Backscatter coefficient imaging using a clinical scanner.

A clinical ultrasound scanner has been integrated with a digital data acquisition system to record echo signals for off-line processing of quantitative acoustic backscatter images. The method used to determine backscatter coefficients accounts for experimental factors related to the beam directivity function, the transmitting and receiving electronics, and the attenuation path of the beam. After characterization and calibration of the ultrasound scanner according to the data processing requirements, the quantitative backscatter coefficient for tissue-mimicking phantoms are within 14% of a value predicted by scattering theory. On five normal volunteers, preliminary in vivo liver images of the acoustic backscatter coefficient are obtained. Results from this study are compared to previously published in vitro results.     

Analytical study of performance in a 3D PET scanner.

The use of arrays of small discrete detectors and thin slices to achieve a high isotropic spatial resolution in positron emission tomography (PET) results in systems with a low ring sensitivity. In a multi-ring system, the overall sensitivity can be considerably improved by removing the interslice collimators to make full use of all cross slices coincidences, but this is achieved at the expense of increased scatter and accidental rates in the image. For imaging of small laboratory animals (diameter of 10 cm or less), the relieved burden of scatters, and to some extent accidentals, suggests that volumetric imaging may be of particular value. In order to evaluate the performance to be expected from a small animal PET scanner (10 cm diameter field) with and without the interplane collimators, the incident event rates for singles (unscattered and single scattered) and true, scatter and accidental coincidences were evaluated analytically. The performance was evaluated for various source sizes and activities in terms of five criteria: true/single ratio, scatter fraction, accidental fraction, image contrast and noise effective sensitivity. As a result of a 3-fold increase in scatter fraction and of a significant increase in accidental fraction for larger sources, the image contrast (true/(scatter+accidental)) is observed to always be inferior with the collimators removed. However, a significant improvement in noise effective sensitivity is obtained with the volumetric configuration, especially for small size sources placed at the centre of the field of view. It is concluded that the volumetric configuration is more advantageous than the multislice configuration to image small animals because the gain in sensitivity overcomes the loss of accuracy due to higher scatter and accidental rates.     

A fully 3D small PET scanner.

A fully 3D small PET scanner based on a novel detection principle for gamma rays is described. It uses BaF2 scintillator and photosensitive wire chambers. Extensive tests with technical prototypes have shown that such a system will have a detection efficiency for gamma rays comparable with what can be obtained with the more traditional approach, and a spatial resolution determined by the size of the crystals. The expected performances of the scanner, based on our measurements and on simulations, are given.     

Hybrid PET/MR imaging of tumors using an oleanolic acid-conjugated nanoparticle

Research into multifunctional nanoparticles is focused on creating an agent for use in an all-in-one multimodal imaging system that includes diagnostic imaging, drug delivery, and therapeutic monitoring. We designed a new dual-modality tumor-targeting agent with a new tumor-targeting molecule, oleanolic acid (OA), which is derived from a natural compound and coupled with a macrocyclic chelating agent such as 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), iron oxide nanoparticles (IONP), and radiolabeling components such as ⁶⁸Ga for dual-modality positron emission tomography (PET)/magnetic resonance imaging (MRI). We attempted to obtain fusion PET/MR images with the ⁶⁸Ga–NOTA–OA–IONP hybrid tumor-targeting imaging agent using colon cancer (HT-29) xenograft mice models. The HT-29 cancer cells showed high uptake of ⁶⁸Ga–NOTA–OA–IONP, which also had an inhibitory effect on the cells. Moreover, we obtained PET and MRI tumor images as well as fusion PET/MRI images of the tumors using ⁶⁸Ga–NOTA–OA–IONP. Therefore, the dual-modality cancer-targeting radiolabeled nanoparticle reported here is a potent imaging agent that is suitable for PET, MRI, and PET/MRI-based diagnosis of tumors; it also has the advantage of not only detecting tumor functionality, but also simultaneously aiding in tumor resolution.     

Computer phantom study of brain PET glucose metabolism imaging using a rotating SPECT/PET camera

Positron emission tomography (PET) with [18F] fluoro-deoxy-glucose (FDG) provides information about glucose metabolism and is used to measure tissue glucose kinetics in the brain. The recent interest in hybrid SPECT/PET systems emerged as a practical approach to reduce the high cost of purchasing a dedicated ring-detector PET system. We have implemented interpolation methods for processing the projection data that could potentially reduce artifacts when reconstructing a dynamic imaging sequence in a PET study from a dual-head rotating SPECT/PET system. The computer simulations predict that parameter estimates from the dedicated PET system will be superior to results using the rotating camera system. However, the rotating camera system using projection interpolation may approach the accuracy of the dedicated PET system if the data noise is below 20%.     

Impact of metal artefacts due to EEG electrodes in brain PET/CT imaging

The goal of this study is to investigate the impact of electroencephalogram (EEG) electrodes on the visual quality and quantification of (18)F-FDG PET images in neurological PET/CT examinations. For this purpose, the scans of 20 epilepsy patients with EEG monitoring were used. The CT data were reconstructed with filtered backprojection (FBP) and with a metal artefact reduction (MAR) algorithm. Both data sets were used for CT-based attenuation correction (AC) of the PET data. Also, a calculated AC (CALC) technique was considered. A volume of interest (VOI)-based analysis and a voxel-based quantitative analysis were performed to compare the different AC methods. Images were also evaluated visually by two observers. It was shown with simulations and phantom measurements that from the considered AC methods, the MAR-AC can be used as the reference in this setting. The visual assessment of PET images showed local hot spots outside the brain corresponding to the locations of the electrodes when using FBP-AC. In the brain, no abnormalities were observed. The quantitative analysis showed a very good correlation between PET-FBP-AC and PET-MAR-AC, with a statistically significant positive bias in the PET-FBP-AC images of about 5-7% in most brain voxels. There was also good correlation between PET-CALC-AC and PET-MAR-AC, but in the PET-CALC-AC images, regions with both a significant positive and negative bias were observed. EEG electrodes give rise to local hot spots outside the brain and a positive quantification bias in the brain. However, when diagnosis is made by mere visual assessment, the presence of EEG electrodes does not seem to alter the diagnosis. When quantification is performed, the bias becomes an issue especially when comparing brain images with and without EEG monitoring.     

Detector development for microPET II: a 1 microl resolution PET scanner for small animal imaging.

We are currently developing a small animal positron emission tomography (PET) scanner with a design goal of 1 microlitre (1 mm3) image resolution. The detectors consist of a 12 x 12 array of 1 x 1 x 10 mm lutetium oxyorthosilicate (LSO) scintillator crystals coupled to a 64-channel photomultiplier tube (PMT) via 5 cm long optical fibre bundles. The optical fibre connection allows a high detector packing fraction despite the dead space surrounding the active region of the PMT. Optical fibre bundles made from different types of glass were tested for light transmission, and also their effects on crystal identification and energy resolution, and compared to direct coupling of the LSO arrays to the PMTs. We also investigated the effects of extramural absorber (EMA) in the fibre bundles. Based on these results, fibre bundles manufactured from F2 glass were selected. We built three pairs of prototype detectors (directly coupled LSO array, fibre bundle without EMA and fibre bundle with EMA) and measured flood histograms, energy resolution, intrinsic spatial resolution and timing resolution. The results demonstrated an intrinsic spatial resolution (FWHM) of 1.12 mm (directly coupled), 1.23 mm (fibre bundle without EMA coupling) and 1.27 mm (fibre bundle with EMA coupling) using an approximately 500 microm diameter Na-22 point source. Using a 330 microm outer diameter steel needle line source filled with F-18, spatial resolution for the detector with the EMA optical fibre bundle improved to 1.05 mm. The respective timing and energy FWHM values were 1.96 ns, 21% (directly coupled), 2.20 ns, 23% (fibre bundle without EMA) and 2.99 ns, 30% (fibre bundle with EMA). The peak-to-valley ratio in the flood histograms was better with EMA (5:1) compared to the optical fibre bundle without EMA (2.5:1), due to the decreased optical cross-talk. In comparison to the detectors used in our current generation microPET scanner, these detectors substantially improve on the spatial resolution, preserve the timing resolution and provide adequate energy resolution for a modern high-resolution animal PET tomograph.     

Cardiac PET imaging in mice with simultaneous cardiac and respiratory gating

Gating firmware and software were developed for the microPET II small animal scanner. The measured cardiac and respiratory signals were collected and converted to TTL gating signals by a Biopac MP150 data acquisition system and sent to microPET II through two BNC connectors on the front panel. During acquisition, the coincidence monitor takes the average of the last eight gate input cycles and inserts this into the list mode data stream on the falling edge of the gating pulse. This value is then used to determine the current time interval of the next gate cycle when the list mode data are sorted into sinograms. The gating firmware and software were validated by an experiment using a rotating point source. Mouse heart (18F-FDG) and bone (18F(-)) imaging was performed with simultaneous cardiac and respiratory gating. It was clearly demonstrated that the contractile function of the mouse heart can be studied by cardiac-gated imaging with microPET II. The left ventricular volumes at different times of the cardiac cycle were measured and the ejection fraction was calculated. In the bone scan, no detectable movement caused by heart contraction was observed. Respiratory motion was more subtle with virtually no motion for more than 75% of the respiratory cycle. The motion of the mouse heart and bones in the thorax caused by respiration was less than 1 mm. It appears with the current resolution of PET, and the small fraction of the respiratory cycle in which motion occurs, that respiratory gating is probably not necessary for most mouse cardiac studies.     

Performance of a block detector PET scanner in imaging non-pure positron emitters--modelling and experimental validation with 124I

The key performance measures of resolution, count rate, sensitivity and scatter fraction are predicted for a dedicated BGO block detector patient PET scanner (GE Advance) in 2D mode for imaging with the non-pure positron-emitting radionuclides 124I, 55Co, 61Cu, 62Cu, 64Cu and 76Br. Model calculations including parameters of the scanner, decay characteristics of the radionuclides and measured parameters in imaging the pure positron-emitter 18F are used to predict performance according to the National Electrical Manufacturers Association (NEMA) NU 2-1994 criteria. Predictions are tested with measurements made using 124I and show that, in comparison with 18F, resolution degrades by 1.2 mm radially and tangentially throughout the field-of-view (prediction: 1.2 mm), count-rate performance reduces considerably and in close accordance with calculations, sensitivity decreases to 23.4% of that with 18F (prediction: 22.9%) and measured scatter fraction increases from 10.0% to 14.5% (prediction: 14.7%). Model predictions are expected to be equally accurate for other radionuclides and may be extended to similar scanners. Although performance is worse with 124I than 18F, imaging is not precluded in 2D mode. The viability of 124I imaging and performance in a clinical context compared with 18F is illustrated with images of a patient with recurrent thyroid cancer acquired using both [124I]-sodium iodide and [18F]-2-fluoro-2-deoxyglucose.     

Design of a very high-resolution small animal PET scanner using a silicon scatter detector insert

A small animal positron emission tomography (PET) instrument using a high-resolution solid-state detector insert in a conventional PET system was investigated for its potential to achieve sub-millimeter spatial resolution for mouse imaging. Monte Carlo simulations were used to estimate the effect of detector configurations (thickness, length and radius) on sensitivity. From this initial study, a PET system having an inner cylindrical silicon detector (4 cm ID, 4 cm length and 1.6 cm thickness composed of 16 layers of 300 microm x 300 microm x 1 mm pads), for scattering, surrounded by an outer cylindrical BGO scintillation detector (17.6 cm ID, 16 cm length and 2 cm thickness segmented into 3 mm x 3 mm x 20 mm crystals), for capture was evaluated in detail. In order to evaluate spatial resolution, sensitivity and image quality of the PET system, 2D images of multiple point and cylinder sources were reconstructed with the simulation data including blurring from positron range and annihilation photon acollinearity using filtered backprojection (FBP). Simulation results for (18)F demonstrate 340 microm FWHM at the center of the field of view with 1.0% sensitivity from the coincidence of single scattering events in both silicon detectors and 1.0 mm FWHM with 9.0% sensitivity from the coincidence of single scattering in the silicon and full energy absorption of the second photon in the BGO detector.     

Construction of a modified capacitive overlap MR coil for imaging of small animals and objects in a clinical whole-body scanner

During the last two decades, there has been an explosive increase in the number of MR investigations involving genetically manipulated mice and rats. Many of the animal studies are performed in a more or less clinical environment, where whole-body MR scanners are the only option available. The quality and acquisition time of MR images have improved with the development of novel RF coil technologies. This communication describes the construction of a small inductively coupled capacitive overlap transmit-receive MR coil for imaging of small animals and objects in a clinical MR scanner. The MR coil presented here is a modified version of the bridged loop-gap coil and consists of two tube-shaped coupled resonance circuits, where the primary circuit partly encapsulates the imaging (secondary) circuit. By rotating the concentric primary coil relative to the secondary coil tuning over a range of several hundred kilohertz is obtained. The coil performance was characterized experimentally by acquiring high-resolution anatomical, diffusion and perfusion MR images as well as the acquisition of proton spectra of a mouse tumour.     

Characterizing hypoxia in human glioma: A simultaneous multimodal MRI and PET study

Hypoxia plays an important role for the prognosis and therapy response of cancer. Thus, hypoxia imaging would be a valuable tool for pre‐therapeutic assessment of tumor malignancy. However, there is no standard validated technique for clinical application available yet. Therefore, we performed a study in 12 patients with high‐grade glioma, where we directly compared the two currently most promising techniques, namely the MR‐based relative oxygen extraction fraction (MR‐rOEF) and the PET hypoxia marker H‐1‐(3‐[¹⁸F]‐fluoro‐2‐hydroxypropyl)‐2‐nitroimidazole ([¹⁸F]‐FMISO). MR‐rOEF was determined from separate measurements of T₂, T₂* and relative cerebral blood volume (rCBV) employing a multi‐parametric approach for quantification of the blood‐oxygenation‐level‐dependent (BOLD) effect. With respect to [¹⁸F]‐FMISO‐PET, besides the commonly used late uptake between 120 and 130 min ([¹⁸F]‐FMISO_{120–130 min}), we also analyzed the hypoxia specific uptake rate [¹⁸F]‐FMISO‐k₃, as obtained by pharmacokinetic modeling of dynamic uptake data. Since pharmacokinetic modeling of partially acquired dynamic [¹⁸F]‐FMISO data was sensitive to a low signal‐to‐noise‐ratio, analysis was restricted to high‐uptake tumor regions. Individual spatial analyses of deoxygenation and hypoxia‐related parameter maps revealed that high MR‐rOEF values clustered in (edematous) peritumoral tissue, while areas with high [¹⁸F]‐FMISO_{120–130 min} concentrated in and around active tumor with disrupted blood–brain barrier, i.e. contrast enhancement in T₁‐weighted MRI. Volume‐of‐interest‐based correlations between MR‐rOEF and [¹⁸F]‐FMISO_{120–130 min} as well as [¹⁸F]‐FMISO‐k₃, and voxel‐wise analyses in individual patients, yielded limited correlations, supporting the notion that [¹⁸F]‐FMISO uptake, even after 2 h, might still be influenced by perfusion while [¹⁸F]‐FMISO‐k₃ was severely hampered by noise. According to these results, vascular deoxygenation, as measured by MR‐rOEF, and severe tissue hypoxia, as measured by [¹⁸F]‐FMISO, show a poor spatial correspondence. Overall, the two methods appear to rather provide complementary than redundant information about high‐grade glioma biology.     

Effects of injected dose, BMI and scanner type on NECR and image noise in PET imaging

Noise equivalent count rate (NECR) and image noise are two different but related metrics that have been used to predict and assess image quality, respectively. The aim of this study is to investigate, using patient studies, the relationships between injected dose (ID), body mass index (BMI) and scanner type on NECR and image noise measurements in PET imaging. Two groups of 90 patients each were imaged on a GE DSTE and a DRX PET/CT scanner, respectively. The patients in each group were divided into nine subgroups according to three BMI (20-24.9, 25-29.9, 30-45 kg m(-2)) and three ID (296-444, 444-555, 555-740 MBq) ranges, resulting in ten patients/subgroup. All PET data were acquired in 3D mode and reconstructed using the VuePoint HD? fully 3D OSEM algorithm (2 iterations, 21(DRX) or 20 (DSTE) subsets). NECR and image noise measurements for bed positions covering the liver were calculated for each patient. NECR was calculated from the trues, randoms and scatter events recorded in the DICOM header of each patient study, while image noise was determined as the standard deviation of 50 non-neighboring voxels in the liver of each patient. A t-test compared the NECR and image noise for different scanners but with the same BMI and ID. An ANOVA test on the other hand was used to compare the results of patients with different BMI but the same ID and scanner type as well as different ID but the same BMI and scanner type. As expected the t-test showed a significant difference in NECR between the two scanners for all BMI and ID subgroups. However, contrary to what is expected no such findings were observed for image noise measurement. The ANOVA results showed a statistically significant difference in both NECR and image noise among the different BMI for each ID and scanner subgroup. However, there was no statistically significant difference in NECR and image noise across different ID for each BMI and scanner subgroup. Although the GE DRX PET/CT scanner has better count rate performance than the GE DSTE PET/CT scanner, this improvement does not translate to a lower image noise when using OSEM reconstruction. Our results show that patients with larger BMI consistently generate poorer image quality. Dose reduction from >555 to 296-444 MBq has minimal impact on image quality independent of the scanner used. A reduction in ID decreases patient and technologist exposure and can potentially reduce the overall cost of the study.     

Lutetium oxyorthosilicate (LSO) intrinsic activity correction and minimal detectable target activity study for SPECT imaging with a LSO-based animal PET scanner

This work is part of a feasibility study to develop SPECT imaging capability on a lutetium oxyorthosilicate (LSO) based animal PET system. The SPECT acquisition was enabled by inserting a collimator assembly inside the detector ring and acquiring data in singles mode. The same LSO detectors were used for both PET and SPECT imaging. The intrinsic radioactivity of (176)Lu in the LSO crystals, however, contaminates the SPECT data, and can generate image artifacts and introduce quantification error. The objectives of this study were to evaluate the effectiveness of a LSO background subtraction method, and to estimate the minimal detectable target activity (MDTA) of image object for SPECT imaging. For LSO background correction, the LSO contribution in an image study was estimated based on a pre-measured long LSO background scan and subtracted prior to the image reconstruction. The MDTA was estimated in two ways. The empirical MDTA (eMDTA) was estimated from screening the tomographic images at different activity levels. The calculated MDTA (cMDTA) was estimated from using a formula based on applying a modified Currie equation on an average projection dataset. Two simulated and two experimental phantoms with different object activity distributions and levels were used in this study. The results showed that LSO background adds concentric ring artifacts to the reconstructed image, and the simple subtraction method can effectively remove these artifacts-the effect of the correction was more visible when the object activity level was near or above the eMDTA. For the four phantoms studied, the cMDTA was consistently about five times of the corresponding eMDTA. In summary, we implemented a simple LSO background subtraction method and demonstrated its effectiveness. The projection-based calculation formula yielded MDTA results that closely correlate with that obtained empirically and may have predicative value for imaging applications.     

Intracellular ion imaging using fluorescent dyes: artefacts and limits to resolution

Development of highly efficient fluorescent ratio indicators has made imaging of ion concentrations within individual cells possible (Grynkiewicz et al. 1985; Tsien and Poenie 1986). Ion imaging is a complex technique and is therefore prone to artefacts. In this paper we investigate the limits of the technique and its potential pitfalls. The spatial resolution of an imaging system is determined for different cell geometries. We describe a technique to increase the time resolution of existing systems by using a single excitation wavelength to measure changes in ion concentration. We demonstrate examples of potential artefacts arising from hardware limitations, image processing and fundamental optics. Methods for recognition and minimization of these problems are discussed.     

Optimal whole-body PET scanner configurations for different volumes of LSO scintillator: a simulation study

The axial field of view (AFOV) of the current generation of clinical whole-body PET scanners range from 15-22?cm, which limits sensitivity and renders applications such as whole-body dynamic imaging or imaging of very low activities in whole-body cellular tracking studies, almost impossible. Generally, extending the AFOV significantly increases the sensitivity and count-rate performance. However, extending the AFOV while maintaining detector thickness has significant cost implications. In addition, random coincidences, detector dead time, and object attenuation may reduce scanner performance as the AFOV increases. In this paper, we use Monte Carlo simulations to find the optimal scanner geometry (i.e. AFOV, detector thickness and acceptance angle) based on count-rate performance for a range of scintillator volumes ranging from 10 to 93 l with detector thickness varying from 5 to 20?mm. We compare the results to the performance of a scanner based on the current Siemens Biograph mCT geometry and electronics. Our simulation models were developed based on individual components of the Siemens Biograph mCT and were validated against experimental data using the NEMA NU-2 2007 count-rate protocol. In the study, noise-equivalent count rate (NECR) was computed as a function of maximum ring difference (i.e. acceptance angle) and activity concentration using a 27?cm diameter, 200?cm uniformly filled cylindrical phantom for each scanner configuration. To reduce the effect of random coincidences, we implemented a variable coincidence time window based on the length of the lines of response, which increased NECR performance up to 10% compared to using a static coincidence time window for scanners with a large maximum ring difference values. For a given scintillator volume, the optimal configuration results in modest count-rate performance gains of up to 16% compared to the shortest AFOV scanner with the thickest detectors. However, the longest AFOV of approximately 2?m with 20?mm thick detectors resulted in performance gains of 25-31?times higher NECR relative to the current Siemens Biograph mCT scanner configuration.     

Design study of an in situ PET scanner for use in proton beam therapy

Proton beam therapy can deliver a high radiation dose to a tumor without significant damage to surrounding healthy tissue or organs. One way of verifying the delivered dose distribution is to image the short-lived positron emitters produced by the proton beam as it travels through the patient. A potential solution to the limitations of PET imaging in proton beam therapy is the development of a high sensitivity, in situ PET scanner that starts PET imaging almost immediately after patient irradiation while the patient is still lying on the treatment bed. A partial ring PET design is needed for this application in order to avoid interference between the PET detectors and the proton beam, as well as restrictions on patient positioning on the couch. A partial ring also allows us to optimize the detector separation (and hence the sensitivity) for different patient sizes. Our goal in this investigation is to evaluate an in situ PET scanner design for use in proton therapy that provides tomographic imaging in a partial ring scanner design using time-of-flight (TOF) information and an iterative reconstruction algorithm. GEANT4 simulation of an incident proton beam was used to produce a positron emitter distribution, which was parameterized and then used as the source distribution inside a water-filled cylinder for EGS4 simulations of a PET system. Design optimization studies were performed as a function of crystal type and size, system timing resolution, scanner angular coverage and number of positron emitter decays. Data analysis was performed to measure the accuracy of the reconstructed positron emitter distribution as well as the range of the positron emitter distribution. We simulated scanners with varying crystal sizes (2-4 mm) and type (LYSO and LaBr(3)) and our results indicate that 4 mm wide LYSO or LaBr(3) crystals (resulting in 4-5 mm spatial resolution) are adequate; for a full-ring, non-TOF scanner we predict a low bias (<0.6 mm) and a good precision (<1 mm) in the estimated range relative to the simulated positron distribution. We then varied the angular acceptance of the scanner ranging from 1/2 to 2/3 of 2π; a partial ring TOF imaging with good timing resolution (≤600 ps) is necessary to produce accurate tomographic images. A two-third ring scanner with 300 ps timing resolution leads to a bias of 1.0 mm and a precision of 1.4 mm in the range estimate. With a timing resolution of 600 ps, the bias increases to 2.0 mm while the precision in the range estimate is similar. For a half-ring scanner design, more distortions are present in the image, which is characterized by the increased error in the profile difference estimate. We varied the number of positron decays imaged by the PET scanner by an order of magnitude and we observe some decrease in the precision of the range estimate for lower number of decays, but all partial ring scanner designs studied have a precision ≤1.5 mm. The largest number tested, 150 M total positron decays, is considered realistic for a clinical fraction of delivered dose, while the range of positron decays investigated in this work covers a variable number of situations corresponding to delays in scan start time and the total scan time. Thus, we conclude that for partial ring systems, an angular acceptance of at least 1/2 (of 2π) together with timing resolution of 300 ps is needed to achieve accurate and precise range estimates. With 600 ps timing resolution an angular acceptance of 2/3 (of 2π) is required to achieve satisfactory range estimates. These results indicate that it would be feasible to develop a partial-ring dedicated PET scanner based on either LaBr(3) or LYSO to accurately characterize the proton dose for therapy planning.