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Int J Clin Exp Med 2012;5(2):154-164
Original Article
Brain metabolomic profiles of lung cancer patients prior to treatment characterized
by proton magnetic resonance spectroscopy
Helene Benveniste, Shaonan Zhang, Ruth Reinsel, Haifang Li, Hedok Lee, Mario Rebecchi, William Moore, Christoffer Johansen,
Douglas L Rothman, Thomas V Bilfinger
Department of Anesthesiology, Stony Brook University, Stony Brook, NY, USA; Department of Applied Mathematics & Statistics, Stony
Brook University, NY, USA; Department of Radiology, Stony Brook University, Stony Brook, NY, USA; Department of Psychosocial Cancer
Research, Institute of Cancer Epidemiology, Copenhagen, Denmark; Departments of Diagnostic Radiology and Biomedical
Engineering, Yale University School of Medicine, New Haven, CT, USA; Department of Surgery, Stony Brook University, Stony Brook, NY,
USA
Received February 13, 2012; accepted February 25, 2012; Epub April 6, 2012; Published April 30, 2012
Abstract: Cancer patients without evidence of brain metastases often exhibit constitutional symptoms, cognitive dysfunction and mood
changes at the time of clinical diagnosis, i.e. prior to surgical and/or chemotherapy treatment. At present however, there is limited
information on brain metabolic and functional status in patients with systemic cancers such as lung cancer prior to initiation of
treatment. Therefore, a prospective, observational study was conducted on patients with a clinical diagnosis of lung cancer to assess
the cerebral metabolic status before treatment using proton magnetic resonance spectroscopy (1HMRS). Together with neurocognitive
testing, 1HMRS was performed in the parietal and occipital cortices of patients diagnosed with a lung mass (N=17) and an age-
matched control group (N=15). Glutamate concentrations in the occipital cortex were found to be lower in the patients compared to
controls and the concentrations of creatine and phosphocreatine were significantly lower in the parietal cortex of the patients. The lung
cancer patients were also characterized by greater fatigue scores (but not depression) prior to treatment when compared to controls. In
addition, the serum concentration of interleukin-6 (proinflammatory cytokine) was higher in patients compared to controls; and the
concentration of tumor-necrosis factor alpha ([TNF-α]) was positively correlated to the metabolic activity of the lung tumor as defined by
the 2-deoxy-2-(18F)fluoro-D-glucose (18FDG) positron emission tomography (PET) derived maximal standardized uptake values
(SUVmax). Finally, multivariate statistical modeling revealed that the concentration of N-acetyl-aspartate in the occipital was negatively
associated with [TNF-α]. In conclusion, our data demonstrate that the cerebral metabolic status of patients with lung cancer is changed
even prior to treatment. In addition, the association between inflammatory cytokines, SUVmax and [NAA] points towards interactions
between the cancer’s inherent metabolic activity, systemic subclinical inflammation and brain function. (IJCEM1202005).
Keywords: Lung cancer, proton magnetic resonance spectroscopy, brain, glutamate, proinflammatory cytokines, fatigue
Address all correspondence to:
Dr. Helene Benveniste
Health Sciences Center Level 4-060
Stony Brook University
Stony Brook, NY 11794-8480, USA.
Tel: (631) 444 2358; Fax: (631) 444 2907
E-mail: helene.benveniste@sbumed.org
Original Article
Brain metabolomic profiles of lung cancer patients prior to treatment characterized
by proton magnetic resonance spectroscopy
Helene Benveniste, Shaonan Zhang, Ruth Reinsel, Haifang Li, Hedok Lee, Mario Rebecchi, William Moore, Christoffer Johansen,
Douglas L Rothman, Thomas V Bilfinger
Department of Anesthesiology, Stony Brook University, Stony Brook, NY, USA; Department of Applied Mathematics & Statistics, Stony
Brook University, NY, USA; Department of Radiology, Stony Brook University, Stony Brook, NY, USA; Department of Psychosocial Cancer
Research, Institute of Cancer Epidemiology, Copenhagen, Denmark; Departments of Diagnostic Radiology and Biomedical
Engineering, Yale University School of Medicine, New Haven, CT, USA; Department of Surgery, Stony Brook University, Stony Brook, NY,
USA
Received February 13, 2012; accepted February 25, 2012; Epub April 6, 2012; Published April 30, 2012
Abstract: Cancer patients without evidence of brain metastases often exhibit constitutional symptoms, cognitive dysfunction and mood
changes at the time of clinical diagnosis, i.e. prior to surgical and/or chemotherapy treatment. At present however, there is limited
information on brain metabolic and functional status in patients with systemic cancers such as lung cancer prior to initiation of
treatment. Therefore, a prospective, observational study was conducted on patients with a clinical diagnosis of lung cancer to assess
the cerebral metabolic status before treatment using proton magnetic resonance spectroscopy (1HMRS). Together with neurocognitive
testing, 1HMRS was performed in the parietal and occipital cortices of patients diagnosed with a lung mass (N=17) and an age-
matched control group (N=15). Glutamate concentrations in the occipital cortex were found to be lower in the patients compared to
controls and the concentrations of creatine and phosphocreatine were significantly lower in the parietal cortex of the patients. The lung
cancer patients were also characterized by greater fatigue scores (but not depression) prior to treatment when compared to controls. In
addition, the serum concentration of interleukin-6 (proinflammatory cytokine) was higher in patients compared to controls; and the
concentration of tumor-necrosis factor alpha ([TNF-α]) was positively correlated to the metabolic activity of the lung tumor as defined by
the 2-deoxy-2-(18F)fluoro-D-glucose (18FDG) positron emission tomography (PET) derived maximal standardized uptake values
(SUVmax). Finally, multivariate statistical modeling revealed that the concentration of N-acetyl-aspartate in the occipital was negatively
associated with [TNF-α]. In conclusion, our data demonstrate that the cerebral metabolic status of patients with lung cancer is changed
even prior to treatment. In addition, the association between inflammatory cytokines, SUVmax and [NAA] points towards interactions
between the cancer’s inherent metabolic activity, systemic subclinical inflammation and brain function. (IJCEM1202005).
Keywords: Lung cancer, proton magnetic resonance spectroscopy, brain, glutamate, proinflammatory cytokines, fatigue
Address all correspondence to:
Dr. Helene Benveniste
Health Sciences Center Level 4-060
Stony Brook University
Stony Brook, NY 11794-8480, USA.
Tel: (631) 444 2358; Fax: (631) 444 2907
E-mail: helene.benveniste@sbumed.org
