Reproducibility of liver iron concentration estimates in MRI through R2* measurement determined by least-squares curve fitting.

Measuring transverse relaxation rate (R2* = 1/T2*) via MRI allows for noninvasive evaluation of multiple clinical parameters, including liver iron concentration (LIC) and fat fraction. Both fat and iron contribute to diffuse liver disease when stored in excess in the liver. This liver damage leads to fibrosis and cirrhosis with an increased risk of developing hepatocellular carcinoma. Liver iron concentration is linearly related to R2* measurements using MRI. A phantom was constructed to assess R2* quantification variability on 1.5 and 3 T MRI systems. Quantification was executed using least-squares curve fitting techniques. The phantom was created using readily available, low-cost materials. It contains four vials with R2* values that cover a clinically relevant range (100 to 420 Hz at 1.5 T). Iron content was achieved using ferric chloride solutions contained in glass vials, each affixed in a three-dimensional (3D)-printed polylactide (PLA) structure, surrounded by distilled water, all housed in a sealed acrylic cylinder. Multiple phantom stands were also 3D-printed using PLA for precise orientation of the phantom with respect to the direction of the static magnetic field. Acquisitions at different phantom angles, across multiple MRI systems, and with different pulse sequence parameters were evaluated. The variability between any two R2* measurements, taken in the same vial under these various acquisition conditions, on a 1.5 T MRI system, was <7% for each of the four vials. For 3 T MRI systems, variability was less than 14% in all cases. Variability was <6% for both 1.5 and 3 T acquisitions when unchanged pulse sequence parameters were used. The phantom can be used to mimic a range of clinically relevant levels of R2* relaxation rates, as measured using MRI. These measurements were found to be reproducible relative to the gold-standard method, liver biopsy, across several different image acquisition conditions.

Realistic phantoms to characterize dosimetry in pediatric CT.

BACKGROUND: The estimation of organ doses and effective doses for children receiving CT examinations is of high interest. Newer, more realistic anthropomorphic body models can provide information on individual organ doses and improved estimates of effective dose. MATERIALS AND METHODS: Previously developed body models representing 50th-percentile individuals at reference ages (newborn, 1, 5, 10 and 15 years) were modified to represent 10th, 25th, 75th and 90th height percentiles for both genders and an expanded range of ages (3, 8 and 13 years). We calculated doses for 80 pediatric reference phantoms from simulated chest-abdomen-pelvis exams on a model of a Philips Brilliance 64 CT scanner. Individual organ and effective doses were normalized to dose-length product (DLP) and fit as a function of body diameter. RESULTS: We calculated organ and effective doses for 80 reference phantoms and plotted them against body diameter. The data were well fit with an exponential function. We found DLP-normalized organ dose to correlate strongly with body diameter (R2>0.95 for most organs). Similarly, we found a very strong correlation with body diameter for DLP-normalized effective dose (R2>0.99). Our results were compared to other studies and we found average agreement of approximately 10%. CONCLUSION: We provide organ and effective doses for a total of 80 reference phantoms representing normal-stature children ranging in age and body size. This information will be valuable in replacing the types of vendor-reported doses available. These data will also permit the recording and tracking of individual patient doses. Moreover, this comprehensive dose database will facilitate patient matching and the ability to predict patient-individualized dose prior to examination.

Patient-specific dose calculations for pediatric CT of the chest, abdomen and pelvis.

BACKGROUND: Organ dose is essential for accurate estimates of patient dose from CT. OBJECTIVE: To determine organ doses from a broad range of pediatric patients undergoing diagnostic chest-abdomen-pelvis CT and investigate how these relate to patient size. MATERIALS AND METHODS: We used a previously validated Monte Carlo simulation model of a Philips Brilliance 64 multi-detector CT scanner (Philips Healthcare, Best, The Netherlands) to calculate organ doses for 40 pediatric patients (M:F = 21:19; range 0.6-17 years). Organ volumes and positions were determined from the images using standard segmentation techniques. Non-linear regression was performed to determine the relationship between volume CT dose index (CTDIvol)-normalized organ doses and abdominopelvic diameter. We then compared results with values obtained from independent studies. RESULTS: We found that CTDIvol-normalized organ dose correlated strongly with exponentially decreasing abdominopelvic diameter (R(2) > 0.8 for most organs). A similar relationship was determined for effective dose when normalized by dose-length product (R(2) = 0.95). Our results agreed with previous studies within 12% using similar scan parameters (e.g., bowtie filter size, beam collimation); however results varied up to 25% when compared to studies using different bowtie filters. CONCLUSION: Our study determined that organ doses can be estimated from measurements of patient size, namely body diameter, and CTDIvol prior to CT examination. This information provides an improved method for patient dose estimation.

Phase-contrast digital tomosynthesis.

PURPOSE: Phase-contrast (PC) edge enhancement occurs at the boundary between different tissues and is an interference effect that results from the differential phase-shifts that the x-rays acquire while traversing the two tissues. While observable in planar phase-contrast radiographs, the impact of digital tomosynthesis on this edge enhancement effect has not been previously reported. The purpose of this work is to demonstrate: (1) that phase-contrast digital tomosynthesis (PC-DTS) is possible with a conventional x-ray source, (2) that the reconstructed tomosynthesis images demonstrate and retain edge enhancement as compared to planar phase-contrast radiographs and (3) tomosynthesis improves object contrast by reducing the effects of superimposed structures. METHODS: An unmodified, commercially available cabinet x-ray system (Faxitron LX-60) was used. The system contains a tungsten anode x-ray tube that was operated at 24 kVp and 3 mAs for each PC radiographic image taken, with a nominal focal spot size of 0.010 mm. The digital detector uses CsI/CMOS with a pixel size of 0.054 mm x 0.054 mm. Objects to be imaged were attached to a computer-controlled rotating motor and are rotated +/- 25 degrees about a central position in one degree increments. At each increment, three phase-contrast radiographs are taken and then averaged to reduce the effect of noise. These planar images are then used to reconstruct a series of 56 longitudinal tomographic images with an image offset increment of about 0.7 mm. RESULTS: Tomographic z-plane resolution was measured to be approximately 4 mm. When compared to planar PC images, the tomosynthesis images were shown to retain the PC boundary edge enhancement in addition to an improvement in object contrast. CONCLUSIONS: Our work demonstrates that PC digital tomosynthesis retains the edge-enhancement observed in planar PC radiograph and further improves soft-tissue conspicuity by reducing the effects of superimposed tissue structure.

Polychromatic phase-contrast computed tomography.

Polychromatic phase-contrast radiography differs from traditional (absorption-only) radiography in that the method requires at least a partially coherent x-ray source and the resulting images contain information about the phase shifts of x-rays in addition to the traditional absorption information. In a typical embodiment, this effect results in a measurable enhancement in image contrast at the edges of objects. In this study, a phase-contrast imaging system was adapted to allow an object to be imaged at multiple projections, and these projections were used to generate phase-contrast computed tomography images. The images obtained with this technique show edge enhancements surrounding the objects within the image.

Accounting for signal loss due to dephasing in the correction of distortions in gradient-echo EPI via nonrigid registration.

Gradient-echo (GE) echo planar imaging (EPI) is susceptible to both geometric distortions and signal loss. This paper presents a retrospective correction approach based on nonrigid image registration. A new physics-based intensity correction factor derived to compensate for intravoxel dephasing in GE EPI images is incorporated into a previously reported nonrigid registration algorithm. Intravoxel dephasing causes signal loss and thus intensity attenuation in the images. The new rephasing factor we introduce, which changes the intensity of a voxel in images during the registration, is used to improve the accuracy of the intensity-based nonrigid registration method and mitigate the intensity attenuation effect. Simulation-based experiments are first used to evaluate the method. A magnetic resonance (MR) simulator and a real field map are used to generate a realistic GE EPI image. The geometric distortion computed from the field map is used as the ground truth to which the estimated nonrigid deformation is compared. We then apply the algorithm to a set of real human brain images. The results show that, after registration, alignment between EPI and multi-shot, spin-echo images, which have relatively long acquisition times but negligible distortion, is improved and that signal loss caused by dephasing can be recovered.

Computer-generated fMRI phantoms with motion-distortion interaction.

As an extension of previous work on computer-generated phantoms, more accurate, realistic phantoms are generated by integrating image distortion and signal loss caused by susceptibility variations. With the addition of real motions and activations determined from actual functional MRI studies, these phantoms can be used by the fMRI community to assess with higher fidelity pre-processing algorithms such as motion correction, distortion correction and signal-loss compensation. These phantoms were validated by comparison to real echo-planar images. Specifically, studies have shown the effects of motion-distortion interactions on fMRI. We performed motion correction and activation analysis on these phantoms based on a block paradigm design using SPM2, and the results demonstrate that interactions between motion and distortion affect both motion correction and activation detection and thus represent a critical component of phantom generation.

Comparison of fMRI statistical software packages and strategies for analysis of images containing random and stimulus-correlated motion.

The objectives of this study were to use computer-generated phantoms containing real subject motion to: (1) compare the sensitivity of four commonly used fMRI software packages and (2) compare the sensitivity of three statistical analysis strategies with respect to motion correction. The results suggest that all four packages perform similarly in fMRI statistical analysis with SPM2 having slightly higher sensitivity. The most sensitive analysis technique was to perform motion correction and include the realignment parameters as regressors in the general linear model. This approach applies to all four packages examined and can be most beneficial when stimulus-correlated motion is present.

Characterization of the phase-contrast radiography edge-enhancement effect in a cabinet x-ray system.

The purpose of this study was to demonstrate that a commercially available cabinet x-ray system is capable of phase-contrast radiography (PC-R) and to evaluate the effect of different system parameters on the degree of edge enhancement. An acrylic plastic edge phantom was imaged at different tube potentials (25-60 kV) and in different geometries (variable object-to-detector distances, R(2), at a constant source-to-detector distance, R(1) + R(2)). In addition, the effect of noise on the perceived edge enhancement was studied as a function of exposure time. Our results show that a modest degree of phase contrast can be achieved in an unmodified cabinet x-ray system. In addition, the particular system evaluated allowed low-noise PC-R images to be obtained with short (6 s or less) exposures. These results suggest that with appropriate geometric choices PC-R is already available to a wide range of research scientists for use in both small-animal and human-specimen experiments.

Extracting data from a DICOM file.

DICOM v3.0 is a vendor-independent standard for digital medical images that describes a file format and network protocol for the exchange of images between computer systems. When simply viewing a DICOM file, it is not necessary for the user to understand the details of the entire DICOM standard. However, understanding parts of the standard is essential when DICOM files are read and processed by a user-generated program. This paper offers an overview of information a user needs to write a program for extracting the image and acquisition parameters from a DICOM file.

Experimental validation of the Wigner distributions theory of phase-contrast imaging.

Recently, a new theory of phase-contrast imaging has been proposed by Wu and Liu [Med. Phys. 31, 2378-2384 (2004)]. This theory, based upon Wigner distributions, provides a much stronger foundation for the evaluation of phase-contrast imaging systems than did the prior theories based upon Fresnel-Kirchhoff diffraction theory. In this paper, we compare results of measurements made in our laboratory of phase contrast for different geometries and tube voltages to the predictions of the Wu and Liu model. In our previous publications, we have used an empirical measurement (the edge enhancement index) to parametrize the degree of phase-contrast effects in an image. While the Wu and Liu model itself does not predict image contrast, it does measure the degree of phase contrast that the system can image for a given spatial frequency. We have found that our previously published experimental results relating phase-contrast effects to geometry and x-ray tube voltage are consistent with the predictions of the Wu and Liu model.

Development of computer-generated phantoms for FMRI software evaluation.

Functional magnetic resonance imaging (FMRI) is a major tool for the evaluation of brain function and architecture. It is widely used by physicians, neuroscientists, psychologists and others. In order to process the data collected using FMRI, it is necessary to use post-acquisition processing software that employs motion correction and statistical modeling capabilities. These types of programs permit the user to extract the information about areas of brain activations that have occurred during a study. How well a particular motion-correction technique works and what effect it has on statistical processing are difficult to evaluate, since the level of activation present is not known a priori. This paper provides a description of the construction of a software phantom for use with FMRI post-acquisition processing tools with the properties that it is based on real subject data, has known locations and levels of activation, has known amounts of rigid body motion and noise added, and can be used to evaluate a processing system as if it were a real data set. Versions of the software phantom are available for downloading at the website: .

Quantification of the effect of system and object parameters on edge enhancement in phase-contrast radiography.

The purpose of this study was to evaluate the effects of system parameters (focal spot size, tube voltage, geometry, detector resolution, and image noise) and object characteristics (edge gradient/ shape, composition, thickness, and overlying attenuating material) upon the edge enhancement effect in phase-contrast radiography. Each variable of interest was adjusted and images of a 3 mm lucite phantom were obtained with the other variables remaining constant. A microfocus x-ray source coupled to a CCD camera with an intensifying screen was used to acquire the digital images. Two parameters of image analysis were used to quantify the effects. The edge enhancement index (EEI) was used to measure the absolute degree of edge enhancement, while the edge enhancement to noise ratio (EE/N) was used to measure the conspicuity of the edge enhancement relative to image noise. Little effect on EEI was seen from tube voltage, object thickness, overlying attenuating material, while focal spot size and system geometry demonstrated measurable effects upon the degree of edge enhancement. It was also shown that while the edge enhancement effect over straight edges is highly dependent upon how the edge aligns with the x-ray beam, rounded edges, which better model biological objects, do not suffer from this dependence and the EEI reaches its maximal level at any alignment. Decreasing detector resolution diminished the EEI slightly, but even with pixel sizes of 0.360 x 0.360 mm edge enhancement effects were readily visible. The effect of image noise on EE/N was evaluated using different exposure times showing an expected improvement with longer exposure time with EE/N approaching a plateau at 5 min. Many of the parameters that will go into the design of a future PC-R imaging system have been quantified in terms of their effect on the degree of edge enhancement in the acquired image. These results, taken together, indicate that either a specimen or even clinical breast imaging system could be created with currently available technology. The major limitation to a clinical system would be the low x-ray flux from the microfocal x-ray source.

Dual focal-spot imaging for phase extraction in phase-contrast radiography.

The purpose of this study was to evaluate dual focal spot imaging as a method for extracting the phase component from a phase-contrast radiography image. All measurements were performed using a microfocus tungsten-target x-ray tube with an adjustable focal-spot size (0.01 mm to 0.045 mm). For each object, high-resolution digital radiographs were obtained with two different focal spot sizes to produce matched image pairs in which all other geometric variables as well as total exposure and tube kVp were held constant. For each image pair, a phase extraction was performed using pixel-wise division. The phase-extracted image resulted in an image similar to the standard image processing tool commonly referred to as "unsharp masking" but with the additional edge-enhancement produced by phase-contrast effects. The phase-extracted image illustrates the differences between the two images whose imaging parameters differ only in focal spot size. The resulting image shows effects from both phase contrast as well as geometric unsharpness. In weakly attenuating materials the phase-contrast effect predominates, while in strongly attenuating materials the phase effects are so small that they are not detectable. The phase-extracted image in the strongly attenuating object reflects differences in geometric unsharpness. The degree of phase extraction depends strongly on the size of the smallest focal spot used. This technique of dual-focal spot phase-contrast radiography provides a simple technique for phase-component (edge) extraction in phase-contrast radiography. In strongly attenuating materials the phase-component is overwhelmed by differences in geometric unsharpness. In these cases the technique provides a form of unsharp masking which also accentuates the edges. Thus, the two effects are complimentary and may be useful in the detection of small objects.

In-line phase shift tomosynthesis.

PURPOSE: The purpose of this work is to (1) demonstrate laboratory measurements of phase shift images derived from in-line phase-contrast radiographs using the attenuation-partition based algorithm (APBA) of Yan et al. [Opt. Express 18(15), 16074-16089 (2010)], (2) verify that the APBA reconstructed images obey the linearity principle, and (3) reconstruct tomosynthesis phase shift images from a collection of angularly sampled planar phase shift images. METHODS: An unmodified, commercially available cabinet x-ray system (Faxitron LX-60) was used in this experiment. This system contains a tungsten anode x-ray tube with a nominal focal spot size of 10 µm. The digital detector uses CsI∕CMOS with a pixel size of 50×50 µm. The phantoms used consisted of one acrylic plate, two polystyrene plates, and a habanero pepper. Tomosynthesis images were reconstructed from 51 images acquired over a ±25° arc. All phase shift images were reconstructed using the APBA. RESULTS: Image contrast derived from the planar phase shift image of an acrylic plate of uniform thickness exceeded the contrast of the traditional attenuation image by an approximate factor of two. Comparison of the planar phase shift images from a single, uniform thickness polystyrene plate with two polystyrene plates demonstrated an approximate linearity of the estimated phase shift with plate thickness (-1600 rad vs -2970 rad). Tomographic phase shift images of the habanero pepper exhibited acceptable spatial resolution and contrast comparable to the corresponding attenuation image. CONCLUSIONS: This work demonstrated the feasibility of laboratory-based phase shift tomosynthesis and suggests that phase shift imaging could potentially provide a new imaging biomarker. Further investigation will be needed to determine if phase shift contrast will be able to provide new tissue contrast information or improved clinical performance.

Brain fMRI activation associated with self-paced finger tapping in chronic alcohol-dependent patients.

BACKGROUND: Fine and gross motor dysfunction in chronic alcoholic patients is prevalent, but not extensively studied. Brain autopsy studies of brain regions involved in motor movements indicate cerebellum and frontal lobes are particularly sensitive to alcohol-induced damage, in contrast to motor cortex. METHODS: Using functional magnetic resonance imaging (fMRI), we compared the pattern of activation of the cerebral cortex and cerebellum during repetitive, self-paced dominant (DH) and nondominant (NDH) index finger tapping in eight uncomplicated alcohol-dependent patients after approximately 2 weeks of abstinence and in nine normal controls. RESULTS: Whereas alcoholic patients tapped significantly more slowly than normal controls, a greater percentage of pixels were activated in the ipsilateral cortex during DH tapping. Furthermore, alcoholics tapped significantly less efficiently (tapping rate divided by percent pixels activated [weighted by pixel intensity] in a given region of interest [ROI]) than normal controls in every ROI examined while using DH, but only in ipsilateral hemi-cerebellum using NDH. Finally, the alcohol-dependent patients did not demonstrate the greater mean pixel activation, percentage activated pixels, and lesser activation efficiency in the ipsilateral cortex during NDH compared to DH tapping that was observed in the normal control group. CONCLUSIONS: These findings are compatible with motor inefficiency and compensatory alterations of cortical-cerebellar circuits. Further studies are needed to determine whether these deficits recover with prolonged abstinence and how they relate to cognitive inefficiency throughout the clinical course of alcoholism.

Experimental model for functional magnetic resonance imaging of somatic sensory cortex in the unanesthetized rat.

Functional magnetic resonance imaging (fMRI) has evolved into a method widely used to map neural activation in the human brain. fMRI is a method for recording blood oxygen level-dependent (BOLD) signals. These signals change with local cerebral blood flow coupled to neural activity. However, the relationship between BOLD signals and neural function is poorly understood and requires the development of animal models. Here we use an unanesthetized rat preparation to study BOLD responses to whisker stimulation in somatic sensory barrel cortex. Five rats were trained to tolerate restraint in a holder and fMRI noise with positive reinforcement. For maximal immobilization, the head was fastened to the holder with nuts screwed on threaded bolts attached to the head. On scanning day, residual stress was alleviated with injections of diazepam, and the rats were restrained in the holder and transferred into the scanner. After >75 min to allow the tranquilization to abate, structural images were acquired from three coronal brain slices. Subsequently, functional images were taken utilizing 4-min epochs without stimulation alternated with equivalent epochs during which the right caudal whiskers were stimulated with three air puffs/s. After 4 weeks, fMRI could be repeated in four rats. In seven of the nine functional runs, head motion was minimal and whisker stimulation resulted in a statistically significant (P