Andrew L. Goertzen

Bone microarchitecture assessed by TBS predicts osteoporotic fractures independent of bone density: The manitoba study

The measurement of BMD by dual‐energy X‐ray absorptiometry (DXA) is the “gold standard” for diagnosing osteoporosis but does not directly reflect deterioration in bone microarchitecture. The trabecular bone score (TBS), a novel gray‐level texture measurement that can be extracted from DXA images, correlates with 3D parameters of bone microarchitecture. Our aim was to evaluate the ability of lumbar spine TBS to predict future clinical osteoporotic fractures. A total of 29,407 women 50 years of age or older at the time of baseline hip and spine DXA were identified from a database containing all clinical results for the Province of Manitoba, Canada. Health service records were assessed for the incidence of nontraumatic osteoporotic fracture codes subsequent to BMD testing (mean follow‐up 4.7 years). Lumbar spine TBS was derived for each spine DXA examination blinded to clinical parameters and outcomes. Osteoporotic fractures were identified in 1668 (5.7%) women, including 439 (1.5%) spine and 293 (1.0%) hip fractures. Significantly lower spine TBS and BMD were identified in women with major osteoporotic, spine, and hip fractures (all p < 0.0001). Spine TBS and BMD predicted fractures equally well, and the combination was superior to either measurement alone (p < 0.001). Spine TBS predicts osteoporotic fractures and provides information that is independent of spine and hip BMD. Combining the TBS trabecular texture index with BMD incrementally improves fracture prediction in postmenopausal women.

NEMA NU 4-2008 Comparison of Preclinical PET Imaging Systems

The National Electrical Manufacturers Association (NEMA) standard NU 4-2008 for performance measurements of small-animal tomographs was recently published. Before this standard, there were no standard testing procedures for preclinical PET systems, and manufacturers could not provide clear specifications similar to those available for clinical systems under NEMA NU 2-1994 and 2-2001. Consequently, performance evaluation papers used methods that were modified ad hoc from the clinical PET NEMA standard, thus making comparisons between systems difficult. Methods: We acquired NEMA NU 4-2008 performance data for a collection of commercial animal PET systems manufactured since 2000: microPET P4, microPET R4, microPET Focus 120, microPET Focus 220, Inveon, ClearPET, Mosaic HP, Argus (formerly eXplore Vista), VrPET, LabPET 8, and LabPET 12. The data included spatial resolution, counting-rate performance, scatter fraction, sensitivity, and image quality and were acquired using settings for routine PET. Results: The data showed a steady improvement in system performance for newer systems as compared with first-generation systems, with notable improvements in spatial resolution and sensitivity. Conclusion: Variation in system design makes direct comparisons between systems from different vendors difficult. When considering the results from NEMA testing, one must also consider the suitability of the PET system for the specific imaging task at hand.

Imaging of Weak-Source Distributions in LSO-Based Small-Animal PET Scanners

Lutetium oxyorthosilicate (LSO)- or lutetium-yttrium oxyorthosilicate (LYSO)–based PET scanners have intrinsic radioactivity in the scintillator crystals due to the presence of 176Lu, which decays by β-emission followed by one or more prompt γ-ray emissions. This leads to intrinsic true counts that can influence the image when scanning low levels of activity. An evaluation of the effects of this intrinsic activity for low levels of activity and different energy windows is performed on an LSO-based small-animal PET scanner. Methods: Intrinsic count rate and sensitivity were measured for a range of lower-level discriminators (LLDs) ranging from 100 to 750 keV. The noise equivalent count rate (NECR) as a function of LLD for activity levels from 100 Bq to 100 kBq was estimated using a combination of measurement and previously published data for this scanner. Phantom imaging was performed using three 68Ge sources of strength 55, 220, and 940 Bq and LLD levels of 250, 350, and 400 keV. The images were assessed using a contrast-to-noise ratio (CNR) analysis and by comparing the observed ratio of source activities to the true ratio value. Results: The intrinsic true count rate is reduced from 940 counts per second (cps) for a 250- to 750-keV energy window to <2 cps for a 400- to 750-keV window. There is a corresponding 2-fold drop in sensitivity for detected true events for external positron sources for these 2 energy windows. The NECR versus LLD curves showed a highly peaked shape, with the optimum LLD being approximately 425 keV. The phantom image results were dominated by the intrinsic true counts when an energy window of 250–750 keV was used. The intrinsic true counts were almost completely removed by raising the LLD to 400 keV. The CNR for each of the sources was higher for the narrow energy window and the 55 Bq could be easily visualized in images acquired with LLD levels of 350 and 400 keV but not when the 250-keV LLD was used. Images acquired with an LLD of 400 keV and reconstructed with 2-dimensional filtered backprojection were the most quantitatively accurate. Conclusion: It is possible to visualize sources of <1 kBq in LSO-based animal PET systems by raising the LLD to 400 keV to exclude the majority of the counts due to the intrinsic activity present in the LSO.

Design and Performance of a Resistor Multiplexing Readout Circuit for a SiPM Detector

A silicon photomultiplier (SiPM)-based positron emission tomography (PET) detector was developed using a resistor network charge division multiplexing circuit for detector readout. The detector consists of a lutetium-yttrium oxy-orthosilicate (LYSO) scintillation crystal array, an SiPM array detector (SPMArray 4, SensL Inc., Cork, Ireland) and the resistor multiplexing network implemented in a through-hole package to facilitate changing of resistor values. For purposes of optimizing the readout circuit, the LYSO array used was a 4 4 crystal array with crystal size mm on a pitch of 3.37 mm, matched to the SiPM pixel size. Flood image, energy resolution, photopeak amplitude, timing resolution, and signal time-pickoff measurements were performed using standard NIM electronics. The resistor network values were optimized through an iterative process. The performance of the detector was evaluated over a range of temperatures from 23°C to 60°C by heating the detector. The ability of the detector to resolve crystals smaller than the SiPM pixel pitch was evaluated using a dual-layer LYSO array with crystals of 1.67-mm pitch. The optimal resistor network values were found to be 100 Ω along the rows connecting the SiPM pixels and 56 Ω for the columns. For these resistor value settings, the average energy resolution for the central four crystals in the array at 23.5°C was 13.3% ± 0.3% and degraded to 16.3% ± 0.3% at 60°C. The photopeak amplitude decreased by 2%/°C, and the timing resolution degraded from 3.43 ± 0.22 ns to 4.64 ± 0.25 ns for a 350-750-keV energy window over this temperature range. The signal time-pick-off point shifted earlier by 2.7 ns as the temperature increased, an effect likely due to changes in the signal shape with temperature. The detector was able to resolve all 113 crystals in the dual-layer LYSO array. These results demonstrate that the resistor multiplexing readout circuit functions well for reading out SiPM array based detectors, which use scintillator crystal arrays much smaller than the SiPM pixel pitch. The reduced number of output signals achieved through this signal multiplexing greatly reduces the number of signal cables required. In addition, the ability of this detector to function over a wide range of temperatures offers significant flexibility in defining the system operating temperature set point.

Evaluation of High Density Pixellated Crystal Blocks With SiPM Readout as Candidates for PET/MR Detectors in a Small Animal PET Insert

Arrays of silicon photo-multipliers (SiPMs) are good candidates for the readout of detectors in PET/MR inserts due to their high packing density, efficiency, low bias voltage and insensitivity to magnetic fields. We tested two dual-layer blocks of pixellated lutetium oxy-orthosilicate (LYSO) coupled to SensL 4 × 4 SiPM arrays in terms of their ability to resolve all elements using resolvability index (RI) defined by the FWHM of the crystal response function divided by the separation. Our crystal blocks had 49 1.67 × 1.67 × 6.0 mm3 crystals on the bottom layer and 36 1.67 × 1.67 × 4.0 mm3 crystals in the top layer (offset by 1/2 of the crystal pitch). All 85 crystals were well resolved: compared with for a conventional pre-clinical PET scanners block with 40% lower crystal density. A pair of crystal blocks mounted on translation stages scanned a 0.25 mm 22Na source in 60 0.25 mm steps with the detectors angulated as if there were 16 blocks in a ring. The FWHM of the coincidence response function near the centre of the field of view was 1.31 mm and FWTM was 2.7 mm with the detectors separated by 200 mm.

Quantitative computed tomography in porcine lung injury with variable versus conventional ventilation: Recruitment and surfactant replacement*

Objectives:Biologically variable ventilation improves lung function in acute respiratory distress models. If enhanced recruitment is responsible for these results, then biologically variable ventilation might promote distribution of exogenous surfactant to nonaerated areas. Our objectives were to confirm model predictions of enhanced recruitment with biologically variable ventilation using computed tomography and to determine whether surfactant replacement with biologically variable ventilation provides additional benefit in a porcine oleic acid injury model. Design:Prospective, randomized, controlled experimental animal investigation. Setting:University research laboratory. Subjects:Domestic pigs. Interventions:Standardized oleic acid lung injury in pigs randomized to conventional mechanical ventilation or biologically variable ventilation with or without green dye labeled surfactant replacement. Measurements and Main Results:Computed tomography-derived total and regional masses and volumes were determined at injury and after 4 hrs of ventilation at the same average low tidal volume and minute ventilation. Hemodynamics, gas exchange, and lung mechanics were determined hourly. Surfactant distribution was determined in postmortem cut lung sections. Biologically variable ventilation alone resulted in 7% recruitment of nonaerated regions (p < .03) and 15% recruitment of nonaerated and poorly aerated regions combined (p < .04). Total and normally aerated regional volumes increased significantly with biologically variable ventilation, biologically variable ventilation with surfactant replacement, and conventional mechanical ventilation with surfactant replacement, while poorly and nonaerated regions decreased after 4 hrs of ventilation with biologically variable ventilation alone (p < .01). Biologically variable ventilation showed the greatest improvement (p < .003, biologically variable ventilation vs. all other groups). Hyperaerated regional gas volume increased significantly with biologically variable ventilation, biologically variable ventilation with surfactant replacement, and conventional mechanical ventilation with surfactant replacement. Biologically variable ventilation was associated with restoration of respiratory compliance to preinjury levels and significantly greater improvements in gas exchange at lower peak airway pressures compared to all other groups. Paradoxically, gas exchange and lung mechanics were impaired to a greater extent initially with biologically variable ventilation with surfactant replacement. Peak airway pressure was greater in surfactant-treated animals with either ventilation mode. Surfactant was distributed to the more caudal/injured lung sections with biologically variable ventilation. Conclusions:Quantitative computed tomography analysis confirms lung recruitment with biologically variable ventilation in a porcine oleic acid injury model. Surfactant replacement with biologically variable ventilation provided no additional recruitment benefit and may in fact be harmful.

Evaluation of a 16:3 Signal Multiplexor to Acquire Signals From a SPM Array With Dual and Single Layer LYSO Crystal Blocks

For many years most PET scanners have used a large number of crystals with some form of light sharing technique to couple them to four photo-multiplier tubes (PMT). While the resolution of the scanners was improved by using a larger number of smaller crystals, the PMT size had remained about the same since it is not practical to make PMTs very small. Avalanche photo-diodes (APD) and silicon photo-multipliers (SPM) are now replacing PMTs in small animal PET scanners and in MR-PET scanners in which PMTs are not practical due to their sensitivity to magnetic fields. In this paper we study the performance of a dual layer PET detector consisting a 4 × 4 array of 3.3 mm × 3.3 mm LYSO crystals in the lower layer and an upper offset layer of 3 × 3 crystals coupled to a SensL SPMArray4 4 × 4 array of SPMs. A single layer array of 1.68 mm × 1.68 mm crystals is also studied. The standard SensL pre-amplifier and evaluation board were used to process the signals. The 16 outputs of the evaluation board were connected directly to 16 ADC channels or through a 16:3 multiplexor which uses simple summing amplifiers to provide bipolar X and Y signals as well as the sum of all inputs. In this case only 3 ADCs are required to encode the signals. In both cases a crystal identification map is produced in software. The use of the multiplexor has a negligible effect on the size of each crystals foot-print or its energy resolution. We introduce the concept of “resolvability index” (RI) to compare the size of each crystals foot-print and distance to its neighbour. Our results suggest that the RI with the multiplexed SPM readout is comparable to that of a conventional PS-PMT readout, and superior to that of conventional PET detectors with four PMTs. We anticipate that even smaller crystals could be used on the SPM making this a good choice for small animal PET scanners.

Long-Term Proton Pump Inhibitor Use Is Not Associated With Changes in Bone Strength and Structure

OBJECTIVES:Multiple studies have reported an association between proton pump inhibitor (PPI) use and fracture. However, the causality of this association is questionable, as there is not a well defined mechanism of action, nor is there evidence of an effect on PPIs on areal bone mineral density (aBMD) using dual photon X-ray absorptiometry (DXA). It is possible that PPIs may induce changes in bone structure which would predispose to fracture in the absence of changes in aBMD. We used three-dimensional quantitative computed tomography (3D-QCT) imaging to determine if long-term PPI use was associated with structural changes in bone independent of aBMD.METHODS:We enrolled a sample of long-term (≥5 years) PPI users matched to a similar cohort of persons with no PPI use in the previous 5 years. All subjects underwent assessment of aBMD using DXA, volumetric BMD using 3D-QCT, as well as markers of bone metabolism. Measures of bone strength, including buckling ratio and section modulus, were also compared between the two samples.RESULTS:104 subjects were enrolled (52 PPI users and 52 PPI non-users). There were no differences detected in standard BMD, volumetric BMD, markers of bone metabolism or measures of bone strength between the two groups.CONCLUSIONS:Long-term PPI use is not associated with any changes in bone mineral density or bone strength that would predispose to an increased risk of fracture. These findings provide further evidence that the association between PPI use and fracture is not causal.

Improvement of the spatial resolution of the MicroPET R4 scanner by wobbling the bed

The MicroPET R4 scanner was designed for imaging small rodents such as mice and rats. In many cases the spatial resolution of this system is not sufficient for resolving structures of interest. In order to improve the spatial resolution of the MicroPET R4 through improved spatial sampling, the authors have implemented a variable radius eccentric motion, commonly referred to as wobbling, which is applied to the animal bed during scanning. The wobble motion is incorporated into the sinograms using modified histogramming software, capable of reading the bed wobble position from the list-mode data. The histogramming software corrects the data for the dwell time, apparent crystal location, and crystal-pair efficiency and applies a resolution matching filter. The data acquisition, reconstruction, and image display programs provided from the manufacturer required no modifications. For all studies a wobble period of 8 s was used. The optimal wobble radius was found to be 1.50 mm. The wobbled bed acquisition technique was tested by scanning a resolution phantom and a rat. Images from both studies acquired when using the wobble motion showed an improved spatial resolution when compared with comparable images acquired without the wobble motion. The bed wobbling mechanism can be added to any MicroPET system without major changes and without compromising any imaging modes. Implementing the wobble mechanism may represent a cost-effective method to upgrade the spatial resolution of a MicroPET when compared to the purchase of a newer generation system.

Development and evaluation of a LOR-based image reconstruction with 3D system response modeling for a PET insert with dual-layer offset crystal design

In this study we present a method of 3D system response calculation for analytical computer simulation and statistical image reconstruction for a magnetic resonance imaging (MRI) compatible positron emission tomography (PET) insert system that uses a dual-layer offset (DLO) crystal design. The general analytical system response functions (SRFs) for detector geometric and inter-crystal penetration of coincident crystal pairs are derived first. We implemented a 3D ray-tracing algorithm with 4π sampling for calculating the SRFs of coincident pairs of individual DLO crystals. The determination of which detector blocks are intersected by a gamma ray is made by calculating the intersection of the ray with virtual cylinders with radii just inside the inner surface and just outside the outer-edge of each crystal layer of the detector ring. For efficient ray-tracing computation, the detector block and ray to be traced are then rotated so that the crystals are aligned along the X-axis, facilitating calculation of ray/crystal boundary intersection points. This algorithm can be applied to any system geometry using either single-layer (SL) or multi-layer array design with or without offset crystals. For effective data organization, a direct lines of response (LOR)-based indexed histogram-mode method is also presented in this work. SRF calculation is performed on-the-fly in both forward and back projection procedures during each iteration of image reconstruction, with acceleration through use of eight-fold geometric symmetry and multi-threaded parallel computation. To validate the proposed methods, we performed a series of analytical and Monte Carlo computer simulations for different system geometry and detector designs. The full-width-at-half-maximum of the numerical SRFs in both radial and tangential directions are calculated and compared for various system designs. By inspecting the sinograms obtained for different detector geometries, it can be seen that the DLO crystal design can provide better sampling density than SL or dual-layer no-offset system designs with the same total crystal length. The results of the image reconstruction with SRFs modeling for phantom studies exhibit promising image recovery capability for crystal widths of 1.27-1.43 mm and top/bottom layer lengths of 4/6 mm. In conclusion, we have developed efficient algorithms for system response modeling of our proposed PET insert with DLO crystal arrays. This provides an effective method for both 3D computer simulation and quantitative image reconstruction, and will aid in the optimization of our PET insert system with various crystal designs.