We assess the performance of a cadmium zinc telluride (CZT)-based Medipix3RX energy-resolving and photon-counting x-ray detector as a candidate for spectral microcomputed tomography (micro-CT) imaging. It features an array of 128 × 128, 110-μm2 pixels, each with four simultaneous threshold counters that utilize real-time charge summing. Each pixel’s response is assessed by imaging with a range of incident x-ray intensities and detector integration times. Energy-related assessments are made by exposing the detector to the emission from an I-125 radioisotope brachytherapy seed. Long-term stability is assessed by repeating identical exposures over the course of 1 h. The high yield of properly functioning pixels (98.8%), long-term stability (linear regression of whole-chip response over 1 h of acquisitions: y = − 0.0038x + 2284; standard deviation: 3.7 counts), and energy resolution [2.5 keV full-width half-maximum (FWHM) (single pixel), 3.7 keV FWHM (across the full image)] make this device suitable for spectral micro-CT.
Changes in arterial wall perfusion mark the onset of atherosclerosis. A characteristic change is the increased spatial density of vasa vasorum (VV), the microvessels in the arterial walls. Measuring this increased VV (IVV) density using contrast-enhanced computed tomography (CT) has had limited success due to blooming effects from contrast media. If the system point-spread function (PSF) is known, then the blooming effect can be modeled as a convolution between the true signal and the PSF. We report the application of image deconvolution to improve the CT number accuracy in the arterial wall of a phantom and in a porcine model of IVV density, both scanned using a whole-body research photon-counting CT scanner. A 3D-printed carotid phantom filled with three concentrations of iodinated contrast material was scanned to assess blooming and its effect on wall CT number accuracy. The results showed a reduction in blooming effects following image deconvolution, and, consequently, a better delineation between lumen and wall was achieved. Results from the animal experiment showed improved CT number difference between the carotid with IVV density and the normal carotid artery after deconvolution, enabling the detection of VV proliferation, which may serve as an early indicator of atherosclerosis.
Changes in arterial wall perfusion are an indicator of early atherosclerosis. This is characterized by an increased spatial density of vasa vasorum (VV), the micro-vessels that supply oxygen and nutrients to the arterial wall. Detection of increased VV during contrast-enhanced computed tomography (CT) imaging is limited due to contamination from blooming effect from the contrast-enhanced lumen. We report the application of an image deconvolution technique using a measured system point-spread function, on CT data obtained from a photon-counting CT system to reduce blooming and to improve the CT number accuracy of arterial wall, which enhances detection of increased VV. A phantom study was performed to assess the accuracy of the deconvolution technique. A porcine model was created with enhanced VV in one carotid artery; the other carotid artery served as a control. CT images at an energy range of 25-120 keV were reconstructed. CT numbers were measured for multiple locations in the carotid walls and for multiple time points, pre and post contrast injection. The mean CT number in the carotid wall was compared between the left (increased VV) and right (control) carotid arteries. Prior to deconvolution, results showed similar mean CT numbers in the left and right carotid wall due to the contamination from blooming effect, limiting the detection of increased VV in the left carotid artery. After deconvolution, the mean CT number difference between the left and right carotid arteries was substantially increased at all the time points, enabling detection of the increased VV in the artery wall.
An ultrahigh-resolution (UHR) data collection mode was enabled on a whole-body, research photon counting detector (PCD) computed tomography system. In this mode, 64 rows of 0.45 mm×0.45 mm detector pixels were used, which corresponded to a pixel size of 0.25 mm×0.25 mm at the isocenter. Spatial resolution and image noise were quantitatively assessed for the UHR PCD scan mode, as well as for a commercially available UHR scan mode that uses an energy-integrating detector (EID) and a set of comb filters to decrease the effective detector size. Images of an anthropomorphic lung phantom, cadaveric swine lung, swine heart specimen, and cadaveric human temporal bone were qualitatively assessed. Nearly equivalent spatial resolution was demonstrated by the modulation transfer function measurements: 15.3 and 20.3 lp/cm spatial frequencies were achieved at 10% and 2% modulation, respectively, for the PCD system and 14.2 and 18.6 lp/cm for the EID system. Noise was 29% lower in the PCD UHR images compared to the EID UHR images, representing a potential dose savings of 50% for equivalent image noise. PCD UHR images from the anthropomorphic phantom and cadaveric specimens showed clear delineation of small structures.
Early atherosclerosis changes perfusion of the arterial wall due to localized proliferation of the vasa vasorum. When
contrast agent passes through the artery, some enters the vasa vasorum and increases radiopacity of the arterial wall.
Technical challenges to detecting changes in vasa vasorum density include the thin arterial wall, partial volume
averaging at the arterial lumen/wall interface and calcification within the wall. We used a photon-counting spectral CT
scanner to study carotid arteries of anesthetized pigs and micro-CT of these arteries to quantify vasa vasorum density.
The left carotid artery wall was injected with autologous blood to stimulate vasa vasorum angiogenesis. The scans were
performed at 25-120 keV; the tube-current-time product was 550 mAs. A 60 mL bolus of iodine contrast agent was
injected into the femoral vein at 5mL/s. Two seconds post injection, an axial scan was acquired at every 3 s over 60 s
(i.e., 20 time points). Each time point acquired 28 contiguous transaxial slices with reconstructed voxels 0.16 x 0.16 x 1
mm3. Regions-of-interest in the outer 2/3 of the arterial wall and in the middle 2/3 of the lumen were drawn and their
enhancements plotted versus time. Lumenal CT values peaked several seconds after injection and then returned towards
baseline. Arterial wall CT values peaked concurrent to the lumen. The peak arterial wall enhancement in the left carotid
arterial wall correlated with increased vasa vasorum density observed in micro-CT images of the isolated arteries.
We assessed the performance of a cadmium zinc telluride (CZT)-based Medipix3RX x-ray detector as a candidate for
micro-computed tomography (micro-CT) imaging. This technology was developed at CERN for the Large Hadron
Collider. It features an array of 128 by 128, 110 micrometer square pixels, each with eight simultaneous threshold
counters, five of which utilize real-time charge summing, significantly reducing the charge sharing between contiguous
pixels. Pixel response curves were created by imaging a range of x-ray intensities by varying x-ray tube current and by
varying the exposure time with fixed x-ray current. Photon energy-related assessments were made by flooding the
detector with the tin foil filtered emission of an I-125 radioisotope brachytherapy seed and sweeping the energy
threshold of each of the four charge-summed counters of each pixel in 1 keV steps. Long term stability assessments were
made by repeating exposures over the course of one hour. The high properly-functioning pixel yield (99%), long term
stability (linear regression of whole-chip response over one hour of acquisitions: y = -0.0038x + 2284; standard
deviation: 3.7 counts) and energy resolution (2.5 keV FWHM (single pixel), 3.7 keV FWHM across the full image)
make this device suitable for spectral micro-CT. The charge summing performance effectively reduced the measurement
corruption caused by charge sharing which, when unaccounted for, shifts the photon energy assignment to lower
energies, degrading both count and energy accuracy. Effective charge summing greatly improves the potential for
calibrated, energy-specific material decomposition and K edge difference imaging approaches.
A high-resolution (HR) data collection mode has been introduced to a whole-body, research photon-counting-detector
CT system installed in our laboratory. In this mode, 64 rows of 0.45 mm x 0.45 mm detector pixels were used, which
corresponded to a pixel size of 0.25 mm x 0.25 mm at the iso-center. Spatial resolution of this HR mode was quantified
by measuring the MTF from a scan of a 50 micron wire phantom. An anthropomorphic lung phantom, cadaveric swine
lung, temporal bone and heart specimens were scanned using the HR mode, and image quality was subjectively assessed
by two experienced radiologists. High spatial resolution of the HR mode was evidenced by the MTF measurement, with
15 lp/cm and 20 lp/cm at 10% and 2% modulation. Images from anthropomorphic phantom and cadaveric specimens
showed clear delineation of small structures, such as lung vessels, lung nodules, temporal bone structures, and coronary
arteries. Temporal bone images showed critical anatomy (i.e. stapes superstructure) that was clearly visible in the PCD
system. These results demonstrated the potential application of this imaging mode in lung, temporal bone, and vascular
imaging. Other clinical applications that require high spatial resolution, such as musculoskeletal imaging, may also
benefit from this high resolution mode.
X-ray computed tomography (CT) with energy-discriminating capabilities presents exciting opportunities for increased dose efficiency and improved material decomposition analyses. However, due to constraints imposed by the inability of photon-counting detectors (PCD) to respond accurately at high photon flux, to date there has been no clinical application of PCD-CT. Recently, our lab installed a research prototype system consisting of two x-ray sources and two corresponding detectors, one using an energy-integrating detector (EID) and the other using a PCD. In this work, we report the first third-party evaluation of this prototype CT system using both phantoms and a cadaver head. The phantom studies demonstrated several promising characteristics of the PCD sub-system, including improved longitudinal spatial resolution and reduced beam hardening artifacts, relative to the EID sub-system. More importantly, we found that the PCD sub-system offers excellent pulse pileup control in cases of x-ray flux up to 550 mA at 140 kV, which corresponds to approximately 2.5×1011 photons per cm2 per second. In an anthropomorphic phantom and a cadaver head, the PCD sub-system provided image quality comparable to the EID sub-system for the same dose level. Our results demonstrate the potential of the prototype system to produce clinically-acceptable images in vivo.
With the increasing use of microspheres and nanoparticles for diagnostic and therapeutic purposes, the need to quantify
the spatial distribution and concentration of those particles in a minimally invasive manner, such as by imaging, is
required. In the case of CT-imaging, labelling of those particles with elements that have high contrast, and when possible
that is specific for that element, is an obvious approach, but this still begs the question as to what extent particles that are
smaller than the detector pixel can be quantified over relatively large volumes of tissue. This study is an exploration of
three approaches to quantify the spatial distribution and/or size of those microscopic particles by use of; (i) a model of
the impact of high contrast opaque particle on the detected x-ray attenuation, (ii) quasi-monochromatic energy CT and
(iii) the statistics of random clustering of particles resulting in clusters that are larger than detector pixels and using that
information to extrapolate to sub-resolution information about individual particles. To explore the role of particle size
relative to detector pixel size we recorded x-ray attenuation in detector pixels smaller than the particle and then
retrospectively increased the effective detector pixel size by summing the x-ray signal in contiguous pixels around the
particle location.
Imaging arrays with sub-millimeter detector pixels that count and allocate energy to each detected photon are now
being introduced into biomedical computed tomography scanners. Consequently, bremsstrahlung x-ray can provide
the advantages of simultaneous recording of multiple quasi-monochromatic x-ray images which can be used for
identification of various materials within the image field. This capability increases the inherent contrast within
biomedical CT images and also introduces the ability to use high atomic weight "foreign" elements (e.g., strontium)
which are surrogates for "native" biological elements (e.g., calcium) to monitor tissue function (e.g., bone deposition).
Challenges for this methodology include limited maximum fluence due to photon pile-up, charge-sharing between
contiguous pixels and heterogeneous pixel characteristics due to manufacturing difficulties.
Quantitation of coherent x-ray scatter traditionally involves measuring the intensity of the scattered x-ray over a range of
angles (θ) from the illuminating monochromatic x-ray beam. Spectral x-ray imaging produces the same information at a
single θ when bremsstrahlung x-ray exposure is used. We used a 200μm thick sheet-illumination of a phantom (lucite
cylinder containing holes with water, polyethylene, collagen, polycarbonate, and nylon) and a polycapillary x-ray optic
collimator to provide measurements at a fixed θ. A Medipix2 x-ray detection array (2562 (55μm)2 pixels) provided the spectral (E, 10 - 22 keV in 3keV energy bins) spread needed to generate the momentum transfer (q) profile information
at one angle. The tungsten x-ray source anode (aluminum filter) was operated at 35kVp at 20mA. The detected scatter
intensity was corrected for attenuation of the incident and the scattered x-ray by use of the regular CT image of the
phantom generated at the same energy bins. The phantom was translated normal to the plane of the fan beam in 65,
0.2mm, steps to generate the 3D image data. The momentum transfer profiles generated with this approach were
compared to published momentum transfer profiles obtained by other methods.
It has been shown that coherently scattered x-rays can be used to discriminate and identify specific components in a mixture of materials. To assess the feasibility of using coherent x-ray scatter (CXS) to characterize the material components within tissue scaffolds, we studied the CXS properties of the bio-compatible materials of polymers (polypropylene fumarate, polycaprolactone, epoxy, etc.), sugar and salt solutions at different concentration, and
complex materials consisting of more than one polymer. We also investigated the effects of x-ray spectra on the CXS functions of polymers by measuring them with different x-ray source anodes.
It is shown that the synthesized polymers with different portions of base polymers can be characterized with CXS. The polymerization process does not significantly change the CXS characteristics of the measured polymers. When protein is denatured, no substantial change in scatter was detected. Solutions of different concentration
can be characterized and quantified by the CXS features corresponding to the solutes. The difference among CXS of solutions of different concentration makes it possible to image and trace fluids and their concentration changes in tissues or scaffolds. Our results show that CXS of complex specimens can be decomposed with the scatter functions of the component materials. By simulating a tissue scaffold with a phantom with several bio-compatible materials, we demonstrated that significant contrast can be achieved at proper scatter angles by
measuring the coherent x-ray scatter, despite the low attenuation-based contrast between them. We conclude that use of x-ray scatter makes it possible to track and map the fate (e.g., its breakdown and/or removal) of specific components within tissue scaffolds.
The objective was to develop a method for high-resolution imaging of dynamic solute transport in cyclically
deforming porous scaffolds for tissue engineering applications. A flexible cubic scaffold with single cylindrical
channel was fabricated from a biodegradable polymer blend using a combined 3D printing and injection molding
technique. The scaffold was attached to the bottom of a fluid reservoir mounted underneath a compression
apparatus placed inside the X-ray scanner. The scaffold was positioned with the channel axis perpendicular to
the X-ray beam. The container was filled with glycerin, and a solution of the contrast agent sodium iodide (NaI)
in glycerin was injected into the scaffold channel. Intervals of compression cycles (14.5 ± 2.1 % compression
at 1.0 Hz) were applied to the top face of the scaffold. After each interval the compression was temporarily
paused to obtain a two-dimensional image at 20 μm pixel resolution. A series of images was also obtained
without application of the compression cycles to quantify the effect of passive diffusional removal of NaI from
the channel. The average NaI concentration in the channel decreased by 82% after 300 cycles (5 min.) of
compression, by 40% after 60 min. of passive removal. Spatial profiles of the NaI concentration along the
channel axis indicated that compression-induced transport preferentially removed the contrast agent at the pore
openings. We conclude that convective transport induced by cyclic mechanical deformation of artificial tissue
scaffolds could significantly contribute to the rate and depth of nutrient transport inside the scaffold, as compared
to slow diffusive transport alone.
Repeated micro-CT scanning of a number of iliac crest biopsies enabled us to quantitate the variation in CT image gray-scale and spatial geometry due to variables such as specimen orientation, projection magnification, voxel size and slight differences in x-ray photon energy in each of the different scans. Using the micro-CT scanner on beamline X2B at the Brookhaven National Laboratory's National Synchrotron Light Source, we rescanned several iliac crest bone biopsy specimens, and a test phantom made of calcium hydroxyapatite, at repeated scanning sessions and evaluated the reproducibility of the spatial geometry and gray-scale haracteristics of the specimens. This scanner consists of a Bragg diffiaction source of monochromatic x-rays, a computer controlled high precision specimen rotation and translation stage assembly, and a fluorescent crystal and CCD array system for imaging the specimen at each of the angles of view around its axis of rotation during the scanning sequence. The 3-D micro-CT images consisted of up to 1024x24002, 4 μm, cubic voxels, each with 16-bit gray-scale. We also reconstructed the images at 16,32 and 48 μm voxel resolution. Partial volume effects at the surface of the bone were diminished by 'eroding' the surface voxels in the 4 μm images, but significantly changed the outcome at greater voxel size. Reproducibility of the mineral content of bone, at mean bone opacity value, was ± 28.8 mg/cm3, i.e., 2.56%, in a 4 μm cubic voxel at the 95% confidence level.
Polycapillary x-ray optics are bundles of micron size hollow tubes, inside of which x rays are propagated by total reflection much like visible light in solid fiber optics. The small critical angle for total reflection from the glass walls of the tubes, 0.06° at 27 keV, results in very high angular selectivity. The field of view of each capillary tube is limited by this angular acceptance to less than 50 microns at a source-to-optic distance of 2 cm. Each adjacent tube works in parallel so that a large area can be covered at this resolution with much higher count rate than for a single collimator. Measurements have been performed using 125I brachytherapy seeds in Lucite phantoms using the optics and imaging detectors. Measured resolutions were detector-limited at better than 0.1 mm. Calculations for expected sensitivity and signal-to-background ratios were developed from geometrical models and show good agreement with measurements. Results indicate that the optics provide superior signal count rates to conventional collimators for geometries such as small animal imaging in which sub millimeter resolution with inch-wide or larger fields of view are desirable.
To show the feasibility of a combined micro-CT and micro-SPECT scanner based on use of polycapillary optics we inserted an optic between the radio-labeled specimen and our micro-CT scanner's imaging system. The micro-CT x-ray focal spot was placed at the focal point of the optic so that x-ray micro-CT of the specimen could also be performed without having to move the specimen. Using this set-up we scanned a 2 cm diameter Plexiglas cylinder with three (177 μCi) prostate brachytherapy seeds embedded in it. Each seed was 0.5 mm diameter, 4 mm long and filled with 0.4 mm diameter ceramic beads coated with 125Iodine. The SPECT images clearly resolve the layer of 125Iodine on the beads. That the SPECT image is spatially correct was cofirmed by the concurrent CT image. We also used a parallel polycapillary optic to scan a 1.5 cm Plexiglas cylinder with holes (2, 1, and 0.5 mm diameter, parallel to the cylinder axis) filled with a solution containing 11.56μCi/mm3 of 125Iodine. These data indicate a spatial resolution of 5 line pairs per mm at 10% modulation. Based on these results we propose a design that is more efficient at acquiring the scintigraphic image data.
A double walled copper vessel, 32 cc in volume, was fabricated for micro-CT scanning tissue specimens maintained at cryogenic temperature. The space between the two nested vessels was evacuated and in two opposing sides of the vessel the copper has been replaced by beryllium foil. Nitrogen gas, boiling off liquid nitrogen, is injected continuously into the top of the chamber during the scanning process. Just prior to venting from the vessel the gas is heated and directed through a narrow gap over the outside of the beryllium windows so as to maintain the beryllium windows frost free. A temperature detector within the chamber is used to control the rate of inflow of the nitrogen gas. The frozen specimen is attached to a small horizontal platform on top of a vertical stainless steel pin which exits the base of the vessel through a closely fitting hole and is attached to the computer-controlled rotating stage under the vessel. The vessel and rotation-stage assembly is mounted on a computer-controlled horizontal translation stage which can move the specimen out of the x- ray beam, from time to time, for x-ray beam calibration purposes. The purpose of this arrangement is to permit scanning of specimens that: 1) either cannot be fixed (e.g., with formalin) because of biomolecular analyses which are incompatible with prior fixation, or 2) are snap-frozen during a transient process, such as the accumulation and/or washout of radiopaque indicators distributed in microvascular or extravascular compartments, which lasts only seconds and hence is too fast for normal micro-CT methods to capture.
A bench-top x-ray micro-CT scanner was used to evaluate a focusing x-ray optic as a means to augment micro-CT scanner performance. The optic consists of a bundle of hollow glass fibers (25 micrometer diameter) which are arranged and curved so that the optic has an 8 degree input focus and a 4.1 degree output focus cone angle. This optic was placed between our spectroscopy x-ray source (18 keV) and the specimen. The x-ray fluorescent crystal plate was placed as close as possible behind the specimen and the light image generated within it was projected onto a CCD with a lens. The specimen was imaged and rotated about its axis in 1 degree steps until a 360 degree rotation was completed. The resulting, normalized, projection images were submitted to modified Feldkamp cone- beam reconstruction. A 1 cm diameter plastic cylinder, in which glass microspheres (nominally 10, 30, 100 or 300 micrometer diameter) were suspended, was used to compare the spatial resolution of the x-ray optic versus the no-optic scans performed at a range of comparable focal spot-to- specimen distances. The increased flux at the specimen obtained by placing the specimen (and fluorescent crystal) closer to the output focal spot of the optic resulted in increased x-ray flux, thereby reducing scan duration several- fold without increase in penumbral blurring.
Use of synchrotron generated x-ray for micro-CT is particularly powerful for several reasons. These include the high x-ray flux which permits short duration exposure and hence scan durations, the narrow bandwidth of the x-ray energy which permits quantitative CT imaging with high accuracy of the measured attenuation coefficient and the fact that the x-ray photon energy can be adjusted allows element selective imaging. Another advantage is that the radiation is close to parallel so that the tomographic image reconstruction process is facilitated. On the other hand, synchrotron-based micro-CT imaging does have the limitation of a rather small field of view being illuminated. This means that specimens larger than the field of view also create problems for the conventional 'global' tomographic image reconstruction algorithms. Fortunately, recently developed 'local' reconstruction algorithms can, in large measure, overcome this limitation of the synchrotron generated x-ray field.
The DynamicSpatial Reconstructor (DSR) is a 14 x-ray source video imaging system which operates on the computerized tomography scanning principle. It scans a cylindrical volume 18. 5 cm in axial height with equal resolution in the transverse and axial directions and repeats this volume scan (of up to 240 0. 7 mm thick parallel slices) at 16. 67 ms intervals. The output of each of the 14 video imaging systems is A/D converted shading corrected and stored in 64 megabytes of memory. The memory is used efficiently because the shading correction reduces the gray scale information of the pixels from 12 to 10 bits and because we need record only a selectable region of interest within the full video image. 1_. THE DSR SCANNER SYSTEM The DSR imaging system (Figure 1) consists of 14 rotating-anodeS x-ray sources which sequentially irradiate the object of study during the first 10. 5 ms of each 16. 67 ms sequence. '' Figure 1 - Photograph of the DSR scanner. Note several of the x-ray tubes in left upper corner and array of TV camera electronics in middle. Scanner is cantilevered from bearing just to left of person on left. Tail end of a slip ring assembly is just visible to right of person a t r igh t . High vo 1 tage supp ly is in right lower corner. The x-ray sources lie in
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