Dean M. Connor

Design and implementation of a compact low-dose diffraction enhanced medical imaging system.

RATIONALE AND OBJECTIVES Diffraction-enhanced imaging (DEI) is a new x-ray imaging modality that differs from conventional radiography in its use of three physical mechanisms to generate contrast. DEI is able to generate contrast from x-ray absorption, refraction, and ultra-small-angle scatter rejection (extinction) to produce high-contrast images with a much lower radiation dose compared to conventional radiography. MATERIALS AND METHODS A prototype DEI system was constructed using a 1-kW tungsten x-ray tube and a single silicon monochromator and analyzer crystal. The monochromator crystal was aligned to reflect the combined Kalpha1 (59.32 keV) and Kalpha2 (57.98 keV) characteristic emission lines of tungsten using a tube voltage of 160 kV. System performance and demonstration of contrast were evaluated using a nylon monofilament refraction phantom, full-thickness breast specimens, a human thumb, and a live mouse. RESULTS Images acquired using this system successfully demonstrated all three DEI contrast mechanisms. Flux measurements acquired using this 1-kW prototype system demonstrated that this design can be scaled to use a more powerful 60-kW x-ray tube to generate similar images with an image time of approximately 30 seconds. This single-crystal pair design can be further modified to allow for an array of crystals to reduce clinical image times to <3 seconds. CONCLUSIONS This paper describes the design, construction, and performance of a new DEI system using a commercially available tungsten anode x-ray tube and includes the first high-quality low-dose diffraction-enhanced images of full-thickness human tissue specimens.

An extended diffraction-enhanced imaging method for implementing multiple-image radiography

Diffraction-enhanced imaging (DEI) is an analyser-based x-ray imaging method that produces separate images depicting the projected x-ray absorption and refractive properties of an object. Because the imaging model of DEI does not account for ultra-small-angle x-ray scattering (USAXS), the images produced in DEI can contain artefacts and inaccuracies in medical imaging applications. In this work, we investigate an extended DEI method for concurrent reconstruction of three images that depict an objects projected x-ray absorption, refraction and USAXS properties. The extended DEI method can be viewed as an implementation of the recently proposed multiple-image radiography paradigm. Validation studies are conducted by use of computer-simulated and synchrotron measurement data.

Computed tomography of amyloid plaques in a mouse model of Alzheimer's disease using diffraction enhanced imaging

Our understanding of early development in Alzheimers disease (AD) is clouded by the scale at which the disease progresses; amyloid beta (Abeta) plaques, a hallmark feature of AD, are small (approximately 50 microm) and low contrast in diagnostic clinical imaging techniques. Diffraction enhanced imaging (DEI), a phase contrast x-ray imaging technique, has greater soft tissue contrast than conventional radiography and generates higher resolution images than magnetic resonance microimaging. Thus, in this proof of principle study, DEI in micro-CT mode was performed on the brains of AD-model mice to determine if DEI can visualize Abeta plaques. Results revealed small nodules in the cortex and hippocampus of the brain. Histology confirmed that the features seen in the DEI images of the brain were Abeta plaques. Several anatomical structures, including hippocampal subregions and white matter tracks, were also observed. Thus, DEI has strong promise in early diagnosis of AD, as well as general studies of the mouse brain.

Diffraction-Enhanced Imaging of Musculoskeletal Tissues Using a Conventional X-Ray Tube

RATIONALE AND OBJECTIVES In conventional projection radiography, cartilage and other soft tissues do not produce enough radiographic contrast to be distinguishable from each other. Diffraction-enhanced imaging (DEI) uses a monochromatic x-ray beam and a silicon crystal analyzer to produce images in which attenuation contrast is greatly enhanced and x-ray refraction at tissue boundaries can be detected. The aim of this study was to test the efficacy of conventional x-ray tube-based DEI for the detection of soft tissues in experimental samples. MATERIALS AND METHODS Cadaveric human tali (normal and degenerated) and a knee and thumb were imaged with DEI using a conventional x-ray tube and DEI setup that included a double-silicon crystal monochromator and a silicon crystal analyzer positioned between the imaged object and the detector. RESULTS Diffraction-enhanced images of the cadaveric tali allowed the visualization of cartilage and its specific level of degeneration for each specimen. There was a significant correlation between the grade of cartilage integrity as assessed on the tube diffraction-enhanced images and on their respective histologic sections (r = 0.97, P = .01). Images of the intact knee showed the articular cartilage edge of the femoral condyle, even when superimposed by the tibia. In the thumb image, it was possible to visualize articular cartilage, tendons, and other soft tissues. CONCLUSION DEI based on a conventional x-ray tube allows the visualization of skeletal and soft tissues simultaneously. Although more in-depth testing and optimization of the DEI setup must be carried out, these data demonstrate a proof of principle for further development of the technology for future clinical imaging.

Diffraction enhanced imaging of controlled defects within bone, including bone-metal gaps.

Gap regions between a bone and an implant, whether existing upon insertion or developing over time, can lead to implant failure. Currently, planar x-ray imaging and CT are the most commonly used methods to evaluate the gap region. An alternative to these available clinical imaging modalities could help to better evaluate bone resorption. Previous experiments with diffraction enhanced imaging (DEI) have shown significant contrast advantages over monochromatic synchrotron radiation (SR) imaging. DEI and planar SR radiography images of bone samples with drill holes and gap regions of known geometry were acquired at the NSLS beamline X15A (Upton, NY, USA). The images acquired with DEI show measurable contrast-to-noise gains when compared to the images acquired using SR radiography.

Phase-sensitive X-ray imaging of synovial joints

OBJECTIVE To test the efficacy of phase-sensitive X-ray imaging for intact synovial joints, whereby refraction effects, along with the attenuation of conventional radiography, can be exploited. DESIGN Intact cadaveric human knee joints were imaged, in the computed tomographic mode, using an analyzer-based X-ray system at the National Synchrotron Light Source, Brookhaven National Laboratory. A collimated fan beam of 51 keV X-rays was prepared by a silicon [1,1,1 reflection] double-crystal monochromator. The X-ray beam transmitted through the specimen was imaged after diffraction in the vertical plane by means of the analyzer crystal with the analyzer crystal tuned to its half-reflectivity point (6.5 microrad). A two-dimensional filtered backprojection (FBP) algorithm was used for reconstructing transverse slices of images. RESULTS The resulting images demonstrate simultaneous soft tissue and bone contrast at a level that has not been achieved previously. Identifiable structures include articular cartilage, cruciate ligaments, loose connective tissue, menisci, and chondrocalcinosis. CONCLUSION Phase-sensitive X-ray imaging using an analyzer-based system renders exceptionally high quality images of soft and hard tissues within synovial joints, with high contrast and resolution, and thus holds promise for the eventual clinical utility.

Characterization of diffraction-enhanced imaging contrast in breast cancer

Diffraction-enhanced imaging (DEI) is a new x-ray imaging modality that has been shown to enhance contrast between normal and cancerous breast tissues. In this study, diffraction-enhanced imaging in computed tomography (DEI-CT) mode was used to quantitatively characterize the refraction contrasts of the organized structures associated with invasive human breast cancer. Using a high-sensitivity Si (3 3 3) reflection, the individual features of breast cancer, including masses, calcifications and spiculations, were observed. DEI-CT yields 14, 5 and 7 times higher CT numbers and 10, 9 and 6 times higher signal-to-noise ratios (SNR) for masses, calcifications and spiculations, respectively, as compared to conventional CT of the same specimen performed using the same detector, x-ray energy and dose. Furthermore, DEI-CT at ten times lower dose yields better SNR than conventional CT. In light of the recent development of a compact DEI prototype using an x-ray tube as its source, these results, acquired at a clinically relevant x-ray energy for which a pre-clinical DEI prototype currently exists, suggest the potential of clinical implementation of mammography with DEI-CT to provide high-contrast, high-resolution images of breast cancer (Parham 2006 PhD Dissertation University of North Carolina at Chapel Hill).

Comparison of diffraction-enhanced computed tomography and monochromatic synchrotron radiation computed tomography of human trabecular bone

Diffraction-enhanced imaging (DEI) is an x-ray-based medical imaging modality that, when used in tomography mode (DECT), can generate a three-dimensional map of both the apparent absorption coefficient and the out-of-plane gradient of the index of refraction of the sample. DECT is known to have contrast gains over monochromatic synchrotron radiation CT (SRCT) for soft tissue structures. The goal of this experiment was to compare contrast-to-noise ratio (CNR) and resolution in images of human trabecular bone acquired using SRCT with images acquired using DECT. All images were acquired at the National Synchrotron Light Source (Upton, NY, USA) at beamline X15 A at an x-ray energy of 40 keV and the silicon [3 3 3] reflection. SRCT, apparent absorption DECT and refraction DECT slice images of the trabecular bone were created. The apparent absorption DECT images have significantly higher spatial resolution and CNR than the corresponding SRCT images. Thus, DECT will prove to be a useful tool for imaging applications in which high contrast and high spatial resolution are required for both soft tissue features and bone.

Diffraction enhanced imaging of a rat model of gastric acid aspiration pneumonitis.

RATIONALE AND OBJECTIVES Diffraction-enhanced imaging (DEI) is a type of phase contrast x-ray imaging that has improved image contrast at a lower dose than conventional radiography for many imaging applications, but no studies have been done to determine if DEI might be useful for diagnosing lung injury. The goals of this study were to determine if DEI could differentiate between healthy and injured lungs for a rat model of gastric aspiration and to compare diffraction-enhanced images with chest radiographs. MATERIALS AND METHODS Radiographs and diffraction-enhanced chest images of adult Sprague Dawley rats were obtained before and 4 hours after the aspiration of 0.4 mL/kg of 0.1 mol/L hydrochloric acid. Lung damage was confirmed with histopathology. RESULTS The radiographs and diffraction-enhanced peak images revealed regions of atelectasis in the injured rat lung. The diffraction-enhanced peak images revealed the full extent of the lung with improved clarity relative to the chest radiographs, especially in the portion of the lower lobe that extended behind the diaphragm on the anteroposterior projection. CONCLUSIONS For a rat model of gastric acid aspiration, DEI is capable of distinguishing between a healthy and an injured lung and more clearly than radiography reveals the full extent of the lung and the lung damage.

Effect of Breast Compression on Lesion Characteristic Visibility with Diffraction-Enhanced Imaging

RATIONALE AND OBJECTIVES Conventional mammography can not distinguish between transmitted, scattered, or refracted x-rays, thus requiring breast compression to decrease tissue depth and separate overlapping structures. Diffraction-enhanced imaging (DEI) uses monochromatic x-rays and perfect crystal diffraction to generate images with contrast based on absorption, refraction, or scatter. Because DEI possesses inherently superior contrast mechanisms, the current study assesses the effect of breast compression on lesion characteristic visibility with DEI imaging of breast specimens. MATERIALS AND METHODS Eleven breast tissue specimens, containing a total of 21 regions of interest, were imaged by DEI uncompressed, half-compressed, or fully compressed. A fully compressed DEI image was displayed on a soft-copy mammography review workstation, next to a DEI image acquired with reduced compression, maintaining all other imaging parameters. Five breast imaging radiologists scored image quality metrics considering known lesion pathology, ranking their findings on a 7-point Likert scale. RESULTS When fully compressed DEI images were compared to those acquired with approximately a 25% difference in tissue thickness, there was no difference in scoring of lesion feature visibility. For fully compressed DEI images compared to those acquired with approximately a 50% difference in tissue thickness, across the five readers, there was a difference in scoring of lesion feature visibility. The scores for this difference in tissue thickness were significantly different at one rocking curve position and for benign lesion characterizations. These results should be verified in a larger study because when evaluating the radiologist scores overall, we detected a significant difference between the scores reported by the five radiologists. CONCLUSIONS Reducing the need for breast compression might increase patient comfort during mammography. Our results suggest that DEI may allow a reduction in compression without substantially compromising clinical image quality.