Epigenetic MRI: Noninvasive imaging of DNA methylation in the brain.

Both neuronal and genetic mechanisms regulate brain function. While there are excellent methods to study neuronal activity in vivo, there are no nondestructive methods to measure global gene expression in living brains. Here, we present a method, epigenetic MRI (eMRI), that overcomes this limitation via direct imaging of DNA methylation, a major gene-expression regulator. eMRI exploits the methionine metabolic pathways for DNA methylation to label genomic DNA through 13C-enriched diets. A 13C magnetic resonance spectroscopic imaging method then maps the spatial distribution of labeled DNA. We validated eMRI using pigs, whose brains have stronger similarity to humans in volume and anatomy than rodents, and confirmed efficient 13C-labeling of brain DNA. We also discovered strong regional differences in global DNA methylation. Just as functional MRI measurements of regional neuronal activity have had a transformational effect on neuroscience, we expect that the eMRI signal, both as a measure of regional epigenetic activity and as a possible surrogate for regional gene expression, will enable many new investigations of human brain function, behavior, and disease.

Whole-brain deuterium metabolic imaging via concentric ring trajectory readout enables assessment of regional variations in neuronal glucose metabolism.

Deuterium metabolic imaging (DMI) is an emerging magnetic resonance technique, for non-invasive mapping of human brain glucose metabolism following oral or intravenous administration of deuterium-labeled glucose. Regional differences in glucose metabolism can be observed in various brain pathologies, such as Alzheimer's disease, cancer, epilepsy or schizophrenia, but the achievable spatial resolution of conventional phase-encoded DMI methods is limited due to prolonged acquisition times rendering submilliliter isotropic spatial resolution for dynamic whole brain DMI not feasible. The purpose of this study was to implement non-Cartesian spatial-spectral sampling schemes for whole-brain 2H FID-MR Spectroscopic Imaging to assess time-resolved metabolic maps with sufficient spatial resolution to reliably detect metabolic differences between healthy gray and white matter regions. Results were compared with lower-resolution DMI maps, conventionally acquired within the same session. Six healthy volunteers (4 m/2 f) were scanned for ~90 min after administration of 0.8 g/kg oral [6,6']-2H glucose. Time-resolved whole brain 2H FID-DMI maps of glucose (Glc) and glutamate + glutamine (Glx) were acquired with 0.75 and 2 mL isotropic spatial resolution using density-weighted concentric ring trajectory (CRT) and conventional phase encoding (PE) readout, respectively, at 7 T. To minimize the effect of decreased signal-to-noise ratios associated with smaller voxels, low-rank denoising of the spatiotemporal data was performed during reconstruction. Sixty-three minutes after oral tracer uptake three-dimensional (3D) CRT-DMI maps featured 19% higher (p = .006) deuterium-labeled Glc concentrations in GM (1.98 ± 0.43 mM) compared with WM (1.66 ± 0.36 mM) dominated regions, across all volunteers. Similarly, 48% higher (p = .01) 2H-Glx concentrations were observed in GM (2.21 ± 0.44 mM) compared with WM (1.49 ± 0.20 mM). Low-resolution PE-DMI maps acquired 70 min after tracer uptake featured smaller regional differences between GM- and WM-dominated areas for 2H-Glc concentrations with 2.00 ± 0.35 mM and 1.71 ± 0.31 mM, respectively (+16%; p = .045), while no regional differences were observed for 2H-Glx concentrations. In this study, we successfully implemented 3D FID-MRSI with fast CRT encoding for dynamic whole-brain DMI at 7 T with 2.5-fold increased spatial resolution compared with conventional whole-brain phase encoded (PE) DMI to visualize regional metabolic differences. The faster metabolic activity represented by 48% higher Glx concentrations was observed in GM- compared with WM-dominated regions, which could not be reproduced using whole-brain DMI with the low spatial resolution protocol. Improved assessment of regional pathologic alterations using a fully non-invasive imaging method is of high clinical relevance and could push DMI one step toward clinical applications.

Age, sex, and lung volume dependence of dissolved xenon-129 MRI gas exchange metrics.

PURPOSE: To characterize the dependence of Xe-MRI gas transfer metrics upon age, sex, and lung volume in a group of healthy volunteers. METHODS: Sixty-five subjects with no history of chronic lung disease were assessed with 129Xe-MRI using a four-echo 3D radial spectroscopic imaging sequence and a dose of xenon titrated according to subject height that was inhaled from a lung volume of functional residual capacity (FRC). Imaging was repeated in 34 subjects at total lung capacity (TLC). Regional maps of the fractions of dissolved xenon in red blood cells (RBC), membrane (M), and airspace (Gas) were acquired at an isotropic resolution of 2 cm, from which global averages of the ratios RBC:M, RBC:Gas, and M:Gas were computed. RESULTS: Data from 26 males and 36 females with a median age of 43 y (range: 20-69 y) were of sufficient quality to analyze. Age (p = 0.0006) and sex (p < 0.0001) were significant predictors for RBC:M, and a linear regression showed higher values and steeper decline in males: RBC:M(Males) = -0.00362 × Age + 0.60 (p = 0.01, R2 = 0.25); RBC:M(Females) = -0.00170 × Age + 0.44 (p = 0.02, R2 = 0.15). Similarly, age and sex were significant predictors for RBC:Gas but not for M:Gas. RBC:M, M:Gas and RBC:Gas were significantly lower at TLC than at FRC (plus inhaled volume), with an average 9%, 30% and 35% decrease, respectively. CONCLUSION: Expected age and sex dependence of pulmonary function concurs with 129Xe RBC:M imaging results, demonstrating that these variables must be considered when reporting Xe-MRI metrics. Xenon doses and breathing maneuvers should be controlled due to the strong dependence of Xe-MRI metrics upon lung volume.

Water removal in MR spectroscopic imaging with Casorati singular value decomposition.

PURPOSE: Water removal is one of the computational bottlenecks in the processing of high-resolution MRSI data. The purpose of this work is to propose an approach to reduce the computing time required for water removal in large MRS data. METHODS: In this work, we describe a singular value decomposition-based approach that uses the partial position-time separability and the time-domain linear predictability of MRSI data to reduce the computational time required for water removal. Our approach arranges MRS signals in a Casorati matrix form, applies low-rank approximations utilizing singular value decomposition, removes residual water from the most prominent left-singular vectors, and finally reconstructs the water-free matrix using the processed left-singular vectors. RESULTS: We have demonstrated the effectiveness of our proposed algorithm for water removal using both simulated and in vivo data. The proposed algorithm encompasses a pip-installable tool ( https://pypi.org/project/CSVD/), available on GitHub ( https://github.com/amirshamaei/CSVD), empowering researchers to use it in future studies. Additionally, to further promote transparency and reproducibility, we provide comprehensive code for result replication. CONCLUSIONS: The findings of this study suggest that the proposed method is a promising alternative to existing water removal methods due to its low processing time and good performance in removing water signals.

High-field downfield MR spectroscopic imaging in the human brain.

PURPOSE: To investigate the feasibility of downfield MR spectroscopic imaging (DF-MRSI) in the human brain at 7T. METHODS: A 7T DF-MRSI pulse sequence was implemented based on the previously described methodology at 3T, with 3D phase-encoding, 1 3 ‾ 3 1 ‾ $$ 1\overline{3}3\overline{1} $$ spectral-spatial excitation, and frequency selective refocusing. Data were pre-processed followed by analysis using the "LCModel" software package, and metabolite maps created from the LCModel results. Total scan time, including brain MRI and a water-reference MRSI, was 24 min. The sequence was tested in 10 normal volunteers. Estimated metabolite levels and uncertainty values (Cramer Rao lower bounds, CRLBs) for nine downfield peaks were compared between seven different brain regions, anterior cingulate cortex (ACC), centrum semiovale (CSO), corpus callosum (CC), cerebellar vermis (CV), dorsolateral prefrontal cortex (DLPFC), posterior cingulate cortex (PCC), and thalamus (Thal). RESULTS: DF peaks were relatively uniformly distributed throughout the brain, with only a small number of peaks showing any significant regional variations. Most DF peaks had average CRLB<25% in most brain regions. Average SNR values were higher for the brain regions ACC and DLPFC (˜7 ± 0.95, mean ± SD) while in a range of 3.4-6.0 for other brain regions. Average linewidth (FWHM) values were greater than 35 Hz in the ACC, CV, and Thal, and 22 Hz in CC, CSO, DLPFC, and PCC. CONCLUSION: High-field DF-MRSI is able to spatially map exchangeable protons in the human brain at high resolution and with near whole-brain coverage in acceptable scan times, and in the future may be used to study metabolism of brain tumors or other neuropathological disorders.

Diffusion-weighted MR spectroscopy of the prostate.

PURPOSE: Prostate tissue has a complex microstructure, mainly composed of epithelial and stromal cells, and of extracellular (acinar-luminal) spaces. Diffusion-weighted MR spectroscopy (DW-MRS) is ideally suited to explore complex microstructure in vivo with metabolites selectively distributed in different subspaces. To date, this technique has been applied to brain and muscle. This study presents the development and pioneering utilization of 1H-DW-MRS in the prostate, accompanied by in vitro studies to support interpretations of in vivo findings. METHODS: Nine healthy volunteers underwent a prostate MR examination (mean age, 56 years; range, 31-66). Metabolic complexation was studied in vitro using solutions with major compounds found in prostatic fluid of the lumen. DW-MRS was performed at 3 T with a non-water-suppressed single-voxel sequence with metabolite-cycling to concurrently measure metabolite and water signals. The water signal was used in postprocessing as a reference in a motion-compensation scheme. The spectra were fitted simultaneously in the spectral and diffusion-weighting dimensions. Apparent diffusion coefficients (ADCs) were derived by fitting signal decays that were assumed to be mono-exponential for metabolites and biexponential for water. RESULTS: DW-MRS of the prostate revealed relatively low ADCs for Cho and Cr compounds, aligning with their intracellular location and higher ADCs for citrate and spermine supporting their luminal origin. In vitro assessments of the ADCs of citrate and spermine demonstrated their complex formation and protein binding. Tissue concentrations of MRS-detectable metabolites were as expected for the voxel location. CONCLUSIONS: This work successfully demonstrates the feasibility of 1H-DW-MRS of the prostate and its potential for providing valuable microstructural information.

Single-shot diffusion trace spectroscopic imaging using radial echo planar trajectories.

PURPOSE: Demonstrate the feasibility and evaluate the performance of single-shot diffusion trace-weighted radial echo planar spectroscopic imaging (Trace DW-REPSI) for quantifying the trace ADC in phantom and in vivo using a 3T clinical scanner. THEORY AND METHODS: Trace DW-REPSI datasets were acquired in 10 phantom and 10 healthy volunteers, with a maximum b-value of 1601 s/mm2 and diffusion time of 10.75 ms. The self-navigation properties of radial acquisitions were used for corrections of shot-to-shot phase and frequency shift fluctuations of the raw data. In vivo trace ADCs of total NAA (tNAA), total creatine (tCr), and total choline (tCho) extrapolated to pure gray and white matter fractions were compared, as well as trace ADCs estimated in voxels within white or gray matter-dominant regions. RESULTS: Trace ADCs in phantom show excellent agreement with reported values, and in vivo ADCs agree well with the expected differences between gray and white matter. For tNAA, tCr, and tCho, the trace ADCs extrapolated to pure gray and white matter ranged from 0.18-0.27 and 0.26-0.38 µm2/ms, respectively. In sets of gray and white matter-dominant voxels, the values ranged from 0.21 to 0.27 and 0.24 to 0.31 µm2/ms, respectively. The overestimated trace ADCs from this sequence can be attributed to the short diffusion time. CONCLUSION: This study presents the first demonstration of the single-shot diffusion trace-weighted spectroscopic imaging sequence using radial echo planar trajectories. The Trace DW-REPSI sequence could provide an estimate of the trace ADC in a much shorter scan time compared to conventional approaches that require three separate measurements.

High-resolution proton metabolic mapping of the human brain at 7 T using free induction decay rosette spectroscopic imaging.

Magnetic resonance spectroscopic imaging (MRSI) provides information about the spatial distribution of metabolites in the brain. These metabolite maps can be valuable in diagnosing central nervous system pathology. However, MRSI generally suffers from a long acquisition time, poor spatial resolution, and a low metabolite signal-to-noise ratio (SNR). Ultrahigh field strengths (≥ 7 T) can benefit MRSI with an improved SNR and allow high-resolution metabolic mapping. Non-Cartesian spatial-spectral encoding techniques, such as rosette spectroscopic imaging, can efficiently sample spatial and temporal domains, which significantly reduces the imaging time and enables high-resolution metabolic mapping in a clinically relevant scan time. In the current study, high-resolution (in-plane resolution of 2 × 2 mm2 ) mapping of proton (1 H) metabolites in the human brain at 7 T, is demonstrated. Five healthy subjects participated in the study. Using a time-efficient rosette trajectory and short TR/TE free induction decay MRSI, high-resolution maps of 1 H metabolites were obtained in a clinically relevant imaging time (6 min). Suppression of the water signal was achieved with an optimized water suppression enhanced through T1 effects approach and lipid removal was performed using L2 -regularization in the postprocessing. Spatial distributions of N-acetyl-aspartate, total choline, creatine, N-acetyl-aspartyl glutamate, myo-inositol, and glutamate were generated with Cramer-Rao lower bounds of less than 20%.

A birdcage transmit, 24-channel conformal receive array coil for sensitive 31P magnetic resonance spectroscopic imaging of the human brain at 7 T.

Phosphorus (31P) magnetic resonance spectroscopic imaging (MRSI) can serve as a critical tool for more direct quantification of brain energy metabolism, tissue pH, and cell membrane turnover. However, the low concentration of 31P metabolites in biological tissue may result in low signal-to-noise ratio (SNR) in 31P MRS images. In this work, we present an innovative design and construction of a 31P radiofrequency coil for whole-brain MRSI at 7 T. Our coil builds on current literature in ultra-high field 31P coil design and offers complete coverage of the brain, including the cerebellum and brainstem. The coil consists of an actively detunable volume transmit (Tx) resonator and a custom 24-channel receive (Rx) array. The volume Tx resonator is a 16-rung high-pass birdcage coil. The Rx coil consists of a 24-element phased array composed of catered loop shapes and sizes built onto a custom, close-fitting, head-shaped housing. The Rx array was designed to provide complete coverage of the head, while minimizing mutual coupling. The Rx configuration had a mean S 11 $$ {S}_{11} $$ reflection coefficient better than -20 decibels (dB) when the coil was loaded with a human head. The mean mutual coupling ( S 21 $$ {S}_{21} $$ ) among Rx elements, when loaded with a human head, was -16 dB. In phantom imaging, the phased array produced a central SNR that was 4.4-fold higher than the corresponding central SNR when operating the 31P birdcage as a transceiver. The peripheral SNR was 12-fold higher when applying the optimized phased array. In vivo 3D 31P MRSI experiments produced high-quality spectra in the cerebrum gray and white matter, as well as in the cerebellum. Characteristic phosphorus metabolites related to adenosine triphosphate metabolism and cell membrane turnover were distinguishable across all brain regions. In summary, our results demonstrate the potential of our novel coil for accurate, whole-brain 31P metabolite quantification.

Fast 19 F spectroscopic imaging with pseudo-spiral k-space sampling.

Fluorine MRI is finding wider acceptance in theranostics applications where imaging of 19 F hotspots of fluorinated contrast material is central. The essence of such applications is to capture ghosting-artifact-free images of the inherently low MR response under clinically viable conditions. To serve this purpose, this work introduces the balanced spiral spectroscopic imaging (BaSSI) sequence, which is implemented on a 3.0 T clinical scanner and is capable of generating 19 F hotspot images in an efficient manner. The sequence utilizes an all-phase-encoded pseudo-spiral k-space trajectory, enabling the acquisition of broadband (80 ppm) fluorine spectra free from chemical shift ghosting. BaSSI can acquire a 64 × 64 image with 1 mm × 1 mm voxels in just 14 s, significantly outperforming typical MRSI sequences used in 1 H or 31 P imaging. The study employed in silico characterization to verify essential design choices such as the excitation pulse, as well as to identify the boundaries of the parameter space explored for optimization. BaSSI's performance was further benchmarked against the 3D ultrashort-echo-time balanced steady-state free precession (3D UTE BSSFP) sequence, a well established method used in 19 F MRI, in vitro. Both sequences underwent extensive optimization through exploration of a wide parameter space on a small phantom containing 10 µL of non-diluted bulk perfluorooctylbromide (PFOB) prior to comparative experiments. Subsequent to optimization, BaSSI and 3D UTE BSSFP were employed to capture images of small non-diluted bulk PFOB samples (0.10 and 0.05 µL), with variations in the number of signal averages, and thus the total scan time, in order to assess the detection sensitivities of the sequences. In these experiments, the detection sensitivity was evaluated using the Rose criterion (Rc ), which provides a quantitative metric for assessing object visibility. The study further demonstrated BaSSI's utility as a (pre)clinical tool through postmortem imaging of polymer microspheres filled with PFOB in a BALB/c mouse. Anatomic localization of 19 F hotspots was achieved by denoising raw data obtained with BaSSI using a filter based on the Rose criterion. These data were then successfully registered to 1 H anatomical images. BaSSI demonstrated superior detection sensitivity in the benchmarking analysis, achieving Rc values approximately twice as high as those obtained with the 3D UTE BSSFP method. The technique successfully facilitated imaging and precise localization of 19 F hotspots in postmortem experiments. However, it is important to highlight that imaging 10 mM PFOB in small mice postmortem, utilizing a 48 × 48 × 48 3D scan, demanded a substantial scan time of 1 h and 45 min. Further studies will explore accelerated imaging techniques, such as compressed sensing, to enhance BaSSI's clinical utility.

Noise-reduction techniques for 1H-FID-MRSI at 14.1 T: Monte Carlo validation and in vivo application.

Proton magnetic resonance spectroscopic imaging (1H-MRSI) is a powerful tool that enables the multidimensional non-invasive mapping of the neurochemical profile at high resolution over the entire brain. The constant demand for higher spatial resolution in 1H-MRSI has led to increased interest in post-processing-based denoising methods aimed at reducing noise variance. The aim of the present study was to implement two noise-reduction techniques, Marchenko-Pastur principal component analysis (MP-PCA) based denoising and low-rank total generalized variation (LR-TGV) reconstruction, and to test their potential with and impact on preclinical 14.1 T fast in vivo 1H-FID-MRSI datasets. Since there is no known ground truth for in vivo metabolite maps, additional evaluations of the performance of both noise-reduction strategies were conducted using Monte Carlo simulations. Results showed that both denoising techniques increased the apparent signal-to-noise ratio (SNR) while preserving noise properties in each spectrum for both in vivo and Monte Carlo datasets. Relative metabolite concentrations were not significantly altered by either method and brain regional differences were preserved in both synthetic and in vivo datasets. Increased precision of metabolite estimates was observed for the two methods, with inconsistencies noted for lower-concentration metabolites. Our study provided a framework for how to evaluate the performance of MP-PCA and LR-TGV methods for preclinical 1H-FID MRSI data at 14.1 T. While gains in apparent SNR and precision were observed, concentration estimations ought to be treated with care, especially for low-concentration metabolites.

High-resolution 1H-MRSI at 9.4 T by integrating relaxation enhancement and subspace imaging.

Achieving high-resolution and high signal-to-noise ratio (SNR) in vivo metabolic imaging via fast magnetic resonance spectroscopic imaging (MRSI) has been a longstanding challenge. This study combines the methods of relaxation enhancement (RE) and subspace imaging for the first time, enabling high-resolution and high-SNR in vivo MRSI of rodent brains at 9.4 T. Specifically, an RE-based chemical shift imaging sequence, which combines a frequency-selective pulse to excite only the metabolite frequencies with minimum perturbation of the water spins and a pair of adiabatic pulses to spatially localize the slice of interest, is designed and evaluated in vivo. This strategy effectively shortens the apparent T1 of metabolites, thereby increasing the SNR during relatively short repetition time ((TR) compared with acquisitions with only spatially selective wideband excitations, and does not require water suppression. The SNR was further enhanced via a state-of-the-art subspace reconstruction method. A novel subspace learning strategy tailored for 9.4 T and RE acquisitions is developed. In vivo, high-resolution (e.g., voxel size of 0.6 × 0.6 × 1.5 mm3) MRSI of both healthy mouse brains and a glioma-bearing mouse brain in 12.5 min has been demonstrated.

A multivariate curve resolution analysis of multicenter proton spectroscopic imaging of the prostate for cancer localization and assessment of aggressiveness.

In this study, we investigated the potential of the multivariate curve resolution alternating least squares (MCR-ALS) algorithm for analyzing three-dimensional (3D) 1 H-MRSI data of the prostate in prostate cancer (PCa) patients. MCR-ALS generates relative intensities of components representing spectral profiles derived from a large training set of patients, providing an interpretable model. Our objectives were to classify magnetic resonance (MR) spectra, differentiating tumor lesions from benign tissue, and to assess PCa aggressiveness. We included multicenter 3D 1 H-MRSI data from 106 PCa patients across eight centers. The patient cohort was divided into a training set (N = 63) and an independent test set (N = 43). Singular value decomposition determined that MR spectra were optimally represented by five components. The profiles of these components were extracted from the training set by MCR-ALS and assigned to specific tissue types. Using these components, MCR-ALS was applied to the test set for a quantitative analysis to discriminate tumor lesions from benign tissue and to assess tumor aggressiveness. Relative intensity maps of the components were reconstructed and compared with histopathology reports. The quantitative analysis demonstrated a significant separation between tumor and benign voxels (t-test, p < 0.001). This result was achieved including voxels with low-quality MR spectra. A receiver operating characteristic analysis of the relative intensity of the tumor component revealed that low- and high-risk tumor lesions could be distinguished with an area under the curve of 0.88. Maps of this component properly identified the extent of tumor lesions. Our study demonstrated that MCR-ALS analysis of 1 H-MRSI of the prostate can reliably identify tumor lesions and assess their aggressiveness. It handled multicenter data with minimal preprocessing and without using prior knowledge or quality control. These findings indicate that MCR-ALS can serve as an automated tool to assess the presence, extent, and aggressiveness of tumor lesions in the prostate, enhancing diagnostic capabilities and treatment planning of PCa patients.

Analysis of the Dissolution Behavior of Theophylline and Its Cocrystal Using ATR-FTIR Spectroscopic Imaging.

Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopic imaging is a powerful tool to visualize the distribution of components, and it has been used to analyze drug release from tablets. In this work, ATR-FTIR spectroscopic imaging was applied for observing the dissolution of molecular crystals from tablet compacts. The IR spectra provided chemically specific information about the transformation of crystal structures during the dissolution experiments. Theophylline (TPL) anhydrate and its cocrystals were used as model systems of molecular crystals. The IR spectra during the dissolution of TPL revealed information about the crystal structure of TPL, which transformed from anhydrate to monohydrate in water. During a dissolution test of a model cocrystal system, it was suggested that an active pharmaceutical ingredient (API) and a coformer were dissolved in water simultaneously. The IR spectra that were acquired during the dissolution of a cocrystal tablet showed new spectral bands attributed to the API after 5 min. This suggested that the precipitation of API was observed during the dissolution experiment. Measurements from ATR-FTIR spectroscopic imaging can visualize the drug release from the tablet and determine the transformation of molecular crystals during their dissolution. These results will have an impact on clarifying the dissolution mechanism of molecular crystals.

The longitudinal effects of cannabidiol on brain temperature in patients with treatment-resistant epilepsy.

Neuroinflammation (NI) is a key pathophysiological contributor to treatment-resistant epilepsy (TRE) that remains challenging to observe in vivo. Magnetic resonance spectroscopic imaging and thermometry (MRSI-t) is an emerging technique that can be used to non-invasively map brain temperature, whereby brain temperature elevations serve as a surrogate for the cellular and biochemical processes associated with NI. In a previous multimodal imaging study of focal epilepsy patients, we observed MRSI-t-based brain temperature elevations ipsilateral to the seizure onset zone (SOZ) that were concordant with evidence of edema (Sharma et al., 2023). Despite its potential as tool, it is unclear if MRSI-t can monitor changes in brain temperature in response to treatment. We imaged 25 participants approximately 12-weeks apart. Eight patients with TRE were imaged before receiving highly-purified pharmaceutical grade cannabidiol (CBD; pre-CBD) and after 12-weeks of CBD (on-CBD) therapy. Seventeen healthy controls (HCs) were also imaged twice. Repeated measures t-tests computed changes in TRE patients' seizure symptoms, mood, and brain temperature within their respective SOZs. Repeated measures ANOVAs tested Group*Time changes in imaging data. Participants with TRE had abnormally high peak brain temperatures within their SOZs that decreased after CBD initiation (p < 0.0001). Seizure severity scores also improved after CBD initiation (p < 0.001). These findings provide insights into the possible neural effects of CBD, and further demonstrate MRSI-t's potential as a tool for delineating SOZ. Further investigations into MRSI-t as a longitudinal measure of therapy-induced changes in NI are warranted.

Isotope labeled 3D-Raman confocal imaging and atomic force microscopy study on epithelial cells interacting with the fungus Candida albicans.

The human pathogenic fungus Candida albicans damages epithelial cells during superficial infections. Here we use three-dimensional-sequential-confocal Raman spectroscopic imaging and atomic force microscopy to investigate the interaction of C. albicans wild type cells, the secreted C. albicans peptide toxin candidalysin and mutant cells lacking candidalysin with epithelial cells. The candidalysin is responsible for epithelial cell damage and exhibits in its deuterated form an identifiable Raman signal in a frequency region distinct from the cellular frequency region. Vibration modes at 2100-2200 cm-1 attributed to carbon­deuterium bending and at 477 cm-1, attributed to the nitrogen­deuterium out-of-plane bending, found around the nucleus, can be assigned to deuterated candidalysin. Atomic force microscopy visualized 100 nm deep lesions on the cell and force-distance curves indicate the higher adhesion on pore surrounding after incubation with candidalysin. Candidalysin targets the plasma membrane, but is also found inside of the cytosol of epithelial cells during C. albicans infection.

To characterize small renal cell carcinoma using diffusion relaxation correlation spectroscopic imaging and apparent diffusion coefficient based histogram analysis: a preliminary study.

PURPOSE: To study the capability of diffusion-relaxation correlation spectroscopic imaging (DR-CSI) on subtype classification and grade differentiation for small renal cell carcinoma (RCC). Histogram analysis for apparent diffusion coefficient (ADC) was studied for comparison. MATERIALS AND METHODS: A total of 61 patients with small RCC (< 4 cm) were included in the retrospective study. MRI data were reviewed, including a multi-b (0-1500 s/mm2) multi-TE (51-200 ms) diffusion weighted imaging (DWI) sequence. Region of interest (ROI) was delineated manually on DWI to include solid tumor. For each patient, a D-T2 spectrum was fitted and segmented into 5 compartments, and the volume fractions VA, VB, VC, VD, VE were obtained. ADC mapping was calculated, and histogram parameters ADC 90th, 10th, median, standard deviation, skewness and kurtosis were obtained. All MRI metrices were compared between clear cell RCC (ccRCC) and non-ccRCC group, and between high-grade and low-grade group. Receiver operator curve analysis was used to assess the corresponding diagnostic performance. RESULTS: Significantly higher ADC 90th, ADC 10th and ADC median, and significantly lower DR-CSI VB was found for ccRCC compared to non-ccRCC. Significantly lower ADC 90th, ADC median and significantly higher VB was found for high-grade RCC compared to low-grade. For identifying ccRCC from non-ccRCC, VB showed the highest area under curve (AUC, 0.861) and specificity (0.882). For differentiating high- from low-grade, ADC 90th showed the highest AUC (0.726) and specificity (0.786), while VB also displayed a moderate AUC (0.715). CONCLUSION: DR-CSI may offer improved accuracy in subtype identification for small RCC, while do not show better performance for small RCC grading compared to ADC histogram.

Fast Twist Angle Mapping of Bilayer Graphene Using Spectroscopic Ellipsometric Contrast Microscopy.

Twisted bilayer graphene provides an ideal solid-state model to explore correlated material properties and opportunities for a variety of optoelectronic applications, but reliable, fast characterization of the twist angle remains a challenge. Here we introduce spectroscopic ellipsometric contrast microscopy (SECM) as a tool for mapping twist angle disorder in optically resonant twisted bilayer graphene. We optimize the ellipsometric angles to enhance the image contrast based on measured and calculated reflection coefficients of incident light. The optical resonances associated with van Hove singularities correlate well to Raman and angle-resolved photoelectron emission spectroscopy, confirming the accuracy of SECM. The results highlight the advantages of SECM, which proves to be a fast, nondestructive method for characterization of twisted bilayer graphene over large areas, unlocking process, material, and device screening and cross-correlative measurement potential for bilayer and multilayer materials.

Hierarchical Self-Assembly of Carbon Dots into High-Aspect-Ratio Nanowires.

We report a spontaneous and hierarchical self-assembly mechanism of carbon dots prepared from citric acid and urea into nanowire structures with large aspect ratios (>50). Scattering-type scanning near-field optical microscopy (s-SNOM) with broadly tunable mid-IR excitation was used to interrogate details of the self-assembly process by generating nanoscopic chemical maps of local wire morphology and composition. s-SNOM images capture the evolution of wire formation and the complex interplay between different chemical constituents directing assembly over the nano- to microscopic length scales. We propose that residual citrate promotes tautomerization of melamine surface functionalities to produce supramolecular shape synthons comprised of melamine-cyanurate adducts capable of forming long-range and highly directional hydrogen-bonding networks. This intrinsic, heterogeneity-driven self-assembly mechanism reflects synergistic combinations of high chemical specificity and long-range cooperativity that may be harnessed to reproducibly fabricate functional structures on arbitrary surfaces.

Neurometabolic topography and associations with cognition in Alzheimer's disease: A whole-brain high-resolution 3D MRSI study.

INTRODUCTION: Altered neurometabolism, detectable via proton magnetic resonance spectroscopic imaging (1H-MRSI), is spatially heterogeneous and underpins cognitive impairments in Alzheimer's disease (AD). However, the spatial relationships between neurometabolic topography and cognitive impairment in AD remain unexplored due to technical limitations. METHODS: We used a novel whole-brain high-resolution 1H-MRSI technique, with simultaneously acquired 18F-florbetapir positron emission tomography (PET) imaging, to investigate the relationship between neurometabolic topography and cognitive functions in 117 participants, including 22 prodromal AD, 51 AD dementia, and 44 controls. RESULTS: Prodromal AD and AD dementia patients exhibited spatially distinct reductions in N-acetylaspartate, and increases in myo-inositol. Reduced N-acetylaspartate and increased myo-inositol were associated with worse global cognitive performance, and N-acetylaspartate correlated with five specific cognitive scores. Neurometabolic topography provides biological insights into diverse cognitive dysfunctions. DISCUSSION: Whole-brain high-resolution 1H-MRSI revealed spatially distinct neurometabolic topographies associated with cognitive decline in AD, suggesting potential for noninvasive brain metabolic imaging to track AD progression. HIGHLIGHTS: Whole-brain high-resolution 1H-MRSI unveils neurometabolic topography in AD. Spatially distinct reductions in NAA, and increases in mI, are demonstrated. NAA and mI topography correlates with global cognitive performance. NAA topography correlates with specific cognitive performance.