Potential value of vertebral proton MR spectroscopy in determining bone weakness.

BACKGROUND AND PURPOSE: Increased fat content in vertebrae may indicate bone weakness. Vertebral proton MR spectroscopy ((1)H MRS) quantitatively measures vertebral fat relative to water. Thus, (1)H MRS measurements of percent fat fraction (%FF) and spectral line width (LW) of vertebral bone marrow may differ between subjects with and those without MR imaging evidence of weakened bone. METHODS: We measured %FF and LW in 22 subjects with (15 men and 7 women, aged 26 to 80 years) and 72 control subjects without (33 male and 39 female subjects, aged 15 to 87 years) MR findings of weakened bone, including prominent Schmorl's nodes, endplate depression, vertebral wedging, and vertebral compression fractures. In those with bone weakness, (1)H MRS data were sampled from an intact vertebra, usually L2. Data were analyzed for differences by age and sex. We compared the mean %FF and LW in subjects with and in those without bone weakness by use of Student's t test. RESULTS: The %FF increased linearly with age in the control subjects, ranging from 20.5% in the second and third decades of life to 49.4% in eighth or ninth decades of life. Across all age groups, male control subjects had a higher aggregate %FF than did female control subjects. Male control subjects tended to have a greater LW than did female control subjects, but differences between the sexes within or across age groups were not significant. Contrary to expectations, LW was greatest in the oldest control subjects and lowest among younger control subjects, but there were insufficient data points to make definitive conclusions. Overall, %FF was a relative 45% higher in subjects with weakened bone compared with control subjects (48.8 vs 33.6 [P <.001]). The subjects with evidence of vertebral bone weakness also had a higher overall mean LW (37 vs 29 Hz [P <.002]), but this finding is of uncertain importance. CONCLUSION: The %FF was significantly higher within the L2 vertebral body in 22 subjects with weakened bone compared with the control group, suggesting that it could serve as a measure of bone quality. The LW measurements did not yield meaningful conclusions.

Normal lumbar vertebrae: anatomic, age, and sex variance in subjects at proton MR spectroscopy--initial experience.

Fifty-seven subjects underwent proton magnetic resonance (MR) spectroscopy of the second lumbar vertebra to evaluate single-voxel and multivoxel techniques. Measurements included lipid-to-water ratios, lipid fractions, and line width. These data provide information about vertebral fat content. There was an age-dependent linear increase in fat content and sex dependence. A higher fat concentration was found in men. The observed spectra provide a basis for future study to determine clinical utility of vertebral proton MR spectroscopy.

2D CSI proton MR spectroscopy of human spinal vertebra: feasibility studies.

This report focuses on proton magnetic resonance spectroscopy (1H MRS) of spine vertebra acquired with two-dimensional chemical shift imaging (2D CSI), utilizing the stimulated echo acquisition mode (STEAM) sequence. Both validity and reproducibility studies were performed. To validate the 2D CSI method, its spectra were compared with those obtained with the single-voxel (SV) method. Five normal volunteers were scanned. The reproducibility of 2D CSI was examined by performing spectroscopy on two different occasions, on three normal volunteers. Data show that the STEAM 2D CSI technique results in MRI spectra comparable to those obtained with the STEAM SV method. 2D CSI offers significant time savings and convenient multi-voxel spectral analysis at a substantially higher signal-to-noise ratio. The 2D CSI method was then applied to a patient with a small vertebral hemangioma. The results demonstrated that the voxels containing the hemangioma exhibit different spectra than the neighboring voxels of the same vertebra. Additionally, a case of vertebral osteoporosis was investigated. Results showed a significant increase in the lipid-to-water ratio (LWR). It is suggested that 2D CSI may be powerful in identifying physiological as well as pathological changes of the bone marrow. Furthermore, covering a more extensive area of the vertebral body will maximize the chances of depicting a small focus of pathologic tissue. A more detailed bone marrow pattern was noticed in on one subject whose spectra show more lipid peaks.

Peripheral-type benzodiazepine receptor (PBR) in human breast cancer: correlation of breast cancer cell aggressive phenotype with PBR expression, nuclear localization, and PBR-mediated cell proliferation and nuclear transport of cholesterol.

Aberrant cell proliferation and increased invasive and metastatic behavior are hallmarks of the advancement of breast cancer. Numerous studies implicate a role for cholesterol in the mechanisms underlying cell proliferation and cancer progression. The peripheral-type benzodiazepine receptor (PBR) is an Mr 18,000 protein primarily localized to the mitochondria. PBR mediates cholesterol transport across the mitochondrial membranes in steroidogenic cells. A role for PBR in the regulation of tumor cell proliferation has also been shown. In this study, we examined the expression, characteristics, localization, and function of PBR in a battery of human breast cancer cell lines differing in their invasive and chemotactic potential as well as in several human tissue biopsies. Expression of PBR ligand binding and mRNA was dramatically increased in the highly aggressive cell lines, such as MDA-231, relative to nonaggressive cell lines, such as MCF-7. PBR was also found to be expressed at high levels in aggressive metastatic human breast tumor biopsies compared with normal breast tissues. Subcellular localization with both antibodies and a fluorescent PBR drug ligand revealed that PBR from the MDA-231 cell line as well as from aggressive metastatic human breast tumor biopsies localized primarily in and around the nucleus. This localization is in direct contrast to the largely cytoplasmic localization seen in MCF-7 cells, normal breast tissue, and to the typical mitochondrial localization seen in mouse tumor Leydig cells. Pharmacological characterization of the receptor and partial nucleotide sequencing of PBR cDNA revealed that the MDA-231 PBR is similar, although not identical, to previously described PBR. Addition of high affinity PBR drug ligands to MDA-231 cells increased the incorporation of bromodeoxyuridine into the cells in a dose-dependent manner, suggesting a role for PBR in the regulation of MDA-231 cell proliferation. Cholesterol uptake into isolated MDA-231 nuclei was found to be 30% greater than into MCF-7 nuclei. High-affinity PBR drug ligands regulated the levels of cholesterol present in MDA-231 nuclei but not in MCF-7. In addition, the PBR-dependent MDA-231 cell proliferation was found to highly correlate (r = -0.99) with the PBR-mediated changes in nuclear membrane cholesterol levels. In conclusion, these data suggest that PBR expression, nuclear localization, and PBR-mediated cholesterol transport into the nucleus are involved in human breast cancer cell proliferation and aggressive phenotype expression, thus participating in the advancement of the disease.