Dual-contrast photon-counting micro-CT using iodine and a novel bismuth-based contrast agent.

Objectives.To characterize for the first timein vivoa novel bismuth-based nanoparticular contrast agent developed for preclinical applications. Then, to design and testin vivoa multi-contrast protocol for functional cardiac imaging using the new bismuth nanoparticles and a well-established iodine-based contrast agent.Approach.A micro-computed tomography scanner was assembled and equipped with a photon-counting detector. Five mice were administered with the bismuth-based contrast agent and systematically scanned over 5 h to quantify the contrast enhancement in relevant organs of interest. Subsequently, the multi-contrast agent protocol was tested on three mice. Material decomposition was performed on the acquired spectral data to quantify the concentration of bismuth and iodine in multiple structures, e.g. the myocardium and vasculature.Main results.In the vasculature, the bismuth agent provides a peak enhancement of 1100 HU and a half-life of about 260 min. After the injection, it accumulates in the liver, spleen and intestinal wall reaching a CT value of 440 HU about 5 h post injection. Phantom measurements showed that the bismuth provides more contrast enhancement than iodine for a variety of tube voltages. The multi-contrast protocol for cardiac imaging successfully allowed the simultaneous decomposition of the vasculature, the brown adipose tissue and the myocardium.Significance.The new bismuth-based contrast agent was proven to have a long circulation time suitable for preclinical applications and to provide more contrast than iodine agents. The proposed multi-contrast protocol resulted in a new tool for cardiac functional imaging. Furthermore, thanks to the contrast enhancement provided in the intestinal wall, the novel contrast agent may be used to develop further multi contrast agent protocols for abdominal and oncological imaging.

Differentiation of Crystals Associated With Arthropathies by Spectral Photon-Counting Radiography: A Proof-of-Concept Study.

OBJECTIVES: The aims of this study were to test whether spectral photon-counting radiography (SPCR) is able to identify and distinguish different crystals associated with arthropathies in vitro and to validate findings in a gouty human third toe ex vivo. MATERIALS AND METHODS: Industry-standard calibration rods of calcium pyrophosphate, calcium hydroxyapatite (HA), and monosodium urate (MSU) were scanned with SPCR in an experimental setup. Each material was available at 3 different concentrations, and a dedicated photon-counting detector was used for SPCR, whereas validation scans were obtained on a clinical dual-energy computed tomography (DECT) scanner. Regions of interest were placed on SPCR images and consecutive DECT images to measure x-ray attenuation characteristics, including effective atomic numbers (Zeff). Statistical tests were performed for differentiation of Zeff between concentrations, materials, and imaging modalities. In addition, a third toe from a patient with chronic gouty arthritis was scanned with SPCR and DECT for differentiation of MSU from HA. RESULTS: In both SPCR and DECT, significant differences in attenuation and Zeff values were found for different concentrations among (P < 0.001) and between different materials (P < 0.001). Overall, quantitative measurements of Zeff did not differ significantly between SPCR- and DECT-derived measurements (P = 0.054-0.412). In the human cadaver toe, gouty bone erosions were visible on standard grayscale radiographic images; however, spectral image decomposition revealed the nature and extent of MSU deposits and was able to separate it from bone HA by Zeff. CONCLUSIONS: Identification and differentiation of different crystals related to arthropathies are possible with SPCR at comparable diagnostic accuracy to DECT. Further research is needed to assess diagnostic accuracy and clinical usability in vivo.

Detection and Characterization of Monosodium Urate and Calcium Hydroxyapatite Crystals Using Spectral Photon-Counting Radiography: A Proof-of-Concept Study.

OBJECTIVE: To assess the potential of spectral photon-counting (PC) radiography (SPCR) for the detection and characterization of monosodium urate (MSU) and calcium hydroxyapatite (HA) crystals, based on effective atomic number (Zeff) values derived from specific X-ray attenuation characteristics at different energy levels. METHODS: Suspensions of either pure agar, synthetic MSU (200 mg/ml) or HA (100 and 150 mg/ml) crystals in agar were sealed in industry-standard polystyrene vials and supported on a 2.5-mm-thick plastic table. Samples were scanned using a vendor microfocus X-ray tube and a spectral PC detector prototype with four energy thresholds per acquisition (15, 25, 30, and 35 keV). Material decomposition calibration was performed using polymethyl methacrylate (PMMA) and polyvinylchloride (PVC) slabs. Using a custom post-processing software based on polynomial material decomposition, Zeff of the respective samples were computed. All samples were additionally scanned using dual-energy CT (DECT, 80 kV and tin-filtered 150 kV) and analyzed with a proprietary post-processing algorithm for gout. RESULTS: MSU crystal suspension attenuated significantly less than both HA samples. MSU and HA suspensions differed significantly in Zeff (mean ± SD: 7.74 ± 0.28 vs. 9.43 ± 0.41, p < .001). Zeff values from SPCR were comparable to DECT-based reference values (p = 0.16) and were independent of the radiation dose level (0.18 - 18 mAs, p = 1). DISCUSSION: This in vitro feasibility study demonstrates the potential of SPCR for discriminating MSU from HA crystal suspensions based on Zeff differences. Further studies have to corroborate these initial findings ex vivo and in vivo, and to compare the diagnostic performance of SPCR with DECT in imaging of crystal-associated arthropathies.

The first analysis and clinical evaluation of native breast tissue using differential phase-contrast mammography.

OBJECTIVES: Phase-contrast and scattering-based x-ray imaging are known to provide additional and complementary information to conventional, absorption-based methods, and therefore have the potential to play a crucial role in medical diagnostics. We report on the first mammographic investigation of 5 native, that is, freshly dissected, breasts carried out with a grating interferometer and a conventional x-ray tube source. Four patients in this study had histopathologically proven invasive breast cancer. One male patient, without the presence of any malignant formations within the resected breast, was included as a control specimen. MATERIALS AND METHODS: We used a Talbot-Lau grating setup installed on a conventional, low-brilliance x-ray source; the interferometer operated at the fifth Talbot distance, at a tube voltage of 40 kVp with mean energy of 28 keV, and at a current of 25 mA. The device simultaneously recorded absorption, differential phase and small-angle scattering signals from the native breast tissue. These quantities were then combined into novel color- and high-frequency-enhanced radiographic images. Presurgical images (conventional mammography, ultrasonography, and magnetic resonance imaging) supported the findings and clinical relevance was verified. RESULTS: Our approach yields complementary and otherwise inaccessible information on the electron density distribution and the small-angle scattering power of the sample at the microscopic scale. This information can be used to potentially answer clinically relevant, yet unresolved questions such as unequivocally discerning between malignant and premalignant changes and postoperative scars and distinguishing cancer-invaded regions within healthy tissue. CONCLUSIONS: We present the first ex vivo images of fresh, native breast tissue obtained from mastectomy specimens using grating interferometry. This technique yields improved diagnostic capabilities when compared with conventional mammography, especially when discerning the type of malignant conversions and their breadth within normal breast tissue. These promising results advance us toward the ultimate goal, using grating interferometry in vivo on humans in a clinical setting.

Non-linear regularized phase retrieval for unidirectional X-ray differential phase contrast radiography.

Phase retrieval from unidirectional radiographic differential phase contrast images requires integration of noisy data. A method is presented, which aims to suppress stripe artifacts arising from direct image integration. It is purely algorithmic and therefore, compared to alternative approaches, neither additional alignment nor an increased scan time is required. We report on the theory of this method and present results using numerical as well as experimental data. The method shows significant improvements on the phase retrieval accuracy and enhances contrast in the phase image. Due to its general applicability, the proposed method provides a valuable tool for various 2D imaging applications using differential data.

Obstacle crossing in a virtual environment with the rehabilitation gait robot LOKOMAT.

The rehabilitation robot LOKOMAT has been developed at the Balgrist University Hospital to automate treadmill training of spinal cord injury and stroke patients. A virtual environment setup was implemented to increase patient's motivation and provide biofeedback, consisting of visual, acoustic and haptic modalities. Based on the knee and hip angles of the orthosis, an animated figurine moves through a virtual environment. This contribution describes the setup of the system and selected technical performance parameters. We focused on delay times caused by the setup, stability of the haptic obstacle rendering and on the level of immersion as judged by four healthy subjects. Results show that subjects judged the system's performance well (questionnaire scores over 80%). Problems exist though for obstacle rendering (questionnaire scores of 55%).