[서평]「Component Software」 - Beyond Object-Oriented Programming -

A major advance in biomedical science and diagnosis was accomplished with the development of in vivo techniques to image radiolabeled molecules, but limited spatial resolution has slowed down applications to small experimental animals. Here, we present a SPECT system (U-SPECT-I) dedicated to radionuclide imaging of murine organs at a submillimeter resolution. Methods: The high performance of U-SPECT-I is based on a static triangular detector setup, with a cylindric imaging cavity in the center and 75 gold micropinhole apertures in the cavity wall. The pinholes are focused on a small volume of interest such as the mouse heart or spine to maximize the detection yield of -photons. Three-dimensional molecular distributions are iteratively estimated using the detector data and a statistical reconstruction algorithm that takes into account system blurring and data noise to increase resolution and reduce image noise. Results: With 0.6-mm-diameter pinholes, the maximum fraction of detected photons emitted by a point source (peak sensitivity) is 0.22% for a 15%-wide energy window and remains higher than 0.12% in the central 12 mm of the central plane. In a resolution phantom, radioactively filled capillaries as small as 0.5 mm and separated by 0.5 mm can be distinguished clearly in reconstructions. Projection data needed for the reconstruction of cross sections of molecular distributions in mouse organs can readily be obtained without the need for any mechanical movements. Images of a mouse spine show 99m Tc-hydroxymethylene diphosphonate uptake down to the level of tiny parts of vertebral processes. These are separated clearly from the vertebral and intervertebral foramina. Using another tracer, one can monitor myocardial perfusion in the left and right ventricular walls, even in structures as small as the papillary muscles. Conclusion: U-SPECT-I allows discrimination between molecular concentrations in adjacent volumes of as small as about 0.1 L, which is significantly smaller than can be imaged by any existing SPECT or PET system. Our initial in vivo images of the mouse heart and spine show that U-SPECT-I can be used for novel applications in the study of dynamic biologic systems with a clear projection to clinical applications. The combination of high resolution and detection efficiency of U-SPECT-I opens up new possibilities for the suborgan-level study of radiotracers in mouse models.

https://jnm.snmjournals.org/content/jnumed/46/7/1194.full.pdf

U-SPECT-I: A Novel System for Submillimeter-Resolution Tomography with Radiolabeled Molecules in Mice

Spherically symmetric volume elements with smooth tapering of the values near their boundaries are alternatives to the more conventional voxels for the construction of volume images in the computer. Their use, instead of voxels, introduces additional parameters which enable the user to control the shape of the volume element (blob) and consequently to control the characteristics of the images produced by iterative methods for reconstruction from projection data. For images composed of blobs, efficient algorithms have been designed for the projection and discrete back-projection operations, which are the crucial parts of iterative reconstruction methods. The authors have investigated the relationship between the values of the blob parameters and the properties of images represented by the blobs. Experiments show that using blobs in iterative reconstruction methods leads to substantial improvement in the reconstruction performance, based on visual quality and on quantitative measures, in comparison with the voxel case. The images reconstructed using appropriately chosen blobs are characterized by less image noise for both noiseless data and noisy data, without loss of image resolution.

Practical considerations for 3-D image reconstruction using spherically symmetric volume elements

Molecular imaging refers to the use of non-invasive imaging techniques to detect signals that originate from molecules, often in the form of an injected tracer, and observe their interaction with a specific cellular target in vivo. Differences in the underlying physical principles of these measurement techniques determine the sensitivity, specificity and length of possible observation of the signal, characteristics that have to be traded off according to the biological question under study. Here, we describe the specific characteristics of single photon emission computed tomography (SPECT) relative to other molecular imaging technologies. SPECT is based on the tracer principle and external radiation detection. It is capable of measuring the biodistribution of minute (<10(-10) molar) concentrations of radio-labelled biomolecules in vivo with sub-millimetre resolution and quantifying the molecular kinetic processes in which they participate. Like some other imaging techniques, SPECT was originally developed for human use and was subsequently adapted for imaging small laboratory animals at high spatial resolution for basic and translational research. Its unique capabilities include (i) the ability to image endogenous ligands such as peptides and antibodies due to the relative ease of labelling these molecules with technetium or iodine, (ii) the ability to measure relatively slow kinetic processes (compared with positron emission tomography, for example) due to the long half-life of the commonly used isotopes and (iii) the ability to probe two or more molecular pathways simultaneously by detecting isotopes with different emission energies. In this paper, we review the technology developments and design tradeoffs that led to the current state-of-the-art in SPECT small animal scanning and describe the position SPECT occupies within the matrix of molecular imaging technologies.

https://sernia.ru/upload/pdf_files/Meikle_2006_Small%20animal%20SPECT%20and%20its%20place%20in%20the%20matrix%20of%20molecular%20imaging%20technologies.pdf

Small animal SPECT and its place in the matrix of molecular imaging technologies.

The authors present a novel SPECT imaging technique for small animal research based on multipinhole collimation. This new method is an extension of single-pinhole tomography and combines high resolution with increased system sensitivity. This paper describes the multipinhole imaging system and its preliminary characterization on simulated and measured phantom data.

High-resolution SPECT using multi-pinhole collimation

The objective of this investigation was to evaluate small-field-of-view, ultra-high-resolution pinhole collimation for a rotating-camera SPECT system that could be used to image small laboratory animals. Pinhole collimation offers distinct advantages over conventional parallel-hole collimation when used to image small objects. Since geometric sensitivity increases markedly for points close to the pinhole, small-diameter and high-magnification pinhole geometries may be useful for selected imaging tasks when used with large-field-of-view scintillation cameras. The use of large magnifications can minimize the loss of system resolution caused by the intrinsic resolution of the scintillation camera. A pinhole collimator has been designed and built that can be mounted on one of the scintillation cameras of a triple-head SPECT system. Three pinhole inserts with approximate aperture diameters of 0.6, 1.2 and 2.0 mm have been built and can be mounted individually on the collimator housing. When a ramp filter is used with a three-dimensional (3D) filtered backprojection (FBP) algorithm, the three apertures have in-plane SPECT spatial resolutions (FWHM) at 4 cm of 1.5, 1.9 and 2.8 mm, respectively. In-air point source sensitivities at 4 cm from the apertures are 0.9, 2.6 and 5.7 counts s(-1) microCi(-1) (24, 70 and 154 counts s(-1) MBq(-1)) for the 0.6, 1.2 and 2.0 mm apertures, respectively. In vitro image quality was evaluated with a micro-cold-rod phantom and a micro-Defrise phantom using both the 3D FBP algorithm and a 3D maximum likelihood-expectation maximization (ML-EM) algorithm. In vivo image quality was evaluated using two (315 and 325 g) rats. Ultra-high-resolution pinhole SPECT is an inexpensive and simple approach for imaging small animals that can be used with existing rotating-camera SPECT system.

https://iopscience.iop.org/article/10.1088/0031-9155/39/3/010/pdf

Pinhole collimation for ultra-high-resolution, small-field-of-view SPECT

A 3D physical model for iterative reconstruction in SPECT. has been developed and applied to experimental data. The model incorporates nonuniform 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 99Tcm 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.

http://iopscience.iop.org/article/10.1088/0031-9155/39/3/017/pdf

A 3D model of non-uniform attenuation and detector response for efficient iterative reconstruction in 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. The authors have also applied the proposed method to their 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.

Determination of both mechanical and electronic shifts in cone beam SPECT

An object model based on combinations of object primitives is proposed for Monte Carlo simulated emission and transmission tomographic imaging systems. The primitives include ellipsoids, elliptic cylinders, tapered elliptic cylinders, rectangular solids, and their subsets: half, quarter, and eighth. The probability of a photon surviving interactions with the phantom medium is used as a weight for variance reduction. Calculation of the probability can be computationally intensive without properly organizing the inclusion of subregions within larger regions. A tree data structure is introduced to organize this inclusion relationship and used as the basis for two computationally efficient schemes for determining the intersection locations of a photon path with primitives and for identifying the attenuation coefficients for adjacent intersections for the survival probability computation. The approach has been validated by emission as well as transmission simulations. A thorax phantom containing overlapped ellipsoids and a heart composed of twelve overlapped quarter ellipsoids are employed to demonstrate the capability of the model. >

Solid geometry-based object model for Monte Carlo simulated emission and transmission tomographic imaging systems

The authors propose the use of a single photon emission computed tomography (SPECT) system equipped with multiple cameras which revolve around a vertical axis-of-rotation (VAOR) for prone-dependent (i.e., patient in prone position) breast tumor imaging. This geometry for nuclear medicine breast imaging reduces the amount of attenuating material between the breast tissue and the gamma camera and, in addition, it offers a minimal radius-of-rotation compared to breast imaging using conventional (i.e., 360/spl deg/, horizontal axis-of-rotation) SPECT. The decrease in attenuation and radius-of-rotation results in an increase in detected counts and increased collimator resolution. Because VAOR SPECT systems are currently not commercially available, the authors conducted their experiments on a conventional SPECT system using an isolated breast phantom to investigate the proposed VAOR method. The authors' experimental setup simulated a VAOR SPECT study with a prone-dependent breast in the camera's field-of-view. The results of the experiment indicate that VAOR breast SPECT with Trionix low-energy super-high resolution (LESR) parallel-hole collimation is capable of detecting a breast lesion with an outer diameter of 10 mm and a lesion-to-background concentration ratio of 6-to-1. The results also demonstrate that VAOR breast SPECT provides improved lesion parallel-hole planar imaging (i.e., scintimammography) and breast imaging using horizontal axis-of-rotation SPECT.

Huili Wang

Papers

Pinhole collimation for ultra-high-resolution, small-field-of-view SPECT

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

Determination of both mechanical and electronic shifts in cone beam SPECT

Solid geometry-based object model for Monte Carlo simulated emission and transmission tomographic imaging systems

Prone breast tumor imaging using vertical axis-of-rotation (VAOR) SPECT systems: an initial study