13C Imaging Research Articles

Dual-Tuned Coaxial-Transmission-Line RF Coils for Hyperpolarized 13C and Deuterium 2H Metabolic MRS Imaging at Ultrahigh Fields.

Information on the metabolism of tissues in healthy and diseased states plays a significant role in the detection and understanding of tumors, neurodegenerative diseases, diabetes, and other metabolic disorders. Hyperpolarized carbon-13 magnetic resonance imaging (13C-HPMRI) and deuterium metabolic imaging (2H-DMI) are two emerging X-nuclei used as practical imaging tools to investigate tissue metabolism. However due to their low gyromagnetic ratios (ɣ13C = 10.7 MHz/T; ɣ2H = 6.5 MHz/T) and natural abundance, such method required a sophisticated dual-tuned radiofrequency (RF) coil. Here, we report a dual-tuned coaxial transmission line (CTL) RF coil agile for metabolite information operating at 7T with independent tuning capability. The design analysis has demonstrated how both resonant frequencies can be individually controlled by simply varying the constituent of the design parameters. Numerical results have demonstrated a broadband tuning range capability, covering most of the X-nucleus signal, especially the 13C and 2H spectra at 7T. Furthermore, in order to validate the feasibility of the proposed design, both dual-tuned 1H/13C and 1H/2H CTLs RF coils are fabricated using a semi-flexible RG-405 .086" coaxial cable and bench test results (scattering parameters and magnetic field efficiency/distribution) are successfully obtained. The proposed dual-tuned RF coils reveal highly effective magnetic field obtained from both proton and heteronuclear signal which is crucial for accurate and detailed imaging. The successful development of this new dual-tuned RF coil technique would provide a tangible and efficient tool for ultrahigh field metabolic MR imaging.

13C MRI of hyperpolarized pyruvate at 120 µT

Nuclear spin hyperpolarization increases the sensitivity of magnetic resonance dramatically, enabling many new applications, including real-time metabolic imaging. Parahydrogen-based signal amplification by reversible exchange (SABRE) was employed to hyperpolarize [1-13C]pyruvate and demonstrate 13C imaging in situ at 120 µT, about twice Earth’s magnetic field, with two different signal amplification by reversible exchange variants: SABRE in shield enables alignment transfer to heteronuclei (SABRE-SHEATH), where hyperpolarization is transferred from parahydrogen to [1-13C]pyruvate at a magnetic field below 1 µT, and low-irradiation generates high tesla (LIGHT-SABRE), where hyperpolarization was prepared at 120 µT, avoiding magnetic field cycling. The 3-dimensional images of a phantom were obtained using a superconducting quantum interference device (SQUID) based magnetic field detector with submillimeter resolution. These 13C images demonstrate the feasibility of low-field 13C metabolic magnetic resonance imaging (MRI) of 50 mM [1-13C]pyruvate hyperpolarized by parahydrogen in reversible exchange imaged at about twice Earth’s magnetic field. Using thermal 13C polarization available at 120 µT, the same experiment would have taken about 300 billion years.

Advanced Hyperpolarized 13C Metabolic Imaging Protocol for Patients with Gliomas: A Comprehensive Multimodal MRI Approach.

This study aimed to implement a multimodal 1H/HP-13C imaging protocol to augment the serial monitoring of patients with glioma, while simultaneously pursuing methods for improving the robustness of HP-13C metabolic data. A total of 100 1H/HP [1-13C]-pyruvate MR examinations (104 HP-13C datasets) were acquired from 42 patients according to the comprehensive multimodal glioma imaging protocol. Serial data coverage, accuracy of frequency reference, and acquisition delay were evaluated using a mixed-effects model to account for multiple exams per patient. Serial atlas-based HP-13C MRI demonstrated consistency in volumetric coverage measured by inter-exam dice coefficients (0.977 ± 0.008, mean ± SD; four patients/11 exams). The atlas-derived prescription provided significantly improved data quality compared to manually prescribed acquisitions (n = 26/78; p = 0.04). The water-based method for referencing [1-13C]-pyruvate center frequency significantly reduced off-resonance excitation relative to the coil-embedded [13C]-urea phantom (4.1 ± 3.7 Hz vs. 9.9 ± 10.7 Hz; p = 0.0007). Significantly improved capture of tracer inflow was achieved with the 2-s versus 5-s HP-13C MRI acquisition delay (p = 0.007). This study demonstrated the implementation of a comprehensive multimodal 1H/HP-13C MR protocol emphasizing the monitoring of steady-state/dynamic metabolism in patients with glioma.

Efficacy of convection enhanced delivery of MTX110 (soluble panobinostat) in preclinical Diffuse Intrinsic Pontine Glioma models using metabolic hyperpolarized 13C imaging

BackgroundDiffuse intrinsic pontine glioma (DIPG) usually occurs in children and has poor outcomes despite treatment. Large drug screens have identified the pan-histone deacetylate inhibitor panobinostat as a promising agent, however clinical response might be hampered by limited blood brain barrier penetration. Hyperpolarized 13C magnetic resonance (MR) metabolic imaging has successfully been applied to non-invasively assess metabolic activity of cancer therapies. Here, we use in vitro and in vivo DIPG models to validate the therapeutic efficacy of MTX110, an aqueous form of panobinostat delivered by convection enhanced delivery (CED) and apply metabolic imaging. MethodsMTX110 inhibitory effect was assessed in 11 DIPG cell lines. Caspase 3/7 levels were measured to assess mode of cell death. FACS analysis was utilized to determine impact on cell cycle. Hyperpolarized 13C imaging determined changes in pyruvate and lactate levels after treatment. In vivo activity of CED of MTX110 was assessed in a patient-derived xenograft rat model and tissue half-life of MTX110 was determined using mass spectrometry. ResultsMTX110 showed similar IC50 to panobinostat ranging from 5.34 nM and 47.96 nM. Anti-proliferative effects of MTX110 are mediated by G1 cell cycle arrest and subsequent apoptosis. Drug treatment led to reduced pyruvate to lactate conversion. CED of MTX110 significantly prolonged survival of tumor-bearing rats (p = 0.0372) with no signs of systemic toxicity. Tissue half-life after single CED of MTX110 is 2 h. ConclusionsOur results demonstrate that CED of MTX110, has potent antitumor activity with limited systemic toxicity and that hyperpolarized 13C imaging is able to assess metabolic impact.

X-nuclear MRS and MRI on a standard clinical proton-only MRI scanner

In light of the growing interest in-vivo deuterium metabolic imaging, hyperpolarized 13C, 15N, 3He, and 129Xe imaging, as well as 31P spectroscopy and imaging in large animals on clinical MR scanners, we demonstrate the use of a (radio)frequency converter system to allow X-nuclear MR spectroscopy (MRS) and MR imaging (MRI) on standard clinical MRI scanners without multinuclear capability. This is not only an economical alternative to the multinuclear system (MNS) provided by the scanner vendors, but also overcomes the frequency bandwidth problem of some vendor-provided MNSs that prohibit users from applications with X-nuclei of low magnetogyric ratio, such as deuterium (6.536 MHz/Tesla) and 15N (-4.316 MHz/Tesla). Here we illustrate the design of the frequency converter system and demonstrate its feasibility for 31P (17.235 MHz/Tesla), 13C (10.708 MHz/Tesla), and 15N MRS and MRI on a clinical MRI scanner without vendor-provided multinuclear hardware.

Multi-parametric hyperpolarized 13C/1H imaging reveals Warburg-related metabolic dysfunction and associated regional heterogeneity in high-grade human gliomas

BackgroundDynamic hyperpolarized (HP)-13C MRI has enabled real-time, non-invasive assessment of Warburg-related metabolic dysregulation in glioma using a [1-13C]pyruvate tracer that undergoes conversion to [1-13C]lactate and [13C]bicarbonate. Using a multi-parametric 1H/HP-13C imaging approach, we investigated dynamic and steady-state metabolism, together with physiological parameters, in high-grade gliomas to characterize active tumor. MethodsMulti-parametric 1H/HP-13C MRI data were acquired from fifteen patients with progressive/treatment-naïve glioblastoma [prog/TN GBM, IDH-wildtype (n = 11)], progressive astrocytoma, IDH-mutant, grade 4 (G4AIDH+, n = 2) and GBM manifesting treatment effects (n = 2). Voxel-wise regional analysis of the cohort with prog/TN GBM assessed imaging heterogeneity across contrast-enhancing/non-enhancing lesions (CEL/NEL) and normal-appearing white matter (NAWM) using a mixed effects model. To enable cross-nucleus parameter association, normalized perfusion, diffusion, and dynamic/steady-state (HP-13C/spectroscopic) metabolic data were collectively examined at the 13C resolution. Prog/TN GBM were similarly compared against progressive G4AIDH+ and treatment effects. ResultsRegional analysis of Prog/TN GBM metabolism revealed statistically significant heterogeneity in 1H choline-to-N-acetylaspartate index (CNI)max, [1-13C]lactate, modified [1-13C]lactate-to-[1-13C]pyruvate ratio (CELval > NELval > NAWMval); [1-13C]lactate-to-[13C]bicarbonate ratio (CELval > NELval/NAWMval); and 1H-lactate (CELval/NELval > NAWMundetected). Significant associations were found between normalized perfusion (cerebral blood volume, nCBV; peak height, nPH) and levels of [1-13C]pyruvate and [1-13C]lactate, as well as between CNImax and levels of [1-13C]pyruvate, [1-13C]lactate and modified ratio. GBM, by comparison to G4AIDH+, displayed lower perfusion %-recovery and modeled rate constants for [1-13C]pyruvate-to-[1-13C]lactate conversion (kPL), and higher 1H-lactate and [1-13C]pyruvate levels, while having higher nCBV, %-recovery, kPL, [1-13C]pyruvate-to-[1-13C]lactate and modified ratios relative to treatment effects. ConclusionsGBM consistently displayed aberrant, Warburg-related metabolism and regional heterogeneity detectable by novel HP-13C/1H imaging techniques.

Imaging telomerase reverse transcriptase expression in oligodendrogliomas using hyperpolarized δ-[1-13C]-gluconolactone.

Telomere maintenance by telomerase reverse transcriptase (TERT) is essential for immortality in most cancers, including oligodendrogliomas. Agents that disrupt telomere maintenance such as the telomere uncapping agent 6-thio-2'-deoxyguanosine (6-thio-dG) are in clinical trials. We previously showed that TERT expression in oligodendrogliomas is associated with upregulation of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway (PPP). We also showed that hyperpolarized δ-[1-13C]-gluconolactone metabolism to 6-phosphogluconate (6-PG) can be used to probe the PPP in glioblastomas. The goal of this study was to determine whether hyperpolarized 13C imaging using δ-[1-13C]-gluconolactone can monitor TERT expression and response to 6-thio-dG in oligodendrogliomas. We examined patient-derived oligodendroglioma cells and orthotopic tumors to assess the link between TERT and hyperpolarized δ-[1-13C]-gluconolactone metabolism. We performed in vivo imaging to assess the ability of hyperpolarized δ-[1-13C]-gluconolactone to report on TERT and response to 6-thio-dG in rats bearing orthotopic oligodendrogliomas in vivo. Doxycycline-inducible TERT silencing abrogated 6-PG production from hyperpolarized δ-[1-13C]-gluconolactone in oligodendroglioma cells, consistent with the loss of G6PD activity. Rescuing TERT expression by doxycycline removal restored G6PD activity and, concomitantly, 6-PG production. 6-PG production from hyperpolarized δ-[1-13C]-gluconolactone demarcated TERT-expressing tumor from surrounding TERT-negative normal brain in vivo. Importantly, 6-thio-dG abrogated 6-PG production at an early timepoint preceding MRI-detectable alterations in rats bearing orthotopic oligodendrogliomas in vivo. These results indicate that hyperpolarized δ-[1-13C]-gluconolactone reports on TERT expression and early response to therapy in oligodendrogliomas. Our studies identify a novel agent for imaging tumor proliferation and treatment response in oligodendroglioma patients.

EXTH-13. COMBINED TARGETING OF TELOMERASE REVERSE TRANSCRIPTASE AND METABOLISM ABROGATES GLIOBLASTOMA PROLIFERATION IN VIVO

Abstract Telomerase reverse transcriptase (TERT) is essential for tumor immortality. Since TERT is silenced in normal cells, it is an attractive therapeutic target and the TERT inhibitor 6-thio-2’-deoxyguanosine (6-thio-dG) is in clinical trials for gliomas. However, there is a lag period following TERT inhibition before tumor shrinkage is observed. Novel strategies that can be combined with TERT inhibition to enhance anti-tumor activity are sorely needed. We previously demonstrated that TERT increases expression of the alanine transporter ASCT2 in gliomas, an effect that could be non-invasively monitored using hyperpolarized 13C imaging of alanine metabolism (Viswanath et al., Nature Communications, 2021). The goals of the current study were to determine whether combined inhibition of TERT and ASCT2 inhibits GBM growth and to assess the ability of hyperpolarized [1-13C]-alanine to monitor treatment response. Our results indicated that, while both the TERT inhibitor 6-thio-dG and the ASCT2 inhibitor V-9302 individually inhibited viability, the combination of 6-thio-dG and V-9302 maximally inhibited cell viability in the patient-derived GBM1 and GBM6 models. In line with the effect on cell viability, while both compounds reduced lactate production from hyperpolarized [1-13C]-alanine, the combination of 6-thio-dG and V-9302 resulted in the highest inhibition of lactate production in both models. Importantly, treatment of rats bearing orthotopic GBM6 tumors with a combination of 6-thio-dG and V-9302 caused tumor shrinkage, an effect that could be visualized by magnetic resonance imaging by day 21 after treatment. Furthermore, lactate production from hyperpolarized [1-13C]-alanine was significantly reduced at day 7 after treatment with 6-thio-dG and V-9302, when anatomical alterations were absent. Collectively, our results indicate that simultaneously targeting TERT and ASCT2 provides a novel therapeutic opportunity for GBMs and that hyperpolarized [1-13C]-alanine serves as a companion agent for imaging early response to therapy. Our findings pave the way for precision therapy and response assessment for GBM patients.

RF coil design for accurate parallel imaging on 13 C MRSI using 23 Na sensitivity profiles.

PurposeTo develop a coil‐based method to obtain accurate sensitivity profiles in 13C MRI at 3T from the endogenous 23Na. An eight‐channel array is designed for 13C MR acquisitions. As application examples, the array is used for two‐fold accelerated acquisitions of both hyperpolarized 13C metabolic imaging of pig kidneys and the human brain.MethodsA flexible coil array was tuned optimally for 13C at 3T (32.1 MHz), with the coil coupling coefficients matched to be nearly identical at the resonance frequency of 23Na (33.8 MHz). This is done by enforcing a high decoupling (obtained through highly mismatched preamplifiers) and adjusting the coupling frequency response. The SNR performance is compared to reference coils.ResultsThe measured sensitivity profiles on a phantom showed high spatial similarity for 13C and 23Na resonances, with average noise correlation of 9 and 11%, respectively. For acceleration factors 2, 3, and 4, the obtained maximum g‐factors were 1.0, 1.1, and 2.6, respectively. The 23Na profiles obtained in vivo could be used successfully to perform two‐fold acceleration of hyperpolarized 13C 3D acquisitions of both pig kidneys and a healthy human brain.ConclusionA receive array has been developed in such a way that the 13C sensitivity profiles could be accurately obtained from measurements at the 23Na frequency. This technique facilitates accelerated acquisitions for hyperpolarized 13C imaging. The SNR performance obtained at the 13C frequency, compares well to other state‐of‐the‐art coils for the same purpose, showing slightly better superficial and central SNR.

A reproducible dynamic phantom for sequence testing in hyperpolarised 13C-magnetic resonance.

To develop a phantom system which can be integrated with an automated injection system, eliminating the experimental variability that arises with manual injection; for the purposes of pulse sequence testing and metric derivation in hyperpolarised 13C-MR. The custom dynamic phantom was machined from Ultem and filled with a nicotinamide adenine dinucleotide and lactate dehydrogenase mixture dissolved in phosphate buffered saline. Hyperpolarised [1-13C]-pyruvate was then injected into the phantom (n = 8) via an automated syringe pump and the conversion of pyruvate to lactate monitored through a 13C imaging sequence. The phantom showed low coefficient of variation for the lactate to pyruvate peak signal heights (11.6%) and dynamic area-under curve ratios (11.0%). The variance for the lactate dehydrogenase enzyme rate constant (kP) was also seen to be low at 15.6%. The dynamic phantom demonstrates high reproducibility for quantification of 13C-hyperpolarised MR-derived metrics. Establishing such a phantom is needed to facilitate development of hyperpolarsed 13C-MR pulse sequenced; and moreover, to enable multisite hyperpolarised 13C-MR clinical trials where assessment of metric variability across sites is critical. The dynamic phantom developed during the course of this study will be a useful tool in testing new pulse sequences and standardisation in future hyperpolarised work.

Characterization of Distinctive In Vivo Metabolism between Enhancing and Non-Enhancing Gliomas Using Hyperpolarized Carbon-13 MRI.

The development of hyperpolarized carbon-13 (13C) metabolic MRI has enabled the sensitive and noninvasive assessment of real-time in vivo metabolism in tumors. Although several studies have explored the feasibility of using hyperpolarized 13C metabolic imaging for neuro-oncology applications, most of these studies utilized high-grade enhancing tumors, and little is known about hyperpolarized 13C metabolic features of a non-enhancing tumor. In this study, 13C MR spectroscopic imaging with hyperpolarized [1-13C]pyruvate was applied for the differential characterization of metabolic profiles between enhancing and non-enhancing gliomas using rodent models of glioblastoma and a diffuse midline glioma. Distinct metabolic profiles were found between the enhancing and non-enhancing tumors, as well as their contralateral normal-appearing brain tissues. The preliminary results from this study suggest that the characterization of metabolic patterns from hyperpolarized 13C imaging between non-enhancing and enhancing tumors may be beneficial not only for understanding distinct metabolic features between the two lesions, but also for providing a basis for understanding 13C metabolic processes in ongoing clinical trials with neuro-oncology patients using this technology.

Probing Cerebral Metabolism with Hyperpolarized 13C Imaging after Opening the Blood–Brain Barrier with Focused Ultrasound

Transient disruption of the blood-brain barrier (BBB) with focused ultrasound (FUS) is an emerging clinical method to facilitate targeted drug delivery to the brain. The focal noninvasive disruption of the BBB can be applied to promote the local delivery of hyperpolarized substrates. In this study, we investigated the effects of FUS on imaging brain metabolism using two hyperpolarized 13C-labeled substrates in rodents: [1-13C]pyruvate and [1-13C]glycerate. The BBB is a rate-limiting factor for pyruvate delivery to the brain, and glycerate minimally passes through the BBB. First, cerebral imaging with hyperpolarized [1-13C]pyruvate resulted in an increase in total 13C signals (p = 0.05) after disrupting the BBB with FUS. Significantly higher levels of both [1-13C]lactate (lactate/total 13C signals, p = 0.01) and [13C]bicarbonate (p = 0.008) were detected in the FUS-applied brain region as compared to the contralateral FUS-unaffected normal-appearing brain region. The application of FUS without opening the BBB in a separate group of rodents resulted in comparable lactate and bicarbonate productions between the FUS-applied and the contralateral brain regions. Second, 13C imaging with hyperpolarized [1-13C]glycerate after opening the BBB showed increased [1-13C]glycerate delivery to the FUS-applied region (p = 0.04) relative to the contralateral side, and [1-13C]lactate production was consistently detected from the FUS-applied region. Our findings suggest that FUS accelerates the delivery of hyperpolarized molecules across the BBB and provides enhanced sensitivity to detect metabolic products in the brain; therefore, hyperpolarized 13C imaging with FUS may provide new opportunities to study cerebral metabolic pathways as well as various neurological pathologies.

Combined 23Na and 13C imaging at 3.0 Tesla using a single‐tuned large FOV birdcage coil

PurposeAn unmet need in carbon‐13 (13C)‐MRI is a transmit system that provides uniform excitation across a large FOV and can accommodate patients of wide‐ranging body habitus. Due to the small difference between the resonant frequencies, sodium‐23 (23Na) coil developments can inform 13C coil design while being simpler to assess due to the higher naturally abundant 23Na signal. Here we present a removable 23Na birdcage, which also allows operation as a 13C abdominal coil.MethodsWe demonstrate a quadrature‐driven 4‐rung 23Na birdcage coil of 50 cm in length for both 23Na and 13C abdominal imaging. The coil transmit efficiencies and maps were compared to a linearly driven 13C Helmholtz‐based (clamshell) coil. SNR was investigated with 23Na and 13C data using an 8‐channel 13C receive array within the 23Na birdcage.ResultsThe 23Na birdcage longitudinal FOV was > 40 cm, whereas the 13C clamshell was < 32 cm. The transmit efficiency of the birdcage at the 23Na frequency was 0.65 µT/sqrt(W), similar to the clamshell for 13C. However, the coefficient of variation of 23Na‐ was 16%, nearly half that with the 13C clamshell. The 8‐channel 13C receive array combined with the 23Na birdcage coil generated a greater than twofold increase in 23Na‐SNR from the central abdomen compared with the birdcage alone.DiscussionThis 23Na birdcage coil has a larger FOV and improved uniformity when compared to the widely used clamshell coil design while also providing similar transmit efficiency. The coil has the potential to be used for both 23Na and 13C imaging.

Hyperpolarized 13 C Magnetic Resonance Imaging of Fumarate Metabolism by Parahydrogen-induced Polarization: A Proof-of-Concept in vivo Study.

Hyperpolarized [1‐13C]fumarate is a promising magnetic resonance imaging (MRI) biomarker for cellular necrosis, which plays an important role in various disease and cancerous pathological processes. To demonstrate the feasibility of MRI of [1‐13C]fumarate metabolism using parahydrogen‐induced polarization (PHIP), a low‐cost alternative to dissolution dynamic nuclear polarization (dDNP), a cost‐effective and high‐yield synthetic pathway of hydrogenation precursor [1‐13C]acetylenedicarboxylate (ADC) was developed. The trans‐selectivity of the hydrogenation reaction of ADC using a ruthenium‐based catalyst was elucidated employing density functional theory (DFT) simulations. A simple PHIP set‐up was used to generate hyperpolarized [1‐13C]fumarate at sufficient 13C polarization for ex vivo detection of hyperpolarized 13C malate metabolized from fumarate in murine liver tissue homogenates, and in vivo 13C MR spectroscopy and imaging in a murine model of acetaminophen‐induced hepatitis.

Analysis Methods for Hyperpolarized Carbon (13C) MRI of the Kidney.

Hyperpolarized 13C MR is a novel medical imaging modality with substantially different signal dynamics as compared to conventional 1H MR, thus requiring new methods for processing the data in order to access and quantify the embedded metabolic and functional information. Here we describe step-by-step analysis protocols for functional renal hyperpolarized 13C imaging. These methods are useful for investigating renal blood flow and function as well as metabolic status of rodents in vivo under various experimental physiological conditions.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This analysis protocol chapter is complemented by two separate chapters describing the basic concept and experimental procedure.

Super-Resolution Hyperpolarized 13C Imaging of Human Brain Using Patch-Based Algorithm.

Spatial resolution of metabolic imaging with hyperpolarized 13C-labeled substrates is limited owing to the multidimensional nature of spectroscopic imaging and the transient characteristics of dissolution dynamic nuclear polarization. In this study, a patch-based algorithm (PA) is proposed to enhance spatial resolution of hyperpolarized 13C human brain images by exploiting compartmental information from the corresponding high-resolution 1H images. PA was validated in simulation and phantom studies. Effects of signal-to-noise ratio, upsampling factor, segmentation, and slice thickness on reconstructing 13C images were evaluated in simulation. PA was further applied to low-resolution human brain metabolite maps of hyperpolarized [1-13C] pyruvate and [1-13C] lactate with 3 compartment segmentations (gray matter, white matter, and cerebrospinal fluid). The performance of PA was compared with other conventional interpolation methods (sinc, nearest-neighbor, bilinear, and spline interpolations). The simulation and the phantom tests showed that PA improved spatial resolution by up to 8 times and enhanced the image contrast without compromising quantification accuracy or losing the intracompartment signal inhomogeneity, even in the case of low signal-to-noise ratio or inaccurate segmentation. PA also improved spatial resolution and image contrast of human 13C brain images. Dynamic analysis showed consistent performance of the proposed method even with the signal decay along time. In conclusion, PA can enhance low-resolution hyperpolarized 13C images in terms of spatial resolution and contrast by using a priori knowledge from high-resolution 1H magnetic resonance imaging while preserving quantification accuracy and intracompartment signal inhomogeneity.

Imaging Acute Metabolic Changes in Patients with Mild Traumatic Brain Injury Using Hyperpolarized [1-13C]Pyruvate.

SummaryTraumatic brain injury (TBI) involves complex secondary injury processes following the primary injury. The secondary injury is often associated with rapid metabolic shifts and impaired brain function immediately after the initial tissue damage. Magnetic resonance spectroscopic imaging (MRSI) coupled with hyperpolarization of 13C-labeled substrates provides a unique opportunity to map the metabolic changes in the brain after traumatic injury in real-time without invasive procedures. In this report, we investigated two patients with acute mild TBI (Glasgow coma scale 15) but no anatomical brain injury or hemorrhage. Patients were imaged with hyperpolarized [1-13C]pyruvate MRSI 1 or 6 days after head trauma. Both patients showed significantly reduced bicarbonate (HCO3–) production, and one showed hyperintense lactate production at the injured sites. This study reports the feasibility of imaging altered metabolism using hyperpolarized pyruvate in patients with TBI, demonstrating the translatability and sensitivity of the technology to cerebral metabolic changes after mild TBI.

Functional kleptoplasts intermediate incorporation of carbon and nitrogen in cells of the Sacoglossa sea slug Elysia viridis

Some sacoglossan sea slugs incorporate intracellular functional algal chloroplasts, a process termed kleptoplasty. “Stolen” chloroplasts (kleptoplasts) can remain photosynthetically active up to several months, contributing to animal nutrition. Whether this contribution occurs by means of translocation of photosynthesis-derived metabolites from functional kleptoplasts to the animal host or by simple digestion of such organelles remains controversial. Imaging of 13C and 15N assimilation over a 12-h incubation period of Elysia viridis sea slugs showed a light-dependent incorporation of carbon and nitrogen, observed first in digestive tubules and followed by a rapid accumulation into chloroplast-free organs. Furthermore, this work revealed the presence of 13C-labeled long-chain fatty acids (FA) typical of marine invertebrates, such as arachidonic (20:4n-6) and adrenic (22:4n-6) acids. The time frame and level of 13C- and 15N-labeling in chloroplast-free organs indicate that photosynthesis-derived primary metabolites were made available to the host through functional kleptoplasts. The presence of specific 13C-labeled long-chain FA, absent from E. viridis algal food, indicates animal based-elongation using kleptoplast-derived FA precursors. Finally, carbon and nitrogen were incorporated in organs and tissues involved in reproductive functions (albumin gland and gonadal follicles), implying a putative role of kleptoplast photosynthesis in the reproductive fitness of the animal host.

New prostate MRI techniques and sequences.

Prostate MRI has seen increasing interest in recent years and has led to the development of new MRI techniques and sequences to improve prostate cancer (PCa) diagnosis which are reviewed in this article. Numerous studies have focused on improving image quality (segmented DWI) and faster acquisition (compressed sensing, k-t-SENSE, PROPELLER). An increasing number of studies have developed new quantitative and computer-aided diagnosis methods including artificial intelligence (PROSTATEx challenge) that mitigate the subjective nature of mpMRI interpretation. MR fingerprinting allows rapid, simultaneous generation of quantitative maps of multiple physical properties (T1, T2), where PCa are characterized by lower T1 and T2 values. New techniques like luminal water imaging (LWI), restriction spectrum imaging (RSI), VERDICT and hybrid multi-dimensional MRI (HM-MRI) have been developed for microstructure imaging, which provide information similar to histology. The distinct MR properties of tissue components and their change with the presence of cancer is used to diagnose prostate cancer. LWI is a T2-based imaging technique where long T2-component corresponding to luminal water is reduced in PCa. RSI and VERDICT are diffusion-based techniques where PCa is characterized by increased signal from intra-cellular restricted water and increased intracellular volume fraction, respectively, due to increased cellularity. VERDICT also reveal loss of extracellular-extravascular space in PCa due to loss of glandular structure. HM-MRI measures volumes of prostate tissue components, where PCa has reduced lumen and stromal and increased epithelium volume similar to results shown in histology. Similarly, molecular imaging using hyperpolarized 13C imaging has been utilized.

A multi spin echo pulse sequence with optimized excitation pulses and a 3D cone readout for hyperpolarized 13 C imaging.

PurposeImaging tumor metabolism in vivo using hyperpolarized [1‐13C]pyruvate is a promising technique for detecting disease, monitoring disease progression, and assessing treatment response. However, the transient nature of the hyperpolarization and its depletion following excitation limits the available time for imaging. We describe here a single‐shot multi spin echo sequence, which improves on previously reported sequences, with a shorter readout time, isotropic point spread function (PSF), and better signal‐to‐noise ratio.MethodsThe sequence uses numerically optimized spectrally selective excitation pulses set to the resonant frequencies of pyruvate and lactate and a hyperbolic secant adiabatic refocusing pulse, all applied in the absence of slice selection gradients. The excitation pulses were designed to be resistant to the effects of B0 and B1 field inhomogeneity. The gradient readout uses a 3D cone trajectory composed of 13 cones, all fully refocused and distributed among 7 spin echoes. The maximal gradient amplitude and slew rate were set to 4 G/cm and 20 G/cm/ms, respectively, to demonstrate the feasibility of clinical translation.ResultsThe pulse sequence gave an isotropic PSF of 2.8 mm. The excitation profiles of the optimized pulses closely matched simulations and a 46.10 ± 0.04% gain in image SNR was observed compared to a conventional Shinnar–Le Roux excitation pulse. The sequence was demonstrated with dynamic imaging of hyperpolarized [1‐13C]pyruvate and [1‐13C]lactate in vivo.ConclusionThe pulse sequence was capable of dynamic imaging of hyperpolarized 13C labeled metabolites in vivo with relatively high spatial and temporal resolution and immunity to system imperfections.