Attacking the Achilles heel of cardiac amyloid nuclear scintigraphy: How to reduce equivocal and false positive studies

Between 2018 and 2019, it was a standard practice at CCAD to use planar imaging, visual grading, H/CL ratio, and SPECT imaging in screening for cardiac amyloidosis. However, with increasing imaging volumes and interpretation experience, the number of equivocal and strongly suggestive results were disproportionately high compared to the number of not suggestive results. The protocol for patients with equivocal results was to reimage after 6–12 months. The rationale for re-scanning equivocal cases after six months, was to identify early disease in these patients and to initiate treatment as soon as possible.

By late 2019, CT was added to our image acquisition; however, as CT was not yet implemented in the guidelines and consensus recommendation at that time,3 attention was not focused on CT fusion. As such, SPECT and CT images were not properly fused and post-processed, and therefore not incorporated in our routine reporting system. H/CL ratio and visual score was the gold standard for diagnosing patients in our center, which was in line with the guidelines and consensus recommendations at that time.

However, we came to realize that the number of equivocal cases for our center (based on H/CL ratio and visual score) exceeded the numbers reported in literature (45% vs 35% in AL amyloid, 19% in no amyloid (not suggestive) and 2% in ATTR (positive)6 or 23% (with SPECT only).7 It is important to note, however, that Tamarappoo et al.6 suggested the use of dual energy thallium (1 mci) acquisition to improve the localization of PYP in the myocardium, which exposes patients to a much higher radiation burden than CT.

Therefore, in early 2020, CT was added to SPECT as a way of determining whether SPECT/CT provides improved diagnostic accuracy. This fusion technique resulted in the elimination of equivocal and false positive results in most of the cases. Once SPECT/CT fusion was recognized to have additional diagnostic value, this technique was adopted as the standard practice for cardiac amyloidosis at CCAD and SPECT and CT images were acquired for all subsequent patients (Figure 1).

Figure 1figure 1

Timeline of cardiac amyloidosis program at CCAD

However, there were initially certain processing and misregistration errors which contributed to suboptimal post-processing of the images. Realizing the learning curve of this new technique, a systematic reanalysis of the images was performed, comparing SPECT with SPECT/CT fusion. Through accurate manual co-registration of SPECT and CT data, equivocal results were eliminated, and many strongly suggestive results were reclassified as not suggestive.

The authors formulated a hypothesis that SPECT/CT fusion eliminates equivocal and false positive results in a great majority of cases. This hypothesis was tested by systematically and manually applying this technique to the entire cohort. The insights gained by continuous quality improvement and reanalysis, have identified common pitfalls in the image interpretation process. Considering that PYP scan is currently the gold standard of non-invasive diagnosis of ATTR cardiac amyloidosis, imaging physicians should consider these pitfalls in image interpretation.

In this paper, the authors share their experience of reclassification of final image interpretation through utilization of the SPECT/CT fusion technique, highlighting potential pitfalls that may lead to erroneous results if SPECT only imaging is utilized.

The objective of this paper is to highlight the significant impact of the SPECT/CT fusion technique in improving precision in diagnosis by truly identifying tracer uptake within the LV myocardium and tracer pooling within the LV cavity. This paper also highlights the importance of accurate post-processing of SPECT/CT images in order to achieve the best outcome from the SPECT/CT technique, which leads to complete reclassification of the initial interpretation.

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