Abstract
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Introduction: Bone marrow (BM) quantification with 18F-FDG PET is of broad clinical significance for detecting BM involvement in cancer staging and early prediction of response to immunotherapy. However, current BM quantification may be inaccurate because a unit volume of bone marrow may also consist of a fraction of spongy bone in which FDG activity is negligible, resulting in a potential underestimation of true BM uptake. In this work, we demonstrate this bone-led tissue fraction effect using dual-energy CT (DECT) material decomposition and its impact on BM quantification in total-body dynamic PET kinetic modeling.
Methods: Four cancer patients were scanned on the uEXPLORER total-body PET/CT scanner. Prior Ethics Committee/IRB approval and informed consent were obtained. Each subject was injected with around 370 MBq of 18F-FDG. Total-body dynamic data was acquired for 60 minutes. Standardized uptake value (SUV) was calculated using the last 20 minutes. A total-body DECT scan was performed with 80 kVp and 140 kVp to decompose each voxel into air, soft tissue (or equivalently water), and bone components. Kinetic modeling using the standard irreversible two-tissue compartmental model was performed for regional quantification in 12 regions of interest (ROIs) (located in the thoracic vertebra and lumbar vertebra, 3/subject) with the image-derived blood input function extracted from the ascending aorta. A bone marrow volume is modeled as a mix of BM, cortical bone and blood and the measured 18F-FDG activity is a weighted sum of the three compositions and FDG uptake in cortical bone is negligible. Once estimated with DECT, the bone volume fraction ( <m:ctrlpr></m:ctrlpr> Vbone ) was fixed in the kinetic model estimation. The SUV with bone volume-fraction correction was calculated via dividing the original SUV value by 1 - <m:ctrlpr></m:ctrlpr> Vbone. FDG delivery rate K1 and net influx rate Ki were estimated with and without the bone-fraction correction and compared using the paired t test.
Results: Voxel-wise material decomposition with DECT was successfully completed for all four patients. The mean ± standard deviation (std) value of bone volume fraction was 0.142±0.029. With bone-fraction correction (BFC), the mean ± std value of the SUV was 1.454±0.275 compared to 1.244±0.215 without BFC. The mean ± std values of the Ki and K1 with BFC achieved 0.0063±0.001 and 0.178±0.051 compared to 0.0054±0.0009 and 0.152±0.044 without BFC. The increase in SUV was 16.6%±4.0% with BFC and its effect on SUV was statistically significant by the paired t test ( p<0.0001 ). Similarly, the gain of Ki and K1 using BFC both achieved 16.9%±4.1% and the changes in them were also statistically significant (both p<0.0001 ) .
Conclusions: Our study using DECT suggests current SUV and kinetic quantification of BM are very likely underestimated in PET due to the presence of significant bone volume fraction. Thus, bone-fraction correction may be needed for accurate PET quantification of BM. A future work is to investigate the impact of this correction for evaluation of BM quantification in blood cancer staging and anti-cancer immunotherapeutic response assessment.