Sensitivity enhancement for detection of hyperpolarized 13 C MRI probes with 1 H spin coupling introduced by enzymatic transformation in vivo

Abstract

Purpose: Although ¹ H spin coupling is generally avoided in probes for hyperpolarized (HP) ¹³ C MRI, enzymatic transformations of biological interest can introduce large ¹³ C-¹ H couplings in vivo. The purpose of this study was to develop and investigate the application of ¹ H decoupling for enhancing the sensitivity for detection of affected HP ¹³ C metabolic products.

Methods: A standalone ¹ H decoupler system and custom concentric ¹³ C/¹ H paddle coil setup were integrated with a clinical 3T MRI scanner for in vivo ¹³ C MR studies using HP [2-¹³ C]dihydroxyacetone, a novel sensor of hepatic energy status. Major ¹³ C-¹ H coupling J_CH = ∼150 Hz) is introduced after adenosine triphosphate-dependent enzymatic transformation of HP [2-¹³ C]dihydroxyacetone to [2-¹³ C]glycerol-3-phosphate in vivo. Application of WALTZ-16 ¹ H decoupling for elimination of large ¹³ C-¹ H couplings was first tested in thermally polarized glycerol phantoms and then for in vivo HP MR studies in three rats, scanned both with and without decoupling.

Results: As configured, ¹ H-decoupled ¹³ C MR of thermally polarized glycerol and the HP metabolic product [2-¹³ C]glycerol-3-phosphate was achieved at forward power of approximately 15 W. High-quality 3-s dynamic in vivo HP ¹³ C MR scans were acquired with decoupling duty cycle of 5%. Application of ¹ H decoupling resulted in sensitivity enhancement of 1.7-fold for detection of metabolic conversion of [2-¹³ C]dihydroxyacetone to HP [2-¹³ C]glycerol-3-phosphate in vivo.

Conclusions: Application of ¹ H decoupling provides significant sensitivity enhancement for detection of HP ¹³ C metabolic products with large ¹ H spin couplings, and is therefore expected to be useful for preclinical and potentially clinical HP ¹³ C MR studies. Magn Reson Med 80:36-41, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Keywords: decoupling; dihydroxyacetone; dynamic nuclear polarization.

FIG. 1

Biochemical conversion of DHA to G3P in vivo. Position of the HP ¹³C label is indicated by stars.

FIG. 2

Photographs of custom ¹³C/¹H paddle coil used for ¹H-decoupled ¹³C MRI experiments. a: Coil exterior and cabling. b: Coil internals consisting of concentric octagonal ¹H (inner) and ¹³C (outer) elements, with key components labeled by arrows.

FIG. 3

Simplified schematic depiction of standalone accessory ¹H decoupler operation in conjunction with clinical 3T scanner used for HP ¹³C MRI. Major components include (in electronics room adjacent to scanner): PC controller, electronic signal generator (ESG), transistor-transistor logic (TTL) trigger signal from system exciter board, 2-kW peak RF amplifier, and low-and high-power filters; and in scanner room: concentric ¹H (outer) and ¹³C (inner, with passive ¹H blocking) coil elements, bandpass (BP) filter on ¹³C channel installed between ¹³C coil and ¹³C transmit-receive (T/R) switch.

FIG. 4

Multinuclear RF coil setup for in vivo ¹H-decoupled HP [2-¹³C]DHA scans in rats (a) and comparison of results with and without ¹H decoupling (b). a: Octagonal ¹H (outer) and ¹³C (inner) coil traces are shown overlaid on a standard coronal anatomic localizer image acquired using the paddle’s ¹H channel. b: ¹³C MR spectra (magnitude) acquired in the clinical 3T MRI scanner with (right column) and without (left column) ¹H decoupling. Top row: Comparison of thermally polarized, nonenriched glycerol phantom spectra. Bottom row: Summed dynamic spectra from a pair of back-to-back HP [2-¹³C]DHA experiments in one rat.

FIG. 5

Dynamics of HP [2-¹³C]DHA spectra in one rat, for the cases of no ¹H decoupling (a) and ¹H-decoupled (b). The temporal dynamic spacing was 3 s, starting 20 s after the start of injection of HP [2-¹³C]DHA. Magnitude NMR data are shown, scaled to approximate signal-to-noise ratio level.