Hyperpolarized 13C Spectroscopy with Simple Slice-and-Frequency-Selective Excitation

Abstract

Hyperpolarized 13C nuclear magnetic resonance spectroscopy can characterize in vivo tissue metabolism, including preclinical models of cancer and inflammatory disease. Broad bandwidth radiofrequency excitation is often paired with free induction decay readout for spectral separation, but quantification of low-signal downstream metabolites using this method can be impeded by spectral peak overlap or when frequency separation of the detected peaks exceeds the excitation bandwidth. In this work, alternating frequency narrow bandwidth (250 Hz) slice-selective excitation was used for 13C spectroscopy at 7 T in a subcutaneous xenograft rat model of human pancreatic cancer (PSN1) to improve quantification while measuring the dynamics of injected hyperpolarized [1-13C]lactate and its metabolite [1-13C]pyruvate. This method does not require sophisticated pulse sequences or specialized radiofrequency and gradient pulses, but rather uses nominally spatially offset slices to produce alternating frequency excitation with simpler slice-selective radiofrequency pulses. Additionally, point-resolved spectroscopy was used to calibrate the 13C frequency from the thermal proton signal in the target region. This excitation scheme isolates the small [1-13C]pyruvate peak from the similar-magnitude tail of the much larger injected [1-13C]lactate peak, facilitates quantification of the [1-13C]pyruvate signal, simplifies data processing, and could be employed for other substrates and preclinical models.

Conversion of Hyperpolarized [1-13C]Pyruvate in Breast Cancer Cells Depends on Their Malignancy, Metabolic Program and Nutrient Microenvironment

“…This illustrates that the metabolic interpretations of k pl needs to be complemented with further metabolic and clinical parameters, for example metabolite levels in plasma from the patient, which may be affected by fasting or a metabolic syndrome. Moreover, to obtain more specific information on the metabolic status of the analyzed tissue for (not only) tumor diagnosis and therapeutic monitoring, the potentials of metabolic imaging using hyperpolarized 13 C-pyruvate could be enhanced by also using other hyperpolarized 13 C-metabolites of energy metabolism; these could include, for example, 13 C-fumarate [ 7 ], 13 C-lactate [ 73 ], or co-polarization of 13 C-pyruvate with 13 C-fumarate [ 74 ] or 13 C-urea [ 75 ].…”

Concentration‐dependent effects of dichloroacetate in type 2 diabetic hearts assessed by hyperpolarized [1‐13C]‐pyruvate magnetic resonance imaging

“…While hyperpolarized imaging is feasible and several groups have demonstrated myocardial hyperpolarized imaging, capable of identifying focal changes, 24,34,35 including with DCA, previous imaging experiments have demonstrated that these changes are homogeneous 36 . Therefore, we performed slice‐selective spectroscopy as a more robust, efficient, and appropriate technique for this study, as has been repeatedly used previously 37–39 . Finally, while intracellular pH (pH i ) can be derived from the H 13 CO 3 − / 13 CO 2 ratio, 40 the 13 CO 2 signal was below the detection level for this experimental setup.…”

“…36 Therefore, we performed slice-selective spectroscopy as a more robust, efficient, and appropriate technique for this study, as has been repeatedly used previously. [37][38][39] Finally, while intracellular pH (pH i ) can be derived from the H 13 CO 3 À / 13 CO 2 ratio, 40 the 13 CO 2 signal was below the detection level for this experimental setup. This precludes the direct investigation of a pH i change; if DCA reduced pH i then the estimated effects of treatment on bicarbonate would have been underestimated.…”

Spectrally selective bSSFP using off‐resonant RF excitations permits high spatiotemporal resolution 3D metabolic imaging of hyperpolarized [1‐13C]Pyruvate‐to‐[1‐13C]lactate conversion

“…For HP measurements, a thermally polarized [1‐ 13 C]lactate phantom (approx. 300 μL, 2.2 M, 1 mM Dotarem) was placed adjacent to the animal for frequency calibration and power adjustments 24 . The imaging setup was as described above for the in vitro imaging experiment, with a shim volume over the abdomen.…”

“…300 μL, 2.2 M, 1 mM Dotarem) was placed adjacent to the animal for frequency calibration and power adjustments. 24 The imaging setup was as described above for the in vitro imaging experiment, with a shim volume over the abdomen. Subjects were imaged twice within the same session, 1 h apart, with the same 3D bSSFP sequence as described above, except: (1) repetitions were acquired instead of averaged;…”