Search

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 β $$ \beta $$ -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., (© 2024 International Society for Magnetic Resonance in Medicine.)

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., (© 2024 International Society for Magnetic Resonance in Medicine.)

Cholesterol ester storage disease (CESD) is a rare autosomal recessive lipid storage disorder associated with mutations of the gene encoding lysosomal acid lipase, manifestations of which include chronic liver disease and early atherosclerosis. Although normally presenting in childhood, severity is variable and the condition can occasionally remain undetected until middle age. Typical presentation is with asymptomatic hepatosplenomegaly and hyperlipidaemia, though the condition is probably underdiagnosed. Treatment is supportive and may include attention to cardiovascular risk factors. Phase I/II trials of enzyme replacement therapy are ongoing, but this approach remains experimental. We present the case of a 42-year-old woman diagnosed with CESD in childhood who ran an indolent course until re-presentation with cirrhotic hydrothorax. She underwent orthotopic liver transplantation but required re-transplantation for hepatic artery thrombosis. She remains well with excellent graft function 2 years later. Although atherosclerosis was apparent at assessment, and may have contributed to hepatic artery thrombosis, partial correction of the metabolic defect and restoration of liver function by transplantation together with ongoing medical therapy should permit reasonable survival over the longer term from both a liver and a vascular perspective. This is the first reported case of orthotopic liver transplantation for CESD in an adult, which was the only available option to improve survival. The case highlights the importance of monitoring patients with CESD through adulthood and suggests that liver replacement at a later stage may yet be indicated and remain of benefit.