Examples

Medical Student Research Project Proposal

 

Student:  Harvey E. Smith, Student Box 215, Class of 2002

Faculty Advisor:  Dr. Michael B. Smith, PhD, Department of Radiology, Chief, NMR

Expected Research Period:  May 20 - Aug 23, 1998

Objectives

To characterize the multiple T2 components of porcine articular cartilage.

Background

Articular cartilage consists of a structural matrix of proteoglycan and collagen that binds water via hydrogen bonding to anionic sites on the proteoglycan molecule, hydrophobic inclusion, and nonspecific hydrate formation. The mobility of water in cartilage is thus restricted, resulting in frictional drag as the water molecules are forced through the tissue. Energy is dissipated through the cartilage via this frictional drag. In osteoarthritis, there is an observed increase in total water content, concurrent with a degradation of the collagen network. Degradation of the extracellular matrix will increase the mobility of the water through the gel, resulting in a corresponding decrease in the efficacy of energy distribution, concurrently with an increase in total water content.

The degree to which water is bound to the extracellular matrix, and its partition coefficient with the surrounding synovial fluid, has been examined by diffusion experiments with tritiated water, resulting in several conflicting models. Current theories revolve around a partition coefficient close to unity, corresponding to the free exchange of all of the water with the surrounding synovial fluid, or an anisotropic model with the partition coefficient inversely related to depth from the articular surface, corresponding to the distribution of proteoglycans.

NMR provides a non-invasive method to determine the distribution of water in articular cartilage. T2 relaxation time is inversely related to the mobility of water, as less mobile water will more facilely dissipate transverse magnetization. The T2 profile of articular cartilage will thus provide a nondestructive means to characterize the nature in which water is bound to the extracellular matrix. The development of a noninvasive means of characterizing the partition of water in articular cartilage will provide a method through which degenerative changes can be quantified. Mosher et al. have demonstrated the feasibility of using a modified CPMG sequence to characterize multiple T2 components in articular cartilage.

Methods

Four millimeter diameter cartilage plugs will be obtained from the patella and tibial plateau of fresh porcine knees. The plugs will be stacked within a 5 mm NMR tube within a solenoid coil, oriented perpendicular to the Bo field within an Oxford 1.9T magnet interfaced to a Tecmag (Taurus) upgraded console. The T2 profiles will be generated using a 96-echo CPMG pulse sequence that samples a single point at the center of the spin-echo. The inter-echo delay will be incremented logarithmically from 60 us to 79 ms with a TR of 2 seconds and 128 signal averages. The total duration of the echo train will be 1.7 seconds. The T2 profiles will be calculated from a multi-component exponential decay using a non-linear least squares fit. The number of components in the T2 profile will be determined by the r2 of the fit.

Student's Responsibilities

  1. Review literature on NMR, specifically the classical description of the concepts as they pertain to transverse relaxation.
  2. Review literature on the composition of cartilage.
  3. Become familiar with the operation of the 1.9 T spectrometer
  4. Sample preparation, and data collection
  5. Numerical analysis of data
  6. Prepare and submit a final MSR project manuscript

 

Sponsor's Responsibilities

  1. Provide overall guidance in project development and implementation
  2. Provide training in the operation of the spectrometer, sample preparation, and in the numerical methods for data analysis
  3. Review draft and final MSR project manuscript

 

Signatures

Michael B Smith, PhD
Michael B. Smith, PhD

Harvey E. Smith
Harvey E. Smith

References

  1. Jaffe, Fredrick F. et. Al. Water Binding in the Articular Cartilage of Rabbits. The Journal of Bone and Joint Surgery. 56-A, 1974, 1031.
  2. Venn, M. and Maroudas, A. Chemical Composition and Swelling of Normal and Osteoarthritic Femoral Head Cartilage. Annals of the Rheumatic Diseases, 36, 1977, 121.
  3. Maroudas, A. and Schneiderman, R. Free and Exchangeable or Trapped and non-exchangeable Water in Cartilage. J Orthop Res. 5, 1987, 133.
  4. Torzilli, Peter A., et. al. Equilibrium Water partition in Articular Cartilage. Biorheology, 19, 1982, 519.
  5. Mankin, Henry J., et. al. Water Content and Binding in Normal and Osteoarthritic Human Cartilage. J. Bone and Joint Surg., 57-A, 1975, 76.
  6. Torzilli, Peter A. Influence of Cartilage Conformation on its Equilibrium Water Partition. J. Orthop Res. 3, 1985. 473.
  7. Callaghan, Paul T. Principles of Nuclear Magnetic Resonance Microscopy. Clarendon Press, 1995.
  8. Dardzinski, B., et al. Radiology. 205, 1997, 546.
  9. Dardzinski, B., et al. Radiology. 205, 1997, 546.
  10. Mosher, Timothy J. et al. Characterization of Multiple T2 Components in Articular Cartilage. Proceedings of the International Society for Magnetic Resonance in Medicine. 1997, 1331.
  11. Carr, H.Y. and Purcell, E.M. Phys. Rev. 94, 1954, 630.
  12. Meiboom, S. and Gill, D. Rev. Sci. lnstr. 29, 1959, 688.