Abstract: Assessment of transthyretin amyloid cardiomyopathy (ATTR-CM) can be performed by calculating a cardiac pyrophosphate activity (CPA) measurement from single-photon emission computed tomography (SPECT) images. SPECT images obtained using 99mTechnetium-pyrophosphate as a radiotracer can be analyzed to calculate CPA. Scan-specific thresholds for abnormal myocardial activity are identified based on left ventricular blood pool (LVBP) radiotracer counts, then radiotracer activity in regions of the myocardium with abnormal myocardial activity is determined. Finally, a CPA measurement can be calculated as a function of the mean radiotracer counts in such regions over the maximal LVBP radiotracer activity multiplied by the volume of involvement (e.g., the volume of abnormal activity). This CPA measurement can then be used as an assessment of ATTR-CM.