Author: Li Liu, MD Affiliations: University of Pennsylvania Cancer Center Posted Date: January 9, 2000
The sensitivity of magnetic resonance imaging (MRI) for detection of soft-tissue tumors remains unchallenged. However, its specificity for characterizing the lesion type or grade is often suboptimal. The definitive diagnosis remains dependent on tissue biopsies. So, any techniques that would provide information that complements the sensitivity of the MRI exam and increases confidence in a non-invasive diagnosis would be a welcome addition to diagnostic imaging.
One such imaging modality is Magnetic resonance spectroscopy (MRS). Magnetic resonance spectroscopy was first introduced in the 1940s and rapidly became an indispensable structural analysis tool for analytical chemistry laboratories. Since clinical MRI became available in 1980s, MRS has been used as a platform for performing in vivo exams to obtain biochemical information that could complement the exquisite anatomic detail obtained by MRI.
The major physical principles that apply to MRI are also important with regard to MRS. MRI is a cross-sectional imaging technique utilizing strong magnetic fields and multiple radio-frequency pulses to generate an image with outstanding spatial resolution and tissue contrast. Certain nuclei have a magnetic moment (magnetic physical characteristics) because they are composed of an odd number of protons and neutrons. In the absence of an applied magnetic field, the nuclear magnetic moments point in random directions, so that there is no measurable net magnetization. When placed in a relatively large and highly homogeneous magnetic field, however, these nuclei attempt to align with the field and rotate, or spin, about the axis of the magnetic field. The most commonly imaged nucleus is hydrogen (1H). The signals emitted by hydrogen nuclei can be picked up and regenerated with modern computer techniques to create images. The signals from water, fat, and other hydrogen-containing molecules all combine to produce a single net signal from each voxel (a minute volume region in the tissue). In general, we have little ability to distinguish the relative contributions of each tissue type. MRS seeks to extract additional chemical shift information in both a qualitative and a quantitative manner to assess the heterogeneity of tissue. Additionally, MRS techniques probe the signals and chemical shift information from other nuclei of potential physiological interest (e.g., 31P, 19F).
MRS has been used in a variety of normal and pathological conditions. The research in this area has been very active, particularly with regard to neoplasms such as intracranial tumors, head and neck cancers, breast cancers, urologic cancers, sarcomas, and melanoma.
Adenosine triphosphate (ATP) is necessary for all life processes that require energy. 31P MRS can provide information concerning tissue energetics, phospholipid metabolism and intracellular pH. Metabolites of phospholipid represent precursors to membrane synthesis and breakdown products, respectively. Therefore, changes in MRS signal may be used as markers of cell proliferation to determine the grade of tumor. 1H MRS can provide information concerning neuronal density, membrane constituents, and metabolism of amino acid and glucose. Tumor spectra can be discerned easily from normal tissue using 1H MRS. 1H MRS can also be used to detect early radiation damage, either alone or in conjunction with PET scan.
The use of proton MRS of plasma as a serologic test for the detection of malignancy was first described in 1986. However, some early studies did not support the use of proton MRS as a clinically useful test for the diagnosis of head and neck malignancy.
The metabolic activity of breast tumors measured by MRS is greater than that of surrounding breast tissue. The biochemical information obtained from MRS can be used to characterize and distinguish disease and nondisease states for diagnostic and therapeutic purposes.
Some early studies suggested that the combined use of serum tumor markers, such as carcinoembryonic antigen (CEA) and CA19.9, and 1H MRS of plasma slightly improved accuracy in the diagnosis of pancreatic cancer. MRS is also used to analyze intratumoral pharmocokinetics of chemotherapy agents, such as 5-FU and gemcitabine .
Proton MRS in patients with prostate cancer has shown statistically significant higher choline levels and lower citrate levels in regions of cancer than in normal prostatic tissue. MRS can be used to differentiate among prostate cancer, benign prostatic hypertrophy (BPH) and necrosis when local recurrence is suspected.
Research in this area remains immature. Contamination with phospholipid metabolite signals from adjacent tissues is especially problematic.