Bone marrow microcirculation analysis in multiple myeloma by contrast-enhanced dynamic magnetic resonance imaging

Michel, Thomas; Hawighorst, H.; Neben, Kai; Egerer, Gerlinde; Hillengaß, Jens; Max, Regina; Benner, Axel; Ho, Anthony D.; Kaick, G. van; Goldschmidt, Hartmut

doi:10.1002/ijc.1421

Cited by 70 publications

(58 citation statements)

References 26 publications

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“…Different patterns of bone marrow involvement of MM in conventional as well as DCE-MRI have been described concordantly by different authors (14,23,29,30). Diffuse distribution of microcirculation was found in healthy controls as well as in all stages of plasma cell disease.…”

Section: Discussionsupporting

confidence: 53%

“…To visualize the distribution of microcirculation parameters in the examined area, a colorcoded pharmacokinetic map is superimposed onto the static MR image. DCE-MRI parameters amplitude A and exchange rate constant kep are significantly increased in patients with active MM compared with healthy controls and correlate with osteolytic bone involvement and prognosis (14). Earlier work of our group shown in 24 myeloma patients the significant correlation of high Amplitude A of DCE-MRI with increased micro vessel density (15).…”

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confidence: 63%

“…The limitation of kep to values below 13 min -1 because of restrictions of the pharmacokinetic model lowers the reliability of this parameter. However, it is interesting that the significance of differences between controls and patients as well as between different patient groups parallels in kep and A, which has been shown to be a reliable factor (14,16,17). Significant differences only of kep can be found between MGUS and aMM and only of A between aMM and sMM.…”

Section: Discussionmentioning

confidence: 99%

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Dynamic Contrast-Enhanced Magnetic Resonance Imaging Identifies a Subgroup of Patients with Asymptomatic Monoclonal Plasma Cell Disease and Pathologic Microcirculation

Hillengaß

Zechmann

Bäuerle

et al. 2009

Clinical Cancer Research

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Purpose: The aim of our study was to investigate whether dynamic contrast^enhanced magnetic resonance imaging (DCE-MRI) allows visualization of changes in microcirculation between healthy controls on the one side and early/advanced stages of plasma cell disease on the other. Experimental Design: We examined a group of 222 individuals consisting of 60 patients with monoclonal gammopathy of undetermined significance (MGUS), 65 patients with asymptomatic multiple myeloma (aMM), 75 patients with newly diagnosed symptomatic MM (sMM), and 22 healthy controls with DCE-MRI of the lumbar spine. Results: A continuous increase in microcirculation parameters amplitude A and exchange rate constant kep reflecting vascular volume and permeability, respectively, was detected from normal controls over MGUS and aMM to sMM. For A and kep, significant differences were found between controls and aMM (P = 0.03 and P = 0.004, respectively) as well as controls and sMM (P = 0.001and P < 0.001, respectively). Although diffuse microcirculation patterns were found in healthy controls as well as MGUS and MM, a pattern with focal hotspots was exclusively detected in 42.6% of sMM and in 3 MGUS and 3 aMM patients. MGUS and aMM patients with increased microcirculation patterns showed significantly higher bone marrow plasmocytosis compared with patients with a low microcirculation pattern. Conclusions: Our investigations substantiate the concept of an angiogenic switch from early plasma cell disorders to sMM. Pathologic DCE-MRI findings correlate with adverse prognostic factors and DCE-MRI identifies a distinct group of patients with increased microcirculation parameters in aMM and MGUS patients.

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Section: Discussionsupporting

confidence: 53%

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confidence: 63%

Section: Discussionmentioning

confidence: 99%

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Dynamic Contrast-Enhanced Magnetic Resonance Imaging Identifies a Subgroup of Patients with Asymptomatic Monoclonal Plasma Cell Disease and Pathologic Microcirculation

Hillengaß

Zechmann

Bäuerle

et al. 2009

Clinical Cancer Research

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“…5 Dynamic contrastenhanced magnetic resonance imaging (DCE-MRI) is a noninvasive technique to assess changes in microcirculation associated with cancer in various tissues. [6][7][8] In prior studies, we have demonstrated that DCE-MRI as a functional imaging technique highly correlates with histologically determined bone marrow angiogenesis in MM. 9 The quantitative results obtained with DCE-MRI do not only reflect increased blood vessel density described by Amplitude A (A) but also increased vessel permeability represented by exchange rate constant kep (kep).…”

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confidence: 99%

“…10 Evaluation of color coded maps superimposed on conventional MR images permits differentiation of 4 distinct microcirculation patterns. 6,11,12 It is largely unknown, however, which genetic features in myeloma cells induce the angiogenic change in microcirculation (''angiogenic switch''). 13 Schreiber et al demonstrated an increased micro vessel density detected by immunhistochemical staining of CD34 in bone marrow samples of MM patients with deletion 13q14.…”

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confidence: 99%

Gain of 1q21 and distinct adverse cytogenetic abnormalities correlate with increased microcirculation in multiple myeloma

Hillengaß

Zechmann

Nadler

et al. 2008

Intl Journal of Cancer

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To identify genetic mechanisms controlling bone marrow microcirculation and angiogenesis in patients with plasma cell disease we simultaneously performed bone marrow dynamic contrastenhanced magnetic resonance imaging (DCE-MRI) and cytogenetics (iFISH) on CD138 purified plasma cells of MGUS (n531) and untreated multiple myeloma (MM) (n 5 87) patients. The adverse cytogenetic abnormalities gain of 1q21, deletion 17p13 and deletion 13q14 significantly correlated with at least one DCE-MRI finding (aberrant ''focal'' microcirculation pattern, increase in median microcirculation parameter Amplitude A or exchange rate constant kep). We conclude that gain of 1q21, deletion 13q14 and deletion 17p13 trigger the angiogenic cascade in MM. Our findings will have important implications for the design, analysis and stratification for clinical studies of patients with MM in particular if compounds with antiangiogenic activity are used.

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

Huang

Chen

et al. 2012

American J Hematol

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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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Bone marrow microcirculation analysis in multiple myeloma by contrast-enhanced dynamic magnetic resonance imaging

Cited by 70 publications

References 26 publications

Dynamic Contrast-Enhanced Magnetic Resonance Imaging Identifies a Subgroup of Patients with Asymptomatic Monoclonal Plasma Cell Disease and Pathologic Microcirculation

Dynamic Contrast-Enhanced Magnetic Resonance Imaging Identifies a Subgroup of Patients with Asymptomatic Monoclonal Plasma Cell Disease and Pathologic Microcirculation

Gain of 1q21 and distinct adverse cytogenetic abnormalities correlate with increased microcirculation in multiple myeloma

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

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