Shreefal Mehta

Rensselaer Polytechnic Institute, Biomedical Engineering, Faculty Member

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Bone biomechanics research on non destructive ultrasound reflectometry, Tissue engineering 3D tissue culture, entrepreneurship, BioBusiness, Materials and energy commercialization
Address: Albany, New York, United States

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Bone material ultrasound velocity is predictive of whole bone strength

Ultrasound in Medicine and Biology, 2001

In humans, bone strength is assessed indirectly by the noninvasive measurement of structure or ma... more In humans, bone strength is assessed indirectly by the noninvasive measurement of structure or mass. Recent clinical application of an ultrasonic critical-angle reflectometry technique (UCR) has demonstrated the measurement of the regional and directional distribution of mechanical stiffness. This study investigates the specific question: are these measurements of a local material level property predictive of the strength of whole bone? Maximum values of pressure wave velocity and breaking strength were recorded at two locations (midshaft and base of neck) on rat femurs from growing rats. The results demonstrate a strong empirical relationship between material-level ultrasound (US) velocity and whole bone mechanical strength. However, the US velocity at a specific bone site can be used to assess bone strength at that site only, explaining discrepancies in other published studies that negate a relationship between strength and US velocity. The results indicate an important role for US velocity measurement in clinical evaluation of bone health.

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Ultrasound critical-angle reflectometry (UCR): a new modality for functional elastometric imaging

Physics in Medicine and Biology, 1997

This paper discusses the measurement of velocity in a solid based on the analysis of the amplitud... more This paper discusses the measurement of velocity in a solid based on the analysis of the amplitude and phase of ultrasound waves reflected by a solid, a technique called ultrasound critical-angle reflectometry (UCR). To this end, the complete formulation of ultrasound wave reflection and refraction from a liquid - solid interface is described. Differences between this formulation and previously published ones are briefly discussed. Based on this analysis it is in particular possible to measure by this technique not only pressure but also, for the first time in such studies, shear wave velocities, an experimentally confirmed result. The measurement of the complete stiffness matrix of a transversely isotropic solid, specifically cortical bone, by applying UCR elastometry to any point on the solid's surface is demonstrated. Finally this method is extended to functional elastometric imaging. The techniques presented in this paper offer new opportunities for applications of UCR imaging to the assessment of bone metabolism, formation and disease and also to the analysis of composite materials in general.

Measurement of shear-wave velocity by ultrasound critical-angle reflectometry (UCR

Ultrasound in Medicine and Biology, 1997

There exists a growing body of research that relates the measurement of pressure-wave velocity in... more There exists a growing body of research that relates the measurement of pressure-wave velocity in bone to different physiological conditions and treatment modalities. The shear-wave velocity has been less studied, although it is necessary for a more complete understanding of the mechanical properties of bone. Ultrasound critical-angle reflectometry (UCR) is a noninvasive and nondestructive technique previously used to measure pressure-wave velocities both in vi&o and in vim. This note describes its application to the measurement of shear-wave velocity in bone, whether directly accessible or covered by soft tissue. 0 1997 World Federation for Ultrasound in Medicine & Biology.

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Effects of high levels of fluoride on bone formation: An in vitro model system

by Shreefal Mehta and Berenice Reed

Biomaterials, 1995

In order to develop an in vitro model for the study of the effects of different agents on biomine... more In order to develop an in vitro model for the study of the effects of different agents on biomineralization, a three-dimensional cell culture system was investigated at different levels of fluoride. Rat fetal osteoblasts were seeded onto collagen discs and maintained in a culture medium for 40 days. Results showed that, at 40 days, the cultured matrices had a Ca:P ratio, mineral content and Fourier transform infrared (FTIR) spectrum that were close to those seen for normal rat bone. Viable cells, observed by light microscopy, were present in the matrix at 40 days. The formation of a mineralized matrix in this experimental set-up provided a model for exploring in vitro the effects of high levels of fluoride on bone. The fluoride content of the mineral formed in the cultures showed a dose-dependent increase in fluoride content with time. Also, an increase in the crystallinity of the apatite in the presence of fluoride, was observed by FTIR. The Ca:P ratio and percentage mineral by weight showed no apparent differences among the groups. The three-dimensional model used for this study has the potential to be a powerful tool in the study of time-dependent effects of drugs and other factors on osteoblast cell functions and subsequently on matrix mineralization.

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Reflection Ultrasound Velocities and Histomorphometric and Connectivity Analyses: Correlations and Effect of SlowRelease Sodium Fluoride

by Shreefal Mehta and Khashayar Sakhaee

Journal of Bone and Mineral Research, 1997

To better understand how structural and functional bone properties contribute to the changes in b... more To better understand how structural and functional bone properties contribute to the changes in bone biomechanical properties revealed by ultrasound critical angle reflectometry (UCR) analysis, we measured both UCR velocities and histomorphometric properties in bone biopsy specimens from 33 osteoporotic patients before and following intermittent slow-release sodium fluoride (SRNaF) and continuous calcium citrate administration. Mean skeletal fluoride exposure was 17 months, and mean skeletal fluoride content was 0.203 ± 0.088 SD% bone ash. Intermittent SRNaF and continuous calcium citrate promoted significant increases in trabecular thickness (122 ± 18 SDμm to 131 ± 20, p = 0.020), mineral apposition rate (0.79 ± 0.26 to 1.05 ± 0.40 μm/day, p = 0.014), and a significant decline in eroded surface (3.9 ± 1.6 to 2.8 ± 1.4%, p = 0.002). There were also significant increases in node number (0.193 ± 0.100 to 0.368 ± 0.245, p < 0.01) and node-to-node strut length (0.076 ± 0.087 to 0.191 ± 0.173, p < 0.01) relative to total cancellous area. Cortical UCR velocity did not change but cancellous velocity significantly increased by 97 m/s following therapy (p = 0.0005). When compared against the significant changes in bone histomorphometry and connectivity, the sum of both cancellous and cortical ultrasound velocities was significantly correlated with node number/area (R2 = 0.305, p < 0.0001) and node-to-node strut length/area (R2 = 0.372, p < 0.0001) and to a lesser extent with mineral apposition rate (R2 = 0.106, p = 0.032). Multiple regression analysis demonstrated that 40% of the variance in the sum of the UCR velocities can be accounted for by the variability in these histomorphometric and connectivity parameters. There were no significant correlations between the sum of cortical and cancellous ultrasound velocities and cancellous bone volume (R2 = 0.014, p = 0.533), trabecular thickness (R2 = 0.012, p = 0.47), or bone mineral density (R2 = 0.003, p = 0.80). These observations indicate that velocity measurements with the UCR methodology show an improvement in bone elasticity associated, in part, with an improvement in the rate of bone mineralization and an improvement in bone quality at the structural level as shown by microarchitecture.

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Bone Material Elasticity in a Murine Model of Osteogenesis Imperfecta

Connective Tissue Research, 1999

To investigate the source of bone brittleness in the disease osteogenesis imperfecta (OI), biomec... more To investigate the source of bone brittleness in the disease osteogenesis imperfecta (OI), biomechanical properties have been measured in the femurs from a homozygous (oim/oim) mutant mouse model of OI, its heterozygous littermates, and wild-type animals. The novel technique of ultrasound critical-angle reflectometry (UCR) was used to determine bone material elasticity matrix from measurements of the pressure and shear wave velocity at different orientations about selected points of the bone specimens. This nondestructive method is the only available means for obtaining measurements of this nature from a single surface. The ultrasound pressure wave velocity showed an increased isotropy in the homozygous compared to the wild-type specimens. This was reflected in a significant decrease in the principal elastic modulus measured along the length of the oim/oim bones (E33) while the modulus along the width (E11) did not change significantly, compared to wild-type specimens. The Poisson&#39;s ratio, v12, also had a significantly increased value in oim/oim bones. Measurements of these parameters in heterozygous animals generally fell between those from homozygous and control mice. The differences in the elasticity components in oim/oim bones indicate an altered stress distribution and a modified elastic response to loads, compared to normal bone.

Biostatistics: the hidden path to life science innovation

This exploratory paper investigates the infrastructure for life-science-based new product develop... more This exploratory paper investigates the infrastructure for life-science-based new product development. The practice of biostatistics has long been seen as a crucial element of the regulatory process for approving the release of new drugs and medical devices, but the authors hypothesize that it serves a larger role in the new product development process in pharmaceutical and biotechnology firms. To this end, they focus on the management of Biostatistics and related know how such as data mining in the discovery, testing, and commercialization of new products. Their results are drawn from a number of in-depth case studies of biostatistical practices in a variety of firms engaged in life-science product development. The findings point to the importance of biostatistics in providing both technical and strategic information. To the extent that Biostatistics is managed as a learning system, it is critical for building core capability and enabling resource configurations that create value

Awakening the dragon's breath: biostatistics, competency and competition in the pharmaceutical industry

Photodiagnosis and Photodynamic Therapy, 2003

Innovations in chemistry and biology have generated multiple products and built significant reven... more Innovations in chemistry and biology have generated multiple products and built significant revenue streams in the pharmaceutical industry. However, the complex and multi-disciplinary process of drug discovery and drug development makes it difficult to identify specific core competencies within a company. There is a need to better identify and manage sources of innovation that lead to new markets as ever-increasing investments in R&D have recently been accompanied by mediocre success in new product introduction. Additionally, outsourcing of clinical research and even early-stage discovery research continues to increase, creating a need to better define core competencies for strategic management decisions in pharmaceutical innovation In this context, we investigated the possible role that biostatistics -a key competence-could play in innovation in the drug development process. A sampling of case interviews from biostatisticians and executives in the pharma industry indicate that biostatisticians do contribute to innovation in the drug development process. Data gathered from contract research companies in the pharma industry suggests that outsourcing practices in the pharmaceutical industry increasingly include the outsourcing of biostatistics capabilities. We conclude that pharmaceutical companies should consider directing their management and outsourcing practices to retain and gain novel innovation through biostatistics.

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