First pass angiocardiography 1. Principle

First pass radionuclide angiocardiography (FPRNA) is a rapid, reliable and reproducible method of assessing cardiac function based on a few monitored heartbeats. It involves the imaging of an intravenously injected radionuclide bolus during its initial transit through the central circulation. A time–activity curve is generated, and the temporal separation of the right and left ventricular phases allows evaluation of individual ventricular function. This is based on the assumption that thorough mixing of the tracer has occurred in the blood pool and that the detected count rate reflects the changes in ventricular volume during contraction and relaxation.

Left and right ventricular function assessed at rest, or during stress with first pass imaging, gives a comprehensive evaluation of short duration changes that may affect the ventricles. This includes evaluation of global and regional wall motion, estimation of ejection fraction and other systolic and diastolic parameters. Such information has proved significant in the diagnosis, prognosis, decision making and management of certain clinical problems such as coronary artery disease and chronic obstructive lung disease, as well as congenital and valvular heart disease.

5.2.2.2. Clinical indications (a) Coronary artery disease

Rest and exercise FPRNA has been used extensively in diagnosing and managing patients with known or suspected coronary artery disease, as well as with complications of acute myocardial infarction.

Wall motion abnormalities, changes in end systolic volume and changes in diastolic filling rate are suggestive of ischaemia and the presence of coronary artery disease. Evaluation of the left ventricular regional wall motion is, however, limited since the FPRNA is done one projection at a time. The anterolateral, apical and inferoseptal walls are visible in the anterior view while the right anterior oblique (RAO) view provides images of the anterior, apical and inferior walls. Regional wall motion in the RAO first pass study correlates well with contrast angiocardiography. Correlation is likewise good between the left ventricular ejection fraction (LVEF) calculated using FPRNA and the values obtained by contrast and equilibrium radionuclide ventriculography. For the measurement of right ventricular ejection fraction (RVEF), FPRNA is considered the method of choice. The technique allows images to be acquired in the RAO view, giving a maximal separation of the right atrium from the right ventricle. The tracer bolus might not, however, mix completely with the right atrial blood prior to entering the right ventricle and may exit without mixing completely with apical blood, giving rise to potential sources of errors.

(b) Congenital heart disease

Detection and quantification of left-to-right shunts are possible using FPRNA. The presence of a shunt is confirmed by simultaneous tracer appearance in the right and left ventricles. In a normal study, the left ventricle is free of any right ventricular activity. Quantitation of a left-to-right shunt is dependent on the quality of the bolus injected. A delayed or fragmented bolus may affect the shape of the pulmonary curve generated, which should be monoexponential, even in the absence of a shunt. Shunting separates the pulmonary activity curve into two components, which are proportional to the systemic and shunt flows, respectively, giving an index of the severity of the shunt.

(c) Valvular heart disease

Assessment of valvular insufficiency is possible with resting FPRNA.

Studies showing prolonged tracer transit through the left side of the heart may

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reflect mitral or aortic insufficiency. From the pulmonary and left ventricular time–activity curves, the degree of regurgitation may be calculated and quantified. Data from FPRNA have been shown to correlate with measure-ments obtained by catheterization. Resting studies performed serially can be helpful in monitoring the severity of the valvular insufficiency and in deciding when valve replacement is necessary.

5.2.2.3. Radiopharmaceuticals

The ideal radionuclide as a first pass imaging agent must remain intravas-cular as it moves through the central circulation. It should also be safe for application in large doses in order to generate the necessary high count rates.

(a) Technetium-99m agents

The high specific activity of ^99mTc makes it suitable as a first pass agent.

For multiple or sequential studies, ^99mTc diethylene triamine pentaacetic acid (DTPA) is preferred to ^99mTc-pertechnetate. DTPA has rapid renal excretion, making possible a repeat injection 20 min later. Technetium-99m pertechnetate can be used when a single assessment of ventricular function is needed. The usual dose for ^99mTc agents is 925 MBq and a maximum of three injections, 370 MBq (10 mCi) each, can be given (Table 5.1).

Other technetium based compounds such as sestamibi and tetrofosmin are also suitable. First pass imaging can be performed upon injection of the tracer during peak exercise, thus combining information on regional and global ventricular function as well as myocardial perfusion in one setting.

(b) Short lived radioisotopes

The need for first pass studies to be performed repeatedly in a short period of time presents some restrictions with ^99mTc agents. The half-life of 6 h and varying biological clearance times limit the number of acquisitions that can be done in a given period. In order to reduce the patient’s radiation exposure and allow for a greater number of studies to be performed, radionuclides with half-lives in terms of seconds or minutes would be ideal.

Tantalum-178 produces suboptimal results when used with standard gamma cameras because of its low energy; more satisfactory results have been reported with a multiwire proportional gamma camera. The short half-life of

191mIr makes it suitable for paediatric patients. Gold-195m is ideal for adult patients, and the calculated ejection fraction correlates well with that obtained using ^99mTc agents. Evaluation of myocardial perfusion could possibly be done

with ^195mAu in combination with ventricular function assessment. Table 5.2 summarizes the physical characteristics of the above mentioned short lived radioisotopes.

5.2.2.4. Equipment

Monitoring of the radionuclide bolus during its transit through the central circulation requires a gamma camera with a high count rate capability, a high sensitivity collimator, a computer software capable of processing high temporal resolution data and a small matrix acquisition, as well as an ECG gating device.

A bicycle ergometer is an additional requirement for first pass studies during exercise.

More than 200 000 counts/s are needed to achieve an adequate image quality. The use of cameras with low count rate capabilities leads to an inaccurate measurement of ejection fraction and assessment of wall motion.

Originally, only multicrystal gamma cameras could record such high counts, although with some loss of spatial resolution. Newer generations of multi-crystal cameras can now acquire the same range of counts with enhanced energy and spatial resolutions. Modern single crystal cameras are also capable of achieving rates of up to 200 000 counts/s, as opposed to older cameras with rates of only up to 60 000 counts/s.

The choice of collimator depends on the objective of the study and the dose to be injected. Computer software should allow acquisitions to be performed with 64 ¥ 64 or smaller matrices.

An ECG signal is unnecessary for high count rate studies, since there are enough counts to distinguish between end-diastolic and end-systolic frames. It TABLE 5.1. FIRST PASS STANDARD Tc-99m DOSES

Type of study Rest Exercise

LV/RV^a function – multicrystal camera

370–925 MBq (10–25 mCi) (0.3–0.5 mL)

925 MBq (25 mCi) (0.3–0.5 mL) LV function –

single crystal camera

925 MBq (25 mCi) (0.3–0.5 mL)

925 MBq (25 mCi) (0.3–0.5 mL) RV function –

single crystal camera

740–925 MBq (20–25 mCi) (0.3–0.5 mL)

740–925 MBq (20–25 mCi) (0.3–0.5 mL) Shunt study 370–555 MBq (10–15 mCi)

(0.3–0.5 mL)

a LV, left ventricular; RV, right ventricular.

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may be more helpful with single crystal camera acquisitions to facilitate data processing of low count rate studies.

5.2.2.5. Procedure (a) Tracer injection

First pass studies require the injection of a small volume of radionuclide bolus. The quality of the study largely depends on the integrity of the bolus.

Large proximal veins must be used as injection sites, since smaller, peripheral veins may cause bolus fragmentation. The injection parameters appropriate to the various kinds of study are listed in Table 5.3.

For left ventricular evaluation or shunt studies, it is important that the bolus arrive in the heart as a single front. Rapid injection of the radionuclide and a 10–20 mL saline flush (within 2–3 s) is necessary. In right ventricular studies, since the bolus reaches the right ventricle without significant dispersion, an antecubital vein is preferred since the use of the external jugular vein may result in too rapid transit of the bolus through the chamber. A slower bolus is preferred to increase the number of beats available for analysis; the saline flush may be then infused without interruption for 3–4 min.

(b) Radionuclide dose

The appropriate dose depends upon the sensitivity of the gamma camera, the number of times the study will be performed and the specific radionuclide used. Recommended doses for ^99mTc agents are listed in Table 5.1. Short lived radionuclides have been given at doses as high as 50 mCi. The acquisition parameters for FPRNA are given in Table 5.4.

TABLE 5.2. CHARACTERISTICS OF SHORT LIVED RADIOISOTOPES

Radioisotope Half-life Photon energy (keV)

Ta-178 9.3 min 55–65

Ir-191m 4.9 s 129

Au-195m 30.5 s 262

(c) Imaging angles

Proper positioning of the patient must be verified prior to the start of the study. A radioactive source or dose syringe may be used to check areas of interest in the FOV and allow identification of the lungs.

Temporal separation of the cardiac chambers allows the study to be acquired in any view, although the RAO and anterior projections are most commonly used. The shallow RAO view — best for direct comparison with contrast angiography — separates the atria from the ventricles and the left ventricle from the descending aorta. The 30^o RAO view enhances the separation of the right chambers, making it the ideal view for right ventricular assessment.

The upright straight anterior view is best for exercise studies since the chest is stabilized against the detector. The pulmonary background is also reduced, enhancing study quality. The descending aorta and the basal portion of the inferoseptal wall may, however, overlap with the left atrium and basal portion of the left ventricle. The left anterior oblique view is useful when the circumflex artery territory is in question, but may result in underestimation of the LVEF.

(d) Frame rates

A standard frame time of 25 ms/frame can be applied for RV and LV function studies regardless of the type of camera used, but theoretically the frame time should be adjusted according to the heart rate. Fifty ms/frame is adequate at heart rates lower than 80 beats per minute decreasing to 10–20 ms/

frame for faster heart rates, especially if diastolic function is of interest. Two thousand frames are sufficient to encompass the entire left ventricular phase.

TABLE 5.3. INJECTION PARAMETERS

LV^a function studies RV^b function studies Shunt studies Site Medial antecubital or

external jugular vein

Antecubital vein Antecubital or external jugular vein

Cannula 18–20 gauge 18–20 gauge 18–20 gauge

Rate Rapid (FWHM < 1 s) Slow (FWHM 2–3 s) Rapid (FWHM < 1 s)

a LV, left ventricular.

b RV, right ventricular.

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Frame rates are not as essential in a shunt study since data analysis uses curves of lower temporal resolution.

(e) Stress protocol

Bicycle ergometry is the method of choice for exercise studies. Although supine bicycle exercise results have been shown to correlate with catheteri-zation, upright bicycles are more often used since they minimize chest motion and are better tolerated by patients. Any graded exercise protocol is acceptable and no time is required to stabilize the heart rate. Exercise should be continued until the bolus clears from the left ventricle.

(f) Data processing

Processing of a first pass radionuclide study can be divided into four major steps:

(1) Generation of an initial time–activity curve over the cardiac region;

(2) Beat selection;

(3) Background subtraction;

(4) Creation of the final representative cardiac cycle.

The initial time–activity curve is important for quality control. It permits inspection of the separation of the right and left ventricular phases, allows the estimation of the peak count achieved, and detects the presence of irregular beats. An ROI is drawn around the ventricle, grouping frames from the raw data. This is used to generate a time–activity curve from which an initial repre-sentative cycle is created and used to draw separated diastolic and end-systolic ROIs.

TABLE 5.4. ACQUISITION PARAMETERS FOR FPRNA

Parameter LV^a function RV^b function Shunt study

Position Upright Upright Upright

Angle Anterior 20–30^o RAO Anterior

Frame time (ms) 25 25 50

Total frames 1500–2000 1500–2000 2000

a LV, left ventricular.

b RV, right ventricular.

Once the left ventricular ROI has been identified, cardiac cycles to be included in the final analysis may be selected from the ventricular time–

activity curve. The cycles before and after the beat with the maximum number of counts are selected. Premature ventricular beats and post-extrasystolic beats should be excluded. Beats whose end-diastolic counts are below 50% of the maximum end-diastolic count should also be omitted if they do not preclude a statistically adequate representative cycle. Only beats around the peak of the time–activity curve (80% or more of maximum activity) are to be used. This leaves one or two beats during the right ventricular phase and four to five beats during the left ventricular phase available for analysis. Averaging of several individual beats can also be done to form a summed representative cycle.

Background subtraction can be performed using several methods. The most accurate appears to be the lung frame method. Image counts in the ROI just prior to the appearance of tracer activity in the left ventricle are chosen as background counts and used to correct the left ventricular phase. Background correction is crucial for the LVEF, and any variations in background counts can lead to changes in the calculated ejection fraction, volumes and wall motion.

Once the background has been corrected, initial ROIs are adjusted and the final ROIs are used to regenerate the time–activity curve from which the final representative cycle is created from the previously selected beats. This cycle may be displayed in a cine-loop for analysis of regional wall motion. All quantitative data are also derived from this cycle.

The LVEF and RVEF are calculated from the end-diastolic (ED) and end-systolic (ES) counts as follows: (ED counts – ES counts)/ED counts. The systolic emptying rates and diastolic filling rates are calculated with appropriate software using a Fourier filter applied to the representative cycle and taking the first derivative of the filtered curve. Left ventricular end-diastolic volume may be measured using the geometric or count proportional method. The geometric method measures the area of the left ventricle and the length of the major axis in pixels. Converted to centimetres, the pixels are used to calculate the volume. In the count proportional method, volume is derived from the total counts and the counts in the hottest pixel in the left ventricle.

This method requires validation for each laboratory.

5.2.2.6. Interpretation

The radionuclide bolus appears sequentially in the superior vena cava, right atrium, right ventricle, pulmonary circulation, left side of the heart and aorta. Any changes in this pattern would suggest the presence of a congenital abnormality. Delayed tracer transit through the right side of the heart suggests

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pulmonary hypertension, tricuspid or pulmonary valve insufficiency or a left-to-right shunt. Delayed tracer transit on the left side of the heart would suggest mitral or aortic insufficiency.

Regional wall motion is analysed by superimposing the end-diastolic outline against the end-systolic image or by viewing the representative cycle in cine-mode. However, it has to be noted that since the study was acquired in only one projection, regional wall motion abnormalities may be difficult to identify in overlapping segments. Ischaemic responses applicable to the diagnosis of coronary artery disease are typically a new onset of a regional wall motion abnormality or a worsening of a previous one, an increase in the end-systolic volume and alterations in diastolic filling parameters.