Correlation of Bone Marrow Cellularity, Plasma Cell Infiltration and Microcirculation with Apparent Diffusion Coefficient of Diffusion Weighted Imaging In Patients with Monoclonal Plasma Cell Disease
Authors: Hillengass Jens , Stieltjes Bram , Baeuerle Tobias , McClanahan Fabienne , Heiss Christiane , Andrulis Mindaugas , Bartl Reiner , Shah Rajiv , Simon Dirk , Hose Dirk , Ho Anthony D. , Schlemmer Heinz Peter , Goldschmidt Hartmut , Delorme Stefan 
Published: October 2019

Abstract
Abstract 2978
Bone marrow infiltration of monoclonal plasma cells can be displayed by magnetic resonance imaging (MRI). While focal lesions - which have been shown to be of prognostic significance in multiple myeloma - can be measured and counted, until now diffuse infiltration could only be estimated qualitatively mainly by subjective comparison of the appearance of the respective vertebra with the intervertebral discs. Diffusion weighted imaging (DWI) which does not require application of contrast medium is established in neuro-radiology as method for early ischemia detection. DWI provides a so called apparent diffusion coefficient (ADC) which hypothetically correlates inversely with cellular density. The measured ADC is dependent of preset b-values with lower values being more influenced by perfusion and higher b-values by diffusion. In our study, we used b-values of 0, 400 and 750 s/mm2 to assess tissue cellularity. In 56 patients with monoclonal plasma cell disease ranging from monoclonal gammopathy of undetermined significance (MGUS) to symptomatic multiple myeloma (MM), correlation of the findings of immuno-histology of a trephine of the iliac crest, cytological smear and apparent diffusion coefficient of DWI of the iliac crest and the lumbar spine were analyzed. Furthermore the DWI-parameters of 30 healthy controls were evaluated for comparison. For histological correlation 25 patients were evaluable. A trend test for comparison of ADC and histological parameters revealed a significantly increasing trend of both plasma cell infiltration level and vessel density compared to ADC (p<0.001 for both histological parameters and both b-values). A significant positive correlation of ADC at b = 400 s/mm2 and b = 750 s/mm2 with bone marrow cellularity (p=0.04 for both b-values) and a moderate positive correlation with the degree of plasma cell infiltration (Spearman's correlation coefficient of 0.32 [95%-CI: 0.07, 0.57], p=0.04 and 0.37 [95%-CI: 0.11, 0.63], p=0.01) could be demonstrated. Of 26 patients with symptomatic MM, 15 were examined before and after therapy. ADC at b = 400 s/mm2 and 750 s/mm2 respectively decreased significantly after therapy (p<0.001 for both b-values). We conclude that DWI is a valuable non-invasive tool not only for assessment of initial tumor mass but also for monitoring of treatment in patients with monoclonal plasma cell disease. The finding that ADC increased with bone marrow cellularity in our opinion is caused by the also increasing perfusion which overlays the diffusion effect as confirmed by the positive correlation of ADC and vessel density in histology. Further development should aim at differentiating the diffusion and perfusion effects. First investigations on this subject are currently under way.

Disclosures:
No relevant conflicts of interest to declare.