Molly D. Wong

A method of measuring gold nanoparticle concentrations by X-ray fluorescence for biomedical applications.

PURPOSE This paper reports a technique that enables the quantitative determination of the concentration of gold nanoparticles (GNPs) through the accurate detection of their fluorescence radiation in the diagnostic x-ray spectrum. METHODS Experimentally, x-ray fluorescence spectra of 1.9 and 15 nm GNP solutions are measured using an x-ray spectrometer, individually and within chicken breast tissue samples. An optimal combination of excitation and emission filters is determined to segregate the fluorescence spectra at 66.99 and 68.80 keV from the background scattering. A roadmap method is developed that subtracts the scattered radiation (acquired before the insertion of GNP solutions) from the signal radiation acquired after the GNP solutions are inserted. RESULTS The methods effectively minimize the background scattering in the spectrum measurements, showing linear relationships between GNP solutions from 0.1% to 10% weight concentration and from 0.1% to 1.0% weight concentration inside a chicken breast tissue sample. CONCLUSIONS The investigation demonstrated the potential of imaging gold nanoparticles quantitatively in vivo for in-tissue studies, but future studies will be needed to investigate the ability to apply this method to clinical applications.

Characterization of a high-energy in-line phase contrast tomosynthesis prototype.

PURPOSE In this research, a high-energy in-line phase contrast tomosynthesis prototype was developed and characterized through quantitative investigations and phantom studies. METHODS The prototype system consists of an x-ray source, a motorized rotation stage, and a CMOS detector with a pixel pitch of 0.05 mm. The x-ray source was operated at 120 kVp for this study, and the objects were mounted on the rotation stage 76.2 cm (R1) from the source and 114.3 cm (R2) from the detector. The large air gap between the object and detector guarantees sufficient phase-shift effects. The quantitative evaluation of this prototype included modulation transfer function and noise power spectrum measurements conducted under both projection mode and tomosynthesis mode. Phantom studies were performed including three custom designed phantoms with complex structures: a five-layer bubble wrap phantom, a fishbone phantom, and a chicken breast phantom with embedded fibrils and mass structures extracted from an ACR phantom. In-plane images of the phantoms were acquired to investigate their image qualities through observation, intensity profile plots, edge enhancement evaluations, and/or contrast-to-noise ratio calculations. In addition, the robust phase-attenuation duality (PAD)-based phase retrieval method was applied to tomosynthesis for the first time in this research. It was utilized as a preprocessing method to fully exhibit phase contrast on the angular projection before reconstruction. RESULTS The resolution and noise characteristics of this high-energy in-line phase contrast tomosynthesis prototype were successfully investigated and demonstrated. The phantom studies demonstrated that this imaging prototype can successfully remove the structure overlapping in phantom projections, obtain delineate interfaces, and achieve better contrast-to-noise ratio after applying phase retrieval to the angular projections. CONCLUSIONS This research successfully demonstrated a high-energy in-line phase contrast tomosynthesis prototype. In addition, the PAD-based method of phase retrieval was combined with tomosynthesis imaging for the first time, which demonstrated its capability in significantly improving the contrast-to-noise ratios in the images.

Image quality and dose efficiency of high energy phase sensitive x-ray imaging: Phantom studies

The goal of this preliminary study was to perform an image quality comparison of high energy phase sensitive imaging with low energy conventional imaging at similar radiation doses. The comparison was performed with the following phantoms: American College of Radiology (ACR), contrast-detail (CD), acrylic edge and tissue-equivalent. Visual comparison of the phantom images indicated comparable or improved image quality for all phantoms. Quantitative comparisons were performed through ACR and CD observer studies, both of which indicated higher image quality in the high energy phase sensitive images. The results of this study demonstrate the ability of high energy phase sensitive imaging to overcome existing challenges with the clinical implementation of phase contrast imaging and improve the image quality for a similar radiation dose as compared to conventional imaging near typical mammography energies. In addition, the results illustrate the capability of phase sensitive imaging to sustain the image quality improvement at high x-ray energies and for breast simulating phantoms, both of which indicate the potential to benefit fields such as mammography. Future studies will continue to investigate the potential for dose reduction and image quality improvement provided by high energy phase sensitive imaging.

Low dose high energy x-ray in-line phase sensitive imaging prototype: Investigation of optimal geometric conditions and design parameters.

The objective of this study was to investigate the optimization of a high energy in-line phase sensitive x-ray imaging prototype under different geometric and operating conditions for mammography application. A phase retrieval algorithm based on phase attenuation duality (PAD) was applied to the phase contrast images acquired by the prototype. Imaging performance was investigated at four magnification values of 1.67, 2, 2.5 and 3 using an acrylic edge, an American College of Radiology (ACR) mammography phantom and contrast detail (CD) phantom with tube potentials of 100, 120 and 140 kVp. The ACR and CD images were acquired at the same mean glandular dose (MGD) of 1.29 mGy with a computed radiography (CR) detector of 43.75 μm pixel pitch at a fixed source to image distance (SID) of 170 cm. The x-ray tube focal spot size was kept constant as 7 μm while a 2.5 mm thick aluminum (Al) filter was used for beam hardening. The performance of phase contrast and phase retrieved images were compared with computer simulations based on the relative phase contrast factor (RPF) at high x-ray energies. The imaging results showed that the x-ray tube operated at 100 kVp under the magnification of 2.5 exhibits superior imaging performance which is in accordance to the computer simulations. As compared to the phase contrast images, the phase retrieved images of the ACR and CD phantoms demonstrated improved imaging contrast and target discrimination. We compared the CD phantom images acquired in conventional contact mode with and without the anti-scatter grid using the same prototype at 1.295 mGy and 2.59 mGy using 40 kVp, a 25 μm rhodium (Rh) filter. At the same radiation dose, the phase sensitive images provided improved detection capabilities for both the large and small discs, while compared to the double dose image acquired in conventional mode, the observer study also indicated that the phase sensitive images provided improved detection capabilities for the large discs. This study therefore validates the potential of using high energy phase contrast x-ray imaging to improve lesion detection and reduce radiation dose for clinical applications such as mammography.

The effects of x-ray beam hardening on detective quantum efficiency and radiation dose

The goal of this preliminary study was to investigate the effects of x-ray beam hardening on the detective quantum efficiency (DQE) and the radiation dose of an inline x-ray imaging system. The ability to decrease the risk of harmful radiation to the patient without compromising the detection capability would more effectively balance the tradeoff between image quality and radiation dose, and therefore benefit the fields of diagnostic x-ray imaging, especially mammography. The DQE and the average glandular dose were both calculated under the same experimental conditions for a range of beam hardening levels, corresponding to no added beam hardening and two thicknesses each of Rhodium (Rh) and Molybdenum (Mo) filters. The dose calculation results demonstrate a reduction of 15% to 24% for the range of beam hardening levels. The comparison of all quantities comprising the DQE exhibit very close correlation between the results obtained without added beam hardening to the results corresponding to the range of beam hardening levels. For the specific experimental conditions utilized in this preliminary study, the results are an indication that the use of beam hardening holds the potential to reduce the radiation dose without decreasing the performance of the system. Future studies will seek to apply this method in a clinical environment and perform a comprehensive image quality evaluation, in an effort to further evaluate the potential of beam hardening to balance the tradeoff between dose and image quality.

Detectability comparison between a high energy x-ray phase sensitive and mammography systems in imaging phantoms with varying glandular-adipose ratios

The objective of this study was to demonstrate the potential benefits of using high energy x-rays in comparison with the conventional mammography imaging systems for phase sensitive imaging of breast tissues with varying glandular-adipose ratios. This study employed two modular phantoms simulating the glandular (G) and adipose (A) breast tissue composition in 50 G-50 A and 70 G-30 A percentage densities. Each phantom had a thickness of 5 cm with a contrast detail test pattern embedded in the middle. For both phantoms, the phase contrast images were acquired using a micro-focus x-ray source operated at 120 kVp and 4.5 mAs, with a magnification factor (M) of 2.5 and a detector with a 50 µm pixel pitch. The mean glandular dose delivered to the 50 G-50 A and 70 G-30 A phantom sets were 1.33 and 1.3 mGy, respectively. A phase retrieval algorithm based on the phase attenuation duality that required only a single phase contrast image was applied. Conventional low energy mammography images were acquired using GE Senographe DS and Hologic Selenia systems utilizing their automatic exposure control (AEC) settings. In addition, the automatic contrast mode (CNT) was also used for the acquisition with the GE system. The AEC mode applied higher dose settings for the 70 G-30 A phantom set. As compared to the phase contrast images, the dose levels for the AEC mode acquired images were similar while the dose levels for the CNT mode were almost double. The observer study, contrast-to-noise ratio and figure of merit comparisons indicated a large improvement with the phase retrieved images in comparison to the AEC mode images acquired with the clinical systems for both density levels. As the glandular composition increased, the detectability of smaller discs decreased with the clinical systems, particularly with the GE system, even at higher dose settings. As compared to the CNT mode (double dose) images, the observer study also indicated that the phase retrieved images provided similar or improved detection for all disc sizes except for the disk diameters of 2 mm and 1 mm for the 50 G-50 A phantom and 3 mm and 0.5 mm for the 70 G-30 A phantom. This study demonstrated the potential of utilizing a high energy phase sensitive x-ray imaging system to improve lesion detection and reduce radiation dose when imaging breast tissues with varying glandular compositions.

Error analysis in the measurement of x-ray photon fluence: an analysis on the uncertainty from energy calibration

The measurements of x-ray spectra and photon fluence are of significant importance in medical imaging applications. The complexity of the spectral measurements and photon fluence calculation leads to possible errors which may come from various sources. The focus of this project is to study the mathematical method to determine the uncertainty that is propagated from the energy calibration process into the photon fluence calculation. In order to form a basis for the uncertainty analysis, a straightforward derivation on the calculation of the photon fluence based on spectral and exposure measurements is provided. Then the uncertainty in the determination of the energy-channel linear relationship is calculated. Instead of using this linear relationship to calibrate the measured spectra, we calibrate the mass energy absorption coefficients, in an effort to separate the calibration uncertainty from the measurement uncertainty in the spectra, and to simplify the subsequent derivation on uncertainty propagation. Finally, the formula on the uncertainty in photon fluence that is from the calibration process is derived.

Using Microbubble as Contrast Agent for High-Energy X-Ray In-line Phase Contrast Imaging: Demonstration and Comparison Study

The ability of microbubbles to benefit the imaging quality of high-energy in-line phase contrast as compared with conventional low-energy contact mode radiography was investigated. The study was conducted by comparing in-line phase contrast imaging with conventional contact-mode projection imaging under the same dose delivered to a phantom. A custom-designed phantom was employed to simulate a segment of human blood vessel injected with microbubble suspensions. The microbubbles were suspended in deionized water to obtain different volume concentrations. The area contrast-to-noise ratio (CNR) values corresponding to both imaging methods were measured for different microbubble volume concentrations. The phase contrast images were processed by phase-attenuation duality phase retrieval to preserve the imaging quality. Comparison of the resultant CNR values indicates that the microbubble suspension images deliver a higher CNR than the water-only image, with monotonically increasing trends between the CNR values and microbubble concentrations. Compared to low-energy conventional images of the microbubble suspensions, high-energy in-line phase contrast CNRs are lower at high concentrations and are comparable, even better than, at low concentrations. This result suggests that 1) the performance of copolymer-shell microbubble employed in this study as x-ray contrast agent is constrained by the detective quantum efficiency of the system and the attenuation properties of the shell materials, 2) the phase-attenuation duality phase retrieval method has the potential to preserve image quality for areas with low concentration of microbubbles, and 3) the selection of microbubble products as a phase contrast agent may follow criteria of minimizing the impact of absorption attenuation properties of the shells and maximizing the difference factor of electron densities.

DQE characterization of a high-energy in-line phase contrast prototype under different kVp and beam filtration

The objective of this research is to characterize the detective quantum efficiency (DQE) of a high-energy in-line phase contrast prototype operated under different x-ray exposure conditions. First of all, an imaging prototype was demonstrated based on a high-energy in-line phase contrast system prototype. The DQE of this system is calculated through modulation transfer function (MTF), noise power spectrum (NPS) and input signal to noise ratio under a fixed radiation dose. The radiation dose was estimated by employing a 4-cm-thick BR12 phantom. In this research, the x-ray exposure conditions were modified by not only using different tube voltage but also different prime beam filtration. Aluminum, Molybdenum, Rhodium, and a combined filter were selected to acquire a variety of x-ray energy compositions with 100, 110 and 120 kVp exposures. The resultant curves are compared through the modes of different kVp/same filter and different filter/same kVp. As a result, the curves obtained under a fixed radiation dose, indicate that the MTF performs similar behavior under different experimental mode; the NPS is majorly affected by the composition of x-ray photon energies; and the overall DQE decreases with the increasing portion of high-energy x-ray photons in the exposure.

Preliminary investigation on the effect of x-ray beam hardening on detective quantum efficiency and radiation dose

The goal of this study was to evaluate the effect of beam hardening on the detective quantum efficiency and the radiation dose provided by the imaging system. Both studies involved a comparison of values determined without added beam hardening to those resulting from a range of beam hardening. Under the specific experimental conditions of the study, the detective quantum efficiency comparison revealed only small changes in the system performance, and the dose comparison indicated the potential of reducing the dose through the use of beam hardening. Future studies are needed to further evaluate the effects of beam hardening on both quantities, as well as the correlation between them.