Comparison Between Diffusion-Weighted MRI and 123 I-mIBG Uptake in Primary High-Risk Neuroblastoma

Abstract

Background: High-risk neuroblastoma (HR-NB) has a variable response to preoperative chemotherapy. It is not possible to differentiate viable vs. nonviable residual tumor before surgery.

Purpose: To explore the association between apparent diffusion coefficient (ADC) values from diffusion-weighted magnetic resonance imaging (DW-MRI), ¹²³ I-meta-iodobenzyl-guanidine (¹²³ I-mIBG) uptake, and histology before and after chemotherapy.

Study type: Retrospective.

Subjects: Forty patients with HR-NB.

Field strength/sequence: 1.5T axial DW-MRI (b = 0,1000 s/mm² ) and T₂ -weighted sequences. ¹²³ I-mIBG scintigraphy planar imaging (all patients), with additional ¹²³ I-mIBG single-photon emission computed tomography / computerized tomography (SPECT/CT) imaging (15 patients).

Assessment: ADC maps and ¹²³ I-mIBG SPECT/CT images were coregistered to the T₂ -weighted images. ¹²³ I-mIBG uptake was normalized with a tumor-to-liver count ratio (TLCR). Regions of interest (ROIs) for primary tumor volume and different intratumor subregions were drawn. The lower quartile ADC value (ADC_25prc ) was used over the entire tumor volume and the overall level of ¹²³ I-mIBG uptake was graded into avidity groups.

Statistical tests: Analysis of variance (ANOVA) and linear regression were used to compare ADC and MIBG values before and after treatment. Threshold values to classify tumors as viable/necrotic were obtained using ROC analysis of ADC and TLCR values.

Results: No significant difference in whole-tumor ADC_25prc values were found between different ¹²³ I-mIBG avidity groups pre- (P = 0.31) or postchemotherapy (P = 0.35). In the "intratumor" analysis, 5/15 patients (prechemotherapy) and 0/14 patients (postchemotherapy) showed a significant correlation between ADC and TLCR values (P < 0.05). Increased tumor shrinkage was associated with lower pretreatment tumor ADC_25prc values (P < 0.001); no association was found with pretreatment ¹²³ I-mIBG avidity (P = 0.17). Completely nonviable tumors had significantly lower postchemotherapy ADC_25prc values than tumors with >10% viable tumor (P < 0.05). Both pre- and posttreatment TLCR values were significantly higher in patients with >50% viable tumor than those with 10-50% viable tumor (P < 0.05). DATA CONCLUSION: ¹²³ I-mIBG avidity and ADC values are complementary noninvasive biomarkers of therapeutic response in HR-NB.

Level of evidence: 4.

Technical efficacy stage: 3.

Keywords: 123I-mIBG uptake; apparent diffusion coefficient; diffusion weighted-imaging; high-risk neuroblastoma; histopathology.

FIGURE 1

Representative images from the same patient (male, 20 months of age at diagnosis) before and after induction chemotherapy. Coregistered axial T₂‐weighted image (a) and apparent diffusion coefficient (ADC) map (b) acquired prior to chemotherapy with the primary tumor ROI overlaid (yellow line). SPECT ¹²³I‐mIBG image overlaid on T₂‐weighted image (c) and ADC map (d) acquired postchemotherapy with the liver ROI (orange) used for normalizations and tumor subregion ROIs shown: high ¹²³I‐mIBG avidity (green), moderate avidity (pink), low avidity (blue), and no avidity (red). In this example the “high avidity” ROI corresponded with the most avid part of the entire tumor volume.

FIGURE 2

Box‐and‐whisker plots of 25^th percentile apparent diffusion coefficient values (ADC_25prc) in each patient's primary tumor at prechemotherapy (a) and postchemotherapy (b) timepoints. Primary tumors are grouped according to the qualitative assessment of their ¹²³I‐mIBG avidity as follows: non‐avid (0), mildly (+), moderately (++), or strongly (+++) avid. Data points for individual tumors are overlaid (circles).

FIGURE 3

Plots of median ¹²³I‐mIBG tumor‐to‐liver count ratio (TLCR) values vs. median apparent diffusion coefficient (ADC) values in the most avid part of each primary tumor. Data points (circles) represent values from each individual tumor with the trend line and associated 95% confidence interval shown as solid and dashed lines, respectively. Data are shown before (a) and after (b) chemotherapy.

FIGURE 4

Apparent diffusion coefficient (ADC) value distributions on a whole tumor basis from the subcohort of 15 patients who receieved SPECT/CT imaging, at the prechemotherapy (blue) and postchemotherapy (orange) timepoints.

FIGURE 5

Box‐and‐whisker plots of chemotherapy‐induced percentage change in whole‐tumor 25^th percentile apparent diffusion coefficient (ADC_25prc) values, grouped by change in ¹²³I‐mIBG avidity in the same tumor.

FIGURE 6

(a) Plot of prechemotherapy, whole‐tumor 25^th percentile apparent diffusion coefficient (ADC_25prc) values vs. tumor shrinkage following chemotherapy. Data points (circles) represent individual primary tumors, with the linear fit (solid line) and associated 95% confidence intervals (dashed lines) overlaid. (b) Box‐and‐whisker plots of tumor shrinkage values grouped by the level of ¹²³I‐mIBG avidity in the primary tumor prior to treatment.

FIGURE 7

Box‐and‐whisker plots of pre‐ and postchemotherapy whole‐tumor 25^th percentile apparent diffusion coefficient (ADC_25prc) values (a,b) and median tumor‐to‐liver count ratio (TLCR) values (c,d) grouped according to the level of viable tumor remaining in the excised tissue following chemotherapy. Note that fewer tumors were available for the analysis shown in (c) and (d), as quantitative TLCR values were only available in a subset of 15 patients. Significant differences between groups are indicated (*P < 0.05). The optimum threshold value for identifying completely nonviable tumors based on their postchemotherapy ADC_25prc values is indicated with a dashed line in (b) (ADC_25prc threshold = 0.57 × 10⁻³ mm²/s), and the optimum median TLCR threshold for identifying tumors with >50% viable tissue is indicated with a dashed line in (d) (TLCR = 0.90).

FIGURE 8

(a) Box‐and‐whisker plots of postchemotherapy whole‐tumor 25^th percentile apparent diffusion coefficient (ADC_25prc) values, grouped by histological subtype (GNB: ganglioneuroblastoma; NB: neuroblastoma). Significant differences between groups are indicated (*P < 0.05). (b) 4 × 3 contingency table for postchemotherapy ¹²³I‐mIBG avidity grouped by histological subtype. Numbers represent the number of patients in each cell.