Andrew Rittenbach

High performance SPECT system for simultaneous SPECT-MR imaging of small animals

Our goal is to develop a high performance SPECT system for simultaneous SPECT-MR imaging of small animals (SA). The SPECT system has inner diameter (ID) of 15.4 cm and outer diameter of 19.8 cm. It comprises five seamless cylindrical detectors, each with 19 CZT modules (2.54×2.54 cm2, 16×16 pixels). The SPECT system can be operated either stand-alone or as an insert into an MRI system with a minimum 20 cm bore. Cylindrical multipinhole (MPH) collimator sleeves (CSs), made with tungsten powder and solid tungsten pinhole apertures, were designed to provide maximum geometric efficiency under the systems geometric constraints. Different MPH collimators were designed for mouse or rat imaging, and for static high-resolution or dynamic imaging without CS rotation. Sparse-view image reconstruction methods reduce CS rotation. Monte Carlo simulations confirm the SPECT imaging characteristics of 2 MPH CSs that have 18 and 36 pinholes with 1 mm and 1.5 mm system resolution, respectively. Sparse-view 3D MPH image reconstruction with system response modeling indicates that 36 pinholes are sufficient to provide artifact-free images at 1.5 mm resolution without CS rotation. The SPECT system with the 2 MPH CSs, the RF coil, and all mechanical and electronics components have been constructed. Initial experimental phantom and small animal studies demonstrated the high performance and imaging characteristics of the SPECT system. In conclusion, a high performance small animal (SA) SPECT system has been designed and constructed for simultaneous SA SPECT-MRI. Initial subsystem testing has demonstrated excellent SPECT and MRI imaging performance that matches design predictions.

Cellular Bioenergetics Is an Important Determinant of the Molecular Imaging Signal Derived From Luciferase and the Sodium-Iodide Symporter

Rationale: Molecular imaging is useful for longitudinal assessment of engraftment. However, it is not known which factors, other than cell number, can influence the molecular imaging signal obtained from reporter genes. Objective: The effects of cell dissociation/suspension on cellular bioenergetics and the signal obtained by firefly luciferase and human sodium-iodide symporter labeling of cardiosphere-derived cells were investigated. Methods and Results: 18Fluorodeoxyglucose uptake, ATP levels, 99mTc-pertechnetate uptake, and bioluminescence were measured in vitro in adherent and suspended cardiosphere-derived cells. In vivo dual-isotope single-photon emission computed tomography/computed tomography imaging or bioluminescence imaging (BLI) was performed 1 hour and 24 hours after cardiosphere-derived cell transplantation. Single-photon emission computed tomography quantification was performed using a phantom for signal calibration. Cell loss between 1 hour and 24 hours after transplantation was quantified by quantitative polymerase chain reaction and ex vivo luciferase assay. Cell dissociation followed by suspension for 1 hour resulted in decreased glucose uptake, cellular ATP, 99mTc uptake, and BLI signal by 82%, 43%, 42%, and 44%, respectively, compared with adherent cells, in vitro. In vivo 99mTc uptake was significantly lower at 1 hour compared with 24 hours after cell transplantation in the noninfarct (P<0.001; n=3) and infarct (P<0.001; n=4) models, despite significant cell loss during this period. The in vivo BLI signal was significantly higher at 1 hour than at 24 hours (P<0.01), with the BLI signal being higher when cardiosphere-derived cells were suspended in glucose-containing medium compared with saline (PBS). Conclusions: Adhesion is an important determinant of cellular bioenergetics, 99mTc-pertechnetate uptake, and BLI signal. BLI and sodium-iodide symporter imaging may be useful for in vivo optimization of bioenergetics in transplanted cells.

Acquisition strategies of a dual head rotating 4-Segment Slant-Hole (R4SSH) SPECT System for Improved Myocardial Perfusion SPECT Imaging

The goal was to evaluate different acquisition strategies (AS) of a dual-head (DH) Rotating 4-Segment Slant-Hole (R4SSH) SPECT system for improved myocardial perfusion (MP) SPECT imaging.

Continuing evaluation of an MR compatible SPECT insert for simultaneous SPECT-MR imaging of small animals

The goal of this conference record is to present the experiments conducted to evaluate a magnetic resonance (MR) compatible, simultaneous SPECT-MR insert for small animal (SA) imaging that we have been working on for the last three years. As previously demonstrated, the insert consists of 5 rings of 19 MR compatible CZT detectors connected seamlessly. A multi-pinhole (MPH) collimator with focused pinholes was built using a plastic shell filled with high-density coated tungsten powder and fitted with solid tungsten pinhole inserts. To acquire SPECT and MR data simultaneously, a shielded transmit/receive radio frequency (RF) coil is inserted into the MPH collimator. The insert was evaluated as a standalone SA SPECT system using both a hot-rod resolution phantom (HR-RP) experiment and SA imaging studies. Furthermore, simultaneous SPECT-MR phantom and SA imaging experiments were conducted by placing the SPECT-MR insert inside a 3T clinical MRI system. From acquired experimental data, SPECT images were reconstructed using an in-house developed 3D MPH ML-EM method with pinhole collimator detector response model and compensation. As a standalone SA SPECT system, the insert provided good quality images in phantom and SA studies. The quality of the SPECT images of the HR-RP acquired during the simultaneous SPECT-MR imaging experiment was comparable to the quality of the images acquired during standalone SPECT acquisition. Despite the fact that the SPECT insert degraded the MR image signal-to-noise-ratio (SNR) and caused field distortions, MR imaging was possible within the specific field-of-view of interest. When registered and fused, the SPECT and MR HR-RP images were found to be in acceptable geometric agreement. Data acquired during the simultaneous SPECT-MR SA study was used to obtain a dynamic SPECT image and Time Activity Curve showing initial uptake and later washout of 99mTc MAG3 into and out of a mouses kidneys. Furthermore, a SPECT kidney image was fused with the simultaneously acquired MR image and showed acceptable geometric agreement. Fast dynamic MR imaging was not possible due to severe geometric distortions present when using high speed sequences. These experimental results demonstrate the ability of the insert to obtain SA SPECT dynamic studies and the feasibility of simultaneous SA SPECT-MR imaging. Further engineering improvements remain to be explored to reduce the interaction between the SPECT and MR systems and to eventually enable simultaneous fast dynamic MR studies over the full volume of subject animals.

The design of optimal multipinhole collimators for a seamless SPECT detector ring

The purpose of the study was to systematically design two multipinhole (MPH) collimators for a MR compatible seamless small animal SPECT detector ring (DR) that, for a given system resolution (SR), maximized detector area usage and achieved highest possible geometric efficiency (GE) within the systems design constraints. The SPECT DR consists of 5 rings of 19 2.56×2.56cm2 individual CZT detectors connected seamlessly with a total area of 62,259mm2. A set of multipinhole apertures was arranged on a cylindrical collimator sleeve (CS) and had a common-volume-of-view (CVOV) of 50mm diameter.

A hyaluronic acid binding peptide-polymer system for treating osteoarthritis

Hyaluronic acid (HA) is found naturally in synovial fluid and is utilized therapeutically to treat osteoarthritis (OA). Here, we employed a peptide-polymer cartilage coating platform to localize HA to the cartilage surface for the purpose of treating post traumatic osteoarthritis. The objective of this study was to increase efficacy of the peptide-polymer platform in reducing OA progression in a mouse model of post-traumatic OA without exogenous HA supplementation. The peptide-polymer is composed of an HA-binding peptide (HABP) conjugated to a heterobifunctional poly (ethylene glycol) (PEG) chain and a collagen binding peptide (COLBP). We created a library of different peptide-polymers and characterized their HA binding properties in vitro using quartz crystal microbalance (QCM-D) and isothermal calorimetry (ITC). The peptide polymers were further tested in vivo in an anterior cruciate ligament transection (ACLT) murine model of post traumatic OA. The peptide-polymer with the highest affinity to HA as tested by QCM-D (∼4-fold greater binding compared to other peptides tested) and by ITC (∼3.8-fold) was HABP2-8-arm PEG-COLBP. Biotin tagging demonstrated that HABP2-8-arm PEG-COLBP localizes to both cartilage defects and synovium. In vivo, HABP2-8-arm PEG-COLBP treatment and the clinical HA comparator Orthovisc lowered levels of inflammatory genes including IL-6, IL-1B, and MMP13 compared to saline treated animals and increased aggrecan expression in young mice. HABP2-8-arm PEG-COLBP and Orthovisc also reduced pain as measured by incapacitance and hotplate testing. Cartilage degeneration as measured by OARSI scoring was also reduced by HABP2-8-arm PEG-COLBP and Orthovisc. In aged mice, HABP2-8-arm PEG-COLBP therapeutic efficacy was similar to its efficacy in young mice, but Orthovisc was less efficacious and did not significantly improve OARSI scoring. These results demonstrate that HABP2-8-arm PEG-COLBP is effective at reducing PTOA progression.

Initial evaluation of a state-of-the-art commercial preclinical PET/CT scanner

We performed an initial evaluation of a state-of-the-art commercial preclinical PET/CT scanner (SuperArgus 4R, SEDECAL, Madrid, Spain). The PET unit consists of 4 rings of 96 detector modules each with an array of 338 1.45 × 1.45 × 15 mm3 pixelated LYSO and GSO phoswich crystals with DOI information. It has a maximum axial FOV of 100 mm and transaxial FOV of 120 mm. The CT unit consists of an x-ray source with variable micro focal spot size and a large 229 × 145 mm2 flat-panel detector that allows imaging of a volume-of-view (VOV) at three different magnifications, at a smallest voxel of 15 micron. We measured the sensitivity and uniformity of the PET unit using a calibrated Na-22 point source and a cylindrical phantom filled with a homogeneous FDG solution. The system resolution was determined from the reconstructed images of a thin FDG-filled capillary tube in air and inside a plastic cylinder, and a hot-rod phantom using the FBP and the 3D iterative reconstruction algorithm at different iteration numbers. The uniformity of the CT unit was evaluated from a summed reconstructed image with low statistical image noise of and at three magnifications. The resolution was determined from the edge functions of images of a set of precision-machined acrylic rods of different diameters at three magnifications and with different acquired and reconstructed pixel sizes. The dual-modality image co-registration was assessed using a set of CT and PET images obtained from a phantom consisting of a Ge-68 annulus ring phantom with an attached Na-22 point source. Finally, the preclinical imaging performance of the PET/CT system were evaluated from sample images several small animal studies. Our preliminary results showed the PET unit was able to achieve a system resolution of 0.85 mm and sensitivity of ∼8.9%, and the CT unit a highest resolution of ∼20 micron. We conclude the preclinical PET/CT system meet the stated specifications and is suitable for high performance preclinical molecular imaging of small animals.

Application of post reconstruction dual respiratory and cardiac motion compensation for 4D high-resolution small animal myocardial SPECT

We investigated the performance of a post reconstruction dual respiratory and cardiac (R&C) motion compensation method for improved image quality of 4D cardiac gated small animal myocardial perfusion (MP) SPECT images. A normal mouse was injected with ~8 mCi of Tc-99m sestamibi, anesthetized, fitted with ECG leads for cardiac gating signal acquisition, and placed on top of a pressure gauge bellow for respiratory motion measurements. A 2-hour list-mode dataset was acquired using a MILab small animal SPECT system fitted with a multi-pinhole collimator with 0.4 mm resolution in 5-minute sections. They were subsequently sorted for different acquisition times and reconstructed using a vendor provided OS-EM algorithm with simultaneous 6 respiratory and 8 cardiac equal-time gates over each motion cycle. Using a group-wise B-spline non-rigid image-based registration method, the deformation fields of the respiratory motion (respiratory motion) were estimated and applied to each cardiac phase for respiratory motion correction. Then, the respiratory motion compensated cardiac gated SPECT images were similarly used to estimate cardiac motion (cardiac motion) and later transformed to a reference frame and summed. Finally, the reference frame was inverse-transformed using the estimated cardiac motion to each of the 8 cardiac frames. The cardiac gated images with dual R&C motion compensation were compared to those without correction but with post-smoothing filter. The results showed the dual R&C motion compensation significantly reduced image noise level. At the same time, the image resolution was improved by 10% to 40% depending on the different acquisition times when compared with that obtained without motion compensation at the same image noise level. We conclude that dual R&C motion compensation provides significant reduction of noise level in 4D cardiac gated small animal MP SPECT images with minimum degradation of resolution. The improved image quality can be traded for reduction of acquisition time or radiation dose to the animal.