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.

Evaluation and comparison of a CdTe based photon counting detector with an energy integrating detector for X-ray phase sensitive imaging of breast cancer.

PURPOSE: To compare imaging performance of a cadmium telluride (CdTe) based photon counting detector (PCD) with a CMOS based energy integrating detector (EID) for potential phase sensitive imaging of breast cancer. METHODS: A high energy inline phase sensitive imaging prototype consisting of a microfocus X-ray source with geometric magnification of 2 was employed. The pixel pitch of the PCD was 55µm, while 50µm for EID. The spatial resolution was quantitatively and qualitatively assessed through modulation transfer function (MTF) and bar pattern images. The edge enhancement visibility was assessed by measuring edge enhancement index (EEI) using the acrylic edge acquired images. A contrast detail (CD) phantom was utilized to compare detectability of simulated tumors, while an American College of Radiology (ACR) accredited phantom for mammography was used to compare detection of simulated calcification clusters. A custom-built phantom was employed to compare detection of fibrous structures. The PCD images were acquired at equal, and 30% less mean glandular dose (MGD) levels as of EID images. Observer studies along with contrast to noise ratio (CNR) and signal to noise ratio (SNR) analyses were performed for comparison of two detection systems. RESULTS: MTF curves and bar pattern images revealed an improvement of about 40% in the cutoff resolution with the PCD. The excellent spatial resolution offered by PCD system complemented superior detection of the diffraction fringes at boundaries of the acrylic edge and resulted in an EEI value of 3.64 as compared to 1.44 produced with EID image. At equal MGD levels (standard dose), observer studies along with CNR and SNR analyses revealed a substantial improvement of PCD acquired images in detection of simulated tumors, calcification clusters, and fibrous structures. At 30% less MGD, PCD images preserved image quality to yield equivalent (slightly better) detection as compared to the standard dose EID images. CONCLUSION: CdTe-based PCDs are technically feasible to image breast abnormalities (low/high contrast structures) at low radiation dose levels using the high energy inline phase sensitive imaging technique.

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).

Dual-energy phase retrieval algorithm for inline phase sensitive x-ray imaging system.

Phase retrieval is vital for quantitative x-ray phase contrast imaging. This work presents an iterative method to simultaneously retrieve the x-ray absorption and phase images from a single x-ray exposure. The proposed approach uses the photon-counting detectors' energy-resolving capability in providing multiple spectrally resolved phase contrast images from a single x-ray exposure. The retrieval method is derived, presented, and experimentally tested with a multi-material phantom in an inline phase contrast imaging setup. By separating the contributions of photoelectric absorption and Compton scattering to the attenuation, the authors divide the phase contrast image into two portions, the attenuation map arises from photoelectric absorption and a pseudo phase contrast image generated by electron density. This way one can apply the Phase Attenuation Dualiby (PAD) algorithm and Fresnel propagation for the iteration. The retrieval results from the experimental images show that this iterative method is fast, accurate, robust against noise, and thus yields noticeable enhancement in contrast to noise ratios.

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.

Predicting fringe visibility in dual-phase grating interferometry with polychromatic X-ray sources.

Dual phase grating X-ray interferometry is radiation dose-efficient as compared to common Talbot-Lau grating interferometry. The authors developed a general quantitative theory to predict the fringe visibility in dual-phase grating X-ray interferometry with polychromatic X-ray sources. The derived formulas are applicable to setups with phase gratings of any phase modulation and with either monochromatic or polychromatic X-rays. Numerical simulations are presented to validate the derived formulas. The theory provides useful tools for design optimization of dual-phase grating X-ray interferometers.

Sample phase gradient and fringe phase shift in triple phase grating X-ray interferometry.

Triple phase grating X-ray interferometry is a promising new technique of grating based X-ray differential phase contrast imaging. Accurate retrieval of sample phase gradients from measured interference fringe shifts is a key task in X-ray interferometry. To fulfill this task in triple phase grating X-ray interferometry with monochromatic X-ray sources, the authors derived exact formulas relating sample phase gradient to fringe phase shift. These formulas not only provide a design optimization tool for triple phase grating interferometry, but also lay a foundation for quantitative phase contrast imaging.

Sample phase gradient and fringe phase shift in dual phase grating X-ray interferometry.

One of the key tasks in grating based x-ray phase contrast imaging is to accurately retrieve local phase gradients of a sample from measured intensity fringe shifts. To fulfill this task in dual phase grating interferometry, one needs to know the exact mathematical relationship between the two. In this work, using intuitive analysis of the sample-generated fringe shifts based on the beat pattern formation mechanism, the authors derived the formulas relating sample phase gradients to fringe phase shifts. These formulas provide also a design optimization tool for dual phase grating interferometry.

Impact of a single distance phase retrieval algorithm on spatial resolution in X-ray inline phase sensitive imaging.

A single-projection based phase retrieval method based on the phase attenuation duality principle (PAD) was used to compare the spatial resolution of the acquired phase sensitive and PAD processed phase retrieved images. An inline phase sensitive prototype was used to acquire the phase sensitive images. The prototype incorporates a micro-focus x-ray source and a flat panel detector with a 50 µm pixel pitch. A phantom composed of a 2 cm thick 50-50 adipose-glandular mimicking slab sandwiched with a 0.82 cm thick slanted PMMA sharp edge was used. Phase sensitive image of the phantom was acquired at 120 kV, 3.35 mAs with a 16 µm tube focal spot size under a geometric magnification (M) of 2.5. The PAD based method was applied to the acquired phase sensitive image for the retrieval of phase values. With necessary data processing, modulation transfer function (MTF) curves were determined for the estimation and comparison of the spatial resolution. The PAD processed phase retrieved values of the phantom were in good agreement with the theoretically calculated values. Phase sensitive images showed higher spatial resolution at all spatial frequencies compared to the phase retrieved images. It was noted that the high-frequency signal components in the retrieved image were suppressed that resulted in lower MTF values. When compared to the phase sensitive image, the cutoff resolution (10% MTF) for phase retrieved image dropped 32% from 15.6 lp/mm (32µm) to 10.6 lp/mm (47µm). The resolution offered by this phase sensitive prototype is radiographically enough to detect breast cancer.

Clarification on generalized Lau condition for X-ray interferometers based on dual phase gratings.

To implement dual phase grating x-ray interferometry with x-ray tubes, one needs to incorporate an absorbing source grating. In order to attain good fringe visibility, the period of a source grating should be subject to a stringent condition. In literature some authors claim that the Lau-condition in Talbot-Lau interferometry can be literally transferred to dual phase grating interferometry. In this work we show that this statement in literature is incorrect. Instead, through an intuitive geometrical analysis of fringe formation, we derived a new generalized Lau-condition that provides a useful design tool for implementation of dual phase grating interferometry.

Image quality assessment of a photon counting detector in x-ray projection imaging.

The recent advancements in the photon counting detection have created a significant growing research interest in the x-ray imaging. It is essential to objectively understand the image quality parameters of a photon counting detector before developing imaging applications. In this work, we have assessed the imaging quality of a cadmium telluride (CdTe) based PCD in projection imaging mode. The detector is 70.4 mm × 6.6 mm dimensions. The detector has a pixel array of 64×4 with a pixel pitch of 1.1 mm×1.65 mm. With each pixel having 4 channels in its corresponding ASIC, this PCD can create three bin images from a single projection. With a microfocus x-ray source, the imaging quality in each bin image was measured in terms of the spatial resolution, noise, and contrast to noise ratio (CNR). We used 70 kV, 50µA, 10 s (0.5mAs) with 0.5mm thick aluminum (Al) filter for the acquisition of each image. The MTF curves indicated that the spatial resolution for the bin-1, bin-2, and bin-3 was almost identical. The NNPS curves indicated that the noise in bin 1 and bin 2 images was almost the same for all frequencies while bin 3 image had relatively less noise. The CNR analyses showed that the bin-1 image had the highest CNR. As the flux was increased from 0.5 to 1 mAs, the number of detected counts also increased that resulted in the CNR increase. Beyond this flux, the pulse pileup occurred due to which multiple counts were read as single that resulted in few detected counts and lower CNR. The knowledge of the spatial resolution, noise, and CNR in terms of energy binning allows the determination and optimization of imaging techniques necessary for various applications.

Quantitative theory of X-ray interferometers based on dual phase grating: Fringe period and visibility.

In most of grating x-ray interferometry one needs an absorbing grating as the analyzer to measure high-resolution interference fringes. Dual phase grating interferometry is a technique to get rid of the absorbing grating for radiation dose reduction. The authors present a quantitative theory of dual grating x-ray interferometry. The theory elucidates the fringe formation mechanism. The derived formulas of fringe period and fringe visibility provide useful tools for design optimization of dual phase grating interferometers.

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.

Beam hardening correction in polychromatic x-ray grating interferometry.

The beam hardening is one of the two causes of the fringe shift distortion in polychromatic X-ray grating interferometry. Based on the assumption of the uniform energy dependence, we developed a novel analytic approach to accurately retrieve the monochromatic attenuation function and fringe phase shift from the polychromatic measurement. This approach provides a useful tool for precise measurement of sample electron density distribution in X-ray grating interferometry.

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.

Polychromatic X-ray effects on fringe phase shifts in grating interferometry.

In order to quantitatively determine the projected electron densities of a sample, one needs to extract the monochromatic fringe phase shifts from the polychromatic fringe phase shifts measured in the grating interferometry with incoherent X-ray sources. In this work the authors propose a novel analytic approach that allows to directly compute the monochromatic fringe shifts from the polychromatic fringe shifts. This approach is validated with numerical simulations of several grating interferometry setups. This work provides a useful tool in quantitative imaging for biomedical and material science applications.