Inactivation of the mouse Huntington's disease gene homolog Hdh.

Huntington's disease (HD) is a dominant neurodegenerative disorder caused by expansion of a CAG repeat in the gene encoding huntingtin, a protein of unknown function. To distinguish between "loss of function" and "gain of function" models of HD, the murine HD homolog Hdh was inactivated by gene targeting. Mice heterozygous for Hdh inactivation were phenotypically normal, whereas homozygosity resulted in embryonic death. Homozygotes displayed abnormal gastrulation at embryonic day 7.5 and were resorbing by day 8.5. Thus, huntingtin is critical early in embryonic development, before the emergence of the nervous system. That Hdh inactivation does not mimic adult HD neuropathology suggests that the human disease involves a gain of function.

Potential value of digital radiography. Preliminary observations on the use of dual-energy subtraction in the evaluation of pulmonary nodules.

The radiographic demonstration of calcification in a solitary pulmonary nodule renders the possibility of malignancy extremely unlikely, although rare exceptions have been reported. Conventional roentgenograms and tomograms sometimes provide inconclusive evidence although CT can be highly accurate in both identifying and quantifying calcium content. An alternative method is dual-energy subtraction utilizing scanned projection digital radiography. Forty-one patients with solitary (occasionally multiple) pulmonary nodules were examined with the technique, employing second-generation fan-beam equipment: 28 nodules or masses were noncalcified and 13 calcified. Of the former, 20 were pathologically proved, 16 being malignant and 4 benign (2 granulomas, 2 bronchiectasis); in 3 of the remaining 8, a presumptive diagnosis was reasonably certain (1 granuloma, 2 metastases), while in 5 the diagnosis was not made. In 8 of the 13 calcified lesions, the diagnosis can reasonably be regarded as confirmed as granulomas; 5 are being followed up with that presumptive diagnosis.

A comparison of dual-energy digital radiography and screen-film imaging in the detection of subtle interstitial pulmonary disease.

An ROC study is described which compares the performance of three types of images--conventional screen-film, single-energy digital and dual energy bone cancelled (soft tissue) digital--in detecting subtle interstitial pulmonary disease. Marginally detectable nodular and reticulonodular patterns (12 different patterns of each) were superimposed over the lungs of a frozen human chest phantom to simulate the clinical situation. The digital images were formatted on film at full size (ie, 35 cm X 43 cm). A total of 156 images (52 of each type, of which 28 were normal and 24 had simulated pathology) were used in the study and read by five experienced chest radiologists. Using a paired t-test, the areas under the individual ROC curves were compared for three combinations of images--single-energy digital and conventional, soft tissue digital and conventional, and soft tissue and single-energy digital. No statistically significant difference was observed between the conventional and single-energy digital images. The readers performed better with both conventional and single-energy digital images than with the soft tissue digital images at statistically significant levels (P = 0.05 for conventional vs. soft tissue digital and P = 0.02 for single-energy digital vs. soft tissue digital). The results suggest that there is no advantage in employing dual-energy soft tissue images to assist in diagnosing interstitial disease in the clinical setting. They also suggest that spatial resolution requirements are less demanding in digital chest systems that obtain scatter-free images than in digital systems utilizing conventional scatter control techniques.

Radiographic mottle: a comprehensive theory.

A comprehensive theory of radiographic density fluctuations is developed. The theory incorporates film granularity, quantum mottle, the absorbed x-ray photon energy distribution, fluctuations in phosphor light photon yield, and phosphor coating weight variations. The resulting expressions allow one to calculate the density fluctuations or, alternatively, the Wiener spectrum that will be obtained with a radiographic screen/film system from the physical parameters of the system. Reasonable agreement is obtained between experimental results and calculated values for three typical screen/film systems. An expression is also derived for the detective quantum efficiency (DQE) of screen/film systems, and the results of DQE calculations are presented for a commonly used screen/film combination as a function of density and of object size.

A method to measure the MTF of digital x-ray systems.

A method has been devised to accurately measure the modulation transfer function (MTF) of digital x-ray systems up to and, for undersampled systems, beyond the pixel Nyquist frequency (fN). A phantom consisting of an array of parallel tungsten or similar wires is imaged, and discrete Fourier transforms of rows of pixel values are computed. Under suitable conditions of phantom orientation, wire diameter, wire spacing, and image magnification, the envelope of the modulus of the mean Fourier transform represents the system MTF. Experimental results extending beyond fN are presented for an undersampled prototype digital chest x-ray system and shown to be in reasonable agreement with predicted values. Employment of the method with other digital imaging modalities [i.e., computerized tomography (CT) scanners and nuclear magnetic resonance (NMR) units] is also discussed as well as error considerations and practical problems in implementing the method.

The design and performance of a scanning multiple slit assembly.

A scanning multiple slit assembly (SMSA) has been constructed for the purpose of reducing scatter in medical radiography. The SMSA consists of a series of long, narrow beam-defining slits above the patient that are aligned and synchronously moved with scatter-eliminating slots beneath the patient during an exposure. Evidence, based on measurements of the ratio of scattered-to-primary radiation imaged and radiographs of patients, is presented indicating that such a device is a practical and efficient method of reducing scatter and improving contrast compared to conventional grids. The design considerations and trade-offs associated with the choice of slit width, slit separation distance, and aft slot depth are discussed along with the effect of these parameters on the SMSA's performance. The various problems encountered in obtaining a uniform scan and the manner in which they were handled are also discussed.

A new type of grid.

A new type of grid is discussed. It is anticipated that it will have the same primary transmission as and will eliminate scatter more efficiently than a conventional linear grid of equal thickness and lead content. The construction of the new type of grid is similar to a conventional one except that the lead strips are arranged in zigzag rather than linear pattern. Geometrically ideal "zigzag" and linear grids were constructed and their performance tested. The scatter transmitted by the ideal zigzag grid was one-half that of the comparable ideal linear grid. The implications regarding the improved scatter-eliminating capabilities of a practical zigzag grid are discussed.

X-ray tube potential, filtration, and detector considerations in dual-energy chest radiography.

The effect of x-ray tube potential and prepatient and interdetector filtration in single exposure dual energy chest imaging has been studied employing a carefully benchmarked model. The analysis utilized published methodology. Noise in simulated lung and mediastinum fields of the aluminum (bone) and Lucite (soft tissue) images were studied at fixed entrance skin exposure (ESE) for commonly employed sandwich detector and sandwich imaging plate configurations. Our results indicate noise in the lung increases slowly with tube potential above 120 kVp, while noise in the mediastinum decreases rapidly. Also, at high tube potential (> or = 120 kVp) adding moderate amounts of prepatient K-edge filtration (approximately equal to 100 mg/cm2) while optimizing imaging conditions for the lung tends to decrease noise in the lungs by approximately equal to 30% while increasing noise in the mediastinum by a similar amount. Without K-edge prepatient filtration, noise in the lung is minimized with Cu interdetector filter weights near 400 mg/cm2. In the mediastinum noise is minimized with heavier interdetector filter and prepatient K-edge filter weights. Prepatient K-edge filter weights that minimize image noise in either field can increase the tube loading by factors ranging from 10 to 10(10). Systems designed with sandwich detectors using commercially available phosphors and coating weights can produce contrast-to-noise ratios (CNRs) as high as 50% of the theoretical limit (defined as an optimized system with a totally absorbing rear detector).

Bone mineral densitometry with x-ray and radionuclide sources: a theoretical comparison.

Two methods of dual-photon absorptiometry (DPA) utilizing an x-ray tube instead of a radionuclide source have recently been introduced. In one method kVp switching is employed and two transmitted intensities at each pixel are determined. In the other method, K-edge filtration combined with a single kVp spectrum is used, but photons in two energy windows are counted. We present a theoretical analysis of the two methods, focusing on a figure of merit which is essentially the exposure efficiency (the precision for a given entrance exposure) and tube loading. We also compare their exposure efficiencies to theoretical limits that no DPA system can exceed. Our study indicates that the K-edge-filtered method is more exposure efficient by about a factor of 2. The switched-kVp method requires less heat units per scan by about a factor of 3. A hybrid K-edge switched-kVp method is suggested which achieves the same exposure efficiency as the K-edge-filtered method at lesser tube loading. Our theoretical model is based on published x-ray spectra and attenuation coefficients and is in good agreement with other simulation work. It is of interest that a point source of Gd-153 would be even more exposure efficient, achieving about 90% of the theoretical limit. However, in practice, the Gd source is of finite size and limited strength, and consequently the radionuclide method cannot achieve as good a precision as either x-ray method in similar scan times.

Signal-to-noise ratio considerations in radiographic imaging.

The methodology employed to calculate radiographic signal-to-noise ratio (SNR) for the commonly used disk-shaped test object is reviewed. Although the "matched" aperture yields the maximum SNR, its shape is difficult to achieve experimentally. On the other hand, a circular aperture having the same size as the object is much simpler to realize. We have performed a numerical analysis of the SNRs obtained with matched and circular apertures for two screen/film systems (a mammographic and a general purpose combination) for a range of test-object sizes. We find that for object sizes greater than 0.5 mm in diameter, there is a less than 4% difference between the SNRs obtained with the two apertures. The shapes of some of the matched apertures are also presented. We conclude that the SNR determined with the circular aperture is a simpler and more useful determinant of system performance for the screen/film combinations studied.

Exposure uniformity considerations in slit radiography.

Slit radiography is a highly efficient means of suppressing scatter. However, when employed with a pulsating x-ray source, a grid line type of artifact results if the movement of the slit is not properly coupled to the periodicity of the source. Taking the exposure of the film to be the convolution of the slit transmittance and the radiation intensity, the conditions for a uniform exposure have been derived for the realistic configuration of a multiple-slit array and a slit transmittance that includes the focal spot and slit geometry. Expressions for the amplitude and spatial frequency of the artifact when the conditions are not met are derived. Methods of suppressing the artifact when its vanishing conditions are not met are also discussed.

Noise correlations in images acquired simultaneously with a dual-energy sandwich detector.

An energy discriminating detector for dual-energy radiography can be configured as a two-layer sandwich, where the mean energy of photons detected by the two layers differs. To characterize the quantum noise of such a detector, the noise covariance between the two layers must be known in addition to the noise variance in each layer. A theory is presented which permits the calculation of the noise covariance, and it is found to be negligibly small. Experimental results, based on measurements with a Na1 sandwich detector and an isotope gamma ray source, are reported and shown to confirm the theory. The quantum noise in each layer is independent and Poisson.

An energy sensitive cassette for dual-energy mammography.

A cassette for simultaneously acquiring dual-energy mammographic images is proposed and studied utilizing a theoretical noise analysis model. The cassette consists of a sandwich of two storage phosphor plates separated by a copper filter. The front, low atomic number, plate was assumed to be comprised of SrFBr and the rear, high atomic number, plate of commercially available BaFBr (98 mg/cm2 coating weight). Assuming a constant x-ray tube voltage of 50 kVp and a typical breast thickness, the theoretical model yielded a front SrFBr phosphor coating weight of approximately 21 mg/cm2. The study indicates that a relatively large separation in the average of x-ray photon energies absorbed in the two plates can be obtained. It also indicates that both a high-quality conventional (single energy) digital image and a tissue canceled digital image (i.e., a calcium image) can be obtained at dose levels comparable to those currently employed. The latter image could potentially improve the early detection of cancerous microcalcifications and also lends itself to computer aided diagnosis.

Slit camera focal spot measurement errors in mammography.

Mammography x-ray tube focal spot sizes are routinely measured during acceptance testing and annual performance audits. The National Electrical Manufactures Association (NEMA) recommends the slit camera for this purpose. Investigated were the effect of slit rotational misalignment, tilt misalignment, image film density, film and screen-film image receptors, microscope magnification and reticule accuracy, and observer variation on slit camera focal spot measurements. Our results indicate that small rotational misalignment (< 5 degrees) and tilt misalignment (< 3 degrees) introduce insignificant error. Measured focal spot size increased slightly with image optical density, indicating that for consistent results the image optical density variations should be minimized. Also desirable for accurate field measurements is a high power microscope (25-50x) and a reticule with divisions of < or = 0.02 mm. Screen-film imaging consistently resulted in a slightly smaller measured focal spot size than direct film. The greatest source of error was due to observer variation. Of interest is that reader variability showed a consistent pattern and variation between two measurements by the same observer was much smaller than between observer variation, suggesting that standardized criteria should be established and a method of reader training developed. The length of the focal spot is defined at a reference axis angle specified by the mammography unit manufacturer. Presented is a tabulation of the focal spot geometry and reference axis angles for the majority of mammography units currently and recently marketed in North America.

Effect of reduced scatter on radiographic information content and patient exposure: a quantitative demonstration.

If a normal screen-film exposure is made using a conventional grid, a reduced exposure may be used with a superior scatter removal device to record the same image information. This theoretical conclusion is not readily demonstrated because of the limited visibility on the underexposed film. In this study radiographs underexposed by a factor of three with a scanning multiple slit assembly (SMSA) were enhanced autoradiographically and found visually to contain more information than properly exposed radiographs obtained under similar conditions using a conventional Bucky grid. This observation was confirmed by contrast scale and noise measurements. Furthermore, the entrance skin exposure of the radiograph using the SMSA was 45% of that required with the grid technique at the same beam quality.

Performance characteristics of a dual-energy detector for digital scan projection radiography.

An energy discriminating x-ray detector has been developed for dual-energy, scan projection digital radiography. The detector is comprised of a pair of x-ray intensifying screen/linear photodiode arrays, aligned one behind the other. Energy discrimination is achieved by employing a low atomic number phosphor in the front screen and a high atomic number phosphor in the back screen. The x-ray response, modulation transfer function, and defective quantum efficiency of the detector are reported along with the experimental methodology utilized for the measurements. Also presented is an analysis which indicates that in a typical patient's lung field, the detector can resolve the projected density (g/cm2) of a 3-mm-thick, 1-cm2 area of bone to better than 1.5%.

Experimental measurements of the scatter reduction obtained in mammography with a scanning multiple slit assembly.

A nonconventional and sensitive method of measuring scatter is described. The method was employed to quantitate the scatter imaged in mammography with a conventional unit, a unit equipped with a grid, and a unit equipped with a scanning multiple slit assembly (SMSA). The results indicate that the grid technique significantly reduces the scatter imaged, while the SMSA virtually eliminates it. The resultant increase in large area contrast is readily apparent on radiographs with greater improvement obtained with the SMSA than with the grid. The effect of the increase in contrast on small detail visibility was assessed with a phantom having simulated fibrils and calcifications. Significantly more fibril and calcification detail was visible with the grid and SMSA technique than with the conventional technique. The detail visible with the grid and SMSA technique was comparable, and the lack of better performance by the SMSA unit is attributed to its poorer MTF.

Molybdenum target x-ray spectra: a semiempirical model.

A semiempirical model for generating molybdenum target x-ray spectra is presented. The model is an extension of a previous model developed by the authors for tungsten and takes into account the depth of production for both bremsstrahlung and characteristic x-ray photons. As in the previous work, the optimal model parameters were determined using nonlinear least-squares fits to experimental data. Good agreement between the two was obtained. By varying target angle, off-axis angle, and filtration in the model in accordance with the x-ray tube and geometry of interest, results consistent with tabulated spectra for different conditions have been obtained.

Assessing fluoroscopic contrast resolution: a practical and quantitative test tool.

Fluoroscopic contrast resolution is commonly determined at a specified kVp by imaging a test object comprised of targets where contrast decreases gradually and sequentially. Threshold contrast or contrast resolution is the contrast of the lowest contrast target that can be perceived. This approach suffers from two problems. First, test object contrast is specified at a x-ray tube voltage that is not always obtainable in practice. Second, the small change in contrast between adjacent targets contributes to observer variability making consistent and reproducible contrast threshold determinations difficult. Described is a contrast resolution test tool that eliminates or reduces these problems. The novel target arrangement allows one to quickly and easily specify the contrast resolution of a fluoroscopic imaging chain to a precision approximately equal to 0.5%. Tables of target contrast versus x-ray tube potential are developed that permit one to employ the test object for contrast resolution determination over the normal range of tube potentials encountered on clinical units.

Semiempirical model for generating tungsten target x-ray spectra.

A semiempirical model for generating tungsten target x-ray spectra is presented. This model extends earlier work in two significant areas. First, both bremsstrahlung and characteristic x-ray production are assumed to occur at varying depths within the target. Second, optimal parameters for the model were determined from experimental spectra utilizing nonlinear least-squares techniques. As a result, good agreement is obtained between calculated and measured x-ray tube spectra and output for different target angles and a wide range of x-ray tube potentials. Such is not the case with previously published models.