Angiogenesis Core Services at PERFUSE

Qualitative Visual Techniques 

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Click here for an overview of quantitative techniques

Click here for an overview of digital subtraction techniques to quantitate angiographically inapparent vessel growth 

Qualitative Angiographic Analysis     

        Please find described below the Qualitative Visual Methods that are used in the PERFUSE Core Laboratory to Assess Angiogenesis Films. The following assessments are performed for the qualitative analysis of each film: the PERFUSE Collateral Flow Grade to classify the collateral flow; the Rentrop Grade to assess the extent of recipient vessel filling; the Length Grade to classify the length of the collateral according to the number of 8ths of the parent vessel length, (for example, a collateral that is one-half the length of the parent vessel has a Length Grade of 4 (4 eighths)); the PERFUSE Bifurcation Count to grade the number of bifurcations present within each collateral system.  The duration and intensity of the PERFUSE myocardial blush are also assessed.

 

General Technique for Viewing Films

       The analysis of angiograms for a single patient at two timepoints is performed using side by side projectors with identical illuminating characteristics. The angiograms are initially reviewed in toto to obtain an overview of the patient's coronary anatomy, extent of coronary artery disease, and collateralization.  If a change in the collateral network is identified, then this change is confirmed after swapping the film between the two projectors.  Subtle differences in illumination can have a profound impact on the detection of these small vessels.  Confirmation by two observers is required to assure that a change has indeed occurred. From multiple views taken, the optimal single plane projection is selected to assess the originating and recipient vessel (if applicable) of each collateral using the Coronary Artery Surgery Study (CASS) Code and PERFUSE Anatomic Location Code.

 

Criteria to Distinguish Between a Parent Epicardial Vessel and a Collateral Vessel

Determining where a collateral begins and where a parent epicardial vessel ends can often be quite difficult. The criteria used to classify a vessel as a collateral and not a segment of a major epicardial artery are listed below. If a vessel meets any these criteria, it is considered a collateral vessel:

Criterion 1: If the vessel anastomoses with a distal segment of the same epicardial artery.

Criterion 2: If the vessel anastomoses with another vessel classified as a collateral.

Criterion 3: If the vessel has a mean diameter less than 0.7 mm. We have found that most collaterals have a diameter between 0.3 mm and 0.7 mm by calipered measurement. Vessels with a diameter less than 0.3 mm may not be angiographically apparent or discernible from the background quantum mottle.

Criterion 4: If the vessel (<0.7 mm) extends beyond one half the distance between the epicardial artery segment that it originates from, and any adjacent epicardial artery segment. For example, a vessel extending from the distal portion of a septal artery beyond one half of the distance to the posterior descending artery would be considered a collateral.

Criterion 5: If the vessel arises at a branch angle less than 135 degrees from the upstream vessel, thereby deviating from the normal range of epicardial branching angles.

Criterion 6: If the vessel has excessive tortuosity manifested by either a sine wave appearance or by a doubling back upon itself.

Criterion 7: If the vessel has a corkscrew appearance.

Criterion 8: If the vessel is a branch arising from a major epicardial artery that was not apparent at both initial and follow-up time points.

A common criterion used to identify collaterals is the 0.7 mm size criteria; but several small branches often present in patients with normal anatomy are not considered to be collaterals. Such branches include: 1) the distal bifurcation of the left anterior descending artery (commonly referred to as the moustache, whale’s tail, or pitchfork) as long as each branch does not extend beyond 10 mm from the parent artery (5 six French catheter widths); 2) septal branches that do not extend more than half the distance to the inferior border of the heart; 3) diagonal branches that follow a conventional 30 to 45 degree branch pattern off the left anterior descending artery; 4) acute marginal branches in the right coronary artery may arise at an acute angle, but are not considered collaterals if they are >0.7 mm unless they meet any of the aforementioned criteria; 5) the sinoatrial and atrioventricular nodal branches of the right coronary artery are not considered collaterals unless they meet the aforementioned criteria for length or termination at an epicardial artery.

 Analysis of Collateral Flow

The following definitions are used to describe the collateral flow grade.

 PERFUSE Collateral Flow Grade:

            While previous systems have focused upon filling of a distinct recipient epicardial vessel, these classification schemes have ignored flow in the collateral vessel which often may have no angiographically apparent epicardial recipient vessel.  The following system is used to distinguish between various levels of collateral flow:

PERFUSE Grade 0 Flow: No flow in the collateral.  This would be documented if a collateral had been visible at one timepoint, but was not angiographically apparent at the other timepoint.

PERFUSE  Grade 1 Flow: The collateral is barely apparent.  Dye is not visible throughout the cardiac cycle, but is present in at least 3 consecutive frames.  There may not be clear antegrade dye motion in the collateral, it fills faintly and diffusely.  There may be no clear connection with a major epicardial artery or side branch.

PERFUSE Grade 2 Flow: The collateral is moderately opaque, but is present throughout at least 75% of the cardiac cycle.  There is antegrade motion of the dye rather than diffuse filling.

PERFUSE Grade 3 Flow: The collateral is well opacified and the column of dye is well defined (i.e. greater than 0.5 mm in diameter), but is <0.7 mm wide throughout the majority of its length. The collateral has clear antegrade dye motion.

PERFUSE Grade 4 Flow: The collateral is well opacified, fills antegrade, and is very large.  It is over 1 mm in diameter throughout the majority of its length.

 

Rentrop Scoring of Angiogenesis:

Grade 0: No evidence of collaterals

Grade 1: Minimal evidence of collaterals (side branches fill, epicardial segments do not)

Grade 2: Moderate evidence of collaterals (side branches fill, epicardial segments fill partially)

Grade 3: Extensive evidence of collaterals (epicardial segments fill completely via collaterals)

The PERFUSE Myocardial Blush Grade

Myocardial blush is the opacification of the myocardial microvasculature via vessels which are beyond the resolution of the imaging chain. The size of the myocardial blush can be planimetered so that the circumference of the blush can be determined. It should be noted, however, that the circumference is determined from a two dimensional view of a three dimensional structure and therefore is not a representation of the volume of myocardium that blushes and will vary in size depending upon the angulation of the gantry. Also collaterals in two separate myocardial walls may overlap in many views (e.g. collaterals in within the septum and lateral left ventricular free wall overlap in right anterior oblique views). The use of this measure underscores the need to record and reproduce the angle and skew of the gantry at both time points.

While the previous technique is used to assess the size (circumference) of the myocardial blush, the following classification scheme is used to classify myocardial blush presence and duration:

PERFUSE Blush Duration Grade 0: No myocardial blush apparent.

PERFUSE Blush Duration Grade 1: Myocardial blush is apparent during contrast injection but washes out immediately following dye washout from the epicardial artery.

PERFUSE Blush Duration Grade 2: Myocardial blush persists mildly for less than 3 cardiac cycles after dye washout from the epicardial artery.

PERFUSE Blush Duration Grade 3: Myocardial blush persists for over three cardiac cycles after dye washout from the epicardial artery, but has resolved before the next contrast media injection.

PERFUSE Blush Duration Grade 4: Myocardial blush persists long after dye washout from the epicardial artery and is present before the next injection of contrast media.

 

The PERFUSE Blush Intensity:

The PERFUSE Blush Duration Grade above focuses mainly on the duration of the blush in reference to the cardiac cycle.  The following blush intensity, classification scheme characterizes the brightness of the blush:

PERFUSE Blush Intensity Grade 0:  No or minimal myocardial blush apparent.

PERFUSE Blush Intensity Grade 1:  Myocardial blush is present, but not as bright as the surrounding collaterals.

PERFUSE Blush Intensity Grade 2:  Myocardial blush, at its maximum intensity, is as bright as the surrounding collaterals, and at its average, is not as bright as the surrounding collaterals.

PERFUSE Blush Intensity Grade 3:  Myocardial blush, at its maximum intensity, is as bright as the parent epicardial artery, and at its average intensity, is as bright as the surrounding collaterals.

 

Assessment and Classification of the Branching Pattern of Collaterals:

In order to quantify the development of new branches of a collateral artery and to assess the complexity of a collateral network, a quantitative scheme called the Bifurcation Count was developed.  The Bifurcation Count is the number of terminating arms in a collateral system with a single origin.  For example, a collateral with two termination arms stemming from the bifurcation, would have a Bifurcation Count equal to 2.  If one of these arms went on to again bifurcate, the Bifurcation Count for the collateral system would be equal to 3.  A collateral which does not bifurcate is a single terminating arm and has a Bifurcation Count equal to 0.  Increasing bifurcation counts reflect increasing complexity of the collateral network.  There is no upper limit to the Bifurcation Count in a single collateral system.

Click here for an overview of quantitative techniques

Click here for an overview of digital subtraction techniques to quantitate angiographically inapparent vessel growth