Tissue Optimisation Strategies for High Quality Ex Vivo Diffusion Imaging

Ex vivo diffusion imaging can be used to study healthy and pathological tissue microstructure in the rodent brain with microscopic resolution, providing a link between in vivo MRI and ex vivo microscopy techniques. A major challenge for the successful acquisition of ex vivo diffusion imaging data however are changes in the relaxivity and diffusivity of brain tissue following perfusion fixation. In this study we address this question by examining the combined effects of tissue preparation factors that influence image quality, including tissue rehydration time, fixative concentration and contrast agent concentration. We present an optimisation strategy combining these factors to manipulate the T1 and T2 of fixed tissue and maximise signal-to-noise ratio (SNR) efficiency. Applying this strategy in the rat brain resulted in a doubling of SNR and an increase in SNR per unit time by 135% in grey matter and 88% in white matter. This enabled the acquisition of excellent quality high-resolution (78 μm isotropic voxel size) diffusion data in less than 4 days, with a b-value of 4000 s/mm2, 30 diffusion directions and a field of view of 40 x 13 x 18 mm, using a 9.4 Tesla scanner with a standard 39 mm volume coil and a 660 mT/m 114 mm gradient insert. It was also possible to achieve comparable data quality for a standard resolution (150 μm) diffusion dataset in 21/4 hours. In conclusion, the optimisation strategy presented here may be used to improve signal quality, increase spatial resolution and/or allow faster acquisitions in preclinical ex vivo diffusion MRI experiments.

Volume and surface coil simultaneous reception (VSSR) method for intensity inhomogeneity correction in MRI

BACKGROUND: Addressing intensity inhomogeneity is critical in magnetic resonance imaging (MRI) because associated errors can adversely affect post-processing and quantitative analysis of images (i.e., segmentation, registration, etc.), as well as the accuracy of clinical diagnosis. Although several prior methods have been proposed to eliminate or correct intensity inhomogeneity, some significant disadvantages have remained, including alteration of tissue contrast, poor reliability and robustness of algorithms, and prolonged acquisition time. OBJECTIVE: In this study, we propose an intensity inhomogeneity correction method based on volume and surface coils simultaneous reception (VSSR). METHODS: The VSSR method comprises of two major steps: 1) simultaneous image acquisition from both volume and surface coils and 2) denoising of volume coil images and polynomial surface fitting of bias field. Extensive in vivo experiments were performed considering various anatomical structures, acquisition sequences, imaging resolutions, and orientations. In terms of correction performance, the proposed VSSR method was comparatively evaluated against several popular methods, including multiplicative intrinsic component optimization and improved nonparametric nonuniform intensity normalization bias correction methods. RESULTS: Experimental results show that VSSR is more robust and reliable and does not require prolonged acquisition time with the volume coil. CONCLUSION: The VSSR may be considered suitable for general implementation.

Phosphate Brain Energy Metabolism and Cognition in Alzheimer’s Disease: A Spectroscopy Study Using Whole-Brain Volume-Coil 31Phosphorus Magnetic Resonance Spectroscopy at 7Tesla

IntroductionMitochondrial dysfunction is a neurometabolic hallmark signaling abnormal brain energy metabolism (BEM) targeted as a potential early marker of Alzheimer’s disease (AD). Advanced imaging technologies, such as 31phosphorus magnetic resonance spectroscopy (31P MRS) at ultra-high-field (UHF) magnetic strength 7T, provide sensitive phosphate-BEM (p-BEM) data with precision. The study’s first goal was to develop a methodology to measure phosphate energy and membrane metabolites simultaneously across the whole-brain using volume-coil 31P MRS at 7T in three groups-cognitively normal (CN), amnestic mild cognitive impairment (aMCI), and AD. The second aim investigated whether p-BEM markers in the four brain regions-frontal, temporal, parietal, and occipital were significantly different across the three groups. The final goal examined correspondence between the p-BEM markers and cognition in the three groups.MethodsForty-one participants (CN = 15, aMCI = 15, AD = 11) were enrolled and completed cognitive assessment and scan. The cognitive domains included executive function (EF), memory, attention, visuospatial skills, and language. The p-BEM markers were measured using energy reserve index (PCr/t-ATP), energy consumption index (intracellular_Pi/t-ATP), metabolic state indicator (intracellular_Pi/PCr), and regulatory co-factors [magnesium (Mg2+) and intracellular pH].ResultsThirteen metabolites were measured simultaneously from the whole brain for all three group with high spectral resolution at UHF. In the aMCI group, a lower p-BEM was observed compared to CN group based on two markers, i.e., energy reserve (p = 0.009) and energy consumption (p = 0.05) indices; whereas in AD a significant increase was found in metabolic stress indicator (p = 0.007) and lower Mg2+ (p = 0.004) in the temporal lobes compared to aMCI using ANOVA between group analytical approach. Finally, using a linear mixed model, a significant positive correlation was found between Mg2+ and cognitive performance of memory (p = 0.013), EF (p = 0.023), and attention (p = 0.0003) in CN but not in aMCI or AD.ConclusionTo our knowledge, this is the first study to show that it is possible to measure p-BEM in vivo with precision at UHF across the three groups. Moreover, the findings suggest that p-BEM may be compromised in aMCI even before an AD diagnosis, which in future studies should explore to examine whether this energy crisis contributes to some of the earliest neuropathophysiologic changes in AD.

Implantable NMR Microcoils in Rats: A New Tool for Exploring Tumor Metabolism at Sub-Microliter Scale?

The aim of this study was to evaluate the potential of a miniaturized implantable nuclear magnetic resonance (NMR) coil to acquire in vivo proton NMR spectra in sub-microliter regions of interest and to obtain metabolic information using magnetic resonance spectroscopy (MRS) in these small volumes. For this purpose, the NMR microcoils were implanted in the right cortex of healthy rats and in C6 glioma-bearing rats. The dimensions of the microcoil were 450 micrometers wide and 3 mm long. The MRS acquisitions were performed at 7 Tesla using volume coil for RF excitation and microcoil for signal reception. The detection volume of the microcoil was measured equal to 450 nL. A gain in sensitivity equal to 76 was found in favor of implanted microcoil as compared to external surface coil. Nine resonances from metabolites were assigned in the spectra acquired in healthy rats (n = 5) and in glioma-bearing rat (n = 1). The differences in relative amplitude of choline, lactate and creatine resonances observed in glioma-bearing animal were in agreement with published findings on this tumor model. In conclusion, the designed implantable microcoil is suitable for in vivo MRS and can be used for probing the metabolism in localized and very small regions of interest in a tumor.

Abstract 12881: Noninvasive In Vivo Assessment of Cardiac Metabolism in Dobutamine-stressed Ischemic Rat Hearts Using Hyperpolarized 13 C MRI

Introduction and Hypothesis: Conventional metabolic imaging methods such as PET, dobutamine stress echo or late gadolinium enhancement do not directly detect the functional state of the critical organelle in oxidative metabolism, the mitochondrion. Hyperpolarized (HP) 13 C-metabolic imaging has been used to assess mitochondrial function in preclinical models and is an exciting new imaging method for evaluating the ischemic myocardium noninvasively. This study aims to evaluate myocardial response to dobutamine stress in ischemic rat hearts using HP-[1- 13 C]pyruvate. Methods: Metabolism of HP[1- 13 C]pyruvate was investigated in male SD rats in four groups: 1. normal myocardium (NM), 2. ischemic myocardium (IM), 3. NM+dobutamine, 4. IM+dobutamine. The myocardial ischemic model was developed by partial occlusion of the coronary artery as described in earlier studies by others. For dobutamine stress HP-MRS, intra-peritoneal injection of 1.5 mg/kg of dobutamine was administered before positioning the animal in the MRI scanner. 13 C data were acquired 7 days after the surgery in a 4.7 T MRI scanner using a Varian 60 mm dual-tuned 1 H/ 13 C linear volume coil. Anatomical 1 H images were acquired for slice planning and positioning. 13 C intensity maps were generated and displayed as overlays on grayscale 1 H images. In separate experiments, in vivo HP- 13 C-MRS data acquisition was initiated immediately after the pyruvate injection. Results: The HP signals from [1- 13 C]lactate, [1- 13 C]alanine, and 13 C-bicarbonate were detected in real-time 13 C spectra from hearts following injection of HP[1- 13 C]pyruvate. In hearts with partial coronary ligation, the MRS data were acquired from a mixture of ischemic and nonischemic myocardium. A 27% decrease in bicarbonate production was observed in hearts with ischemic myocardium compared to control hearts. After stimulation of NM hearts with dobutamine, less bicarbonate was produced from HP-pyruvate likely due to an increased contribution of other endogenous substrates to acetyl-CoA. Production of bicarbonate was unchanged in IM hearts following adrenergic stimulation. Conclusions: Our results demonstrated that decreased oxidative metabolism of pyruvate as a result of myocardial ischemia and dobutamine stress.