Dynamic Contrast-Enhanced MRI Identifies a Distinct Group of Asymptomatic Myeloma Patients with Increased Bone Marrow Microcirculation.
Authors: Hillengass Jens , Zechmann Christian , Nadler Andreas , Delorme Stefan , Benner Axel , Heiss Christiane , Ho Anthony D. , Goldschmidt Hartmut , Moehler Thomas 
Published: April 2020

Abstract
Introduction: Dynamic contrast enhanced MRI (dceMRI) is an imaging technique detecting changes in local microcirculation reflecting increased angiogenesis. The dceMRI parameters Amplitude A and exchange rate constant kep have been shown to be significantly increased in patients with active multiple myeloma (MM) compared to healthy controls and to correlate with osteolytic bone involvement and prognosis. We now compared the parameters and infiltration patterns of dceMRI in patients with monoclonal gammopathy of undetermined significance (MGUS) as well as in patients with asymptomatic MM not requiring chemotherapy (NRC-group) with those in patients with symptomatic MM requiring chemotherapy according to international standards.
Methods: The NRC group contained 71 patients: 29 patients with MGUS, 39 patients with MM stage I and 3 patients with MM stage IIA according to Durie and Salmon. 24 patients had a diagnosis of a MM in stage II in progression (n = 3) or stage III (n = 21). All patients underwent standardized dceMRI with high temporal resolution (T1w-turboFLASH) of the lumbar spine before start of therapy. Color coded pharmacokinetic maps of imaged area were classified according to three distinct patterns of microcirculation: “normal” (as in healthy controls), “diffuse” or “focal”. The contrast uptake was quantified using a two compartment model with the output parameters Amplitude A and distribution constant rate kep reflecting bone marrow microcirculation.
Results: 63 % of patients in the NRC group were found to have changes in the microcirculation pattern with 26 patients (37%) displaying a normal, 43 (60%) a diffuse and 2 (3%) a focal pattern. Within the NRC group 11 MGUS patients (38%) were found to have a normal pattern, 17 patients (59%) had a diffuse and 1 patient (3%) presented with a focal pattern. 79 % of patients with symptomatic MM had an abnormal microcirculation pattern with 5 (21%) MM patients showing a normal, 12 (50%) a diffuse and 7 (29%) a focal pattern. Statistical comparison did not reveal a significant difference in the total incidence between NRC and symptomatic MM group.
Comparison of quantitative microcirculation parameters did not show a significant difference of Amplitude A (p=0.87) and exchange rate constant kep (p=0.3) in MGUS patients compared to patients with asymptomatic MM. Comparing the NRC group with the symptomatic myeloma group revealed a significant higher Amplitude A in the symptomatic MM group (p=0.01). There was no significant difference in exchange rate constant kep.
Conclusion: Our investigations revealed a group of patients with asymptomatic myeloma and MGUS that display significant increase in bone marrow microcirculation. Our findings could be the basis for stratified treatment of patients with novel therapeutics targeting the vascular system. Prognostic implications for systemic and local development of the malignant disease are topic of current investigations.