Molecular characterization and quantification using state of the art solid-state adiabatic TOBSY NMR in burn trauma

We describe a novel solid-state nuclear magnetic resonance (NMR) method that maximizes the advantages of high-resolution magic-angle-spinning (HRMAS), relative conventional liquid-state NMR approaches, when applied to intact biopsies of skeletal muscle specimens collected from burn trauma patients. This novel method, termed optimized adiabatic TOtal through Bond correlation SpectroscopY (TOBSY) solid-state NMR pulse sequence for two-dimensional (2D)1H-1H homonuclear scalar-coupling longitudinal isotropic mixing, was demonstrated to provide a 40–60% improvement in signal-to-noise ratio (SNR) relative to its liquid-state analogue TOCSY (TOtal Correlation SpectroscopY). Using 1-and 2-dimensional HRMAS NMR experiments, we identified several metabolites in burned tissues. Quantification of metabolites in burned tissues showed increased levels of lipid compounds, intracellular metabolites (e.g., taurine and phosphocreatine) and substantially decreased water-soluble metabolites (e.g., glutathione, carnosine, glucose, glutamine/glutamate and alanine). These findings demonstrate that HRMAS NMR Spectroscopy using TOBSY is a feasible technique that reveals new insights into the pathophysiology of burn trauma. Moreover, this method has applications that facilitate the development of novel therapeutic strategies

ECCENTRIC: a fast and unrestrained approach for high-resolution in vivo metabolic imaging at ultra-high field MR

A novel method for fast and high-resolution metabolic imaging, called ECcentric Circle ENcoding TRajectorIes for Compressed sensing (ECCENTRIC), has been developed and implemented on 7 Tesla human MRI. ECCENTRIC is a non-Cartesian spatial-spectral encoding method optimized for random undersampling of magnetic resonance spectroscopic imaging (MRSI) at ultra-high field. The approach provides flexible and random (k,t) sampling without temporal interleaving to improve spatial response function and spectral quality. ECCENTRIC needs low gradient amplitudes and slew-rates that reduces electrical, mechanical and thermal stress of the scanner hardware, and is robust to timing imperfection and eddy-current delays. Combined with a model-based low-rank reconstruction, this approach enables simultaneous imaging of up to 14 metabolites over the whole-brain at 2-3mm isotropic resolution in 4-10 minutes with high signal-to-noise ratio. In 20 healthy volunteers and 20 glioma patients ECCENTRIC demonstrated unprecedented mapping of fine structural details of metabolism in healthy brains and an extended metabolic fingerprinting of glioma tumors.Comment: 20 pages, 7 figures,2 tables, 10 pages supplementary materia

Early changes in glioblastoma metabolism measured by MR spectroscopic imaging during combination of anti-angiogenic cediranib and chemoradiation therapy are associated with survival

Precise assessment of treatment response in glioblastoma during combined anti-angiogenic and chemoradiation remains a challenge. In particular, early detection of treatment response by standard anatomical imaging is confounded by pseudo-response or pseudo-progression. Metabolic changes may be more specific for tumor physiology and less confounded by changes in blood-brain barrier permeability. We hypothesize that metabolic changes probed by magnetic resonance spectroscopic imaging can stratify patient response early during combination therapy. We performed a prospective longitudinal imaging study in newly diagnosed glioblastoma patients enrolled in a phase II clinical trial of the pan-vascular endothelial growth factor receptor inhibitor cediranib in combination with standard fractionated radiation and temozolomide (chemoradiation). Forty patients were imaged weekly during therapy with an imaging protocol that included magnetic resonance spectroscopic imaging, perfusion magnetic resonance imaging, and anatomical magnetic resonance imaging. Data were analyzed using receiver operator characteristics, Cox proportional hazards model, and Kaplan-Meier survival plots. We observed that the ratio of total choline to healthy creatine after 1 month of treatment was significantly associated with overall survival, and provided as single parameter: (1) the largest area under curve (0.859) in receiver operator characteristics, (2) the highest hazard ratio (HR = 85.85, P = 0.006) in Cox proportional hazards model, (3) the largest separation (P = 0.004) in Kaplan-Meier survival plots. An inverse correlation was observed between total choline/healthy creatine and cerebral blood flow, but no significant relation to tumor volumetrics was identified. Our results suggest that in vivo metabolic biomarkers obtained by magnetic resonance spectroscopic imaging may be an early indicator of response to anti-angiogenic therapy combined with standard chemoradiation in newly diagnosed glioblastoma

Low-power adiabatic sequences for in vivo localized two-dimensional chemical shift correlated MR spectroscopy

Novel low-power adiabatic sequences are demonstrated for in vivo localized two-dimensional correlated MR spectroscopy, such as correlated spectroscopy and total correlated spectroscopy. The design is based on three new elements for in vivo two-dimensional MRS: the use of gradient modulated constant adiabaticity GOIA-W(16,4) pulses for \ud \ud - (i) localization (correlated spectroscopy and total correlated spectroscopy) and \ud \ud - (ii) mixing (total correlated spectroscopy), and \ud \ud - (iii) the use of longitudinal mixing (z-filter) for magnetization transfer during total correlated spectroscopy. \ud \ud GOIA-W(16,4) provides accurate signal localization, and more importantly, lowers the SAR for both total correlated spectroscopy mixing and localization. Longitudinal mixing improves considerably (fivefolds) the efficiency of total correlated spectroscopy transfer. These are markedly different from previous 1D editing total correlated spectroscopy sequences using spatially nonselective pulses and transverse mixing. Fully adiabatic (adiabatic mixing with adiabatic localization) and semiadiabatic (adiabatic mixing with nonadiabatic localization) methods for two-dimensional total correlated spectroscopy are compared. Results are presented for simulations, phantoms, and in vivo two-dimensional spectra from healthy volunteers and patients with brain tumors obtained on 3T clinical platforms equipped with standard hardware. To the best of our knowledge, this is the first demonstration of in vivo adiabatic two-dimensional total correlated spectroscopy and fully adiabatic two-dimensional correlated spectroscopy. It is expected that these methodological developments will advance the in vivo applicability of multi(spectrally)dimensional MRS to reliably identify metabolic biomarkers

Achieving high-resolution ¹H-MRSI of the human brain with compressed-sensing and low-rank reconstruction at 7 Tesla

Low sensitivity MR techniques such as magnetic resonance spectroscopic imaging (MRSI) greatly benefit from the gain in signal-to-noise provided by ultra-high field MR. High-resolution and whole-slab brain MRSI remains however very challenging due to lengthy acquisition, low signal, lipid contamination and field inhomogeneity. In this study, we propose an acquisition-reconstruction scheme that combines 1H free-induction-decay (FID)-MRSI sequence, short TR acquisition, compressed sensing acceleration and low-rank modeling with total-generalized-variation constraint to achieve metabolite imaging in two and three dimensions at 7 Tesla. The resulting images and volumes reveal highly detailed distributions that are specific to each metabolite and follow the underlying brain anatomy. The MRSI method was validated in a high-resolution phantom containing fine metabolite structures, and in five healthy volunteers. This new application of compressed sensing acceleration paves the way for high-resolution MRSI in clinical setting with acquisition times of 5 min for 2D MRSI at 2.5 mm and of 20 min for 3D MRSI at 3.3 mm isotropic

Adiabatic L-COSY at 7T

In vivo Localized Correlation Spectroscopy (L-COSY, 90ss 180ss t1 90ss Acq) is a developing technique that enables researchers to un-scramble spectroscopic findings in a relatively narrow spectral bandwidth along a second dimension, and thus, facilitating analysis and improving reliability. However, using this technique at high Bo fields requires appropriate optimization. Namely, the following issues must be addressed: (1) lower available peak RF amplitude, (2) easily reaching a high SAR level (3) higher B1 inhomogeneity due to dielectric resonances and long RF wavelength and (4) requirement of larger excitation and refocusing pulses bandwidths to reduce chemical shift misregistration, Δ x , where it can be quantified as Δ x = Δω / γ G, where Δω is resonance frequency difference between any 2 spectral lines, γ is the gyromagnetic ratio and G is the amplitude of slice selective gradient. Inhomogeneous B1 fields at 7T means that Shinnar-Le Roux optimized refocusing pulses cannot be used, let alone the associated SAR levels. We here present the first application of adiabatic-Localized-COSY (AL-COSY ) where spatial selection and excitation along two orientations is achieved by two pairs of slice-selective adiabatic inversion pulses, thereby increasing bandwidth and reducing B1 sensitivity