A Pilot Study to Assess the Performance of Phase-Sensitive Breast Tomosynthesis.

Background A new modality, phase-sensitive breast tomosynthesis (PBT), may have similar diagnostic performance to conventional breast tomosynthesis but with a reduced radiation dose. Purpose To perform a pilot study of the performance of a novel PBT system compared with conventional digital breast tomosynthesis (DBT) in patients undergoing additional diagnostic imaging workup for breast lesions. Materials and Methods In a prospective study from June 2020 to March 2021, participants with suspicious breast lesions detected at screening DBT or MRI were recruited for additional PBT imaging before additional diagnostic workup or biopsy. In this pilot study, nine radiologists independently evaluated image quality and assessed the likelihood of lesion malignancy by retrospectively evaluating DBT and PBT images in two separate reading sessions. Image quality was rated subjectively using a Likert scale from 1 to 5. Areas under the receiver operating characteristic curve (AUCs) were used to compare the lesion classification (malignant vs benign) performance of the radiologists. Results Images in 50 patients (mean age, 56 years ± 12 [SD]; 49 women) with 52 evaluable lesions (28 malignant) were assessed. For image appearance and general feature visibility, DBT images had a higher total mean image quality score (3.8) than PBT images (2.9), with P < .002 for each comparison. For classification of lesions as benign or malignant, the AUCs were 0.74 for both PBT and DBT. PBT images were acquired at a 24% mean radiation dose reduction (mean, 1.78 mGy vs 2.34 mGy for DBT; P < .001). Conclusion The phase-sensitive breast tomosynthesis system had a 24% lower mean radiation dose compared with digital breast tomosynthesis, although with lower image quality. Diagnostic performance of the system remains to be determined in larger studies. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Gao and Moy in this issue.

A phase sensitive x-ray breast tomosynthesis system: Preliminary patient images with cancer lesions.

Phase-sensitive x-ray imaging continues to attract research for its ability to visualize weakly absorbing details like those often encountered in biology and medicine. We have developed and assembled the first inline-based high-energy phase sensitive breast tomosynthesis (PBT) system, which is currently undergoing patient imaging testing at a clinical site. The PBT system consists of a microfocus polychromatic x-ray source and a direct conversion-based flat panel detector coated with a 1 mm thick amorphous selenium layer allowing a high detective quantum efficiency at high energies. The PBT system scans a compressed breast over 15° with 9 angular projection views. The high-energy scan parameters are carefully selected to ensure similar or lower mean glandular dose levels to the clinical standard of care systems. Phase retrieval and data binning are applied to the phase contrast angular projection views and a filtered back-projection algorithm is used to reconstruct the final images. This article reports the distributions of radiation dose versus thickness of the compressed breasts at 59 and 89 kV and sample PBT images acquired from 3 patients. Preliminary PBT images demonstrate the feasibility of this new imaging modality to acquire breast images at lower radiation dose as compared to the clinical digital breast tomosynthesis system with enhanced lesion characteristics (i.e. lesion spiculation and margins).

Mathematical estimation of half-value layer thicknesses.

OBJECTIVE: The objective of this article is to introduce a simplified and swift method to satisfactorily estimate the half-value layers (HVL), quarter-value layer (QVL), and tenth-value layer (TVL) from the x-ray spectra emitted by any diagnostic radiology or kV radiotherapy x-ray tubes. METHODS: A CdTe x-ray and Gamma detector (X-123 CdTe, AmpTek Inc.) is used to measure the x-ray spectra at four different x-ray energies (low, mid, high energy x-rays) with different external filtering. The software "SpekCalc GUI" (Developed in McGill University, Montreal, Canada) is also used to obtain the simulated x-ray spectra. Both measured and simulated spectra are used to compute the HVL thicknesses of Aluminum by a mathematical method presented in this article. Next, the HVL thicknesses for corresponding tube potentials are also measured by calibrated ionization chamber and varying thicknesses of aluminum plates. Finally, the computed and measured HVL, QVL, and TVL thicknesses are compared to evaluate the efficacy of the presented method. RESULTS: The results show acceptable concordance between computed and measured quantities. The disagreement rates between measured HVL and the values derived mathematically from the x-ray spectra are 10 to 90 micrometers of Aluminum at tube potentials of 31 kV to 120 kV. As it is shown, a negligible discrepancy is observed between the analytical estimation and the experimental assessments. CONCLUSION: The HVL is an essential component in the evaluation of the quality of an x-ray beam. However, its measurement could occasionally be challenging, time-consuming, or uncertain due to some technical difficulties. Although the scope of this study is not to undermine the value of conventional and widely accepted practice to determine the HVL thickness, the introduced method provides the fast, more convenient, and comparably reliable technique to estimate the HVL, QVL, and TVL by employing the given x-ray spectrum.

Development and preclinical evaluation of a patient-specific high energy x-ray phase sensitive breast tomosynthesis system.

BACKGROUND: This article reports the first x-ray phase sensitive breast tomosynthesis (PBT) system that is aimed for direct translation to clinical practice for the diagnosis of breast cancer. PURPOSE: To report the preclinical evaluation and comparison of the newly built PBT system with a conventional digital breast tomosynthesis (DBT) system. METHODS AND MATERIALS: The PBT system is developed based on a comprehensive inline phase contrast theoretical model. The system consists of a polyenergetic microfocus x-ray source and a flat panel detector mounted on an arm that is attached to a rotating gantry. It acquires nine projections over a 15° angular span in a stop-and-shoot manner. A dedicated phase retrieval algorithm is integrated with a filtered back-projection method that reconstructs tomographic slices. The American College of Radiology (ACR) accreditation phantom, a contrast detail (CD) phantom and mastectomy tissue samples were imaged at the same glandular dose levels by both the PBT and a standard of care DBT system for image quality characterizations and comparisons. RESULTS: The PBT imaging scores with the ACR phantom are in good to excellent range and meet the quality assurance criteria set by the Mammography Quality Standard Act. The CD phantom image comparison and associated statistical analyses from two-alternative forced-choice reader studies confirm the improvement offered by the PBT system in terms of contrast resolution, spatial resolution, and conspicuity. The artifact spread function (ASF) analyses revealed a sizable lateral spread of metal artifacts in PBT slices as compared to DBT slices. Signal-to-noise ratio values for various inserts of the ACR and CD phantoms further validated the superiority of the PBT system. Mastectomy sample images acquired by the PBT system showed a superior depiction of microcalcifications vs the DBT system. CONCLUSION: The PBT imaging technology can be clinically employed for improving the accuracy of breast cancer screening and diagnosis.

The role of chest computed tomography in the management of COVID-19: A review of results and recommendations.

IMPACT STATEMENT: The impact of the COVID-19 pandemic has been worldwide, and clinicians and researchers around the world have been working to develop effective and efficient methods for early detection as well as monitoring of the disease progression. This minireview compiles the various agency and expert recommendations, along with results from studies published in numerous countries, in an effort to facilitate the research in imaging technology development to benefit the detection and monitoring of COVID-19. To the best of our knowledge, this is the first review paper on the topic, and it provides a brief, yet comprehensive analysis.

Simultaneous quantification of candesartan and irbesartan in rabbit eye tissues by liquid chromatography-tandem mass spectrometry.

Diabetic retinopathy is a major cause of vision loss in adults. Novel eye-drop formulations of candesartan and irbesartan are being developed for its cure or treatment. To support a preclinical trial in rabbits, it was critical to develop and validate a new LC-MS/MS method for simultaneous quantification of candesartan and irbesartan in rabbit eye tissues (cornea, aqueous humor, vitreous body and retina/choroid). Eye tissue samples were first homogenized in H2 O-diluted rabbit plasma. The candesartan and irbesartan in the supernatants together with their respective internal standards (candesartan-d4 and irbesartan-d4 ) were extracted by solid-phase extraction. The extracted samples were injected onto a C18 column for gradient separation. The MS detection was in the positive electrospray ionization mode using the multiple reaction monitoring transitions of m/z 441 → 263, 445 → 267, 429 → 207, and 433 → 211 for candesartan, candesartan-d4 , irbesartan and irbesartan-d4 , respectively. For the validated concentration ranges (2-2000 and 5-5000 ng/g for candesartan and irbesartan, respectively), the within-run and between-run accuracies (% bias) were within the range of -8.0-10.0. The percentage CV ranged from 0.6 to 7.3. There was no significant matrix interference nor matrix effect from different eye tissues and different rabbits. The validated method was successfully used in the Good Laboratory Practice (GLP) study of rabbits.

Aberrant DNA Methylation in Acute Myeloid Leukemia and Its Clinical Implications.

Acute myeloid leukemia (AML) is a heterogeneous disease that is characterized by distinct cytogenetic or genetic abnormalities. Recent discoveries in cancer epigenetics demonstrated a critical role of epigenetic dysregulation in AML pathogenesis. Unlike genetic alterations, the reversible nature of epigenetic modifications is therapeutically attractive in cancer therapy. DNA methylation is an epigenetic modification that regulates gene expression and plays a pivotal role in mammalian development including hematopoiesis. DNA methyltransferases (DNMTs) and Ten-eleven-translocation (TET) dioxygenases are responsible for the dynamics of DNA methylation. Genetic alterations of DNMTs or TETs disrupt normal hematopoiesis and subsequently result in hematological malignancies. Emerging evidence reveals that the dysregulation of DNA methylation is a key event for AML initiation and progression. Importantly, aberrant DNA methylation is regarded as a hallmark of AML, which is heralded as a powerful epigenetic marker in early diagnosis, prognostic prediction, and therapeutic decision-making. In this review, we summarize the current knowledge of DNA methylation in normal hematopoiesis and AML pathogenesis. We also discuss the clinical implications of DNA methylation and the current therapeutic strategies of targeting DNA methylation in AML therapy.

A defective flexible loop contributes to the processing and gating defects of the predominant cystic fibrosis-causing mutation.

People with the genetic disease cystic fibrosis (CF) often carry a deletion mutation ΔF508 on the gene encoding the CF transmembrane conductance regulator (CFTR) Cl- channel. This mutation greatly reduces the CFTR maturation process and slows the channel opening rate. Here, we investigate whether residues near F508 contribute to these defects in ΔF508-CFTR. Most deletion mutations, but not alanine substitutions, of individual residues from positions 503 to 513 impaired CFTR maturation. Interestingly, only protein processing of ΔY512-CFTR, like that of ΔF508-CFTR, was greatly improved by low-temperature culture at 27°C or small-molecule corrector C18. The 2 mutant Cl- channels were equally slow to open, suggesting that they may share common structural flaws. Studies on the H3-H4 loop that links residues F508 and Y512 demonstrate that G509A/V510G mutations, moving G509 1 position backward in the loop, markedly enhanced ΔF508-CFTR maturation and opening rate while promoting protein stability and persistence of the H3 helix in ΔF508 nucleotide-binding domain 1. Moreover, V510A/S511A mutations noticeably increased ΔY512-CFTR maturation at 27°C and its opening rate. Thus, loop abnormalities may contribute to ΔF508- and ΔY512-CFTR defects. Importantly, correcting defects from G509 displacement in ΔF508-CFTR may offer a new avenue for drug discovery and CF treatments.-Chen, X., Zhu, S., Zhenin, M., Xu, W., Bose, S. J., Wong, M. P.-F., Leung, G. P. H., Senderowitz, H., Chen, J.-H. A defective flexible loop contributes to the processing and gating defects of the predominant cystic fibrosis-causing mutation.

Detectability comparison of simulated tumors in digital breast tomosynthesis using high-energy X-ray inline phase sensitive and commercial imaging systems.

This study compared the detectability of simulated tumors using a high-energy X-ray inline phase sensitive digital breast tomosynthesis (DBT) prototype and a commercial attenuation-based DBT system. Each system imaged a 5-cm thick modular breast phantom with 50-50 adipose-glandular percentage density containing contrast-detail (CD) test objects to simulate different tumor sizes. A commercial DBT system acquired 15 projection views over 15 degrees (15d-15p) was used to acquire the attenuation-based projection views and to reconstruct the conventional DBT slices. Attenuation-based projection views were acquired at 32 kV, 46 mAs with a mean glandular dose (Dg) of 1.6 mGy. For acquiring phase sensitive projection views, the prototype utilized two acquisition geometries: 11 projection views were acquired over 15 degrees (15d-11p), and 17 projection views were acquired over 16 degrees (16d-17p) at 120 kV, 5.27 mAs with 1.51 mGy under the magnification (M) of 2. A phase retrieval algorithm based on the phase-attenuation duality (PAD) was applied to each projection view, and a modified Feldkamp-Davis-Kress (FDK) algorithm was used to reconstruct the phase sensitive DBT slices. Simulated tumor margins were rated as more conspicuous and better visualized for both phase sensitive acquisition geometries versus conventional DBT imaging. The CD curves confirmed the improvement in both contrast and spatial resolutions with the phase sensitive DBT imaging. The superiority of the phase sensitive DBT imaging was further endorsed by higher contrast to noise ratio (CNR) and figure-of-merit (FOM) values. The CNR improvements provided by the phase sensitive DBT prototype were sufficient to offset the noise reduction provided by the attenuation-based DBT imaging.

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.

Quantitative investigation of the edge enhancement in in-line phase contrast projections and tomosynthesis provided by distributing microbubbles on the interface between two tissues: a phantom study.

The objective of this study was to quantitatively investigate the ability to distribute microbubbles along the interface between two tissues, in an effort to improve the edge and/or boundary features in phase contrast imaging. The experiments were conducted by employing a custom designed tissue simulating phantom, which also simulated a clinical condition where the ligand-targeted microbubbles are self-aggregated on the endothelium of blood vessels surrounding malignant cells. Four different concentrations of microbubble suspensions were injected into the phantom: 0%, 0.1%, 0.2%, and 0.4%. A time delay of 5 min was implemented before image acquisition to allow the microbubbles to become distributed at the interface between the acrylic and the cavity simulating a blood vessel segment. For comparison purposes, images were acquired using three system configurations for both projection and tomosynthesis imaging with a fixed radiation dose delivery: conventional low-energy contact mode, low-energy in-line phase contrast and high-energy in-line phase contrast. The resultant images illustrate the edge feature enhancements in the in-line phase contrast imaging mode when the microbubble concentration is extremely low. The quantitative edge-enhancement-to-noise ratio calculations not only agree with the direct image observations, but also indicate that the edge feature enhancement can be improved by increasing the microbubble concentration. In addition, high-energy in-line phase contrast imaging provided better performance in detecting low-concentration microbubble distributions.

Characterization of Continuous and Pulsed Emission modes of a Hybrid Micro Focus X-ray Source for Medical Imaging Applications.

The aim of this study was to quantitatively characterize a micro focus x-ray tube that can operate in both continuous and pulsed emission modes. The micro focus x-ray source (Model L9181-06, Hamamatsu Photonics, Japan) has a varying focal spot size ranging from 16-50 µm as the source output power changes from 10-39 W. We measured the source output, beam quality, focal spot sizes, kV accuracy, spectra shapes and spatial resolution. Source output was measured using an ionization chamber for various tube voltages (kVs) with varying current (µA) and distances. The beam quality was measured in terms of half value layer (HVL), kV accuracy was measured with a non-invasive kV meter, and the spectra was measured using a compact integrated spectrometer system. The focal spot sizes were measured using a slit method with a CCD detector with a pixel pitch of 22 µm. The spatial resolution was quantitatively measured using the slit method with a CMOS flat panel detector with a 50 µm pixel pitch, and compared to the qualitative results obtained by imaging a contrast bar pattern. The focal spot sizes in the vertical direction were smaller than that of the horizontal direction, the impact of which was visible when comparing the spatial resolution values. Our analyses revealed that both emission modes yield comparable imaging performances in terms of beam quality, spectra shape and spatial resolution effects. There were no significantly large differences, thus providing the motivation for future studies to design and develop stable and robust cone beam imaging systems for various diagnostic applications.

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.

Noise Power Characteristics of a Micro-Computed Tomography System.

OBJECTIVE: The aim of this study was to investigate the noise power properties of a micro-computed tomography (micro-CT) system under different operating conditions. METHODS: A commercial micro-CT was used in the study that used a flat panel detector with a 127-µm-pixel pitch and a micro-focus x-ray tube. Conical tubes of various diameters were used under different acquisition conditions. Multidimensional noise power spectrums were used as a metric to investigate the noise properties of the system. Noise power spectrum was calculated from the difference data generated by subtraction of 2 identical scans. The noise properties with respect to various parameters that include the impact of number of projections, x-ray spectra, milliampere-second, slice location, object diameter, voxel size, geometric magnification (M), back-projection filters, and reconstruction magnification (Mrecon) were studied. RESULTS: At a same isocentric exposure rate of 270 mR/s, the noise power was much lower for the image reconstructed with 3672 views (122 seconds) as compared with the 511 views (17 seconds), whereas at a fixed isocentric exposure of 4600 mR, the noise power levels were almost similar. Image noise with a 50-kV beam was higher as compared with the 90-kV beam at a same isocentric exposure. Image noise from a 16-mm-diameter conical tube was much lower as compared with the 28- and 56-mm tubes under identical isocentric exposures. The choice of back-projection filter influences noise power spectrum curves in terms of width and amplitudes. Reconstruction magnification applied during the reconstruction process increased the noise power at lower spatial frequencies but reduced the noise power at higher spatial frequencies. It can be established that, for small details corresponding to high spatial frequencies, reconstruction magnification can provide an improved signal-to-noise ratio. At all spatial frequencies, the in-plane images had lower noise power levels as compared with the z-plane images. CONCLUSIONS: The noise power properties investigated in this study provide important image quality references for refined cone beam system development, optimization, and operations.

Use of basic mobile phase to improve chromatography and boost sensitivity for quantifying tetrahydrocurcumin in human plasma by LC-MS/MS.

Tetrahydrocurcumin (THC), a major metabolite of curcumin, is often quantified by LC-MS or LC-MS/MS using acidic mobile phases due to the concern of its instability in a basic medium. However, acidic mobile phases often lead to poor chromatography (e.g. split or double peaks) and reduced detection sensitivity in the commonly used negative ionization mode. To overcome these shortcomings, a basic mobile phase was used for the first time in the LC-MS/MS quantification of THC. In comparison with the acidic mobile phases, a single symmetrical chromatographic peak was obtained and the sensitivity increased by 7-fold or more under the equivalent conditions. The new LC-MS/MS method using the basic mobile phase has been successfully validated for the quantification of THC in human EDTA plasma over the concentration range of 5-2500ng/ml. The within-batch accuracy (% nominal concentration) was between 88.7 and 104.9 and the between-batch accuracy ranged from 96.7 to 108.6. The CVs for within- and between-batch precisions were equal to or less than 5.5% and 9.1%, respectively. No significant matrix interference or matrix effect was observed from normal or lipemic and hemolytic plasma matrices. In addition, the common stabilities with adequate durations were established, including up to 5days of post-preparative stability. Furthermore, when the validated method was applied to a clinical study, the passing rate of ISR samples was 83%, indicating the good reproducibility of the method. The success of the unconventional approach presented in this article demonstrates that a mobile phase could be selected based mainly on its merits to facilitate LC separation and/or MS detection. There is no need for excessive concern about the stability of the compound(s) of interest in the selected mobile phase because the run time of modern LC-MS or LC-MS/MS methods is typically only a few minutes.

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.

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.

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.

Dose and detectability improvements with high energy phase sensitive x-ray imaging in comparison to low energy conventional imaging.

The objective of this study was to demonstrate the potential benefits of using high energy x-rays for phase sensitive breast imaging through a comparison with conventional mammography imaging. We compared images of a contrast-detail phantom acquired on a prototype phase sensitive x-ray imaging system with images acquired on a commercial flat panel digital mammography unit. The phase contrast images were acquired using a micro-focus x-ray source with a 50 µm focal spot at 120 kVp and 4.5 mAs, with a magnification factor of 2.46 and a 50 µm pixel pitch. A phase attenuation duality-based phase retrieval algorithm that requires only a single phase contrast image was applied. Conventional digital mammography images were acquired at 27 kVp, 131 mAs and 28 kVp, 54 mAs. For the same radiation dose, both the observer study and signal-to-noise ratio (SNR)/figure of merit comparisons indicated a large improvement by the phase retrieved image as compared to the clinical system for the larger disc sizes, but the improvement was not enough to detect the smallest discs. Compared to the double dose image acquired with the clinical system, the observer study also indicated that the phase retrieved image provided improved detection capabilities for all disc sizes except the smallest discs. Thus the SNR improvement provided by phase contrast imaging is not yet enough to offset the noise reduction provided by the clinical system at the doubled dose level. However, the potential demonstrated by this study for high energy phase sensitive x-ray imaging to improve lesion detection and reduce radiation dose in mammography warrants further investigation of this technique.

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.