Comparison of Apparent Diffusion Coefficient and Intravoxel Incoherent Motion for Differentiating among Glioblastoma, Metastasis, and Lymphoma Focusing on Diffusion-Related Parameter

<div><p>Background and Purpose</p><p>Brain tumor cellularity has been assessed by using apparent diffusion coefficient (ADC). However, the ADC value might be influenced by both perfusion and true molecular diffusion, and the perfusion effect on ADC can limit the reliability of ADC in the characterization of tumor cellularity, especially, in hypervascular brain tumors. In contrast, the IVIM technique estimates parameter values for diffusion and perfusion effects separately. The purpose of our study was to compare ADC and IVIM for differentiating among glioblastoma, metastatic tumor, and primary CNS lymphoma (PCNSL) focusing on diffusion-related parameter.</p><p>Materials and Methods</p><p>We retrospectively reviewed the data of 128 patients with pathologically confirmed glioblastoma (n = 55), metastasis (n = 31), and PCNSL (n = 42) prior to any treatment. Two neuroradiologists independently calculated the maximum IVIM-f (f_max) and minimum IVIM-D (D_min) by using 16 different b-values with a bi-exponential fitting of diffusion signal decay, minimum ADC (ADC_min) by using 0 and 1000 b-values with a mono-exponential fitting and maximum normalized cerebral blood volume (nCBV_max). The differences in f_max, D_min, nCBV_max, and ADC_min among the three tumor pathologies were determined by one-way ANOVA with multiple comparisons. The f_max and D_min were correlated to the corresponding nCBV and ADC using partial correlation analysis, respectively.</p><p>Results</p><p>Using a mono-exponential fitting of diffusion signal decay, the mean ADC_min was significantly lower in PCNSL than in glioblastoma and metastasis. However, using a bi-exponential fitting, the mean D_min did not significantly differ in the three groups. The mean f_max significantly increased in the glioblastomas (reader 1, 0.103; reader 2, 0.109) and the metastasis (reader 1, 0.105; reader 2, 0.107), compared to the primary CNS lymphomas (reader 1, 0.025; reader 2, 0.023) (<i>P</i> < .001 for each). The correlation between f_max and the corresponding nCBV was highest in glioblastoma group, and the correlation between D_min and the corresponding ADC was highest in primary CNS lymphomas group.</p><p>Conclusion</p><p>Unlike ADC value derived from a mono-exponential fitting of diffusion signal, diffusion-related parametric value derived from a bi-exponential fitting with separation of perfusion effect doesn’t differ among glioblastoma, metastasis, and PCNSL.</p></div

Intravoxel incoherent motion imaging of glioblastoma.

<p>Glioblastoma, centered in the left frontal lobe, as seen on axial, contrast-enhanced, T1-weighted imaging (A). IVIM-derived f shows increased perfusion in the corresponding, solid, enhancing lesion of the tumor (B). IVIM-derived D shows a similar D value to that of the surrounding, normal white matter (C). A diffusion signal decay as a function of multiple b values within the tumor solid area is biexponential (D).</p

Intravoxel incoherent motion imaging of Primary CNS lymphoma.

<p>Primary CNS lymphoma of the left medial fronto-parietal lobe, as seen on axial, contrast-enhanced, T1-weighted imaging (A). IVIM-derived f shows no increase of perfusion in the corresponding, solid, enhancing lesion of the tumor (B). IVIM-derived D shows a similar D value to that of the surrounding, normal white matter (C). A diffusion signal decay as a function of multiple b values within the ROI of the tumor solid area is monoexponential (D).</p

Subgroup analysis for correlation of the imaging parameters.

<p>Abbreviations: nCBV = normalized cerebral blood volume and ADC = apparent diffusion coefficient.</p><p>^a indicates statistical significance.</p><p>Subgroup analysis for correlation of the imaging parameters.</p

Intravoxel incoherent motion imaging of metastatic tumor.

<p>Metastatic tumor of the left frontal lobe in a patient with lung cancer, as seen on axial, contrast-enhanced T1-weighted imaging (A). IVIM-derived f shows increased perfusion in the corresponding, solid, enhancing lesion of the tumor (B). IVIM-derived D shows a similar D value to that of the surrounding, normal white matter (C). A diffusion signal decay as a function of multiple b values within the ROI of the tumor solid area is biexponential (D).</p

Inter-reader ICC for measurement of the imaging parameters.

<p>Abbreviations: f_max = maximum perfusion fraction, D*_max = maximum pseudodiffusion coefficient, D_min = minimum diffusion coefficient, nCBV_max = maximum normalized cerebral blood volume, and ADC_min = minimum apparent diffusion coefficient.</p><p>^aNumbers in parentheses are the 95% confidence intervals.</p><p>Inter-reader ICC for measurement of the imaging parameters.</p

The image processing steps and workflows of imaging parameters.

<p>The image processing steps and workflows of imaging parameters.</p

Uninterpretable Dynamic Susceptibility Contrast-Enhanced Perfusion MR Images in Patients with Post-Treatment Glioblastomas: Cross-Validation of Alternative Imaging Options

<div><p>Purpose</p><p>The purpose of this study was to evaluate the accuracy of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) perfusion MR imaging for distinguishing tumor recurrence from post-treatment effect as alternatives to dynamic-susceptibility contrast-enhanced (DSC) perfusion MR imaging when the DSC image is uninterpretable.</p><p>Materials and Methods</p><p>This retrospective study was approved by our institutional review board. Seventy one post-treatment glioblastoma patients who showed enlarged contrast-enhancing lesions on follow-up MR images after concurrent chemoradiotherapy and uninterpretable DSC images for corresponding enhancing lesions, underwent additional DWI and DCE MR imaging. The primary outcome was the frequency of interpretable DWI and DCE MR cases in these 71 patients. The secondary outcome was the area under the receiver operating characteristic curve (AUC) of DWI and DCE imaging parameters for distinguishing tumor recurrence from post-treatment effect in selected patients with interpretable DWI and DCE images. The imaging parameters were quantified as 10% cumulative histogram cutoff of apparent diffusion coefficient (ADC10) and 90% cumulative histogram cutoff of initial area under the time signal intensity curve (IAUC90). The AUCs were cross-validated by using leave-one-out method.</p><p>Results</p><p>Of the 71 patients, the uninterpretable DSC images were associated with treatment-related hemorrhage within the corresponding enhancing lesions (n = 54, 76.1%) and a near skull base location (n = 17, 23.9%). The frequencies of interpretable DWI and DCE image were 51 (71.8%) and 59 (83.1%) of the 71 cases with uninterpretable DSC images, respectively. Of the 45 selected patients with interpretable DWI and DCE images, the combination of DWI with DCE imaging showed a superior diagnostic performance than DWI or DCE imaging alone for differentiating tumor recurrence from post-treatment effect (cross-validated AUC: 0.78 versus 0.55 and 0.73 for reader 1; cross-validated AUC: 0.78 versus 0.53 and 0.75 for reader 2, respectively). Cross-validated accuracy of the single and combined imaging parameters also showed the highest for the combination of DWI with DCE MR imaging (72.9% for reader 1; 72.5% for reader 2) and the lowest for DWI alone (54.0% for reader 1; 56.4% for reader 2). Inter-reader agreement for DCE imaging was higher than that for DWI (intraclass correlation coefficient: 0.95 versus 0.87).</p><p>Conclusion</p><p>DCE MR imaging could be a superior and more reproducible imaging biomarker than DWI for differentiating tumor recurrence from post-treatment effect in patients with post-treatment glioblastoma when DSC MR images are not interpretable.</p></div

An example of an uninterpretable DSC perfusion MR image. Images obtained in a 56-year-old man clinicoradiologically considered as having tumor progression.

<p>Contrast-enhanced, T1-weighted image (A) acquired 19 weeks after concomitant chemoradiotherapy (CCRT) shows an enhancing lesion in the temporal lobe. DSC perfusion MR image (B) shows signal loss in the corresponding contrast-enhancing lesion due to treatment-related hemorrhage confirmed on susceptibility weighted image (C).</p

Images obtained in a 72-year-old man clinicoradiologically considered as having tumor progression.

<p>Contrast-enhanced, T1-weighted image (A) acquired 14 weeks after concomitant chemoradiotherapy (CCRT) shows a rim-enhancing lesion in the right hemisphere. DSC perfusion MR image (B) shows signal loss in the corresponding area possibly caused by treatment-related hemorrhage. The corresponding contrast-enhancing solid tumor portion shows intermediate to low ADC value (C) as well as increased permeability on the DCE perfusion MR image (D). Contrast-enhanced, T1-weighted image (E) acquired 22 weeks after CCRT shows the contrast-enhancing lesion is more enlarged, suggesting tumor progression.</p