Quo Vadis Hyperpolarized 13C MRI?

Over the last two decades, hyperpolarized 13C MRI has gained significance in both preclinical and clinical studies, hereby relying on technologies like PHIP-SAH (ParaHydrogen-Induced Polarization-Side Arm Hydrogenation), SABRE (Signal Amplification by Reversible Exchange), and dDNP (dissolution Dynamic Nuclear Polarization), with dDNP being applied in humans. A clinical dDNP polarizer has enabled studies across 24 sites, despite challenges like high cost and slow polarization. Parahydrogen-based techniques like SABRE and PHIP offer faster, more cost-efficient alternatives but require molecule-specific optimization. The focus has been on imaging metabolism of hyperpolarized probes, which requires long T1, high polarization and rapid contrast generation. Efforts to establish novel probes, improve acquisition techniques and enhance data analysis methods including artificial intelligence are ongoing. Potential clinical value of hyperpolarized 13C MRI was demonstrated primarily for treatment response assessment in oncology, but also in cardiology, nephrology, hepatology and CNS characterization. In this review on biomedical hyperpolarized 13C MRI, we summarize important and recent advances in polarization techniques, probe development, acquisition and analysis methods as well as clinical trials. Starting from those we try to sketch a trajectory where the field of biomedical hyperpolarized 13C MRI might go.

Hyperpolarised 13C-MRI using 13C-pyruvate in breast cancer: A review.

Tumour metabolism can be imaged with a novel imaging technique termed hyperpolarised carbon-13 (13C)-MRI using probes, i.e., endogenously found molecules that are labeled with 13C. Hyperpolarisation of the 13C label increases the sensitivity to a level that allows dynamic imaging of the distribution and metabolism of the probes. Dynamic imaging of [1-13C]pyruvate metabolism is of particular biological interest in cancer because of the Warburg effect resulting in the intratumoural accumulation of [1-13C]pyruvate and conversion to [1-13C]lactate. Numerous preclinical studies in breast cancer and other tumours have shown that hyperpolarised 13C-pyruvate has potential for metabolic phenotyping and response assessment at earlier timepoints than the current clinical imaging techniques allow. The clinical feasibility of hyperpolarised 13C-MRI after the injection of pyruvate in patients with breast cancer has now been demonstrated, with increased 13C-label exchange between pyruvate and lactate present in higher grade tumours with associated increased expression of the monocarboxylate transporter 1 (MCT1), the transmembrane transporter mediating intracellular pyruvate uptake, and lactate dehydrogenase (LDH) as the enzyme catalysing the conversion of pyruvate to lactate. Furthermore, a study in patients with breast cancer undergoing neoadjuvant chemotherapy suggested that early changes in 13C-label exchange can distinguish between patients who reach pathologic complete response (pCR) and those who do not. This review summarises the current literature on preclinical and clinical research on hyperpolarised 13C-MRI with [1-13C]-pyruvate in breast cancer imaging.

Simultaneous magnetic resonance imaging of pH, perfusion and renal filtration using hyperpolarized 13C-labelled Z-OMPD.

pH alterations are a hallmark of many pathologies including cancer and kidney disease. Here, we introduce [1,5-13C2]Z-OMPD as a hyperpolarized extracellular pH and perfusion sensor for MRI which allows to generate a multiparametric fingerprint of renal disease status and to detect local tumor acidification. Exceptional long T1 of two minutes at 1 T, high pH sensitivity of up to 1.9 ppm per pH unit and suitability of using the C1-label as internal frequency reference enables pH imaging in vivo of three pH compartments in healthy rat kidneys. Spectrally selective targeting of both 13C-resonances enables simultaneous imaging of perfusion and filtration in 3D and pH in 2D within one minute to quantify renal blood flow, glomerular filtration rates and renal pH in healthy and hydronephrotic kidneys with superior sensitivity compared to clinical routine methods. Imaging multiple biomarkers within a single session renders [1,5-13C2]Z-OMPD a promising new hyperpolarized agent for oncology and nephrology.