Design and development of the DE-SPECT system: a clinical SPECT system for broadband multi-isotope imaging of peripheral vascular disease.

Objective. Peripheral Vascular Disease (PVD) affects more than 230 million people worldwide and is one of the leading causes of disability among people over age 60. Nowadays, PVD remains largely underdiagnosed and undertreated, and requires the development of tailored diagnostic approaches. We present the full design of the Dynamic Extremity SPECT (DE-SPECT) system, the first organ-dedicated SPECT system for lower extremity imaging, based on 1 cm thick Cadmium Zinc Telluride (CZT) spectrometers and a dynamic dual field-of-view (FOV) synthetic compound-eye (SCE) collimator.Approach. The proposed DE-SPECT detection system consists of 48 1 cm thick 3D-position-sensitive CZT spectrometers arranged in a partial ring of 59 cm in diameter in a checkerboard pattern. The detection system is coupled with a compact dynamic SCE collimator that allows the user to select between two different FOVs at any time during an imaging study: a wide-FOV (28 cm diameter) configuration for dual-leg or scout imaging or a high-resolution and high-sensitivity (HR-HS) FOV (16 cm diameter) for single-leg or focused imaging.Main results.The preliminary experimental data show that the CZT spectrometer achieves a 3D intrinsic spatial resolution of <0.75 mm FWHM and an excellent energy resolution over a broad energy range (2.6 keV FWHM at 218, 3.3 keV at 440 keV). From simulations, the wide-FOV configuration offers a 0.034% averaged sensitivity at 140 keV and <8 mm spatial resolution, whereas the HR-HS configuration presents a peak central sensitivity of 0.07% at 140 keV and a ∼5 mm spatial resolution. The dynamic SCE collimator enables the capability to perform joint reconstructions that would ensure an overall improvement in imaging performance.Significance. The DE-SPECT system is a stationary and high-performance SPECT system that offers an excellent spectroscopic performance with a unique computer-controlled dual-FOV imaging capability, and a relatively high sensitivity for multi-tracer and multi-functional SPECT imaging of the extremities.

Determining the effect of cardiac blood volume on accuracy of uptake rate constants by simulation.

Objective. There is great interest in better understanding coronary microvascular disease using mouse models. Typical quantification requires dynamic imaging to estimate the rate constantK1of the tracer moving from the blood into the myocardium. In addition toK1, it is also desirable to determine blood volume fractionV, which if known allows for more accurate fitting ofK1. Our previously published kinetic modeling software did not consider the effect ofV. To ensure a better fit of experimental data to the model for myocardialµSPECT imaging, in this work we updated our kinetic modeling software to include a blood volume fractionV, which adds a fraction of the arterial activity concentration into the tissue concentration.Approach. The tissue and blood time-activity curves (TACs) used for fit input were generated using ideal equations with known values in MATLAB. This allowed post-fit results to be compared to known values to determine fit errors. Parameters that were varied in generating the TACs included blood volume fraction (0, 0.05, 0.1, 0.2 and 0.3),K1(0.5, 1.5, 2.5 ml min-1g-1), frame length (1, 2, 5, 10, 15, 20 s), FWHM of the input Gaussian (10, 20, 40 s), and time of the injection peak relative to frame duration. Blood volume-fraction results have low error when blood volume is lowest, but results worsen as frame length andK1increase.Main results. We demonstrated that blood volume can be accurately determined, and also show how fit accuracy varies across TACs with different input properties.Significance. This information allows for robust use of the fitting algorithm and aids in understanding fit performance when used in animal studies.

Development and feasibility of quantitative dynamic cardiac imaging for mice using µSPECT.

BACKGROUND: Despite growing interest in coronary microvascular disease (CMVD), there is a dearth of mechanistic understanding. Mouse models offer opportunities to understand molecular processes in CMVD. We have sought to develop quantitative mouse imaging to assess coronary microvascular function. METHODS: We used 99mTc-sestamibi to measure myocardial blood flow in mice with MILabs U-SPECT+ system. We determined recovery and crosstalk coefficients, the influx rate constant from blood to myocardium (K1), and, using microsphere perfusion, constraints on the extraction fraction curve. We used 99mTc and stannous pyrophosphate for red blood cell imaging to measure intramyocardial blood volume (IMBV) as an alternate measure of microvascular function. RESULTS: The recovery coefficients for myocardial tissue (RT) and left ventricular arterial blood (RA) were 0.81 ± 0.16 and 1.07 ± 0.12, respectively. The assumption RT = 1 - FBV (fraction blood volume) does not hold in mice. Using a complete mixing matrix to fit a one-compartment model, we measured K1 of 0.57 ± 0.08 min-1. Constraints on the extraction fraction curve for 99mTc-sestamibi in mice for best-fit Renkin-Crone parameters were α = 0.99 and ß = 0.39. Additionally, we found that wild-type mice increase their IMBV by 22.9 ± 3.3% under hyperemic conditions. CONCLUSIONS: We have developed a framework for measuring K1 and change in IMBV in mice, demonstrating non-invasive µSPECT-based quantitative imaging of mouse microvascular function.

Effect of pinhole shape on projection resolution.

We are designing a dual-resolution pre-clinical SPECT system based on square-pinhole apertures for use in applications with a small field-of-view (FOV), such as cardiac imaging of mice. Square pinholes allow for increased sensitivity due to more efficient projection tiling on the detector compared to circular pinholes. Aperture fabrication techniques cannot produce a perfect square, giving the square pinholes some amount of roundedness at the corners. This work investigates how this roundedness affects the physical properties of projection images in terms of spatial resolution. Different pinhole full-acceptance angles and roundedness values were simulated. To facilitate a fair comparison, properties of the non-square pinholes were manipulated to yield pinholes with approximately the same sensitivity (to within 0.1%) and FOV (to within 0.5%) as those of the square pinholes, subsequently referred to as matched apertures. The aperture size (flat-to-flat edge length) of each non-square aperture was increased until its sensitivity was approximately equal to that of the square pinhole. Next, the full acceptance angle was increased until the FOV of each non-square aperture was approximately equivalent to that of the square pinhole. Sensitivity was calculated to include both the geometric and penetrative sensitivity of a point source, as well as the packing faction of the multi-pinhole collimator. Using the sensitivity-matched and FOV-matched apertures, spatial resolution was estimated. For the 0.3 mm, 0.5 mm, and 1 mm edge-length square apertures studied, the full-width at half-maximum widened as pinhole shape changed from square to circle, while full-width tenth-maximum showed little change. These results indicate that a perfect square pinhole shape is more desirable than a rounded-square pinhole with regard to spatial resolution when sensitivity and FOV-matched pinholes are compared.

Evaluation of image reconstruction for mouse brain imaging with synthetic collimation from highly multiplexed SiliSPECT projections.

We have performed a theoretical study to explore the potential and limitations of synthetic collimation for SPECT imaging with stacked-detector acquisition (dual magnification). This study will be used to optimize SiliSPECT, a small-animal SPECT for imaging small volumes such as a mouse brain at high sensitivity and resolution. The synthetic collimation enables image reconstruction with a limited number of camera views and in the presence of significant multiplexing. We also developed a new formulation to quantify the multiplexed object sensitivity and investigated how this changes for different acquisition parameters such as number of pinholes and combinations of front and back detector distances for imaging objects as small as the mouse brain. In our theoretical studies, we were not only able to demonstrate better reconstruction results by incorporating two detector magnifications in comparison to either one alone, but also observed an improved image reconstruction by optimizing the detector-collimator distances to change the multiplexing ratio between the front and back detectors.

Multi-pinhole collimator design for small-object imaging with SiliSPECT: a high-resolution SPECT.

We have designed a multi-pinhole collimator for a dual-headed, stationary SPECT system that incorporates high-resolution silicon double-sided strip detectors. The compact camera design of our system enables imaging at source-collimator distances between 20 and 30 mm. Our analytical calculations show that using knife-edge pinholes with small-opening angles or cylindrically shaped pinholes in a focused, multi-pinhole configuration in combination with this camera geometry can generate narrow sensitivity profiles across the field of view that can be useful for imaging small objects at high sensitivity and resolution. The current prototype system uses two collimators each containing 127 cylindrically shaped pinholes that are focused toward a target volume. Our goal is imaging objects such as a mouse brain, which could find potential applications in molecular imaging.

Derivation and validation of a sensitivity formula for slit-slat collimation.

An analytic formula is derived for the sensitivity of collimators achieving transverse collimation with a slit and axial collimation with a slat assembly whose septa may be parallel or focus on a line. The formula predicts sin(3) phi dependence on the incidence angle and, in the particular case of parallel slats, 1/h dependence on the distance from the slit. More complex expressions for sensitivity that do not diverge at points near the slit or the focal line of the slat assembly are also derived. The predictions of the formulas are checked against simple cases for which solutions are available from direct calculation as well as against Monte Carlo simulation and published experimental data. Agreement is good in all cases analyzed. An approximate penetration model is also introduced: it involves the use of a sensitivity-effective slit width and septal length. Its predictions are compared to simulation results. Agreement was found to be compatible with statistical fluctuation (+/- 0.3%) for geometric sensitivity and better than 3% of total sensitivity in the worst case of septa designed for high-energy (364.5 keV) photons.

Verification of the sensitivity and resolution dependence on the incidence angle for slit-slat collimation.

Single photon emission computed tomography (SPECT) can be performed with various collimator types, which have an inherent tradeoff between the properties of sensitivity, resolution, field of view and complete sampling. Slit-slat collimation, which has seen recent interest in the literature, combines a slit parallel to the axis of rotation of a gamma camera with a set of septa perpendicular to the slit. This collimator geometry exhibits properties that may enhance some SPECT imaging applications, specifically imaging of the breast, limbs and medium-sized animals. However, a complete description of its system response is critical for a comparison to other collimator types and for accurate reconstruction of projection data. Herein, experimental and Monte Carlo methods are used to determine the sensitivity and transaxial and axial resolutions as a function of the incidence angle theta, which is the angle formed by the line from the photon source to the center of the slit and the plane of the slit, to compare to theoretical expectations. Four configurations are investigated by varying the slit width, septal spacing and septal height. Monte Carlo sensitivity data not modeling penetration and scatter exhibit a sin(3)theta dependence. Experimental and Monte Carlo-derived sensitivity data modeling scatter and penetration are consistent with each other and have a sin(x)theta dependence, where x is greater than 3. Transaxial resolution data show a small dependence on theta, and axial resolution data are consistent with no angular dependence.

Non-diverging analytic expression for the on-axis sensitivity of converging collimators: analytic derivation.

The expressions for the sensitivity of converging collimators found in the literature diverge at points near the focal locus of the collimator. In this paper, an analytical formula that does not diverge is derived and compared to that available in the literature. An analysis is provided to predict the cases in which use of the new formula is advisable. Since the first expression derived is rather complex, approximations were made to reach simpler formulae. The formulae derived can be used to define and extend the realm of applicability of the literature expression in the cases identified in their derivation.

Non-diverging analytic expression for the on-axis sensitivity of converging collimators: experimental verification.

The previous paper presented the derivation of an analytical formula for the sensitivity of converging collimators that does not diverge at the focal locus of the collimator. Its predictions, those from a simplified version, and those from the most commonly referenced formula are compared to Monte Carlo and experimental data. Agreement is excellent for all formulae far from the focal locus of the collimator, where it is markedly better for the new formula and its approximation. It is inferred that such formulae should be used in the cases identified by theory, namely around the focal locus of collimators of any focal length and over a substantial part of the field-of-view for short focal length collimators.

Resolution- versus sensitivity-effective diameter in pinhole collimation: experimental verification.

To account for photon penetration, the formulae used to calculate the geometric resolution of a pinhole collimator use an effective diameter d(e) rather than the physical diameter of the aperture. The expressions commonly used for d(e), however, were originally derived to include penetration in sensitivity calculations. To predict the full width at half maximum (FWHM) resolution of the point-spread function (PSF) of a knife-edge pinhole collimator, we have previously proposed simple expressions for a resolution-effective diameter d(re). Unlike those for d(e), expressions for d(re) predict both a dependence on the polar angle of the source (theta) and a non-isotropic PSF. In this paper, the new theory was tested by measuring experimentally the FWHM of the PSF. Results confirm the theoretical predictions that (a) d(re) provides the best estimates of the experimental FWHM as a function of theta and of the direction in the plane of the pinhole, (b) Paix's expression for d(e) tends to overestimate the FWHM, (c) Anger's is a better approximation, but still cannot predict the dependence on theta, and (d) the FWHM decreases with decreasing theta, i.e. resolution improves for sources at the edge of the field-of-view.

Molecular imaging of small animals with a triple-head SPECT system using pinhole collimation.

Pinhole collimation yields high sensitivity when the distance from the object to the aperture is small, as in the case of imaging small animals. Fine-resolution images may be obtained when the magnification is large since this mitigates the effect of detector resolution. Large magnifications in pinhole single-photon emission computed tomography (SPECT) may be obtained by using a collimator whose focal length is many times the radius of rotation. This may be achieved without truncation if the gamma camera is large. We describe a commercially available clinical scanner mated with pinhole collimation and an external linear stage. The pinhole collimation gives high magnification. The linear stage allows for helical pinhole SPECT. We have used the system to image radiolabeled molecules in phantoms and small animals.

Determination of mechanical and electronic shifts for pinhole SPECT using a single point source.

The effects of uncompensated electronic and mechanical shifts may compromise the resolution of pinhole single photon emission computed tomography. The resolution degradation due to uncompensated shifts is estimated through simulated data. A method for determining the transverse mechanical and axial electronic shifts is described and evaluated. This method assumes that the tilt of the detector and the radius of rotation (ROR) are previously determined using another method. When this assumption is made, it is possible to determine the rest of the calibration parameters using a single point source. A method that determines the electronic and mechanical shifts as well as the tilt has been previously described; this method requires three point sources. It may be reasonable in most circumstances to calibrate tilt much less frequently than the mechanical shifts since the tilt is a property of the scanner whereas the mechanical shift may change every time the collimator is replaced. An alternative method for determining the ROR may also be used. Lastly, we take the view that the transverse electronic shift and the focal length change slowly and find these parameters independently.

Analytic determination of the pinhole collimator's point-spread function and RMS resolution with penetration.

Pinhole collimators are widely used to image small organs and animals. The pinhole response function (PRF) of knife-edge pinhole collimators has been estimated previously using geometric constructions without considering penetration and using "roll-off" models that employ an exponential model for the flux. An analytic expression for the PRF on the imaging plane that includes the effect of aperture penetration is derived in this paper by calculating the flux for photons passing through the aperture and those passing through the attenuating material. The PRF is then used to approximate the angular-dependent root-mean-square resolution in the directions parallel and perpendicular to the tilt of the point source. The corresponding aspect ratio is then obtained. The formulas are then compared with experimental data.

Analytic determination of pinhole collimator sensitivity with penetration.

Pinhole collimators are widely used to image small organs and animals. The sensitivity of knife-edge pinhole collimators has been previously estimated using an "effective diameter" formulation and experimentally described using a sin(x) theta fit, where theta is the angle between the line segment from the center of the aperture to the photon source and its projection onto the plane of the aperture. An analytic form of the sensitivity of the pinhole collimator is derived in this paper. A numerical formula for predicting the sin(x) theta form of the sensitivity is calculated from the analytic form. Experimental data are compared with the theoretical estimate and the sin(x) theta prediction. The agreement is excellent.