Cardiovascular System

Abstract

Scintigraphy of the cardiovascular system in children is less common than in adults, reflecting the different nature and prevalence of cardiac diseases in paediatrics. Congenital malformations of the heart and their effect on cardiac and pulmonary functions and on myocardial perfusion are common indications in children. The first pass study is an investigation that can detect and quantify cardiac left-to-right shunts. It is used only in selected cases. Myocardial perfusion scintigraphy (MPS), with or without physical or pharmacological stress, provides important information on blood supply to the myocardium. It can also evaluate myocardial contractility with gated SPECT. The gated cardiac blood pool scan, also known as radionuclide ventriculography or multigated acquisition (MUGA) scan assesses the cardiac blood pool synchronized to the child’s ECG and allows measurement of the left ventricular (LV) ejection fraction (EF). In most centres, this study has been replaced in the last decade by echocardiography and MRI to assess the quality of the ventricular contraction and is therefore not discussed further in this chapter (Milanesi et al., Semin Nucl Med 47(2): 158–169, 2017; Venet et al., Front Pediatr 10: 909994, 2022). Vascular anomalies in children include benign tumors such as infantile hemangiomas and hemangioendotheliomas as well as low and high-flow vascular malformations. Whole-body blood pool scintigraphy with focused SPECT or SPECT/CT provides specific diagnosis for vascular anomalies and is commonly used in conjunction with radiological imaging methods, especially when those are inconclusive.

3.1 First Pass Study

3.1.1 Clinical Indications [1, 2]

• Evaluation and quantification of cardiac left-to-right shunts

• To determine cardiac functional parameters such as LVEF in children with:

  • Atrial septal defect

  • Ventricular septal defect

  • Truncus arteriosus

  • Patent ductus arteriosus

  • Complete atrio-ventricular canal

  • Aorto-pulmonary collaterals

Study Protocol for First Pass Studies [3]

Radiopharmaceutical, Activity and Mode of Delivery

Radiopharmaceuticals:

One of the following can be used:

• [^99mTc]pertechnetate (Pertechnetate). In this case, premedication with perchlorate is advised to avoid unnecessary thyroid uptake.

• [^99mTc]diethylene-triamine-pentaacetate (DTPA).

• [^99mTc]sestamibi (MIBI) or [^99mTc]Tetrofosmin. In this case, myocardial perfusion can be assessed after first pass acquisition.

• [^99mTc]red blood cells (RBCs)—using the in vivo labelling kit has the additional benefit that an RVG can be performed after the first pass.

Activity:

• Weight-based; 9.6 MBq/kg (0.26 mCi/kg), range 80 MBq (2.16 mCi)—490 MBq (13.24 mCi).

  Refer to the EANM paediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective European Association of Nuclear Medicine (EANM) and Society of Nuclear Medicine and Molecular Imaging (SNMMI) and image gently web sites.

Reference to national regulation guidelines, if available, should be considered.

Delivery:

Injection technique:

• Arm used for injection is extended with a 90-degree angle from the body.

• Use of a central line is recommended, otherwise use the largest possible size intravenous (IV) cannula (not a butterfly needle!), placed and checked for patency before the study.

• The bolus should be small, less than 0.2 ml, with high specific activity.

• Rapid, uninterrupted, bolus injection should be followed by a rapid bolus of normal saline to flush the activity. This is best achieved using a three-way stopcock, connected to the radiotracer syringe and to a second syringe filled with saline (5–20 ml, depending on the calibre of the venous access).

Acquisition Protocol

• Collimator: low energy, high sensitivity

• Matrix 64 × 64

• Acquisition:

  • Dynamic study and anterior supine position.

  • Has to be gated if equilibrium LVEF measurements are performed in addition to evaluation of the shunt.

  • Should start a few seconds before injection, to avoid missing the first frames.

  • It is critical to center precisely the cardiac region in the field-of-view (FOV) before injecting the bolus. FOV should extend from the suprasternal notch to just below the xiphoid and include most lung parenchyma.

  • Adequate zooming, considering the small dimensions of the cardiac cavities, particularly in younger children.

  • For shunt evaluation a 2–4 frames/s rate is adequate.

  • If LVEF measurements are required, a rate of at least 25 frames/s should be used for a total of 15–30 s, taking into account an early start of the acquisition.

3.1.2 Study Interpretation

Assessment of adequacy of bolus (Fig. 3.1)

• Quality control (QC) of the injected bolus should be the first step prior to processing.

  • A ROI is placed over the superior vena cava (SVC) and a time activity curve (TAC) is generated.

  • This TAC is used to check the adequacy of the bolus.

  • If the bolus is adequate, the TAC shows a single peak with a full-width half maximum (FWHM) of less than 3 s.

Left-to-right shunt calculation (Fig. 3.1)

• A ROI is drawn over the lungs taking care to avoid the heart and large vessels and a TAC is generated.

• The normal pulmonary TAC shows a sharp peak, due to the transient tracer passage through the lungs followed by a smaller, wide-based peak representing the portion of the initial bolus returning to the lungs after recirculating through the systemic circulation.

• In case of a left-to-right shunt, there is persistence of tracer activity in the lungs due to premature pulmonary recirculation of the tracer through the shunt.

  • The magnitude of the persistent pulmonary activity is proportional to the size of the shunt.

  • In moderate-to-severe shunts, there is poor visualization of the left side of the heart and the aorta.

• The TAC is further fitted with a gamma-variate curve. The area under the gamma-variate lung fitted curve is calculated. The value obtained is denoted as Qp.

• The gamma-variate fitted curve is then subtracted from the original lung curve in order to get the recirculation shunt curve.

• A second gamma-variate fit is performed on the recirculation curve and the area under the new fitted curve is denoted as Qshunt.

• The systemic flow denoted as Qs is calculated as the difference between Qp and Qshunt and is consistent with the recirculation after the first pass through the body.

• The ratio between the Qp/Qs is considered normal if below 1.4–1.6.

• The report should include a description of the passage of tracer through the cardiac right atrium, right ventricle, lungs, left atrium and ventricle and systemic circulation.

Fig. 3.1

Assessment of bolus adequacy and left-to-right shunt calculation. The square ROI depicts the SVC. The solid line represents the TAC obtained from counts measured in a ROI drawn over the lungs taking care to avoid the heart and large vessels. The broken line represents the area under the gamma-variate lung fitted curve. No additional curve is seen early after the lung curve to suggest premature recirculation related to a left-to-right shunt. The calculated Qp/Qs is 1.59. There is no evidence for a physiologically significant left-to-right shunt

3.1.3 Correlative Imaging

• Trans-esophageal echocardiography and ultrasound (US) bubble study may be used to identify shunt.

• Magnetic resonance angiography (MRA) and CT angiography (CTA) may also show the presence of a left-to-right shunt.

• Echocardiography and MRI have replaced in most instances this modality for calculations of the left and right ventricular EF.

3.1.4 Red Flags

• Meticulous injection and imaging technique and data processing are mandatory to obtain reliable and reproducible results.

• Avoid injecting whilst the patient is crying because rapid changes in intrathoracic pressure will likely cause bolus fragmentation and render the study inadequate.

• QC of the injected bolus should be the first step prior to processing. A fragmented or spread bolus will introduce errors in the computation of the first pass study.

• If the bolus is inadequate, a second study can be performed with approximately twice the initial activity. This applies only to studies performed with DTPA and Pertechnetate. If both injections fail, the study should be postponed to another day.

• The ROI drawn over the lungs should avoid the heart and large vessels.

3.1.5 Take Home Messages

• Anterior supine position offers the best spatial resolution since the detector is at a minimum distance from the heart. Left anterior oblique (LAO) view gives the best separation between LV and right ventricle (RV) and is preferred if evaluation of ventricular function is required. Right anterior oblique (RAO) view offers the best separation between the right atrium and RV.

• Left-to-right shunts mostly involve the atrial and/or ventricular septa.

• The first pass study is a sensitive technique to detect the presence of a left-to-right shunt and to quantify the magnitude of the shunt by calculating the ratio between the pulmonary and systemic circulations (Qp/Qs).

3.1.6 Representative Case Examples

Case 3.1. Normal First Pass Study, Exclusion of Left-to-Right Shunt (Fig. 3.2)

Fig. 3.2

History: The study was requested to exclude a left-to-right cardiac shunt. Study report: Dynamic images demonstrate sequential arrival of activity into the superior vena cava, the right side of heart, pulmonary arteries, lungs, pulmonary veins and the left side of heart. Impression: Normal study. No left-to-right shunt was detected

Case 3.2. Left-to-Right Shunt (Fig. 3.3)

Fig. 3.3

History: A child with a heart murmur was detected on routine stethoscope auscultation. Study report: Dynamic images show a sharp bolus travelling via the superior vena cava into the RV and the lungs. There is persisting tracer activity within the lungs due to premature recirculation through the left-to-right shunt, as well as in the LV and systemic circulation. Impression: Left-to-right shunt

3.2 Myocardial Perfusion Scintigraphy

3.2.1 Clinical Indications [4]

• Coronary malformations.

• Post-surgical coronary abnormalities (i.e., arterial switch in transposition of great arteries).

• Kawasaki disease.

• Arteritis (Takayasu).

• Cardiomyopathy.

• Chest pain (not a common indication in pediatrics population).

• Chest trauma.

Study Protocol for Myocardial Perfusion Studies [5, 6]

Patient Preparation

• Knowledge of a number of factors that may influence the final interpretation of the study, such as the patient’s cardiac and coronary anatomy and/or cardiac surgery history.

• Results of prior MPS studies.

• Medication—in case the patient is taking any of the below drugs and if clinically feasible stop.

  • Vasodilators for 24 h.

  • Calcium antagonists for 2 days.

  • Beta-blockers for 3 days.

  • Theophylline for 24 days (particularly for adenosine test).

• Avoid caffeine for 24 hours.

• Sedation is often required up to the age of 5–6 years.

Stress Testing [7]

• Physical stress (ergometer or treadmill): should be performed when possible.

• Pharmacological stress: is preferred in younger children and whenever patients and/or parents/caregivers cannot offer the necessary compliance.

  • Adenosine is preferred over dipyridamole because it has a shorter biological half-life (around 10 s).

  • For the use of adenosine or dipyridamole as a cardiac stressor reference to national regulation guidelines, if available, should be considered.

  • Pump infusion is desirable for adenosine intravenous administration (0.14 mg/kg/min for 6 min).

  • Only scarce literature is available for the paediatric use of regadenoson, but data are promising [8].

  • A second venous access should be used for the infusion of the tracer. If it is not feasible, a two-way stopcock positioned directly on the cannula is the best solution to inject quickly, stopping the adenosine infusion for a few seconds and avoiding an adenosine bolus.

Radiopharmaceutical, Administration Activity, Mode of Delivery

Radiopharmaceuticals:

• [^99mTc]SestaMIBI (MIBI)

• [^99mTc]Tetrofosmin.

Activity:

• Depends heavily on the sensitivity of the available camera.

• As a rule of thumb, a minimum recommended activity of 80 MBq (2.2 mCi) is considered acceptable, but lower activities are possible (and desirable).

  Refer to the EANM paediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective European Association of Nuclear Medicine (EANM) and Society of Nuclear Medicine and Molecular Imaging (SNMMI) and image gently web sites.

  Reference to national regulation guidelines, if available, should be considered.

Acquisition Protocol

• Camera: a dual-heads camera in 90 degrees configuration is preferred.

• Collimators: low-energy high-resolution or dedicated cardiac collimators. Consider ultra-high resolution (UHR) collimators in newborns and younger infants.

• Position: supine, arms above head.

• Orbit: 180°, from RAO to left posterior oblique (LPO), keep the orbit as tight as possible.

• 60 projections, 128 × 128 matrix, 25–30 s/frame, depending on camera sensitivity.

• Adequate acquisition zooming.

• Gated SPECT should be acquired whenever possible.

3.2.2 Study Interpretation

• Evaluation of raw images in cine mode to determine the presence of potential sources of image artefact and the distribution of extracardiac tracer activity.

• Check proper orientation of the post-stress and rest images.

• Assess whether myocardial perfusion defects are present and if so determine their:

  • Extent/size: small, medium, large.

  • Severity: mild, moderate, severe.

  • Presence and extent of reversibility: reversible or irreversible.

  • Location: based on segment model [9, 10].

3.2.3 Red Flags

• Requirements for performing stress tests: continuous ECG monitoring, blood pressure measurements and pediatric resuscitation equipment.

• Physical stress is difficult to perform in younger children, for the lack of suitable equipment and because of the short attention span.

• When performing physical stress it can be difficult to reach the target heart rate in some congenital situations, due to sinus node dysfunction (e.g. Fontan circulation) or pharmacological interference.

• Adequate zooming during acquisition is essential to get enough detail in the images.

• Reconstruction parameters (e.g. filter) have to be adapted to the small size of the heart.

• Normal myocardial perfusion patterns may differ widely from normal distribution as seen in adult ischemic heart disease, such as visualization of the RV, a different ventricular septum morphology.

• Normalcy databases for quantitative perfusion scoring are not validated for pediatric patients.

• In order to avoid unnecessary sedation and reduce radiation exposure, it is advisable to perform stress testing first. In case of a negative stress study, the rest study is omitted.

• Reporting functional data obtained from the gated images can be helpful, but requires careful quality control before processing, because of the difficult delineation of the myocardial profile of the small heart chambers.

3.2.4 Take Home Messages

• Acquisition techniques must be adapted to the clinical and anatomical situation.

• Ergometer or treadmill stressing should be performed when possible. It is more physiologic and can offer useful additional information such as exercise capacity or symptoms.

• Pharmacological stress is often preferred in young children.

• Pump infusion is desirable for adenosine intravenous administration to achieve a constant infusion rate.

• Adenosine with a shorter biological half-life, around 10 s, is preferred over dipyridamole. Its side effects are easily managed, usually without the need for the antidote (theophylline).

3.2.5 Representative Case Examples

Case 3.3. Normal Myocardial Perfusion Study (Fig. 3.4)

Fig. 3.4

History: Patient with Takayasu’s arteritis. Study report: An exercise gated myocardial perfusion stress test was performed. Overall study quality is excellent. There is normal myocardial perfusion at stress and rest. The LVEF is 89%. Conclusion: Normal myocardial perfusion scintigraphy

Case 3.4. Reversible Perfusion Defect in Anterior Wall (Fig. 3.5)

Fig. 3.5

History: A 11-year-old boy after arterial switch operation for transposition of the great arteries with left coronary malformation complained of mild chest discomfort during exercise. Exercise ischemia is suspected. Stress/rest test (ergometer) followed by MIBI injection was performed. Study report: There is decreased perfusion in the anterior wall (apical and mid-planes, white arrows) improving at rest. Impression: Reversible hypoperfusion of the anterior wall

Case 3.5. Partially Reversible Perfusion Defects (Fig. 3.6)

Fig. 3.6

History: A 14-year-old boy after arterial switch operation for transposition of the great arteries and anomalous origin of the coronary arteries. Stress/rest test (ergometer) followed by MIBI injection was performed. Study report: On the stress study (upper row) there is mild hypoperfusion of the antero-lateral wall (white arrows) and the septum (green arrows) with partial improvement on the rest study (lower row). Impression: Partially reversible hypoperfusion in antero-lateral wall and septum

3.3 Blood Pool Scintigraphy of Vascular Structures

3.3.1 Clinical Indications [11, 12]

• Evaluation of hemangiomas or other vascular malformations.

• To rule out unsuspected additional lesions.

• In cases with high clinical suspicion but with inconclusive US, CT and/or MRI.

3.3.2 Pre-Exam Information

• Location and size of the lesion(s) suspected as hemangiomas.

• Findings on correlative radiologic imaging.

Study Protocol for RBC Scintigraphy [13]

Radiopharmaceutical, Activity and Mode of delivery.

Radiopharmaceutical:

[^99mTc]RBCs (RBC) [14].

• In vitro labelling is the method of choice and should be employed when an adequate facility and proper radiopharmacy practices are available because of significantly higher labelling efficiency and a lower likelihood of artefacts related to free ^99mTc.

  • 1–3 ml of the patient’s blood are drawn anticoagulated with heparin or acid citrate dextrose (ACD).

  • RBCs are labelled with a commercially available preparation according to the manufacturer’s instructions.

  • General blood manipulation/handling precautions should be implemented. The labelled blood should be slowly re-injected to the patient from whom it was drawn.

• In vivo labelling:

  • ⁺²Sn pyrophosphate is injected in appropriate, weight-based amount obtained from the package insert of the commercial cold kit.

  • Administration of [^99m Tc]Pertechnetate follows 20 minutes later.

Activity (Pertechnetate):

• 74 MBq/Kg (2 mCi/kg), a minimum dose of 74 MBq (2 mCi).

  Refer to the EANM paediatric dosage card and to the North American consensus guidelines on radiopharmaceutical administration in children in the respective European Association of Nuclear Medicine (EANM) and Society of Nuclear Medicine and Molecular Imaging (SNMMI) and image gently web sites.

  Reference to national regulation guidelines, if available, should be considered.

Acquisition Protocol

• Collimator: low energy, all purpose.

• Position: supine.

• FOV: according to the location of the lesion to be investigated, preferably whole body.

• Dynamic study: 1 s/frame, 60 s, matrix 128 × 128, zoom according to child’s size.

• Static blood pool images: early, following the dynamic study and late, 2 h after tracer injection: 500 Kcounts, projections according to body region, matrix 256 × 256.

• SPECT following late static images: 25 s/step, 120 projections, matrix 128 × 128, size-appropriate zoom.

• When available SPECT/CT can clarify foci of uncertain origin.

3.3.3 Study Interpretation

• Vascular malformations may show an arterial blush on the dynamic phase when bolus injection is performed.

• Foci of increased tracer accumulation on the late blood pool planar or SPECT images are likely to represent haemangiomas.

3.3.4 Correlative Imaging

• US may be used to characterize the solid and cystic component of vascular lesions and with Doppler assessment may provide some information on vascularity.

• CTA or MRI/MRA may also identify and characterize vascular lesions.

3.3.5 Red Flags

• Injection of in vitro labelled RBC requires extreme caution to ensure that the blood is injected into the patient from whom it was drawn. To reduce the chance of misadministration, it is advised to avoid booking more than one in vitro labelled RBC study per day.

• In vivo RBC labelling allows optimal bolus injection.

• Inadequate RBC labelling may result in free Pertechnetate in circulation. Uptake in the thyroid gland and gastric mucosa will suggest improper labelling. Care should be taken not to confuse physiologic uptake and excretion of Pertechnetate with foci of increased blood pool activity.

• The ability to detect hemangiomas depends on their size and location. Those smaller than 1.5 cm in diameter may not be evident especially when situated in organs with high blood pool activity or when they are adjacent to large blood vessels.

• Small hemangiomas are better evaluated with contrast-enhanced CT or MRI.

3.3.6 Take Home Messages

• Hemangiomas and vascular malformations might be multifocal, especially in infants. It is advised to perform a whole-body scan to screen for additional findings throughout the body.

• SPECT/CT improves the accuracy and diagnostic confidence.

3.3.7 Representative Case Examples

Case 3.6. Facial Hemangioma (Fig. 3.7)

Fig. 3.7

History: A 17-year-old girl presented with a 15-mm pulsatile mass in left face, suspected to be of vascular origin. Study report: Dynamic study of the head (a) following the injection of Tc-RBC does not show areas of increased blood flow. Early planar anterior view of the head (b) shows a slightly increased blood pool in the lateral aspect of the left face. Transaxial slices of SPECT/CT performed at 2 h after radiotracer administration (c) demonstrate an area of increased blood pool corresponding to swelling of soft tissues in the left temporal-zygomatic area. Impression: The findings are consistent with a vascular lesion with venous blood supply in the left face. US-guided fine needle aspiration confirmed the diagnosis of hemangioma