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Magnetic resonance imaging with hyperpolarized agents: methods and applications.

ABSTRACT: In the past decade, hyperpolarized (HP) contrast agents have been under active development for MRI applications to address the twin challenges of functional and quantitative imaging. Both HP helium (3He) and xenon (129Xe) gases have reached the stage where they are under study in clinical research. HP 129Xe, in particular, is poised for larger scale clinical research to investigate asthma, chronic obstructive pulmonary disease, and fibrotic lung diseases. With advances in polarizer technology and unique capabilities for imaging of 129Xe gas exchange into lung tissue and blood, HP 129Xe MRI is attracting new attention. In parallel, HP 13C and 15N MRI methods have steadily advanced in a wide range of pre-clinical research applications for imaging metabolism in various cancers and cardiac disease. The HP [1-13C] pyruvate MRI technique, in particular, has undergone phase I trials in prostate cancer and is poised for investigational new drug trials at multiple institutions in cancer and cardiac applications. This review treats the methodology behind both HP gases and HP 13C and 15N liquid state agents. Gas and liquid phase HP agents share similar technologies for achieving non-equilibrium polarization outside the field of the MRI scanner, strategies for image data acquisition, and translational challenges in moving from pre-clinical to clinical research. To cover the wide array of methods and applications, this review is organized by numerical section into (1) a brief introduction, (2) the physical and biological properties of the most common polarized agents with a brief summary of applications and methods of polarization, (3) methods for image acquisition and reconstruction specific to improving data acquisition efficiency for HP MRI, (4) the main physical properties that enable unique measures of physiology or metabolic pathways, followed by a more detailed review of the literature describing the use of HP agents to study: (5) metabolic pathways in cancer and cardiac disease and (6) lung function in both pre-clinical and clinical research studies, concluding with (7) some future directions and challenges, and (8) an overall summary.

SUBMITTER: Adamson EB

PROVIDER: S-EPMC5730331 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Magnetic resonance imaging with hyperpolarized agents: methods and applications.

Adamson Erin B EB Ludwig Kai D KD Mummy David G DG Fain Sean B SB

Physics in medicine and biology 20170406 13

In the past decade, hyperpolarized (HP) contrast agents have been under active development for MRI applications to address the twin challenges of functional and quantitative imaging. Both HP helium (3He) and xenon (129Xe) gases have reached the stage where they are under study in clinical research. HP 129Xe, in particular, is poised for larger scale clinical research to investigate asthma, chronic obstructive pulmonary disease, and fibrotic lung diseases. With ad ...[more]

PMID: 28384123

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Project description:OBJECTIVES:The aim of this study was to determine if hyperpolarized [1,4-13C2]malate imaging could measure cardiomyocyte necrosis after myocardial infarction (MI). BACKGROUND:MI is defined by an acute burst of cellular necrosis and the subsequent cascade of structural and functional adaptations. Quantifying necrosis in the clinic after MI remains challenging. Magnetic resonance-based detection of the conversion of hyperpolarized [1,4-13C2]fumarate to [1,4-13C2]malate, enabled by disrupted cell membrane integrity, has measured cellular necrosis in vivo in other tissue types. Our aim was to determine whether hyperpolarized [1,4-13C2]malate imaging could measure necrosis after MI. METHODS:Isolated perfused hearts were given hyperpolarized [1,4-13C2]fumarate at baseline, immediately after 20 min of ischemia, and after 45 min of reperfusion. Magnetic resonance spectroscopy measured conversion into [1,4-13C2]malate. Left ventricular function and energetics were monitored throughout the protocol, buffer samples were collected and hearts were preserved for further analyses. For in vivo studies, magnetic resonance spectroscopy and a novel spatial-spectral magnetic resonance imaging sequence were implemented to assess cardiomyocyte necrosis in rats, 1 day and 1 week after cryo-induced MI. RESULTS:In isolated hearts, [1,4-13C2]malate production became apparent after 45 min of reperfusion, and increased 2.7-fold compared with baseline. Expression of dicarboxylic acid transporter genes were negligible in healthy and reperfused hearts, and lactate dehydrogenase release and infarct size were significantly increased in reperfused hearts. Nonlinear regression revealed that [1,4-13C2]malate production was induced when adenosine triphosphate was depleted by >50%, below 5.3 mmol/l (R2 = 0.904). In vivo, the quantity of [1,4-13C2]malate visible increased 82-fold over controls 1 day after infarction, maintaining a 31-fold increase 7 days post-infarct. [1,4-13C2]Malate could be resolved using hyperpolarized magnetic resonance imaging in the infarct region one day after MI; [1,4-13C2]malate was not visible in control hearts. CONCLUSIONS:Malate production in the infarcted heart appears to provide a specific probe of necrosis acutely after MI, and for at least 1 week afterward. This technique could offer an alternative noninvasive method to measure cellular necrosis in heart disease, and warrants further investigation in patients.

Project description:BackgroundThere is an unmet need for noninvasive imaging markers that can help identify the aggressive subtype(s) of pancreatic ductal adenocarcinoma (PDAC) at diagnosis and at an earlier time point, and evaluate the efficacy of therapy prior to tumor reduction. In the past few years, there have been two major developments with potential for a significant impact in establishing imaging biomarkers for PDAC and pancreatic cancer premalignancy: (1) hyperpolarized metabolic (HP)-magnetic resonance (MR), which increases the sensitivity of conventional MR by over 10,000-fold, enabling real-time metabolic measurements; and (2) applications of artificial intelligence (AI).ObjectiveOur objective of this review was to discuss these two exciting but independent developments (HP-MR and AI) in the realm of PDAC imaging and detection from the available literature to date.MethodsA systematic review following the PRISMA extension for Scoping Reviews (PRISMA-ScR) guidelines was performed. Studies addressing the utilization of HP-MR and/or AI for early detection, assessment of aggressiveness, and interrogating the early efficacy of therapy in patients with PDAC cited in recent clinical guidelines were extracted from the PubMed and Google Scholar databases. The studies were reviewed following predefined exclusion and inclusion criteria, and grouped based on the utilization of HP-MR and/or AI in PDAC diagnosis.ResultsPart of the goal of this review was to highlight the knowledge gap of early detection in pancreatic cancer by any imaging modality, and to emphasize how AI and HP-MR can address this critical gap. We reviewed every paper published on HP-MR applications in PDAC, including six preclinical studies and one clinical trial. We also reviewed several HP-MR-related articles describing new probes with many functional applications in PDAC. On the AI side, we reviewed all existing papers that met our inclusion criteria on AI applications for evaluating computed tomography (CT) and MR images in PDAC. With the emergence of AI and its unique capability to learn across multimodal data, along with sensitive metabolic imaging using HP-MR, this knowledge gap in PDAC can be adequately addressed. CT is an accessible and widespread imaging modality worldwide as it is affordable; because of this reason alone, most of the data discussed are based on CT imaging datasets. Although there were relatively few MR-related papers included in this review, we believe that with rapid adoption of MR imaging and HP-MR, more clinical data on pancreatic cancer imaging will be available in the near future.ConclusionsIntegration of AI, HP-MR, and multimodal imaging information in pancreatic cancer may lead to the development of real-time biomarkers of early detection, assessing aggressiveness, and interrogating early efficacy of therapy in PDAC.

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Magnetic resonance imaging with hyperpolarized agents: methods and applications.

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Magnetic resonance imaging with hyperpolarized agents: methods and applications.

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