Cornelius von Morze

Purpose To develop a flexible, vendor‐neutral EPI sequence for hyperpolarized 13 C metabolic imaging. Methods An open‐source EPI sequence consisting of a metabolite‐specific spectral‐spatial RF excitation pulse and a customizable EPI readout was created using the Pulseq framework. To explore the flexibility of our sequence, we tested several versions of the sequence including a symmetric 3D readout with different spatial resolutions for each metabolite (1.0 cm 3 and 1.5 cm 3 ). A multichamber phantom constructed with a Shepp‐Logan geometry, containing two chambers filled with either natural abundance 13 C compounds or hyperpolarized (HP) [1– 13 C]pyruvate, was used to test each sequence. For experiments involving HP [1– 13 C]pyruvate, a single chamber was prefilled with nicotinamide adenine dinucleotide hydride and lactate dehydrogenase to facilitate the conversion of [1– 13 C]pyruvate to [1– 13 C]lactate. All experiments were performed on a Siemens Prisma 3T scanner. Results All the sequence variations localized natural‐abundance 13 C ethylene glycol and methanol to the appropriate compartment of the multichamber phantom. [1– 13 C]pyruvate was detectable in both chambers following the injection of HP [1– 13 C]pyruvate, whereas [1– 13 C]lactate was only found in the chamber containing nicotinamide adenine dinucleotide hydride and lactate dehydrogenase. The conversion rate from [1– 13 C]pyruvate to [1– 13 C]lactate ( k PL ) was 0.01 s −1 (95% confidence interval [0.00, 0.02]). Conclusion We have developed and tested a vendor‐neutral EPI sequence for imaging HP 13 C agents. We have made all of our sequence creation and image reconstruction code freely available online for other investigators to use.

Purpose To demonstrate hyperpolarization of 15 N‐caffeine and report exploratory findings as a potential probe of liver function and perfusion. Methods An amorphous formulation of [1,3‐ 15 N 2 ]caffeine was developed for hyperpolarization via dissolution dynamic nuclear polarization. Polarizer hardware was augmented to support monitoring of solid‐state 15 N MR signals during the buildup of hyperpolarization. Liquid state hyperpolarized 15 N MR signals were obtained in a preclinical 3T magnet by interfacing an external spectrometer console with home‐built RF surface coils. 15 N signal decay constants were estimated in H 2 O and in vivo in liver and brain regions of rats at 3 T. Decays were also measured at 9.4 T to assess the effect of B 0 , and in the presence of albumin to assess the impact of protein binding. Results Polarization levels of 3.5% and aqueous T 1 relaxation times of nearly 200 s were attained for both N1 and N3 positions at 3 T. Shorter apparent decay constants were observed in vivo, ranging from 25 s to 43 s, with modest extensions possible by exploiting competitive binding of iophenoxate with plasma albumin. Downstream products of caffeine could not be detected on in vivo 15 N‐MR spectra of the liver region, even with metabolic stimulation by ‐naphthoflavone treatment. Considering the high perfusion rate of brain, persistence of caffeine signal in this region is consistent with potential value as a perfusion imaging agent. Conclusion These results establish the feasibility of hyperpolarization of hyperpolarized 15 N‐caffeine, but further work is necessary to establish the role of this new agent to probe liver metabolism and perfusion.

Purpose Nonalcoholic fatty liver disease is an important cause of chronic liver disease. There are limited methods for monitoring metabolic changes during progression to steatohepatitis. Hyperpolarized 13 C MRSI (HP 13 C MRSI) was used to measure metabolic changes in a rodent model of fatty liver disease. Methods Fifteen Wistar rats were placed on a methionine‐ and choline‐deficient (MCD) diet for 1–18 weeks. HP 13 C MRSI, T 2 ‐weighted imaging, and fat‐fraction measurements were obtained at 3 T. Serum aspartate aminotransaminase, alanine aminotransaminase, and triglycerides were measured. Animals were sacrificed for histology and measurement of tissue lactate dehydrogenase (LDH) activity. Results Animals lost significant weight (13.6% ± 2.34%), an expected characteristic of the MCD diet. Steatosis, inflammation, and mild fibrosis were observed. Liver fat fraction was 31.7% ± 4.5% after 4 weeks and 22.2% ± 4.3% after 9 weeks. Lactate‐to‐pyruvate and alanine‐to‐pyruvate ratios decreased significantly over the study course; were negatively correlated with aspartate aminotransaminase and alanine aminotransaminase ( r = −[0.39–0.61]); and were positively correlated with triglycerides ( r = 0.59–0.60). Despite observed decreases in hyperpolarized lactate signal, LDH activity increased by a factor of 3 in MCD diet–fed animals. Observed decreases in lactate and alanine hyperpolarized signals on the MCD diet stand in contrast to other studies of liver injury, where lactate and alanine increased. Observed hyperpolarized metabolite changes were not explained by alterations in LDH activity, suggesting that changes may reflect co‐factor depletion known to occur as a result of oxidative stress in the MCD diet. Conclusion HP 13 C MRSI can noninvasively measure metabolic changes in the MCD model of chronic liver disease.