DPD Quantification in Cardiac Amyloidosis: A Novel Imaging Biomarker

Abstract

Objectives: To assess whether single-photon emission computed tomography (SPECT/CT) quantification of bone scintigraphy would improve diagnostic accuracy and offer a means of quantifying amyloid burden.

Background: Transthyretin-related cardiac amyloidosis is common and can be diagnosed noninvasively using bone scintigraphy; interpretation, however, relies on planar images. SPECT/CT imaging offers 3-dimensional visualization.

Methods: This was a single-center, retrospective analysis of ^99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scans reported using the Perugini grading system (0 = negative; 1 to 3 = increasingly positive). Conventional planar quantification techniques (heart/contralateral lung, and heart/whole-body retention ratios) were performed. Heart, adjacent vertebra, paraspinal muscle and liver peak standardized uptake values (SUV_peak) were recorded from SPECT/CT acquisitions. An SUV retention index was also calculated: (cardiac SUV_peak/vertebral SUV_peak) × paraspinal muscle SUV_peak. In a subgroup of patients, SPECT/CT quantification was compared with myocardial extracellular volume quantification by CT imaging (ECV_CT).

Results: A total of 100 DPD scans were analyzed (patient age 84 ± 9 years; 52% male): 40 were Perugini grade 0, 12 were grade 1, 41 were grade 2, and 7 were grade 3. Cardiac SUV_peak increased from grade 0 to grade 2; however, it plateaued between grades 2 and 3 (p < 0.001). Paraspinal muscle SUV_peak increased with grade (p < 0.001), whereas vertebral SUV_peak decreased (p < 0.001). The composite parameter of SUV retention index overcame the plateauing of the cardiac SUV_peak and increased across all grades (p < 0.001). Cardiac SUV_peak correlated well (r² = 0.73; p < 0.001) with ECV_CT. Both the cardiac SUV_peak and SUV retention index had excellent diagnostic accuracy (area under the curve [AUC]: 0.999). The heart to contralateral lung ratio performed the best of the planar quantification techniques (AUC: 0.987).

Conclusions: SPECT/CT quantification in DPD scintigraphy is possible and outperforms planar quantification techniques. Differentiation of Perugini grade 2 or 3 is confounded by soft tissue uptake, which can be overcome by a composite SUV retention index. This index can help in the diagnosis of cardiac amyloidosis and may offer a means of monitoring response to therapy.

Keywords: DPD scintigraphy; SPECT/CT quantification; cardiac amyloidosis.

Graphical abstract

Figure 1

SPECT/CT and H/CL Ratio Quantification Fused axial single-photon emission computed tomography/computed tomography (SPECT/CT) ^99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid images demonstrating volume of interest (VOI) (green) positioning for standardized uptake value (SUV) quantification on the left. The small green square within each VOI represents the peak SUV (SUV_peak), which enables the reporter to ensure that the recorded SUV_peak lies within the desired organ/tissue. On the right, 3-h planar, whole-body ^99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid image of a different patient with regions of interest over the heart (1) and contralateral lung (4). H/CL = heart/contralateral lung.

Figure 2

Trends in SPECT/CT Quantification by DPD Perugini Grade Box and whisker plots illustrating the trend seen with increasing ^99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) Perugini grade in SUV_peak in the heart (A), vertebra (B), paraspinal muscle (C), and the composite SUV retention index (D). Whisker lengths extend to 1.5 times the box height, or if no case has a value in that range, to the minimum and maximum. Dots represent outliers. Abbreviations as in Figure 1.

Figure 3

Diagnostic Accuracy for the Detection of Cardiac Amyloid Receiver-operating characteristic curves for the detection of cardiac amyloidosis using the different methods of quantification of ^99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy. Values in parentheses represent 95% confidence intervals. AUC = area under the curve; other abbreviations as in Figure 1.

Figure 4

Correlation Between SPECT/CT Quantification and ECV Quantification by CT Scatter plot of cardiac SUV_peak against myocardial extracellular volume quantification (ECV) by computed tomography (CT), showing good correlation across DPD Perugini grades 0 to 2. Abbreviations as in Figures 1 and 2.

Figure 5

The Unappreciated Spectrum of Disease Planar images from three patients all demonstrating Perugini grade 2 cardiac uptake with some long bone suppression. The cardiac peak standardized uptake value (peak SUV) is markedly different between patients, illustrating the wide range of cardiac involvement that is not apparent or appreciated on planar imaging alone.

Central Illustration

Planar and SPECT/CT Quantification in DPD Scintigraphy Planar and single-photon emission computed tomography/computed tomography (SPECT/CT) quantification was performed retrospectively on 100 ^99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scans. SPECT/CT quantification outperformed planar quantification and correlated with extracellular volume quantification by computed tomography (ECV_CT). Differentiation of Perugini grade 2 and 3 was confounded by soft tissue uptake, which may be overcome by using a composite standardized uptake value (SUV) retention index, providing a potential novel biomarker for monitoring.