K.L. Greer

Intracerebral infusion of an EGFR-targeted toxin in recurrent malignant brain tumors

The purpose of this study is to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and intracerebral distribution of a recombinant toxin (TP-38) targeting the epidermal growth factor receptor in patients with recurrent malignant brain tumors using the intracerebral infusion technique of convection-enhanced delivery (CED). Twenty patients were enrolled and stratified for dose escalation by the presence of residual tumor from 25 to 100 ng/ml in a 40-ml infusion volume. In the last eight patients, coinfusion of (123)I-albumin was performed to monitor distribution within the brain. The MTD was not reached in this study. Dose escalation was stopped at 100 ng/ml due to inconsistent drug delivery as evidenced by imaging the coinfused (123)I-albumin. Two DLTs were seen, and both were neurologic. Median survival after TP-38 was 28 weeks (95% confidence interval, 26.5-102.8). Of 15 patients treated with residual disease, two (13.3%) demonstrated radiographic responses, including one patient with glioblastoma multiforme who had a nearly complete response and remains alive >260 weeks after therapy. Coinfusion of (123)I-albumin demonstrated that high concentrations of the infusate could be delivered >4 cm from the catheter tip. However, only 3 of 16 (19%) catheters produced intraparenchymal infusate distribution, while the majority leaked infusate into the cerebrospinal fluid spaces. Intracerebral CED of TP-38 was well tolerated and produced some durable radiographic responses at doses <or=100 ng/ml. CED has significant potential for enhancing delivery of therapeutic macromolecules throughout the human brain. However, the potential efficacy of drugs delivered by this technique may be severely constrained by ineffective infusion in many patients.

Cone beam collimation for single photon emission computed tomography: analysis, simulation, and image reconstruction using filtered backprojection

This paper presents an analysis of two cone beam configurations (having focal lengths of 40 and 60 cm) for the acquisition of single photon emission computed tomography (SPECT) projection data. A three-dimensional filtered backprojection algorithm is used to reconstruct SPECT images of cone beam projection data obtained using Monte Carlo simulations. The mathematical analysis resulted in on-axis point source sensitivities (calculated for a distance of 15 cm from the collimator surface) for cone beam configurations that were 1.4-3 times the sensitivities of parallel-hole and fan beam geometries having similar geometric resolutions. Cone beam collimation offers the potential for improved sensitivity for SPECT devices using large-field-of-view scintillation cameras.

On Bayesian image reconstruction from projections: uniform and nonuniform a priori source information

A method that incorporates a priori uniform or nonuniform source distribution probabilistic information and data fluctuations of a Poisson nature is presented. The source distributions are modeled in terms of a priori source probability density functions. Maximum a posteriori probability solutions, as determined by a system of equations, are given. Interactive Bayesian imaging algorithms for the solutions are derived using an expectation maximization technique. Comparisons of the a priori uniform and nonuniform Bayesian algorithms to the maximum-likelihood algorithm are carried out using computer-generated noise-free and Poisson randomized projections. Improvement in image reconstruction from projections with the Bayesian algorithm is demonstrated. Superior results are obtained using the a priori nonuniform source distribution.

A 3D model of non-uniform attenuation and detector response for efficient iterative reconstruction in SPECT

A 3D physical model for iterative reconstruction in SPECT has been developed and applied to experimental data. The model incorporates non-uniform attenuation using reconstructed transmission CT data and distance-dependent detector response based on response function measurements over a range of distances from the detector. The 3D model has been implemented in a computationally efficient manner with practical memory requirements. The features of the model that provide efficiency are described including a new region-dependent reconstruction (RDR) technique. With RDR, filtered backprojection is used to reconstruct areas of the image of minimal clinical importance, and the result is used to supplement the iterative reconstruction of the clinically important areas of the image. The 3D model was incorporated into the maximum likelihood-expectation maximization (ML-EM) reconstruction algorithm and tested in three phantom studies--a point source, a uniform cylinder, and an anthropomorphic thorax--and a patient 9Tc(m) sestamibi study. Reconstructed images with the 3D method exhibited excellent noise and resolution characteristics. With the sestamibi data, the RDR technique produced essentially the conventional ML-EM estimate in the cardiac region with substantial time savings.

Determination of both mechanical and electronic shifts in cone beam SPECT

The difference between the displacement of the centre of rotation (mechanical shift, MS) and the electronic centring misalignment (electronic shift, ES) in cone beam SPECT is evaluated. A method is proposed to determine both MS and ES using the centroid of a projected point source sampled over 360 degrees and the Marquardt non-linear fitting algorithm. Both shifts are characterized by two orthogonal components. This method is verified using Monte Carlo simulated point source data with different combinations of mechanical and electronic shifts. Both shifts can be determined correctly. We have also applied the proposed method to our cone beam SPECT system to determine both shifts as well as the focal length. The determined ES parameters are then used to correct the projections and the MS parameters are incorporated into a reconstruction algorithm. The point source images are reconstructed and the image resolutions with and without the shift corrections are measured. The experimental results demonstrate that the image resolution is improved after shift corrections. The experimental results also indicate that the shift parameters determined in the same experiment with the point source located at different places are consistent but change from time to time, suggesting that calibration of the system is needed on a periodic basis.

Helical pinhole SPECT for small-animal imaging: a method for addressing sampling completeness

Pinhole collimators are widely used to image small organs and small animals because sensitivity and resolution improve as the distance between the aperture and the object decreases. Axial blurring is present in reconstruction of SPECT projection data when pinhole apertures follow a circular orbit because the object is incompletely sampled. For an object with constant axial extent, the blurring worsens as the radius of rotation (ROR) decreases. In contrast, helical orbits of pinhole collimators can give complete sampling at small ROR, where sensitivity and resolution are improved. Herein, a metric of sampling completeness is introduced. It is used to evaluate the sampling of an object as a function of ROR, axial position, and radial position for circular orbits. The metric is also used to determine the completely sampled volume for a helical orbit of a pinhole aperture. Experimental and computer-simulated projections of circular orbits and helical orbits are reconstructed, yielding similar results; helical orbits reduce axial blurring because of their sampling properties.

Experimentally measured scatter fractions and energy spectra as a test of Monte Carlo simulations

A method for the validation of Monte Carlo photon transport calculations is presented, with particular emphasis on the scatter component of such calculations. The method is based on a quantitative comparison of calculated and experimental scatter fractions. In addition, the method includes a qualitative comparison of point spread functions and energy spectra. An application of the method is demonstrated by comparing the results of an existing Monte Carlo code with experimental results obtained with a gamma camera viewing a point source of 99Tcm (140 keV gamma rays) centred within a water-filled cylinder. The results of the comparisons show good agreement between experiment and calculation. These results allow the code to be used with increased confidence in a variety of situations, and they define more precisely the region of applicability of the code. In addition, the determination of scatter fractions and energy spectra is useful for other applications. For example, scatter fractions can be a useful parameter for evaluating possible techniques for scatter compensation.

Tc-99m attenuation coefficients in water-filled phantoms determined with gamma cameras

Quantitative imaging with gamma cameras requires compensation for attenuation of source photons. Some methods of compensation make use of a constant or average estimated attenuation coefficient mu. A value for mu of 0.15 cm-1 for 140.5-keV photons in water or tissue is commonly used. This value, however, neglects scattered photons which are detected within the energy window in gamma camera imaging. Values for mu of 0.12 cm-1 used in attenuation compensation of Tc-99m single-photon emission computed tomography scans of uniform cylindrical sources have been shown to give improved results compared with use of mu = 0.15 cm-1. In this study, gamma cameras and a multichannel pulse-height analyzer were used to determine effective values of mu for photons in water as a function of energy window. Two cylindrical water-filled phantoms, circular and elliptical, were used with a point source of Tc-99m at depths up to 18 cm. Energy data were integrated over the top half of the photopeak, and over 10%, 20%, and 30% windows centered on the photopeak. Attenuation curves were exponential for all photopeak windows with values of mu of 0.12 +/- 0.014 cm-1 for all windows up to 20% and 0.1 cm-1 for a 30% window. This study suggests that a value of mu of 0.11-0.12 cm-1 is, in fact, appropriate for use in attenuation compensations where an average is required.

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.

Implementation of an accelerated iterative algorithm for cone-beam SPECT

In this paper we describe the implementation of an accelerated iterative reconstruction algorithm (AIRA) for cone-beam (CB) projections using a single circular orbit in single-photon-emission computed tomography (SPECT). This algorithm is a modified maximum-likelihood-expectation-maximization (ML-EM) algorithm and several approaches have been used to accelerate the reconstruction process. These approaches include: (i) the use of ordered subsets; (ii) the use of active areas and volumes; and (iii) the storing in memory of the transition vector for a given ray (during the forward projection step). This algorithm, which compensates for collimator geometric sensitivity variation as a function of position and makes uniform attenuation corrections has been evaluated using experimentally acquired phantom data. The results demonstrate a two-orders-of-magnitude decrease of the computational time of this algorithm over the conventional ML-EM algorithm with similar convergence properties.