Probing human heart TCA cycle metabolism and response to glucose load using hyperpolarized [2- C]pyruvate MRS.

Introduction: The healthy heart has remarkable metabolic flexibility that permits rapid switching between mitochondrial glucose oxidation and fatty acid oxidation to generate ATP. Loss of metabolic flexibility has been implicated in the genesis of contractile dysfunction seen in cardiomyopathy. Metabolic flexibility has been imaged in experimental models, using hyperpolarized (HP) [2- C]pyruvate MRI, which enables interrogation of metabolites that reflect tricarboxylic acid (TCA) cycle flux in cardiac myocytes.

Probing Human Heart TCA Cycle Metabolism and Response to Glucose Load using Hyperpolarized [2-C]Pyruvate MR Spectroscopy.

Introduction: The normal heart has remarkable metabolic flexibility that permits rapid switching between mitochondrial glucose oxidation and fatty acid (FA) oxidation to generate ATP. Loss of metabolic flexibility has been implicated in the genesis of contractile dysfunction seen in cardiomyopathy. Metabolic flexibility has been imaged in experimental models, using hyperpolarized (HP) [2-C]pyruvate MRI, which enables interrogation of metabolites that reflect tricarboxylic acid (TCA) cycle flux in cardiac myocytes.

Metabolic imaging with hyperpolarized C pyruvate magnetic resonance imaging in patients with renal tumors-Initial experience.

Background: Optimal treatment selection for localized renal tumors is challenging because of their variable biologic behavior and limitations in the preoperative assessment of tumor aggressiveness. The authors investigated the emerging hyperpolarized (HP) C magnetic resonance imaging (MRI) technique to noninvasively assess tumor lactate production, which is strongly associated with tumor aggressiveness.

Methods: Eleven patients with renal tumors underwent HP C pyruvate MRI before surgical resection.

Characterization of serial hyperpolarized C metabolic imaging in patients with glioma.

Background: Hyperpolarized carbon-13 (HP-C) MRI is a non-invasive imaging technique for probing brain metabolism, which may improve clinical cancer surveillance. This work aimed to characterize the consistency of serial HP-C imaging in patients undergoing treatment for brain tumors and determine whether there is evidence of aberrant metabolism in the tumor lesion compared to normal-appearing tissue.

Methods: Serial dynamic HP [1-C]pyruvate MRI was performed on 3 healthy volunteers (6 total examinations) and 5 patients (21 total examinations) with diffuse infiltrating glioma during their course of treatment, using a frequency-selective echo-planar imaging (EPI) sequence.

Hyperpolarized C-pyruvate MRI detects real-time metabolic flux in prostate cancer metastases to bone and liver: a clinical feasibility study.

Background: Hyperpolarized (HP) C-pyruvate MRI is a stable-isotope molecular imaging modality that provides real-time assessment of the rate of metabolism through glycolytic pathways in human prostate cancer. Heretofore this imaging modality has been successfully utilized in prostate cancer only in localized disease. This pilot clinical study investigated the feasibility and imaging performance of HP C-pyruvate MR metabolic imaging in prostate cancer patients with metastases to the bone and/or viscera.

Kinetic Modeling of Hyperpolarized Carbon-13 Pyruvate Metabolism in the Human Brain.

Kinetic modeling of the in vivo pyruvate-to-lactate conversion is crucial to investigating aberrant cancer metabolism that demonstrates Warburg effect modifications. Non-invasive detection of alterations to metabolic flux might offer prognostic value and improve the monitoring of response to treatment. In this clinical research project, hyperpolarized [1-C] pyruvate was intravenously injected in a total of 10 brain tumor patients to measure its rate of conversion to lactate ( k ) and bicarbonate ( k ) via echo-planar imaging.

Translation of Carbon-13 EPI for hyperpolarized MR molecular imaging of prostate and brain cancer patients.

Purpose: To develop and translate a metabolite-specific imaging sequence using a symmetric echo planar readout for clinical hyperpolarized (HP) Carbon-13 ( C) applications.

Methods: Initial data were acquired from patients with prostate cancer (N = 3) and high-grade brain tumors (N = 3) on a 3T scanner. Samples of [1- C]pyruvate were polarized for at least 2 h using a 5T SPINlab system operating at 0.

Investigation of analysis methods for hyperpolarized 13C-pyruvate metabolic MRI in prostate cancer patients.

MRI using hyperpolarized (HP) carbon-13 pyruvate is being investigated in clinical trials to provide non-invasive measurements of metabolism for cancer and cardiac imaging. In this project, we applied HP [1- C]pyruvate dynamic MRI in prostate cancer to measure the conversion from pyruvate to lactate, which is expected to increase in aggressive cancers. The goal of this work was to develop and test analysis methods for improved quantification of this metabolic conversion.

Spatio-Temporally Constrained Reconstruction for Hyperpolarized Carbon-13 MRI Using Kinetic Models.

We present a method of generating spatial maps of kinetic parameters from dynamic sequences of images collected in hyperpolarized carbon-13 magnetic resonance imaging (MRI) experiments. The technique exploits spatial correlations in the dynamic traces via regularization in the space of parameter maps. Similar techniques have proven successful in other dynamic imaging problems, such as dynamic contrast enhanced MRI.

Technique development of 3D dynamic CS-EPSI for hyperpolarized C pyruvate MR molecular imaging of human prostate cancer.

Purpose: The purpose of this study was to develop a new 3D dynamic carbon-13 compressed sensing echoplanar spectroscopic imaging (EPSI) MR sequence and test it in phantoms, animal models, and then in prostate cancer patients to image the metabolic conversion of hyperpolarized [1- C]pyruvate to [1- C]lactate with whole gland coverage at high spatial and temporal resolution.

Methods: A 3D dynamic compressed sensing (CS)-EPSI sequence with spectral-spatial excitation was designed to meet the required spatial coverage, time and spatial resolution, and RF limitations of the 3T MR scanner for its clinical translation for prostate cancer patient imaging. After phantom testing, animal studies were performed in rats and transgenic mice with prostate cancers.

Development of methods and feasibility of using hyperpolarized carbon-13 imaging data for evaluating brain metabolism in patient studies.

Purpose: Hyperpolarized C metabolic imaging is a non-invasive imaging modality for evaluating real-time metabolism. The purpose of this study was to develop and implement experimental strategies for using [1-C]pyruvate to probe metabolism for patients with brain tumors and other neurological diseases.

Methods: The C RF coils and pulse sequences were tested in a phantom and were performed using a 3T whole body scanner.

A PET Imaging Strategy to Visualize Activated T Cells in Acute Graft-versus-Host Disease Elicited by Allogenic Hematopoietic Cell Transplant.

A major barrier to successful use of allogeneic hematopoietic cell transplantation is acute graft-versus-host disease (aGVHD), a devastating condition that arises when donor T cells attack host tissues. With current technologies, aGVHD diagnosis is typically made after end-organ injury and often requires invasive tests and tissue biopsies. This affects patient prognosis as treatments are dramatically less effective at late disease stages.