Development of pulse sequences for hyperpolarized 13C magnetic resonance spectroscopic imaging of tumour metabolism

Metabolic imaging with hyperpolarized 13C-labeled cell substrates is a promising technique for imaging tissue metabolism in vivo. However, the transient nature of the hyperpolarization - and its depletion following excitation - limits the imaging time and the number of excitation pulses that can be used. A single-shot 3D imaging sequence has been developed and it is shown in this thesis to generate 13C MR images in tumour-bearing mice injected with hyperpolarized [1-13C]pyruvate. The pulse sequence acquires a stack-of-spirals at two spin echoes after a single excitation pulse and encodes the kz-dimension in an interleaved manner to enhance robustness to B0 inhomogeneity. Spectral-spatial pulses are used to acquire dynamic 3D images from selected hyperpolarized 13C-labeled metabolites. A nominal spatial/temporal resolution of 1.25 x 1.25 x 2.5 $mm^3$ x 2 s was achieved in tumour images of hyperpolarized [1-13C]pyruvate and [1-13C]lactate acquired in vivo. An advanced sequence is also described in this thesis in a later study to acquire higher resolution images with isotropic voxels (1.25 x 1.25 x 1.25 $mm^3$) at no cost of temporal resolution. EPI is a sequence widely used in hyperpolarized 13C MRI because images can be acquired rapidly with limited RF exposure. However, EPI suffers from Nyquist ghosting, which is normally corrected for by acquiring a reference scan. In this thesis a workflow for hyperpolarized 13C EPI is proposed that requires no reference scan and, therefore, that does not sacrifice a time point in the dynamic monitoring of tissue metabolism. To date, most of the hyperpolarized MRI on metabolism are based on 13C imaging, while 1H is a better imaging target for its 4 times higher gyromagnetic ratio and hence 16 times signal. In this thesis the world’s first dynamic 1H imaging in vivo of hyperpolarized [1-13C]lactate is presented, via a novel double-dual-spin-echo INEPT sequence that transfers the hyperpolarization from 13C to 1H, achieving a spatial resolution of 1.25 x 1.25 $mm^2$

Correlation chemical shift imaging with low-power adiabatic pulses and constant-density spiral trajectories

In this work we introduce the concept of correlation chemical shift imaging (CCSI). Novel CCSI pulse sequences are demonstrated on clinical scanners for two-dimensional Correlation Spectroscopy (COSY) and Total Correlation Spectroscopy (TOCSY) imaging experiments. To date there has been limited progress reported towards a feasible and robust multivoxel 2D COSY. Localized 2D TOCSY imaging is shown for the first time in this work. Excitation with adiabatic GOIA-W(16,4) pulses (Gradient Offset Independent Adiabaticity Wurst modulation) provides minimal chemical shift displacement error, reduced lipid contamination from subcutaneous fat, uniform optimal flip angles, and efficient mixing for coupled spins, while enabling short repetition times due to low power requirements. Constant-density spiral readout trajectories are used to acquire simultaneously two spatial dimensions and f2 frequency dimension in (kx,ky,t2) space in order to speed up data collection, while f1 frequency dimension is encoded by consecutive time increments of t1 in (kx,ky,t1,t2) space. The efficient spiral sampling of the k-space enables the acquisition of a single-slice 2D COSY dataset with an 8 × 8 matrix in 8:32 min on 3 T clinical scanners, which makes it feasible for in vivo studies on human subjects. Here we present the first results obtained on phantoms, human volunteers and patients with brain tumors. The patient data obtained by us represent the first clinical demonstration of a feasible and robust multivoxel 2D COSY. Compared to the 2D J-resolved method, 2D COSY and TOCSY provide increased spectral dispersion which scales up with increasing main magnetic field strength and may have improved ability to unambiguously identify overlapping metabolites. It is expected that the new developments presented in this work will facilitate in vivo application of 2D chemical shift correlation MRS in basic science and clinical studies.National Institutes of Health (U.S.) (NIH grant R01 1200-206456)National Institutes of Health (U.S.) (NIH grant R01 EB007942)Siemens Aktiengesellschaft (Siemens-MIT Alliance

State-selective transport of single neutral atoms

The present work investigates the state-selective transport of single neutral cesium atoms in a one-dimensional optical lattice. It demonstrates experimental applications of this transport, including a single atom interferometer, a quantum walk and controlled two-atom collisions. The atoms are stored one by one in an optical lattice formed by a standing wave dipole trap. Their positions are determined with sub-micrometer precision, while atom pair separations are reliably inferred down to neighboring lattice sites using real-time numerical processing. Using microwave pulses in the presence of a magnetic field gradient, the internal qubit states, encoded in the hyperfine levels of the atoms, can be separately initialized and manipulated. This allows us to perform arbitrary single-qubit operations and prepare arbitrary patterns of atoms in the lattice with single-site precision. Chapter 1 presents the experimental setup for trapping a small number of cesium atoms in a one-dimensional optical lattice. Chapter 2 is devoted to fluorescence imaging of atoms, discussing the imaging setup, numeric methods and their performance in detail. Chapter 3 focuses on engineering of internal states of trapped atoms in the lattice using optical methods and microwave radiation. It provides a detailed investigation of coherence properties of our experimental system. Finally manipulation of individual atoms with almost single-site resolution and preparation of regular strings of atoms with predefined distances are presented. In Chapter 4, basic concepts, the experimental realization and the performance of the state-selective transport of neutral atoms over several lattice sites are presented and discussed in detail. Coherence properties of this transport are investigated in Chapter 5, using various two-arms single atom interferometer sequences in which atomic matter waves are split, delocalized, merged and recombined on the initial lattice site, while the interference contrast and the accumulated phase difference are measured. By delocalizing a single atom over several lattice sites, possible spatial inhomogeneities of fields along the lattice axis in the trapping region are probed. In Chapter 6, experimental realization of a discrete time quantum walk on a line with single optically trapped atoms is presented as an advanced application of multiple path quantum interference in the context of quantum information processing. Using this simple example of a quantum walk, fundamental properties of and differences between the quantum and classical regimes are investigated and discussed in detail. Finally, by combining preparation of atom strings, position-dependent manipulation of qubit states and state-selective transport, in Chapter 7, two atoms are deterministically brought together into contact, forming a starting point for investigating two-atom interactions on the most fundamental level. Future prospects and suggestions are finally presented in Chapter 8

Absolute Quantitation for MR Molecular Imaging of Angiogenesis

Medical imaging is undergoing a transition from an art that is used to make static images of human physiology into a scientific tool that employs advanced techniques to measure clinically relevant data. Recently, the role of magnetic resonance imaging in cardiovascular and oncological research has grown, largely due to the implementation of new quantitative techniques in the clinic. Magnetic resonance imaging (MRI) and spectroscopy (MRS) are particularly rich in their capability to quantify both physiology and disease via biomarker detection. While this is true for many applications of MRI in cardiovascular and oncological research, 19F MR molecular imaging is particularly useful when coupled to the use of emerging site-targeted molecular imaging agents for diagnosis and therapy, such as αvβ3 integrin-targeted perfluorocarbon (PFC) nanoparticle (NP) emulsions. Unfortunately, the radiological world is realizing that although image quality may be consistently high, the absolute quantitative values being calculated vary widely across time, techniques, laboratories, and imaging platforms. The overall objective of this work is to advance the state of the art for 19F MR molecular imaging of perfluorocarbon nanoparticle emulsion contrast agents. To reach this objective, three specific aims have been identified: (1) to create new tools and techniques for 19F MR molecular imaging of PFC nanoparticles, (2) to develop translatable procedures for absolute quantification of 19F nuclei with MR molecular imaging, and (3) to evaluate the potential for clinical translation with ex vivo and in vivo preclinical experiments. Robust, standardized techniques are developed in this work to improve the accuracy of in vivo quantitative 19F MR molecular imaging, validate system performance, calibrate measurements to ensure repeatability of these quantitative metrics, and evaluate the potential for clinical translation. As these quantitative metrics become routine in medical imaging procedures, these standardized calibrations and techniques are expected to be critical for accurate interpretation of underlying pathophysiology. This will also impact the development of new therapies and diagnostic techniques/agents by reducing the variability of image-based measurements, thereby increasing the impact of the studies and reducing the overall time and cost to translate new technologies into the clinic

Photoionisation dynamics and ion-ion interaction of individual erbium ions in silicon nanotransistors

Erbium has been widely studied in a variety of host materials for its 1.5 m optical transition, which is compatible with fibre communication systems. Recent studies demonstrated 4.4 ms optical coherence time and 1.3 s nuclear spin coherence time with Er-doped Y2SiO5. This has stimulated the interest in building Er-based quantum memory and spin qubits with optical interface for large-scale quantum systems. This thesis focuses on the investigation of erbium ions in silicon nanotransistors for developing erbium quantum devices on the silicon platform. First, an efficient detection method for individual erbium ions is introduced. This method relies on the short laser pulse excitation and latched current signal readout. The latched signal can be reset by an off-resonance laser pulse and the latching period can be tuned by a gate voltage. This allows for adjustment of the detection speed for higher readout fidelity or faster readout speed. Based on the pulsed method, the dependence of the linewidth and signal intensity on excitation pulse length have been investigated. This allows us to understand the line shape and broadening of the spectrum under laser excitation. Finally, the higher bound of the optical lifetime was estimated based on a Markov model, and a Rabi oscillation process is simulated base on the optical Bloch equation. Then, the Zeeman effect of two coupled erbium ions was studied at high spectral resolution. The spectrum is distinctly different from that of a single Er ion as there are zero field splitting and anticrossings at multiple places. A model based on magnetic dipole-dipole interaction can match not only the Zeeman splitting slopes, but also the anti-crossings in the observed spectrum. Additionally, the potential of using single Er ions to map the electric field and strain in silicon nanotransistors has been explored. This provides a new method to characterise the electric field and strain in silicon sub-10-nanometer-node devices for optimising modern microelectronic devices

Laser diagnostics and minor species detection in combustion using resonant four-wave mixing

Peer reviewedPostprin

Nonlinear optics of planar metamaterial arrays and spectroscopy of inidvidual "photonic atoms"

In this work, we present experiments and corresponding numerical calculations on second-harmonic generation from metamaterial arrays. Measuring the absolute extinction-cross-section spectra of individual split-ring resonators and pairs of split-ring resonators reveals a deeper understanding of the electromagnetic coupling. Furthermore, we could map the near-fields of a split-ring resonator on the nanometer-scale by electron-energy-loss spectroscopy