally applied in the treatment of differentiated thyroid cancer was assessed using (124)I PET/CT. Pretherapeutic (124)I PET/CT images of 47 patients scheduled for radioiodine therapy were retrospectively analyzed. (124)I PET/CT images were acquired 24 and 96 h after oral administration of approximately 28 MBq of (124)I-sodium iodide. Lesions were identified as thyroid remnants or metastases (lymph node, lung, bone). After a neoteric segmentation technique allowing accurate volume estimation down to the (124)I PET spatial resolution of 0.15 mL was applied, lesions were divided into a known-volume group and a small-volume group. For the known-volume group, average lesion-absorbed dose (AD) values were calculated, whereas for the small-volume group a minimum lesion AD was estimated. Lesion response was determined on the basis of (124)I PET/CT and (131)I SPECT/CT follow-up images. A lesion not detectable on any of the follow-up images was considered a completely responding lesion. Differences in lesion AD estimations between completely and incompletely responding lesions were evaluated by Mann-Whitney U test. Moreover, receiver-operating-characteristic curves were used to test the performance of pretherapeutic (124)I PET/CT lesion AD for prediction of complete lesion response. In the approach of fixed radioiodine activity (3.0 ± 1.0 GBq), 89% of thyroid remnants and 69% of metastases responded completely. Except for the small-volume groups, the lesion AD of completely responding lesions was significantly higher than that of incompletely responding lesions. Using receiver-operating-characteristic curve analysis, it was shown that for the known-volume group, pretherapeutic (124)I PET/CT lesion dosimetry can be used as a prognostic tool to predict lesion-based (131)I therapy response with an area under the curve of 0.76 for remnants and 0.97 for metastases. The corresponding lesion AD threshold value maximizing correct complete response prediction was 90 Gy for remnants and 40 Gy for metastases. In a fixed-activity approach, a statistically significant dose-response relationship for both thyroid remnants and metastases using pretherapeutic (124)I PET/CT lesion dosimetry was found. The findings may be useful in patient management.

A DOI Detector With Crystal Scatter Identification Capability for High Sensitivity and High Spatial Resolution PET Imaging.

A new phoswich detector is being developed at the Crump Institute, aiming to provide improvements in sensitivity, and spatial resolution for PET. The detector configuration is comprised of two layers of pixelated scintillator crystal arrays, a glass light guide and a light detector. The annihilation photon entrance (top) layer is a 48 × 48 array of 1.01 × 1.01 × 7 mm3 LYSO crystals. The bottom layer is a 32 × 32 array of 1.55 × 1.55 × 9 mm3 BGO crystals. A tapered, multiple-element glass lightguide is used to couple the exit end of the BGO crystal array (52 × 52 mm2) to the photosensitive area of the Position Sensitive Photomultiplier Tube (46 × 46 mm2), allowing the creation of flat panel detectors without gaps between the detector modules. Both simulations and measurements were performed to evaluate the characteristics and benefits of the proposed design. The GATE Monte Carlo simulation indicated that the total fraction of the cross layer crystal scatter (CLCS) events in singles detection mode for this detector geometry is 13.2%. The large majority of these CLCS events (10.1% out of 13.2%) deposit most of their energy in a scintillator layer other than the layer of first interaction. Identification of those CLCS events for rejection or correction may lead to improvements in data quality and imaging performance. Physical measurements with the prototype detector showed that the LYSO, BGO and CLCS events were successfully identified using the delayed charge integration (DCI) technique, with more than 95% of the LYSO and BGO crystal elements clearly resolved. The measured peak-to-valley ratios (PVR) in the flood histograms were 3.5 for LYSO and 2.0 for BGO. For LYSO, the energy resolution ranged from 9.7% to 37.0% full width at half maximum (FWHM), with a mean of 13.4 ± 4.8%. For BGO the energy resolution ranged from 16.0% to 33.9% FWHM, with a mean of 18.6 ± 3.2%. In conclusion, these results demonstrate that the proposed detector is feasible and can potentially lead to a high spatial resolution, high sensitivity and DOI PET system.

Evaluation of the Effect of Magnetic Field on PET Spatial Resolution and Contrast Recovery Using Clinical PET Scanners and EGSnrc Simulations

We describe an evaluation of the effect of the magnetic field on the PET spatial resolution and contrast recovery for short and long range positron emitters using experimental phantoms scanned on clinical PET/CT and PET/MR scanners as well as using electron transport simulations. A $^{22}{\rm Na}$ (a short range positron emitter) point source surrounded by Lucite, a $^{68}{\rm Ga}$ (a relatively long range positron emitter) line source surrounded by water, and a $^{{68}{\rm Ga}}$ contrast phantom with various sphere sizes were scanned on Siemens’ Biograph-mMR (magnetic field strength: 3 Tesla) and Biograph-40 (no magnetic field). The electron transport simulations were performed from 0T to 11T for $^{22}{\rm Na}$ , $^{68}{\rm Ga}$ , and $^{15}{\rm O}$ for the point source, line source, and the contrast phantom. It was observed that the magnetic field has very small effect ( $ ) on the resolution of short range nuclides such as $^{22}{\rm Na}$ based on both simulation and experimental results as expected. For long range nuclides such as $^{68}{\rm Ga}$ slight improvements in spatial resolution and contrast recovery were observed on the plane perpendicular to the direction of the magnetic field from phantom experiments and simulations with 3T magnetic field for the human scanner. The degree of improvement is proportional to the positron range of the nuclides as well as the strength of the magnetic field, and it saturates at $\sim 7\hbox{T}$ for all nuclides used in this study according to simulation results. For the plane parallel to the direction of the magnetic field, worse resolution and better contrast recovery were observed due to more positron annihilations deposited along the direction of the magnetic field (i.e. re-distribution of positrons). With regard to the results obtained from the simulations for a scanner with better intrinsic resolution (2 mm PSF), the improvement in FWHM saturates at a higher field strength ( $ >11~\hbox{T}$ ) as compared to that for a human scanner (4.7 mm PSF). However, worse FWHM was observed in all directions at 3T as compared to that at 0T due to re-distribution of positrons and the interaction between the low frequency high energy positrons and the scanner’s narrower intrinsic resolution kernel, while the FWTM and contrast recovery still improve at 3T. FWHM was observed to improve with higher magnetic field strength ( $ >3~\hbox{T}$ ). It was also found that the intrinsic resolution of the PET scanner needs to be worse/wider than 2.35 mm to observe an improvement in FWHM for a $^{68}{\rm Ga}$ point source in water under a 3T magnetic field as compared to that under 0T. In addition, a directionally dependent resolution modeling which accounts for the effect of the magnetic field in iterative PET reconstruction was observed to improve the resolution recovery and produce more uniform resolution in all directions within the magnetic field.

Design and Performance of a High Spatial Resolution, Time-of-Flight PET Detector

This paper describes the design and performance of a high spatial resolution PET detector with time-of-flight capabilities. With an emphasis on high spatial resolution and sensitivity, we initially evaluated the performance of several 1.5 × 1.5 and 2.0 × 2.0 mm2 and 12-15 mm long LYSO crystals read out by several appropriately sized PMTs. Experiments to evaluate the impact of reflector on detector performance were performed and the final detector consisted of a 32 × 32 array of 1.5 × 1.5 × 15 mm3 LYSO crystals packed with a diffuse reflector and read out by a single Hamamatsu 64 channel multi-anode PMT. Such a design made it compact, modular and offered a cost-effective solution to obtaining excellent energy and timing resolution. To minimize the number of readout signals, a compact front-end readout electronics that summed anode signals along each of the orthogonal directions was also developed. Experimental evaluation of detector performance demonstrates clear discrimination of the crystals within the detector. An average energy resolution (FWHM) of 12.7 ± 2.6% and average coincidence timing resolution (FWHM) of 348 ps was measured, demonstrating suitability for use in the development of a high spatial resolution time-of-flight scanner for dedicated breast PET imaging.

Quantitative PET and SPECT performance characteristics of the Albira Trimodal pre-clinical tomograph

The Albira Trimodal pre-clinical scanner comprises PET, SPECT and CT sub-systems and thus provides a range of pre-clinical imaging options. The PET component consists of three rings of single-crystal LYSO detectors with axial/transverse fields-of-view (FOVs) of 148/80 mm. The SPECT component has two opposing CsI detectors (100 × 100 mm2) with single-pinhole (SPH) or multi(9)-pinhole (MPH) collimators; the detectors rotate in 6° increments and their spacing can be adjusted to provide different FOVs (25 to 120 mm). The CT sub-system provides ‘low’ (200 µA, 35 kVp) or ‘high’ (400 µA, 45 kVp) power x-rays onto a flat-panel CsI detector. This study examines the performance characteristics and quantitative accuracy of the PET and SPECT components. Using the NEMA NU 4-2008 specifications (22Na point source), the PET spatial resolution is 1.5 + 0.1 mm on axis and sensitivity 6.3% (axial centre) and 4.6% (central 70 mm). The usable activity range is ≤ 10 MBq (18F) over which good linearity (within 5%) is obtained for a uniform cylinder spanning the axial FOV; increasing deviation from linearity with activity is, however, observed for the NEMA (mouse) line source phantom. Image uniformity axially is within 5%. Spatial resolution (SPH/MPH) for the minimum SPECT FOV used for mouse imaging (50 mm) is 1.5/1.7 mm and point source sensitivity 69/750 cps MBq–1. Axial uniformity of SPECT images (%CV of regions-of-interest counts along the axis) is mostly within 8% although there is a range of 30–40% for the largest FOV. The variation is significantly smaller within the central 40 mm. Instances of count rate nonlinearity (PET) and axial non-uniformity (SPECT) were found to be reproducible and thus amenable to empirical correction.

MRI and PET Compatible Bed for Direct Co-Registration in Small Animals

To obtain an accurate co-registration with stand-alone PET and MRI scanners, we developed a compatible bed system for mice and rats that enables both images to be acquired without repositioning the animals. MRI acquisitions were performed on a preclinical 7T scanner (Pharmascan, Bruker), whereas PET scans were acquired on a YAP-(S)PET (ISE s.r.l.). The bed performance was tested both on a phantom (NEMA Image Quality phantom) and in vivo (healthy rats and mice brain). Fiducial markers filled up with a drop of 18 F were visible in both modalities. Co-registration process was performed using the point-based registration technique. The reproducibility and accuracy of the co-registration were assessed using the phantom. The reproducibility of the translation distances was 0.2 mm along the z axis. On the other hand, the accuracy depended on the physical size of the phantom structures under investigation but was always lower than 4%. Regions of Interest (ROIs) drawn on the fused images were used for quantification purposes. PET and MRI intensity profiles on small structures of the phantom showed that the underestimation in activity concentration reached 90% in regions that were smaller than the PET spatial resolution, while the MRI allowed a good visualization of the 1 mm 0 rod. PET/MRI images of healthy mice and rats highlighted the expected superior capability of MRI to define brain structures. The simplicity of our developed MRI/PET compatible bed and the quality of the fused images obtained offers a promising opportunity for a future preclinical translation, particularly for neuroimaging studies.

The effect of regularization in motion compensated PET image reconstruction: a realistic numerical 4D simulation study

Following continuous improvement in PET spatial resolution, respiratory motion correction has become an important task. Two of the most common approaches that utilize all detected PET events to motion-correct PET data are the reconstruct-transform-average method (RTA) and motion-compensated image reconstruction (MCIR). In RTA, separate images are reconstructed for each respiratory frame, subsequently transformed to one reference frame and finally averaged to produce a motion-corrected image. In MCIR, the projection data from all frames are reconstructed by including motion information in the system matrix so that a motion-corrected image is reconstructed directly. Previous theoretical analyses have explained why MCIR is expected to outperform RTA. It has been suggested that MCIR creates less noise than RTA because the images for each separate respiratory frame will be severely affected by noise. However, recent investigations have shown that in the unregularized case RTA images can have fewer noise artefacts, while MCIR images are more quantitatively accurate but have the common salt-and-pepper noise. In this paper, we perform a realistic numerical 4D simulation study to compare the advantages gained by including regularization within reconstruction for RTA and MCIR, in particular using the median-root-prior incorporated in the ordered subsets maximum a posteriori one-step-late algorithm. In this investigation we have demonstrated that MCIR with proper regularization parameters reconstructs lesions with less bias and root mean square error and similar CNR and standard deviation to regularized RTA. This finding is reproducible for a variety of noise levels (25, 50, 100 million counts), lesion sizes (8 mm, 14 mm diameter) and iterations. Nevertheless, regularized RTA can also be a practical solution for motion compensation as a proper level of regularization reduces both bias and mean square error.

Performance characterization of the Inveon preclinical small-animal PET/SPECT/CT system for multimodality imaging

We investigated the performance of the Inveon small-animal PET/SPECT/CT system and compared the imaging capabilities of the SPECT and PET components. For SPECT, the energy resolution, tomographic spatial resolution and system sensitivity were evaluated with a (99m)Tc solution using a single pinhole collimator. For PET, the spatial resolution, absolute sensitivity, scatter fraction and peak noise equivalent count were evaluated. Phantoms and a normal rat were scanned to compare the imaging capabilities of SPECT and PET. The SPECT spatial resolution was 0.84mm full-width at half-maximum (FWHM) at a radius of rotation of 25mm using a 0.5-mm pinhole aperture collimator, while the PET spatial resolution was 1.63mm FWHM at the centre. The SPECT system sensitivity at a radius of rotation of 25mm was 35.3cps/MBq (4 × 10(-3)%) using the 0.5-mm pinhole aperture, while the PET absolute sensitivity was 3.2% for 350-650keV and 3.432ns. Accordingly, the volume sensitivity of PET was three orders of magnitude higher than that of SPECT. This integrated PET/SPECT/CT system showed high performance with excellent spatial resolution for SPECT and sensitivity for PET. Based on the tracer availability and system performance, SPECT and PET have complementary roles in multimodality small-animal imaging.

Phoswich solutions for the PET DOI problem

A high spatial resolution in PET can be achieved by using small detector elements. To maintain good sensitivity these elements have to be quite long, thus introducing parallax error and making the spatial resolution non-uniform over the image volume. Uniformity of spatial resolution can be improved by utilizing depth-of-interaction (DOI) information to reduce the parallax error. In the present study we have focused on phoswich approaches based on interacting scintillators, that is, a phoswich combination in which one scintillator emits light in the excitation band of the other. We have looked at LaBr 3:Ce and LaCl 3:Ce and the interactions of those two scintillators with LSO:Ce, GSO:Ce and YSO:Ce. The reasons to use the two Lanthanum scintillators are twofold: light output is high and the two different emission wavelengths, 350 nm (LaCl 3:Ce) and 380 nm (LaBr 3:Ce) may produce different interactions with the three oxyorthosilicate scintillators. In addition a possible DOI detector comprising LuAG:Pr pixels with a thin LSO:Ce layer at one end has been evaluated. A Bollinger–Thomas set-up was used to measure luminescence rise and luminescence decay time characteristics in all cases. When using LaCl 3:Ce, the phoswich combinations with YSO:Ce and GSO:Ce showed phoswich decay time characteristics as expected for a simple convolution of the decay times of the two phoswich components. A correction was needed, however, for the LaCl 3:Ce–LSO:Ce phoswich due to the LSO:Ce intrinsic activity. For the LaBr 3:Ce–LSO:Ce phoswich, corrections were needed for non-interacting LaBr 3:Ce light in addition to the expected phoswich interaction.

Significance of subcentimetre18F-FDG PET/CT pulmonary abnormality in patients with known extrapulmonary malignancy

The significance of a subcentimetre 18F-FDG PET/CT pulmonary abnormality in a patient with known extrapulmonary primary malignancy can have a major impact on the clinical management of the patient. The clinician’s reliance on the semi-quantitative and qualitative PET/CT analysis of the abnormality has, at times, led to untoward diagnostic problems, given the limited spatial resolution of PET for a small volume lesion performed as part of the standard PET/CT study. This paper highlights a case each of an FDG-positive and an FDG-negative focal pulmonary abnormality in a combined PET/CT study of patients with known extrapulmonary malignancy. © 2010 Biomedical Imaging and Intervention Journal. All rights reserved.

PET/CT for Adrenal Assessment

W91 Imaging Features Normal Adrenal Gland The normal adrenal gland is larger than the spatial resolution of PET; however, it is usually barely visible on FDG PET. Combined PET/ CT can show normal mild FDG uptake in the location of the glands visible on the coregistered CT (Figs. 1 and 2). The average mean and maximum standardized uptake values (SUVs) are 0.90 ± 0.15 (SD) and 0.83 ± 0.17, respectively, for the right adrenal and 1.10 ± 0.15 and 0.946 ± 0.15 for the left adrenal. The maximum SUVs of normal adrenal glands range from 0.95 to 2.46 [4]. An adrenal is usually considered malignant if its intensity is higher than that of the liver; however, because the average mean SUV of the liver is 1.5–2.0, physiologic adrenal uptake may, in some cases, be in the range of malignant lesions.

Abstract CN01-04: Imaging-guided therapy in different tumor models using positron emission tomography (PET) and optical imaging

Abstract Positron emission tomography (PET) allows non-invasive assessment of physiological, metabolic and molecular processes in vivo. With the achievements in detector technology, spatial resolution of PET has been improved (1–2mm) enabling investigations in small experimental animals such as mice. With the development in tracer technology a variety of endogenously expressed and exogenously introduced genes can be analyzed by PET. This opens up the exciting and rapidly evolving field of molecular imaging aiming towards the non-invasive localization of the dynamics of disease specific molecular alterations and biological processes in animal models and humans in vivo. The main and most intriguing advantage of molecular imaging is the kinetic analysis of a given molecular event in the same experimental subject over time. This allows non-invasive characterization of animal models of human disease at various disease stages and after therapeutic intervention. Optical imaging (OI) is a non-invasive molecular imaging technology that uses light to interrogate cellular and molecular function in the living body. Although OI technologies are still limited by light scattering and depth of light penetration they provide a low cost and rapid alternative to the more expensive and time-consuming PET imaging. By introducing multi-modality reporter constructs (PET, fluorescence and/or bioluminescence) drawbacks of each modality can be overcome and advantages will complement one another. Thus, allowing on the one side rapid, cost-effective optical reporter imaging and on the other side tomographic as well as quantitative imaging of reporter gene expression by PET. With PET being a modality well developed for imaging in human subjects as well as small animals it provides a link from bench-to-bedside and may facilitate translation into clinical applications. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):CN01-04.

Computerized method for nonrigid MR-to-PET breast-image registration

We have developed and tested a new simple computerized finite element method (FEM) approach to MR-to-PET nonrigid breast-image registration. The method requires five–nine fiducial skin markers (FSMs) visible in MRI and PET that need to be located in the same spots on the breast and two on the flanks during both scans. Patients need to be similarly positioned prone during MRI and PET scans. This is accomplished by means of a low gamma-ray attenuation breast coil replica used as the breast support during the PET scan. We demonstrate that, under such conditions, the observed FSM displacement vectors between MR and PET images, distributed piecewise linearly over the breast volume, produce a deformed FEM mesh that reasonably approximates nonrigid deformation of the breast tissue between the MRI and PET scans. This method, which does not require a biomechanical breast tissue model, is robust and fast. Contrary to other approaches utilizing voxel intensity-based similarity measures or surface matching, our method works for matching MR with pure molecular images (i.e. PET or SPECT only). Our method does not require a good initialization and would not be trapped by local minima during registration process. All processing including FSMs detection and matching, and mesh generation can be fully automated. We tested our method on MR and PET breast images acquired for 15 subjects. The procedure yielded good quality images with an average target registration error below 4 mm (i.e. well below PET spatial resolution of 6–7 mm). Based on the results obtained for 15 subjects studied to date, we conclude that this is a very fast and a well-performing method for MR-to-PET breast-image nonrigid registration. Therefore, it is a promising approach in clinical practice. This method can be easily applied to nonrigid registration of MRI or CT of any type of soft-tissue images to their molecular counterparts such as obtained using PET and SPECT.

A Practical, Automated Quality Assurance Method for Measuring Spatial Resolution in PET

The use of different scanners, acquisition protocols, and reconstruction algorithms has been identified as a problem that limits the use of PET in multicenter trials. The aim of this project was to aid standardization of data collection by developing a quality assurance method for measuring the spatial resolution achieved with clinical imaging protocols. A commercially available (68)Ge cylinder phantom (diameter, 20 cm) with a uniform activity concentration was positioned in the center of the PET field of view, and an image was acquired using typical clinical parameters. Spatial resolution was measured by artificially generating an object function (O) with uniform activity within a 20-cm-diameter cylinder, assuming no noise and perfect spatial resolution, centered on the original image (I); dividing F[I] by F[O], where F indicates a 2-dimensional Fourier transform, to produce a modulation transfer function; and taking the inverse Fourier transform of the modulation transfer function to produce a point-spread function in image space. The method was validated using data acquired on 4 different commercial PET systems. Spatial resolution on the Discovery LS was measured at 5.75 +/- 0.58 mm, compared with 5.54 +/- 0.19 mm from separate point source measurements. Variability of the resolution measurements differed between scanners and protocols, but the typical SD was approximately 0.15 mm when iterative reconstruction was used. The potential for predicting resolution recovery coefficients for small objects was also demonstrated. The proposed method does not require elaborate phantom preparation and is practical to perform, and data analysis is fully automated. This approach is useful for evaluating clinical reconstruction protocols across varying scanners and reconstruction algorithms and should greatly aid standardization of data collection between centers.