Fast Spectroscopic Imaging Research Articles

Predicting the Onset of Ischemic Stroke With Fast High-Resolution 3D MR Spectroscopic Imaging.

Neurometabolite concentrations provide a direct index of infarction progression in stroke. However, their relationship with stroke onset time remains unclear. To assess the temporal dynamics of N-acetylaspartate (NAA), creatine, choline, and lactate and estimate their value in predicting early (<6 hours) vs. late (6-24hours) hyperacute stroke groups. Cross-sectional cohort. A total of 73 ischemic stroke patients scanned at 1.8-302.5 hours after symptom onset, including 25 patients with follow-up scans. A 3 T/magnetization-prepared rapid acquisition gradient echo sequence for anatomical imaging, diffusion-weighted imaging and fluid-attenuated inversion recovery imaging for lesion delineation, and 3D MR spectroscopic imaging (MRSI) for neurometabolic mapping. Patients were divided into hyperacute (0-24hours), acute (24hours to 1 week), and subacute (1-2 weeks) groups, and into early (<6 hours) and late (6-24hours) hyperacute groups. Bayesian logistic regression was used to compare classification performance between early and late hyperacute groups by using different combinations of neurometabolites as inputs. Linear mixed effects modeling was applied for group-wise comparisons between NAA, creatine, choline, and lactate. Pearson's correlation analysis was used for neurometabolites vs. time. P < 0.05 was considered statistically significant. Lesional NAA and creatine were significantly lower in subacute than in acute stroke. The main effects of time were shown on NAA (F=14.321) and creatine (F= 12.261). NAA was significantly lower in late than early hyperacute patients, and was inversely related to time from symptom onset across both groups (r=-0.440). The decrease of NAA and increase of lactate were correlated with lesion volume (NAA: r=-0.472; lactate: r=0.366) in hyperacute stroke. Discrimination was improved by combining NAA, creatine, and choline signals (area under the curve [AUC]=0.90). High-resolution 3D MRSI effectively assessed the neurometabolite changes and discriminated early and late hyperacute stroke lesions. 1. Stage 2.

BIMG-04. MAPPING HETEROGENEITY OF HIGH-GRADE GLIOMA METABOLISM USING HIGH RESOLUTION 7T MRSI

OBJECTIVESNeurosurgical resection in gliomas depends on the precise preoperative definition of the tumor and its margins to realize a safe maximum resection that translates into a better patient outcome. New metabolic imaging techniques could improve this delineation as well as designate targets for biopsies. We validated the performance of our fast high-resolution whole-brain 3D-magnetic resonance spectroscopic imaging (MRSI) method at 7T in high-grade gliomas (HGGs) as first step to this regard.METHODSWe measured 23 patients with HGGs at 7T with MRSI covering the whole cerebrum with 3.4mm isotropic resolution in 15 min. Quantification used a basis-set of 17 neurochemical components. They were evaluated for their reliability/quality and compared to neuroradiologically segmented tumor regions-of-interest (necrosis, contrast-enhanced, non-contrast-enhanced+edema, peritumoral) and histopathology (e.g., grade, IDH-status).RESULTSWe found 18/23 measurements to be usable and ten neurochemicals quantified with acceptable quality. The most common denominators were increases of glutamine, glycine, and total choline as well as decreases of N-acetyl-aspartate and total creatine over most tumor regions. Other metabolites like taurine and serine showed mixed behavior. We further found that heterogeneity in the metabolic images often continued into the peritumoral region. While 2-hydroxy-glutarate could not be satisfyingly quantified, we found a tendency for a decrease of glutamate in IDH1-mutant HGGs.DISCUSSIONOur findings corresponded well to clinical tumor segmentation but were more heterogeneous and often extended into the peritumoral region. Our results corresponded to previous knowledge, but with previously not feasible resolution. Apart from glycine/glutamine and their role in glioma progression, more research on the connection of glutamate and others to specific mutations is necessary. The addition of low-grade gliomas and statistical ROI analysis in a larger cohort will be the next important steps to define the benefits of our 7T MRSI approach for the definition of spatial metabolic tumor profiles.

Principal component analysis facilitated fast and noninvasive Raman spectroscopic imaging of plant cell wall pectin distribution and interaction with enzymatic hydrolysis

AbstractThe plant cell wall is a complex network of polysaccharides. A better understanding of the plant cell wall polysaccharide content, distribution, and interactions among them could be instrumental for our further understanding of plant cell wall in general. Confocal Raman microscopy (CRM) is a powerful tool that could reveal details about chemical landscape of the plant cell wall with micrometer resolution. However, the low signal‐to‐noise (S/N) ratio of Raman spectral signal led to low throughput of Raman imaging, which limited its application in plant cell wall study. In this study, the interaction between the cell wall polysaccharides and the pectin enzyme endo‐polygalacturonase (EPG) was characterized by analyzing Raman images collected before and after EPG treatment at high scanning speed. The obtained low S/N ratio Raman spectra were processed with principal component analysis (PCA) and hierarchical clustering analysis (HCA) to recover information‐rich signature changes in Raman signal dataset that reflected the changes in the polysaccharides caused specifically by the enzymatic hydrolysis. The PCA reconstruction technique significantly improved the S/N ratio of the spectra dataset while kept the Raman signal intact. Further analysis of principal components (PCs) revealed the pectin distribution and its interaction with the enzyme, which provided organizational details of pectin inside the onion plant cell wall. The technique could be used to reveal polysaccharide organization and distribution inside plant cell walls.

Realistic head-shaped phantom with brain-mimicking metabolites for 7 T spectroscopy and spectroscopic imaging.

PurposeMoving to ultra‐high fields (≥7 T), the inhomogeneity of both RF (B 1) and static (B 0) magnetic fields increases, which further motivates us to design a realistic head‐shaped phantom, especially for spectroscopic imaging. Such phantoms provide images similar to the human brain and serve as a reliable tool for developing and examining methods in MRI. This study aims to develop and characterize a realistic head‐shaped phantom filled with brain‐mimicking metabolites for MRS and magnetic resonance spectroscopic imaging in a 7 T MRI scanner.MethodsA 3D head‐shaped container with three sections—mimicking brain, muscle and precranial lipid—was constructed. The phantom was designed to provide robustness to heating, mechanical damage and leakage, with easy refilling. The head’s shape and the agarose mixture were optimized to provide B 0 and B 1 distributions and T 1/T 2 relaxation values similar to those of human brain. Eight brain‐tissue‐mimicking metabolites were included for spectroscopy. The phantom was evaluated for localized spectroscopy, fast spectroscopic imaging and fat suppression.ResultsThe B 0 and B 1 maps showed distribution similar to that of human brain, with increased B 0 inhomogeneity near the nasal and ear areas and reduced B 1 in the temporal lobe and brain stem regions, as expected in vivo. The metabolites’ concentrations were verified by single‐voxel spectroscopy, showing an average deviation of 11%. Fast spectroscopic imaging and imaging with fat suppression were demonstrated.ConclusionA 3D head‐shaped phantom for human brain imaging and spectroscopic imaging in 7 T MRI was demonstrated, making it a realistic phantom for methodology development at 7 T.

High-resolution metabolic imaging of high-grade gliomas using 7T-CRT-FID-MRSI

ObjectivesSuccessful neurosurgical intervention in gliomas depends on the precision of the preoperative definition of the tumor and its margins since a safe maximum resection translates into a better patient outcome. Metabolic high-resolution imaging might result in improved presurgical tumor characterization, and thus optimized glioma resection. To this end, we validated the performance of a fast high-resolution whole-brain 3D-magnetic resonance spectroscopic imaging (MRSI) method at 7T in a patient cohort of 23 high-grade gliomas (HGG). Materials and methodsWe preoperatively measured 23 patients with histologically verified HGGs (17 male, 8 female, age 53 ± 15) with an MRSI sequence based on concentric ring trajectories with a 64 × 64 × 39 measurement matrix, and a 3.4 × 3.4 × 3.4 mm3 nominal voxel volume in 15 min. Quantification used a basis-set of 17 components including N-acetyl-aspartate (NAA), total choline (tCho), total creatine (tCr), glutamate (Glu), glutamine (Gln), glycine (Gly) and 2-hydroxyglutarate (2HG). The resultant metabolic images were evaluated for their reliability as well as their quality and compared to spatially segmented tumor regions-of-interest (necrosis, contrast-enhanced, non-contrast enhanced + edema, peritumoral) based on clinical data and also compared to histopathology (e.g., grade, IDH-status). ResultsEighteen of the patient measurements were considered usable. In these patients, ten metabolites were quantified with acceptable quality. Gln, Gly, and tCho were increased and NAA and tCr decreased in nearly all tumor regions, with other metabolites such as serine, showing mixed trends. Overall, there was a reliable characterization of metabolic tumor areas. We also found heterogeneity in the metabolic images often continued into the peritumoral region. While 2HG could not be satisfyingly quantified, we found an increase of Glu in the contrast-enhancing region of IDH-wildtype HGGs and a decrease of Glu in IDH1-mutant HGGs. ConclusionsWe successfully demonstrated high-resolution 7T 3D-MRSI in HGG patients, showing metabolic differences between tumor regions and peritumoral tissue for multiple metabolites. Increases of tCho, Gln (related to tumor metabolism), Gly (related to tumor proliferation), as well as decreases in NAA, tCr, and others, corresponded very well to clinical tumor segmentation, but were more heterogeneous and often extended into the peritumoral region.

Low SAR 31 P (multi-echo) spectroscopic imaging using an integrated whole-body transmit coil at 7T.

Phosphorus (31P) MRSI provides opportunities to monitor potential biomarkers. However, current applications of 31P MRS are generally restricted to relatively small volumes as small coils are used. Conventional surface coils require high energy adiabatic RF pulses to achieve flip angle homogeneity, leading to high specific absorption rates (SARs), and occupy space within the MRI bore. A birdcage coil behind the bore cover can potentially reduce the SAR constraints massively by use of conventional amplitude modulated pulses without sacrificing patient space. Here, we demonstrate that the integrated 31P birdcage coil setup with a high power RF amplifier at 7 T allows for low flip angle excitations with short repetition time (T R) for fast 3D chemical shift imaging (CSI) and 3D T 1‐weighted CSI as well as high flip angle multi‐refocusing pulses, enabling multi‐echo CSI that can measure metabolite T 2, over a large field of view in the body. B 1 + calibration showed a variation of only 30% in maximum B 1 in four volunteers. High signal‐to‐noise ratio (SNR) MRSI was obtained in the gluteal muscle using two fast in vivo 3D spectroscopic imaging protocols, with low and high flip angles, and with multi‐echo MRSI without exceeding SAR levels. In addition, full liver MRSI was achieved within SAR constraints. The integrated 31P body coil allowed for fast spectroscopic imaging and successful implementation of the multi‐echo method in the body at 7 T. Moreover, no additional enclosing hardware was needed for 31P excitation, paving the way to include larger subjects and more space for receiver arrays. The increase in possible number of RF excitations per scan time, due to the improved B 1 + homogeneity and low SAR, allows SNR to be exchanged for spatial resolution in CSI and/or T 1 weighting by simply manipulating T R and/or flip angle to detect and quantify ratios from different molecular species.

Combining multiband slice selection with consistent k-t-space EPSI for accelerated spectral imaging.

To design and implement a multislice MRSI method for fast spectroscopic imaging, using a modified version of echo planar spectroscopic imaging (EPSI) that offers higher spectral width and/or shorter scan time. Echo planar spectroscopic imaging suffers from inconsistencies between readout lines acquired with gradients of opposite signs, which has typically been addressed by reconstructing the "positive" and "negative" data sets separately and averaging the two. Nevertheless, consistency between the readout lines of each phase encode can be achieved by interposing the EPSI readouts with alternating "blipped" phase-encode gradients. This method exchanges inconsistencies along the temporal dimension with inconsistencies along the phase-encode dimension, which are straightforward to correct, as is conventionally done in various EPI reconstruction schemes. Such consistent k-t-space EPSI doubles the spectral width in comparison to EPSI, or, in an alternative realization, yields the same spectral width as EPSI, but at half the acquisition time. In this work, multiband CAIPIRINHA (controlled aliasing in parallel imaging results in higher acceleration) slice selection was integrated with consistent k-t-space EPSI to further accelerate the measurement 2-fold. The feasibility of a consistent k-t-space EPSI was demonstrated in both phantoms and in vivo brain imaging at 3 T, and four pulse scheme variants were evaluated. It was demonstrated to be useful in optimizing the spectral width and scan acceleration, both of which are limiting factors in vivo. Dual-band implementation was shown to shorten the duration of the scan 4-fold. The consistent k-t-space EPSI can be used to accelerate MRSI or, alternatively, double its spectral width. Adding dual-band CAIPIRINHA further accelerates the acquisition by a factor of 2.

Fast data acquisition techniques in magnetic resonance spectroscopic imaging.

Magnetic resonance spectroscopic imaging (MRSI) is an important technique for assessing the spatial variation of metabolites in vivo. The long scan times in MRSI limit clinical applicability due to patient discomfort, increased costs, motion artifacts, and limited protocol flexibility. Faster acquisition strategies can address these limitations and could potentially facilitate increased adoption of MRSI into routine clinical protocols with minimal addition to the current anatomical and functional acquisition protocols in terms of imaging time. Not surprisingly, a lot of effort has been devoted to the development of faster MRSI techniques that aim to capture the same underlying metabolic information (relative metabolite peak areas and spatial distribution) as obtained by conventional MRSI, in greatly reduced time. The gain in imaging time results, in some cases, in a loss of signal-to-noise ratio and/or in spatial and spectral blurring. This review examines the current techniques and advances in fast MRSI in two and three spatial dimensions and their applications. This review categorizes the acceleration techniques according to their strategy for acquisition of the k-space. Techniques such as fast/turbo-spin echo MRSI, echo-planar spectroscopic imaging, and non-Cartesian MRSI effectively cover the full k-space in a more efficient manner per TR . On the other hand, techniques such as parallel imaging and compressed sensing acquire fewer k-space points and employ advanced reconstruction algorithms to recreate the spatial-spectral information, which maintains statistical fidelity in test conditions (ie no statistically significant differences on voxel-wise comparisions) with the fully sampled data. The advantages and limitations of each state-of-the-art technique are reviewed in detail, concluding with a note on future directions and challenges in the field of fast spectroscopic imaging.

A Programmable Optical Filter With Arbitrary Transmittance for Fast Spectroscopic Imaging and Spectral Data Post-Processing

Spectral reconstruction method based on narrow-band measurements has been demonstrated to achieve ultrafast spectroscopic imaging with high spatial and spectral resolution, in which multiple narrow-band images are collected by using several specific filters. Although commercially available filters can be employed in such method, filters with complex transmittance that are difficult to be fabricated typically show significant improvement in spectral reconstruction accuracy. In this study, a two dimensional programmable optical filter based on digital micromirror device (DMD) is proposed, in which its transmittance spectrum can be arbitrarily and quickly switched to realize complex transmittance. Furthermore, its flexible transmittance enables directly hardware-based spectral data post-processing, which can perform data acquisition and analysis simultaneously. Those have been evaluated by the diffuse reflectance spectra from normal and occluded skin flaps, as well as Raman spectra from live, apoptosis and necrosis leukemia cells. Our simulation results show that much higher spectral reconstruction accuracies can be achieved by the optimized filters with complex transmittance. Furthermore, the classification accuracy by using the proposed method is comparable to those achieved by conventional numerical methods. Therefore, based on the proposed programmable optical filter, fast spectroscopic imaging with high spatial and spectral resolution can be achieved for observing fast changing phenomena and even real-time target identification.

Fast 3D rosette spectroscopic imaging of neocortical abnormalities at 3 T: Assessment of spectral quality.

To use a fast 3D rosette spectroscopic imaging acquisition to quantitatively evaluate how spectral quality influences detection of the endogenous variation of gray and white matter metabolite differences in controls, and demonstrate how rosette spectroscopic imaging can detect metabolic dysfunction in patients with neocortical abnormalities. Data were acquired on a 3T MR scanner and 32-channel head coil, with rosette spectroscopic imaging covering a 4-cm slab of fronto-parietal-temporal lobes. The influence of acquisition parameters and filtering on spectral quality and sensitivity to tissue composition was assessed by LCModel analysis, the Cramer-Rao lower bound, and the standard errors from regression analyses. The optimized protocol was used to generate normative white and gray matter regressions and evaluate three patients with neocortical abnormalities. As a measure of the sensitivity to detect abnormalities, the standard errors of regression for Cr/NAA and Ch/NAA were significantly correlated with the Cramer-Rao lower bound values (R = 0.89 and 0.92, respectively, both with P < 0.001). The rosette acquisition with a duration of 9.6 min, produces a mean Cramer-Rao lower bound (%) over the entire slab of 4.6 ± 2.6 and 5.8 ± 2.3 for NAA and Cr, respectively. This enables a Cr/NAA standard error of 0.08 (i.e., detection sensitivity of 25% for a 50/50 mixed gray and white matter voxel). In healthy controls, the regression of Cr/NAA versus fraction gray matter in the cingulate differs from frontal and parietal regions. Fast rosette spectroscopic imaging acquisitions with regression analyses are able to identify metabolic differences across 4-cm slabs of the brain centrally and over the cortical periphery with high efficiency, generating results that are consistent with clinical findings. Magn Reson Med 79:2470-2480, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Metabolic voxel-based analysis of the complete human brain using fast 3D-MRSI: Proof of concept in multiple sclerosis.

To detect local metabolic abnormalities over the complete human brain in multiple sclerosis (MS) patients, we used optimized fast volumic echo planar spectroscopic imaging (3D-EPSI). Weighted mean combination of two 3D-EPSI covering the whole brain acquired at 3T in AC-PC and AC-PC+15° axial planes was performed to obtain high-quality metabolite maps for five metabolites: N-acetyl aspartate (NAA), glutamate+glutamine (Glx), choline (Cho), myo-inositol (m-Ins), and creatine+phosphocreatine (tCr). After spatial normalization, maps from 19 patients suffering from relapsing-remitting MS were compared to 19 matched controls using statistical mapping analyses to determine the topography of metabolic abnormalities. Probabilistic white matter (WM) T2 lesion maps and gray matter (GM) atrophy maps were also generated. Two-group analysis of variance (ANOVA) (SPM8, P < 0.005, false discovery rate [FDR]-corrected P < 0.05 at the cluster level with age and sex as confounding covariates) comparing patients and controls matched for age and sex showed clusters of abnormal metabolite levels with 1) decreased NAA (around -15%) and Glx (around 20%) predominantly in GM within prefrontal cortices, motor cortices, bilateral thalami, and mesial temporal cortices in line with neuronal/neuro-astrocytic dysfunction; 2) increased m-Ins (around + 20%) inside WM T2 lesions and in the normal-appearing WM of temporal-occipital lobes, suggesting glial activation. We demonstrate the ability to noninvasively map over the complete brain-from vertex to cerebellum-with a validated sequence, the metabolic abnormalities associated with MS, for characterizing the topography of pathological processes affecting widespread areas of WM and GM and its functional impact. J. Magn. Reson. Imaging 2016;44:411-419.

Feasibility and reproducibility of echo planar spectroscopic imaging on the quantification of hepatic fat.

Objectives1H-MRS is widely regarded as the most accurate noninvasive method to quantify hepatic fat content (HFC). When practical period of breath holding, and acquisition of HFC over multiple liver areas is considered, a fast MR spectroscopic imaging technique is desired. The aim of this study is to examine the feasibility and reproducibility of echo planar spectroscopic imaging (EPSI) on the quantification of HFC in subject with various HFCs.MethodsTwenty two volunteers were examined in a 3T MR system. The acquisition time of proposed EPSI protocol was 18 seconds. The EPSI scans were repeated 8 times for each subject to test reproducibility. The peak of water and individual peaks of fat including methyl, methylene, and allylic peaks at 0.9, 1.3, and 2.0 ppm were fitted. Calculated amount of water and fat content were corrected for T2 relaxation. The total HFC was defined as the combination of individual peaks. Standard deviation (SD), coefficient of variance (COV) and fitting reliability of HFC quantified by LCModel were calculated.ResultsOur results show that the SDs of total HFC for all subjects are less than 2.5%. Fitting reliability is mostly under 10% and positively correlates with COV. Subjects separated into three subgroups according to quantified total HFC show that improved fitting reliability and reproducibility can be achieved on subjects with higher total HFC.ConclusionsWe have demonstrated feasibility of the proposed EPSI protocols on the quantification of HFC over a whole slice of liver with scan time in a single breath hold.

Shockwave generation by a semiconductor bridge operation in water

A semiconductor bridge (SCB) is a silicon device, used in explosive systems as the electrical initiator element. In recent years, SCB plasma has been extensively studied, both electrically and using fast photography and spectroscopic imaging. However, the value of the pressure buildup at the bridge remains unknown. In this study, we operated SCB devices in water and, using shadow imaging and reference beam interferometry, obtained the velocity of the shock wave propagation and distribution of the density of water. These results, together with a self-similar hydrodynamic model, were used to calculate the pressure generated by the exploding SCB. In addition, the results obtained showed that the energy of the water flow exceeds significantly the energy deposited into the exploded SCB. The latter can be explained by the combustion of the aluminum and silicon atoms released in water, which acts as an oxidizing medium.

Fast spectroscopic imaging with pixel semiconductor detector Timepix and parallel data reading

Non-invasive techniques utilizing X-ray radiation offer a powerful tool for the inspection of the inner composition of a wide variety of objects. The highly sensitive hybrid semiconductor pixel detector Timepix is capable of detecting and resolving subtle and low-contrast differences in radiography measurements. Moreover the Timepix detector offers 65536 individual pixels with spectrometric capabilities. With proper per-pixel energy calibration this feature enables the application of various energy based imaging techniques - from basic energy windowing to fully spectroscopic imaging. The main limitations of these methods are the detector energy resolution and data acquisition speed of 100 frames per second - the necessity of taking frames with low occupancy for event by event cluster analysis leads to several hours long measurements. The latter nuisance can be overcome by the utilization of the newly developed modular read-out FITPix3 with the adapter chipboard designed for parallel data reading. This read-out version can acquire over 850 compressed frames per second which reduces the measurement time of many spectroscopic measurements by factor of ten (spectra with high enough statistics are taken in tens of minutes). The short description of the new FITPix3 parallel read-out together with the progression in spectroscopic multi-channel energy imaging demonstrated on model samples are presented in this contribution.

In vivo single-shot 13C spectroscopic imaging of hyperpolarized metabolites by spatiotemporal encoding

Hyperpolarized metabolic imaging is a growing field that has provided a new tool for analyzing metabolism, particularly in cancer. Given the short life times of the hyperpolarized signal, fast and effective spectroscopic imaging methods compatible with dynamic metabolic characterizations are necessary. Several approaches have been customized for hyperpolarized 13C MRI, including CSI with a center-out k-space encoding, EPSI, and spectrally selective pulses in combination with spiral EPI acquisitions. Recent studies have described the potential of single-shot alternatives based on spatiotemporal encoding (SPEN) principles, to derive chemical-shift images within a sub-second period. By contrast to EPSI, SPEN does not require oscillating acquisition gradients to deliver chemical-shift information: its signal encodes both spatial as well as chemical shift information, at no extra cost in experimental complexity. SPEN MRI sequences with slice-selection and arbitrary excitation pulses can also be devised, endowing SPEN with the potential to deliver single-shot multi-slice chemical shift images, with a temporal resolution required for hyperpolarized dynamic metabolic imaging. The present work demonstrates this with initial in vivo results obtained from SPEN-based imaging of pyruvate and its metabolic products, after injection of hyperpolarized [1-13C]pyruvate. Multi-slice chemical-shift images of healthy rats were obtained at 4.7T in the region of the kidney, and 4D (2D spatial, 1D spectral, 1D temporal) data sets were obtained at 7T from a murine lymphoma tumor model.

Dual-wavelength differential spectroscopic imaging for diagnostics of laser-induced plasma

A specific configuration for plasma fast spectroscopic imaging was developed, where a pair of narrowband filters, one fitting an emission line of a species to be studied and the other out of its emission line, allowed double images to be taken for a laser-induced plasma. A dedicated software was developed for the subtraction between the double images. The result represents therefore the monochromatic emission image of the species in the plasma. We have shown in this work that such configuration is especially efficient for the monitoring of a plasma generated under the atmospheric pressure at very short delays after the impact of the laser pulse on the target, when a strong continuum emission is observed. The efficiency of the technique has been particularly demonstrated in the study of laser-induced plasma on a polymer target. Molecular species, such as C2 and CN, as well as atomic species, such as C and N, were imaged starting from 50ns after the laser impact. Moreover space segregation of different species, atomic or molecular, inside of the plasma was clearly observed.

Developing Hyperpolarized 13C Spectroscopy and Imaging for Metabolic Studies in the Isolated Perfused Rat Heart

Hyperpolarized 13C magnetic resonance is a powerful tool for the study of cardiac metabolism. In this work, we have implemented protocols for the real-time hyperpolarized 13C investigation of Langendorff-perfused rat hearts using both non-selective non-localized spectroscopy and fast spectroscopic imaging. Following [1-13C] pyruvate infusion, we observed both catabolic and anaplerotic metabolic processes resulting in a number of metabolites, including bicarbonate, carbon dioxide, lactate, alanine and aspartate. Employing fast spectroscopic imaging, we were able to observe regional variations in pyruvate perfusion as well as in lactate and bicarbonate production.

Noble Metal Coated Single-Walled Carbon Nanotubes for Applications in Surface Enhanced Raman Scattering Imaging and Photothermal Therapy

Single-walled carbon nanotubes (SWNTs) with various unique optical properties are interesting nanoprobes widely explored in biomedical imaging and phototherapies. Herein, DNA-functionalized SWNTs are modified with noble metal (Ag or Au) nanoparticles via an in situ solution phase synthesis method comprised of seed attachment, seeded growth, and surface modification with polyethylene glycol (PEG), yielding SWNT-Ag-PEG and SWNT-Au-PEG nanocomposites stable in physiological environments. With gold or silver nanoparticles decorated on the surface, the SWNT-metal nanocomposites gain an excellent concentration and excitation-source dependent surface-enhanced Raman scattering (SERS) effect. Using a near-infrared (NIR) laser as the excitation source, targeted Raman imaging of cancer cells labeled with folic acid (FA) conjugated SWNT-Au nanocomposite (SWNT-Au-PEG-FA) is realized, with images acquired in significantly shortened periods of time as compared to that of using nonenhanced SWNT Raman probes. Owing to the strong surface plasmon resonance absorption contributed by the gold shell, the SWNTs-Au-PEG-FA nanocomposite also offers remarkably improved photothermal cancer cell killing efficacy. This work presents a facile approach to synthesize water-soluble noble metal coated SWNTs with a strong SERS effect suitable for labeling and fast Raman spectroscopic imaging of biological samples, which has been rarely realized before. The SWNT-Au-PEG nanocomposite developed here may thus be an interesting optical theranostic probe for cancer imaging and therapy.

In Vivo Clinical Measures of Intermediary Metabolism Are Inadequate

The heart derives most of its energy via mitochondrial oxidative metabolism. The heart's fuels or energy substrates include fatty acids, lactate, glucose, and ketones. Substrate concentrations vary during the day, driven mainly by postprandial status. Entry into mitochondrial oxidation requires metabolism to acetyl-coenzyme A (CoA), the fuel of the tricarboxylic acid (TCA) cycle. Acetyl-CoA oxidation generates reduced Nicotinamide adenine dinucleotide (NADH), which drives oxidative phosphorylation, the reduction of O2 to H2O, and, ultimately, the synthesis of ATP, which is essential for myocardial mechanics. The heart uses this highly regulated series of enzyme-catalyzed reactions to convert chemical energy into mechanical energy.1 Metabolism and function in the heart are inextricably linked. Article see p 201 The pathological states of the heart, such as ischemia, hypertrophy, and failure, modify metabolism. Available technologies to measure intermediary metabolism have been inadequate. Magnetic resonance spectroscopy (MRS) can be used to spatially map or at least locally measure metabolism in vivo. Measurement of endogenous triglycerides in patients using 1H MRS has demonstrated that cardiac steatosis precedes the onset of type 2 diabetes mellitus and left ventricular systolic dysfunction.2 In the failing human heart and in preclinical heart failure models, 31P MRS has shown that flux through the creatinine kinase reaction is altered.3,4 Also, ATP and phosphocreatine are reduced after myocardial infarction due to myocyte loss.5 Myocardial energy substrate can be measured with 13C MRS. It has the chemical specificity, but its inherently low sensitivity limits the spatial and temporal resolution necessary for clinical application. In isolated hearts, 13C MRS has to be used with labeled substrate molecules to define TCA cycle kinetics. The metabolites of the TCA cycle have not been measured directly in these experiments. The content of the TCA cycle metabolites is …

Metabolic MR imaging of regional triglyceride and creatine content in the human heart

An optimized echo-planar spectroscopic imaging sequence is proposed to facilitate spatial mapping of triglyceride and total creatine content in the human heart. The sequence integrates local-look field of view reduction, cardiac and respiratory gating, and dedicated reconstruction steps to account for gradient channel delays, field inhomogeneity, and phase incoherence due to residual motion. The technique is demonstrated in 12 volunteers in comparison to single voxel point-resolved spectroscopy in the septal wall at 1.5 T. Triglyceride-to-water and total creatine-to-water ratios derived from echo-planar spectroscopic imaging (0.48 ± 0.18% and 0.06 ± 0.03%) and point-resolved spectroscopy (0.52 ± 0.17% and 0.07 ± 0.02%) were found to agree well. In the septal region, intraclass correlation coefficients ranging from 0.67 to 0.72 were estimated. A relatively weak agreement (intraclass correlation coefficients: 0.34 and 0.52) was found for sectors in the lateral wall due to field gradients induced by the posterior vein and limited sensitivity of the receive coil array in this area. On the basis of the findings, it is concluded that fast spectroscopic imaging of both cardiac triglyceride and total creatine content is feasible. Shimming and sensitivity challenges in the lateral region remain, however, to be addressed.