Mapping intracellular NAD content in entire human brain using phosphorus-31 MR spectroscopic imaging at 7 Tesla.

Introduction: Nicotinamide adenine dinucleotide (NAD) is a crucial molecule in cellular metabolism and signaling. Mapping intracellular NAD content of human brain has long been of interest. However, the sub-millimolar level of cerebral NAD concentration poses significant challenges for in vivo measurement and imaging. Methods: In this study, we demonstrated the feasibility of non-invasively mapping NAD contents in entire human brain by employing a phosphorus-31 magnetic resonance spectroscopic imaging (31P-MRSI)-based NAD assay at ultrahigh field (7 Tesla), in combination with a probabilistic subspace-based processing method. Results: The processing method achieved about a 10-fold reduction in noise over raw measurements, resulting in remarkably reduced estimation errors of NAD. Quantified NAD levels, observed at approximately 0.4 mM, exhibited good reproducibility within repeated scans on the same subject and good consistency across subjects in group data (2.3 cc nominal resolution). One set of higher-resolution data (1.0 cc nominal resolution) unveiled potential for assessing tissue metabolic heterogeneity, showing similar NAD distributions in white and gray matter. Preliminary analysis of age dependence suggested that the NAD level decreases with age. Discussion: These results illustrate favorable outcomes of our first attempt to use ultrahigh field 31P-MRSI and advanced processing techniques to generate a whole-brain map of low-concentration intracellular NAD content in the human brain.

Noninvasive assessment of myocardial energy metabolism and dynamics using in vivo deuterium MRS imaging.

PURPOSE: The assessment of cellular energy metabolism is crucial for understanding myocardial physiopathology. Here, we conducted a pilot study to develop an alternative imaging approach for the assessment of myocardial energy metabolism. METHODS: We developed a deuterium MRSI method to noninvasively monitor the accumulation of deuterated downstream metabolites and deuterated water in rat hearts infused with deuterated glucose or acetate substrate on a 16.4 Tesla animal scanner. RESULTS: We found that the deuterated water accumulation rate and isotopic turnover rate of deuterated glutamate/glutamine via the tricarboxylic acid cycle and exchange in rat hearts were much higher when infused with acetate compared to that with glucose, demonstrating the myocardium substrate preference for acetate over glucose. CONCLUSION: We demonstrated the feasibility of deuterium MRSI for noninvasive imaging and assessment of myocardial energy metabolism in vivo. Although the strong signal and large dynamics of myocardial deuterated water may provide a sensitive imaging biomarker, quantifying the metabolic rates still poses a challenge due to the confounding effects of blood recirculation, perfusion, and multiple deuterated water production pathways. In contrast, the deuterated glutamate/glutamine signal and change should directly reflect the metabolic activity of the myocardial tricarboxylic acid cycle, which can be used to study the metabolic shift in substance preference between acetate and glucose in the diseased state. Deuterium MRSI is noninvasive and robust and may have the potential to assess myocardial energy metabolism in human patients.

Quantitative and simultaneous measurement of oxygen consumption rates in rat brain and skeletal muscle using 17 O MRS imaging at 16.4T.

PURPOSE: Oxygen-17 (17 O) MRS imaging, successfully used in the brain, is extended by imaging the oxygen metabolic rate in the resting skeletal muscle and used to determine the total whole-body oxygen metabolic rate in the rat. METHODS: During and after inhalations of 17 O2 gas, dynamic 17 O MRSI was performed in rats (n = 8) ventilated with N2 O or N2 at 16.4 T. Time courses of the H217 O concentration from regions of interest located in brain and muscle tissue were examined and used to fit an animal-adapted 3-phase metabolic model of oxygen consumption. CBF was determined with an independent washout method. Finally, body oxygen metabolic rate was calculated using a global steady-state approach. RESULTS: Cerebral metabolic rate of oxygen consumption was 1.97 ± 0.19 µmol/g/min on average. The resting metabolic rate of oxygen consumption in skeletal muscle was 0.32 ± 0.12 µmol/g/min and >6 times lower than cerebral metabolic rate of oxygen consumption. Global oxygen consumed by the body was 24.2 ± 3.6 mL O2 /kg body weight/min. CBF was estimated to be 0.28 ± 0.02 mL/g/min and 0.34 ± 0.06 mL/g/min for the N2 and N2 O ventilation condition, respectively. CONCLUSION: We have evaluated the feasibility of 17 O MRSI for imaging and quantifying the oxygen consumption rate in low metabolizing organs such as the skeletal muscle at rest. Additionally, we have shown that CBF is slightly increased in the case of ventilation with N2 O. We expect this study to be beneficial to the application of 17 O MRSI to a wider range of organs, although further validation is advised.

Tunable Ultrahigh Dielectric Constant (tuHDC) Ceramic Technique to Largely Improve RF Coil Efficiency and MR Imaging Performance.

This work introduces an innovative magnetic resonance (MR) imaging technology that incorporates radiofrequency (RF) coil(s) with permittivity-tunable ultrahigh dielectric constant (tuHDC) ceramics to significantly improve RF coil transmission and reception efficiencies, MR imaging sensitivity and signal-to-noise ratio (SNR). The tuHDC ceramics made of composite barium strontium titanate (BST) compounds (Ba0.6 Sr0.4 TiO3) have low dielectric loss and very high permittivity tunability from 2,000 to 15000 by varying the ceramic temperature between 0°C and 40°C to achieve an optimal permittivity for MR imaging application. We demonstrated for the first time the proof of concept using the BST-based tuHDC-RF-coil technology to improve MR spectroscopic imaging performance of 17O nuclide at 10.5 Tesla (T) at a low ceramic temperature and 23Na nuclide at 7T at room temperature. We discovered a large and spatially independent noise reduction under an optimal ceramic temperature, which synergistically resulted in an unprecedented SNR improvement. Large improvements were also demonstrated for 1H MRI on a 1.5T clinical scanner using the same ceramics. The tuHDC-RF-coil technology is robust, flexible and cost-effective; it presents a technical breakthrough to significantly improve imaging sensitivity and resolution for broad MR imaging applications; which is critical for advancing biomedical and neuroscience research, and improving diagnostic imaging.

(17)O relaxation times in the rat brain at 16.4 tesla.

PURPOSE: Measurement of the cerebral metabolic rate of oxygen (CMRO2 ) by means of direct imaging of the (17) O signal can be a valuable tool in neuroscientific research. However, knowledge of the longitudinal and transverse relaxation times of different brain tissue types is required, which is difficult to obtain because of the low sensitivity of natural abundance H2 (17) O measurements. METHODS: Using the improved sensitivity at a field strength of 16.4 Tesla, relaxation time measurements in the rat brain were performed in vivo and postmortem with relatively high spatial resolutions, using a chemical shift imaging sequence. RESULTS: In vivo relaxation times of rat brain were found to be T1 = 6.84 ± 0.67 ms and T2 * = 1.77 ± 0.04 ms. Postmortem H2 (17) O relaxometry at enriched concentrations after inhalation of (17) O2 showed similar T2 * values for gray matter (1.87 ± 0.04 ms) and white matter, significantly longer than muscle (1.27 ± 0.05 ms) and shorter than cerebrospinal fluid (2.30 ± 0.16 ms). CONCLUSION: Relaxation times of brain H2 (17) O were measured for the first time in vivo in different types of tissues with high spatial resolution. Because the relaxation times of H2 (17) O are expected to be independent of field strength, our results should help in optimizing the acquisition parameters for experiments also at other MRI field strengths.

Monitoring the stress-level of rats with different types of anesthesia: a tail-artery cannulation protocol.

INTRODUCTION: Functional MRI in rats under anesthesia can largely minimize motion artifacts and attenuate the stress of the animal. However, two issues remain to be clarified and improved. First, fMRI results obtained with different types of anesthesia during surgical preparation and imaging show a large variability, which could be caused by the variable stress level of the rodents. Second, the most common surgical procedure used for anesthesia, blood gas analysis and mean arterial blood-pressure (MABP) monitoring is the femoral vein and artery catheterization that makes longitudinal studies difficult. METHODS: In order to examine the variability of the stress level with three different anesthesia protocols using isoflurane (Iso), medetomidine-ketamine (MK) or propofol-remifentanil (PR), we measured the plasma corticosterone (CORT) concentration with (125)I-radioimmunoassay in blood samples collected prior to, immediately after and 60min after surgery. Tail-artery and vein catheterization was adapted for long-term monitoring of MABP with periodic blood sampling and is proposed as a less invasive and technically simple alternative to femoral vessel catheterization in fMRI preparation protocols. RESULTS: We show that the CORT concentration depends on the anesthesia protocol with both alternatives providing more efficient stress reduction than the protocol using Iso. However, only the protocol using PR achieved a significant hormone reduction during surgery. Stress was not reliably manifested in changes in heart-rate and breathing-rate. Anesthesia and strain related changes in these two physiological parameters may be assigned to the pharmacological effects of the premedication and anesthetic agents. The results indicate also that MABP can be monitored over a long period of time (e.g. functional imaging session) through an arterial access point in the rat tail after cannulation with the proposed procedure. DISCUSSION AND CONCLUSION: Animals can experience stress during fMRI preparation protocols without obvious signs in commonly monitored physiological parameters. Our results challenge the efficiency of surgical protocols using Iso as mono-anesthetic agent, even when extended with topical analgesia. It was demonstrated that the CORT-based stress-level measurement through tail-artery cannulation can be used for developing anesthesia protocols (i.e. the presented PR protocol) when setting up future fMRI studies. The proposed surgical method for the tail is expected to facilitate longitudinal fMRI studies with permanent arterial access.

In vivo measurement of CBF using ¹7O NMR signal of metabolically produced H2¹7O as a perfusion tracer.

The cerebral metabolic rate of oxygen of small animals can be reliably imaged using the in vivo (17) O magnetic resonance approach at high field. However, a separate measurement is required for imaging the cerebral blood flow in the same animal. In this study, we demonstrate that the (17) O NMR signal of metabolically produced H2 (17) O in the rat brain following an (17) O2 inhalation can serve as a perfusion tracer and its decay rate can be used to determine the absolute values of cerebral blood flow across a wide range of animal conditions. This finding suggests that the in vivo (17) O magnetic resonance approach is capable of imaging both cerebral metabolic rate of oxygen and cerebral blood flow simultaneously and noninvasively; and it provides new utilities for studying the cerebral oxygen metabolism and perfusion commonly associated with brain function and diseases.