Diffusion-weighted MR imaging derived apparent diffusion coefficient is predictive of clinical outcome in primary central nervous system lymphoma

Abstract

Background and purpose: There is evidence that increased tumor cellular density within diagnostic specimens of primary central nervous system lymphoma (PCNSL) may have significant prognostic implications. Because cellular density may influence measurements of apparent diffusion coefficient (ADC) by using diffusion-weighted MR imaging (DWI), we hypothesized that ADC measured from contrast-enhancing regions might correlate with clinical outcome in patients with PCNSL.

Materials and methods: PCNSL tumors from 18 immunocompetent patients, treated uniformly with methotrexate-based chemotherapy, were studied with pretherapeutic DWI. Enhancing lesions were diagnosed by pathologic analysis as high-grade B-cell lymphomas. Regions of interest were placed around all enhancing lesions allowing calculation of mean, 25th percentile (ADC(25%)), and minimum ADC values. Histopathologic tumor cellularity was quantitatively measured in all patients. High and low ADC groups were stratified by the median ADC value of the cohort. The Welch t test assessed differences between groups. The Pearson correlation examined relationships between ADC measurements and tumor cellular density. Single and multivariable survival analysis was performed.

Results: We detected significant intra- and intertumor heterogeneity in ADC measurements. An inverse correlation between cellular density and ADC measurements was observed (P < .05). ADC(25%) measurements less than the median value of 692 (low ADC group) were associated with significantly shorter progression-free and overall survival. Patients with improved clinical outcome were noted to exhibit a significant decrease in ADC measurements following high-dose methotrexate chemotherapy.

Conclusions: Our study provides evidence that ADC measurements within contrast-enhancing regions of PCNSL tumors may provide noninvasive insight into clinical outcome.

Fig 1.

Comparison of diffusion-weighted imaging (DWI) and cellular density between high and low apparent diffusion coefficient (ADC) groups (A and F). Contrast-enhanced T1-weighted image with regions of interest surrounding enhancing regions that were pathologically diagnosed as primary central nervous system non-Hodgkin lymphoma. Arrow indicates enhancing region subjected to stereotactic biopsy. DWI (B and G), black and white ADC map (C and H), color ADC map (D and I), and biopsy specimens (E and J) from patient 2 (low ADC group) and patient 17 (high ADC group) (hematoxylin-eosin, original magnification ×100).

Fig 2.

Scatterplots of cellular density measurements versus 25th percentile (ADC_25%, A) and mean ADC (ADC_mean, B) values within contrast-enhancing tumor regions for all 18 subjects included in this study, demonstrating statistically significant inverse correlations (ADC_25%, R = −0.47, P = .05; ADC_mean, R = −0.54, P = .02).

Fig 3.

A and B, Patient outcome as a function of ADC_25% stratification into low and high groups. Kaplan Meier analysis (A) of progression-free survival (PFS) for patients stratified into the low ADC_25% group (<692, blue line) with a mean progression time of 9.4 months versus those stratified into high ADC_25% group (>692, red line) with a mean progression time of 30.0 months (P = .02, logrank test). Kaplan Meier plot (B) of overall survival (OS) for patients stratified into the low ADC_25% group (<692, blue line) with a mean survival of 15.8 months versus those stratified into high ADC_25% group (>692, red line) with a mean survival of 30.9 months (P = .01, logrank test). C and D, Patient outcome as a function of minimum ADC value shows a statistically significant difference in PFS and OS between low and high groups (P < .05).