Metabolic imaging with hyperpolarized [1-13 C]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- Within the past decade, hyperpolarization for in vivo MR imaging and spectroscopy has expanded from gaseous imaging agents toward liquid ones. Among others, dynamic nuclear polarization (DNP) in the amorphous state followed by rapid dissolution has demonstrated as a versatile method to increase the polarization of liquidstate MR imaging agents by more than four orders of magnitude as compared with thermal polarization levels (1,2). The lifetime of the obtained hyperpolarized liquid MR imaging agent is determined by the spin-lattice T 1 relaxation time, which is dependent on the nuclei and its relative position within the molecule considered.Among possible choices, in particular, labeled [1-13 C]pyruvate (noted subsequently as Pyr) has emerged as a promising marker for metabolic MR imaging due to its endogenous character and favorable properties in terms of hyperpolarization, i.e., high polarization levels of up to $50% and long T 1 relaxation times on the order of $30 s in vivo and $65 s ex vivo (2,3). In vivo, hyperpolarized Pyr gets converted into other MR detectable down-stream metabolites, namely lactate (Lac), alanine (Ala), pyruvate-hydrate (PyrH), and bicarbonate (BiC). The metabolites can be distinguished based on their spectral fingerprint, which consists of approximately singlet peaks at well-separated chemical-shift (CS) frequencies. Information about metabolic pathways and the corresponding turn-over ratios can be derived from the time evolution of the individual metabolite concentrations (4,5).Accordingly, hyperpolarized Pyr provides a wealth of detailed metabolic information during limited time duration, which is on the order of the T 1 relaxation time. Various sequences with different trade-offs between temporal and spatial resolution have been suggested for capturing the available information (6,7): small flip-angle (FA), short repetition time (TR), and slice-selective freeinduction decay (FID) acquisition of full spectra provide high temporal resolution with volume selection only along the...

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Transmit gain (B 1+) calibration is necessary for the adjustment of radiofrequency (RF) power levels to the desired flip angles. In proton MRI, this is generally an automated process before the actual scan without any user interaction. For other nuclei, it is usually time consuming and difficult, especially in the case of hyperpolarised MR. In the current work, transmit gain calibration was implemented on the basis of the Bloch-Siegert phase shift. From the same data, the centre frequency, line broadening and SNR could also be determined. The T(1) and B(0) insensitivity, and the wide range of B 1+ over which this technique is effective, make it well suited for nonproton applications. Examples are shown for hyperpolarised (13)C and (3)He applications.

BackgroundThe aim of the present study was to evaluate the recovery potential of the parotid glands after using either 3D-conformal-radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) by sparing one single parotid gland.MethodsBetween 06/2002 and 10/2008, 117 patients with head and neck cancer were included in this prospective, non-randomised clinical study. All patients were treated with curative intent. Salivary gland function was assessed by measuring stimulated salivary flow at the beginning, during and at the end of radiotherapy as well as 1, 6, 12, 24, and 36 months after treatment. Measurements were converted to flow rates and normalized relative to rates before treatment. Mean doses (Dmean) were calculated from dose-volume histograms based on computed tomographies of the parotid glands.ResultsPatients were grouped according to the Dmean of the spared parotid gland having the lowest radiation exposure: Group I - Dmean < 26 Gy (n = 36), group II - Dmean 26-40 Gy (n = 45), and group III - Dmean > 40 Gy (n = 36). 15/117 (13%) patients received IMRT. By using IMRT as compared to 3D-CRT the Dmean of the spared parotid gland could be significantly reduced (Dmean IMRT vs. 3D-CRT: 21.7 vs. 34.4 Gy, p < 0.001). The relative salivary flow rates (RFSR) as a function of the mean parotid dose after 24 and 36 months was in group I 66% and 74%, in group II 56% and 49%, and in group III 31% and 24%, respectively. Multiple linear regression analyses revealed that the parotid gland dose and the tumor site were the independent determinants 12 and 36 months after the end of RT. Patients of group I and II parotid gland function did recover at 12, 24, and 36 months after the end of RT.ConclusionsIf a Dmean < 26 Gy for at least one parotid gland can be achieved then this is sufficient to reach complete recovery of pre-RT salivary flow rates. The radiation volume which depends on tumor site did significantly impact on the Dmean of the parotids, and thus on the saliva flow and recovery of parotid gland.

Magnetic Resonance Imaging has become nowadays an indispensable tool with applications ranging from medicine to material science. However, so far the physical limits of the maximum achievable experimental contrast were unknown. We introduce an approach based on principles of optimal control theory to explore these physical limits, providing a benchmark for numerically optimized robust pulse sequences which can take into account experimental imperfections. This approach is demonstrated experimentally using a model system of two spatially separated liquids corresponding to blood in its oxygenated and deoxygenated forms. Since its discovery in the forties, Nuclear Magnetic Resonance (NMR) has become a powerful tool 1,2 to study the state of matter in a variety of domains extending from biology and chemistry 3 to solid-state physics and quantum computing 4,5 . The power of NMR techniques is maybe best illustrated by medical imaging 6 , where it is possible e.g. to produce a three-dimensional picture of the human brain. NMR spectroscopy and Magnetic Resonance Imaging (MRI) involve the manipulation of nuclear spins via their interaction with magnetic fields. All experiments in liquid phase can be described in a first approach as follows. A sample is held in a strong and uniform longitudinal magnetic field denoted B 0 . The magnetization of the sample is then manipulated by a particular sequence of transverse radio-frequency magnetic pulses B 1 in order to prepare the system in a particular state. The analysis of the radio-frequency signal that is subsequently emitted by the nuclear spins leads to information about the structure of the molecule and its spatial position. One deduces from this simple description that the crucial point of this process is the initial preparation of the sample, i.e. to design a corresponding pulse sequence to reach this particular state with maximum efficiency. The maximum achievable efficiency can be determined for the transfer between well defined initial and target states 7 if relaxation effects can be neglected. In imaging applications, where relaxation forms the basis for contrast, a very large number of different strategies have been proposed and implemented so far with the rapid improvement of NMR and MRI technology 2,6 . However, there was no general approach to provide the maximum possible performance and the majority of these pulse sequences have been built on the basis of intuitive and qualitative reasonings or on inversion methods such as the Shinnar-Le Roux algorithm 8 . Note that this latter can be applied only in the case where there is no relaxation effect and radio-frequency inhomogeneity.A completely different point of view emerges if this problem is approached from an optimal control perspective. Optimal control theory was created in its modern version at the end of the 1950s with the Pontryagin Maximum Principle (PMP) [9][10][11] . Developed originally for problems in space mechanics, optimal control has become a key tool in a large spectrum of applications including eng...

Extended static and dynamic light scattering results on micellar solutions of the dihydroxy bile salt NaGDC (sodium glycodeoxycholate) are presented. From the measurements the apparent molar mass and the mean aggregation number, the apparent diffusion coefficient and the mean hydrodynamic radius for the micelles as a function of NaGDC concentration (8.5-28.0 g/L), ionic strength of the solution (0.03-0.2 M NaCl added), and temperature (20-35 °C) are deduced. The apparent micellar size versus surfactant concentration is discussed only in the context of intermicellar interactions. Growth processes are not taken into account. A self-consistent calculation of the concentration dependence of the diffusion coefficient very similar to that of Dorshow et al. 1,2 is applied in order to determine the potential of the micelles using the DLVO theory. The fractional ionization of the micelle surface is estimated. Moreover, the expansion of the analysis from Dorshow et al. shows that Hamaker's constant is proportional to the mean molar mass of the micelles.

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.

Hyperpolarized (13) C-bicarbonate pH mapping was shown to be sensitive in the biologically relevant pH range. The mapping of pH was applied to healthy in vivo organs and interpreted within inflammation and acute metabolic alkalosis models.