Validation of a Computed Tomography (CT) Based Fractional Flow Reserve (FFR) Software Using the 320 Detector Aquilion ONE CT Scanner.

Study Overview
=================
Brief Summary
-----------------
Coronary Computed Tomography Angiography (CCTA) contrast opacification gradients and FFR-CT estimation can aid in the severity estimation of significant atherosclerotic lesions. Currently, FFR-CT algorithms can only be optimized using theoretical models and can only be validated in large multi-center clinical trials. Using patient specific 3D printed coronary phantoms would allow optimization of FFR-CT algorithms with a measured validation technique without the need for large clinical trials. Thus the investigators believe that this study will result in a FFR-CT algorithm/method with a better predictability for arterial lesion severity than those existing on the market today. Flow measurements will be compared with: CT-FFR for both patients and phantoms, angio lab FFR measurements and 30 days follow-up. This pilot clinical study includes  50 patients over a year and half at GVI.

Detailed Description
-----------------
Coronary Computed Tomography Angiography (CCTA) contrast opacification gradients and FFR-CT estimation can aid in the severity estimation of significant atherosclerotic lesions. Following this trend, the investigators recently developed a collaboration between Brigham and Women's Hospital (BWH) and Gates Vascular Institute (GVI). The investigators 3D-printed patient specific coronary phantoms at (GVI) and scanned them with a Toshiba Aquilion scanner to test several aspects of the contrast opacification gradients using a method established at BWH. The initial results showed strong correlation between the flow in the phantom and opacification gradients. The investigators believe that this approach could be further developed to test and validate FFR-CT algorithms. Currently, FFR-CT algorithms can only be optimized using theoretical models and can only be validated in large multi-center clinical trials. This phantom approach would allow optimization of FFR-CT algorithms with a measured validation technique without the need for large clinical trials. Thus the investigators believe that this study will result in a FFR-CT algorithm/method with a better predictability for arterial lesion severity than those existing on the market today. The approach is to use the infrastructure at GVI to perform a detailed validation of the FFR-CT method using 3D printed patient specific phantoms. The subject enrollment criteria is: at least one CCTA, at least one lesion with >50% stenosis or 30-50% and an angio based FFR. Each patient will have a 3D phantom printed, containing the culprit lesion and used in a benchtop flow analysis. Flow measurements will be compared with: CT-FFR for both patients and phantoms, angio lab FFR measurements and 30 days follow-up. This pilot clinical study will include  50 patients over a year and half at GVI. The investigators are confident that this approach performed via 3D-phantom testing will prove the validity of FFR-CT based measurements as well as develop a new standard for validating FFR-CT algorithms.

Official Title
-----------------
Validation of a Computed Tomography (CT) Based Fractional Flow Reserve (FFR) Software Using the 320 Detector Aquilion ONE CT Scanner.

Conditions
-----------------
Atherosclerosis, Coronary

Intervention / Treatment
-----------------
* Diagnostic Test: CCTA


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All the patients >18 yrs of age , who are undergoing CCTA and angio-FFR. Patients who are (1) scheduled for clinically mandated elective invasive coronary angiography (ICA) at Buffalo General Hospital or (2) clinically mandated CTA will be screened. Exclusion Criteria: Adults unable to consent Individuals who are not yet adults (infants, children, teenagers) Pregnant women Prisoners atrial fibrillation, Renal insufficiency (estimated glomerular filtration rate (GFR) <60 ml/min/1.73 m2), Active Bronchospasm prohibiting the use of beta blockers Morbid obesity (body mass index 40 kg/m2) Contraindications to iodinated contrast. Emergencies requiring immediate intervention or patients unable to consent. Patients not showing coronary calcium during Calcium Scoring procedures

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CCTA<br>Patients who are scheduled for clinically mandated elective invasive coronary angiography (ICA) at Buffalo General Hospital. | Diagnostic Test: CCTA<br>* Diagnostic Test<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of CT Based FFR With Invasive FFR, ROC Analysis | Patient CCTA images were imported into Vitrea segmentation software (Vital Images, Minnetonka, MN) for use in the research-based CT based FFR algorithm. The software analyzes four data volumes acquired a 70%, 80%, 90% and 99% of the R-R interval and computes the FFR based on the changes in vessel diameter and computational fluid dynamics. Within the algorithm, the aortic root and three main coronary arteries (LAD, LCX, and RCA) were automatically segmented, and then manually adjusted to obtain accurate centerline and contours. The CT based FFR was calculated and the user adjusted the location of the distal pressure measurement to calculate the CT basedFFR at the same location as Invasive-FFR, two lesion lengths below the distal end of the lesion. Area under the Receiver Operator Characteristic were measured where an Invasive FFR<=0.8 was considered positive. | 24 hours | 
| Comparison of CT Based FFR With Invasive FFR, Correlation Analysis | Patient CCTA images were imported into Vitrea segmentation software (Vital Images, Minnetonka, MN) for use in the research-based CT based FFR algorithm. The software analyzes four data volumes acquired a 70%, 80%, 90% and 99% of the R-R interval and computes the FFR based on the changes in vessel diameter and computational fluid dynamics. Within the algorithm, the aortic root and three main coronary arteries (LAD, LCX, and RCA) were automatically segmented, and then manually adjusted to obtain accurate centerline and contours. The CT based FFR was calculated and the user adjusted the location of the distal pressure measurement to calculate the CT basedFFR at the same location as Invasive-FFR, two lesion lengths below the distal end of the lesion. Pearson Correlation between Invasive FFR and CT based FFR was measured | 24 hours | 
| Comparison of CT Based FFR With Invasive FFR, Sensitivity | Patient CCTA images were imported into Vitrea segmentation software (Vital Images, Minnetonka, MN) for use in the research-based CT based FFR algorithm. The software analyzes four data volumes acquired a 70%, 80%, 90% and 99% of the R-R interval and computes the FFR based on the changes in vessel diameter and computational fluid dynamics. Within the algorithm, the aortic root and three main coronary arteries (LAD, LCX, and RCA) were automatically segmented, and then manually adjusted to obtain accurate centerline and contours. The CT based FFR was calculated and the user adjusted the location of the distal pressure measurement to calculate the CT basedFFR at the same location as Invasive-FFR, two lesion lengths below the distal end of the lesion. Sensitivity were measured where an Invasive FFR<=0.8 was considered positive. Sensitivity reflects the percentage of true positive cases identified by CT-FFR compared to I-FFR | 24 hours | 
| Comparison of CT Based FFR With Invasive FFR, Specificity | Patient CCTA images were imported into Vitrea segmentation software (Vital Images, Minnetonka, MN) for use in the research-based CT based FFR algorithm. The software analyzes four data volumes acquired a 70%, 80%, 90% and 99% of the R-R interval and computes the FFR based on the changes in vessel diameter and computational fluid dynamics. Within the algorithm, the aortic root and three main coronary arteries (LAD, LCX, and RCA) were automatically segmented, and then manually adjusted to obtain accurate centerline and contours. The CT based FFR was calculated and the user adjusted the location of the distal pressure measurement to calculate the CT basedFFR at the same location as Invasive-FFR, two lesion lengths below the distal end of the lesion. Specificity was measured, where an Invasive FFR<=0.8 was considered positive. Specificity reflects the percentage of true negative cases identified by CT-FFR compared to I-FFR | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of CT Based FFR With Bench-top FFR Using 3D Printed Patient Specific Phantoms | CT images were used to measure CT-FFR and to generate patient-specific 3D printed models of the aortic root and three main coronary arteries. Each patient-specific 3D printed model was connected to a programmable pulsatile pump and bench-top FFR (B-FFR) was derived from pressures measured proximal and distal to coronary stenosis using pressure transducers. B-FFR was measured for hyperemic, 500 mL/min by adjusting the model's distal coronary resistance. Linear regression and Pearson correlation was calculated. | 4 weeks from baseline | 
| Comparison of Bench-top FFR Using 3D Printed Patient Specific Phantoms With Invasive FFR, ROC Analysis | CT images were used to create patient specific 3d-printed phantom. Each patient-specific 3D printed model was connected to a programmable pulsatile pump and benchtop FFR (B-FFR) was derived from pressures measured proximal and distal to coronary stenosis using pressure transducers. B-FFR was measured for hyperemic, 500 mL/min by adjusting the model's distal coronary resistance. Benchtop-FFR was compared with Invasive-FFR. Area under the Receiver Operator Characteristic were measured where an Invasive FFR<=0.8 was considered positive. | 4 weeks from baseline | 
| Comparison of Bench-top FFR Using 3D Printed Patient Specific Phantoms With Invasive FFR, Pearson Correlation | CT images were used to create patient specific 3d-printed phantom. Each patient-specific 3D printed model was connected to a programmable pulsatile pump and benchtop FFR (B-FFR) was derived from pressures measured proximal and distal to coronary stenosis using pressure transducers. B-FFR was measured for hyperemic, 500 mL/min by adjusting the model's distal coronary resistance. Benchtop-FFR was compared with Invasive-FFR. Pearson Correlation factor was calculated. | 4 weeks from baseline | 
| Comparison of Bench-top FFR Using 3D Printed Patient Specific Phantoms With Invasive FFR, Sensitivity | CT images were used to create patient specific 3d-printed phantom. Each patient-specific 3D printed model was connected to a programmable pulsatile pump and benchtop FFR (B-FFR) was derived from pressures measured proximal and distal to coronary stenosis using pressure transducers. B-FFR was measured for hyperemic, 500 mL/min by adjusting the model's distal coronary resistance. Benchtop-FFR was compared with Invasive-FFR. Sensitivity was measure, where an Invasive FFR<=0.8 was considered positive.Sensitivity reflects the percentage of true positive cases identified by B-FFR compared to I-FFR | 4 weeks from baseline | 
| Comparison of Bench-top FFR Using 3D Printed Patient Specific Phantoms With Invasive FFR, Specificity | CT images were used to create patient specific 3d-printed phantom. Each patient-specific 3D printed model was connected to a programmable pulsatile pump and benchtop FFR (B-FFR) was derived from pressures measured proximal and distal to coronary stenosis using pressure transducers. B-FFR was measured for hyperemic, 500 mL/min by adjusting the model's distal coronary resistance. Benchtop-FFR was compared with Invasive-FFR. Specificity was calculated, where an Invasive FFR<=0.8 was considered positive. Specificity reflects the percentage of true negative cases identified by B-FFR compared to I-FFR | 4 weeks from baseline | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
FFR, Fractional Flow Reserve, Atherosclerosis, Coronary, stenosis