Rationale and Objectives
We sought to ( ) describe associations between measures of tumor perfusion by dynamic contrast-enhanced breast magnetic resonance imaging (DCE-MRI), blood flow by 15 O-water positron emission tomography (PET) and metabolism by 18 F-fluorodeoxyglucose ( 18 F)-FDG PET and ( ) improve our understanding of tumor enhancement on MRI through independent measures of tumor metabolism and blood flow.
Materials and Methods
We performed a retrospective analysis of the existing PET and MRI databases from the Departments of Nuclear Medicine and Radiology. We identified patients with locally advanced breast cancer who underwent 15 O-water/ 18 F-FDG PET within 1 month of clinical DCE-MRI between February 2004 and August 2006. The 15 O-water PET blood flow and 18 F-FDG metabolic rate and tissue transport constant ( K 1 ) in the primary malignancy were calculated. DCE-MRI peak percent enhancement and peak signal enhancement ratio (SER) were measured for each tumor. Correlations and regression analysis of these variables were performed.
Results
Fifteen patients with complete PET and DCE-MRI data were included in the analysis cohort. Peak SER correlated significantly with blood flow ( r = 0.73, P = .002) and K 1 ( r = 0.76, P = .001). However, peak SER did not correlate significantly with FDG metabolic rate ( r = 0.44, P = .101). There were no significant correlations between peak percent enhancement and any of the PET parameters.
Conclusions
Our findings suggest that tumor perfusion, represented by 15 O-water PET blood flow, is an important factor in the MRI enhancement of locally advanced breast cancer. A lack of correlation of FDG metabolic rate with blood flow and DCE-MRI kinetics suggests that 18 F-FDG PET provides complementary metabolic information independent of vascular factors.
Locally advanced breast cancer (LABC) is most frequently treated by neoadjuvant systemic therapy prior to definitive surgical resection. Dynamic contrast-enhanced breast magnetic resonance imaging (DCE-MRI) and positron emission tomography (PET) have been used to evaluate response to traditional cytotoxic neoadjuvant chemotherapy ( ). In addition, there is growing interest in targeted breast cancer therapy, such as antiangiogenic agents, for which noninvasive imaging may be particularly advantageous for response evaluation ( ).
Prior studies have examined DCE-MRI and PET functional studies independently. DCE-MRI defines the extent of breast cancer in vivo more accurately than any other imaging modality ( ). In addition, DCE-MRI data can provide measurements of tumor volume and enhancement kinetics. Changes in tumor volume following neoadjuvant therapy, as measured using DCE-MRI, are predictive of recurrence-free survival ( ). Measurements of tumor enhancement, including semiquantitative parameters such as initial percent enhancement (PE) and delayed signal enhancement ratio (SER), have been shown to be helpful and accurate for tumor detection and response evaluation ( ). Tumor enhancement likely reflects a combination of blood flow and capillary permeability ( ). However, the precise biologic factors underlying enhancement and the relative contributions of blood flow and capillary permeability are not completely understood.
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Materials and Methods
Case/Patient Selection
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MRI Acquisition Protocols
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MRI Image Analysis
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PE=S1−S0S0×100% P
E
=
S
1
−
S
0
S
0
×
100
%
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SER=S1−S0S2−S0 S
E
R
=
S
1
−
S
0
S
2
−
S
0
where S 2 is the value of the post-contrast sequence centered at 270 seconds. SER values model the shape of the enhancement curve for each voxel with SER >1.1 indicating washout, SER between 1.1 and 0.9 indicating plateau enhancement, and SER <0.9 indicating persistent enhancement. SER was previously shown to reflect both microvessel density and tumor grade ( ).
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PET Acquisition Protocol
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PET Imaging Analysis
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Kinetic Models
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FDG metabolic rate =[Glucose]∗Ki FDG metabolic rate =
[
Glucose
]
∗
K
i
where [Glucose] is the plasma glucose concentration (micromoles per millier) at the time of FDG PET. We have previously examined the relationship between FDG K 1 and FDG metabolic rate and blood flow measured by 15 O-water PET and to response to therapy ( ).
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Statistical Analysis
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Results
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Table 1
Correlations Between PET and DCE-MRI Variables
DCE-MRI Variable 15 O-Water PET Blood Flow 18 F-FDG PET Metabolic Rate 18 F-FDG PET K 1 Peak SER_r_ = 0.73 ( P = .002)r = 0.44 ( P = .10)r = 0.76 ( P = .001) Peak PE_r_ = 0.28 ( P = .30)r = 0.15 ( P = .59)r = 0.30 ( P = .28)
DCE: dynamic contrast-enhanced; 18 F-FDG: 18 F-fluorodeoxyglucose; K 1 : tissue transport constant; MRI: magnetic resonance imaging; PE: percent enhancement; PET: positron emission tomography; SER: signal enhancement ratio.
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Discussion
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Limitations
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Conclusions
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