DPD Quantification in Cardiac Amyloidosis: A Novel Imaging Biomarker

ObjectivesTo 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.BackgroundTransthyretin-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.MethodsThis 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).ResultsA 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).ConclusionsSPECT/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.