PET Myocardial Perfusion Imaging: ⁸²Rb

Abstract

Rubidium 82 (⁸²Rb) is a positron emitter tracer, produced by the nuclear decay of Strontium-82 by electron capture via a commercially available generator. It is used for PET myocardial perfusion imaging (MPI) and quantification of myocardial blood flow (MBF) that has been shown accurate despite the limits of quantification intrinsic to non-diffusible tracers.

The short physical half-life of ⁸²Rb, 76 s, allows for an efficient fast protocol and let a considerable dosimetric advantage for the patient and staff, but hinders the use of stress test, allowing only pharmacologic stressor tests. List mode ⁸²Rb PET acquisition and a mono-compartmental model approach are recommended for MBF and myocardial flow reserve (MFR) quantification. Multimodality technique allows higher accuracy in defining ischemic vessel pertaining and calcified plaques of coronary vessels with a stronger clinical impact.

Due to the diagnostic accuracy over the traditional MPI, quantitative ⁸²Rb PET has been widely used to facilitate diagnosis, establish the patient’s workup, and predict successfully outcome in patients with obstructive and nonobstructive CAD. If the oxygen extraction is already maximal in basic conditions, an increase in the oxygen demand can be satisfied only with an increase of MBF that is in dependence of microcirculation, endothelial function, and metabolic factors. Impairment of these systems invalidates the flow and reduces the coronary reserve, thus affecting vasodilation in particular at the subendocardium, which is earlier affected by the ischemia. A strong clinical impact of MBF quantification is achieved also in patients with multi vessels disease (MVD) or left main artery stenoses where MPI alone can underestimate the balanced ischemia, and in patients with intermediate pretest probability of CAD, where quantitative ⁸²Rb PET allows a more accurate assessment of the ischemic burden and supports the clinical decision-making.

A growing interest regards ⁸²Rb PET in the study of suspect acute coronary syndrome and in cardiac allograft vasculopathy after transplant (HTx). Correlations between ⁸²Rb PET MPI, invasive coronary angiography (ICA) and intravascular ultrasound (IVUS) confirmed that ⁸²Rb PET MPI correlates with intravascular ultrasound and angiograms findings, so ⁸²Rb PET MPI can be suggested to improve HTx patient’s management by reducing the frequency of invasive techniques and to establish the functional significance of cardiac allograft vasculopathy (CAV) involvement. Moreover MBF ⁸²Rb can target viability assessment in those patients where clinical yield is likely to be highest.

The monthly cost of acquiring the ⁸²Sr/⁸²Rb generator was initially considered prohibitive, but it is now clear that it can be amortized by scheduling a number of at least 30 patients for each generator and it can become economically sustainable in relation to a very high number of scans.

⁸²Rb PET-MPI submit the patients at radiation dosimetry less than the SPECT-MPI, moreover it should be emphasized that the limited dosimetry of ⁸²Rb PET vs. the SPECT one regards both patients and the staff.

A new trend of scientific research for ⁸²Rb is emerging in the recent years in the field of oncology. On this purpose ⁸²Rb is a nonspecific radiotracer; therefore, the uptake by the tumor primarily depends on the tumor vascularization. Theoretically, the rationale of use of this radiotracer can be firstly identified in its capability to explore angiogenesis which, in turn, can directly correlate with the aggressiveness of the tumors.

Appendices

Clinical Case N. 1: Follow-Up of Revascularized MVD: Capability of ⁸²Rb PET/CT in Evaluating Transient ISCHEMIA Target for Vessel

Male, 75 years old with stable chest pain stress induced.

History of chronic CAD (Fig. 9.4a): AMI inferior wall; ICA: MVD, stenting on LDA and RCX; RCA occluded.

Patient underwent ⁸²Rb PET/CT basal/dipyridamole (Figs. 9.4b, 9.4c) (0.56 mg/Kg/4′): fast protocol 35′. Dynamic list-mode acquisition.

Fig. 9.4a

EKG dipyridamole: diffuse abnormality of LV repolarization; ST segment depression in inferior and lateral leads

Fig. 9.4b

Dipyridamole ⁸²Rb PET MPI/CT Fusion imaging: chronic ischemia with necrosis in inferior wall

Dipyridamole ⁸²Rb PET/CT, from right to left:

(1) CT-AC: metallic Stent (red cross) on LAD and Cx artery; (2) SPECT SA (3) Fusion imaging PET/CT

Fig. 9.4c

Dipyridamole ⁸²Rb PET/CT, from right to left: (1) CT-AC: metallic stent (red cross) on LAD and Cx artery; (2) SPECT SA; (3) fusion imaging PET/CT

In a patient with revascularized MVD, the evidence of metallic stent at fusion images let better recognize the pertinence of vessel inducing ischemia.

Clinical Case N. 2: Match Normoperfusion, No Significant Calcific Atheromasia

Female, 67 years old, with history of hyperlipidemia and hypertension, referring atypical chest pain.

⁸²Rb PET/CT basal/dipyridamole (Fig. 9.5a), fast protocol: dynamic list-mode acquisition with a total of 35 min for basal and stressor dipyridamole (0.56 mg/Kg/4′). EKG test: No ischemia during vasodilator. Acquisition of CT gated for obtaining calcium score (Fig. 9.5b).

Fig. 9.5a

⁸²Rb PET/TC basal/dipyridamole: normoperfusion

Fig. 9.5b

No significant calcium score index

Clinical Case N. 3: Transient Ischemia and Coronary Artery Calcific Atheromasia

Male, 68 years old.

Cardiovascular risk factor: Diabetes type 2 for almost 12 years, smoker.

No history of CAD. The patient referred shortness of breath stress induced.

At baseline 3D transthoracic echocardiography: Preserved LV ejection fraction (LVEF 57%) and LV regional contractile function.

Patient underwent ⁸²Rb PET MPI/CT basal—dipyridamole, showing severe perfusion defect at the apex referring to transient ischemia in regimen of vasodilation by dipyridamole. At CT and fusion PET/CT imaging: Calcific atheromasia diffuse on LAD. High value of CAC score (Fig. 9.6).

Dipyridamole 82 Rb PET MPI (QPS Cedars Sinai)	SSS	SDS	% Defect extension
	14	12	12

Fig. 9.6

(a) ⁸²Rb PET MPI stressor dipyridamole: Transient perfusion defect on antero-apical myocardial segments. (b) Extensive calcified plaque on LDA. (c) CACS = >400, consistent with ischemia with high risk of future coronary events

Calcific atheromasia on coronary main vessels is becoming a relatively frequent evidence in multimodality studies of MPI/CT. It doesn’t imply necessarily functional evolution to ischemia, but it can affect the long-term prognosis.

When it is associated with perfusion defects, the prognostic significance gets a stronger value.

According to the literature, report underlined the evidence of transient ischemia corresponding to the LAD calcific atheromasia, as a prognostic tool added to the transient perfusion defect.

Patient underwent coronary-angiography and LAD revascularization (stenting) 1 week after.

Clinical Case N. 4: Obstructive CAD

Male, 63 years old.

Cardiovascular risk factor: History of hyperlipidemia and hypertension.

For about three months, the patient complains of feeling of easy tiredness and chest pain symptoms during sleep.

Basal EKG: Normal. Stress EKG: BEV, also organized in run at the acme of stress.

Patient underwent:

⁻⁸²Rb PET/CT basal/dipyridamole, fast protocol: 35 min for both phases; basal conditions and stressor dipyridamole (0.56 mg/Kg/4′) in dynamic list-mode acquisition.

Report: extensive transient ischemia evocated during dipyridamole infusion (Fig. 9.7a).

Fig. 9.7a

⁸²Rb PET/TC MPI: Short axis slices dipyridamole slices and polar map: dipyridamole (up); basal (down)

LV perfusion summed scores and contractile function indexes are reported, respectively, in Table Clinical Case A and Table Clinical Case B.

Table clinical case A semiquantitative analysis AutoQuant-QPS-(PFQ)
Scores	Dipyridamole	Rest
Summed scores	SSS 16	SDS 14
	SS% 18	SD% 15
Perfusion defect extension	15% LV	2% LV
TPD	12%	3%

Transient ischemic dilation value (abnormal TID >1.13 (0.98 + 2.5 SD) = 1.1.

Table clinical case B semiquantitative analysis AutoQuant QGS (n.v. LVEF > 46%; EDV < 126 mL; ESV < 68 mL)
LV contractile function	Dipyridamole	Rest
EF	52%	57%
EDV	138 mL	127 mL
ESV	69 mL	66 mL

Patient underwent ICA, with evidence of RCx occlusion, treated with stenting (Fig. 9.7b).

Fig. 9.7b

RCx at ICA, red arrows show respecteively: -stenosis (on the left) and -post Stenting Revascularization (on the right)

Clinical Case N. 5: LV Pseudoaneurysm

Male, 54 years old.

Diabetes type 2 for almost 3 years, smoker, abdominal obesity, hypertension.

Known history of chronic CAD with transmural anterior and apex AMI, LDA stenting.

At the time of study, hospital admission for syncopal episode. Baseline Echo: LV dysfunction.

⁸²Rb PET/TC MPI: Dipyridamole/rest was scheduled in the aim to evaluate LV perfusion for transient ischemia and/or viability (Figs. 9.8a, 9.8b), in order to planning new target revascularization.

Fig. 9.8a

⁸²Rb PET/TC MPI: dipyridamole/rest. Semiquantitative analysis results are reported in Table Clinical Cases A

At CT and PET/CT fusion imaging analysis, clear evidence of pseudoaneurysm at the apex, with a wide and unknown component of calcific dystrophy in the area of previous necrosis (Fig. 9.8c).

Table clinical case A semiquantitative analysis AutoQuant-QPS-(PFQ) – Cedars Sinai LA
Scores	Dipyridamole	Rest
Summed scores	SSS 24	SD 4
	SS% 25	SD% 5
Perfusion defect extension	27% LV	24% LV
TPD	21%	19%

Transient ischemic dilation value was also obtained: 1.28 (abnormal TID >1.13 (0.98 + 2.5 SD).

(n.v. LVEF > 46%; EDV < 126 mL; ESV < 68 mL)

Fig. 9.8b

⁸²Rb gated PET/TC MPI: dipyridamole/rest. LV surface

Image analysis shows: dysfunctionally LV with volumetric overload, associated with extensive chronic CAD.

It is suggestive of:

• Transmural necrosis involving the apex and anterior-septal wall.

• Inferior-septal: chronically hypoperfused but viable myocardium.

• Mild transient ischemia at basal segment of anterior-septal wall and at basal-septum.

• Mild additional impairment of LVEF related to stressor test.

• Note: It must be underlined the efficacy of multimodality technique and the capability of 82Rb PET for assessing LVEF in real time with stressor test, as a prognostic factor of main relevance.

⁸²Rb PET/TC MPI addressed the patient to surgery.

• Clinical Impact: ⁸²Rb PET/CT MPI modified the therapeutic strategy of the patient.

Before surgery patients underwent cardiac MRI and ICA. Images at comparison are shown in Fig. 9.8c.

Fig. 9.8c

LV Transaxial images show the perfect morphologic overlapping of calcific dystrophy with the transmural perfusion defect

Fig. 9.8d

ICA: LDA obstruction

Clinical Case N. 6: ⁸²Rb PET/CT in the Monitoring the Efficacy of Medical Therapy versus Progression Disease

Male patient, 62 years old. Multiple risk factor for CAD. Atypical chest pain.

• A. (1 control) Rest/dipyridamole ⁸²Rb PET/CT (Fig. 9.9a): transient ischemia involving the 7% of LV, pertinent to the apical-medium segments of inferior wall; limited hypoperfusion in anterior wall. Severe calcium score on LDA. Patient underwent medical therapy, but one year later, he referred angina stress induced.

• B. (2 control). A new ⁸²Rb PET/CT showed progression of CAD (Fig. 9.9b), involving the 15% of LV, thus doubling the previous extent, pertinent the same region of inferior wall in respect of the previous control, but involving more extensively the LDA territory.

Patient underwent stenting revascularization on LDA and RCA.

Fig. 9.9a

⁸²Rb PET/CT: The three-standard level of slices and polar map at comparison. At the 2 control, clear evidence of progression of disease extension with the prevalence of territories of LDA pertinence. Severe calcific atheromasia on LDA is also evident

Clinical Impact: capability of ⁸²Rb PET/CT in monitoring the efficacy of therapy and in suggesting a shift of treatment when progression disease occurred.

Clinical Case N. 7: Ischemic, Dysfunctional CMD Associated with Balanced Ischemia

Male, 54 years old. Diabetes type 2 for almost 3 years, smoker, abdominal obesity, hypertension.

Known history of chronic CAD: Acute coronary syndrome in anterior wall and apex; LDA stenting (at that time the patient rejected CABG recommended by the clinicians).

New hospital admission because of stress-induced shortness of breath (Fig. 9.10a).

• 3D transthoracic echocardiography: LV ejection fraction (LVEF 40%). Akinesia at apex, anterior wall; septum. Conclusion: dysfunctional CMD.

Fig. 9.10a

Basal EKG: disappearance of R wave in leads V1–V6

Patient underwent:

⁻¹⁸F-FDG PET/CT (for viability assessment) and MSCT CE coronary angiography (CTA) showing MVD with:

• LDA: Obstructive stenosis distal segment; stenosis 1 diagonal artery 75%.

• RCX: 65% Stenosis.

• RCA: 80% Stenosis distal segment.

⁻¹⁸F-FDG PET/CT: main results are shown in the Figure 9.10b.

Fig. 9.10b

¹⁸F-FDG PET/MSCT coronary angiography fusion imaging

⁻⁸²Rb PET/CT basal/dipyridamole was also obtained for perfusion analysis (Fig. 9.10c) to better quantify risk stratification and schedule therapeutic strategy.

Protocol: Fast protocol 35 min for basal conditions and stressor dipyridamole (0.56 mg/Kg/4′). Dynamic list-mode acquisition.

Fig. 9.10c

⁸²Rb PET/TC MPI: short axis slices

SSS	SDS	Perfusion defect extension dipyridamole	Perfusion defect extension basal	LVEF dipyridamole	LVEF basal
27	2	37%	35%	39%	45%

Transient ischemic dilation TID = 1.35 r.v. >1.13 (0.98 + 2.5 SD)

Severe perfusion defect of wide extension involving: Apex, septum, anterior and inferior wall at medio-ventricular level

Fig. 9.10d

At ⁸²Rb PET/CT MPI: LV Fusion Imaging show Transaxial slices soon after Dipyridamole (up) and at Basal scan (down). The yellow lines show clearly the difference between the maximum diameters of LV soon after Stressor Test in respect of the Basal scan, due to Transient Ischemic Dilation of LV related to Dipyridamole induced ischemia

• Transmural necrosis involving the apex, apical-medium segment of septum, anterior-septal and inferior wall.

• Mild transient ischemia and viable myocardium at medium-basal segment of anterior-septal wall; septum; inferior wall.

• Mild impairment of LVEF related to stressor test.

• Transient ischemic dilation (Fig. 9.10d).

^-82Rb PET/TC suggested the need of revascularization. Patient underwent CABG five days after PET-MPI

Clinical Case N. 8: ⁸²Rb PET/CT MPI—Impaired Regional LV MBF

Female, 65 years old.

Cardiovascular risk factor: Diabetes type 2 for almost 12 years, hypertension.

Shortness of breath and chest pain stress induced (Figs. 9.11a, 9.11b).

• 3D transthoracic echocardiography: LV ejection fraction (LVEF 55%). No abnormalities of regional wall motion.

• ECK stress test: inconclusive.

Fig. 9.11a

Basal ECK: LV hypertrophy, unspecific abnormalities

⁻⁸²Rb PET/CT dipyridamole/basal (dynamic, list mode, fast protocol: 35 min for both phases) (Fig. 9.11c).

Stressor dipyridamole (0.56 mg/Kg/4′): ECK: N.

Fig. 9.11b

⁸²Rb PET MPI: No evidence of transient ischemia in response to the vasodilation due to dipyridamole

Fig. 9.11c

MBF at stressor dipyridamole. Analysis obtained by QPET (G. Germano-Cedars-Sinai Medical Center, LA, CA). Impairment of regional MBF at apex, septal-inferior wall, according with microcirculation impairment

Patient underwent ICA that confirmed: No epicardial coronaries stenosis (Fig. 9.11d).

Fig. 9.11d

No epicardial coronaries stenosis, FFR impairment on the selected areas

MBF at ⁸²Rb PET/CT dipyridamole/basal was suggestive of microcirculation impairment.

Clinical Case N. 9: ⁸²Rb PET/CT in the Emergency of Cath-lab

Female patient, 77 years old. Two different hospital admission for acute coronary syndrome (ACS), at ICA (48 h post ACS): MVD. LVEF:40%.

At the end of ICA in Cath-lab she underwent rest/dipyridamole ⁸²Rb PET/CT fast protocol, showing:

Perfusion defect corresponding to LDA and RCA territories, but more severe at RCA level that was identified as culprit lesion (Fig. 9.12).

Fig. 9.12

⁸²Rb PET/CT: transient ischemia at vasodilator test, more severe in infero-lateral, inferior wall. ICA: MVD. Severe stenosis at RCA was treated with stent target on the basis of ⁸²Rb PET evidence of dipyridamole-induced ischemia results

Within 35 min of PET scanning, patient was re-addressed in Cath-lab for RCA stenting revascularization.

At 24 h post revascularization, EKG: ST resolution; Echo: improvement of LV compliance. This condition is especially meaningful of real life clinical practice for helping the workup of patients affected with MVD, where MPI with fast protocol can identify the functional significance of stenosis and suggest which one to revascularize, given priority.

Clinical impact: ⁸²Rb PET/CT can address target revascularization of culprit lesion, early out of the beginning of acute coronary syndrome (ACS).