MR and proton spectroscopy of white matter disease induced by high-dose chemotherapy with bone marrow transplant in advanced breast carcinoma.

PURPOSE To determine whether the MR-detectable white matter changes associated with high-dose chemotherapy and bone marrow transplant in patients with advanced breast carcinoma are accompanied by neurochemical disturbances detectable by proton MR spectroscopy. METHODS MR studies were obtained in 13 patients, and single-voxel proton MR spectra were acquired in vivo in 12 of these 13 for comparison with 13 age- and sex-matched control subjects. RESULTS Considerable white matter change determined with MR was found in 10 of 13 patients with volume white matter change ranging from 1 to 153 cm3 (mean, 49 cm3; SD, 50 cm3). Single-voxel spectra successfully acquired in 12 patients revealed no significant difference in patients compared with control subjects for the spectral ratios N-acetyl aspartate to creatine or N-acetyl aspartate to choline at either short or long echo times (30 and 136 milliseconds). CONCLUSION Extensive, late-stage white matter change induced by high-dose chemotherapy is not accompanied by measurable disturbances in the putative neuronal marker N-acetyl aspartate, suggesting that chemotherapy-induced white matter disease is predominantly a water space and possibly an extraneuronal process rather than a primary neuronal (axonal) disease. The MR spectroscopic examination, accomplished at the time of the MR imaging examination, complements the MR imaging study by increasing the specificity of the MR-based clinical evaluation.