Marion I. Menzel

Accelerated diffusion spectrum imaging in the human brain using compressed sensing

We developed a novel method to accelerate diffusion spectrum imaging using compressed sensing. The method can be applied to either reduce acquisition time of diffusion spectrum imaging acquisition without losing critical information or to improve the resolution in diffusion space without increasing scan time. Unlike parallel imaging, compressed sensing can be applied to reconstruct a sub‐Nyquist sampled dataset in domains other than the spatial one. Simulations of fiber crossings in 2D and 3D were performed to systematically evaluate the effect of compressed sensing reconstruction with different types of undersampling patterns (random, gaussian, Poisson disk) and different acceleration factors on radial and axial diffusion information. Experiments in brains of healthy volunteers were performed, where diffusion space was undersampled with different sampling patterns and reconstructed using compressed sensing. Essential information on diffusion properties, such as orientation distribution function, diffusion coefficient, and kurtosis is preserved up to an acceleration factor of R = 4. Magn Reson Med, 2011.

IDEAL spiral CSI for dynamic metabolic MR imaging of hyperpolarized [1‐13C]pyruvate

Metabolic imaging with hyperpolarized [1‐13C]pyruvate offers the unique opportunity for a minimally invasive detection of cellular metabolism. Efficient and robust acquisition and reconstruction techniques are required for capturing the wealth of information present for the limited duration of the hyperpolarized state (∼1 min). In this study, the Dixon/IDEAL type of water–fat separation is expanded toward spectroscopic imaging of [1‐13C]pyruvate and its down‐stream metabolites. For this purpose, the spectral–spatial encoding is based on single‐shot spiral image encoding and echo‐time shifting in between excitations for the chemical‐shift encoding. In addition, also a free‐induction decay spectrum is acquired and the obtained chemical‐shift prior knowledge is efficiently used in the reconstruction. The spectral–spatial reconstruction problem is found to efficiently separate into a chemical‐shift inversion followed by a spatial reconstruction. The method is successfully demonstrated for dynamic, multislice [1‐13C]pyruvate metabolic MR imaging in phantom and in vivo rat experiments. Magn Reson Med, 2012.

Saturation-recovery metabolic-exchange rate imaging with hyperpolarized [1-13C] pyruvate using spectral-spatial excitation.

Within the last decade hyperpolarized [1‐13C] pyruvate chemical‐shift imaging has demonstrated impressive potential for metabolic MR imaging for a wide range of applications in oncology, cardiology, and neurology. In this work, a highly efficient pulse sequence is described for time‐resolved, multislice chemical shift imaging of the injected substrate and obtained downstream metabolites. Using spectral‐spatial excitation in combination with single‐shot spiral data acquisition, the overall encoding is evenly distributed between excitation and signal reception, allowing the encoding of one full two‐dimensional metabolite image per excitation. The signal‐to‐noise ratio can be flexibly adjusted and optimized using lower flip angles for the pyruvate substrate and larger ones for the downstream metabolites. Selectively adjusting the excitation of the down‐stream metabolites to 90° leads to a so‐called “saturation‐recovery” scheme with the detected signal content being determined by forward conversion of the available pyruvate. In case of repetitive excitations, the polarization is preserved using smaller flip angles for pyruvate. Metabolic exchange rates are determined spatially resolved from the metabolite images using a simplified two‐site exchange model. This novel contrast is an important step toward more quantitative metabolic imaging. Goal of this work was to derive, analyze, and implement this “saturation‐recovery metabolic exchange rate imaging” and demonstrate its capabilities in four rats bearing subcutaneous tumors. Magn Reson Med, 2013.

q-Space Deep Learning: Twelve-Fold Shorter and Model-Free Diffusion MRI Scans

Numerous scientific fields rely on elaborate but partly suboptimal data processing pipelines. An example is diffusion magnetic resonance imaging (diffusion MRI), a non-invasive microstructure assessment method with a prominent application in neuroimaging. Advanced diffusion models providing accurate microstructural characterization so far have required long acquisition times and thus have been inapplicable for children and adults who are uncooperative, uncomfortable, or unwell. We show that the long scan time requirements are mainly due to disadvantages of classical data processing. We demonstrate how deep learning, a group of algorithms based on recent advances in the field of artificial neural networks, can be applied to reduce diffusion MRI data processing to a single optimized step. This modification allows obtaining scalar measures from advanced models at twelve-fold reduced scan time and detecting abnormalities without using diffusion models. We set a new state of the art by estimating diffusion kurtosis measures from only 12 data points and neurite orientation dispersion and density measures from only 8 data points. This allows unprecedentedly fast and robust protocols facilitating clinical routine and demonstrates how classical data processing can be streamlined by means of deep learning.

Diffusion of hyperpolarized 13C-metabolites in tumor cell spheroids using real-time NMR spectroscopy

The detection of tumors noninvasively, the characterization of their progression by defined markers and the monitoring of response to treatment are goals of medical imaging techniques. In this article, a method which measures the apparent diffusion coefficients (ADCs) of metabolites using hyperpolarized 13C diffusion‐weighted spectroscopy is presented. A pulse sequence based on the pulsed gradient spin echo (PGSE) was developed that encodes both kinetics and diffusion information. In experiments with MCF‐7 human breast cancer cells, we detected an ADC of intracellularly produced lactate of 1.06 ± 0.15 µm2/ms, which is about one‐half of the value measured with pyruvate in extracellular culture medium. When monitoring tumor cell spheroids during progressive membrane permeabilization with Triton X‐100, the ratio of lactate ADC to pyruvate ADC increases as the fraction of dead cells increases. Therefore, 13C ADC detection can yield sensitive information on changes in membrane permeability and subsequent cell death. Our results suggest that both metabolic label exchange and 13C ADCs can be acquired simultaneously, and may potentially serve as noninvasive biomarkers for pathological changes in tumor cells. Copyright

In vivo measurement of apparent diffusion coefficients of hyperpolarized 13C‐labeled metabolites

The combination of hyperpolarized MRS with diffusion weighting (dw) allows for determination of the apparent diffusion coefficient (ADC), which is indicative of the intra‐ or extracellular localization of the metabolite. Here, a slice‐selective pulsed‐gradient spin echo sequence was implemented to acquire a series of dw spectra from rat muscle in vivo to determine the ADCs of multiple metabolites after a single injection of hyperpolarized [1‐13C]pyruvate. An optimal control optimized universal‐rotation pulse was used for refocusing to minimize signal loss caused by B1 imperfections.

Metabolic Imaging of Hyperpolarized (1- 13 C)Acetate and (1- 13 C)Acetylcarnitine - Investigation of the Influence of Dobutamine Induced Stress

The metabolism of acetate in the heart resembles fatty acid metabolism, which is altered in several diseases like ischemia, diabetes mellitus, and heart failure. A signal‐to‐noise ratio (SNR) optimized imaging framework for in vivo measurements of hyperpolarized [1‐13C]acetate and its metabolic product [1‐13C]acetylcarnitine (ALCAR) in rats at 3 Tesla (T) is presented in this work.

Apparent rate constant mapping using hyperpolarized [1- 13 C]pyruvate

Hyperpolarization of [1‐13C]pyruvate in solution allows real‐time measurement of uptake and metabolism using MR spectroscopic methods. After injection and perfusion, pyruvate is taken up by the cells and enzymatically metabolized into downstream metabolites such as lactate, alanine, and bicarbonate. In this work, we present comprehensive methods for the quantification and interpretation of hyperpolarized 13C metabolite signals. First, a time‐domain spectral fitting method is described for the decomposition of FID signals into their metabolic constituents. For this purpose, the required chemical shift frequencies are automatically estimated using a matching pursuit algorithm. Second, a time‐discretized formulation of the two‐site exchange kinetic model is used to quantify metabolite signal dynamics by two characteristic rate constants in the form of (i) an apparent build‐up rate (quantifying the build‐up of downstream metabolites from the pyruvate substrate) and (ii) an effective decay rate (summarizing signal depletion due to repetitive excitation, T1‐relaxation and backward conversion). The presented spectral and kinetic quantification were experimentally verified in vitro and in vivo using hyperpolarized [1‐13C]pyruvate. Using temporally resolved IDEAL spiral CSI, spatially resolved apparent rate constant maps are also extracted. In comparison to single metabolite images, apparent build‐up rate constant maps provide improved contrast by emphasizing metabolically active tissues (e.g. tumors) and suppression of high perfusion regions with low conversion (e.g. blood vessels). Apparent build‐up rate constant mapping provides a novel quantitative image contrast for the characterization of metabolic activity. Its possible implementation as a quantitative standard will be subject to further studies. Copyright

Quantified pH imaging with hyperpolarized (13) C-bicarbonate.

Because pH plays a crucial role in several diseases, it is desirable to measure pH in vivo noninvasively and in a spatially localized manner. Spatial maps of pH were quantified in vitro, with a focus on method‐based errors, and applied in vivo.

Effects of pyruvate dose on in vivo metabolism and quantification of hyperpolarized 13C spectra

Real‐time in vivo measurements of metabolites are performed by signal enhancement of [1‐13C]pyruvate using dynamic nuclear polarization, rapid dissolution and intravenous injection, acquisition of free induction decay signals and subsequent quantification of spectra. The commonly injected dose of hyperpolarized pyruvate is larger than typical tracer doses, with measurement before complete dilution of the injected bolus. Pyruvate is in exchange with its downstream metabolites lactate, alanine and bicarbonate. A transient exposure to high pyruvate blood concentrations may cause the saturation of cellular uptake and metabolic conversion. The goal of this study was to examine the effects of a [1‐13C]pyruvate bolus on metabolic conversion in vivo.