Biomedical subjects

Melanie T M Davidson

Publications and source records attributed to Melanie T M Davidson.

5 recordsLinked to original sources

PubMed2006

Establishing composition and structure of intact urinary calculi by x-ray coherent scatter for clinical laboratory investigations.

PURPOSE: Current urinary stone analysis techniques are limited in their abilities to simultaneously characterize composition and structure. Laboratory techniques such as IRS and x-ray diffractometry require small powdered samples for analysis, rendering composition results dependent on the choice of sample and its preparation. We investigated the application of x-ray CS analysis to identify topographic urinary stone composition ex vivo. CS is essentially a transmission based x-ray diffractometry method that depends on molecular structure and, therefore, can distinguish different compounds. Diagnostic x-ray equipment facilitates the examination of structural arrangements of minerals in intact calculi. MATERIALS AND METHODS: Tomographic images of intact calculi CS properties were acquired with a purposely built scanner. Composition is extracted from CS by fitting a library of common pure stone component CS signatures to those of the unknown sample in each image pixel. Two zones per stone were isolated (powdered) for IRS composition analysis for comparison with CS maps at these locations. Each stone was also independently analyzed for bulk composition by IRS analysis. RESULTS: CS composition maps revealed the spatial arrangement of minerals in intact calculi. IRS results showed good agreement with CS in the selected regions of interest. Bulk composition by IRS was noted to miss some important stone components, indicating that the choice of sample may skew composition results. CONCLUSIONS: CS from diagnostic x-rays can be used to identify structure and composition in mixed urinary calculi nondestructively. The tissue specific CS images presented support the development of CS analysis as a means of identifying stone composition characteristics in the laboratory.

Crystallography, X-Ray↗

PubMed2006

Bone-composition imaging using coherent-scatter computed tomography: assessing bone health beyond bone mineral density.

Quantitative analysis of bone composition is necessary for the accurate diagnosis and monitoring of metabolic bone diseases. Accurate assessment of the bone mineralization state is the first requirement for a comprehensive analysis. In diagnostic imaging, x-ray coherent scatter depends upon the molecular structure of tissues. Coherent-scatter computed tomography (CSCT) exploits this feature to identify tissue types in composite biological specimens. We have used CSCT to map the distributions of tissues relevant to bone disease (fat, soft tissue, collagen, and mineral) within bone-tissue phantoms and an excised cadaveric bone sample. Using a purpose-built scanner, we have measured hydroxyapatite (bone mineral) concentrations based on coherent-scatter patterns from a series of samples with varying hydroxyapatite content. The measured scatter intensity is proportional to mineral density in true g/cm3. Repeated measurements of the hydroxyapatite concentration in each sample were within, at most, 2% of each other, revealing an excellent precision in determining hydroxyapatite concentration. All measurements were also found to be accurate to within 3% of the known values. Phantoms simulating normal, over-, and under-mineralized bone were created by mixing known masses of pure collagen and hydroxyapatite. An analysis of the composite scatter patterns gave the density of each material. For each composite, the densities were within 2% of the known values. Collagen and hydroxyapatite concentrations were also examined in a bone-mimicking phantom, incorporating other bone constituents (fat, soft tissue). Tomographic maps of the coherent-scatter properties of each specimen were reconstructed, from which material-specific images were generated. Each tissue was clearly distinguished and the collagen-mineral ratio determined from this phantom was also within 2% of the known value. Existing bone analysis techniques cannot determine the collagen-mineral ratio in intact specimens. Finally, to demonstrate the in situ potential of this technique, the mineralization state of an excised normal cadaveric radius was examined. The average collagen-mineral ratio of the cortical bone derived from material-specific images of the radius was 0.53+/-0.04, which is in agreement with the expected value of 0.55 for healthy bones.

Algorithms↗

PubMed2005

Laboratory coherent-scatter analysis of intact urinary stones with crystalline composition: a tomographic approach.

Knowledge of urinary stone composition and structure provides important insights in guiding treatment and preventing recurrence. No current method can successfully provide information relating structure and composition of intact stones. We are developing a tomographic technique that uses measures of coherently scattered diagnostic x-rays to yield stone composition. Coherent-scatter (CS) properties depend on molecular structure and are, therefore, sensitive to material composition. Powdered, amorphous or polycrystalline materials with no significant orientation produce circularly symmetric CS patterns. However, in materials with preferred crystallite orientation, like urinary stones, bright spots in CS patterns are observed. This compromises a composition analysis based on comparing CS measurements from calculi to a library of CS signatures from powdered chemicals. We show that a computed tomographic reconstruction of CS measurements using filtered backprojection (CSCT) effectively eliminates bright spots and yields CS patterns equivalent to powdered materials. This allows for direct comparison with a powdered chemical reference library to establish composition. Validation is achieved through a tomographic CS analysis of an aluminium (Al) rod phantom. Much like calculi, CS patterns from a solid polycrystalline Al rod exhibit diffraction spots, absent in the ring-like Al powder CS pattern. We show that the reconstructed Al CS cross-section is equivalent to its powdered counterpart and results in clearly defined composition images. The potential of CSCT to identify stone composition is demonstrated through images of intact stones deemed chemically pure by infrared spectroscopy. Computed tomographic reconstruction of CS signals allowed the generation of composition maps, showing the distribution of stone components. These images provide strong evidence that current laboratory techniques risk missing critical stone components due to inadequate sampling. This is of particular importance since follow-up treatments are based on these composition analyses. CS analysis can distinguish common stone components and can provide topographic composition maps of intact stones. Such details offer invaluable clinical information regarding stone formation, treatment and follow-up, and thus support the development of CS analysis as a laboratory stone analysis technique.

Calcium↗

PubMed2005

Analysis of urinary stone components by x-ray coherent scatter: characterizing composition beyond laboratory x-ray diffractometry.

Monoenergetic x-ray diffraction (XRD) analysis is an established standard for the assessment of urinary stone composition. The inherent low energy of x-rays used (8 keV), however, restricts penetration depth and imposes a requirement for small powdered samples. A technique capable of producing detailed information regarding component structural arrangements in calculi non-destructively would provide clearer insights into causes of formation and subsequent growth and allow the selection of more appropriate courses of therapy. We describe a new method based on the detection of coherent scatter (CS) in stone components using polyenergetic x-rays (70 kVp) from diagnostic equipment. While the higher energy allows the analysis of intact calculi, the polyenergetic source causes an angular broadening of measured CS patterns. We show that it is possible to relate the polyenergetic (CS) and monoenergetic (XRD) measurements through a superposition integral of the monoenergetic XRD cross-section with a function representative of the polyenergetic spectrum used in CS. Experimentally acquired diffractometry cross-sections of the seven major urinary stone components were subjected to this operation, revealing good agreement of diffraction features with CS. Therefore, our CS analysis is sensitive to stone component structure, similar to conventional XRD analysis. This indicates that CS analysis can be used as a basis to classify urinary calculi by composition. The potential of identifying stone components non-destructively was demonstrated from a tomographic CS analysis of a stone-mimicking phantom. Tomographic composition maps were generated from CS patterns, showing the structural arrangement of multiple stone components within the phantom. CS analysis has the ability to detect components in the presence of many others. The ability to perform CS measurements in intact calculi would allow for the identification of stone structures critical to patient metaprophylaxis.

Algorithms↗

PubMed2002

Activated ras regulates the proliferation/apoptosis balance and early survival of developing micrometastases.

Mutant, activated ras oncogenes are found in many human cancers. Experimental studies have shown that Ras enhances metastatic ability in several cell types. However, the biological mechanisms by which Ras contributes to metastasis remain poorly understood. Our goal was to determine which steps in the formation of macroscopic metastases were affected by Ras. Green fluorescent protein-transfected NIH 3T3 and T24 H-ras-transformed (PAP2) fibroblasts were injected via mesenteric vein to target mouse liver. The proportion of cells that survived at each step of the metastatic process (at 60 min to 14 days after injection) were quantified. We found that Ras did not enhance the ability of cells to extravasate from liver sinusoids or to survive as solitary undivided cells in liver tissue. Furthermore, we found that a subset of cells from both cell lines initiated growth to form micrometastases by day 3. Only micrometastases formed by ras-transformed cells, however, persisted to form macroscopic metastases by day 14, whereas most NIH 3T3 micrometastases disappeared. We investigated this difference in maintenance of developing metastases by quantifying apoptosis and proliferation within the micrometastases. PAP2 metastases had a significantly higher proportion of proliferating cells as compared with apoptosing cells, whereas NIH 3T3 metastases had low proliferation and high apoptosis levels. Whereas the ability of Ras to induce vascular endothelial growth factor has suggested one way that Ras might affect metastatic ability (through induction of angiogenesis), our study provides in vivo evidence for a direct role for Ras in maintenance of metastatic growth via a shift in proliferation/apoptosis balance to favor metastatic growth.

3T3 Cells↗