Total-body 11C-PIB PET/CT imaging of systemic amyloidosis: inter-organ connectivity in cardiac amyloidosis for prognostic insights

Background: Amyloidosis is a systemic disorder characterized by amyloid fibril deposition in multiple organs, including the heart, brain, liver, kidneys, and lungs, leading to organ dysfunction and affecting survival. In cardiac amyloidosis (CA), where the heart is primarily affected, the broader impact on other organs, particularly the brain, is not fully understood. This study aimed to assess the extent of amyloid deposition across systemic organs in CA, investigate brain-organ, brain-brain and organ-organ connections, and evaluate their effects on patients’ survival. Methods: A retrospective analysis was conducted on 70 patients, categorized into three groups by biopsy: cardiac amyloidosis (CA) (n = 31), non-cardiac amyloidosis (non-CA) (n = 12), and no amyloidosis control (NC) (n = 27). 11C-PIB PET/CT scans were performed, and standard uptake value mean (SUVmean) values were extracted using automated segmentation techniques. Brain-organ, brain-brain, organ-organ connectivity analyses were conducted using Spearman correlation. Survival outcomes and prognostic factors were evaluated using Kaplan–Meier analysis. Results: Amyloid deposition in CA patients was prominent in the myocardium, liver, and kidneys, reflected by increased SUVmean values. Significant brain-organ connectivity was observed, particularly between the posterior cingulate cortex (PCC), parietal lobes, and myocardial amyloid burden. Additionally, CA patients demonstrated markedly stronger inter-organ connectivity, indicating systemic involvement. In contrast, Non-CA and NC patients demonstrated weaker brain-organ and inter-organ interactions. The CA group exhibited a higher mortality rate, highlighting the severe prognosis, particularly in systemic CA (SCA). Furthermore, elevated amyloid deposition in the bone marrow, lungs and spleen within SCA group was strongly associated with increased mortality. Conclusion: In CA patients, amyloidosis was associated with extensive systemic involvement, as shown by significant brain-organ and inter-organ connectivity patterns. Findings emphasize that cardiac amyloidosis substantially impacts survival, particularly when accompanied by amyloid deposition in the bone marrow, lungs, and spleen, indicating the need for a comprehensive diagnostic and management approach. Clinical trial number: Not applicable.