Correlation among DCE‐MRI measurements of bone marrow angiogenesis, microvessel density, and extramedullary disease in patients with multiple myeloma

Abstract

We investigated correlations among angiogenesis parameters of the lumbar vertebrae measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), microvessel density (MVD) in bone marrow (BM), and extramedullary disease (EMD) in patients with multiple myeloma (MM). Forty-nine MM patients were enrolled. Two semiquantitative parameters, Peak and Slope, were obtained from the DCE-MRI signal-intensity curve; three more quantitative parameters, Amp, Kep, and Kel, were generated from bicompartmental modeling. Apart from Kep, all parameters were found to correlate positively with MVD (r range, 0.323-0.594; all P < 0.03). Multivariate analysis indicated that the only factors significantly associated with MVD were Amp and plasma cell percentage in BM. Comparing angiogenesis parameters for patients with EMD at the time of DCE-MRI versus those who did not showed a high Amp ( 0.08) as the only significant factor associated with EMD (odds 6.33; P 5 0.045). During follow-up (median, 76 months), 4 more patients developed EMD. Accumulative incidence for developing EMD over time was significantly higher for patients with high Amp than those with low Amp (P 5 0.0254). In conclusion, Amp correlated strongly with MVD in BM and also EMD in patients with MM. Amp measurement might be helpful for identifying MM patients at risk for EMD.Multiple myeloma (MM) is a malignant plasma cell proliferation typically found in bone marrow (BM) [1]. Although MM cells (MCs) depend on the BM microenvironment to provide the signals essential for their growth and survival [2], in a fraction of patients MCs acquire the ability to proliferate in sites outside the BM. Such occurrences appear as extramedullary disease (EMD), indicating that MCs have become independent of the BM microenvironment [1]. The exact mechanism underlying the development of EMD in MM patients is not clear. One hypothesis suggests an alteration in the interaction between MCs and the BM microenvironment [2,3]. Within the BM microenvironment, angiogenesis might play a major role in not only promoting the growth and survival of MCs but also the disease progression itself [2][3][4]. The interaction between MCs and BM endothelial cells upregulates a number of angiogenic cytokines, such as vascular endothelial growth factor or matrix metalloproteinases. Such cytokines further stimulate BM angiogenesis and myeloma progression [5,6], as well as possible extramedullary dissemination [4]. To date, dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) is one of the most widely used noninvasive methods of measuring the perfusion and permeability of a biological tissue in the body, such as vertebral BM [7]. In MM patients, the angiogenesis parameters generated from DCE-MRI of vertebral BM reportedly correlate strongly with histological grade of infiltration, osteolytic bone involvement, microvessel density (MVD), and serum markers of disease activity [8,9]. However, prior to our study no data were available on the correlation between degree of BM angiogenesis and the de...

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