Rationale and Objectives
The aim of this work was to compare a high-resolution diffusion-weighted imaging (HR-DWI) acquisition (voxel size = 4.8 mm 3 ) to a standard diffusion-weighted imaging (STD-DWI) acquisition (voxel size = 29.3 mm 3 ) for monitoring neoadjuvant therapy-induced changes in breast tumors.
Materials and Methods
Nine women with locally advanced breast cancer were imaged with both HR-DWI and STD-DWI before and after 3 weeks (early treatment) of neoadjuvant taxane-based treatment. Tumor apparent diffusion coefficient (ADC) metrics (mean and histogram percentiles) from both DWI methods were calculated, and their relationship to tumor volume change after 12 weeks of treatment (posttreatment) measured by dynamic contrast enhanced magnetic resonance imaging was evaluated with a Spearman’s rank correlation.
Results
The HR-DWI pretreatment 15th percentile tumor ADC ( P = .03) and early treatment 15th, 25th, and 50th percentile tumor ADCs ( P = .008, .010, .04, respectively) were significantly lower than the corresponding STD-DWI percentile ADCs. The mean tumor HR-ADC was significantly lower than STD-ADC at the early treatment time point ( P = .02), but not at the pretreatment time point ( P = .07). A significant early treatment increase in tumor ADC was found with both methods ( P < .05). Correlations between HR-DWI tumor ADC and posttreatment tumor volume change were higher than the STD-DWI correlations at both time points and the lower percentile ADCs had the strongest correlations.
Conclusion
These initial results suggest that the HR-DWI technique has potential for improving characterization of low tumor ADC values over STD-DWI and that HR-DWI may be of value in evaluating tumor change with treatment.
Magnetic resonance imaging (MRI) techniques are increasingly used to evaluate tumors in patients with locally advanced breast cancer who are undergoing neoadjuvant (preoperative) chemotherapy. Although change in tumor size is recognized as a surrogate predictor of response to chemotherapy , tumor morphologic changes tend to occur later in therapy and typically become apparent after biologic effects . Thus, there is an increasing clinical need to identify early markers for monitoring therapeutic response and improving treatment strategy.
Diffusion-weighted imaging (DWI) has shown promise as a potential imaging biomarker of early treatment response. DWI sequences use diffusion sensitizing gradients to detect differences in water mobility that reflect tissue microenvironment and microstructure. Unlike dynamic contrast-enhanced (DCE) MRI, DWI has the advantage of not requiring the use of a contrast agent.
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Materials and methods
Patient Population
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MRI Data Acquisition
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Standard DCE-MRI
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Diffusion-weighted MRI
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MRI Data Analysis
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ADC=−ln(SD/S0)/Δb(mm2/s) A
D
C
=
−
ln
(
S
D
/
S
0
)
/
Δ
b
(
mm
2
/
s
)
where S 0 and S D are the b = 0 (s/mm 2 ) and b = 600 (s/mm 2 ) signals, respectively, and Δb = 600 (s/mm 2 ). ADC maps for HR-DWI data were constructed automatically from complex averaged images using previously published methods .
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DWI ROI Delineation
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DWI Quantitative Analysis
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Tumor Volume
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Statistical Analysis
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Results
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Pretreatment
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Table 1a
Pretreatment Tumor ADC Metrics Measured with Both HR-DWI and STD-DWI
Tumor ADC Variable (×10 −3 mm 2 /second) Mean HR-DWI (SD) Pretreatment Mean STD-DWI (SD) Median Difference (95% CI) Wilcoxon P Value Mean ADC 1.31 (0.30) 1.37 (0.30) 0.062 (−0.021, 0.152) .07 15th percentile 1.02 (0.22) 1.11 (0.24) 0.095 (0.006, 0.184) .03 25th percentile 1.11 (0.25) 1.18 (0.25) 0.082 (−0.005, 0.159) .07 50th percentile 1.28 (0.32) 1.34 (0.31) 0.047 (−0.033, 0.140) .20 75th percentile 1.48 (0.39) 1.52 (0.35) 0.037 (−0.058, 0.133) .36 90th percentile 1.59 (0.42) 1.61 (0.38) 0.022 (−0.068, 0.115) .50
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Early Treatment
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Table 1b
Early Treatment Tumor ADC Metrics for the Same Group of Tumors Measured with Both HR-DWI and STD-DWI
Tumor ADC Variable (×10 −3 mm 2 /second) Mean HR-DWI (SD) Early Treatment Mean STD-DWI (SD) Median Difference (95% CI) Wilcoxon P Value Mean ADC 1.50 (0.37) 1.57 (0.40) 0.117 (0.008, 0.224) .02 15th percentile 1.17 (0.31) 1.33 (0.38) 0.170 (0.077, 0.247) .01 25th percentile 1.29 (0.33) 1.41 (0.39) 0.117 (0.036, 0.192) .01 50th percentile 1.50 (0.39) 1.60 (0.40) 0.117 (0.001, 0.231) .04 75th percentile 1.69 (0.43) 1.75 (0.43) 0.053 (−0.059, 0.183) .50 90th percentile 1.79 (0.44) 1.83 (0.44) 0.050 (−0.099, 0.193) .55
ADC, apparent diffusion coefficient; HR-DWI, high-resolution diffusion-weighted imaging; SD, standard deviation; STD-DWI, standard diffusion-weighted imaging.
Mean tumor ADC as well as the mean ADC values for the 15th, 25th, 50th, 75th, and 90th percentiles for HR and STD-DWI were compared using a Wilcoxon signed-rank test.
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Difference between Pretreatment and Early Treatment
Within the same DWI technique
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Table 2
Comparison of HR-DWI and STD-DWI Tumor ADC Change: Pretreatment to Early Treatment
Tumor ADC Variable (× 10 −3 mm 2 /second) HR-DWI Median (95% CI), P Value STD-DWI Median (95% CI), P Value STD/HR Difference Median (95% CI), P Value Mean ADC 0.16 (0.021, 0.36) 0.02 0.23 (0.059, 0.40) 0.02 0.045 (−0.045, 0.13) 0.4 15th percentile 0.13 (0.020, 0.29) 0.02 0.23 (0.058, 0.37) 0.03 0.087 (−0.044, 0.16) 0.2 25th percentile 0.17 (0.032, 0.33) 0.01 0.24 (0.078, 0.38) 0.02 0.040 (−0.065, 0.12) 0.3 50th percentile 0.20 (0.029, 0.42) 0.02 0.26 (0.084, 0.48) 0.02 0.045 (−0.047, 0.16) 0.3 75th percentile 0.14 (0.014, 0.40) 0.02 0.21 (0.025, 0.45) 0.02 0.022 (−0.062, 0.13) 0.6 90th percentile 0.11 (0.004, 0.40) 0.04 0.22 (0.025, 0.45) 0.03 0.041 (−0.058, 0.26) 0.5
ADC, apparent diffusion coefficient; HR-DWI, high-resolution diffusion-weighted imaging; STD-DWI, standard diffusion-weighted imaging.
Changes in tumor ADC metrics from pre- to early treatment measured with HR-DWI (column 2) and STD-DWI (column 3), and the difference between HR-DWI and STD-DWI (last column). Changes in mean ADC as well as changes in the 15th, 25th, 50th, 70th, and 90th percentiles for HR-DWI and STD-DWI were compared using a Wilcoxon signed-rank test.
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Between the two DWI techniques
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Tumor Volume Change with Treatment
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Correlation between Tumor ADC and Tumor Volume Change
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Table 3a
Pretreatment HR-DWI and STD-DWI Tumor ADC Metrics for the Group with >65% Tumor Volume Reduction and the Group with <65% Tumor Volume Reduction at the end of Treatment
Tumor ADC Variable (×10 −3 mm 2 /s) Pretreatment HR-DWI >65% volume change Mean HR-DWI <65% volume change mean STD-DWI Mean > 65% volume change STD-DWI mean < 65% volume change Mean ADC 1.30 1.34 1.38 1.32 15th percentile 1.02 1.02 1.14 1.03 25th percentile 1.11 1.11 1.21 1.11 50th percentile 1.28 1.40 1.35 1.27 75th percentile 1.46 1.55 1.52 1.49 90th percentile 1.56 1.70 1.60 1.63
Table 3b
Early Treatment HR-DWI and STD-DWI Tumor ADC Metrics for the Group with >65% Tumor Volume Reduction and the Group with <65% Tumor Volume Reduction at the End of Treatment
Tumor ADC Variable (× 10 −3 mm 2 /s) Early-Treatment HR-DWI >65% volume change Mean HR-DWI <65% volume change mean STD-DWI Mean > 65% volume change STD-DWI mean < 65% volume change Mean ADC 1.50 1.46 1.64 1.44 15th percentile 1.19 1.11 1.37 1.19 25th percentile 1.31 1.23 1.45 1.27 50th percentile 1.51 1.45 1.65 1.43 75th percentile 1.69 1.69 1.79 1.60 90th percentile 1.79 1.81 1.87 1.69
ADC, apparent diffusion coefficient; HR-DWI, high-resolution diffusion-weighted imaging; STD-DWI, standard diffusion-weighted imaging.
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Discussion
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Conclusion
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Acknowledgment
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