Cardiac Molecular Imaging

Ashlee Patterson, CNMT, NMTCB(CT) April 14th, 2018 Disclosures

§ None

2 Objectives

• Discuss various radiotracers used for MPI • Understand pitfalls of different tracers • Discuss and distinguish various sources of image artifact • Review practices used to minimize image artifact • Review Stress protocols • Discuss Rb82 for PET cardiac • Discuss PYP for Amyloidosis

3 Why We Image

1

4 Why We Image

§Diagnosing cardiovascular disease

§ Establishing prognosis

§Assessing the effectiveness of therapy

§Evaluating viability

5 Why not CTA?

A. shows significant lesion in the LAD (Curved multiplanar) B. severe positive arterial remodeling of a mixed plaque (cross-sectional view) C. Severe discrete stenosis in LAD (Volume- rendering) D. Significant stenosis in same area (Conventional angio) 1

6 MPI Pitfalls

2

7 8 Radiotracers

§Thallium

§Tc99m Sestamibi

§Tc99m Tetrofosmin

9 Thallium

§1971 §88 X-ray photons at 70 to 80 keV and approximately 12 gamma photons at 135 and 167 keV for each 100 disintegrations. §Half life of 72.1 hours (physical) § normal distribution: – Myocardium – skeletal muscle – GI tract – Liver – kidneys

3

10 Thallium

§Potassium analog

–poisonous to mammalian species in a dose of approximately 20 mg/kg.

§Typically has less diaphragmatic uptake

§Limited image quality

–4 mCi associated with a relatively high absorbed dose.

3,5

11 Thallium

§Viability

§Dual-isotope stress test

12 Tl201 Viability

§Hibernating Myocardium

–Wall motion abnormality at rest which improves during redistribution

§3mCi-4mCi TI201 IV

–10 min post inj, 4 hour post inj, possible 24 hour post inj

§Pt prep

–Fasting until redistribution

13 Hibernating Myocardium Presentation on Images

Rest images: Several areas of reduced resting blood flow Redistribution: Substantial redistribution, indicating myocardial viability

Routine stress/rest imaging would have given misleading information about viability because there are some of the irreversible defects 4 14 Tc99m Sestamibi & Viability

§ Does not redistribute

§ Uptake : Blood flow

§ Weaknesses for viability due to impairment of blood flow

–Uptake at rest correlates more strongly with 201Tl redistribution activity, than with initial uptake of 201Tl.

§ Study showed: Tc-99m sestamibi underestimates viable myocardium in patients with chronic CAD and LV dysfunction

5

15 Tc99m Sestamibi

§ FDA Approval in 1991

– Originally inferior to thallium for the determination of regional myocardial perfusion

– “Reduced contrast”

–Lipophilic cationic complexes cross the cell membrane by passive diffusion and localize in the mitochondria, binding to intramitochondrial proteins.

§ 6 hour half life

– Lower effective dose

– More dose= more counts = better quality images

– Detects inducible myocardial ischemia & determining whether LV function is normal

6, 5

16 Tc99m Tetrofosmin (Myoview)

§photon energy: 140 keV

§Half life: 6 hours

§excretion: renal (40%) Feces (26%)

–66% of total dose excreted in first 48 hours

§Clears more rapidly from liver (vs. sestamibi)

4

17 18 Tc99m Artifacts: GI Uptake

2

19 Tc99m Artifacts: Breast Attenuation

2

20 Tc99m Artifacts: Infiltration & Malignancy

Infiltration w/ lymph Lymph Node node uptake

2

21 General Artifact: Motion

2

22 General Artifact: Motion Correction

2

23 Gated Rest & Stress Images

§ Gating: – Simultaneous assessment of perfusion, function, and viability – Small dose of tracer = fuzzy images – Gating rest & stress will help accommodate for low count rate – More accurate LV function – LVF may decrease w/ stress

24 25 Stress Protocols

• One- day protocol • Rest images followed by stress with 1:10 ratio (mibi)

• Two- day protocol (high BMI) • Stress image on day one • Rest image to rule out artifact and ischemia • Max dose (~30 mCi tc99m) on both days

• Treadmill • Bruce protocol • Modified Bruce protocol

• Chemical • Dobutamine • Adenosine • Regadenoson

26 Stress Protocols- Treadmill

§ Functional Tolerance

–Aides in distinguishing artifact and ischemia

§ Bruce Protocol

–3 min stages

–85% of max HR

– 1-2 min walk after injection

27 Treadmill Contraindications

§ Physical Limitations § EKG changes & LBBB –Do not raise HR! –Possible reversible septal defect due to the erroneous blood flow from the block if the HR is increased. § CAD Medications –Beta Blockers –Calcium channel blockers

§ Post treadmill stress imaging: 15 minutes

–Cardiac creep – post stress images too quickly –Expanded lugs draw heart downward

4

28 Stress Protocols- Vasodilator – Lexiscan

• Adenosine A2A receptor agonist

• low affinity for receptors that are responsible for the major side effects of adenosine and dipyridamole

• A1, A2B, and A3

• Patient Prep: • NPO 4 HR • No caffeine products 12 hr • Hold Beta and calcium channel blockers 24 hours

• IV dose of 0.4 mg (10 sec), followed by a saline flush followed by radio tracer 10-20 seconds after flush. 7

29 Lexiscan Considerations

•GI Artifact • Have pt eat fatty meal to increase liver & gallbladder clearance §Bronchospastic airway disease –bronchodilator should be immediately available §Seizures –Ativan or patient’s medication

150 mg of IV aminophylline can be injected at least 3–4 minutes after the radiotracer injection 5, 7

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Images

§ Polar Maps

–2D display of 3D distribution of radiotracer activity in the left ventricle

–Review of MP information for the whole LV in a single image

§ Normalize to the region of myocardium that has the highest counts

–Relative imaging (no absolute values)

–Normalization to test 7 patients

33 Images Cont’

§Black out map

–The degree of hypoperfusion can be expressed locally as a as a percentage of the total defect belonging to a given region or segment

34 Summed Stress Score

35

PET For Cardiac

§ Powerful, versatile non-invasive diagnostic tool with utility in the identification of high-risk plaques, myocardial perfusion defects, and viable myocardial tissue

–Assess function and viability

4 37 General PET for Cardiac Pro’s

• Image Quality • high myocardial counts • high spatial and contrast resolution • high signal-to-noise ratio • accurate and reliable correction for the effects of tissue attenuation and scatter.

• Exposure • complete rest-stress scan routinely exposes patients to less than 5 mSv and as little as 1 mSv effective dose using 3D imaging protocols

• Time & Throughput • A complete rest/stress study can be acquired in less than one hour if rubidium-82 is used

10

38 82-Rubidium

§ Decay product of Strontium 82

§ Half-life 76s

–Primarily pharmaceutical stressing

§ Exposure

–Staff Exposure: WB Effective dose 0.4 uSv (RB82) 3.3 uSv (MIBI)

–Patients: 80mrem (Rb82) 1500 mrem (mibi)

8

39 82-Rubidium Protocol

1. Topogram

2. CT

3. Inject 25-30mCi Rb82 (~2min uptake)

4. 6 min Acquisition

5. 2nd CT (optional)

6. Chemical stress w/ 25-30 mCi Rb82 (~2min uptake)

7. 6 min Acquisition

10 40 82-Rubidium

• Detection of obstructive CAD: • sensitivity 90% • specificity 88% • Provides an accurate assessment of the absolute MBF and CFR • Viability • Also potassium analog • Optimized to cope with the high count levels during first-pass • List mode can help reconstruct relative & absolute BF • Simultaneous examination of anatomy with hybrid systems

2,10

41 RB82 for Viability

42 82-Rubidium Considerations

§ Cost

–Growing re-imbursment

§ Isotope availability

–In-house generator

–Two IV’s

10

43 44 Cardiac Amyloidosis

Autosomal dominant disease caused by a mutation in the transthyretin (TTR) gene that results in misfolded TTR proteins accumulating as 9 amyloid fibrils

45

PYP Images

1 hour delayed imaging

Ratio of >1.5 at 1 hour Positive

9, 11

46 PYP for Cardiac Amyloidosis Considerations

§ Renal Failure

–May have persistent blood pool

§ Bone artifact

–SPECT/CT

11 47 Conclusion

• PET imaging • Better for patient and staff • Increasing reimbursement • Generator needed

• NM Imaging • Great for patients with known disease • Various tracers • Many road blocks • Artifacts

• Stress Testing • Treadmill V. Chemical V. Combination

• PYP Imaging for ATTR Cardiac Amyloidosis

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References & Resources

1. “Nuclear Cardiac Imaging.” Google Books, books.google.com/books?hl=en&lr=&id=CpVoAgAAQBAJ&oi=fnd&pg=PP1&dq=how%2Bto%2Bin terpret%2Bmyocardial%2Bperfusion%2Bimages&ots=kMQt-5QAxJ&sig=8I7DjVVOaehZ- kgQcxlxsePg9N4#v=onepage&q=how%20to%20interpret%20myocardial%20perfusion%20images &f=false.

2. Burrell, Steven. “Steven Burrell.” Journal of Nuclear Medicine Technology, 1 Dec. 2006, tech.snmjournals.org/content/34/4/193.full.

3. Strauss, H. William, and Dale Bailey. “Resurrection of Thallium-201 for Myocardial Perfusion Imaging.” JACC: Cardiovascular Imaging, JACC: Cardiovascular Imaging, 1 Mar. 2009, imaging.onlinejacc.org/content/2/3/283.

4. “Hibernating Myocardium | NEJM.” New England Journal of Medicine, www.nejm.org/doi/full/10.1056/NEJM199807163390307. https://clinicalgate.com/assessment-of- myocardial-viability-with-thallium-201-and-technetium-based-agents/

5. “Technetium (99mTc) Sestamibi.” Technetium (99mTc) Sestamibi - an Overview | ScienceDirect Topics, www.sciencedirect.com/topics/neuroscience/technetium-99mtc-sestamibi.

6. https://myutsouthwestern.swmed.edu/pmc/articles/PMC5701596/,DanaInfo=www.ncbi.nlm.nih.gov,SSL

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References & Resources

7. Dorak, Ryan A, et al. “Interpretation of SPECT/CT Myocardial Perfusion Images: Common Artifacts and Quality Control Techniques.” Radio Graphics, RNSA, 19 Aug. 2011, pubs.rsna.org/doi/full/10.1148/rg.317115090.

8. Deborah, Tout, et al. “Comparison of Occupational Radiation Exposure from... : Nuclear Medicine Communications.” LWW, Oct. 2014, journals.lww.com/nuclearmedicinecomm/Abstract/2014/10000/Comparison_of_occupational_radiatio n_exposure_from.7.aspx.

9. Plitt, Anna, et al. “Cardiac Sarcoidosis: Case Report, Workup, and Review of the Literature.” Cardiology and Therapy, Springer Healthcare, Dec. 2013, www.ncbi.nlm.nih.gov/pmc/articles/PMC4107425/.

10. Bateman, Timothy M, et al. “American Society of Nuclear Cardiology and Society of Nuclear Medicine and Molecular Imaging Joint Position Statement on the Clinical Indications for Myocardial Perfusion PET.” SpringerLink, Springer US, 15 Aug. 2016, link.springer.com/article/10.1007%2Fs12350-016-0626-9.

51 References & Resources

11. Sharmila, Debobala et al “99mTechnetium-Pyrophosphate Imaging for Transthyretin Cardiac Amyloidosis” ASNC, Practice points, https://www.asnc.org/Files/Practice%20Resources/Practice%20Points/ASNC%20Practice%20Point- 99mTechnetiumPyrophosphateImaging2016.pdf

12. Salata, Brian M., and Parmanand Singh. “Role of Cardiac PET in Clinical Practice.” SpringerLink, Springer US, 9 Nov. 2017, link.springer.com/article/10.1007%2Fs11936-017-0591-x.

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