We describe a new method for quantitative imaging of strain and elastic modulus distributions in soft tissues. The method is based on external tissue compression, with subsequent computation of the strain profile along the transducer axis, which is derived from cross-correlation analysis of pre- and post-compression A-line pairs. The strain profile can then be converted to an elastic modulus profile by measuring the stresses applied by the compressing device and applying certain corrections for the nonuniform stress field. We report initial results of several phantom and excised animal tissue experiments which demonstrate the ability of this technique to quantitatively image strain and elastic modulus distributions with good resolution, sensitivity and with diminished speckle. We discuss several potential clinical uses of this technique.
The sensitivity and selectivity of UV-excited resonance Raman spectroscopy indicate that this technique may be useful in studying certain biochemical changes in cells, especially changes in DNA that occur during the development of cancer. To determine whether this technique can distinguish normal from malignant cells, we have measured UV resonance Raman spectra at 257.26 nm excitation of suspensions of normal and malignant cultured breast and cervical cells. Samples were excited with the use of an intracavity doubled argon-ion laser, and the spectra were recorded with a single grating spectrograph and a liquid nitrogen-cooled charge-coupled device. Cell spectra obtained closely resembled that of DNA, with peaks around 1330, 1480, and 1580 cm−1, due to the nucleotide bases. In addition to these, the uracil base in RNA provides a peak at 1230 cm−1. Strong tryptophan and tyrosine contributions appear in the 1520–1670 cm−1 range. The ratios of Raman spectral peaks 1480/1614 cm−1 and 1480/1540 cm−1, which are sensitive to the concentration of nucleic acids relative to cell proteins, were found to be higher in malignant cells than in normal cells. Normal and malignant cells could also be differentiated by using the ratio at 1330/1480 cm−1. This difference may be the result of decreased hypochromism due to changes in stacking of the purine bases. Changes in relative amounts of RNA may also contribute to this ratio. The results of this pilot study indicate that there may be significant differences in the UV resonance Raman spectra of normal and cancerous cells. These differences may be related to changes in nucleotide/protein concentrations in the cell, as well as changes in the vibrational structure of the nucleic acids associated with the malignant cell phenotype.
We describe a new model of graduate education in bioengineering innovation and design- a year long Master's degree program that educates engineers in the process of healthcare technology innovation for both advanced and low-resource global markets. Students are trained in an iterative "Spiral Innovation" approach that ensures early, staged, and repeated examination of all key elements of a successful medical device. This includes clinical immersion based problem identification and assessment (at Johns Hopkins Medicine and abroad), team based concept and business model development, and project planning based on iterative technical and business plan de-risking. The experiential, project based learning process is closely supported by several core courses in business, design, and engineering. Students in the program work on two team based projects, one focused on addressing healthcare needs in advanced markets and a second focused on low-resource settings. The program recently completed its fourth year of existence, and has graduated 61 students, who have continued on to industry or startups (one half), additional graduate education, or medical school (one third), or our own Global Health Innovation Fellowships. Over the 4 years, the program has sponsored 10 global health teams and 14 domestic/advanced market medtech teams, and launched 5 startups, of which 4 are still active. Projects have attracted over US$2.5M in follow-on awards and grants, that are supporting the continued development of over a dozen projects.
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