Optimization of photon counting CT for cardiac imaging in patients with left ventricular assist devices: An in-depth assessment of metal artifacts.

PURPOSE: Photon counting CT (PCCT) holds promise for mitigating metal artifacts and can produce virtual mono-energetic images (VMI), while maintaining temporal resolution, making it a valuable tool for characterizing the heart. This study aimed to evaluate and optimize PCCT for cardiac imaging in patients during left ventricular assistance device (LVAD) therapy by conducting an in-depth objective assessment of metal artifacts and visual grading. METHODS: Various scan and reconstruction settings were tested on a phantom and further evaluated on a patient acquisition to identify the optimal protocol settings. The phantom comprised an empty thoracic cavity, supplemented with heart and lungs from a cadaveric lamb. The heart was implanted with an LVAD (HeartMate 3) and iodine contrast. Scans were performed on a PCCT (NAEOTOM Alpha, Siemens Healthcare). Metal artifacts were assessed by three objective methods: Hounsfield units (HU)/SD measurements (DiffHU and SDARTIFACT), Fourier analysis (AmplitudeLowFreq), and depicted LVAD volume in the images (BloomVol). Radiologists graded metal artifacts and the diagnostic interpretability in the LVAD lumen, cardiac tissue, lung tissue, and spinal cord using a 5-point rating scale. Regression and correlation analysis were conducted to determine the assessment method most closely associated with acquisition and reconstruction parameters, as well as the objective method demonstrating the highest correlation with visual grading. RESULTS: Due to blooming artifacts, the LVAD volume fluctuated between 27.0 and 92.7 cm3. This variance was primarily influenced by kVp, kernel, keV, and iMAR (R2 = 0.989). Radiologists favored pacemaker iMAR, 3 mm slice thickness, and T3D keV and kernel Bv56f for minimal metal artifacts in cardiac tissue assessment, and 110 keV and Qr40f for lung tissue interpretation. The model adequacy for DiffHU SDARTIFACT, AmplitueLowFreq, and BloomVol was 0.28, 0.76, 0.29, and 0.99 respectively for phantom data, and 0.95, 0.98, 1.00, and 0.99 for in-vivo data. For in-vivo data, the correlation between visual grading (VGSUM) and DiffHU SDARTIFACT, AmplitueLowFreq, and BloomVol was -0.16, -0.01, -0.48, and -0.40 respectively. CONCLUSION: We found that optimal scan settings for LVAD imaging involved using 120 kVp and IQ level 80. Employing T3D with pacemaker iMAR, the sharpest allowed vascular kernel (Bv56f), and VMI at 110 keV with kernel Qr40 yields images suitable for cardiac imaging during LVAD-therapy. Volumetric measurements of the LVAD for determination of the extent of blooming artifacts was shown to be the best objective method to assess metal artifacts.

A prospective study comparing the quality of coronary computed tomography angiography images from photon counting and energy integrating detector systems.

BACKGROUND: As guidelines endorse the use of computed tomography (CT) for examining coronary artery disease (CAD), it is important to compare the advantages and disadvantages of the novel photon counting detector CT (PCD-CT) technology with the established energy integrating detector CT (EID-CT). PURPOSE: To compare the image quality of coronary computed tomography angiography (CCTA) and the Agatston scores (AS) derived from EID-CT and PCD-CT. MATERIAL AND METHODS: In this prospective observational study, 28 patients underwent clinical calcium score and CCTA scans on an EID-CT and a PCD-CT scanner. CCTA images were qualitatively analyzed by five observers using visual grading characteristics. The correlation and agreement of the AS were assessed using Spearman's rank correlation and Bland-Altman plots. RESULTS: This qualitative analyses demonstrated a high fraction of "good" or "excellent" ratings for the image criteria in both CT systems. The sharpness of the distal lumen and image quality regarding motion artifacts were rated significantly higher for EID-CT (P < 0.05). However, the sharpness of coronary calcification was rated significantly higher for PCD-CT (P < 0.05). Spearman's rank correlation and Bland-Altman plots showed good correlation (P = 0.95) and agreement regarding the AS between EID-CT and PCD-CT. CONCLUSION: Both CT systems exhibited high CCTA image quality. The sharpness of calcifications was rated significantly higher for PCD-CT. A good correlation was observed between the AS derived from the two systems.

Complete fatty degeneration of thymus associates with male sex, obesity and loss of circulating naïve CD8+ T cells in a Swedish middle-aged population.

BACKGROUND: Fatty degeneration of thymus (or thymus involution) has long been considered a normal ageing process. However, there is emerging evidence that thymic involution is linked to T cell aging, chronic inflammation and increased morbidity. Other factors, aside from chronological age, have been proposed to affect the involution rate. In the present study, we investigated the imaging characteristics of thymus on computed tomography (CT) in a Swedish middle-aged population. The major aims were to establish the prevalence of fatty degeneration of thymus and to determine its associations with demographic, lifestyle and clinical factors, as well as inflammation, T cell differentiation and thymic output. RESULTS: In total, 1 048 randomly invited individuals (aged 50-64 years, 49% females) were included and thoroughly characterized. CT evaluation of thymus included measurements of attenuation, size and a 4-point scoring system, with scale 0-3 based on the ratio of fat and soft tissue. A majority, 615 (59%) showed complete fatty degeneration, 259 (25%) predominantly fatty attenuation, 105 (10%) half fatty and half soft-tissue attenuation, while 69 (6.6%) presented with a solid thymic gland with predominantly soft-tissue attenuation. Age, male sex, high BMI, abdominal obesity and low dietary intake of fiber were independently associated with complete fatty degeneration of thymus. Also, fatty degeneration of thymus as well as low CT attenuation values were independently related to lower proportion of naïve CD8+ T cells, which in turn was related to lower thymic output, assessed by T-cell receptor excision circle (TREC) levels. CONCLUSION: Among Swedish middle-aged subjects, nearly two-thirds showed complete fatty degeneration of thymus on CT. This was linked to depletion of naïve CD8+ T cells indicating that CT scans of thymus might be used to estimate immunological aging. Furthermore, our findings support the intriguing concept that obesity as well as low fiber intake contribute to immunological aging, thereby raising the possibility of preventive strategies.

Assessment of image quality in photon-counting detector computed tomography of the wrist - An ex vivo study.

PURPOSE: The aim of this study was to evaluate the effect of reconstruction parameters on image quality in wrist imaging using photon-counting detector CT (PCD-CT) and to compare the results with images from an energy-integrating detector CT (EID-CT). METHODS: Twelve cadaveric wrist specimens were examined using a prototype PCD-CT and a clinical EID-CT using similar radiation dose. Reconstruction parameters were matched between scanners. Also, sharper reconstruction kernels, a larger matrix size, and smaller slice thicknesses were evaluated for PCD-CT. Image noise, contrast-to-noise ratio (CNR) and image sharpness in trabecular structures were quantitatively measured. Image quality with respect to the visibility of cortical and trabecular bone structures was assessed by six radiologists using visual grading methods. RESULTS: Images obtained with PCD-CT had lower noise (42.6 ± 3.9 HU vs 75.1 ± 6.3 HU), higher CNR (38.9 ± 4.5 vs 19.0 ± 2.4) and higher trabecular sharpness (63.5 ± 6.0 vs 53.7 ± 8.5) than those obtained with EID-CT using similar scan and reconstruction parameters (p < 0.001). The image sharpness in trabecular structures was further improved by using sharper kernels, despite higher noise levels. Radiologists had a strong preference for PCD-CT images both in terms of spatial resolution and suitability for bone imaging. Visual grading analysis showed an improved visibility of cortical bone, trabeculae and nutritive canals (p < 0.005). CONCLUSION: PCD-CT offers improved image quality regarding bone structures in the wrist relative to EID-CT systems, particularly when sharper reconstruction kernels, smaller slice thickness and a larger image matrix size are used.

Safety and pharmacokinetics-pharmacodynamics of a shorter tuberculosis treatment with high-dose pyrazinamide and rifampicin: a study protocol of a phase II clinical trial (HighShort-RP).

INTRODUCTION: Increased dosing of rifampicin and pyrazinamide seems a viable strategy to shorten treatment and prevent relapse of drug-susceptible tuberculosis (TB), but safety and efficacy remains to be confirmed. This clinical trial aims to explore safety and pharmacokinetics-pharmacodynamics of a high-dose pyrazinamide-rifampicin regimen. METHODS AND ANALYSIS: Adult patients with pulmonary TB admitted to six hospitals in Sweden and subjected to receive first-line treatment are included. Patients are randomised (1:3) to either 6-month standardised TB treatment or a 4-month regimen based on high-dose pyrazinamide (40 mg/kg) and rifampicin (35 mg/kg) along with standard doses of isoniazid and ethambutol. Plasma samples for measurement of drug exposure determined by liquid chromatography tandem-mass spectrometry are obtained at 0, 1, 2, 4, 6, 8, 12 and 24 hours, at day 1 and 14. Maximal drug concentration (Cmax) and area under the concentration-time curve (AUC0-24h) are estimated by non-compartmental analysis. Conditions for early model-informed precision dosing of high-dose pyrazinamide-rifampicin are pharmacometrically explored. Adverse drug effects are monitored throughout the study and graded according to Common Terminology Criteria for Adverse Events V.5.0. Early bactericidal activity is assessed by time to positivity in BACTEC MGIT 960 of induced sputum collected at day 0, 5, 8, 15 and week 8. Minimum inhibitory concentrations of first-line drugs are determined using broth microdilution. Disease severity is assessed with X-ray grading and a validated clinical scoring tool (TBscore II). Clinical outcome is registered according to WHO definitions (2020) in addition to occurrence of relapse after end of treatment. Primary endpoint is pyrazinamide AUC0-24h and main secondary endpoint is safety. ETHICS AND DISSEMINATION: The study is approved by the Swedish Ethical Review Authority and the Swedish Medical Products Agency. Informed written consent is collected before study enrolment. The study results will be submitted to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04694586.

Comparison of the Agatston score acquired with photon-counting detector CT and energy-integrating detector CT: ex vivo study of cadaveric hearts.

The purpose of this study was to compare the correlation and agreement between AS derived from either an energy-integrating detector CT (EID-CT) or a photon-counting detector CT (PCD-CT). Reproducibility was also compared. In total, 26 calcified coronary lesions (from five cadaveric hearts) were identified for inclusion. The hearts were positioned in a chest phantom and scanned in both an EID-CT and a prototype PCD-CT. The EID-CT and PCD-CT acquisition and reconstruction parameters were matched. To evaluate the reproducibility, the phantom was manually repositioned, and an additional scan was performed using both methods. The EID-CT reconstructions were performed using the dedicated calcium score kernel Sa36. The PCD-CT reconstructions were performed with a vendor-recommended kernel (Qr36). Several monoenergetic energy levels (50-150 keV) were evaluated to find the closest match with the EID-CT scans. A semi-automatic evaluation of calcium score was performed on a post-processing multimodality workplace. The best match with Sa36 was PCD-CT Qr36 images, at a monoenergetic level of 72 keV. Statistical analyses showed excellent correlation and agreement. The correlation and agreement with regards to the Agatston score (AS) between the two methods, for each position as well as between the two positions for each method, were assessed with the Spearman´s rank correlation. The correlation coefficient, rho, was 0.98 and 0.97 respectively 0.99 and 0.98. The corresponding agreements were investigated by means of Bland-Altman plots. High correlation and agreement was observed between the AS derived from the EID-CT and a PCD-CT. Both methods also demonstrated excellent reproducibility.

Improved coronary calcification quantification using photon-counting-detector CT: an ex vivo study in cadaveric specimens.

OBJECTIVES: To compare the accuracy of coronary calcium quantification of cadaveric specimens imaged from a photon-counting detector (PCD)-CT and an energy-integrating detector (EID)-CT. METHODS: Excised coronary specimens were scanned on a PCD-CT scanner, using both the PCD and EID subsystems. The scanning and reconstruction parameters for EID-CT and PCD-CT were matched: 120 kV, 9.3-9.4 mGy CTDIvol, and a quantitative kernel (D50). PCD-CT images were also reconstructed using a sharper kernel (D60). Scanning the same specimens using micro-CT served as a reference standard for calcified volumes. Calcifications were segmented with a half-maximum thresholding technique. Segmented calcified volume differences were analyzed using the Friedman test and post hoc pairwise Wilcoxon signed rank test with the Bonferroni correction. Image noise measurements were compared between EID-CT and PCD-CT with a repeated-measures ANOVA test and post hoc pairwise comparison with the Bonferroni correction. A p < 0.05 was considered statistically significant. RESULTS: The volume measurements in 12/13 calcifications followed a similar trend: EID-D50 > PCD-D50 > PCD-D60 > micro-CT. The median calcified volumes in EID-D50, PCD-D50, PCD-D60, and micro-CT were 22.1 (IQR 10.2-64.8), 21.0 (IQR 9.0-56.5), 18.2 (IQR 8.3-49.3), and 14.6 (IQR 5.1-42.4) mm3, respectively (p < 0.05 for all pairwise comparisons). The average image noise in EID-D50, PCD-D50, and PCD-D60 was 60.4 (± 3.5), 56.0 (± 4.2), and 113.6 (± 8.5) HU, respectively (p < 0.01 for all pairwise comparisons). CONCLUSION: The PCT-CT system quantified coronary calcifications more accurately than EID-CT, and a sharp PCD-CT kernel further improved the accuracy. The PCD-CT images exhibited lower noise than the EID-CT images. KEY POINTS: • High spatial resolution offered by PCD-CT reduces partial volume averaging and consequently leads to better morphological depiction of coronary calcifications. • Improved quantitative accuracy for coronary calcification volumes could be achieved using high-resolution PCD-CT compared to conventional EID-CT. • PCD-CT images exhibit lower image noise than conventional EID-CT at matched radiation dose and reconstruction kernel.

Evaluation of an AI-based, automatic coronary artery calcium scoring software.

OBJECTIVES: To evaluate an artificial intelligence (AI)-based, automatic coronary artery calcium (CAC) scoring software, using a semi-automatic software as a reference. METHODS: This observational study included 315 consecutive, non-contrast-enhanced calcium scoring computed tomography (CSCT) scans. A semi-automatic and an automatic software obtained the Agatston score (AS), the volume score (VS), the mass score (MS), and the number of calcified coronary lesions. Semi-automatic and automatic analysis time were registered, including a manual double-check of the automatic results. Statistical analyses were Spearman's rank correlation coefficient (⍴), intra-class correlation (ICC), Bland Altman plots, weighted kappa analysis (κ), and Wilcoxon signed-rank test. RESULTS: The correlation and agreement for the AS, VS, and MS were ⍴ = 0.935, 0.932, 0.934 (p < 0.001), and ICC = 0.996, 0.996, 0.991, respectively (p < 0.001). The correlation and agreement for the number of calcified lesions were ⍴ = 0.903 and ICC = 0.977 (p < 0.001), respectively. The Bland Altman mean difference and 1.96 SD upper and lower limits of agreements for the AS, VS, and MS were - 8.2 (- 115.1 to 98.2), - 7.4 (- 93.9 to 79.1), and - 3.8 (- 33.6 to 25.9), respectively. Agreement in risk category assignment was 89.5% and κ = 0.919 (p < 0.001). The median time for the semi-automatic and automatic method was 59 s (IQR 35-100) and 36 s (IQR 29-49), respectively (p < 0.001). CONCLUSIONS: There was an excellent correlation and agreement between the automatic software and the semi-automatic software for three CAC scores and the number of calcified lesions. Risk category classification was accurate but showing an overestimation bias tendency. Also, the automatic method was less time-demanding. KEY POINTS: • Coronary artery calcium (CAC) scoring is an excellent candidate for artificial intelligence (AI) development in a clinical setting. • An AI-based, automatic software obtained CAC scores with excellent correlation and agreement compared with a conventional method but was less time-consuming.

Long-term prognostic value of coronary computed tomography angiography in chest pain patients.

BACKGROUND: Coronary computed tomography angiography (CCTA) is increasingly used to detect coronary artery disease (CAD), but long-term follow-up studies are still scarce. PURPOSE: To evaluate the prognostic value of CCTA in patients with suspected CAD. MATERIAL AND METHODS: A total of 1205 consecutive CCTA patients with chest pain were classified as normal coronary arteries, non-obstructive CAD, or obstructive CAD. The primary outcome was major adverse cardiac event (MACE), defined as a composite outcome including cardiac death, myocardial infarction, unstable angina pectoris, or late revascularization (after >90 days). RESULTS: Over 7.5 years follow-up (median = 3.1 years), Kaplan-Meier estimates demonstrated a MACE in 1.0%, 4.6%, and 20.7% in normal coronary arteries, non-obstructive CAD, and obstructive CAD, respectively. Log rank test for pairwise comparisons showed significant differences between non-obstructive CAD and normal coronary arteries ( P = 0.023) and between obstructive CAD and normal coronary arteries ( P < 0.001). In a multivariable analysis, adjusting for classical risk factors, non-obstructive CAD and obstructive CAD were independent predictors of MACE, with hazard ratios (HR) of 3.22 ( P = 0.041) and 25.18 ( P < 0.001), respectively. CONCLUSION: Patients with normal coronary arteries have excellent long-term prognosis, but the risk for MACE increases with non-obstructive and obstructive CAD. Both non-obstructive and obstructive CAD are independently associated with future ischemic events.

Software-based on-site estimation of fractional flow reserve using standard coronary CT angiography data.

BACKGROUND: The significance of a coronary stenosis can be determined by measuring the fractional flow reserve (FFR) during invasive coronary angiography. Recently, methods have been developed which claim to be able to estimate FFR using image data from standard coronary computed tomography angiography (CCTA) exams. PURPOSE: To evaluate the accuracy of non-invasively computed fractional flow reserve (cFFR) from CCTA. MATERIAL AND METHODS: A total of 23 vessels in 21 patients who had undergone both CCTA and invasive angiography with FFR measurement were evaluated using a cFFR software prototype. The cFFR results were compared to the invasively obtained FFR values. Correlation was calculated using Spearman's rank correlation, and agreement using intraclass correlation coefficient (ICC). Sensitivity, specificity, accuracy, negative predictive value, and positive predictive value for significant stenosis (defined as both FFR ≤0.80 and FFR ≤0.75) were calculated. RESULTS: The mean cFFR value for the whole group was 0.81 and the corresponding mean invFFR value was 0.84. The cFFR sensitivity for significant stenosis (FFR ≤0.80/0.75) on a per-lesion basis was 0.83/0.80, specificity was 0.76/0.89, and accuracy 0.78/0.87. The positive predictive value was 0.56/0.67 and the negative predictive value was 0.93/0.94. The Spearman rank correlation coefficient was ρ = 0.77 (P < 0.001) and ICC = 0.73 (P < 0.001). CONCLUSION: This particular CCTA-based cFFR software prototype allows for a rapid, non-invasive on-site evaluation of cFFR. The results are encouraging and cFFR may in the future be of help in the triage to invasive coronary angiography.