Grating-based x-ray dark-field CT for lung cancer diagnosis in mice.

BACKGROUND: The low absorption of x-rays in lung tissue and the poor resolution of conventional computed tomography (CT) limits its use to detect lung disease. However, x-ray dark-field imaging can sense the scattered x-rays deflected by the structures being imaged. This technique can facilitate the detection of small alveolar lesions that would be difficult to detect with conventional CT. Therefore, it may provide an alternative imaging modality to diagnose lung disease at an early stage. METHODS: Eight mice were inoculated with lung cancers simultaneously. Each time two mice were scanned using a grating-based dark-field CT on days 4, 8, 12, and 16 after the introduction of the cancer cells. The detectability index was calculated between nodules and healthy parenchyma for both attenuation and dark-field modalities. High-resolution micro-CT and pathological examinations were used to crosscheck and validate our results. Paired t-test was used for comparing the ability of dark-field and attenuation modalities in pulmonary nodule detection. RESULTS: The nodules were shown as a signal decrease in the dark-field modality and a signal increase in the attenuation modality. The number of nodules increased from day 8 to day 16, indicating disease progression. The detectability indices of dark-field modality were higher than those of attenuation modality (p = 0.025). CONCLUSIONS: Compared with the standard attenuation CT, the dark-field CT improved the detection of lung nodules. RELEVANCE STATEMENT: Dark-field CT has a higher detectability index than conventional attenuation CT in lung nodule detection. This technique could improve the early diagnosis of lung cancer. KEY POINTS: • Lung cancer progression was observed using x-ray dark-field CT. • Dark-field modality complements with attenuation modality in lung nodule detection. • Dark-field modality showed a detectability index higher than that attenuation in nodule detection.

Iterative signal retrieval for X-ray grating interferometry with dual-shot.

BACKGROUND: X-ray grating interferometry normally requires multiple steps and exposures, causing a prolonged imaging time. There is motivation to use fewer steps to reduce scanning time and complexity, while keeping fidelity of the retrieved signals. OBJECTIVE: We propose an iterative signal retrieval method, extracting attenuation, dark field contrast (DFC), and differential phase contrast (DPC) signals from two X-ray exposures. METHODS: Two shots were captured at G2 grating positions with difference of 1/4 grating period. The algorithm consists of two stages. At the first stage, amplitude of sample phase stepping curve retrieved by virtual phase stepping (VPS) method, visibility and local phase of background phase stepping curve are used to limit the results to the proximity of the ground truth. After the second stage, three high-quality parameters, amplitude, visibility, and local phase, are retrieved through finetuning, and three signals are calculated. Simulated and real-sample experiments were conducted to validate this method. RESULTS: We used standard phase stepping result as benchmark and calculated structural similarity (SSIM) and peak signal-to-noise ratio (PSNR) between benchmark and parameters retrieved by our dual-shot method and virtual phase stepping (VPS) method. For both simulated and real-sample experiments, the SSIM and PSNR value of dual-shot method are higher than those of VPS method. For real-sample method, we also conducted a three-step PS, and the SSIM and PSNR value of dual-shot method are slightly lower than those of three-step PS. CONCLUSION: Using our dual-shot method demonstrates higher performance than other single-shot method in retrieving high-quality signals, and it also reduces radiation dose and time.

Bacterial and Fungal Infections Promote the Bone Erosion Progression in Acquired Cholesteatoma Revealed by Metagenomic Next-Generation Sequencing.

An acquired cholesteatoma generally occurs as a consequence of otitis media and eustachian tube dysfunction. Patients with acquired cholesteatoma generally present with chronic otorrhea and progressive conductive hearing loss. There are many microbes reportedly associated with acquired cholesteatoma. However, conventional culture-based techniques show a typically low detection rate for various pathogenetic bacteria and fungi. Metagenomic next-generation sequencing (mNGS), an emerging powerful platform offering higher sensitivity and higher throughput for evaluating many samples at once, remains to be studied in acquired cholesteatoma. In this study, 16 consecutive patients from January 2020 to January 2021 at the Second Affiliated Hospital of Zhejiang University School of Medicine (SAHZU) were reviewed. We detected a total of 31 microbial species in patients, mNGS provided a higher detection rate compared to culture (100% vs. 31.25%, p = 0.000034). As the severity of the patient's pathological condition worsens, the more complex types of microbes were identified. The most commonly detected microbial genus was Aspergillus (9/16, 56.25%), especially in patients suffering from severe bone erosion. In summary, mNGS improves the sensibility to identify pathogens of cholesteatoma patients, and Aspergillus infections increase bone destruction in acquired cholesteatoma.

Pathogenic mechanism of congenital cataract caused by the CRYBA1/A3-G91del variant and related intervention strategies.

Congenital cataracts, which are genetically heterogeneous eye disorders, lead to visual impairment in childhood. In our previous study, we identified a novel mutation in exon 4 of the CRYBA1/BA3 gene, which resulted in the deletion of a highly conserved glycine at codon 91 (G91del) and perinuclear zonular cataract. The G91del variant is one of the most frequent pathogenic mutations in CRYBA1/BA3; however, its pathogenic mechanism remains unclear. In this study, we purified ßA3-crystallin and the ßA3-G91del variant. ßA3-G91del was prone to proteolysis and exhibited very low solubility and low structural stability. Next, we constructed a CRYBA1/BA3 mutant cell model and observed that G91del mutant proteins were more sensitive to environmental stress and prone to form aggregates. Size-exclusion chromatography and molecular dynamics simulation showed that the G91del mutation impaired the ability of ßA3 to form homo-oligomers. In addition, the protein folding process of ßA3-G91del was complicated and showed more intermediate states, resulting in amyloid fiber aggregation and induction of cellular apoptosis. Finally, we investigated intervention strategies for congenital cataract caused by the CRYBA1/A3-G91del variant. The addition of lanosterol reversed the negative effects of the G91del mutation under external stress. This study may help explore potential treatment strategies for related cataracts.

Fluence adaptation for contrast-based dose optimization in x-ray phase-contrast imaging.

PURPOSE: X-ray phase-contrast imaging (XPCI) can provide multiple contrasts with great potentials for clinical and industrial applications, including conventional attenuation, phase contrast, and dark field. Grating-based imaging (GBI) and edge-illumination (EI) are two promising types of XPCI as the conventional x-ray sources can be directly utilized. For the GBI and EI systems, the phase-stepping acquisition with multiple exposures at a constant fluence is usually adopted in the literature.This work, however, attempts to challenge such a constant fluence concept during the phase-stepping process and proposes a fluence adaptation mechanism for dose reduction. METHOD: Given the importance of patient radiation dose for clinical applications, numerous studies have tried to reduce patient dose in XPCI by altering imaging system designs, data acquisition, and information retrieval. Recently, analytic multiorder moment analysis has been proposed to improve the computing efficiency. In these algorithms, multiple contrasts can be calculated by summing together the weighted phase-stepping curves (PSCs) with some kernel functions, which suggests us that the raw data at different steps have different contributions for the noise in retrieved contrasts. Therefore, it is possible to improve the noise performance by adjusting the fluence distribution during the phase-stepping process directly. Based on analytic retrieval formulas and the Gaussian noise model for detected signals, we derived an optimal adaptive fluence distribution, which is proportional to the absolute weighting kernel functions and the root of original sample PSCs acquired under the constant fluence. Considering that the original sample PSC might be unavailable, we proposed two practical forms for the GBI and EI systems, which are also able to reduce the contrast noise when comparing with the constant fluence distribution. Since the kernel functions are target contrast-dependent, our proposed fluence adaptation mechanism provides a way of realizing a contrast-based dose optimization while keeping the same noise level. RESULTS: To validate our analyses, simulations and experiments are conducted for the GBI and EI systems. Simulated results demonstrate that the dose reduction ratio between our proposed fluence distributions and the typical constant one can be about 20% for the phase contrast, which is consistent with our theoretical predictions. Although the experimental noise reduction ratios are a little smaller than the theoretical ones, low-dose experiments observe better noise performance by our proposed method. Our simulated results also give out the effective ranges of the parameters of the PSCs, such as the visibility in the GBI, the standard deviation, and the mean value in the EI, providing a guidance for the use of our proposed approach in practice. CONCLUSIONS: In this paper, we propose a fluence adaptation mechanism for contrast-based dose optimization in XPCI, which can be applied to the GBI and EI systems. Our proposed method explores a new direction for dose reduction, and may also be further extended to other types of XPCI systems and information retrieval algorithms.

Fourier-based interpretation and noise analysis of the moments of small-angle x-ray scattering in grating-based x-ray phase contrast imaging.

In grating-based x-ray phase contrast imaging, Fourier component analysis (FCA) is usually recognized as a gold standard to retrieve the contrasts including attenuation, phase and dark-field, since it is well-established on wave optics and is of high computational efficiency. Meanwhile, an alternative approach basing on the particle scattering theory is being developed and can provide similar contrasts with FCA by calculating multi-order moments of deconvolved small-angle x-ray scattering, so called as multi-order moment analysis (MMA). Although originated from quite different physics theories, the high consistency between the contrasts retrieved by FCA and MMA implies us that there may be some intrinsic connections between them, which has not been fully revealed to the best of our knowledge. In this work, we present a Fourier-based interpretation of MMA and conclude that the contrasts retrieved by MMA are actually the weighted compositions of Fourier coefficients, which means MMA delivers similar physical information as FCA. Based on the recognized cosine model, we also provide a truncated analytic MMA method, and its computational efficiency can be hundreds of times faster than the original deconvolution-based MMA method. Moreover, a noise analysis for our proposed truncated method is also conducted to further evaluate its performances. The results of numerical simulation and physical experiments support our analyses and conclusions.

The trigonometric orthogonality of phase-stepping curves in grating-based x-ray phase-contrast imaging: Integral property and its implications for noise optimization.

PURPOSE: Grating-based x-ray phase-contrast imaging (GPCI) is a promising technique for clinical applications as it can provide two newly emerging imaging modalities (differential phase-contrast and dark-field contrast) in addition to the conventional absorption contrast. As far, phase-stepping strategy is the most commonly used approach in GPCI to indirectly acquire differential phase-contrast and dark-field contrast. It is known that the obtained phase-stepping curves (PSCs) have the cosine property and the convolution property, leading to two types of information retrieval approaches in literature: the Fourier component analysis and the multi-order moment analysis. The purpose of this paper is to derive a new property of PSCs and apply the property to noise optimization for information retrieval. METHODS: Based on the cosine expression of the flat PSC without the sample and the well-established convolution relationship between the flat PSC and the sample PSC, we reveal an important integral property of PSCs: the inner product of PSCs and an arbitrary function contains only zero-order and first-order components in the Fourier series. Furthermore, we apply the property to the direct multi-order moment analysis and propose a set of generalized forms including an optimal one in the presence of noise. RESULTS: To validate the effectiveness of our analysis, we compared the simulated and real experiment results retrieved by the original direct multi-order moment analysis with the ones retrieved by our proposed noise-optimal form. A significant improvement of noise performance by our method is observed and the improvement ratio in differential phase-contrast is consistent with our theoretical calculation (39.2%). CONCLUSIONS: In this paper, we reveal a new integral property of the acquired PSCs with and without samples in GPCI, which can be applied to information retrieval approaches like the direct multi-order moment analysis. Then we optimize these approaches to improve the noise performance, offering great potentials of dose reduction in practical applications.