Metabolic profiling of human brain metastases using in vivo proton MR spectroscopy at 3T

Abstract

Background: Metastases to the central nervous system from different primary cancers are an oncologic challenge as the overall prognosis for these patients is generally poor. The incidence of brain metastases varies with type of primary cancer and is probably increasing due to improved therapies of extracranial metastases prolonging patient's overall survival and thereby time for brain metastases to develop. In addition, the greater access to improved neuroimaging techniques can provide earlier diagnosis. The aim of this study was to investigate the feasibility of using proton magnetic resonance spectroscopy (MRS) and multivariate analyses to characterize brain metastases originating from different primary cancers, to assess changes in spectra during radiation treatment and to correlate the spectra to clinical outcome after treatment.

Methods: Patients (n = 26) with brain metastases were examined using single voxel MRS at a 3T clinical MR system. Five patients were excluded due to poor spectral quality. The spectra were obtained before start (n = 21 patients), immediately after (n = 6 patients) and two months after end of treatment (n = 4 patients). Principal component analysis (PCA) and partial least square regression analysis (PLS) were applied in order to identify clustering of spectra due to origin of metastases and to relate clinical outcome (survival) of the patients to spectral data from the first MR examination.

Results: The PCA results indicated that brain metastases from primary lung and breast cancer were separated into two clusters, while the metastases from malignant melanomas showed no uniformity. The PLS analysis showed a significant correlation between MR spectral data and survival five months after MRS before start of treatment.

Conclusion: MRS determined metabolic profiles analysed by PCA and PLS might give valuable clinical information when planning and evaluating the treatment of brain metastases, and also when deciding to terminate further therapies.

Figures

Figure 1

Brain metastases in vivo spectra. Axial T1 weighted contrast enhanced MR images of two patients with brain metastases from breast cancer (patient 1 and 12) with corresponding spectra. A: short echo time spectra of two metastases (a and b). B: Short and long echo time spectra in the same VOI. The lipid peak at 1.3 ppm in the short echo time spectrum is cut due to the chosen scaling.

Figure 2

Mean spectra. Short echo time mean spectra ± 95% CI of brain metastases from different primary cancer. A: lung cancer (n = 11 spectra), B: breast cancer (n = 9 spectra), C: malignant melanoma (n = 5 spectra), D: colon cancer (n = 2 spectra). The 0.7 – 3.4 ppm area of the spectra and the detected metabolites (in ppm) are given; tCho (3.2), Cr (3.0): creatine and lipids (1.3, 0.9): methylene and methyl groups.

Figure 3

PCA results. Part a: Score plot of PC1 versus PC2 of water suppressed in vivo spectra. ● = breast cancer (n = 9), X = lung cancer (n = 11), O = malignant melanoma (n = 5), ▼ = colon cancer (n = 2). Part b: The loading profile of PC1 showing differences in the lipid signals.

Figure 4

PLS score plot. Score plot of spectra from patients who lived longer than five months (○), and they who passed away before five months after the first MR spectra examination (†). The numbers refers to patient numbers in Table 1. Some patients were examined for two metastases (a and b).

Figure 5

Follow-up spectra. Spectra of brain metastases from patients with primary breast (patient 4) and lung cancer (patient 15), before (-I), immediately after (-II) and two months after end of radiation treatment (-III). The patients' survival was more than 16 months and only 3 months, respectively.