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.

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.

Severe cardiomyopathy associated with the VCP p.R155C and c.177_187del MYBPC3 gene variants.

Inclusion Body Myopathy, Paget's Disease of Bone, with Frontotemporal Dementia is a progressive autosomal dominant disease that affects the ubiquitin-proteasome complex, that is caused by variants in the Valosin Containing Protein (VCP) gene. We report the first case of concurrent pathogenic variants in both MYBPC3 and VCP that led to earlier onset of congestive heart failure with features of dilated cardiomyopathy. Cardiomyopathy has previously been associated with VCP inclusion body myopathy mostly at an advanced stage of the disease. Due to acute onset of cardiomyopathy in a previous asymptomatic individual, a cardiomyopathy gene panel was obtained which revealed an additional c.177_187del variant of the MYBPC3 gene. We report a first case of concurrent pathogenic variants in both c.177_187del gene of MYBPC3 and p.R155C VCP that led to earlier onset and a more severe form of the cardiomyopathy.

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.

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.

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.

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.