We report the results of a study of human breast ductal carcinomas, conducted by using high resolution magic angle spinning proton magnetic resonance spectroscopy (HRMAS 1HMRS). This recently developed spectroscopic technique can measure tissue metabolism from intact pathological specimens and identify tissue biochemical changes, which closely correspond to tumor in vivo state.
Microheterogeneity is a routinely observed neuropathologic characteristic in brain tumor pathology. Although microheterogeneity is readily documented by routine histologic techniques, these techniques only measure tumor status at the time of biopsy or surgery and do not indicate likely tumor progression. A biochemical screening technique calibrated against pathologic standards would greatly assist in predicting tumor progression from its biological activity.
Publications of proton high resolution magic angle spinning (1H HRMAS) magnetic resonance spectroscopy (MRS) and its role in identification of metabolic markers for human cancer reported between 2005 and 2009 are reviewed according the anatomic sites of cancer: lung, breast, prostate, brain, colorectal, and cervical. Limited and insufficient screening options for the general public have indicated a need for more advanced tests that can identify and locate cancer at an early stage.
The development of high-resolution magic angle spinning (HR-MAS) NMR spectroscopy for intact tissue analysis and the correlations between the measured tissue metabolites and disease pathologies have inspired investigations of slow-spinning methodologies to maximize the protection of tissue pathology structures from HR-MAS centrifuging damage. Spinning sidebands produced by slow-rate spinning must be suppressed to prevent their complicating the spectral region of metabolites.
Accurate interpretation and correlation of tissue spectroscopy with pathological conditions requires disease-specific tissue metabolite databases; however, specimens for research are often kept in frozen storage for various lengths of time. Whether such frozen storage results in alterations to the measured metabolites is a critical but largely unknown issue.
Choline and the related compounds phosphocholine (PC) and glycerophosphocholine (GPC) are considered to be important metabolites in oncology. Past studies have demonstrated correlations linking the relative ratios and concentrations of these metabolites with the development and progression of cancer. Currently, in vivo and tissue ex vivo magnetic resonance spectroscopy methods have mostly centered on measuring the total concentration of these metabolites and have difficulty in differentiating between them.
The objective of this study was to compare ex vivo proton high-resolution magic angle spinning magnetic resonance spectra of intact tissue with those spectra obtained by solution (1)H NMR of brain extracts of the same sample. Sixteen brain tissue samples from simian immunodeficiency virus-infected rhesus macaques from both frontal cortex and putamen were evaluated by comparing brain metabolite quantities of N-acetylaspartate (NAA), choline-containing compounds (Cho), myo-inositol (MI), creatine (Cr), lactate (Lac), glutamate (Glu) and acetate (Ace).
High-resolution magic angle spinning (HRMAS) NMR spectroscopy has proven useful for analyzing intact tissue and permitting correlations to be made between tissue metabolites and disease pathologies. Extending these studies to slow-spinning methodologies helps protect tissue pathological structures from HRMAS centrifuging damage and may permit the study of larger objects. Spinning sidebands (SSBs), which are produced by slow spinning, must be suppressed to prevent the complication of metabolic spectral regions.
The previously observed improvement in spectral resolution of tissue proton NMR with high-resolution magic angle spinning (HRMAS) was speculated to be due largely to freeze-thawing artifacts resulting from tissue storage. In this study, 12 human prostate samples were analyzed on a 14.1T spectrometer at 3 degrees C, with HRMAS rates of 600 and 700 Hz. These samples were measured fresh and after they were frozen for 12-16 hr prior to thawing. The spectral linewidths measured from fresh and previously frozen samples were identical for all metabolites except citrate and acetate.
Statistical data from prostate cancer (PCa) clinics indicates that a large patient population discovered by annual prostate specific antigen (PSA) screening may have a latent form of the disease. However, current medical tests cannot differentiate slow from fast growing PCa, resulting in many unnecessary radical treatments and morbidities. It is thus necessary to find new screening tests that enable us to differentiate between fast- and slow-growing tumors.
