Regional Distribution of Extracellular Volume Quantified by Cardiac CT in Aortic Stenosis: Insights Into Disease Mechanisms and Impact on Outcomes.

BACKGROUND: Extracellular volume fraction (ECV) is a marker for myocardial fibrosis and infiltration, can be quantified using cardiac computed tomography (ECVCT), and has prognostic utility in several diseases. This study aims to map out regional differences in ECVCT to obtain greater insights into the pathophysiological mechanisms of ECV expansion and its clinical implications. METHODS: Three prospective cohorts were included: patients with aortic stenosis (AS) and coexisting AS and transthyretin cardiac amyloidosis were referred for a transcatheter aortic valve replacement and had ECG-gated CT angiography and Technetium-99m-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy to differentiate between the 2 cohorts. Controls had CT angiography and cardiac magnetic resonance demonstrating no significant coronary artery disease or infarction. Global and regional ECVCT was analyzed, and its association with mortality was assessed for patients with AS. RESULTS: In 199 patients, controls (n=65; 66% male), AS (n=115), and coexisting AS and transthyretin cardiac amyloidosis (n=19) had a global ECVCT of 26.1 (25.0-27.8%) versus 29.1 (27.5-31.1%) versus 37.4 (32.5-46.6%), respectively; P<0.001. Across cohorts, ECVCT was higher at the base (versus apex), the inferoseptum (versus anterolateral wall), and the subendocardium (versus subepicardium); P<0.05 for all. Among patients with AS, epicardial ECVCT, rather than any other regional value or global ECVCT, was the strongest predictor of mortality at a median of 3.9 (max 6.3) years (adjusted hazard ratio, 1.21 [95% CI, 1.08-1.36]; P=0.002). CONCLUSIONS: Regional differences in ECVCT suggest a predilection for fibrosis and amyloid infiltration at the base, subendocardium, inferior wall, and septum more than the anterior and lateral myocardium. ECVCT can predict long-term mortality with the subepicardium demonstrating the strongest discriminatory power. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03029026 and NCT03094143.

A novel method for predicting hepatocellular carcinoma response to chemoembolization using an intraprocedural CT hepatic arteriography-based enhancement mapping: a proof-of-concept analysis.

BACKGROUND: To evaluate the feasibility of a novel approach for predicting hepatocellular carcinoma (HCC) response to drug-eluting beads transarterial chemoembolization (DEB-TACE) using computed tomography hepatic arteriography enhancement mapping (CTHA-EM) method. METHODS: This three-institution retrospective study included 29 patients with 46 HCCs treated with DEB-TACE between 2017 and 2020. Pre- and posttreatment CTHA-EM images were generated using a prototype deformable registration and subtraction software. Relative tumor enhancement (TPost/pre-RE) defined as the ratio of tumor enhancement to normal liver tissue was calculated to categorize tumor response as residual (TPost-RE > 1) versus non-residual (TPost-RE ≤ 1) enhancement, which was blinded compared to the response assessment on first follow-up imaging using modified RECIST criteria. Additionally, for tumors with residual enhancement, CTHA-EM was evaluated to identify its potential feeding arteries. RESULTS: CTHA-EM showed residual enhancement in 18/46 (39.1%) and non-residual enhancement in 28/46 (60.9%) HCCs, with significant differences on TPost-RE (3.05 ± 2.4 versus 0.48 ± 0.23, respectively; p < 0.001). The first follow-up imaging showed non-complete response (partial response or stable disease) in 19/46 (41.3%) and complete response in 27/46 (58.7%) HCCs. CTHA-EM had a response prediction sensitivity of 94.7% (95% CI, 74.0-99.9) and specificity of 100% (95% CI, 87.2-100). Feeding arteries to the residual enhancement areas were demonstrated in all 18 HCCs (20 arteries where DEB-TACE was delivered, 2 newly developed collaterals following DEB-TACE). CONCLUSION: CTHA-EM method was highly accurate in predicting initial HCC response to DEB-TACE and identifying feeding arteries to the areas of residual arterial enhancement.

Photon-Counting Detector CT-Based Vascular Calcium Removal Algorithm: Assessment Using a Cardiac Motion Phantom.

OBJECTIVES: The diagnostic performance of coronary computed tomography angiography is known to be negatively affected by the presence of severely calcified plaques in the coronary arteries. In this article, the performance of a novel image reconstruction algorithm (PureLumen) based on spectral CT data of a first-generation dual-source photon-counting detector computed tomography (PCD-CT) system was assessed in a phantom study. PureLumen tries to remove only the calcified contributions from the image while leaving the rest unmodified. MATERIALS AND METHODS: The study uses 2 iodine contrast filled vessel phantoms (diameter 4 mm) filled with different concentrations of iodine and equipped with calcified stenosis inserts. Each phantom features 2 separate calcified lesions of 25% and 50% percentage diameter stenosis (PDS) size. The vessel phantoms were mounted inside an anthropomorphic thorax phantom attached to an artificial motion device, simulating realistic cardiac motion at heart rates between 50 beats per minute and 100 beats per minute. Acquisitions were performed using a prospectively electrocardiogram triggered dual-source sequence mode on a PCD-CT system (NAEOTOM Alpha, Siemens Healthineers). Images were reconstructed at 80% of the RR interval with virtual monoenergetic images (Mono) and with additional calcium-removal (PureLumen), both at 65 keV. PureLumen is based on a spectral base material decomposition into iodine and calcium, which aims to reconstruct images without calcium contributions, while leaving all other material contribution unchanged. Stenosis grade was assessed individually for each vessel insert in all reconstructed image series by 2 readers. RESULTS: The measured median PDS values for the 50% lesion were 56.0% (52.0%, 57.0%) for the Mono case and 50.0% (48.5%, 51.0%) for PureLumen. The 25% lesion median PDS values were 36.0% (29.5%, 39.5%) for Mono and 31.5% (30.5%, 34.0%) for PureLumen. Both lesion sizes demonstrate a significant difference between Mono and PureLumen in their result (P < 0.05) with PureLumen median values being closer to the actual true stenosis size for the 50% and 25% lesion. A visual assessment of the image quality depending on the heart rate yielded good image quality up to a heart rate of 80 beats per minute in the PureLumen case. CONCLUSIONS: This phantom study shows that a novel calcium-removal image reconstruction algorithm (PureLumen) using a first-generation dual-source PCD-CT effectively decreases blooming artifacts caused by heavily calcified plaques and improves image interpretability. It also shows that PureLumen retains its performance in the presence of motion with simulated heart rates up to 80 beats per minute. Future in vivo clinical studies are needed to confirm the benefits of this type of reconstruction in terms of coronary computed tomography angiography quality and accuracy.

Extracellular Volume Quantification With Cardiac Late Enhancement Scanning Using Dual-Source Photon-Counting Detector CT.

OBJECTIVES: The aim of this study was to evaluate the feasibility and accuracy of cardiac late enhancement (LE) scanning for extracellular volume (ECV) quantification with dual-source photon-counting detector computed tomography (PCD-CT). MATERIALS AND METHODS: In this institutional review board-approved study, 30 patients (mean age, 79 years; 12 women; mean body mass index, 28 kg/m2) with severe aortic stenosis undergoing PCD-CT as part of their preprocedural workup for transcatheter aortic valve replacement were included. The scan protocol consisted of a nonenhanced calcium-scoring scan, coronary CT angiography (CTA) followed by CTA of the thoracoabdominal aorta, and a low-dose LE scan 5 minutes after the administration of 100 mL contrast media (all scans electrocardiogram-gated). Virtual monoenergetic (65 keV) and dual-energy (DE) iodine images were reconstructed from the LE scan. Extracellular volume was calculated using the iodine ratios of myocardium and blood-pool of the LE scan, and additionally based on single-energy (SE) subtraction of the nonenhanced scan from the LE scan. Three-dimensional analysis was performed automatically for the whole-heart myocardial volume by matching a heart model generated from the respective coronary CTA data. Bland-Altman and correlation analysis were used to compare the ECV values determined by both methods. RESULTS: The median dose length product for the LE scan was 84 mGy·cm (interquartile range, 69; 125 mGy·cm). Extracellular volume quantification was feasible in all patients. The median ECV value was 30.5% (interquartile range, 28.4%-33.6%). Two focal ECV elevations matched known prior myocardial infarction. The DE- and SE-based ECV quantification correlated well (r = 0.87, P < 0.001). Bland-Altman analysis showed small mean errors between DE- and SE-based ECV quantification (0.9%; 95% confidence interval, 0.1%-1.6%) with narrow limits of agreement (-3.3% to 5.0%). CONCLUSIONS: Dual-source PCD-CT enables accurate ECV quantification using an LE cardiac DE scan at low radiation dose. Extracellular volume calculation from iodine ratios of the LE scan obviates the need for acquisition of a true nonenhanced scan and is not affected by potential misregistration between 2 separate scans.

Dynamic Myocardial Perfusion CT for the Detection of Hemodynamically Significant Coronary Artery Disease.

OBJECTIVES: In this international, multicenter study, using third-generation dual-source computed tomography (CT), we investigated the diagnostic performance of dynamic stress CT myocardial perfusion imaging (CT-MPI) in addition to coronary CT angiography (CTA) compared to invasive coronary angiography (ICA) and invasive fractional flow reserve (FFR). BACKGROUND: CT-MPI combined with coronary CTA integrates coronary artery anatomy with inducible myocardial ischemia, showing promising results for the diagnosis of hemodynamically significant coronary artery disease in single-center studies. METHODS: At 9 centers in Europe, Japan, and the United States, 132 patients scheduled for ICA were enrolled; 114 patients successfully completed coronary CTA, adenosine-stress dynamic CT-MPI, and ICA. Invasive FFR was performed in vessels with 25% to 90% stenosis. Data were analyzed by independent core laboratories. For the primary analysis, for each coronary artery the presence of hemodynamically significant obstruction was interpreted by coronary CTA with CT-MPI compared to coronary CTA alone, using an FFR of ≤0.80 and angiographic severity as reference. Territorial absolute myocardial blood flow (MBF) and relative MBF were compared using C-statistics. RESULTS: ICA and FFR identified hemodynamically significant stenoses in 74 of 289 coronary vessels (26%). Coronary CTA with ≥50% stenosis demonstrated a per-vessel sensitivity, specificity, and accuracy for the detection of hemodynamically significant stenosis of 96% (95% CI: 91%-100%), 72% (95% CI: 66%-78%), and 78% (95% CI: 73%-83%), respectively. Coronary CTA with CT-MPI showed a lower sensitivity (84%; 95% CI: 75%-92%) but higher specificity (89%; 95% CI: 85%-93%) and accuracy (88%; 95% CI: 84%-92%). The areas under the receiver-operating characteristic curve of absolute MBF and relative MBF were 0.79 (95% CI: 0.71-0.86) and 0.82 (95% CI: 0.74-0.88), respectively. The median dose-length product of CT-MPI and coronary CTA were 313 mGy·cm and 138 mGy·cm, respectively. CONCLUSIONS: Dynamic CT-MPI offers incremental diagnostic value over coronary CTA alone for the identification of hemodynamically significant coronary artery disease. Generalized results from this multicenter study encourage broader consideration of dynamic CT-MPI in clinical practice. (Dynamic Stress Perfusion CT for Detection of Inducible Myocardial Ischemia [SPECIFIC]; NCT02810795).

Fusion of Preinterventional MR Imaging With Liver Perfusion CT After RFA of Hepatocellular Carcinoma: Early Quantitative Prediction of Local Recurrence.

OBJECTIVES: The aim of this study was to evaluate the ability of fusion of pretreatment magnetic resonance (MR) imaging with posttreatment perfusion-CT (P-CT) after radiofrequency ablation (RFA) of hepatocellular carcinomas (HCCs) and to determine treatment success in an objective, quantitative way. MATERIALS AND METHODS: In this institutional review board-approved study, 39 patients (78.4% male; mean age 68.2 ± 8.5 years) with a total of 43 HCCs, who underwent RFA at our institution and had diagnostic pre-RFA MR imaging and post-RFA P-CT, were included in the study. Post-RFA P-CT was performed within 24 hours after RFA. In a first step, the pre-RFA MR imaging, depicting the HCC, was registered onto the post-RFA P-CT using nonrigid image registration. After image registration, the MR data were reloaded jointly with the calculated perfusion parameter volumes into the perfusion application for quantitative analysis. A 3-dimensional volume of interest was drawn around the HCC and the ablation zone; both outlines were automatically projected onto all perfusion maps. Resulting perfusion values (normalized peak enhancement [NPE, %]; arterial liver perfusion [ALP, in mL/min/100 mL]; BF [blood flow, mL/100 mL/min]; and blood volume [BV, mL/100 mL]) and histogram data were recorded. Local tumor recurrence was defined in follow-up imaging according to the EASL guidelines. RESULTS: Image registration of MR imaging and CT data was successful in 37 patients (94.9%). Local tumor recurrence was observed in 5 HCCs (12%). In the local tumor recurrence group (LTR-group), HCC size was significantly larger (22.7 ± 3.9 cm vs 17.8 ± 5.3 cm, P = 0.035) and the ablation zone was significantly smaller (29.8 ± 6.9 cm vs 39.3 ± 6.8 cm, P = 0.014) compared with the no-local tumor recurrence group (no-LTR group). The differences (ablation zone - tumor) of the perfusion parameters NPE, ALP, BF, and BV significantly differed between the 2 groups (all P's < 0.005). Especially, the difference (ablation zone - tumor) of NPE and ALP, with a cutoff value of zero, accurately differentiated between LTR or no-LTR in all cases. A negative difference of these perfusion parameters identified local tumor recurrence in all cases. CONCLUSIONS: Image registration of pre-RFA MR imaging onto post-RFA P-CT is feasible and allows to predict local tumor recurrence within 24 hours after RFA in an objective, quantitative manner and with excellent accuracy.

Identifying Cardiac Amyloid in Aortic Stenosis: ECV Quantification by CT in TAVR Patients.

OBJECTIVES: The purpose of this study was to validate computed tomography measured ECV (ECVCT) as part of routine evaluation for the detection of cardiac amyloid in patients with aortic stenosis (AS)-amyloid. BACKGROUND: AS-amyloid affects 1 in 7 elderly patients referred for transcatheter aortic valve replacement (TAVR). Bone scintigraphy with exclusion of a plasma cell dyscrasia can diagnose transthyretin-related cardiac amyloid noninvasively, for which novel treatments are emerging. Amyloid interstitial expansion increases the myocardial extracellular volume (ECV). METHODS: Patients with severe AS underwent bone scintigraphy (Perugini grade 0, negative; Perugini grades 1 to 3, increasingly positive) and routine TAVR evaluation CT imaging with ECVCT using 3- and 5-min post-contrast acquisitions. Twenty non-AS control patients also had ECVCT performed using the 5-min post-contrast acquisition. RESULTS: A total of 109 patients (43% male; mean age 86 ± 5 years) with severe AS and 20 control subjects were recruited. Sixteen (15%) had AS-amyloid on bone scintigraphy (grade 1, n = 5; grade 2, n = 11). ECVCT was 32 ± 3%, 34 ± 4%, and 43 ± 6% in Perugini grades 0, 1, and 2, respectively (p < 0.001 for trend) with control subjects lower than lone AS (28 ± 2%; p < 0.001). ECVCT accuracy for AS-amyloid detection versus lone AS was 0.87 (0.95 for 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid Perugini grade 2 only), outperforming conventional electrocardiogram and echocardiography parameters. One composite parameter, the voltage/mass ratio, had utility (similar AUC of 0.87 for any cardiac amyloid detection), although in one-third of patients, this could not be calculated due to bundle branch block or ventricular paced rhythm. CONCLUSIONS: ECVCT during routine CT TAVR evaluation can reliably detect AS-amyloid, and the measured ECVCT tracks the degree of infiltration. Another measure of interstitial expansion, the voltage/mass ratio, also performed well.

DPD Quantification in Cardiac Amyloidosis: A Novel Imaging Biomarker.

OBJECTIVES: To assess whether single-photon emission computed tomography (SPECT/CT) quantification of bone scintigraphy would improve diagnostic accuracy and offer a means of quantifying amyloid burden. BACKGROUND: Transthyretin-related cardiac amyloidosis is common and can be diagnosed noninvasively using bone scintigraphy; interpretation, however, relies on planar images. SPECT/CT imaging offers 3-dimensional visualization. METHODS: This was a single-center, retrospective analysis of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scans reported using the Perugini grading system (0 = negative; 1 to 3 = increasingly positive). Conventional planar quantification techniques (heart/contralateral lung, and heart/whole-body retention ratios) were performed. Heart, adjacent vertebra, paraspinal muscle and liver peak standardized uptake values (SUVpeak) were recorded from SPECT/CT acquisitions. An SUV retention index was also calculated: (cardiac SUVpeak/vertebral SUVpeak) × paraspinal muscle SUVpeak. In a subgroup of patients, SPECT/CT quantification was compared with myocardial extracellular volume quantification by CT imaging (ECVCT). RESULTS: A total of 100 DPD scans were analyzed (patient age 84 ± 9 years; 52% male): 40 were Perugini grade 0, 12 were grade 1, 41 were grade 2, and 7 were grade 3. Cardiac SUVpeak increased from grade 0 to grade 2; however, it plateaued between grades 2 and 3 (p < 0.001). Paraspinal muscle SUVpeak increased with grade (p < 0.001), whereas vertebral SUVpeak decreased (p < 0.001). The composite parameter of SUV retention index overcame the plateauing of the cardiac SUVpeak and increased across all grades (p < 0.001). Cardiac SUVpeak correlated well (r2 = 0.73; p < 0.001) with ECVCT. Both the cardiac SUVpeak and SUV retention index had excellent diagnostic accuracy (area under the curve [AUC]: 0.999). The heart to contralateral lung ratio performed the best of the planar quantification techniques (AUC: 0.987). CONCLUSIONS: SPECT/CT quantification in DPD scintigraphy is possible and outperforms planar quantification techniques. Differentiation of Perugini grade 2 or 3 is confounded by soft tissue uptake, which can be overcome by a composite SUV retention index. This index can help in the diagnosis of cardiac amyloidosis and may offer a means of monitoring response to therapy.

Comparing the outcomes of two independent computed tomography perfusion softwares and their impact on therapeutic decisions in acute ischemic stroke.

BACKGROUND: To compare the computed tomography perfusion (CTP) outcomes derived from two commercial CTP processing software and evaluate their concordance in terms of eligibility for mechanical thrombectomy (MT) in acute ischemic stroke (AIS), based on DEFUSE III criteria. METHODS: A total of 118 patients (62 patients in the MT group and 56 patients in the non-MT (NMT) group) were included. Volumetric perfusion outputs were compared between Syngo.via (package A) and RAPID (package B). Influence on proceeding or not-proceeding with MT was based on DEFUSE III imaging eligibility criteria. RESULTS: Median core infarct/hypoperfusion volumes were 12.3/126 mL in the MT group and 7.7/29.3 ml in the NMT group with package A and 10.5/138 mL and 1.9/24.5 mL with package B, respectively. In the MT group (n=62), concordant perfusion results in terms of patient triage were noted in all but two cases. Of these, one patient would not have qualified (low ASPECTS), while the other qualified based on package A results. For the NMT group (n=56), there was discordance in terms of MT eligibility in seven cases. However, none of these patients qualified for MT based on DEFUSE III criteria. CONCLUSIONS: Both perfusion softwares showed high concordance in correctly triaging patients in the MT versus NMT groups (110/118, 93.2%), which further improved when all DEFUSE III imaging criteria were considered (117/118, 99.1%). The core/hypoperfusion volumes in the NMT group and core infarct volumes in the MT groups were comparable. The hypoperfusion volumes in the MT group varied slightly but did not affect triage between groups.