Quantitative 99mTc-DPD-SPECT/CT assessment of cardiac amyloidosis

Abstract

Introduction: Transthyretin (ATTR) amyloidosis is responsible for the majority of cardiac amyloidosis (CA) cases and can be reliably diagnosed with bone scintigraphy and the visual Perugini score. We aimed to implement a quantification method of cardiac amyloid deposits in patients with suspected cardiac amyloidosis and to compare performance to visual scoring.

Methods and materials: 136 patients received ^99mTc-DPD-bone scintigraphy including SPECT/CT of the thorax in case of suspicion of cardiac amyloidosis. Imaging phantom studies were performed to determine the scaling factor for standardized uptake value (SUV) quantification from SPECT/CT. Myocardial tracer uptake was quantified in a whole heart volume of interest.

Results: Forty-five patients were diagnosed with CA. A strong relationship between cardiac SUVmax and Perugini score was found (Spearman r 0.75, p < 0.0001). Additionally, tracer uptake in bone decreased with increasing cardiac SUVmax and Perugini score (p < 0.0001). ROC analysis revealed good performance of the SUVmax for the detection of ATTR-CA with AUC of 0.96 ± 0.02 (p < 0.0001) with sensitivity 98.7% and specificity 87.2%.

Conclusion: We demonstrate an accessible and accurate quantitative SPECT approach in CA. Quantitative assessment of the cardiac tracer uptake may improve diagnostic accuracy and risk classification. This method may enable monitoring and assessment of therapy response in patients with ATTR amyloidosis.

Keywords: AL; ATTR; Cardiac amyloidosis; Perugini; SPECT; imaging; quantification.

Figure 1

Patient selection. 149 patients were screened. Five patients were excluded due to missing clinical data (e.g., weight, accurate acquisition delay, diagnosis). Eight patients were excluded because of missing or insufficient SPECT/CT for quantitative assessment. HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; wtATTR, wildtype transthyretin amyloidosis; hATTR, hereditary transthyretin amyloidosis; AL, light-chain amyloidosis

Figure 2

Scatter diagrams show a linear relationship between the visual Perugini score and tracer uptake parameters (A–C). Spearmans’ r shows strong correlation for all parameters

Figure 3

Quantitative tracer uptake was measured in a freehand VOI of the heart and spherical VOIs in the blood pool and a vertebral bone. Calculated SUVmax shows significantly increase tracer uptake in the heart with increasing Perugini score. Furthermore, a decrease of bone tracer uptake could be observed in patients with Perugini score 2 and 3. *p < 0.05; ****p < 0.0001

Figure 4

Receiver operating characteristics. ROC analysis of patients with any cardiac amyloidosis (A) or ATTR amyloidosis (B) vs. no amyloidosis show similar performance for SUVmax, MBR, MVR. All three methods show acceptable sensitivity and specificity, e.g., cardiac SUVmax with sensitivity 99% and specificity 87% at a cut-off SUVmax of 6.1 for the diagnosis of ATTR amyloidosis. MBR, myocardium-to-blood ratio; MVR, myocardium-to-vertebral bone ratio

Figure 5

Representative example cases. VOI delineation in blue. (A) 66-year-old male with AL amyloidosis does not show any cardiac uptake in planar scintigraphy (Perugini 0) and in SPECT/CT images with a SUVmax of 1.6. (B) 84-year-old male with wtATTR amyloidosis and Perugini score 3 in the planar images with decreasing uptake in bone. SPECT/CT shows high tracer uptake in the left ventricular myocardium and a SUVmax of 26.7. (C) Difference in cardiac uptake of amyloidosis subtypes for the three SUV parameters. Patients with wildtype ATTR amyloidosis exhibited significantly higher uptake values compared (p < 0.001)