DPD Quantification in Cardiac Amyloidosis: A Novel Imaging Biomarker

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 (99m)Tc-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 (r(2) = 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.