Assessment of bone marrow angiogenesis in patients with acute myeloid leukemia by using contrast-enhanced MR imaging with clinically approved iron oxides: initial experience.
OBJECTIVE
To prospectively assess bone marrow (BM) angiogenesis in patients with acute myeloid leukemia (AML) by using iron oxide-enhanced magnetic resonance (MR) imaging.


METHODS
The study was institutional ethics committee approved. Informed signed consent was obtained from each study participant. The requirement for informed consent for use of data from a reference database was waived. Eleven patients (seven women, four men; mean age, 53 years+/-4.40 [standard deviation]) with an initial diagnosis of AML were enrolled in the study and underwent T2*-weighted two-echo echo-planar MR imaging of the pelvis before and after intravenous injection of a clinically approved iron oxide blood-pool contrast agent. Six healthy control subjects (one woman, five men; mean age, 35 years+/-2.31) were examined with the same MR protocol. The iron oxide-induced change in R2* relaxation rate (DeltaR2*) was calculated, and the vascular volume fraction (VVF) of the BM was derived by dividing the DeltaR2* of the BM by the DeltaR2* of the muscle. Parametric DeltaR2* maps were calculated to visualize vessel distribution. Patients underwent BM biopsy for correlative determination of microvessel density (MVD) and vascular endothelial growth factor (VEGF). Differences in DeltaR2*, VVF, VEGF, and MVD were compared by using the Wilcoxon rank sum test.


RESULTS
DeltaR2* maps showed prominent areas of highly vascularized BM in the patients with AML, whereas the control subjects had moderately vascularized BM with homogeneous vessel distribution. Quantitative analysis revealed VVF values to be significantly higher in patients with AML than in control subjects: The mean VVF in the pelvis was 9.18%+/-1.54 for patients versus 3.91%+/-0.61 for control subjects (P=.010). In accordance with MR results, MVD (P=.009) and VEGF expression (P=.017) were significantly elevated in the AML group compared with values in the control group.


CONCLUSIONS
Iron oxide-enhanced MR imaging enables assessment of BM angiogenesis in patients with AML.
Matuszewski
Lars
L
Department of Clinical Radiology, University of Muenster, Albert-Schweitzer-Str 33, D-48129 Münster, Germany.
Persigehl
Thorsten
T
Wall
Alexander
A
Meier
Norbert
N
Bieker
Ralf
R
Kooijman
Hendrik
H
Tombach
Bernd
B
Mesters
Rolf
R
Berdel
Wolfgang E
WE
Heindel
Walter
W
Bremer
Christoph
C
D019046:Bone Marrow Neoplasms / Q000098:blood supply* / Q000175:diagnosis*; D003287:Contrast Media; D017277:Drug Approval; D005260:Female; D005290:Ferric Compounds; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000175:diagnosis*; D010865:Pilot Projects; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D003287:Contrast Media; D005290:Ferric Compounds; C000499:ferric oxide