Pulmonary Embolism

Pulmonary embolism (PE) is a difficult disease to diagnose. Many patients with PE are never studied and the majority of patients suspected of having PE, do not have the disease. PE is often, but not invariably, associated with lower extremity venous thrombosis. The prompt and accurate diagnosis is of major concern because untreated PE is potentially fatal and unnecessary treatment with anticoagulation has a high degree of morbidity and mortality. There are many imaging approaches to PE, each with its own strengths and weaknesses. Usually, more than one test is required to establish a diagnosis. For many years, ventilation-perfusion (V/Q) scintigraphy has been the main imaging modality for the evaluation of patients with suspected PE. Below is a description of each test and then a synopsis of possible imaging strategies.

Ventilation/Perfusion (V/Q) Scintigraphy
V/Q scan is the traditional imaging examination following a chest radiograph. The tracer is 99mTc-MAA (macroaggregated albumin), which is injected intravenously. Segmental perfusion defects denote block in vessels. Following this, a ventilation study is performed using inhalation of 99mTc-DTPA aerosols. If the segments with perfusion defects show filling up of aerosols, i.e.‘mismatched defects’ is diagnostic of PE. A negative perfusion scan virtually eliminates PE. A high-probability ventilation/ perfusion scan, in conjunction with a high clinical probability, is accurate in diagnosing over 95 per cent of PE.

An example of a high probability ventilation/perfusion lung scan. There are multiple
perfusion defects (arrows) with normal ventilation in these regions

Pharmacological Stress Agents for Radionuclide Myocardial Perfusion Imaging

For patients unable to exercise or in some circumstances where it is undesirable or unsafe,pharmacological stress is an excellent alternative.

Patients with the following are suitable for pharmacological stress testing:

a) Poor physical conditioning; limiting non-cardiac symptoms (e.g. atigue) Left bundle branch block (false-positive exercise perfusion scans)

b) Peripheral arterial disease; lung disease Spinal injuries; amputations; or orthopedic problems (e.g. low back pain)

Pharmacological Stress Agents
There are two classes.

The vasodilators include adenosine and dipyridamole. These increase myocardial perfusion and lead to a relative reduction in perfusion in territories supplied by obstructed vessels. These regional variations are not normally associated with ischaemia because they are not accompanied by an increase in myocardial oxygen demand.

The synthetic catecholamines include dobutamine and arbutamine. These also increase myocardial perfusion but less than the vasodilators and they also increase myocardial oxygen demand by increasing cardiac contractility and heart rate. They are therefore, more likely to provoke ischaemia.

Evaluation of Ventricular Function

First Pass Radionuclide Angiography (FPRNA)

First Pass Radionuclide Angiography (FPRNA) is a form of radionuclide angiocardiography in which a rapid sequence of images is taken immediately after administration of a bolus of radionuclide, recording only the initial transit of the isotope through the central circulation.

Equilibrium Gated Radionuclide Angiography (ERNA)

Equilibrium Gated Radionuclide Angiography (ERNA) is a form of radionuclide angiocardiography in which images are taken at specific phases of the cardiac cycle over a series of several hundred cycles. Timing of image recording is set, or gated, by the occurrence of specific electrocardiographic waveforms, and the data can be used to determine average activity during specific cardiac cycle phases or can be accumulated and displayed in rapid sequence, as a movie.

First-pass Radionuclide Angiography (FPRNA), Equilibrium Gated

Radionuclide Angiography (ERNA)

Three-camera imaging techniques are available to measure the ventricular function first-pass radionuclide angiography (FPRNA), equilibrium gated radionuclide angiography (ERNA), and GSPECT. During FPRNA, a dynamic bolus of radioactivity is imaged as it quickly transits through different chambers of the heart and lungs. It is a preferred technique for the assessment of peak-exercise ventricular function, and measurement of the right ventricular (RV) function. Both acquisitions of ERNA and GSPECT are synchronized with the patient’s ECG.

During an ERNA study, a blood-pool agent such as 99mTc-labeled erythrocytes is injected and images are acquired over many hundreds of heartbeats. Ventricular cavity counts are used to generate a time–activity curve, from which functional parameters are derived.There are fundamental differences between these procedures and GSPECT. During a GSPECT study, a perfusion tracer is injected which is taken up by the LV myocardium. Definition of the LV myocardium and LV cavity is achieved by delineating the epicardial and endocardial edges on the perfusion image. LV global and regional contractile function is quantitated based on the changes in the LV volume, excursion of the endocardium, and brightening of the myocardium from the end-diastolic image to the end-systolic image, as identified by the ECG. Because RV myocardium is not adequately visualized on the perfusion images, GSPECT is not suitable for accurate RV function measurement.

ERNA has been used as a standard technique for ventricular function measurements for many years. Despite its accuracy and reproducibility, there has been a decline in this procedure in recent years, mainly because of the widespread availability of echocardiography in clinical settings.

General Principles

Framing; Heartbeat Variation and Tolerance

In routine practice, acquisition of 24-32 frames per cardiac cycle is considered satisfactory. The computer determines the length of the cardiac cycle based on the average of multiple R–R intervals before the acquisition. A range of acceptable beats (“acceptance window”) is specified.This is known as “tolerance” and is expressed as the per centage of the mean R–R interval.

Quantitation

LV volume is calculated by multiplying the number of pixels within the LV cavity with the size of a pixel. LV volume can be generated for each of the frames in the cardiac cycle. The largest volume and the smallest volume represent the end-diastolic volume (EDV) and the end-systolic volume (ESV), respectively. LVEF is derived from the volumes using the formula (EDV –ESV)/EDV x 100.

Once the endocardial edge is detected, regional endocardial wall motion (RWM) can be quantitated by computing the distance of a given point on the endocardial surface between end- diastole and end-systole.

Myocardial Perfusion Imaging (Scintigraphy)

Scintigraphy is a technique whereby the transit of a dosage form through its intended site of delivery can be non-invasively imaged in vivo via the judicious introduction of an appropriate short lived gamma emitting radioisotope. The observed transit of the dosage form can then be correlated with the rate and extent of drug absorption. Information such as the site of disintegration or dispersion can also be obtained. Assistance in product development as well as testing of finished products for corporate sponsors are commonly performed.

Procedures

Stress Test: Treadmill

The procedure for nuclear myocardial scanning almost always involves a stress test, stress SPECT, and a resting SPECT (Fig. 7.3). Patient preparation involves fasting for 4 hours prior to imaging. Prior to the stress test, assessment of the patient’s cardiovascular history and physical examination should be performed; baseline vital signs should be evaluated and a 12-lead ECG
performed.

Protocol for 201Tl

 Image Acquisition and Analysis

Protocols

Several imaging procedures are available. A common protocol is the same-day single-radiopharmaceutical protocol performed by using 8 mCi (370 MBq) of 99mTc-sestamibi for the stress study. This is followed by the rest study with 24 mCi of 99mTc-sestamibi. SPECT imaging is performed for both studies by using a 180° collection. A 64 X 64 matrix with 32 stops is used.One common approach is to gate the stress study. Because sestamibi or tetrofosmin shows minimal redistribution, the perfusion pattern reflects the myocardial distribution of the tracer at the time of injection (peak stress), whereas function represents the LV function at the time of acquisition. The tracer is injected at rest and gated acquisition is repeated.

Gated SPECT (GSPECT): Principle of ECG Gating
The fundamental principle of ECG gating is illustrated in Fig. 7.4. During a SPECT imaging,camera records multiple projections around the chest along a 180° or 360° arc. Dynamic images are acquired at equal intervals during an ECG-gated acquisition. Acquisition starts with the R-wave on the ECG, which corresponds to the end-diastole. One cardiac cycle, represented by the R–R interval, is divided into multiple frames of equal duration. Image data for each of the frames are acquired repeatedly over many cardiac cycles and stored separately in the computer. During processing, all data of a particular frame are added together to construct a specific phase of the cardiac cycle.

Principle of gating

Principle of gating

Reconstruction of Images

Before reconstruction, it is important to check the raw projection data for potential sources of errors and artifacts. Any error during image acquisition (instruments, patient motion, or soft-tissue attenuation artifacts) is likely to compromise the accuracy of the measurements.

Image Evaluation
The overall quality of the study must be initially assessed by looking for artifacts or other sources of error (patient motion, breast or diaphragmatic attenuation) and to evaluate pulmonary and noncardiac uptake. Reconstructed perfusion images are displayed in a standardized format.On top are the short-axis stress and rest images. The second 2 lines display the vertical long-axis stress/rest images. The final 2 lines contain the horizontal stress/rest images. Images are usually reviewed in both a continuous color format, such as gray scale, and in a color scale.

In addition to viewing the wall motion from a 3-dimensional perspective, wall thickening can be visualized by viewing the gated short, vertical long, and horizontal long axes. Polar maps can be helpful in quantifying abnormalities in perfusion, regional ejection fraction, motion and wall thickening. Also arterial territories are superimposed on the images

Arterial territories

Quantitative Measurement and Analysis
LV volumes and LVEF can be obtained easily by applying the software to the reconstructed gated dataset. Software packages developed at Cedars-Sinai Medical Center (QGS), University of Michigan (4D-MSPECT) and Emory University (Emory Cardiac Toolbox) are widely available.LV regional function is more commonly evaluated visually on a cine-loop display. Some programs (e.g., QGS) offer automatic quantitative indices of RWM (in mm) and SWT (per cent diastolic thickness), which are displayed on a segmental, circumferential model of the LV with each segment representing a particular territory of the LV (Fig 7.4). All functional indices should be interpreted in reference to the age-and sex-specific normal database. Normal ranges of the LVEF and regional functional parameters for different programs have been reported.

General Guidelines to Reporting Nuclear Myocardial Scans
The report of technique includes the protocol, the radiopharmaceutical used, and the doses.Results for treadmill stress tests also include the peak heart rate achieved, associated percentage of the maximum predicted heart rate, the duration of the exercise and ECG changes. Comment on ventricular sizes, uptake by the right ventricle, the presence or absence of transient ischaemic dilation and lung uptake should be included. Comment on the size and severity of the defects.

Normal Findings
On perfusion studies result in almost identical stress/rest images with no defects. Tracer distribution is uniform in all the walls of left ventricle.

Fixed Defects

In patients with infarcted myocardium, findings demonstrate fixed defects.

Reversible Defects
Findings in patients with myocardial ischaemia demonstrate reversible defects, i.e., defects on the stress images without a similar defect on the rest images.

Wall Motion Analysis
GSPECT studies can be used to assess regional wall motion and left ventricular ejection fraction when viewed in a cine display. If a perfusion defect is present on stress images and the associated wall is seen to thicken (i.e.: brighten) during systole, one can predict that this represents an area containing viable myocardial tissue. If no thickening is observed, the finding may represent an area of infarction (scar).

Ejection Fraction

LV ejection fraction can be calculated from GSPECT data and provides incremental prognostic information for risk stratification.

LV Dilatation

Left ventricular chamber dilatation may also be noted with pharmacologic stress and is associated with an increased risk for subsequent cardiac event. This represents subendocardial ischaemia or diffuse reduced subendocardial flow reserve.

Pulmonary Activity on Stress Imaging

An increase in tracer uptake in lung on stress imaging is a marker for severe underlying CAD. A lung to heart ratio of greater than 0.33 is suggestive of underlying severe CAD.