Imaging porcine cardiac substrate selection modulations by glucose, insulin and potassium intervention: A hyperpolarized [1-13 C]pyruvate study.

Cardiac metabolism has received considerable attention in terms of both diagnostics and prognostics, as well as a novel target for treatment. As human trials involving hyperpolarized magnetic resonance in the heart are imminent, we sought to evaluate the general feasibility of detection of an imposed shift in metabolic substrate utilization during metabolic modulation with glucose-insulin-potassium (GIK) infusion, and thus the limitations associated with this strategy, in a large animal model resembling human physiology. Four [1-13 C]pyruvate injections did not alter the blood pressure or ejection fraction over 180 min. Hyperpolarized [1-13 C]pyruvate conversion showed a generally high reproducibility, with intraclass correlation coefficients between the baseline measurements at 0 and 30 min as follows: lactate to pyruvate, 0.85; alanine to pyruvate, 1.00; bicarbonate to pyruvate, 0.83. This study demonstrates that hyperpolarized [1-13 C]pyruvate imaging is a feasible technique for cardiac studies and shows a generally high reproducibility in fasted large animals. GIK infusion increases the metabolic conversion of pyruvate to its metabolic derivatives lactate, alanine and bicarbonate, but with increased variability.

Fumarase activity: an in vivo and in vitro biomarker for acute kidney injury.

Renal ischemia/reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI), and at present, there is a lack of reliable biomarkers that can diagnose AKI and measure early progression because the commonly used methods cannot evaluate single-kidney IRI. Hyperpolarized [1,4-13C2]fumarate conversion to [1,4-13C2]malate by fumarase has been proposed as a measure of necrosis in rat tumor models and in chemically induced AKI rats. Here we show that the degradation of cell membranes in connection with necrosis leads to elevated fumarase activity in plasma and urine and secondly that hyperpolarized [1,4-13C2]malate production 24 h after reperfusion correlates with renal necrosis in a 40-min unilateral ischemic rat model. Fumarase activity screening on bio-fluids can detect injury severity, in bilateral as well as unilateral AKI models, differentiating moderate and severe AKI as well as short- and long-term AKI. Furthermore after verification of renal injury by bio-fluid analysis the precise injury location can be monitored by in vivo measurements of the fumarase activity non-invasively by hyperpolarized [1,4-13C]fumarate MR imaging. The combined in vitro and in vivo biomarker of AKI responds to the essential requirements for a new reliable biomarker of AKI.

Autologous stem cell therapy maintains vertebral blood flow and contrast diffusion through the endplate in experimental intervertebral disc degeneration.

STUDY DESIGN: Experimental, controlled, randomized, and paired study. OBJECTIVE: To evaluate regenerative effect of stem cell therapy on the vertebral endplate and introduce dynamic contrast-enhanced magnetic resonance imaging (MRI) as a tool in the investigation of endplate function. SUMMARY OF BACKGROUND DATA: The vertebral endplate plays a crucial role in nutritional supply to the intervertebral disc. Estimation of endplate function is an important parameter in future biologic therapy of intervertebral disc degeneration (IDD). METHODS: Four-level IDD was induced in each of 15 Gottingen minipigs. Percutaneous intradiscal injection of two hydrogels (Zimmer Biologics Inc, Austin, TX) and one loaded with stem cells was used as single interventions after 12 weeks. Total observation time was 24 weeks. MRI was performed before the initiation of treatment and killing of animals. RESULTS: Three animals were excluded because of spondylodiscitis. Stem cell and hydrogel treatment had significantly higher T2 values, relative vertebral blood flow and volume, as well as lower Pfirrmann scores when compared with degenerative controls. No statistical differences were found compared to normal controls. CONCLUSION: Stem cell and hydrogel therapy is able to partly regenerate IDD and maintain perfusion and permeability of the vertebral endplate and subchondral bone. Dynamic contrast-enhanced MRI may become an important tool in future investigation of the vertebral endplate.