Halpern's Lab

Center for EPR Imaging in Vivo Physiology

Research Goals

In collaboration with researchers at the Unviersity of Denver and the University of Maryland, the Center for Electron Paramagnetic Resonance (EPR) Imaging in Vivo Physiology aims to create new imaging technologies in order to better visualize the tissues of living animals.  The EPR imaging technology under development by the Center has powerful implications for the treatment of cancers, strokes, peripheral vascular diseases and heart attacks.


The Center receives funding from the National Institute of Biomedical Imaging and Bioengineering (NIBIB), a part of the National Institutes of Health (NIH), as a Technology Development Resource. The Center assists other NIH-funded researchers with attaining the latest technology in the field of EPR imaging.

    Recent Publications

    From the Center's research in collaboration with the University of Denver and the University of Maryland, several peer-reviewed journal articles have been published. For a full list of publications, see the Center's website. In addition to these articles, the research team has registered several US patents for their innovations.

    Oxidative stress has been the object of considerable biological and biochemical investigation. Quantification has been difficult although the quantitative level of products of biological oxidations in tissues and tissue products has emerged as a widely used technique. The relationship between these products and the amount of oxidative stress is less clear. Imaging oxidative stress with electron paramagnetic resonance related magnetic resonance imaging, while not addressing the specific issue of quantification of initiating events, focuses on the anatomic specific location of the oxidative stress. Moreover, the relative quantification of oxidative stress of one location against another is possible, sharpening our understanding of oxidative stress. This promises to improve our understanding of oxidative stress and its deleterious consequences and enhance our understanding of the effectiveness of interventions to modulate oxidative stress and its consequences.

    Elas M, Ichikawa K and Halpern HJ, Oxidative Stress Imaging in Live Animals with Techniques Based on Electron Paramagnetic Resonance. Radiat Res. 2012. PubMed.

    X-band rapid-scan EPR spectra were obtained for dilute aqueous solutions of nitroxyl radicals (15)N-mHCTPO (4-hydro-3-carbamoyl-2,2,5,5-tetra-perdeuteromethyl-pyrrolin-1-(15)N-oxyl-d(12)) and (15)N-PDT (4-oxo-2,2,6,6-tetra-perdeuteromethyl-piperidinyl-(15)N-oxyl-d(16)). Simulations of spectra for (15)N-mHCTPO and (15)N-PDT agreed well with the experimental spectra. As the scan rate is increased in the rapid scan regime, the region in which signal amplitude increases linearly with B(1) extends to higher power and the maximum signal amplitude increases. In the rapid scan regime, the signal-to-noise for rapid-scan spectra was about a factor of 2 higher than for unbroadened CW EPR, even when the rapid scan spectra were obtained in a mode that had only 4% duty cycle for data acquisition. Further improvement in signal-to-noise per unit time is expected for higher duty cycles. Rapid scan spectra have higher bandwidth than CW spectra and therefore require higher detection bandwidths at faster scan rates. However, when the scan rate is increased by increasing the scan frequency, the increase in noise from the detection bandwidth is compensated by the decrease in noise due to increased number of averages per unit time. Because of the higher signal bandwidth, lower resonator Q is needed for rapid scan than for CW, so the rapid scan method is advantageous for lossy samples that inherently lower resonator Q.

    Mitchell DG, Quine RW, Tseitlin M, Eaton SS and Eaton GR, X-band rapid-scan EPR of nitroxyl radicals. J Magn Reson. 2012. 214(1):221-6. PubMed.

    Triarylmethanols - the direct precursors of persistent trityl radicals - are racemic mixtures of chiral three-bladed molecular propellers. Depending on bulkiness of aryl groups they exhibit various liabilities to interconversion, the half- life time of room temperature racemization varying in a range between 8.4 hours and 1.32 years. NOESY/EXSY experiment performed on two representative models strongly supports the two-ring flip mechanism for the configurational interchange.

    Tormyshev VM, Genaev AM, Sal'nikov GE, Rogozhnikova OY, Troitskaya TI, Trukhin DV, Mamatyuk VI, Fadeev DS and Halpern HJ, Triarylmethanols with Bulky Aryl Groups and the NOESY/EXSY Experimental Observation of a Two-Ring-Flip Mechanism for the Helicity Reversal of Molecular Propeller. Euro. J Organic Chem. 2012. 2012( 3) 623–629

    Polyphase continuous excitation based on the Frank sequence is suggested as an alternative to single pulse excitation in EPR. The method allows reduction of the source power, while preserving the excitation bandwidth of a single pulse. For practical EPR implementation the use of a cross-loop resonator is essential to provide isolation between the spin system and the resonator responses to the excitation. Provided that a line broadening of about 5% is acceptable, the cumulative turning angle of the magnetization vector generated by the excitation sequence can be quite large and can produce signal amplitudes that are comparable to that achieved with a higher power 90° pulse.

    Tseitlin M, Quine RW, Eaton SS and Eaton GR, Use of polyphase continuous excitation based on the Frank sequence in EPR. J Magn Reson. 2011. 211(2):221-7. PubMed.

    Optimization of nitroxides as probes for EPR imaging requires detailed understanding of spectral properties. Spin lattice relaxation times, spin packet line widths, nuclear hyperfine splitting, and overall lineshapes were characterized for six low molecular weight nitroxides in dilute deoxygenated aqueous solution at X-band. The nitroxides included 6-member, unsaturated 5-member, or saturated 5-member rings, most of which were isotopically labeled. The spectra are near the fast tumbling limit with T(1)∼T(2) in the range of 0.50-1.1 μs at ambient temperature. Both spin-lattice relaxation T(1) and spin-spin relaxation T(2) are longer for (15)N- than for (14)N-nitroxides. The dominant contributions to T(1) are modulation of nitrogen hyperfine anisotropy and spin rotation. Dependence of T(1) on nitrogen nuclear spin state m(I) was observed for both (14)N and (15)N. Unresolved hydrogen/deuterium hyperfine couplings dominate overall line widths. Lineshapes were simulated by including all nuclear hyperfine couplings and spin packet line widths that agreed with values obtained by electron spin echo. Line widths and relaxation times are predicted to be about the same at 250 MHz as at X-band.

    Biller JR, Meyer V, Elajaili H, Rosen GM, Kao JP, Eaton SS and Eaton GR, Relaxation times and line widths of isotopically-substituted nitroxides in aqueous solution at X-band. J Magn Reson. 2011. 212(2):370-7. PubMed.