Lipoprotein(a) and Long-Term Plaque Progression, Low-Density Plaque, and Pericoronary Inflammation.

Importance: Lipoprotein(a) (Lp[a]) is a causal risk factor for cardiovascular disease; however, long-term effects on coronary atherosclerotic plaque phenotype, high-risk plaque formation, and pericoronary adipose tissue inflammation remain unknown. Objective: To investigate the association of Lp(a) levels with long-term coronary artery plaque progression, high-risk plaque, and pericoronary adipose tissue inflammation. Design, Setting, and Participants: This single-center prospective cohort study included 299 patients with suspected coronary artery disease (CAD) who underwent per-protocol repeated coronary computed tomography angiography (CCTA) imaging with an interscan interval of 10 years. Thirty-two patients were excluded because of coronary artery bypass grafting, resulting in a study population of 267 patients. Data for this study were collected from October 2008 to October 2022 and analyzed from March 2023 to March 2024. Exposures: The median scan interval was 10.2 years. Lp(a) was measured at follow-up using an isoform-insensitive assay. CCTA scans were analyzed with a previously validated artificial intelligence-based algorithm (atherosclerosis imaging-quantitative computed tomography). Main Outcome and Measures: The association between Lp(a) and change in percent plaque volumes was investigated in linear mixed-effects models adjusted for clinical risk factors. Secondary outcomes were presence of low-density plaque and presence of increased pericoronary adipose tissue attenuation at baseline and follow-up CCTA imaging. Results: The 267 included patients had a mean age of 57.1 (SD, 7.3) years and 153 were male (57%). Patients with Lp(a) levels of 125 nmol/L or higher had twice as high percent atheroma volume (6.9% vs 3.0%; P = .01) compared with patients with Lp(a) levels less than 125 nmol/L. Adjusted for other risk factors, every doubling of Lp(a) resulted in an additional 0.32% (95% CI, 0.04-0.60) increment in percent atheroma volume during the 10 years of follow-up. Every doubling of Lp(a) resulted in an odds ratio of 1.23 (95% CI, 1.00-1.51) and 1.21 (95% CI, 1.01-1.45) for the presence of low-density plaque at baseline and follow-up, respectively. Patients with higher Lp(a) levels had increased pericoronary adipose tissue attenuation around both the right coronary artery and left anterior descending at baseline and follow-up. Conclusions and Relevance: In this long-term prospective serial CCTA imaging study, higher Lp(a) levels were associated with increased progression of coronary plaque burden and increased presence of low-density noncalcified plaque and pericoronary adipose tissue inflammation. These data suggest an impact of elevated Lp(a) levels on coronary atherogenesis of high-risk, inflammatory, rupture-prone plaques over the long term.

Determination of lipid-rich plaques by artificial intelligence-enabled quantitative computed tomography using near-infrared spectroscopy as reference.

BACKGROUND AND AIMS: Artificial intelligence quantitative CT (AI-QCT) determines coronary plaque morphology with high efficiency and accuracy. Yet, its performance to quantify lipid-rich plaque remains unclear. This study investigated the performance of AI-QCT for the detection of low-density noncalcified plaque (LD-NCP) using near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS). METHODS: The INVICTUS Registry is a multi-center registry enrolling patients undergoing clinically indicated coronary CT angiography and IVUS, NIRS-IVUS, or optical coherence tomography. We assessed the performance of various Hounsfield unit (HU) and volume thresholds of LD-NCP using maxLCBI4mm ≥ 400 as the reference standard and the correlation of the vessel area, lumen area, plaque burden, and lesion length between AI-QCT and IVUS. RESULTS: This study included 133 atherosclerotic plaques from 47 patients who underwent coronary CT angiography and NIRS-IVUS The area under the curve of LD-NCP<30HU was 0.97 (95% confidence interval [CI]: 0.93-1.00] with an optimal volume threshold of 2.30 mm3. Accuracy, sensitivity, and specificity were 94% (95% CI: 88-96%], 93% (95% CI: 76-98%), and 94% (95% CI: 88-98%), respectively, using <30 HU and 2.3 mm3, versus 42%, 100%, and 27% using <30 HU and >0 mm3 volume of LD-NCP (p < 0.001 for accuracy and specificity). AI-QCT strongly correlated with IVUS measurements; vessel area (r2 = 0.87), lumen area (r2 = 0.87), plaque burden (r2 = 0.78) and lesion length (r2 = 0.88), respectively. CONCLUSIONS: AI-QCT demonstrated excellent diagnostic performance in detecting significant LD-NCP using maxLCBI4mm ≥ 400 as the reference standard. Additionally, vessel area, lumen area, plaque burden, and lesion length derived from AI-QCT strongly correlated with respective IVUS measurements.

Rationale and design of the INVICTUS Registry: (Multicenter Registry of Invasive and Non-Invasive imaging modalities to compare Coronary Computed Tomography Angiography, Intravascular Ultrasound and Optical Coherence Tomography for the determination of Severity, Volume and Type of coronary atherosclerosiS).

BACKGROUND: Coronary CT angiography (CCTA) is a first-line noninvasive imaging modality for evaluating coronary artery disease (CAD). Recent advances in CCTA technology enabled semi-automated detection of coronary arteries and atherosclerosis. However, there have been to date no large-scale validation studies of automated assessment of coronary atherosclerosis phenotype and coronary artery dimensions by artificial intelligence (AI) compared to current standard invasive imaging. METHODS: INVICTUS registry is a multicenter, retrospective, and prospective study designed to evaluate the dimensions of coronary arteries, as well as the characteristic, volume, and phenotype of coronary atherosclerosis by CCTA, compared with the invasive imaging modalities including intravascular ultrasound (IVUS), near-infrared spectroscopy (NIRS)-IVUS and optical coherence tomography (OCT). All patients clinically underwent both CCTA and invasive imaging modalities within three months. RESULTS: Patients data are sent to the core-laboratories to analyze for stenosis severity, plaque characteristics and volume. The variables for CCTA are measured using an AI-based automated software and assessed independently with the variables measured at the imaging core laboratories for IVUS, NIRS-IVUS, and OCT in a blind fashion. CONCLUSION: The INVICTUS registry will provide new insights into the diagnostic value of CCTA for determining coronary atherosclerosis phenotype and coronary artery dimensions compared to IVUS, NIRS-IVUS, and OCT. Our findings will potentially shed new light on precision medicine informed by an AI-based coronary CTA assessment of coronary atherosclerosis burden, composition, and severity. (ClinicalTrials.gov: NCT04066062).

Validation of an automated technique for quantification of pulmonary perfusion territories using computed tomography angiography.

Background: Computed tomography pulmonary angiography (CTPA) is the primary modality for the detection and diagnosis of pulmonary embolism (PE) while the stratification of PE severity remains challenging using angiography. Hence, an automated minimum-cost path (MCP) technique was validated to quantify the subtended lung tissue distal to emboli using CTPA. Methods: A Swan-Ganz catheter was placed in the pulmonary artery of seven swine (body weight: 42.6±9.6 kg) to produce different PE severities. A total of 33 embolic conditions were generated, where the PE location was adjusted under fluoroscopic guidance. Each PE was induced by balloon inflation followed by computed tomography (CT) pulmonary angiography and dynamic CT perfusion scans using a 320-slice CT scanner. Following image acquisition, the CTPA and the MCP technique were used to automatically assign the ischemic perfusion territory distal to the balloon. Dynamic CT perfusion was used as the reference standard (REF) where the low perfusion territory was designated as the ischemic territory. The accuracy of the MCP technique was then evaluated by quantitatively comparing the MCP-derived distal territories to the perfusion-derived reference distal territories by mass correspondence using linear regression, Bland-Altman analysis, and paired sample t-test. The spatial correspondence was also assessed. Results: The MCP-derived distal territory masses (MassMCP, g) and the reference standard ischemic territory masses (MassREF, g) were related by MassMCP=1.02MassREF - 0.62 g (r=0.99, paired t-test P=0.51). The mean Dice similarity coefficient was 0.84±0.08. Conclusions: The MCP technique enables accurate assessment of lung tissue at risk distal to a PE using CTPA. This technique can potentially be used to quantify the fraction of lung tissue at risk distal to PE to further improve the risk stratification of PE.

Contrast media timing optimization for coronary CT angiography: a retrospective validation study in swine.

OBJECTIVES: The objective was to retrospectively develop a protocol in swine for optimal contrast media timing in coronary CT angiography (CCTA). METHODS: Several dynamic acquisitions were performed in 28 swine (55 ± 24 kg) with cardiac outputs between 1.5 and 5.5 L/min, for 80 total acquisitions. The contrast was injected (1mL/kg, 5mL/s, Isovue 370), followed by dynamic scanning of the entire aortic enhancement curve, from which the true peak time and aortic and coronary enhancements were recorded as the reference standard. Each dataset was then used to simulate two different CCTA protocols-a new optimal protocol and a standard clinical protocol. For the optimal protocol, the CCTA was acquired after bolus tracking-based trigging using a variable time delay of one-half the contrast injection time interval plus 1.5 s. For the standard protocol, the CCTA was acquired after bolus tracking-based triggering using a fixed time delay of 5 s. For both protocols, the CCTA time, aortic enhancement, coronary enhancement, and coronary contrast-to-noise ratio (CNR) were quantitatively compared to the reference standard measurements. RESULTS: For the optimal protocol, the angiogram was acquired within -0.15 ± 0.75 s of the true peak time, for a mean coronary CNR within 7% of the peak coronary CNR. Conversely, for the standard CCTA protocol, the angiogram was acquired within -1.82 ± 1.71 s of the true peak time, for a mean coronary CNR that was 23% lower than the peak coronary CNR. CONCLUSIONS: The optimal CCTA protocol improves contrast media timing and coronary CNR by acquiring the angiogram at the true aortic root peak time. KEY POINTS: • This study in swine retrospectively developed the mathematical basis of an improved approach for optimal contrast media timing in CCTA. • By combining dynamic bolus tracking with a simple contrast injection timing relation, CCTA can be acquired at the peak of the aortic root enhancement. • CCTA acquisition at the peak of the aortic root enhancement should maximize the coronary enhancement and CNR, potentially improving the accuracy of CT-based assessment of coronary artery disease.

A patient-specific timing protocol for improved CT pulmonary angiography.

Rationale and objectives: To improve the image quality of CT pulmonary angiography (CTPA) using a patient-specific timing protocol. Material and methods: A total of 24 swine (48.5 ± 14.3 kg) underwent continuous contrast-enhanced dynamic CT acquisition over 30 s to capture the pulmonary arterial input function (AIF). Multiple contrast injections were made under different cardiac outputs (1.4-5.1 L/min), resulting in a total of 154 AIF curves. The volume scans with maximal enhancement in these AIF curves were retrospectively selected as the reference standard (group A). Two prospective CTPA protocols with bolus-tracking were then simulated using these AIF curves: one used a fixed delay of 5 s between triggering and CTPA acquisition (group B), while the other used a specific delay based on one-half of the contrast injection duration (group C). The mean attenuation, signal-to-noise (SNR) and contrast-to-noise ratios (CNR) between the three groups were then compared using independent sample t-test. Subjective image quality scores were also compared using Wilcoxon-Mann-Whitney test. Results: The mean attenuation of pulmonary arteries for group A, B and C (expressed in [HU]) were 870.1 ± 242.5 HU, 761.1 ± 246.7 HU and 825.2 ± 236.8 HU, respectively. The differences in the mean SNR and CNR between Group A and Group C were not significant (SNR: 65.2 vs. 62.4, CNR: 59.6 vs. 56.4, both p > 0.05), while Group B was significantly lower than Group A (p < 0.05). Conclusion: The image quality of CT pulmonary angiography is significantly improved with a timing protocol determined using contrast injection delivery time, as compared with a standard timing protocol with a fixed delay between bolus triggering and image acquisition.

Dynamic CT myocardial perfusion without image registration.

The aim of this study was to validate a motion-immune (MI) solution to dynamic CT myocardial perfusion measurement, in the presence of motion without image registration. The MI perfusion technique was retrospectively validated in six swine (37.3 ± 7.5 kg) with a motion-susceptible (MS) perfusion technique performed for comparison. In each swine, varying severities of stenoses were generated in the left anterior descending (LAD) coronary artery using a balloon under intracoronary adenosine stress, followed by contrast-enhanced imaging with 20 consecutive volume scans per stenosis. Two volume scans were then systematically selected from each acquisition for both MI and MS perfusion measurement, where the resulting LAD and left circumflex (LCx) measurements were compared to reference microsphere perfusion measurements using regression and diagnostic performance analysis. The MI (PMI) and microsphere (PMICRO) perfusion measurements were related through regression by PMI = 0.98 PMICRO + 0.03 (r = 0.97), while the MS (PMS) and microsphere (PMICRO) perfusion measurements were related by PMS = 0.62 PMICRO + 0.15 (r = 0.89). The accuracy of the MI and MS techniques in detecting functionally significant stenosis was 93% and 84%, respectively. The motion-immune (MI) perfusion technique provides accurate myocardial perfusion measurement in the presence of motion without image registration.

Contrast timing optimization of a two-volume dynamic CT pulmonary perfusion technique.

The purpose of this study is to develop and validate an optimal timing protocol for a low-radiation-dose CT pulmonary perfusion technique using only two volume scans. A total of 24 swine (48.5 ± 14.3 kg) underwent contrast-enhanced dynamic CT. Multiple contrast injections were made under different pulmonary perfusion conditions, resulting in a total of 141 complete pulmonary arterial input functions (AIFs). Using all the AIF curves, an optimal contrast timing protocol was developed for a first-pass, two-volume dynamic CT perfusion technique (one at the base and the other at the peak of AIF curve). A subset of swine was used to validate the prospective two-volume pulmonary perfusion technique. The prospective two-volume perfusion measurements were quantitatively compared to the previously validated retrospective perfusion measurements with t-test, linear regression, and Bland-Altman analysis. As a result, the pulmonary artery time-to-peak ([Formula: see text]) was related to one-half of the contrast injection duration ([Formula: see text]) by [Formula: see text] (r = 0.95). The prospective two-volume perfusion measurements (PPRO) were related to the retrospective measurements (PRETRO) by PPRO = 0.87PRETRO + 0.56 (r = 0.88). The CT dose index and size-specific dose estimate of the two-volume CT technique were estimated to be 28.4 and 47.0 mGy, respectively. The optimal timing protocol can enable an accurate, low-radiation-dose two-volume dynamic CT perfusion technique.

Absolute cerebral blood flow: Assessment with a novel low-radiation-dose dynamic CT perfusion technique in a swine model.

RATIONALE AND OBJECTIVES: To validate the accuracy of a novel low-dose dynamic CT perfusion technique in a swine model using fluorescent microsphere measurement as the reference standard. MATERIALS AND METHODS: Contrast-enhanced dynamic CT perfusion was performed in five swine at baseline and following brain embolization. Reference microspheres and intravenous contrast (370 mg/ml iodine, 1 ml/kg) were injected (5 ml/s), followed by dynamic CT perfusion. Scan parameters were 320×0.5 mm, 100 kVp and 200 mA. On average, 47 contrast-enhanced volume scans were acquired per acquisition to capture the time attenuation curve. For each acquisition, only two systematically selected volume scans were used to quantify brain perfusion with first-pass analysis technique. The first volume scan was selected at the base, simulating bolus tracking, while the second volume at the peak of the time attenuation curve similar to a CT angiogram. Regional low-dose CT perfusion measurements were compared to the microsphere perfusion measurements with t-test, linear regression and Bland-Altman analysis. The radiation dose of the two-volume CT perfusion technique was determined. RESULTS: Low-dose CT perfusion measurements (PCT) showed excellent correlation with reference microsphere perfusion measurements (PMICRO) by PCT = 1.15 PMICRO - 0.01 (r = 0.93, p ≤ 0.01). The CT dose index and dose-length product for the two-volume CT perfusion technique were 25.6 mGy and 409.6 mGy, respectively. CONCLUSIONS: The accuracy and repeatability of a low-dose dynamic CT perfusion technique was validated in a swine model. This technique has the potential for accurate diagnosis and follow up of stroke and vasospasm.

Combining perfusion and angiography with a low-dose cardiac CT technique: a preliminary investigation in a swine model.

Morphological and physiological assessment of coronary artery disease (CAD) is necessary for proper stratification of CAD risk. The objective was to evaluate a low-dose cardiac CT technique that combines morphological and physiological assessment of CAD. The low-dose technique was evaluated in twelve swine, where three of the twelve had coronary balloon stenosis. The technique consisted of rest perfusion measurement combined with angiography followed by stress perfusion measurement, where the ratio of stress to rest was used to derive coronary flow reserve (CFR). The technique only required two volume scans for perfusion measurement in mL/min/g; hence, four volume scans were acquired in total; two for rest with angiography and two for stress. All rest, stress, and CFR measurements were compared to a previously validated reference technique that employed 20 consecutive volume scans for rest perfusion measurement combined with angiography, and stress perfusion measurement, respectively. The 32 cm diameter volumetric CT dose index ([Formula: see text]) and size-specific dose estimate (SSDE) of the low-dose technique were also recorded. All low-dose perfusion measurements (PLOW) in mL/min/g were related to reference perfusion measurements (PREF) through regression by PLOW = 1.04 PREF - 0.08 (r = 0.94, RMSE = 0.32 mL/min/g). The [Formula: see text] and SSDE of the low-dose cardiac CT technique were 8.05 mGy and 12.80 mGy respectively, corresponding to an estimated effective dose and size-specific effective dose of 1.8 and 2.87 mSv, respectively. Combined morphological and physiological assessment of coronary artery disease is feasible using a low-dose cardiac CT technique.

Characterization of arterial plaque composition with dual energy computed tomography: a simulation study.

To investigate the feasibility of quantifying the chemical composition of coronary artery plaque in terms of water, lipid, protein, and calcium contents using dual-energy computed tomography (CT) in a simulation study. A CT simulation package was developed based on physical parameters of a clinical CT scanner. A digital thorax phantom was designed to simulate coronary arterial plaques in the range of 2-5 mm in diameter. Both non-calcified and calcified plaques were studied. The non-calcified plaques were simulated as a mixture of water, lipid, and protein, while the calcified plaques also contained calcium. The water, lipid, protein, and calcium compositions of the plaques were selected to be within the expected clinical range. A total of 95 plaques for each lesion size were simulated using the CT simulation package at 80 and 135 kVp. Half-value layer measurements were made to make sure the simulated dose was within the range of clinical dual energy scanning protocols. Dual-energy material decomposition using a previously developed technique was performed to determine the volumetric fraction of water, lipid, protein, and calcium contents in each plaque. For non-calcified plaque, the total volume conservation provides the third constrain for three-material decomposition with dual energy CT. For calcified plaque, a fourth criterion was introduced from a previous report suggesting a linear correlation between water and protein contents in soft tissue. For non-calcified plaque, the root mean-squared error (RMSE) of the image-based decomposition was estimated to be 0.7%, 1.5%, and 0.3% for water, lipid, and protein contents, respectively. As for the calcified plaques, the RMSE of the 5 mm plaques were estimated to be 5.6%, 5.7%, 0.2%, and 3.1%, for water, lipid, calcium, and protein contents, respectively. The RMSE increases as the plaque size reduces. The simulation results indicate that chemical composition of coronary arterial plaques can be quantified using dual-energy CT. By accurately quantifying the content of a coronary plaque lesion, our decomposition method may provide valuable insight for the assessment and stratification of coronary artery disease.

Dynamic pulmonary CT perfusion using first-pass analysis technique with only two volume scans: Validation in a swine model.

PURPOSE: To evaluate the accuracy of a low-dose first-pass analysis (FPA) CT pulmonary perfusion technique in comparison to fluorescent microsphere measurement as the reference standard. METHOD: The first-pass analysis CT perfusion technique was validated in six swine (41.7 ± 10.2 kg) for a total of 39 successful perfusion measurements. Different perfusion conditions were generated in each animal using serial balloon occlusions in the pulmonary artery. For each occlusion, over 20 contrast-enhanced CT images were acquired within one breath (320 x 0.5mm collimation, 100kVp, 200mA or 400mA, 350ms gantry rotation time). All volume scans were used for maximum slope model (MSM) perfusion measurement, but only two volume scans were used for the FPA measurement. Both MSM and FPA perfusion measurements were then compared to the reference fluorescent microsphere measurements. RESULTS: The mean lung perfusion of MSM, FPA, and microsphere measurements were 6.21 ± 3.08 (p = 0.008), 6.59 ± 3.41 (p = 0.44) and 6.68 ± 3.89 ml/min/g, respectively. The MSM (PMSM) and FPA (PFPA) perfusion measurements were related to the corresponding reference microsphere measurement (PMIC) by PMSM = 0.51PMIC + 2.78 (r = 0.64) and PFPA = 0.79PMIC + 1.32 (r = 0.90). The root-mean-square-error for the MSM and FPA techniques were 3.09 and 1.72 ml/min/g, respectively. The root-mean-square-deviation for the MSM and FPA techniques were 2.38 and 1.50 ml/min/g, respectively. The CT dose index for MSM and FPA techniques were 138.7 and 8.4mGy, respectively. CONCLUSIONS: The first-pass analysis technique can accurately measure regional pulmonary perfusion and has the potential to reduce the radiation dose associated with dynamic CT perfusion for assessment of pulmonary disease.

Vessel-specific coronary perfusion territories using a CT angiogram with a minimum cost path technique and its direct comparison to the American Heart Association 17-segment model.

OBJECTIVES: This study compared the accuracy of an automated, vessel-specific minimum cost path (MCP) myocardial perfusion territory assignment technique as compared with the standard American Heart Association 17-segment (AHA) model. METHODS: Six swine (42 ± 9 kg) were used to evaluate the accuracy of the MCP technique and the AHA method. In each swine, a dynamic acquisition, comprised of twenty consecutive whole heart volume scans, was acquired with a computed tomography scanner, following peripheral injection of contrast material. From this acquisition, MCP and AHA perfusion territories were determined, for the left (LCA) and right (RCA) coronary arteries. Each animal underwent additional dynamic acquisitions, consisting of twenty consecutive volume scans, following direct intracoronary contrast injection into the LCA or RCA. These images were used as the reference standard (REF) LCA and RCA perfusion territories. The MCP and AHA techniques' perfusion territories were then quantitatively compared with the REF perfusion territories. RESULTS: The myocardial mass of MCP perfusion territories (MMCP) was related to the mass of reference standard perfusion territories (MREF) by MMCP = 0.99MREF + 0.39 g (r = 1.00; R2 = 1.00). The mass of AHA perfusion territories (MAHA) was related to MREF by MAHA = 0.81MREF + 5.03 g (r = 0.99; R2 = 0.98). CONCLUSION: The vessel-specific MCP myocardial perfusion territory assignment technique more accurately quantifies LCA and RCA perfusion territories as compared with the current standard AHA 17-segment model. Therefore, it can potentially provide a more comprehensive and patient-specific evaluation of coronary artery disease. KEY POINTS: • The minimum cost path (MCP) technique accurately determines left and right coronary artery perfusion territories, as compared with the American Heart Association 17-segment (AHA) model. • The minimum cost path (MCP) technique could be applied to cardiac computed-tomography angiography images to accurately determine patient-specific left and right coronary artery perfusion territories. • The American Heart Association 17-segment (AHA) model often fails to accurately determine left and right coronary artery perfusion territories, especially in the inferior and inferoseptal walls of the left ventricular myocardium.

Low-Radiation-Dose Stress Myocardial Perfusion Measurement Using First-Pass Analysis Dynamic Computed Tomography: A Preliminary Investigation in a Swine Model.

OBJECTIVES: The aim of this study was to assess the feasibility of a prospective first-pass analysis (FPA) dynamic computed tomography (CT) perfusion technique for accurate low-radiation-dose global stress perfusion measurement. MATERIALS AND METHODS: The prospective FPA technique was evaluated in 10 swine (42 ± 12 kg) by direct comparison to a previously validated retrospective FPA technique. Of the 10 swine, 3 had intermediate stenoses with fractional flow reserve severities of 0.70 to 0.90. In each swine, contrast and saline were injected peripherally followed by dynamic volume scanning with a 320-slice CT scanner. Specifically, for the reference standard retrospective FPA technique, volume scans were acquired continuously at 100 kVp and 200 mA over 15 to 20 seconds, followed by systematic selection of only 2 volume scans for global perfusion measurement. For the prospective FPA technique, only 2 volume scans were acquired at 100 kVp and 50 mA for global perfusion measurement. All prospective global stress perfusion measurements were then compared with the corresponding reference standard retrospective global stress perfusion measurements through regression analysis. The CTDIvol and size-specific dose estimate of the prospective FPA technique were also determined. RESULTS: All prospective global stress perfusion measurements (PPRO) at 50 mA were in good agreement with the reference standard retrospective global stress perfusion measurements (PREF) at 200 mA (PPRO = 1.07 PREF -0.09, r = 0.94; root-mean-square error = 0.30 mL/min per gram). The CTDIvol and size-specific dose estimate of the prospective FPA technique were 2.3 and 3.7 mGy, respectively. CONCLUSIONS: Accurate low-radiation-dose global stress perfusion measurement is feasible using a prospective FPA dynamic CT perfusion technique.

Timing optimization of low-dose first-pass analysis dynamic CT myocardial perfusion measurement: validation in a swine model.

BACKGROUND: Myocardial perfusion measurement with a low-dose first-pass analysis (FPA) dynamic computed tomography (CT) perfusion technique depends upon acquisition of two whole-heart volume scans at the base and peak of the aortic enhancement. Hence, the objective of this study was to validate an optimal timing protocol for volume scan acquisition at the base and peak of the aortic enhancement. METHODS: Contrast-enhanced CT of 28 Yorkshire swine (weight, 55 ± 24 kg, mean ± standard deviation) was performed under rest and stress conditions over 20-30 s to capture the aortic enhancement curves. From these curves, an optimal timing protocol was simulated, where one volume scan was acquired at the base of the aortic enhancement while a second volume scan was acquired at the peak of the aortic enhancement. Low-dose FPA perfusion measurements (PFPA) were then derived and quantitatively compared to the previously validated retrospective FPA perfusion measurements as a reference standard (PREF). The 32-cm diameter volume CT dose index, [Formula: see text] and size-specific dose estimate (SSDE) of the low-dose FPA perfusion protocol were also determined. RESULTS: PFPA were related to the reference standard by PFPA = 0.95 · PREF + 0.07 (r = 0.94, root-mean-square error = 0.27 mL/min/g, root-mean-square deviation = 0.04 mL/min/g). The [Formula: see text] and SSDE of the low-dose FPA perfusion protocol were 9.2 mGy and 14.6 mGy, respectively. CONCLUSIONS: An optimal timing protocol for volume scan acquisition at the base and peak of the aortic enhancement was retrospectively validated and has the potential to be used to implement an accurate, low-dose, FPA perfusion technique.

Contrast-to-Noise Ratio Optimization in Coronary Computed Tomography Angiography: Validation in a Swine Model.

RATIONALE AND OBJECTIVES: The accuracy of coronary computed tomography (CT) angiography depends upon the degree of coronary enhancement as compared to the background noise. Unfortunately, coronary contrast-to-noise ratio (CNR) optimization is difficult on a patient-specific basis. Hence, the objective of this study was to validate a new combined diluted test bolus and CT angiography protocol for improved coronary enhancement and CNR. MATERIALS AND METHODS: The combined diluted test bolus and CT angiography protocol was validated in six swine (28.9 ± 2.7 kg). Specifically, the aortic and coronary enhancement and CNR of a standard CT angiography protocol, and a new combined diluted test bolus and CT angiography protocol were compared to a reference retrospective CT angiography protocol. Comparisons for all data were made using box plots, t tests, regression, Bland-Altman, root-mean-square error and deviation, as well as Lin's concordance correlation. RESULTS: The combined diluted test bolus and CT angiography protocol was found to improve aortic and coronary enhancement by 26% and 13%, respectively, as compared to the standard CT angiography protocol. More importantly, the combined protocol was found to improve aortic and coronary CNR by 29% and 20%, respectively, as compared to the standard protocol. CONCLUSION: A new combined diluted test bolus and CT angiography protocol was shown to improve coronary enhancement and CNR as compared to an existing standard CT angiography protocol.

Quantification of vessel-specific coronary perfusion territories using minimum-cost path assignment and computed tomography angiography: Validation in a swine model.

BACKGROUND: As combined morphological and physiological assessment of coronary artery disease (CAD) is necessary to reliably resolve CAD severity, the objective of this study was to validate an automated minimum-cost path assignment (MCP) technique which enables accurate, vessel-specific assignment of the left (LCA) and right (RCA) coronary perfusion territories using computed tomography (CT) angiography data for both left and right ventricles. METHODS: Six swine were used to validate the MCP technique. In each swine, a dynamic acquisition comprised of twenty consecutive volume scans was acquired with a 320-slice CT scanner following peripheral injection of contrast material. From this acquisition the MCP technique was used to automatically assign LCA and RCA perfusion territories for the left and right ventricles, independently. Each animal underwent another dynamic CT acquisition following direct injection of contrast material into the LCA or RCA. Using this acquisition, reference standard LCA and RCA perfusion territories were isolated from the myocardial blush. The accuracy of the MCP technique was evaluated by quantitatively comparing the MCP-derived LCA and RCA perfusion territories to these reference standard territories. RESULTS: All MCP perfusion territory masses (MassMCP) and all reference standard perfusion territory masses (MassRS) in the left ventricle were related by MassMCP = 0.99MassRS+0.35 g (r = 1.00). MassMCP and MassRS in the right ventricle were related by MassMCP = 0.94MassRS+0.39 g (r = 0.96). CONCLUSION: The MCP technique was validated in a swine animal model and has the potential to be used for accurate, vessel-specific assignment of LCA and RCA perfusion territories in both the left and right ventricular myocardium using CT angiography data.

Comprehensive Assessment of Coronary Artery Disease by Using First-Pass Analysis Dynamic CT Perfusion: Validation in a Swine Model.

Purpose To retrospectively validate a first-pass analysis (FPA) technique that combines computed tomographic (CT) angiography and dynamic CT perfusion measurement into one low-dose examination. Materials and Methods The study was approved by the animal care committee. The FPA technique was retrospectively validated in six swine (mean weight, 37.3 kg ± 7.5 [standard deviation]) between April 2015 and October 2016. Four to five intermediate-severity stenoses were generated in the left anterior descending artery (LAD), and 20 contrast material-enhanced volume scans were acquired per stenosis. All volume scans were used for maximum slope model (MSM) perfusion measurement, but only two volume scans were used for FPA perfusion measurement. Perfusion measurements in the LAD, left circumflex artery (LCx), right coronary artery, and all three coronary arteries combined were compared with microsphere perfusion measurements by using regression, root-mean-square error, root-mean-square deviation, Lin concordance correlation, and diagnostic outcomes analysis. The CT dose index and size-specific dose estimate per two-volume FPA perfusion measurement were also determined. Results FPA and MSM perfusion measurements (PFPA and PMSM) in all three coronary arteries combined were related to reference standard microsphere perfusion measurements (PMICRO), as follows: PFPA_COMBINED = 1.02 PMICRO_COMBINED + 0.11 (r = 0.96) and PMSM_COMBINED = 0.28 PMICRO_COMBINED + 0.23 (r = 0.89). The CT dose index and size-specific dose estimate per two-volume FPA perfusion measurement were 10.8 and 17.8 mGy, respectively. Conclusion The FPA technique was retrospectively validated in a swine model and has the potential to be used for accurate, low-dose vessel-specific morphologic and physiologic assessment of coronary artery disease. © RSNA, 2017.

Functional Assessment of Coronary Artery Disease Using Whole-Heart Dynamic Computed Tomographic Perfusion.

BACKGROUND: Computed tomographic (CT) angiography is an important tool for the evaluation of coronary artery disease but often correlates poorly with myocardial ischemia. Current dynamic CT perfusion techniques can assess ischemia but have limited accuracy and deliver high radiation dose. Therefore, an accurate, low-dose, dynamic CT perfusion technique is needed. METHODS AND RESULTS: A total of 20 contrast-enhanced CT volume scans were acquired in 5 swine (40±10 kg) to generate CT angiography and perfusion images. Varying degrees of stenosis were induced using a balloon catheter in the proximal left anterior descending coronary artery, and a pressure wire was used for reference fractional flow reserve (FFR) measurement. Perfusion measurements were made with only 2 volume scans using a new first-pass analysis (FPA) technique and with 20 volume scans using an existing maximum slope model (MSM) technique. Perfusion (P) and FFR measurements were related by PFPA=1.01 FFR-0.03 (R2=0.85) and PMSM=1.03 FFR-0.03 (R2=0.80) for FPA and MSM techniques, respectively. Additionally, the effective radiation doses were calculated to be 2.64 and 26.4 mSv for FPA and MSM techniques, respectively. CONCLUSIONS: A new FPA-based dynamic CT perfusion technique was validated in a swine animal model. The results indicate that the FPA technique can potentially be used for improved anatomical and functional assessment of coronary artery disease at a relatively low radiation dose.