Magnetic resonance spectroscopy (MRS) has evolved from a strictly in vitro research tool for chemists to a powerful, non-invasive, diagnostic technique. However, the full potential of MRS-its ability to quantitatively assess metabolite content in vivo-is rarely achieved in practice. Assessment of metabolite content, commonly referred to as absolute quantification, requires accurate determination of the proportionality factor between the local magnetic field (B1m) generated by excited nuclei within the measurement volume and the integrated area of the corresponding spectral peak in the processed data. An impractical level of diligence is required to quantify or control all of the parameters that affect this proportionality factor. As a result, nearly all MRS results are presented in terms of arbitrary units or as ratios, which are difficult to interpret and of limited clinical value. We have developed a new technique, SPIRIT (Synthetic Peak Injection using a Radiation Immune Tickler coil), that could allow more practical and accurate quantification of MRS. We use a small, inductively coupled RF coil to inject an artificial signal, the pseudo-signal, in the main RF coil used to acquire the in vivo signal. The amplitude, frequency and line-width of the pseudo-signal are easily varied and are first set in proportion to a real peak corresponding to a known in vitro metabolite concentration. The same pseudo-signal is then injected during the data acquisition period of an in vivo measurement and used as a calibration factor to convert the real signals into units of metabolite concentration. The salient feature of the SPIRIT method is the use of inductive coupling to inject the pseudo-signal. Since inductive coupling is also the mechanism by which B1m couples to the main RF coil, any subsequent manipulations of the data that affect the proportionality factor- including coil loading conditions, gain of the receiver amplifiers, and data processing algorithms-have an equal effect on the real and pseudo-signals. This makes the proportionality factor immune to these data manipulations and substantially decreases the burden of the metabolite quantification process. We have built a prototype SPIRIT probe that uses a surface coil to excite and receive the in vivo signals. This simple coil was useful for demonstrating feasibility but, like all surface coils, it creates a nonuniform B1 field, which complicates the quantification process. In this project we will build two additional SPIRIT probes that create uniform B1 fields to excite and receive the metabolite signals, validate the method by comparison against biochemical assays of metabolite content in rat hind limb, and demonstrate the ability to accurately quantify changes in metabolite content in human skeletal muscle during physiological perturbations. Our project focuses on measurements in skeletal muscle but the methods could easily be transferred to other organs. Our goal is to validate a powerful new tool for noninvasive quantification of metabolite content that will allow researchers and clinicians access to the full potential of MRS.

Public Health Relevance

We have developed a new method of converting magnetic resonance spectroscopy (MRS) data into units of metabolite concentration. We propose to validate the method in animal studies and demonstrate its value in humans. Successful completion of the project could have widespread impact on a variety of diseases by providing researchers and clinicians with a more practical noninvasive tool for measuring metabolite concentration.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21EB008166-02
Application #
7845697
Study Section
Special Emphasis Panel (ZRG1-SBIB-J (90))
Program Officer
Liu, Guoying
Project Start
2009-05-15
Project End
2013-04-30
Budget Start
2010-05-01
Budget End
2013-04-30
Support Year
2
Fiscal Year
2010
Total Cost
$193,050
Indirect Cost
Name
University of Washington
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Park, Joshua; Wicki, Jacqueline; Knoblaugh, Sue E et al. (2015) Multi-parametric MRI at 14T for muscular dystrophy mice treated with AAV vector-mediated gene therapy. PLoS One 10:e0124914
Wang, Z; Halbert, C L; Lee, D et al. (2014) Elimination of contaminating cap genes in AAV vector virions reduces immune responses and improves transgene expression in a canine gene therapy model. Gene Ther 21:363-70
Feng, Shu; Chen, Daniel; Kushmerick, Martin et al. (2014) Multiparameter MRI analysis of the time course of induced muscle damage and regeneration. J Magn Reson Imaging 40:779-88
Lee, Donghoon; Marro, Kenneth; Mathis, Mark et al. (2014) In vivo absolute quantification for mouse muscle metabolites using an inductively coupled synthetic signal injection method and newly developed (1) H/(31) P dual tuned probe. J Magn Reson Imaging 39:1039-46
Lee, Donghoon; Thaler, Joshua P; Berkseth, Kathryn E et al. (2013) Longer T(2) relaxation time is a marker of hypothalamic gliosis in mice with diet-induced obesity. Am J Physiol Endocrinol Metab 304:E1245-50
Marro, Kenneth I; Lee, Donghoon; Shankland, Eric G et al. (2011) Synthetic signal injection using a single radiofrequency channel. J Magn Reson Imaging 34:1414-21
Lee, Donghoon; Marro, Kenneth; Shankland, Eric et al. (2010) Quantitative 19F imaging using inductively coupled reference signal injection. Magn Reson Med 63:570-3
Marro, Kenneth I; Lee, Donghoon; Shankland, Eric G et al. (2010) Quantitative in vivo magnetic resonance spectroscopy using synthetic signal injection. PLoS One 5:e15166
Wang, Zejing; Storb, Rainer; Lee, Donghoon et al. (2010) Immune responses to AAV in canine muscle monitored by cellular assays and noninvasive imaging. Mol Ther 18:617-24
Lee, Donghoon; Marcinek, David (2009) Noninvasive in vivo small animal MRI and MRS: basic experimental procedures. J Vis Exp :