Quantification methods for 99mTc-labelled disphosphonates uptake in cardiac amyloidosis

Abstract

Introduction: Bone scintigraphy (BS) has emerged as a non-invasive technique of increasing importance in the diagnosis of transthyretin cardiac amyloidosis (CA). The most commonly used approaches include visual grading and semi-quantitative analysis. However, these techniques are limited by operator dependence and subjectivity in interpretation. To address these challenges, absolute quantification techniques are being explored to enhance diagnostic accuracy and consistency and to minimize interobserver variability. The objective is to identify the quantification methods currently employed in the assessment of CA.

Material and methods: A systematic review was conducted, including 12 articles retrieved from Scopus, PubMed, and Web of Science databases. Studies published in the last 5 years were selected, focusing on quantification methods applied to planar imaging and single photon emission computed tomography combined with computed tomography (SPECT/CT) in the context of CA.

Results: All 12 selected studies (100%) utilized visual grading; semi-quantitative methods were reported in 91.7% of studies, while absolute quantification techniques were applied in 33.3%. Among the semi-quantitative methods, the heart-to-contralateral lung (H/CL) ratio was the most commonly reported, with similar cut-off values (± 1.5) in the different articles. Additional ratios [heart-to-rib (H/R), heart-to-whole-body (H/WB), heart-to-pelvis (H/P), ratio of heart-to-thigh (RHT)] appeared less frequently, though they were investigated as alternative diagnostic markers. Absolute quantification methods reported heterogeneous cut- -off thresholds, ranging from 1.25 to 6.1, based on standardized uptake values (SUVs), to discriminate between individuals with and without CA.

Conclusions: Visual grading remains the clinical standard approach. The H/CL ratio is the most reported semi-quantitative method, although it presents some limitations. Absolute quantification with SPECT/CT (SUVmax, SUVpeak) is promising for diagnosis, prognosis, and monitoring of transthyretin amyloidosis (ATTR) CA, yet consensus reference values are lacking.

Keywords: SPECT/CT; absolute quantification; bone scintigraphy; cardiac amyloidosis (CA); planar and whole-body imaging; semi-quantification; transthyretin amyloidosis; visual score.