Comparison of dynamic susceptibility-weighted contrast-enhanced MR methods: recommendations for measuring relative cerebral blood volume in brain tumors

Abstract

Purpose: To investigate whether estimates of relative cerebral blood volume (rCBV) in brain tumors, obtained by using dynamic susceptibility-weighted contrast material-enhanced magnetic resonance (MR) imaging vary with choice of data acquisition and postprocessing methods.

Materials and methods: Four acquisition methods were used to collect data in 22 high-grade glioma patients, with informed written consent under HIPAA-compliant guidelines approved by the institutional review board. During bolus administration of a standard single dose of gadolinium-based contrast agent (0.1 mmol per kilogram of body weight), one of three acquisition methods was used: gradient-echo (GRE) echo-planar imaging (echo time [TE], 30 msec; flip angle, 90 degrees ; n = 10), small-flip-angle GRE echo-planar imaging (TE, 54 msec; flip angle, 35 degrees ; n = 7), or dual-echo GRE spiral-out imaging (TE, 3.3 and 30 msec; flip angle, 72 degrees ; n = 5). Next, GRE echo-planar imaging (TE, 30 msec; flip angle, 90 degrees ; n = 22) was used to collect data during administration of a second dose of contrast agent (0.2 mmol/kg). Subsequently, six methods of analysis were used to calculate rCBV. Mean rCBV values from whole tumor, tumor hot spots, and contralateral brain were normalized to mean rCBV in normal-appearing white matter.

Results: Friedman two-way analysis of variance and Kruskal-Wallis one-way analysis of variance results indicated that qualitative rCBV values were dependent on acquisition and postprocessing methods for both tumor and contralateral brain. By using the nonparametric Mann-Whitney test, a consistently positive (greater than zero) tumor-contralateral brain rCBV ratio resulted when either the preload-postprocessing correction approach or dual-echo acquisition approach (P < .008 for both methods) was used.

Conclusion: The dependence of tumor rCBV on the choice of acquisition and postprocessing methods is caused by their varying sensitivities to T1 and T2 and/or T2* leakage effects. The preload-correction approach and dual-echo acquisition approach are the most robust choices for the evaluation of brain tumors when the possibility of contrast agent extravasation exists.

Figure 1:

Graphic depiction of experimental paradigm. Acquisition method A, B, or C was used to collect data during primary (1°) injection of contrast agent. After clinical contrast-enhanced imaging protocol, acquisition method D was used to collect data during secondary injection (2°) of contrast agent. Primary injection of contrast agent served as preload for acquisition method D. FLAIR = fluid-attenuated inversion-recovery, T1+C = T1-weighted contrast-enhanced image.

Figure 2a:

Pictorial representations of six data postprocessing methods used to estimate rCBV from the dynamic susceptibility-weighted contrast-enhanced MR imaging data, as follows: (a) UTI, (b) CTI, (c) gamma-variate fit, (d) PBSI, (e) MSD, and (f) NEI. a.u. = Arbitrary units.

Figure 2b:

Pictorial representations of six data postprocessing methods used to estimate rCBV from the dynamic susceptibility-weighted contrast-enhanced MR imaging data, as follows: (a) UTI, (b) CTI, (c) gamma-variate fit, (d) PBSI, (e) MSD, and (f) NEI. a.u. = Arbitrary units.

Figure 2c:

Pictorial representations of six data postprocessing methods used to estimate rCBV from the dynamic susceptibility-weighted contrast-enhanced MR imaging data, as follows: (a) UTI, (b) CTI, (c) gamma-variate fit, (d) PBSI, (e) MSD, and (f) NEI. a.u. = Arbitrary units.

Figure 2d:

Pictorial representations of six data postprocessing methods used to estimate rCBV from the dynamic susceptibility-weighted contrast-enhanced MR imaging data, as follows: (a) UTI, (b) CTI, (c) gamma-variate fit, (d) PBSI, (e) MSD, and (f) NEI. a.u. = Arbitrary units.

Figure 2e:

Pictorial representations of six data postprocessing methods used to estimate rCBV from the dynamic susceptibility-weighted contrast-enhanced MR imaging data, as follows: (a) UTI, (b) CTI, (c) gamma-variate fit, (d) PBSI, (e) MSD, and (f) NEI. a.u. = Arbitrary units.

Figure 2f:

Pictorial representations of six data postprocessing methods used to estimate rCBV from the dynamic susceptibility-weighted contrast-enhanced MR imaging data, as follows: (a) UTI, (b) CTI, (c) gamma-variate fit, (d) PBSI, (e) MSD, and (f) NEI. a.u. = Arbitrary units.

Figure 3a:

Study results for acquisition methods (a) A, (b) B, (c) C, and (d) D. Six methods of analysis were used to estimate rCBV from data collected with each acquisition method. Values are mean normalized rCBV values from ROIs. a.u. = Arbitrary units, Gd = gadolinium, Neg. Enh. = negative enhancement, PostB Sub = postbolus subtraction, pt = point, reference = contralateral, TI = trapezoidal integration.

Figure 3b:

Study results for acquisition methods (a) A, (b) B, (c) C, and (d) D. Six methods of analysis were used to estimate rCBV from data collected with each acquisition method. Values are mean normalized rCBV values from ROIs. a.u. = Arbitrary units, Gd = gadolinium, Neg. Enh. = negative enhancement, PostB Sub = postbolus subtraction, pt = point, reference = contralateral, TI = trapezoidal integration.

Figure 3c:

Study results for acquisition methods (a) A, (b) B, (c) C, and (d) D. Six methods of analysis were used to estimate rCBV from data collected with each acquisition method. Values are mean normalized rCBV values from ROIs. a.u. = Arbitrary units, Gd = gadolinium, Neg. Enh. = negative enhancement, PostB Sub = postbolus subtraction, pt = point, reference = contralateral, TI = trapezoidal integration.

Figure 3d:

Study results for acquisition methods (a) A, (b) B, (c) C, and (d) D. Six methods of analysis were used to estimate rCBV from data collected with each acquisition method. Values are mean normalized rCBV values from ROIs. a.u. = Arbitrary units, Gd = gadolinium, Neg. Enh. = negative enhancement, PostB Sub = postbolus subtraction, pt = point, reference = contralateral, TI = trapezoidal integration.

Figure 4:

Parametric maps for rCBV demonstrate utility of contrast agent preload. One section of rCBV maps generated for 21-year-old patient diagnosed with malignant glioneuronal tumor. Top (A–F) and bottom (G–L) rCBV maps were created from data collected with acquisition methods A and D, respectively. Although GRE echo-planar imaging sequence with 90° flip angle was used for both methods, method A was collected during primary injection of standard dose of contrast agent, and method D was collected during secondary injection of double dose of contrast agent after administration of preload. Methods of analysis were as follows: UTI (A, G), CTI (B, H), gamma-variate fitting (C, I), PBSI (D, J), MSD (E, K), and NEI (F, L). Note that when preload of contrast agent was not used (top), variability in tumor rCBV was dependent on choice of method of analysis, with negative or zero tumor rCBV results in some cases. Collecting data after preload (bottom) decreases dependence of tumor rCBV on chosen method of analysis.

Figure 5a:

(a) Contrast-enhanced anatomic image from patient 4. (b–e) MR signal– and concentration-time curves demonstrating confounding T1 and T2 leakage and/or residual susceptibility effects. Data in b and c were collected with acquisition method A (GRE echo-planar imaging with 90° flip angle during primary injection of standard dose of contrast agent). Data acquired during primary injection demonstrate strong T1 leakage effect, as evidenced by the fact that postbolus signal continues rising above its prebolus baseline on b, which corresponds to postbolus portion of ΔR2*(t) decreasing below its prebolus baseline level on c. Data on d and e are same types of curves, taken from same voxel, but were acquired with acquisition method D (GRE echo-planar imaging with 90° flip angle during secondary injection of double dose of contrast agent after preload administration). Postbolus signal remains below its prebolus baseline level on d, which corresponds to elevated postbolus portion of ΔR2*(t) on e. This is consistent with a dipolar T2 leakage effect or a residual susceptibility leakage effect. a.u. = Arbitrary units.

Figure 5b:

(a) Contrast-enhanced anatomic image from patient 4. (b–e) MR signal– and concentration-time curves demonstrating confounding T1 and T2 leakage and/or residual susceptibility effects. Data in b and c were collected with acquisition method A (GRE echo-planar imaging with 90° flip angle during primary injection of standard dose of contrast agent). Data acquired during primary injection demonstrate strong T1 leakage effect, as evidenced by the fact that postbolus signal continues rising above its prebolus baseline on b, which corresponds to postbolus portion of ΔR2*(t) decreasing below its prebolus baseline level on c. Data on d and e are same types of curves, taken from same voxel, but were acquired with acquisition method D (GRE echo-planar imaging with 90° flip angle during secondary injection of double dose of contrast agent after preload administration). Postbolus signal remains below its prebolus baseline level on d, which corresponds to elevated postbolus portion of ΔR2*(t) on e. This is consistent with a dipolar T2 leakage effect or a residual susceptibility leakage effect. a.u. = Arbitrary units.

Figure 5c:

(a) Contrast-enhanced anatomic image from patient 4. (b–e) MR signal– and concentration-time curves demonstrating confounding T1 and T2 leakage and/or residual susceptibility effects. Data in b and c were collected with acquisition method A (GRE echo-planar imaging with 90° flip angle during primary injection of standard dose of contrast agent). Data acquired during primary injection demonstrate strong T1 leakage effect, as evidenced by the fact that postbolus signal continues rising above its prebolus baseline on b, which corresponds to postbolus portion of ΔR2*(t) decreasing below its prebolus baseline level on c. Data on d and e are same types of curves, taken from same voxel, but were acquired with acquisition method D (GRE echo-planar imaging with 90° flip angle during secondary injection of double dose of contrast agent after preload administration). Postbolus signal remains below its prebolus baseline level on d, which corresponds to elevated postbolus portion of ΔR2*(t) on e. This is consistent with a dipolar T2 leakage effect or a residual susceptibility leakage effect. a.u. = Arbitrary units.

Figure 5d:

(a) Contrast-enhanced anatomic image from patient 4. (b–e) MR signal– and concentration-time curves demonstrating confounding T1 and T2 leakage and/or residual susceptibility effects. Data in b and c were collected with acquisition method A (GRE echo-planar imaging with 90° flip angle during primary injection of standard dose of contrast agent). Data acquired during primary injection demonstrate strong T1 leakage effect, as evidenced by the fact that postbolus signal continues rising above its prebolus baseline on b, which corresponds to postbolus portion of ΔR2*(t) decreasing below its prebolus baseline level on c. Data on d and e are same types of curves, taken from same voxel, but were acquired with acquisition method D (GRE echo-planar imaging with 90° flip angle during secondary injection of double dose of contrast agent after preload administration). Postbolus signal remains below its prebolus baseline level on d, which corresponds to elevated postbolus portion of ΔR2*(t) on e. This is consistent with a dipolar T2 leakage effect or a residual susceptibility leakage effect. a.u. = Arbitrary units.

Figure 5e:

(a) Contrast-enhanced anatomic image from patient 4. (b–e) MR signal– and concentration-time curves demonstrating confounding T1 and T2 leakage and/or residual susceptibility effects. Data in b and c were collected with acquisition method A (GRE echo-planar imaging with 90° flip angle during primary injection of standard dose of contrast agent). Data acquired during primary injection demonstrate strong T1 leakage effect, as evidenced by the fact that postbolus signal continues rising above its prebolus baseline on b, which corresponds to postbolus portion of ΔR2*(t) decreasing below its prebolus baseline level on c. Data on d and e are same types of curves, taken from same voxel, but were acquired with acquisition method D (GRE echo-planar imaging with 90° flip angle during secondary injection of double dose of contrast agent after preload administration). Postbolus signal remains below its prebolus baseline level on d, which corresponds to elevated postbolus portion of ΔR2*(t) on e. This is consistent with a dipolar T2 leakage effect or a residual susceptibility leakage effect. a.u. = Arbitrary units.