|
||||||||
|
RESEARCH BRIEFSLung Imaging Method Allows Visualization of AirwaysA new dynamic imaging technique described by Mitchell Albert, HMS assistant professor of radiology at Brigham and Women's Hospital; Angela Tooker, MIT graduate student; Kwan Soo Hong, HMS research fellow in radiology at BWH; and colleagues in the May Radiology promises to open new venues in research on lung diseases by creating clear MRI images of lung airways during breathing.
Alveoli in the lung periphery conceal most of the airways that feed them in static images, left. These airways are revealed by dynamic images, right. (Images courtesy of Hyperpolarized Noble Gas MRI Lab) "Traditional hyperpolarized helium lung images are taken during a breath hold. There are so many alveoli, you get a continuous-looking image of the peripheral airspaces of the lungs," said Albert. "We're using a dynamic sequence during inspiration of the gas in which the airways light up. Imaging of the airways with MRI hasn't been done before in humans." In this technique, helium gas is polarized by bombardment with laser-polarized rubidium atoms and maintained in a magnetic field. One liter of the gas mixed with nitrogen is pumped into a bag and rushed to the next room to a patient lying inside an MRI scanner. As the patient breathes in, the MRI scanner records two images per second to create a movie during one breath. The technique has promise for advancing knowledge of an array of lung conditions. Traditional static images do not provide good visualization of the blockages and constrictions of the airways caused by diseases like asthma. "Researchers and physicians have never actually seen the bronchoconstriction and airway closure in images," Albert said, "so they had to guess what they look like." --Jennifer Frazer
International Survey of Mental Illness Finds High Prevalence, Low Treatment Rates in U.S.The U.S. has higher prevalence and lower treatment rates of serious mental illness than a set of other developed countries, a recent study reports. The results appear in the May/June Health Affairs, a special edition of the journal focusing on international health care. Treatment in the U.S. also was found to be more strongly related to the ability to pay and less to the need for care than that in the other countries. The study analyzed data from community surveys developed in 1990 by the World Health Organization, with more than 22,000 respondents in Canada, Chile, Germany, the Netherlands, and the U.S. All these countries except the U.S. have universal health insurance. Despite differences in treatment, researchers found remarkably similar high proportions of the population with mental disorders (17 to 29 percent), early age of onset (mostly in childhood through the early adult years), high rates of chronic mental illness, and high levels of adverse effects on jobs, marriages, and other aspects of life, said corresponding author Ronald Kessler, professor of health care policy at HMS. "The consistency across countries is striking," he said. "Issue number one is that we can't wait as long as we do to get young people into treatment. Issue number two is that we have to do a better job of making sure patients are treated with the best available therapies once we get them into treatment." --Carol Cruzan Morton
New PCR Technology Makes Rapid Haplotyping PossibleA technology that was dreamed up when thinking of ways to combine blotting techniques with PCR has led to a rapid method of determining genotypes and haplotypes in individuals with genetic ailments. The technique--digital genotyping with polymerase colonies--was described online May 2 in the Proceedings of the National Academy of Sciences by George Church, HMS professor of genetics; Robi Mitra, an MIT doctoral student in his lab; and their colleagues. While genotypes describe the alleles at a given locus on both chromosomes in a pair, haplotypes describe the combination of alleles present at loci on the same chromosome. This can be important knowledge in identifying the basis for phenotypic differences in certain diseases; recent studies have shown that for conditions such as asthma, heroin dependence, and cystic fibrosis, a single nucleotide polymorphism (SNP) may not be so important as the combination of SNPs present on a single chromosome. Until now, no simple, rapid haplotype diagnostic technique was available. Polymerase colonies--or polonies-- are analogous to bacterial colonies and can be made from DNA at the concentrations in human saliva. At least two different PCRs are involved in genotyping polonies. Swabs taken from patients' mouths are mixed with acrylamide and plated directly onto special slides. The first PCR makes the DNA colonies, whose constituents are all descendants of single chromosomal fragments. The second PCR identifies the SNPs. A single-base-extension PCR is employed with special primers that flank the SNP. Because the primers covalently attach one of the amplified strands to the acrylamide matrix, the unattached strand can be removed by heating and washing the slide. The nucleotides in this reaction are fluorescent so the base can be identified from the color of the polony. Haplotyping is possible through a clever twist: add two sets of primers to the initial amplification mixture. Then two sets of polonies--each from different locations on the same chromosome--grow directly on top of one another. Two successive single-base-extension PCRs can be performed by stripping the fluorescence added by the first extension. When the colors of identical polonies are overlapped, the haplotype of each chromosome in the pair can be determined. "This method allows you to get more accurate genotype information on individual people, where you have less control over the genetics and more curiosity and health consequences," Church said. --Jennifer Frazer
NMR Technique Bares Chemistry of BoneTextbooks often refer to bone mineral crystals as calcium hydroxyapatite. But while synthetic hydroxyapatite resembles natural bone mineral, cells that remodel bone shun implants made of the synthetic material. And attempts to study the chemical composition of bone mineral have often turned up no trace of the hydroxyl ions found in hydroxyapatite. So the composition of bone mineral has remained in doubt. A team led by Jerome Ackerman, HMS associate professor of radiology at Massachusetts General Hospital, reports in the May 16 Science that they have used a method of NMR spectroscopy to solve the enduring riddle of whether or not bone mineral contains hydroxyl ions. The mineral crystals of bone are locked in a thick mesh of collagen fibers that have thwarted previous attempts to analyze them. "Collagen itself produces a huge NMR signal," said Ackerman, and this noise makes it difficult to separate collagen from crystal. Chemically removing the collagen matrix may alter the composition of the mineral left behind, which Ackerman said may explain the missing hydroxyl ions in previous analyses. The team, which included Gyunggoo Cho, HMS research fellow in radiology at MGH, and Yaotang Wu, HMS instructor in orthopedic surgery at Children's Hospital, used an NMR technique that records only the magnetic signatures of hydrogen atoms in the vicinity of a phosphorous atom, rather than all hydrogen atoms in a sample. Since collagen has only negligible levels of phosphorous compared to that in bone mineral, the technique gets down to the bone, so to speak, while eliminating the noise. Using this technique with samples from several mammals, including humans, the team was able to detect hydroxyl ions in fresh bone, ground at low temperature. However, they estimated that a sample of human bone contains about 20 percent of the hydroxyl ions that one would expect in a similar sample of hydroxyapatite, supporting the idea that the natural mineral is more complex. Ackerman said that while much of the limelight lately has turned toward the study of genes and proteins as the molecular basis for disease, "if you want to understand the molecular basis of osteoporosis, obviously the mineral crystals are very important." He added that the technique could also be used to study coronary calcium deposits in atherosclerosis. --Courtney Humphries |
