January 1994, Volume 44, Issue 1

Review Articles

Thallium-201: An Agent for Myocardial Perfusion and Viability Imaging

Maseeh-uz-Zaman  ( Atomic Energy Medical Centre, Jinnah Postgraduate Medical Centre, Karachi. )
Shahid Kamal  ( Atomic Energy Medical Centre, Jinnah Postgraduate Medical Centre, Karachi. )
Akhtar Ahmad  ( Atomic Energy Medical Centre, Jinnah Postgraduate Medical Centre, Karachi. )
Rashid Hashmi  ( Atomic Energy Medical Centre, Jinnah Postgraduate Medical Centre, Karachi. )
Khalid Niaz  ( Atomic Energy Medical Centre, Jinnah Postgraduate Medical Centre, Karachi. )

Myocardial perfusion imaging (MN) was first viewed as an alternative to coronary angiography for detecting coronary artery disease (CAD). A more appro­priate and probably more important use is for the demonstration of myocardial ischaemia and detection of viable myocardium. In these latter applications, MPI is complimentary to coronary angiography and provides information relevant to patient management. Thallium-201 was first proposed and introduced for MPI in early seventies1,2. Since then thallium has evolved as an important diagnostic modality aiding significantly in the diagnosis and management of patients with CAD.Physical Properties and Biokinetics of 201Tl: It is a cyclotron produced radionuclide having a half life of about 73 hrs which allows convenient preparation and shipment of the material. A relative disadvantage of 11-201 is the low photon energy (68-80 key) which results in significant tissue attenuation and scatter, degenerating the images. Less than 40 sec after an i.v. injection approximately 50% of Tl-201 is extracted by various tissues of the body. Myocardial extraction efficiency is extremely high -about 88% of thallium that reaches the myocardial cells will be taken up and concentrated intracellularly. The cellular uptake is mediated by active transport through Na-K ATPase pumps. Typically 4-5% of the injected dose concentrates in the myocardium while the remainder is distributed throughout other tissues3. The largest radiation dose is absorbed by the kidneys. The renal dose varies from 0.84-1.34 rad/mCi and whole body radiation is 0.21 rad/mCi4. Localization ofTl-201 in the myocardial cells involves two phases:
a) Initial distribution:
The initial myocardial concentration of thallium is equal to the product of myocardial blood flow and extraction fraction.
b) Redistribution:
This concept was put forward by Pohost et al,5 in 1977 and during this phase thallium initially taken up by the well perfused myocardial and skeletal muscles slowly begins to migrate out of the cells into the blood stream (wash out). Therefore, the difference between intracel­lular concentration of thallium in well perfused and ischaemic cells decreases over time, as the large amount of the thallium concentrated within the well perfused cells tend to be reabsorbed by the blood stream and transported to adjacent is chaemic tissue. It has been demonstrated that significant redistribution may occur as early as 20 min after injection and it is normally completed by 4 hours. Based on these facts, 201TI defects may be classified as completely reversible, partially reversible and irreversible defects (i.e. infarction). How­ever, in a recent study it has been found that 30% of irreversible defects at 4 hrs redistribution images did show viability (redistribution) after 24 hr or 30-60 min after a second dose of thallium given after 4 hr redistribu­tion image (re-injection)6.
c)  Reverse Redistribution:
In 5-7% of cases, the phenomenon of reverse redistribution may be seen which is defined as the appearance of new perfusion defects or worsening of stress induced defects on redistribution images. Pre­viously it was considered as having correlation with significant CAD but recent studies do not show any such relationship7.
Patient Preparation
1) The patient should be kept fasting for at least 4 hours prior to the study to minimize the splanchnic uptake.
2) To avoid interference with physiological stress induced heart rate response, all beta-blocker and calcium channel antagonist should be discon­tinued about 24-48 hrs before the test.
3) An i.v. cannula of about 20G is inserted in a large vein (median cubital vein) for effective bolus administration of 201TI.
4) FCC electrodes are placed for recording of 12 leads FCC at rest, during exercise and recovery phase.
Stress Test
Patient is stressed according to Bruce protocol consisting of seven-3min stages of progressively increas­ing speed and angle (treadmill) or load (ergometer bicycle). During the whole exercise BP, pulse and ECG is recorded for every stage of the test. For optimal results, the patient should attain 90% of his predicted maximal HR (100% 220-age in years). Accepted end points of exercise before the desired FIR is achieved are i) angina, ii) severe fatigue and dyspnea, iii) hypotension, iv) severe arryrthmia and v) significant ST depression. At peak exercise (or symptom limited end point of exercise) about 74 MBq (2 mCi) of 201TI is injected i.v. as bolus and the patient is encouraged to maintain the reacnect level of stress for another 1-2 min to ensure proper thallium delivery to the myocardium and mini­mum splanchnic pooling.
Thaffluni-201 Dipyridamole Test
In a significant number of patients requiring evalu­ation of CAD, stress 201TI is not feasible due to either limited exercise tolerance, musculoskeletal problem like arthritis or paralysis or amputation of a limb, LBBB, previous non-diagnostic Efl and if the patient is really dependent on beta-blockers or calcium channel block­ers. In such cases pharmacological intervention with dipyridamole (persantin) is recommended. Dipyridamole, a pyridimine derivative, induces myocardial hyperaemia by elevating the endogenous adenosine level which is a potent vasodilator. Myocar­chum supplied by a coronary artery with significant stenosis will demonstrate reduced perfusion and conse­quently diminished thallium-201 uptake ifinjected within minute after the coronary vasodilatation by dipyridam­ole. The presumed mechanism includes increase in coronary blood flow, 3-5 times over baseline; and coronary steal phenomenon to areas with normal coro­nary artery supply. A typical protocol for dipyridamole 11-201 imaging includes 0.568 mg/kg of dipyridamole infused over a period of 4 mm followed by a bolus of 74 MBq (2mCi) of 201TI 3-4 min later. Systemic and cardiac side effects can occur of which headache, dizziness, angina and ST depression are most common. Aminophylline. axanthine derivative, in a dose of 50-200 mg i.v. can effectively counteract the systemic and local side effects8. In a large multicentric study no significant differ­ence was found regarding the sensitivity and specificity of thallium stress and dipyridamole testing. However, an­gina occurred more frequently in conjunction with thallium stress test (63%) than with dipyridamole (31%)9.
Imaging
Imaging of 201TI uptake should start within 3-10 min after the injection of tracer. A standardised protocol with strict quality control is necessary to ensure high diagnos­tic quality. Planar images are acquired in anterior, left anterior oblique 45 and 70 degree (LAO 45° & 70°) position followed by 3-4 hr delayed (redistribution) images. Alternatively, single photon emission computer­ized tomography (SPECT) imaging can be obtained started with an acquisition protocol shortly after the thallium injection and a repeat acquisition 3-4 hr later with identical parameters. In patients where the viability of myocardium in an affected territory is questioned, delayed images after 24 hr are acquired. Alternatively, after 4 hr redistribution images another dose of37 MBq (1 mCi) of201TI is injected at rest followed by acquisition of another set of images with identical parameters.
Thallium Images
The normal myocardial perfusion images at stress and rest show uniform distribution of the tracer (TI- 201) over left ventricle with a central photon deficient area concomitant with ventricular cavity (Figures 1 and 2).


Areas of reduced 11-201 Werfusion defect) on stress images is suggestive of myocardial ischaemia and it is the disappearance or persistence of this perfusion defect on redistribution image which decides about the reversible or irreversible (infarct) nature of the ischaemia respec­tively (Figures 3 and 4).


The right ventricle is not normally visualized on the rest images and only faintly on exercise images. It is due to 3 times lesser myocardial mass and 10% lesser perfusion of the RV. Pronounced visualization of the BY is seen in cases of RV hypertrophy, pulmonary hypertension or extensive LV infarction. Non-visualiza­lion or perfusion defect in RV on stress images is seen in 30% cases of inferior wall myocardial infarction (Right Coronary Artery territory). Increased lung uptake of Thallium-201 can occur on the initial images immediately after exercise. This is an important marker of exercise induced LV dysfunction and can be correlated with an abnormally increased ED  left ventricular pressure and capillary wedge pressure. This highly abnormal finding is most often seen in patients with significant CAD, frequently related to multivessel disease. In occasional patients with “bal­anced coronary disease” this phenomenon of increased lung uptake may be present as the only abnormality without perfusion defect10.
Sensitivity and Specificity of 201TITest
Exercise 11-201 imaging has a sensitivity and speci­ficity in the range of 80- 90% as compared with a sensitivity of 60-70% for exercise ECG11. The accuracy of detecting an individual stenosis is dependent on several factors. These include the severity of stenosis and also the number of vessel involved. Because thallium-201 imaging is based on relative distribution of tracer, the region with the most severe reduction in blood is the region with a visual thallium defect; in patients with multivessel or tripple vessel disease of same severity, no perfusion abnormality may be appreciated (false negative). The sensitivity for three major coronary vessels is usually best for left anterior descending artery, intermediate for right coronary artery and relatively less for left circumflex artery.
Clinical Applications
The clinical utility of thallium-201 imaging depends to a great extent on its predictive value. It should be remembered that a positive test result in a group with a high probability of disease pre-test adds little to the diagnostic accuracy beyond that achieved by a proper clinical evaluation. A negative test in a group with a low probability of disease pre-test only confirms that pre-test low likelihood of CAD. Therefore, the patients most suited for thallium stress scanning are 4iose with moderate likelihood of CAD as symptomatic individual with negative Efl or vice-versa. Thallium imaging may also be used to evaluate patients who have undergone coronary artery bypass graft (CABG), patients who have had AMI and to monitor the result of percutaneous transluminal coronary an­gioplasty (PTCA). In this latter group of patients the suggested clinical procedure is to image the patients prior to PTCA and then again three or more days following the angioplasty. Single Photon Emission Computerized Tomogra­phy (SPECT) imaging allows the quantitation of the size and extent of the lesions, in particular infarct. It also offers a better ability to diagnose the extent of CAD as compared to planar images. However, it should be emphasized that planar imaging when combined with quantitative analysis of circumferential proffles is an adequate clinical method for diagnosing the presence or absence of CAD12.
Detection of Viable “Hibernating” Myocardium
Identifying preserved myocardium viability in the presence of severe left ventricular dysfunction is becom­ing increasingly more important for clinical decision making in identifying which patients with CAD will most benefit from revascularization (CABG, PTCA). In recent years there has been a greater appreciation among clinicians for recognising they henomena of ‘stunned or hibernating” myocardium13,14 . Both of these pathophysi­ologic states may result in profound regional LV dysfunc­tion in the absence of necrosis. Assessing regional systolic function alone by such technique as 2D echo, radionuclide angiography or contrast ventriculography is insufficient to distinguish between irreversibly injured and viable but dysfunctional myocardium. Myocardial thallium imaging of perfusion and metabolism can provide clinically relevant information pertaining to myocardial viability in the presence of regional and global myocardial systolic dysfunction. This ability to differentiate between acute necrosis or scar from viable but asynergic myocardium can assist the clinician in identifying the patients with CAD who might benefit most from bypass surgery or angioplasty (Figure 5).

Refrences

1. Kanawa, M., Krizek, H., Porter,). et al. Use of thallium, a potassium analogue in scan (abstract).). NucI. Med., 1970; 11:333.
2. Lebowitz. a, Greene, M.W., Atkins, FL: TI-201 for medical use. J. Nucl. Med., 1975; 16:151-154.
3. Cook, D.J., Bailey, I., Strauss, H.W. et al. Thallium-201 for myocardial perfusion imaging: appearance of the normal heart.). NucL Med., 1976; 17:583-589.
4. Synder, W.S., Ford, M.R., Warner, G.G. et al. absorbed dose per unit cummulated activity for selected radionuclides and organs. NMIMIRD pamphlet 11. New York: Society of Nuclear Medicine, 1975.
5. Pohost, G.M., Zir. L.M., Moore, R..H.etal. Differentiationof transiently ischaemic from infarcted myocardium by serial imaging after a single dose of thallium-201. circulation, 1977: 55:294-302.
6  Liu, P., Keisa, M.C., Okada, R.D., etaLThe persiatantdefectonexercise thallium imaging and its fate after myocardial revascularisation: Doesit represents scar or ischaemia?. Am. Heart)., 1985;110:996-1001.
7. Edward, B.S. and Donald, F.D. Reverse redistribution phenomenon in thallium-201 stress test: Angiographic correlation and clinical significance. 3. Nucl, Med., 1985; 26:707-712.
&  Homma, A., Gilliand, Y., Guiney, B. et al. Safety of i.v. dipyridamole for stress testing with thallium-201 imaging. Am.). Cardiol., 1987;59:152-154.
9. Leppo, ).A. Dipyridamole thallium imaging: the lazy man’a stress test.). NucL Med., 1989; 30:281-287.
10. Boucher, C.A., Zir, L.M., Belier, GA. etal. Increased lung uptake of thallium-201 during exercise myocardial imaging: clinical, hemodynamic and angiographic implications in patients with C.A.D. Am.). Cardiol., 1980; 46:189-196.
11. Bailey, I.K., Griffith, L5.C, Roulesu,). et al. Thallium-201 myocsrdial perfusionimaging at rest and during exercise, comparative sensitivity to EGG in cAD. Circulation, 1977; 55:79-87.
12. Tamaki, N., Yonikurs, Y. snd Kataoks, H. Planar tbsllium imsging and quantitative circumferential profile. Comparision with SPECT thallium. Eur. 3. NucL Med., 1984:9:99-105.
13. Rahimtoola, S.H., The hibernating myocardium Am. Heart.J., 1989; 117:211 snd 221.
14. Braunwald, B., Rutherford, ).D. Reversible ischaemic LV dysfunction: evaluation for hibernating myocsrdium.). Am. Coil. Cardiol., 1986; 8:1467-1470.

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