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.

3D ultra-short echo time 31P-MRSI with rosette k-space pattern: Feasibility and comparison with conventional weighted CSI.

Phosphorus-31 magnetic resonance spectroscopic imaging (31P-MRSI) provides valuable non-invasive in vivo information on tissue metabolism but is burdened by poor sensitivity and prolonged scan duration. Ultra-short echo time (UTE) acquisitions minimize signal loss when probing signals with relatively short spin-spin relaxation time (T2), while also preventing first-order dephasing. Here, a three-dimensional (3D) UTE sequence with a rosette k-space trajectory is applied to 31P-MRSI at 3T. Conventional chemical shift imaging (CSI) employs highly regular Cartesian k-space sampling, susceptible to substantial artifacts when accelerated via undersampling. In contrast, this novel sequence's "petal-like" pattern offers incoherent sampling more suitable for compressed sensing (CS). These results showcase the competitive performance of UTE rosette 31P-MRSI against conventional weighted CSI with simulation, phantom, and in vivo leg muscle comparisons.

Single-shot diffusion trace-weighted MR spectroscopy: Comparison with unipolar and bipolar diffusion-weighted point-resolved spectroscopy.

This study demonstrates the feasibility and performance of the point-resolved spectroscopy (PRESS)-based, single-shot diffusion trace-weighted sequence in quantifying the trace apparent diffusion coefficient (ADC) in phantom and in vivo using a 3-T MRI/MRS scanner. The single-shot diffusion trace-weighted PRESS sequence was implemented and compared with conventional diffusion-weighted (DW)-PRESS variants using bipolar and unipolar diffusion-sensitizing gradients. Nine phantom datasets were acquired using each sequence, and seven volunteers were scanned in three different brain regions to determine the range and variability of trace ADC values, and to allow a comparison of trace ADCs among the sequences. This sequence results in a comparatively stable range of trace ADC values that are statistically significantly higher than those produced from unipolar and bipolar DW-PRESS sequences. Only total n-acetylaspartate, total creatine, and total choline were reliably estimated in all sequences with Cramér-Rao lower bounds of, at most, 20%. The larger trace ADCs from the single-shot sequences are probably attributable to the shorter diffusion time relative to the other sequences. Overall, this study presents the first demonstration of the single-shot diffusion trace-weighted sequence in a clinical scanner at 3 T. The results show excellent agreement of phantom trace ADCs computed with all sequences, and in vivo ADCs agree well with the expected differences between gray and white matter. The diffusion trace-weighted sequence could provide an estimate of the trace ADC in a shorter scan time (by nearly a factor of 3) compared with conventional DW-PRESS approaches that require three separate orthogonal directions.

Enhanced spectral resolution for correlated spectroscopic imaging using inner-product and covariance transform: a pilot analysis of metabolites and lipids in breast cancer in vivo.

Acquisition duration of correlated spectroscopy in vivo can be longer due to a large number of t1 increments along the indirect (F1) dimension. Limited number of t1 increments on the other hand leads to poor spectral resolution along F1. Covariance transformation (CT) instead of Fourier transform along t1 is an alternative way of increasing the resolution of the 2D COSY spectrum. Prospectively undersampled five-dimensional echo-planar correlated spectroscopic imaging (EP-COSI) data from ten malignant patients and ten healthy women were acquired and reconstructed using compressed sensing. The COSY spectrum at each voxel location was then generated using FFT, CT and a variant of CT called Inner Product (IP). Metabolite and lipid ratios were computed with respect to water from unsuppressed one-dimensional spectrum. The effects of t1-ridging artifacts commonly seen with FFT were not observed with CT/IP. Statistically significant differences were observed in the fat cross peaks measured with CT/IP/FFT. Spectral resolution was increased ~ 8.5 times (~ 19.53 Hz in FFT, ~ 2.32 Hz in CT/IP) without affecting the spectral width along F1 was possible with CT/IP. CT and IP enabled substantially increased F1 resolution effectively with significant gain in scan time and reliable measure of unsaturation index as a biomarker for malignant breast cancer.

Ensemble Learning for Breast Cancer Lesion Classification: A Pilot Validation Using Correlated Spectroscopic Imaging and Diffusion-Weighted Imaging.

The main objective of this work was to evaluate the application of individual and ensemble machine learning models to classify malignant and benign breast masses using features from two-dimensional (2D) correlated spectroscopy spectra extracted from five-dimensional echo-planar correlated spectroscopic imaging (5D EP-COSI) and diffusion-weighted imaging (DWI). Twenty-four different metabolite and lipid ratios with respect to diagonal fat peaks (1.4 ppm, 5.4 ppm) from 2D spectra, and water and fat peaks (4.7 ppm, 1.4 ppm) from one-dimensional non-water-suppressed (NWS) spectra were used as the features. Additionally, water fraction, fat fraction and water-to-fat ratios from NWS spectra and apparent diffusion coefficients (ADC) from DWI were included. The nine most important features were identified using recursive feature elimination, sequential forward selection and correlation analysis. XGBoost (AUC: 93.0%, Accuracy: 85.7%, F1-score: 88.9%, Precision: 88.2%, Sensitivity: 90.4%, Specificity: 84.6%) and GradientBoost (AUC: 94.3%, Accuracy: 89.3%, F1-score: 90.7%, Precision: 87.9%, Sensitivity: 94.2%, Specificity: 83.4%) were the best-performing models. Conventional biomarkers like choline, myo-Inositol, and glycine were statistically significant predictors. Key features contributing to the classification were ADC, 2D diagonal peaks at 0.9 ppm, 2.1 ppm, 3.5 ppm, and 5.4 ppm, cross peaks between 1.4 and 0.9 ppm, 4.3 and 4.1 ppm, 2.3 and 1.6 ppm, and the triglyceryl-fat cross peak. The results highlight the contribution of the 2D spectral peaks to the model, and they demonstrate the potential of 5D EP-COSI for early breast cancer detection.

Alterations of gray and white matter volumes and cortical thickness in treated HIV-positive patients.

Brain structural changes in HIV identified by voxel-based morphometry (VBM) alone could arise from a variety of causes that are difficult to distinguish without further information, such as cortical thickness (CT), gyrification index (GI) or sulcal depth (SD). Hence, our goal was to assess these additional metrics in HIV using high-resolution 3D T1-weighted images and investigate if surface-based morphometric (SBM) analysis would reveal significant changes in the gray matter (GM) and white matter (WM) volumes combined with alterations in cortical thickness (CT), gyrification index (GI), sulcal depth (SD). T1-w magnetization-prepared-rapid-acquisition gradient-echo (MP-RAGE) scans were acquired in 27 HIV-infected individuals on antiretroviral therapy (ART) and 15 HIV-uninfected healthy controls using a 3T MRI scanner equipped with a 16-channel head "receive" and a quadrature body "transmit" coil. Voxel-based and surface-based morphometric analyses were performed using the MATLAB based SPM Computational Anatomy Toolbox (CAT12.7(1700)). HIV-infected patients showed significantly altered GM and WM volumes, CT, GI, and SD, in multiple brain regions. This study showed the association of altered GM and WM volumes in local brain regions with the changes in region-wise CT, GI and SD measures of HIV-infected patients, especially in the parahippocampal and middle frontal regions as compared to uninfected healthy controls. The outcome of this study suggests that the findings of VBM may not necessarily indicate the volumetric shrinkage or increase alone, but might also be due to altered CT, GI, or SD. Correlation analysis showed a significantly accelerated gray matter loss with age in HIV-infected individuals compared to uninfected healthy controls.

Dictionary learning compressed sensing reconstruction: pilot validation of accelerated echo planar J-resolved spectroscopic imaging in prostate cancer.

OBJECTIVES: This study aimed at developing dictionary learning (DL) based compressed sensing (CS) reconstruction for randomly undersampled five-dimensional (5D) MR Spectroscopic Imaging (3D spatial + 2D spectral) data acquired in prostate cancer patients and healthy controls, and test its feasibility at 8x and 12x undersampling factors. MATERIALS AND METHODS: Prospectively undersampled 5D echo-planar J-resolved spectroscopic imaging (EP-JRESI) data were acquired in nine prostate cancer (PCa) patients and three healthy males. The 5D EP-JRESI data were reconstructed using DL and compared with gradient sparsity-based Total Variation (TV) and Perona-Malik (PM) methods. A hybrid reconstruction technique, Dictionary Learning-Total Variation (DLTV), was also designed to further improve the quality of reconstructed spectra. RESULTS: The CS reconstruction of prospectively undersampled (8x and 12x) 5D EP-JRESI data acquired in prostate cancer and healthy subjects were performed using DL, DLTV, TV and PM. It is evident that the hybrid DLTV method can unambiguously resolve 2D J-resolved peaks including myo-inositol, citrate, creatine, spermine and choline. CONCLUSION: Improved reconstruction of the accelerated 5D EP-JRESI data was observed using the hybrid DLTV. Accelerated acquisition of in vivo 5D data with as low as 8.33% samples (12x) corresponds to a total scan time of 14 min as opposed to a fully sampled scan that needs a total duration of 2.4 h (TR = 1.2 s, 32 [Formula: see text]×16 [Formula: see text]×8 [Formula: see text], 512 [Formula: see text] and 64 [Formula: see text]).

In Vivo Renal Lipid Quantification by Accelerated Magnetic Resonance Spectroscopic Imaging at 3T: Feasibility and Reliability Study.

A reliable and practical renal-lipid quantification and imaging method is needed. Here, the feasibility of an accelerated MRSI method to map renal fat fractions (FF) at 3T and its repeatability were investigated. A 2D density-weighted concentric-ring-trajectory MRSI was used for accelerating the acquisition of 48 × 48 voxels (each of 0.25 mL spatial resolution) without respiratory navigation implementations. The data were collected over 512 complex-FID timepoints with a 1250 Hz spectral bandwidth. The MRSI sequence was designed with a metabolite-cycling technique for lipid-water separation. The in vivo repeatability performance of the sequence was assessed by conducting a test-reposition-retest study within healthy subjects. The coefficient of variation (CV) in the estimated FF from the test-retest measurements showed a high degree of repeatability of MRSI-FF (CV = 4.3 ± 2.5%). Additionally, the matching level of the spectral signature within the same anatomical region was also investigated, and their intrasubject repeatability was also high, with a small standard deviation (8.1 ± 6.4%). The MRSI acquisition duration was ~3 min only. The proposed MRSI technique can be a reliable technique to quantify and map renal metabolites within a clinically acceptable scan time at 3T that supports the future application of this technique for the non-invasive characterization of heterogeneous renal diseases and tumors.

Correlated MR spectroscopic imaging of breast cancer to investigate metabolites and lipids: acceleration and compressed sensing reconstruction.

Objectives: The main objective of this work was to detect novel biomarkers in breast cancer by spreading the MR spectra over two dimensions in multiple spatial locations using an accelerated 5D EP-COSI technology. Methods: The 5D EP-COSI data were non-uniformly undersampled with an acceleration factor of 8 and reconstructed using group sparsity-based compressed sensing reconstruction. Different metabolite and lipid ratios were then quantified and statistically analyzed for significance. Linear discriminant models based on the quantified metabolite and lipid ratios were generated. Spectroscopic images of the quantified metabolite and lipid ratios were also reconstructed. Results: The 2D COSY spectra generated using the 5D EP-COSI technique showed differences among healthy, benign, and malignant tissues in terms of their mean values of metabolite and lipid ratios, especially the ratios of potential novel biomarkers based on unsaturated fatty acids, myo-inositol, and glycine. It is further shown the potential of choline and unsaturated lipid ratio maps, generated from the quantified COSY signals across multiple locations in the breast, to serve as complementary markers of malignancy that can be added to the multiparametric MR protocol. Discriminant models using metabolite and lipid ratios were found to be statistically significant for classifying benign and malignant tumor from healthy tissues. Conclusions: Accelerated 5D EP-COSI technique demonstrates the potential to detect novel biomarkers such as glycine, myo-inositol, and unsaturated fatty acids in addition to commonly reported choline in breast cancer, and facilitates metabolite and lipid ratio maps which have the potential to play a significant role in breast cancer detection. Advances in knowledge: This study presents the first evaluation of a multidimensional MR spectroscopic imaging technique for the detection of potentially novel biomarkers based on glycine, myo-inositol, and unsaturated fatty acids, in addition to commonly reported choline. Spatial mapping of choline and unsaturated fatty acid ratios with respect to water in malignant and benign breast masses are also shown. These metabolic characteristics may serve as additional biomarkers for improving the diagnostic and therapeutic evaluation of breast cancer.

Accelerated radial echo-planar spectroscopic imaging using golden angle view-ordering and compressed-sensing reconstruction with total variation regularization.

PURPOSE: To implement a novel, accelerated, 2D radial echo-planar spectroscopic imaging (REPSI) sequence using undersampled radial k-space trajectories and compressed-sensing reconstruction, and to compare results with those from an undersampled Cartesian spectroscopic sequence. METHODS: The REPSI sequence was implemented using golden-angle view-ordering on a 3T MRI scanner. Radial and Cartesian echo-planar spectroscopic imaging (EPSI) data were acquired at six acceleration factors, each with time-equivalent scan durations, and reconstructed using compressed sensing with total variation regularization. Results from prospectively and retrospectively undersampled phantom and in vivo brain data were compared over estimated concentrations and Cramer-Rao lower-bound values, normalized RMS errors of reconstructed metabolite maps, and percent absolute differences between fully sampled and reconstructed spectroscopic images. RESULTS: The REPSI method with compressed sensing is able to tolerate greater reductions in scan time compared with EPSI. The reconstruction and quantitation metrics (i.e., spectral normalized RMS error maps, metabolite map normalized RMS error values [e.g., for total N-acetyl asparate, REPSI = 9.4% vs EPSI = 16.3%; acceleration factor = 2.5], percent absolute difference maps, and concentration and Cramer-Rao lower-bound estimates) showed that accelerated REPSI can reduce the scan time by a factor of 2.5 while retaining image and quantitation quality. CONCLUSION: Accelerated MRSI using undersampled radial echo-planar acquisitions provides greater reconstruction accuracy and more reliable quantitation for a range of acceleration factors compared with time-equivalent compressed-sensing reconstructions of undersampled Cartesian EPSI. Compared to the Cartesian approach, radial undersampling with compressed sensing could help reduce 2D spectroscopic imaging acquisition time, and offers a better trade-off between imaging speed and quality.

White matter of perinatally HIV infected older youths shows low frequency fluctuations that may reflect glial cycling.

In perinatally HIV-infected (PHIV) children, neurodevelopment occurs in the presence of HIV-infection, and even with combination antiretroviral therapy (cART) the brain can be a reservoir for latent HIV. Consequently, patients often demonstrate long-term cognitive deficits and developmental delay, which may be reflected in altered functional brain activity. Our objective was to examine brain function in PHIV on cART by quantifying the amplitude of low frequency fluctuations (ALFF) and regional homogeneity (ReHo). Further, we studied ALFF and ReHo changes with neuropsychological performance and measures of immune health including CD4 count and viral loads in the HIV-infected youths. We found higher ALFF and ReHo in cerebral white matter in the medial orbital lobe for PHIV (N = 11, age mean ± sd = 22.5 ± 2.9 years) compared to controls (N = 16, age = 22.5 ± 3.0 years), with age and gender as co-variates. Bilateral cerebral white matter showed increased spontaneous regional activity in PHIV compared to healthy controls. No brain regions showed lower ALFF or ReHo in PHIV compared to controls. Higher log10 viral load was associated with higher ALFF and ReHo in PHIV in bilateral cerebral white matter and right cerebral white matter respectively after masking the outcomes intrinsic to the brain regions that showed significantly higher ALFF and ReHo in the PHIV compared to the control. Reductions in social cognition and abstract thinking in PHIV were correlated with higher ALFF at the left cerebral white matter in the left medial orbital gyrus and higher ReHo at the right cerebral white matter in the PHIV patients. Although neuroinflammation and associated neuro repair were not directly measured, the findings support their potential role in PHIV impacting neurodevelopment and cognition.

Fat-water separation by fast metabolite cycling magnetic resonance spectroscopic imaging at 3 T: A method to generate separate quantitative distribution maps of musculoskeletal lipid components.

PURPOSE: To provide a rapid, noninvasive fat-water separation technique that allows producing quantitative maps of particular lipid components. METHODS: The calf muscles in 5 healthy adolescents (age 12-16 years; body mass index = 20 ± 3 kg/m2 ) were scanned by two different fat fraction measurement methods. A density-weighted concentric-ring trajectory metabolite-cycling MRSI technique was implemented to collect data with a nominal resolution of 0.25 mL within 3 minutes and 16 seconds. For comparative purposes, the standard Dixon technique was performed. The two techniques were compared using structural similarity analysis. Additionally, the difference in the distribution of each lipid over the adolescent calf muscles was assessed based on the MRSI data. RESULTS: The proposed MRSI technique provided individual fat fraction maps for eight musculoskeletal lipid components identified by LCModel analysis (IMC/L [CH3 ], EMCL [CH3 ], IMC/L [CH2 ]n , EMC/L [CH2 ]n , IMC/L [CH2 -CH], EMC/L [CH2 -CH], IMC/L [-CH=CH-], and EMC/L [-CH=CH-]) with mean structural similarity indices of 0.19, 0.04, 0.03, 0.50, 0.45, 0.04, 0.07, and 0.12, respectively, compared with the maps generated by the used Dixon method. Further analysis of voxels with zero structural similarity demonstrated an increased sensitivity of fat fraction lipid maps from the data acquired using this MRSI technique over the standard Dixon technique. The lipid spatial distribution over calf muscles was consistent with previously published findings in adults. CONCLUSION: This MRSI technique can be a useful tool when individual lipid fat fraction maps are desired within a clinically acceptable time and with a nominal spatial resolution of 0.25 mL.

DTI-based upper limit of voxel free water fraction.

BACKGROUND: Free water (FW) in neuroimaging is non-flowing extracellular water in the cranium and brain tissue, and includes both cerebral spinal fluid (CSF) and fluid in intercellular space or edema. For a region such as a voxel (spatial unit of measurement in neuroimaging), the FW fraction is defined as the volume fraction of FW within that volume. Quantifying the FW fraction allows estimating contamination by fluid of neuroimaging or magnetic resonance spectroscopy measurements within a voxel. NEW METHOD: An upper limit to the fraction of FW within a voxel, based on any diffusion tensor imaging (DTI) sequence including a standard single shell at one b-value, can be derived from the standard diffusion tensor by scaling the third eigenvalue of the diffusion tensor. Assuming a two-compartment model, the diffusivity of a voxel is a combination of tissue and FW diffusivity. FW fraction is FW volume divided by voxel volume. Assuming FW diffuses equally in all directions, the diffusivity component is representable by a single, non-tensor diffusivity value. Since the diffusivity of water is known for a given temperature, and brain temperature is relatively constant, the FW diffusivity value can be assumed constant. The third eigenvector of the voxel diffusion tensor is the direction of least diffusivity and since the FW component of diffusivity is equal in all directions, we show that FW diffusivity cannot be lower than the third eigenvalue. Assuming FW contributes proportionally to voxel diffusivity, we show that the third eigenvalue divided by water diffusivity (as a constant based on known water diffusivity at 36.7 °C) forms an upper limit on the FW-fraction (fUL ). RESULTS: We calculated fUL for 384 subjects from the IXI dataset. Values mostly ranged from 0.1 to 0.6, and were closely related to radial diffusivity.Comparison with Existing Methods:fUL is easily calculated from any DTI data, but is not a true estimate of FW-fraction. CONCLUSIONS: The fUL measure offers a starting point in calculating the true FW-fraction of a voxel, or an easy-to-calculate voxel characteristic.

Obstructive sleep apnea and cortical thickness in females and males.

INTRODUCTION: Obstructive sleep apnea (OSA) affects approximately 10% of adults, and alters brain gray and white matter. Psychological and physiological symptoms of the disorder are sex-specific, perhaps related to greater injury occurs in female than male patients in white matter. Our objective was to identify influences of OSA separated by sex on cortical gray matter. METHODS: We assessed cortical thickness in 48 mild-severe OSA patients (mean age±std[range] = 46.5±9.0[30.8-62.7] years; apnea-hypopnea index = 32.6±21.1[6-102] events/hour; 12 female, 36 male; OSA severity: 5 mild, 18 moderate, 25 severe) and 62 controls (mean age = 47.7±8.9[30.9-65.8] years; 22 female, 40 male). All OSA patients were recently-diagnosed via polysomnography, and control subjects screened and a subset assessed with sleep studies. We used high-resolution magnetic resonance imaging to identify OSA-related cortical thinning, based on a model with condition and sex as independent variables. OSA and OSA-by-sex interaction effects were assessed (P<0.05, corrected for multiple comparisons). RESULTS: Multiple regions of reduced cortical thickness appeared bilaterally in the superior frontal lobe in female OSA vs. all other groups. Significant thinning within the pre- and post-central gyri and the superior temporal gyrus, extending into the insula, appeared between the general OSA populations vs. control subjects. No areas showed increased thickness in OSA vs. controls or positive female OSA interaction effects. CONCLUSIONS: Reduced cortical thickness likely represents tissue atrophy from long term injury, including death of neurons and supporting glia from repeated intermittent hypoxic exposure in OSA, although disease comordities may also contribute to thinning. Lack of polysomnography in all control subjects means results may be confounded by undiagnosed OSA. The greater cortical injury in cognitive areas of female OSA patients may underlie enhanced symptoms in that group. The thinning associated with OSA in male and females OSA patients may contribute to autonomic dysregulation and impaired upper airway sensori-motor function.

Assessment of Lipid and Metabolite Changes in Obese Calf Muscle Using Multi-Echo Echo-planar Correlated Spectroscopic Imaging.

Obesity-related conditions including heart disease, stroke, and type 2 diabetes are leading causes of preventable death. Recent evidence suggests that altered myocellular lipid metabolism in obesity may lead to increased insulin resistance (IR) that predisposes to these disorders. To test the hypothesis that muscles rich in type I vs. type II muscle fibers would exhibit similar changes in intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) content in obesity, we utilized a new four-dimensional multi echo echo-planar correlated spectroscopic imaging technique that allows separate determination of IMCL and EMCL content in individual calf muscles in obese vs. normal healthy human subjects. Calf muscles were scanned in 32 obese and 11 healthy subjects using a 3T MRI/MRS scanner, and IR in the obese subjects was documented by glucose tolerance testing. In obese subjects, elevation of both IMCL and EMCL content was observed in the gastrocnemius and tibialis anterior muscles (with mixed type I and II fiber content), while a significant increase in only IMCL content (+48%, p < 0.001) was observed in the soleus muscle (predominantly type I fibers). These observations indicate unexpected differences in changes in myolipid metabolism in type I vs. type II rich muscle regions in obesity, perhaps related to IR, and warrant further investigation.

Obstructive sleep apnea is associated with altered midbrain chemical concentrations.

Obstructive sleep apnea (OSA) is accompanied by altered structure and function in cortical, limbic, brainstem, and cerebellar regions. The midbrain is relatively unexamined, but contains many integrative nuclei which mediate physiological functions that are disrupted in OSA. We therefore assessed the chemistry of the midbrain in OSA in this exploratory study. We used a recently developed accelerated 2D magnetic resonance spectroscopy (2D-MRS) technique, compressed sensing-based 4D echo-planar J-resolved spectroscopic imaging (4D-EP-JRESI), to measure metabolites in the midbrain of 14 OSA (mean age±SD:54.6±10.6years; AHI:35.0±19.4; SAO2 min:83±7%) and 26 healthy control (50.7±8.5years) subjects. High-resolution T1-weighted scans allowed voxel localization. MRS data were processed with custom MATLAB-based software, and metabolite ratios calculated with respect to the creatine peak using a prior knowledge fitting (ProFit) algorithm. The midbrain in OSA showed decreased N-acetylaspartate (NAA; OSA:1.24±0.43, Control:1.47±0.41; p=0.03; independent samples t-test), a marker of neuronal viability. Increased levels in OSA over control subjects appeared in glutamate (Glu; OSA:1.23±0.57, Control:0.98±0.33; p=0.03), ascorbate (Asc; OSA:0.56±0.28, Control:0.42±0.20; (50.7±8.5years; p=0.03), and myo-inositol (mI; OSA:0.96±0.48, Control:0.72±0.35; p=0.03). No differences between groups appeared in γ-aminobutyric acid (GABA) or taurine. The midbrain in OSA patients shows decreased NAA, indicating neuronal injury or dysfunction. Higher Glu levels may reflect excitotoxic processes and astrocyte activation, and higher mI is also consistent with glial activation. Higher Asc levels may result from oxidative stress induced by intermittent hypoxia in OSA. Additionally, Asc and Glu are involved with glutamatergic processes, which are likely upregulated in the midbrain nuclei of OSA patients. The altered metabolite levels help explain dysfunction and structural deficits in the midbrain of OSA patients.

Prior-knowledge Fitting of Accelerated Five-dimensional Echo Planar J-resolved Spectroscopic Imaging: Effect of Nonlinear Reconstruction on Quantitation.

1H Magnetic Resonance Spectroscopic imaging (SI) is a powerful tool capable of investigating metabolism in vivo from mul- tiple regions. However, SI techniques are time consuming, and are therefore difficult to implement clinically. By applying non-uniform sampling (NUS) and compressed sensing (CS) reconstruction, it is possible to accelerate these scans while re- taining key spectral information. One recently developed method that utilizes this type of acceleration is the five-dimensional echo planar J-resolved spectroscopic imaging (5D EP-JRESI) sequence, which is capable of obtaining two-dimensional (2D) spectra from three spatial dimensions. The prior-knowledge fitting (ProFit) algorithm is typically used to quantify 2D spectra in vivo, however the effects of NUS and CS reconstruction on the quantitation results are unknown. This study utilized a simulated brain phantom to investigate the errors introduced through the acceleration methods. Errors (normalized root mean square error >15%) were found between metabolite concentrations after twelve-fold acceleration for several low concentra- tion (<2 mM) metabolites. The Cramér Rao lower bound% (CRLB%) values, which are typically used for quality control, were not reflective of the increased quantitation error arising from acceleration. Finally, occipital white (OWM) and gray (OGM) human brain matter were quantified in vivo using the 5D EP-JRESI sequence with eight-fold acceleration.

Echo-Planar J-resolved Spectroscopic Imaging using Dual Read-outs: Implementation and Quantitation of Human Brain Metabolites.

Attempts have been made to reduce the total scan time in multi-dimensional J-resolved spectroscopic imaging (JRESI) using an echo-planar (EP) readout gradient, but acquisition duration remains a limitation for routine clinical use in the brain. We present here a significant acceleration achieved with a 4D EP-JRESI sequence that collects dual phase encoded lines within a single repetition time (TR) using two bipolar read-out trains. The performance and reliability of this novel 4D sequence, called Multi-Echo based Echo-Planar J-resolved Spectroscopic Imaging (ME-EP-JRESI), was evaluated in 10 healthy controls and a brain phantom using a 3 T MRI/MRS scanner. The prior knowledge fitting (ProFit) algorithm, with a new simulated basis set consisting of macromolecules and lipids apart from metabolites of interest, was used for quantitation. Both phantom and in-vivo data demonstrated that localization and spatial/spectral profiles of metabolites from the ME-EP-JRESI sequence were in good agreement with that of the EP-JRESI sequence. Both in the occipital and temporal lobe, metabolites with higher physiological concentrations including Glx (Glu+Gln), tNAA (NAA+NAAG), mI all had coefficient of variations between 9-25%. In summary, we have implemented, validated and tested the ME-EP-JRESI sequence, demonstrating that multi-echo acquisition can successfully reduce the total scan duration for EP-JRESI sequences.

Covariance J-resolved spectroscopy: Theory and application in vivo.

Magnetic resonance spectroscopy (MRS) is a powerful tool capable of investigating the metabolic status of several tissues in vivo. In particular, single-voxel-based 1 H spectroscopy provides invaluable biochemical information from a volume of interest (VOI) and has therefore been used in a variety of studies. Unfortunately, typical one-dimensional MRS data suffer from severe signal overlap and thus important metabolites are difficult to distinguish. One method that is used to disentangle overlapping resonances is the two-dimensional J-resolved spectroscopy (JPRESS) experiment. Due to the long acquisition duration of the JPRESS experiment, a limited number of points are acquired in the indirect dimension, leading to poor spectral resolution along this dimension. Poor spectral resolution is problematic because proper peak assignment may be hindered, which is why the zero-filling method is often used to improve resolution as a post-processing step. However, zero-filling leads to spectral artifacts, which may affect visualization and quantitation of spectra. A novel method utilizing a covariance transformation, called covariance J-resolved spectroscopy (CovJ), was developed in order to improve spectral resolution along the indirect dimension (F1 ). Comparison of simulated data demonstrates that peak structures remain qualitatively similar between JPRESS and the novel method along the diagonal region (F1 = 0 Hz), whereas differences arise in the cross-peak (F1 ≠0 Hz) regions. In addition, quantitative results of in vivo JPRESS data acquired on a 3T scanner show significant correlations (r2 >0.86, p<0.001) when comparing the metabolite concentrations between the two methods. Finally, a quantitation algorithm, 'COVariance Spectral Evaluation of 1 H Acquisitions using Representative prior knowledge' (Cov-SEHAR), was developed in order to quantify γ-aminobutyric acid and glutamate from the CovJ spectra. These preliminary findings indicate that the CovJ method may be used to improve spectral resolution without hindering metabolite quantitation for J-resolved spectra.

Non-water-suppressed short-echo-time magnetic resonance spectroscopic imaging using a concentric ring k-space trajectory.

Water-suppressed MRS acquisition techniques have been the standard MRS approach used in research and for clinical scanning to date. The acquisition of a non-water-suppressed MRS spectrum is used for artefact correction, reconstruction of phased-array coil data and metabolite quantification. Here, a two-scan metabolite-cycling magnetic resonance spectroscopic imaging (MRSI) scheme that does not use water suppression is demonstrated and evaluated. Specifically, the feasibility of acquiring and quantifying short-echo (TE  = 14 ms), two-dimensional stimulated echo acquisition mode (STEAM) MRSI spectra in the motor cortex is demonstrated on a 3 T MRI system. The increase in measurement time from the metabolite-cycling is counterbalanced by a time-efficient concentric ring k-space trajectory. To validate the technique, water-suppressed MRSI acquisitions were also performed for comparison. The proposed non-water-suppressed metabolite-cycling MRSI technique was tested for detection and correction of resonance frequency drifts due to subject motion and/or hardware instability, and the feasibility of high-resolution metabolic mapping over a whole brain slice was assessed. Our results show that the metabolite spectra and estimated concentrations are in agreement between non-water-suppressed and water-suppressed techniques. The achieved spectral quality, signal-to-noise ratio (SNR) > 20 and linewidth <7 Hz allowed reliable metabolic mapping of five major brain metabolites in the motor cortex with an in-plane resolution of 10 × 10 mm2 in 8 min and with a Cramér-Rao lower bound of less than 20% using LCModel analysis. In addition, the high SNR of the water peak of the non-water-suppressed technique enabled voxel-wise single-scan frequency, phase and eddy current correction. These findings demonstrate that our non-water-suppressed metabolite-cycling MRSI technique can perform robustly on 3 T MRI systems and within a clinically feasible acquisition time.