We have combined photochemistry and photolithography with solid‐phase DNA synthesis chemistry to form a new technology that makes high density oligonucleotide probe array synthesis possible. Hybridization to these two‐dimensional arrays containing hundreds or thousands of oligonucleotide probes provides a powerful DNA sequence analysis tool. Two types of light‐generated DNA probe arrays have been used to test for a variety of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. One array, made up of 428 probes, was designed to scan through the length of CFTR exon 11 and identify differences from the wild type reference sequence. The second type of array contained 1480 probes chosen to detect known deletions, insertions, or base substitution mutations. The validity of the probe arrays was established by hybridizing them with fluorescently labeled control oligonucleotide targets. Characterized mutant CFTR genomic DNA samples were then used to further test probe array hybridization specificity. Finally, ten unknown patient samples were genotyped using the CFTR probe array assay. The genotype assignments were identical to those obtained by PCR product restriction fragment analysis. Our results show that light‐generated DNA probe arrays are highly effective in analyzing complex mutation and polymorphism patterns in a relatively large gene such as CFTR. © 1996 Wiley‐Liss, Inc.

X-ray detectors in clinical computed tomography (CT) usually operate in current-integrating mode. Their complicated signal statistics often lead to intractable likelihood functions for practical use in model-based image reconstruction (MBIR). It is therefore desirable to design simplified statistical models without losing the essential factors. Depending on whether the CT transmission data are logarithmically transformed, pre-log and post-log models are two major categories of choices in CT MBIR. Both being approximations, it remains an open question whether one model can notably improve image quality over the other on real scanners. In this study, we develop and compare several pre-log and post-log MBIR algorithms under a unified framework. Their reconstruction accuracy based on simulation and clinical datasets are evaluated. The results show that pre-log MBIR can achieve notably better quantitative accuracy than post-log MBIR in ultra-low-dose CT, although in less extreme cases, post-log MBIR with handcrafted pre-processing remains a competitive alternative. Pre-log MBIR could play a growing role in emerging ultra-low-dose CT applications.

A TV minimization strategy incorporated into commonly used PET reconstruction algorithms was useful for reducing the occurrence of artifacts due to gaps between detector modules in small-diameter PET scanners.

The spatial resolution from Compton cameras suffers from measurement uncertainties in interaction positions and energies. The degree of degradation in spatial resolution is shift-variant (SV) over the field-of-view (FOV) because the imaging principle is based on the conical surface integration. In our study, the shift-variant point spread function (SV-PSF) is derived from point source measurements at various positions in the FOV and is incorporated into the system matrix of a fully three-dimensional, accelerated reconstruction, i.e. the listmode ordered subset expectation maximization (LMOSEM) algorithm, for resolution recovery. Simulation data from point sources were used to estimate SV and asymmetric parameters for Gaussian, Cauchy, and general parametric PSFs. Although little difference in the fitness accuracy between Gaussian and general parametric PSFs was observed, the general parametric model showed greater flexibility over the FOV in shaping the curve between that for Gaussian and Cauchy functions. The estimated asymmetric SV-PSFs were incorporated into the LMOSEM for resolution recovery. For simulation data from a single point source at the origin, all LMOSEM-SV-PSFs improved the spatial resolution by 2.6 times over the standard LMOSEM. For two point-source simulations, reconstructions also gave a two-fold improvement in spatial resolution and resulted in a greater recovered activity ratio at different positions in the FOV.

Although the ordered subset expectation maximization (OSEM) algorithm does not converge to a true maximum likelihood solution, it is known to provide a good solution if the projections that constitute each subset are reasonably balanced. The Compton scattered data can be allocated to subsets using scattering angles (SA) or detected positions (DP) or a combination of the two (AP (angles and positions)). To construct balanced subsets, the data were first arranged using three ordering schemes: the random ordering scheme (ROS), the multilevel ordering scheme (MLS) and the weighted-distance ordering scheme (WDS). The arranged data were then split into J subsets. To compare the three ordering schemes, we calculated the coefficients of variation (CVs) of angular and positional differences between the arranged data and the percentage errors between mathematical phantoms and reconstructed images. All ordering schemes showed an order-of-magnitude acceleration over the standard EM, and their computation times were similar. The SA-based MLS and the DP-based WDS led to the best-balanced subsets (they provided the largest angular and positional differences for SA- and DP-based arrangements, respectively). The WDS exhibited minimum CVs for both the SA- and DP-based arrangements (the deviation in mean angular and positional differences between the ordered subsets was smallest). The combination of AP and WDS yielded the best results with the lowest percentage errors by providing larger and more uniform angular and positional differences for the SA and DP arrangements, and thus, is probably optimal Compton camera reconstruction using OSEM.

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We have combined photochemistry and photolithography with solid-phase DNA synthesis chemistry to form a new technology that makes high density oligonucleotide probe array synthesis possible. Hybridization to these two-dimensional arrays containing hundreds or thousands of oligonucleotide probes provides a powerful DNA sequence analysis tool. Two types of light-generated DNA probe arrays have been used to test for a variety of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. One array, made up of 428 probes, was designed to scan through the length of CFTR exon 11 and identify differences from the wild type reference sequence. The second type of array contained 1480 probes chosen to detect known deletions, insertions, or base substitution mutations. The validity of the probe arrays was established by hybridizing them with fluorescently labeled control oligonucleotide targets. Characterized mutant CFTR genomic DNA samples were then used to further test probe array hybridization specificity. Finally, ten unknown patient samples were genotyped using the CFTR probe array assay. The genotype assignments were identical to those obtained by PCR product restriction fragment analysis. Our results show that light-generated DNA probe arrays are highly effective in analyzing complex mutation and polymorphism patterns in a relatively large gene such as CFTR.

The Compton camera can provide 3-D images of radioactive material distribution based on a single measurement at a fixed position. The Compton camera also can image several different kinds of radioactive materials simultaneously, by means of the "multitracing" capability. In the present study, this multitracing capability was tested for a double-scattering-type Compton camera, or Double-Scattering Compton Imager (DOCI), which utilizes two double-sided silicon strip detectors (DSSDs) and one NaI(Tl) scintillation detector. Our experimental result shows that the 137 Cs and 60 Co gamma sources can be clearly distinguished in 2-D and 3-D Compton images, and that there is no significant interference between the two gamma sources. The imaging resolutions were determined to be 6.2 and 4.7 mm FWHM for the 137 Cs (662 keV) and 60 Co (1332 keV) point sources at 4 cm, respectively. The angular resolutions, determined from the angular resolution measure (ARM) distributions, were 7.3 and 6.5 for the source energies of 662 and 1332 keV, respectively. The DOCI remains under development; its imaging resolution will be further improved with the incorporation of more sophisticated detectors and the related electronics, including a faster scintillation detector (LYSO) and higher-spatial-resolution position-sensitive detectors.