Fumarase activity: an in vivo and in vitro biomarker for acute kidney injury: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-C-13(2)] fumarate conversion to [1,4-C-13(2)] 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-C-13(2)] 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-C-13] 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

Development of a Symmetric Echo-Planar Spectroscopy Imaging Framework for Hyperpolarized 13C Imaging in a Clinical PET/MR Scanner

Here, we developed a symmetric echo-planar spectroscopic imaging (EPSI) sequence for hyperpolarized 13C imaging on a clinical hybrid positron emission tomography/magnetic resonance imaging system. The pulse sequence uses parallel reconstruction pipelines to separately reconstruct data from odd-and-even gradient echoes to reduce artifacts from gradient imbalances. The ramp-sampled data in the spatiotemporal frequency space are regridded to compensate for the chemical-shift displacements. Unaliasing of nonoverlapping peaks outside of the sampled spectral width was performed to double the effective spectral width. The sequence was compared with conventional phase-encoded chemical-shift imaging (CSI) in phantoms, and it was evaluated in a canine cancer patient with ameloblastoma after injection of hyperpolarized [1-13C]pyruvate. The relative signal-to-noise ratio of EPSI with respect to CSI was 0.88, which is consistent with the decrease in sampling efficiency due to ramp sampling. Data regridding in the spatiotemporal frequency space significantly reduced spatial blurring compared with direct fast Fourier transform. EPSI captured the spatial distributions of both metabolites and their temporal dynamics in vivo with an in-plane spatial resolution of 5 × 9 mm2 and a temporal resolution of 3 seconds. Significantly higher spatial and temporal resolution for delineating anatomical structures in vivo was achieved for EPSI metabolic maps than for CSI maps, which suffered spatiotemporal blurring. The EPSI sequence showed promising results in terms of short acquisition time and sufficient spectral bandwidth of 500 Hz, allowing to adjust the trade-off between signal-to-noise ratio and encoding speed

Resonant marker design and fabrication techniques for device visualization during interventional magnetic resonance imaging

Magnetic resonance imaging (MRI) has great potential as an imaging modality for guiding minimally invasive interventions because of its superior soft tissue contrast and the possibility of arbitrary slice positioning while avoiding ionizing radiation and nephrotoxic iodine contrast agents. The major constraints are: limited patient access, the insufficient assortment of compatible instruments and the difficult device visualization compared to X-ray based techniques. For the latter, resonant MRI markers, fabricated by using the wire-winding technique, have been developed. This fabrication technique serves as a functional model but has no clinical use. Thus, the aim of this study is to illustrate a four-phase design process of resonant markers involving microsystems technologies. The planning phase comprises the definition of requirements and the simulation of electromagnetic performance of the MRI markers. The following technologies were considered for the realization phase: aerosol-deposition process, hot embossing technology and thin film technology. The subsequent evaluation phase involves several test methods regarding electrical and mechanical characterization as well as MRI visibility aspects. The degree of fulfillment of the predefined requirements is determined within the analysis phase. Furthermore, an exemplary evaluation of four realized MRI markers was conducted, focusing on the performance within the MRI environment.</p