Diagnostic Accuracy of Contrast-Enhanced Thoracic Photon-Counting Computed Tomography for Opportunistic Locoregional Staging of Breast Cancer Compared With Digital Mammography: A Prospective Trial.

OBJECTIVE: Accurate locoregional staging is crucial for effective breast cancer treatment. Photon-counting computed tomography (PC-CT) is an emerging technology with high spatial resolution and the ability to depict uptake of contrast agents in tissues, making it a promising tool for breast cancer imaging. The aim of this study was to establish the feasibility of locoregional staging of breast cancer through contrast-enhanced thoracic PC-CT, assess its diagnostic performance, and compare it with that of digital mammography (DM). MATERIALS AND METHODS: Patients with newly diagnosed breast cancer, DM, and indication of thoracic CT staging were prospectively enrolled in this clinical cohort study over a period of 6 months. Participants underwent contrast-enhanced thoracic PC-CT and breast magnetic resonance imaging in prone position. After blinding to patient data, 2 radiologists independently rated PC-CT and DM regarding the following 6 characteristics: (1) diameter of the largest mass lesion, (2) infiltration of cutis/pectoral muscle/thoracic wall, (3) number of mass lesions, (4) presence/absence of adjacent ductal carcinoma in situ (DCIS), (5) tumor conspicuity, and (6) diagnostic confidence. Reference standard was generated from consensus reading of magnetic resonance imaging combined with all histopathological/clinical data by an independent adjudication committee applying TNM eighth edition. RESULTS: Among 32 enrolled female subjects (mean ± SD age, 59 ± 13.0 years), diagnostic accuracy for T-classification was higher for PC-CT compared with DM (0.94 vs 0.50, P < 0.01). Moreover, the correlation of the number of detected tumor masses with the reference standard was stronger for PC-CT than for DM (0.72 vs 0.50, P < 0.01). We observed that PC-CT significantly (P < 0.04) outperformed DM regarding not only sensitivity (0.83 and 0.25, respectively) but also specificity (0.99 and 0.80, respectively) for adjacent DCIS. The κ values for interreader reliability were higher for PC-CT compared with DM (mean 0.88 vs 0.54, respectively; P = 0.01). CONCLUSIONS: Photon-counting computed tomography outperformed DM in T-classification and provided higher diagnostic accuracy for the detection of adjacent DCIS. Therefore, opportunistic locoregional staging of breast cancer in contrast-enhanced thoracic PC-CT is feasible and could overcome limitations of DM with the potential to improve patient management.

Pilot study on high-resolution radiological methods for the analysis of cerebrospinal fluid (CSF) shunt valves.

OBJECTIVES: Despite their life-saving capabilities, cerebrospinal fluid (CSF) shunts exhibit high failure rates, with a large fraction of failures attributed to the regulating valve. Due to a lack of methods for the detailed analysis of valve malfunctions, failure mechanisms are not well understood, and valves often have to be surgically explanted on the mere suspicion of malfunction. The presented pilot study aims to demonstrate radiological methods for comprehensive analysis of CSF shunt valves, considering both the potential for failure analysis in design optimization, and for future clinical in-vivo application to reduce the number of required shunt revision surgeries. The proposed method could also be utilized to develop and support in situ repair methods (e.g. by lysis or ultrasound) of malfunctioning CSF shunt valves. MATERIALS AND METHODS: The primary methods described are contrast-enhanced radiographic time series of CSF shunt valves, taken in a favorable projection geometry at low radiation dose, and the machine-learning-based diagnosis of CSF shunt valve obstructions. Complimentarily, we investigate CT-based methods capable of providing accurate ground truth for the training of such diagnostic tools. Using simulated test and training data, the performance of the machine-learning diagnostics in identifying and localizing obstructions within a shunt valve is evaluated regarding per-pixel sensitivity and specificity, the Dice similarity coefficient, and the false positive rate in the case of obstruction free test samples. RESULTS: Contrast enhanced subtraction radiography allows high-resolution, time-resolved, low-dose analysis of fluid transport in CSF shunt valves. Complementarily, photon-counting micro-CT allows to investigate valve obstruction mechanisms in detail, and to generate valid ground truth for machine learning-based diagnostics. Machine-learning-based detection of valve obstructions in simulated radiographies shows promising results, with a per-pixel sensitivity >70%, per-pixel specificity >90%, a median Dice coefficient >0.8 and <10% false positives at a detection threshold of 0.5. CONCLUSIONS: This ex-vivo study demonstrates obstruction detection in cerebro-spinal fluid shunt valves, combining radiological methods with machine learning under conditions compatible to future in-vivo application. Results indicate that high-resolution contrast-enhanced subtraction radiography, possibly including time-series data, combined with machine-learning image analysis, has the potential to strongly improve the diagnostics of CSF shunt valve failures. The presented method is in principle suitable for in-vivo application, considering both measurement geometry and radiological dose. Further research is needed to validate these results on real-world data and to refine the employed methods. In combination, the presented methods enable comprehensive analysis of valve failure mechanisms, paving the way for improved product development and clinical diagnostics of CSF shunt valves.

In Vivo Metabolic Imaging of [1-13 C]Pyruvate-d3 Hyperpolarized By Reversible Exchange With Parahydrogen.

Metabolic magnetic resonance imaging (MRI) using hyperpolarized (HP) pyruvate is becoming a non-invasive technique for diagnosing, staging, and monitoring response to treatment in cancer and other diseases. The clinically established method for producing HP pyruvate, dissolution dynamic nuclear polarization, however, is rather complex and slow. Signal Amplification By Reversible Exchange (SABRE) is an ultra-fast and low-cost method based on fast chemical exchange. Here, for the first time, we demonstrate not only in vivo utility, but also metabolic MRI with SABRE. We present a novel routine to produce aqueous HP [1-13 C]pyruvate-d3 for injection in 6 minutes. The injected solution was sterile, non-toxic, pH neutral and contained ≈30 mM [1-13 C]pyruvate-d3 polarized to ≈11 % (residual 250 mM methanol and 20 µM catalyst). It was obtained by rapid solvent evaporation and metal filtering, which we detail in this manuscript. This achievement makes HP pyruvate MRI available to a wide biomedical community for fast metabolic imaging of living organisms.

Accuracy of cone-beam computed tomography, digital mammography and digital breast tomosynthesis for microcalcifications and margins to microcalcifications in breast specimens.

Accurate determination of resection margins in breast specimens is important as complete removal of malignancy is a prerequisite for patients' outcome. Mammography (DM) as 2D-technique provides only limited value in margin assessment. Therefore, we investigated whether cone-beam computed tomography (CBCT) or digital breast tomosynthesis (DBT) has incremental value in assessing margins to microcalcifications. Three independent readers investigated breast specimens for presence of microcalcifications and the smallest distance to margins. Histopathology served as gold standard. Microcalcifications were detected in 15 out of 21 included specimens (71%). Pooled sensitivity for DM, DBT and CBCT for microcalcifications compared to preoperative DM was 0.98 (CI 0.94-0.99), 0.83 (CI 0.73-0.94) and 0.94 (CI 0.87-0.99), pooled specificity was 0.99 (CI 0.99-0.99), 0.73 (CI 0.51-0.96) and 0.60 (CI 0.35-0.85). Mean measurement error for margin determination for DM, DBT and CBCT was 10 mm, 14 mm and 6 mm (p = 0.002) with significant difference between CBCT and the other devices (p < 0.03). Mean reading time required by the readers to analyze DM, DBT and CBCT, was 36, 43 and 54 s (p < 0.001). Although DM allows reliable detection of microcalcifications, measurement of resection margin was significantly more accurate with CBCT. Thus, a combination of methods or improved CBCT might provide a more accurate determination of disease-free margins in breast specimens.