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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

CHARGE (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth, Genital anomalies and Ear abnormalities) syndrome is a disorder caused by mutations in the gene encoding CHD7, an ATP dependent chromatin remodelling factor, and is characterised by a diverse array of congenital anomalies. These include a range of neuroanatomical comorbidities which likely underlie the varied neurodevelopmental disorders associated with CHARGE syndrome, which include intellectual disability, motor coordination deficits, executive dysfunction, and autism spectrum disorder. Cranial imaging studies are challenging in CHARGE syndrome patients, but high‐throughput magnetic resonance imaging (MRI) techniques in mouse models allow for the unbiased identification of neuroanatomical defects. Here, we present a comprehensive neuroanatomical survey of a Chd7 haploinsufficient mouse model of CHARGE syndrome. Our study uncovered widespread brain hypoplasia and reductions in white matter volume across the brain. The severity of hypoplasia appeared more pronounced in posterior areas of the neocortex compared to anterior regions. We also perform the first assessment of white matter tract integrity in this model through diffusion tensor imaging (DTI) to assess the potential functional consequences of widespread reductions in myelin, which suggested the presence of white matter integrity defects. To determine if white matter alterations correspond to cellular changes, we quantified oligodendrocyte lineage cells in the postnatal corpus callosum, uncovering reduced numbers of mature oligodendrocytes. Together, these results present a range of promising avenues of focus for future cranial imaging studies in CHARGE syndrome patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: A total of 15–20% of patients with rectal cancer have liver metastases on presentation. The management of these patients is controversial. Heterogeneity in management strategies is considerable, with management often being dependent on local resources and available expertise. Method: Members of the PelvEx Collaborative were invited to participate in the generation of a consensus statement on the optimal management of patients with advanced rectal cancer with liver involvement. Fifteen statements were created for topical discussion on diagnostic and management issues. Panellists were asked to vote on statements and anonymous feedback was given. A collaborative meeting was used to discuss any nuances and clarify any obscurity. Consensus was considered when > 85% agreement on a statement was achieved. Results: A total of 135 participants were involved in the final round of the Delphi questionnaire. Nine of the 15 statements reached consensus regarding the management of patients with advanced rectal cancer and oligometastatic liver disease. Routine use of liver MRI was not recommended for patients with locally advanced rectal cancer, unless there was concern for metastatic disease on initial computed tomography staging scan. Induction chemotherapy was advocated as first‐line treatment in those with synchronous liver metastases in locally advanced rectal cancer. In the presence of symptomatic primary disease, a diverting stoma may be required to facilitate induction chemotherapy. Overall, only one‐quarter of the panellists would consider simultaneous pelvic exenteration and liver resection. Conclusion: This Delphi process highlights the diverse treatment of advanced rectal cancer with liver metastases and provides recommendations from an experienced international group regarding the multidisciplinary management approach. [ABSTRACT FROM AUTHOR]

The article discusses variable annuities. After describing what a variable annuity is and explaining its objectives, the author discusses the history of stock prices and the cost of living, demonstrating several periods where variable (as opposed to fixed) payments would have been particularly beneficial. Future economic prospects and their implications for annuities are discussed, as are issues arising from the ownership of common stock by life insurance companies. On balance the author concludes that variable rate annuities should not be offered directly by life insurance firms, but rather by their subsidiaries or other financial institutions.

Recent large‐scale exome sequencing studies have identified mutations in several members of the CHD (Chromodomain Helicase DNA‐binding protein) gene family in neurodevelopmental disorders. Mutations in the CHD2 gene have been linked to developmental delay, intellectual disability, autism and seizures, CHD8 mutations to autism and intellectual disability, whereas haploinsufficiency of CHD7 is associated with executive dysfunction and intellectual disability. In addition to these neurodevelopmental features, a wide range of other developmental defects are associated with mutants of these genes, especially with regards to CHD7 haploinsufficiency, which is the primary cause of CHARGE syndrome. Whilst the developmental expression of CHD7 has been reported previously, limited information on the expression of CHD2 and CHD8 during development is available. Here, we compare the expression patterns of all three genes during mouse development directly. We find high, widespread expression of these genes at early stages of development that gradually becomes restricted during later developmental stages. Chd2 and Chd8 are widely expressed in the developing central nervous system (CNS) at all stages of development, with moderate expression remaining in the neocortex, hippocampus, olfactory bulb and cerebellum of the postnatal brain. Similarly, Chd7 expression is seen throughout the CNS during late embryogenesis and early postnatal development, with strong enrichment in the cerebellum, but displays low expression in the cortex and neurogenic niches in early life. In addition to expression in the brain, novel sites of Chd2 and Chd8 expression are reported. These findings suggest additional roles for these genes in organogenesis and predict that mutation of these genes may predispose individuals to a range of other, non‐neurological developmental defects. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Autism Spectrum Disorders ( ASDs) are a heterogeneous group of neurodevelopmental disorders that are diagnosed solely on the basis of behaviour. A large body of work has reported neuroanatomical differences between individuals with ASD and neurotypical controls. Despite the huge clinical and genetic heterogeneity that typifies autism, some of these anatomical features appear to be either present in most cases or so dramatically altered in some that their presence is now reasonably well replicated in a number of studies. One such finding is the tendency towards overgrowth of the frontal cortex during the early postnatal period. Although these reports have been focused primarily on the presumed pathological anatomy, they are providing us with important insights into normal brain anatomy and are stimulating new ideas and hypotheses about the normal trajectory of brain development and the function of specific anatomical brain structures. The use of model systems that include genetic model organisms such as the mouse and, more recently, human induced pluripotent stem cell-derived brain organoids to model normal and pathological human cortical development, is proving particularly informative. Here we review some of the neuroanatomical alterations reported in autism, with a particular focus on well-validated findings and recent advances in the field, and ask what these observations can tell us about normal and abnormal brain development. [ABSTRACT FROM AUTHOR]

The article presents a reply McMahon and Soldofsky's (MS) criticism of the author's use of the Standard and Poor's Stock Price index. Provided is a chart representing the two sets of figures about what has been discussed. MS produced a series of figures in Table one under Variable Annuities Certain. The author discusses various problems with those figures. The author states that he does not believe the Standard and Poor index is misleading. The Variable Annuity Certain figures must be accomplished by performing specific routines of investment.

The insular cortex is injured in obstructive sleep apnea ( OSA) and responds inappropriately to autonomic challenges, suggesting neural reorganization. The objective of this study was to assess whether the neural changes might result from γ-aminobutyric acid ( GABA) and glutamate alterations. We studied 14 OSA patients [mean age ± standard deviation ( SD): 47.5 ± 10.5 years; nine male; apnea-hypopnea index ( AHI): 29.5 ± 15.6 events h−1] and 22 healthy participants (47.5 ± 10.1 years; 11 male), using magnetic resonance spectroscopy to detect GABA and glutamate levels in insular cortices. We localized the cortices with anatomical scans, and measured neurochemical levels from anterior to mid-regions. Left and right anterior insular cortices showed lower GABA and higher glutamate in OSA versus healthy subjects [ GABA left: OSA n = 6: 0.36 ± 0.10 (mean ± SD), healthy n = 5: 0.62 ± 0.18; P < 0.05), right: OSA n = 11: 0.27 ± 0.09, healthy n = 14: 0.45 ± 0.16; P < 0.05; glutamate left: OSA n = 6: 1.61 ± 0.32, healthy n = 8: 0.94 ± 0.34; P < 0.05, right: OSA n = 14: 1.26 ± 0.28, healthy n = 19: 1.02 ± 0.28; P < 0.05]. GABA and glutamate levels were correlated only within the healthy group in the left insula ( r: −0.9, P < 0.05). The altered anterior insular levels of GABA and glutamate may modify integration and projections to autonomic areas, contributing to the impaired cardiovascular regulation in OSA. [ABSTRACT FROM AUTHOR]

Several different pathologies, including many neurodegenerative disorders, affect the energy metabolism of the brain. Glutamate, a neurotransmitter in the brain, can be used as a biomarker to monitor these metabolic processes. One method that is capable of quantifying glutamate concentration reliably in several regions of the brain is TE-averaged 1H spectroscopic imaging. However, this type of method requires the acquisition of multiple TE lines, resulting in long scan durations. The goal of this experiment was to use non-uniform sampling, compressed sensing reconstruction and an echo planar readout gradient to reduce the scan time by a factor of eight to acquire TE-averaged spectra in three spatial dimensions. Simulation of glutamate and glutamine showed that the 2.2-2.4 ppm spectral region contained 95% glutamate signal using the TE-averaged method. Peak integration of this spectral range and home-developed, prior-knowledge-based fitting were used for quantitation. Gray matter brain phantom measurements were acquired on a Siemens 3 T Trio scanner. Non-uniform sampling was applied retrospectively to these phantom measurements and quantitative results of glutamate with respect to creatine 3.0 (Glu/Cr) ratios showed a coefficient of variance of 16% for peak integration and 9% for peak fitting using eight-fold acceleration. In vivo scans of the human brain were acquired as well and five different brain regions were quantified using the prior-knowledge-based algorithm. Glu/Cr ratios from these regions agreed with previously reported results in the literature. The method described here, called accelerated TE-averaged echo planar spectroscopic imaging (TEA-EPSI), is a significant methodological advancement and may be a useful tool for categorizing glutamate changes in pathologies where affected brain regions are not known a priori. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose: To implement an accelerated five-dimensional (5D) echo-planar J-resolved spectroscopic imaging sequence combining 3 spatial and 2 spectral encoding dimensions and to apply the sequence in human brain. Methods: An echo planar readout was used to acquire a single spatial and a single spectral dimension during one readout. Nonuniform sampling was applied to the two phase-encoded spatial directions and the indirect spectral dimension. Nonlinear reconstruction was used to minimize the l1-norm or the total variation and included a spectral mask to enhance sparsity. Retrospective reconstructions at multiple undersamplings were performed in phantom. Ten healthy volunteers were scanned with 8× undersampling and compared to a fully sampled single slice scan. Results: Retrospective reconstruction of fully sampled phantom data showed excellent quality at 4×, 8×, 12×, and 16× undersampling using either reconstruction method. Reconstruction of prospectively acquired in vivo scans with 8× undersampling showed excellent quality in the occipitoparietal lobes and good quality in the frontal lobe, consistent with the fully sampled single slice scan. Conclusion: By utilizing nonuniform sampling with nonlinear reconstruction, 2D J-resolved spectra can be acquired over a 3D spatial volume with a total scan time of 20 min, which is reasonable for in vivo studies. [ABSTRACT FROM AUTHOR]

The overlap of metabolites is a major limitation in one-dimensional (1D) spectral-based single-voxel MRS and multivoxel-based MRSI. By combining echo planar spectroscopic imaging (EPSI) with a two-dimensional (2D) J-resolved spectroscopic (JPRESS) sequence, 2D spectra can be recorded in multiple locations in a single slice of prostate using four-dimensional (4D) echo planar J-resolved spectroscopic imaging (EP-JRESI). The goal of the present work was to validate two different non-linear reconstruction methods independently using compressed sensing-based 4D EP-JRESI in prostate cancer (PCa): maximum entropy (MaxEnt) and total variation (TV). Twenty-two patients with PCa with a mean age of 63.8 years (range, 46-79 years) were investigated in this study. A 4D non-uniformly undersampled (NUS) EP-JRESI sequence was implemented on a Siemens 3-T MRI scanner. The NUS data were reconstructed using two non-linear reconstruction methods, namely MaxEnt and TV. Using both TV and MaxEnt reconstruction methods, the following observations were made in cancerous compared with non-cancerous locations: (i) higher mean (choline + creatine)/citrate metabolite ratios; (ii) increased levels of (choline + creatine)/spermine and (choline + creatine)/myo-inositol; and (iii) decreased levels of (choline + creatine)/(glutamine + glutamate). We have shown that it is possible to accelerate the 4D EP-JRESI sequence by four times and that the data can be reliably reconstructed using the TV and MaxEnt methods. The total acquisition duration was less than 13 min and we were able to detect and quantify several metabolites. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose To implement a 5D (three spatial + two spectral) correlated spectroscopic imaging sequence for application to human calf. Theory and Methods Nonuniform sampling was applied across the two phase encoded dimensions and the indirect spectral dimension of an echo planar-correlated spectroscopic imaging sequence. Reconstruction was applied that minimized the group sparse mixed [ABSTRACT FROM AUTHOR]

Objectives The aim of the present study was to examine N-acetylaspartate (NAA), a general marker of neuronal viability, and total NAA ( tNAA), the combined signal of NAA and N-acetylaspartylglutamate, in bipolar depression before and after lamotrigine treatment. Given that NAA is synthesized through direct acetylation of aspartate by acetyl-coenzyme A- l-aspartate- N-acetyltransferase, we hypothesized that treatment with lamotrigine would be associated with an increase in NAA level. Methods Patients with bipolar depression underwent two-dimensional proton magnetic resonance spectroscopy of the anterior cingulate at baseline (n = 15) and after 12 weeks of lamotrigine treatment (n = 10). A group of age-matched healthy controls (n = 9) underwent scanning at baseline for comparison. Results At baseline, patients with bipolar depression had significantly lower NAA [mean standard deviation (SD) = 1.13 (0.21); p = 0.02] than controls [mean (SD) = 1.37 (0.27)]. Significant increases in NAA [mean (SD) = 1.39 (0.21); p = 0.01] and tNAA [mean (SD) = 1.61 (0.25); p = 0.02] levels were found after 12 weeks of lamotrigine treatment. Conclusions These data suggest an NAA deficit in bipolar depression that is normalized after lamotrigine treatment. Future research is warranted to evaluate whether baseline NAA level is a potential biomarker for identifying lamotrigine response patterns and whether this functional brain change has an associated clinical response. [ABSTRACT FROM AUTHOR]

A current limitation of MR spectroscopic imaging of multiple skeletal muscles is prolonged scan duration. A significant reduction in the total scan duration using the echo-planar correlated spectroscopic imaging (EP-COSI) sequence was accomplished using two bipolar readout trains with different phase-encoded echoes for one of two spatial dimensions within a single repetition time (TR). The second bipolar readout was used for spatially encoding the outer k-space, whereas the first readout was used for the central k-space only. The performance of this novel sequence, called multi-echo based echo-planar correlated spectroscopic imaging (ME-EPCOSI), was demonstrated by localizing specific key features in calf muscles and bone marrow of 11 healthy volunteers and five subjects with type 2 diabetes (T2D). A 3 T MRI-MRS scanner equipped with a transmit-receive extremity coil was used. Localization of the ME-EPCOSI sequence was in good agreement with the earlier single-readout based EP-COSI sequence and the required scan time was reduced by a factor of two. In agreement with an earlier report using single-voxel based 2D MRS, significantly increased unsaturated pools of intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) and decreased IMCL and EMCL unsaturation indices (UIs) were observed in the soleus and tibialis anterior muscle regions of subjects with T2D compared with healthy controls. In addition, significantly decreased choline content was observed in the soleus of T2D subjects compared with healthy controls. Multi-voxel characterization of IMCL and EMCL ratios and UI in the calf muscle may be useful for the non-invasive assessment of altered lipid metabolism in the pathophysiology of T2D. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In vitro 1H MRS of human bile has shown potential in the diagnosis of various hepatopancreatobiliary (HPB) diseases. Previously, in vivo 1H MRS of human bile in gallbladder using a 1.5 T scanner demonstrated the possibility of quantification of choline-containing phospholipids (chol-PLs). However, other lipid components such as bile acids play an important role in the pathophysiology of the HPB system. We have employed a higher magnetic field strength (3 T), and a custom-built receive array coil, to improve the quality of in vivo 1H MRS of human bile in the gallbladder. We obtained significant improvement in the quality of 1D spectra (17 healthy volunteers) using a respiratory-gated PRESS sequence with well distinguished signals for total bile acids (TBAs) plus cholesterol resonating at 0.66 ppm, taurine-conjugated bile acids (TCBAs) at 3.08 ppm, chol-PLs at 3.22 ppm, glycine-conjugated bile acids (GCBAs) at 3.74 ppm, and the amide proton (−NH) arising from GCBAs and TCBAs in the region 7.76-8.05 ppm. The peak areas of these signals were measured by deconvolution, and subsequently the molar concentrations of metabolites were estimated with good accuracy, except for that of TBAs plus cholesterol. The concentration of TBAs plus cholesterol was overestimated in some cases, which could be due to lipid contamination. In addition, we report the first 2D L-COSY spectra of human gallbladder bile in vivo (obtained in 15 healthy volunteers). 2D L-COSY spectra will be helpful in differentiating various biliary chol-PLs in pathological conditions of the HPB system. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: The T-box transcription factor Tbx1, is essential for the normal development of multiple organ systems in the embryo. One of the most striking phenotypes in Tbx1−/− embryos is the failure of the caudal pharyngeal pouches to evaginate from the foregut endoderm. Despite considerable interest in the role of Tbx1 in development, the mechanisms whereby Tbx1 controls caudal pouch formation have remained elusive. In particular, the question as to how Tbx1 expression in the pharyngeal endoderm regulates pharyngeal pouch morphogenesis in the mouse embryo is not known. Results: To address this question, we produced mouse embryos in which Tbx1 was specifically deleted from the pharyngeal endoderm and, as expected, embryos failed to form caudal pharyngeal pouches. To determine the molecular mechanism, we examined expression of Fgf3 and Fgf8 ligands and downstream effectors. Although Fgf8 expression is greatly reduced in Tbx1-deficient endoderm, FGF signaling levels are unaffected. Furthermore, pouch morphogenesis is only partially perturbed by the loss of both Fgf3 and Fgf8 from the endoderm, indicating that neither are required for pouch formation. Conclusions: Tbx1 deletion from the pharyngeal endoderm is sufficient to cause caudal pharyngeal arch segmentation defects by FGF-independent effectors that remain to be identified. Developmental Dynamics 243:1143-1151, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The four-dimensional (4D) echo-planar correlated spectroscopic imaging (EP-COSI) sequence allows for the simultaneous acquisition of two spatial ( ky, kx) and two spectral ( t2, t1) dimensions in vivo in a single recording. However, its scan time is directly proportional to the number of increments in the ky and t1 dimensions, and a single scan can take 20-40 min using typical parameters, which is too long to be used for a routine clinical protocol. The present work describes efforts to accelerate EP-COSI data acquisition by application of non-uniform under-sampling (NUS) to the ky-t1 plane of simulated and in vivo EP-COSI datasets then reconstructing missing samples using maximum entropy (MaxEnt) and compressed sensing (CS). Both reconstruction problems were solved using the Cambridge algorithm, which offers many workflow improvements over other l1-norm solvers. Reconstructions of retrospectively under-sampled simulated data demonstrate that the MaxEnt and CS reconstructions successfully restore data fidelity at signal-to-noise ratios (SNRs) from 4 to 20 and 5× to 1.25× NUS. Retrospectively and prospectively 4× under-sampled 4D EP-COSI in vivo datasets show that both reconstruction methods successfully remove NUS artifacts; however, MaxEnt provides reconstructions equal to or better than CS. Our results show that NUS combined with iterative reconstruction can reduce 4D EP-COSI scan times by 75% to a clinically viable 5 min in vivo, with MaxEnt being the preferred method. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the second most common type of cancer among men in the United States. A major limitation in the management of PCa is an inability to distinguish, early on, cancers that will progress and become life threatening. One-dimensional (1D) proton (1H) MRS of the prostate provides metabolic information such as levels of choline (Ch), creatine (Cr), citrate (Cit), and spermine (Spm) that can be used to detect and diagnose PCa. Ex vivo high-resolution magic angle spinning (HR-MAS) of PCa specimens has revealed detection of more metabolites such as myo-inositol (mI), glutamate (Glu), and glutamine (Gln). Due to the J-modulation and signal overlap, it is difficult to quantitate Spm and other resonances in the prostate clearly by single- and multivoxel-based 1D MR spectroscopy. This limitation can be minimized by adding at least one more spectral dimension by which resonances can be spread apart, thereby increasing the spectral dispersion. However, recording of multivoxel-based two-dimensional (2D) MRS such as J-resolved spectroscopy (JPRESS) and correlated spectroscopy (L-COSY) combined with 2D or three-dimensional (3D) magnetic resonance spectroscopic imaging (MRSI) using conventional phase-encoding can be prohibitively long to be included in a clinical protocol. To reduce the long acquisition time required for spatial encoding, the echo-planar spectroscopic imaging (EPSI) technique has been combined with correlated spectroscopy to give four-dimensional (4D) echo-planar correlated spectroscopic imaging (EP-COSI) as well as J-resolved spectroscopic imaging (EP-JRESI) and the multi-echo (ME) variants. Further acceleration can be achieved using non-uniform undersampling (NUS) and reconstruction using compressed sensing (CS). Earlier versions of 2D MRS, theory of 2D MRS, spectral apodization filters, newer developments and the potential role of multidimensional MRS in PCa detection and management will be reviewed here. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose: To investigate functional changes in prostate cancer patients with three pathologically proven different Gleason scores (GS) (3+3, 3+4, and 4+3) using magnetic resonance spectroscopic imaging (MRSI) and diffusion-weighted imaging (DWI). Materials and Methods: In this study MRSI and DWI data were acquired in 41 prostate cancer patients using a 1.5T MRI scanner with a body matrix combined with an endorectal coil. The metabolite ratios of (Cho+Cr)/Cit were calculated from the peak integrals of total choline (Cho), creatine (Cr), and citrate (Cit) in MRSI. Apparent diffusion coefficient (ADC) values were derived from DWI for three groups of Gleason scores. The sensitivity and specificity of MRSI and DWI in patients were calculated using receiver operating characteristic curve (ROC) analysis. Results: The mean and standard deviation of (Cho+Cr)/Cit ratios of GS 3+3, GS 3+4, and GS 4+3 were: 0.44 ± 0.02, 0.56 ± 0.06, and 0.88 ± 0.11, respectively. For the DWI, the mean and standard deviation of ADC values in GS 3+3, GS 3+4, and GS 4+3 were: 1.13 ± 0.11, 0.97 ± 0.10, and 0.83 ± 0.08 mm2/sec, respectively. Statistical significances were observed between the GS and metabolite ratio as well as ADC values and GS. Conclusion: Combined MRSI and DWI helps identify the presence and the proportion of aggressive cancer (ie, Gleason grade 4) that might not be apparent on biopsy sampling. This information can guide subsequent rebiopsy management, especially for active surveillance programs. J. Magn. Reson. Imaging 2012;36:697-703. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion syndrome in humans, characterized by cardiovascular defects such as interrupted aortic arch, outflow tract defects, thymus and parathyroid hypo- or aplasia, and cleft palate. Heterozygosity of Tbx1, the mouse homolog of the candidate TBX1 gene, results in mild defects dependent on genetic background, whereas complete inactivation results in severe malformations in multiple tissues. Results: The loss of function of two Sprouty genes, which encode feedback antagonists of receptor tyrosine kinase (RTK) signaling, phenocopy many defects associated with 22q11DS in the mouse. The stepwise reduction of Sprouty gene dosage resulted in different phenotypes emerging at specific steps, suggesting that the threshold up to which a given developmental process can tolerate increased RTK signaling is different. Tbx1 heterozygosity significantly exacerbated the severity of all these defects, which correlated with a substantial increase in RTK signaling. Conclusions: Our findings suggest that TBX1 functions as an essential component of a mechanism that protects the embryo against perturbations in RTK signaling that may lead to developmental defects characteristic of 22q11DS. We propose that genetic factors that enhance RTK signaling ought to be considered as potential genetic modifiers of this syndrome. Developmental Dynamics 241:1310-1324, 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

An alternative to the standard echo-planar spectroscopic imaging technique is presented, spectroscopic imaging using concentrically circular echo-planar trajectories (SI-CONCEPT). In contrast to the conventional chemical shift imaging data, the sampled data from each set of concentric rings were regridded into Cartesian space. Usage of concentric k-space trajectories has the advantage of requiring significantly reduced slew rates than echo-planar spectroscopic imaging, allowing for the collection of higher spectral bandwidths and opening the door for high-bandwidth echo-planar styled spectroscopic imaging at higher magnetic fields. Before two-dimensional spatial and one-dimensional spectral encoding, the volume of interest was localized using the standard point-resolved spectroscopy sequence. The feasibility of using concentric k-space trajectories is demonstrated, and the spatial profiles and representative spectra are compared with the standard echo-planar spectroscopic imaging technique in a gray matter phantom containing metabolites at physiological concentrations and healthy human brain in vivo. The symmetric nature of the concentric circles also reduces the number of required excitations for a given resolution by a factor of two. Possible artifacts and limitations are discussed. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The application of compressed sensing is demonstrated in a recently implemented four-dimensional echo-planar based J-resolved spectroscopic imaging sequence combining two spatial and two spectral dimensions. The echo-planar readout simultaneously acquires one spectral and one spatial dimension. Therefore, the compressed sensing undersampling is performed along the indirectly acquired spatial and spectral dimensions, and the reconstruction is performed using the split Bregman algorithm, an efficient TV-minimization solver. The four-dimensional echo-planar-based J-resolved spectroscopic imaging data acquired in a prostate phantom containing metabolites at physiological concentrations are accurately reconstructed with as little as 20% of the original data. Experimental data acquired in six healthy prostates using the external body matrix 'receive' coil on a 3T magnetic resonance imaging scanner are reconstructed with acquisitions using only 25% of the Nyquist-Shannon required amount of data, indicating the potential for a 4-fold acceleration factor in vivo, bringing the required scan time for multidimensional magnetic resonance spectroscopic imaging within clinical feasibility. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose: [ABSTRACT FROM AUTHOR]

Exploiting the speed benefits of echo-planar imaging (EPI), the echo-planar spectroscopic imaging (EPSI) sequence facilitates recording of one spectral and two to three spatial dimensions faster than the conventional magnetic resonance spectroscopic imaging (MRSI). A novel four dimensional (4D) echo-planar correlated spectroscopic imaging (EP-COSI) was implemented on a whole body 3 T MRI scanner combining two spectral with two spatial encodings. Similar to EPSI, the EP-COSI sequence used a bipolar spatial read-out train facilitating simultaneous spatial and spectral encoding, and the conventional phase and spectral encodings for the other spatial and indirect spectral dimensions, respectively. Multiple 2D correlated spectroscopy (COSY) spectra were recorded over the spatially resolved volume of interest (VOI) localized by a train of three slice-selective radiofrequency (RF) pulses (90°-180°-90°). After the initial optimization using phantom solutions, the EP-COSI data were recorded from the lower leg of eight healthy volunteers including one endurance trained volunteer. Pilot results showed acceptable spatial and spectral quality achievable using the EP-COSI sequence. There was a detectable separation of cross peaks arising from the skeletal muscle intramyocellular lipids (IMCLs) and extramyocellular lipids (EMCLs) saturated and unsaturated pools. Residual dipolar interaction between the N-methylene and N-methyl protons of creatine/phosphocreatine (Cr/PCr) was also observed in the tibialis anterior region. Magn Reson Med, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Background: Minimal hepatic encephalopathy (MHE) has recently been reported in patients with extrahepatic portal venous obstruction (EHPVO). Aims: To evaluate brain changes by magnetic resonance studies in EHPVO patients. Methods: Blood ammonia level, critical flicker frequency (CFF), brain metabolites on 1H-magnetic resonance (MR) spectroscopy and brain water content on diffusion tensor imaging and magnetization transfer ratio (MTR) were studied in 31 EHPVO patients with and without MHE, as determined by neuropsychological tests. CFF and magnetic resonance imaging studies were also performed in 23 controls. Results: Fourteen patients (14/31, 45%) had MHE. Blood ammonia level was elevated in all, being significantly higher in the MHE than no MHE group. CFF was abnormal in 13% (4/31) with EHPVO and in 21% (3/14) with MHE. On 1H-MR spectroscopy, increased Glx/Cr, decreased mIns/Cr, and no change in Cho/Cr were noted in patients with MHE compared with controls. Significantly increased mean diffusivity (MD) and decreased (MTR) were observed in the MHE group, suggesting presence of interstitial cerebral oedema (ICE). MD correlated positively with blood ammonia level ( r=0.65, P=0.003) and Glx ( r=0.60, P=0.003). Discussion: MHE was detected in 45% of patients with EHPVO while CFF was abnormal in only 13%. ICE was present in 7/10 brain regions examined, particularly in those with MHE. Hyperammonaemia elevated cerebral Glx levels correlated well with ICE. Conclusions: MHE was common in EHPVO; CFF could identify it only in a minority. ICE was present in EHPVO, particularly in those with MHE. It correlated with blood ammonia and Glx/Cr levels. Hyperammonaemia seems to contribute to ICE in EHPVO. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate regional cerebral metabolic and structural changes in patients with minimal hepatic encephalopathy (MHE) using two-dimensional (2D) MR spectroscopy (MRS) and T [ABSTRACT FROM AUTHOR]

To determine the metabolite ratios of (Cho + Cr)/Cit and (Cho + Cr)/Spm in patients with two ranges of pathological Gleason scores, namely (3 + 4) and (4 + 3). By using the localized two-dimensional (2D) J-resolved spectroscopy (JPRESS) technique, the metabolites ratios can be calculated and correlated with prostate cancer aggressiveness. A total of 24 patients who underwent endorectal 2D JPRESS between April 2006 and July 2007 were included in this study. The 2D JPRESS voxel was localized predominantly in the peripheral zone suspected for malignancy based on pathology. Using the metabolites such as total choline (Cho), creatine (Cr), spermine (Spm) and citrate (Cit), the ratios (Cho + Cr)/Cit and (Cho + Cr)/Spm were calculated. In 14 prostate cancer patients who had a final pathologic Gleason scores of i) (3 + 4 = 7, n = 7) and ii) (4 + 3 = 7, n = 7), the metabolite ratios (mean ± SD) of (Cho + Cr)/Cit and (Cho + Cr)/Spm were calculated using the 2D JPRESS spectra as follows: i) (1.48 ± 0.83) and (1.59 ± 0.73); ii) (2.90 ± 0.94) and (2.71 ± 1.47), respectively. Higher percentage of aggressive disease correlates with higher metabolites ratio. Our pilot study suggests that 2D JPRESS can be reliably evaluated in a clinical setting using an endorectal coil. In addition to the citrate ratio, the spermine ratio also correlates with pathology based Gleason score. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate T2-relaxation changes in patients with minimal hepatic encephalopathy (MHE) using T2 relaxometry and to correlate T2 values with brain metabolites evaluated using 2D magnetic resonance spectroscopy (MRS). Materials and Methods: Eight MHE patients and 13 healthy subjects were evaluated using T2 relaxometry, and eight patients and nine healthy subjects underwent 2D MRS in right frontal and left occipital regions. Whole-brain T2-relaxation maps were compared between MHE and control subjects using analysis-of-covariance, with age and gender included as covariates. T2 values derived from the right frontal and left occipital lobes were correlated with the metabolite ratios. Results: Multiple brain regions including anterior and mid cingulate cortices, right anterior and left posterior insular cortices, right prefrontal, medial frontal, and right superior temporal cortices showed significantly increased T2 values in MHE patients compared to control subjects. MRS showed significantly increased ratios of glutamine/glutamate (Glx) and decreased ratios of myo-inositol, taurine, choline, and myo-inositol/choline (mICh) with respect to creatine (Cr_d) in patients compared to controls. Frontal Glx/Cr_d showed significantly positive correlation with T2 values. Conclusion: MHE patients showed significantly increased T2 values in multiple brain regions reflecting increased free water content and T2 values in frontal lobe correlated with the increased Glx/Cr_d ratio. J. Magn. Reson. Imaging 2009;30:1034-1041. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The cerebellum is derived from the anterior-most segment of the embryonic hindbrain, rhombomere 1 (r1). Previous studies have shown that the early development and patterning of r1 requires fibroblast growth factor (FGF) signaling. However, many of the developmental processes that shape cerebellar morphogenesis take place later in embryonic development and during the first 2 weeks of postnatal life in the mouse. Here, we present a more comprehensive analysis of the expression patterns of genes encoding FGF receptors and secreted FGF ligands during these later stages of cerebellar development. We show that these genes are expressed in multiple cell types in the developing cerebellum, in an astonishing array of distinct patterns. These data suggest that FGF signaling functions throughout cerebellar development to regulate many processes that shape the formation of a functional cerebellum. Developmental Dynamics, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Proton (1H) MRS enables non-invasive biochemical assay with the potential to characterize malignant, benign and healthy breast tissues. In vitro studies using perchloric acid extracts and ex vivo magic angle spinning spectroscopy of intact biopsy tissues have been used to identify detectable metabolic alterations in breast cancer. The challenges of 1H MRS in vivo include low sensitivity and significant overlap of resonances due to limited chemical shift dispersion and significant inhomogeneous broadening at most clinical magnetic field strengths. Improvement in spectral resolution can be achieved in vivo and in vitro by recording the MR spectra spread over more than one dimension, thus facilitating unambiguous assignment of metabolite and lipid resonances in breast cancer. This article reviews the recent progress with two-dimensional MRS of breast cancer in vitro, ex vivo and in vivo. The discussion includes unambiguous detection of saturated and unsaturated fatty acids, as well as choline-containing groups such as free choline, phosphocholine, glycerophosphocholine and ethanolamines using two-dimensional MRS. In addition, characterization of invasive ductal carcinomas and healthy fatty/glandular breast tissues non-invasively using the classification and regression tree (CART) analysis of two-dimensional MRS data is reviewed. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background and Aims: Acute-on-chronic liver failure (ACLF), acute liver failure (ALF) and chronic liver disease (CLD) are common forms of liver failure and present with similar clinical profiles. The aim of this study was to compare brain metabolite alterations in all the three groups of patients with controls, using in vivo proton magnetic resonance spectroscopy (MRS), and to look for any significant differences in metabolites that may help in differentiating between these three conditions. Methods: Nine patients with ACLF, 10 with ALF, 10 patients with CLD and 10 age-matched controls were studied. The relative concentrations of N-acetylaspartate (NAA), choline (Cho), glutamine/glutamate (Glx) and myoinositol (mI) with respect to creatine (Cr) were measured. Results: ACLF (3.07±0.72), ALF (4.39±1.25) and CLD (3.15±0.69) patients exhibited significantly increased Glx/Cr ratios compared with controls (2.14±0.42). The NAA/Cr ratio was significantly decreased in both ACLF (mean=0.84±0.28) and CLD (mean=0.97±0.21) patients as compared with that in controls (mean=1.24±0.20). No significant difference among ALF, ACLF and CLD patients was noted in the Cho/Cr ratios. ACLF patients showed significantly lower mI/Cr and Glx/Cr ratios compared with the ALF group. Conclusion: In vivo proton MRS-derived cerebral metabolite alterations in hepatic encephalopathy owing to ALF are significantly different from the one owing to ACLF and CLD; these may be due to the differences in the pathogenesis of these two overlapping clinical conditions. [ABSTRACT FROM AUTHOR]

Background and Aim: Cerebral edema is a major complication in patients with fulminant hepatic failure (FHF). The aim of this study was to evaluate the metabolite alterations and cerebral edema in patients with FHF using in vivo proton magnetic resonance spectroscopy (MRS) and diffusion tensor imaging, and to look for its reversibility in survivors. Methods: Ten FHF patients along with 10 controls were studied. Five of the 10 patients who recovered had a repeat imaging after three weeks. N-acetylaspartate, choline (Cho), glutamine (Gln), glutamine/glutamate (Glx), and myoinositol ratios were calculated with respect to creatine (Cr). Mean diffusivity (MD) and fractional anisotropy (FA) were calculated in different brain regions. Results: Patients exhibited significantly increased Gln/Cr and Glx/Cr, and reduced Cho/Cr ratios, compared to controls. In the follow-up study, all metabolite ratios were normalized except Glx/Cr. Significantly decreased Cho/Cr were observed in deceased patients compared to controls. In patients, significantly decreased MD and FA values were observed in most topographical locations of the brain compared to controls. MD and FA values showed insignificant increase in the follow-up study compared to their first study. Conclusions: We conclude that the Cho/Cr ratio appears to be an in vivo marker of prognosis in FHF. Decreased MD values suggest predominant cytotoxic edema may be present. Persistence of imaging and MRS abnormalities at three weeks' clinical recovery suggests that metabolic recovery may take longer than clinical recovery in FHF patients. [ABSTRACT FROM AUTHOR]

Purpose To quantify the changes in brain water diffusivity in hepatic encephalopathy (HE) associated with cirrhosis using diffusion tensor imaging (DTI) and to correlate with neuropsychological (NP) scores. Materials and Methods DTI was performed in 14 patients with low-grade HE and age/gender-comparable 16 healthy controls. Whole brain mean diffusivity (MD) and fractional anisotropy (FA) maps were calculated, normalized to common space, smoothed, and compared voxel-by-voxel between groups using analysis of covariance with age included as a covariate. The average MD and FA values were also calculated from individual subjects for selected brain regions and correlated with the neuropsychological scores. Results Patients with HE showed increased MD in the cortical gray and white matter and the internal capsule. Less extensive brain regions with decreased FA were observed in the bilateral frontal and occipital white matter. MD values from the corpus callosum correlated inversely with several NP scores among HE patients and controls. Positive correlations were observed with FA values and cognitive scores. Conclusion Voxel-based DTI analysis showed widespread brain regions with increased MD values, indicating enhanced water content and decreased FA in cirrhotic patients with HE. The MD and FA values from selected regions correlated with the NP scores. J. Magn. Reson. Imaging 2008;27:1061-1068. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Purpose To measure cerebral metabolites in brains of human immunodeficiency virus (HIV)-infected patients using two-dimensional (2D) proton (1H) magnetic resonance spectroscopy (MRS), which enables more sensitive detection of metabolites at lower concentrations and delineation of the components of the different choline (Ch) groups in the frequency domain when compared to one dimensional (1D) 1H-MRS. Materials and Methods We examined metabolite/creatine (Cr) and metabolite/Ch ratios in the left frontal brain of 10 HIV-infected (mean age 13.7 ± 4.7 years) and 11 control (mean age 15.3 ± 4.6 years) adolescents and children using 2D localized chemical shift correlated spectroscopy (L-COSY). The integrated volume under each 2D metabolite peak was calculated with reference to the diagonal creatine methyl peak (Cr_d) or the diagonal choline trimethylamine peak (Ch_d). Results In the HIV-infected patients, myoinositol (mI)/Cr_d (P = 0.009) and mI/Ch_d (P = 0.006) were elevated. The ratios of the following metabolites were also significantly elevated (P < 0.05): mI-Ch/Cr_d, γ-aminobutyrate (GABA)/ Cr_d, GABA/Ch_d, threonine-lactate (Thr-Lac)/Cr_d, Thr-Lac/Ch_d, and N-acetyl aspartate (NAA)/Cr_d. Conclusion We have demonstrated for the first time the feasibility of 2D-MRS in HIV-infected children and adolescents to assess cerebral metabolites and found elevated mI and elevated GABA, in the left frontal brain of clinically stable HIV-infected patients. A larger study population is needed to confirm these pilot GABA findings. J. Magn. Reson. Imaging 2008;27:710-717. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Purpose: To implement and evaluate a novel single-volume two-dimensional localized constant-time-based correlated spectroscopy (2D LCT-COSY) sequence on a clinical 3T MR scanner. This sequence exhibits homonuclear decoupling along the F1 dimension, leading to improved spectral resolution compared to that of non-constant-time localized correlated spectroscopy (L-COSY).Materials and Methods: A GE 3T MR scanner equipped with a quadrature transmit and receive extremity coil was used in this study. The 2D LCT-COSY sequence was programmed using General Electric's EPIC compiler. Simulations for a two-spin 1/2 system were performed using GAMMA libraries to evaluate the theoretical performance of the sequences, and were also compared with corresponding phantom experiments using trans-cinnamic acid. Finally, spectra were acquired from the soleus muscle of healthy volunteers in order to evaluate performance in vivo.Results: Simulations and experimental results confirmed the improved spectral resolution of LCT-COSY over L-COSY, as well as its homonuclear decoupling performance. The behavior of resonance amplitudes as a function of evolution time in the experiment also was appropriately reflected by the simulation. Corresponding results were obtained for the in vivo muscle spectra, in which separation of overlapping olefinic and allylic methylene protons from the intra- and extramyocellular lipids (IMCL and EMCL, respectively) was achieved.Conclusion: Simulations and experimental results in vitro and in vivo demonstrate the strengths of LCT-COSY. This technique can be implemented on systems of any field strength, and has the potential to separate overlapping metabolites in tissue when employed on high-field clinical MRI scanners equipped for proton spectroscopy. [ABSTRACT FROM AUTHOR]

Purpose To compare point-resolved spectroscopy (PRESS) and localized two-dimensional (2D) correlated spectroscopy (L-COSY) in the detection of cerebral metabolites in humans on a clinical scanner at 3T and to estimate their respective inter- and intrasubject variances. Materials and Methods Measurements were made on nine healthy subjects to assess intersubject variance, and daily on a single subject over a period of seven days to assess intrasubject variance. All L-COSY measurements were performed with a voxel size of 27 mL (3 × 3 × 3 cm3) and a measurement time of ∼34 minutes in the occipitoparietal lobe of the brain. Relative metabolite concentrations were estimated with respect to N-methyl creatine. Results While the sensitivity of PRESS is twice that of L-COSY, the greater spectral resolution offered by L-COSY resulted in greater consistency in estimates of the concentrations of several cerebral metabolites, as indicated by a superior intraclass correlation and a significantly lower standard deviation (SD) in a matched pair intrasubject analysis. Conclusion Our pilot results demonstrate that L-COSY is an effective approach for resolving cerebral metabolites, and demonstrates a lower coefficient of variance (CV) than the conventional 1D localized spectroscopic approach using LC Model for quantification. J. Magn. Reson. Imaging 2007;26:405-409. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

In a randomized two-group parallel trial the mean causal effect is typically estimated as the difference in means or proportions for patients receiving, say, either treatment (T) or control (C). Treatment effect heterogeneity (TEH), or unit-treatment interaction, the variability of the causal effect (defined in terms of potential outcomes) across individuals, is often ignored. Since only one of the outcomes, either YT or YC, is observed for each unit in such studies, the TEH is not directly estimable. For convenience, it is often assumed to be minimal or zero. We are particularly interested in the ‘treatment risk’ for binary outcomes, that is, the proportion of individuals who would succeed on C but fail on T. Previous work has shown that the treatment risk can be bounded (Albert, Gadbury and Mascha, 2005), and that the confidence interval width around it can be narrowed using clustered or correlated data (Mascha and Albert, 2006). Without further parameter constraints, treatment risk is unidentifiable. We show, however, that the treatment risk can be directly estimated when the four underlying population counts comprising the joint distribution of the potential outcomes, YT and YC, follow constraints consistent with the Dirichlet multinomial. We propose a test of zero treatment risk and show it to have good size and power. Methods are applied to both a randomized as well as a non-randomized study. Implications for medical decision-making at the policy and individual levels are discussed. (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

Purpose To demonstrate the feasibility of estimating the relative intra- and extramyocellular lipid (IMCL and EMCL) pool magnitudes and calculating the degree of lipid unsaturation within soleus muscle using single-voxel localized one- and two-dimensional (1D and 2D) MR spectroscopy (MRS). Materials and Methods Localized 1D point resolved spectroscopy (PRESS) and 2D correlation spectroscopy (L-COSY) were performed in identical locations in the soleus muscle of 10 healthy subjects. A GE 3-T MRI/MRS scanner and a quadrature extremity transmit/receive coil was used. Results The 1D and 2D MR spectra were used to compute IMCL/creatine (Cr) and EMCL/Cr ratios. In addition to cross peaks between the methyl and methylene protons in the high-field region, the 2D spectra showed cross peaks due to J-coupling between allylic, diallylic methylene pro- tons, and olefinic protons. The cross-peak volume ratios also provided a measure of double bonds, suggesting that this ratio can be used to assess unsaturation within IMCL and EMCL lipid pools. Conclusion We have demonstrated the feasibility of detecting 2D cross peaks between different groups of IMCL and EMCL, including the unsaturated protons within these two lipids pools. This protocol may be easily extended to study the lipids present in other tissues. J. Magn. Reson. Imaging 2007. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Purpose To evaluate a localized two-dimensional correlated magnetic resonance spectroscopic (L-COSY) technique in patients with hepatic encephalopathy (HE) and healthy subjects, and to correlate the cerebral metabolite changes with neuropsychological (NP) test scores. Materials and Methods Eighteen minimal hepatic encephalopathy (MHE) patients and 21 healthy controls have been investigated. A GE 1.5-T magnetic resonance (MR) scanner was used in combination with a body MR coil for transmission and a 3-inch surface coil for reception. A 27-mL voxel was localized by three slice-selective radio frequency (RF) pulses (90°-180°-90°) in the anterior cingulate region. The total duration of each two-dimensional L-COSY spectrum was approximately 25 minutes. The NP battery included a total of 15 tests, which were grouped into six domains. Results MR spectroscopic results showed a statistically significant decrease in myo-inositol (mI) and choline (Ch) and an increase in glutamate/glutamine (Glx) in patients when compared to healthy controls. There was also an increase in taurine (Tau) in patients. The NP results indicated a significant correlation between motor function assessed by NP tests and mI ratios recorded using two-dimensional L-COSY. Conclusion The study demonstrated the feasibility of evaluating the two-dimensional L-COSY sequence in a clinical environment. The results showed additional cerebral metabolites that can be measured with the technique in comparison to one-dimensional study. J. Magn. Reson. Imaging 2005;21:398-405. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

A localized two-dimensional (2D) 1H MR chemical exchange spectroscopic (L-EXSY) sequence has been implemented on a whole-body 1.5-T MRI/MRS scanner. The second spectroscopic encoding to monitor the chemical exchange was an integral part of the single-volume localization using three slice-selective 90° radiofrequency (RF) pulses, thereby eliminating the need for any additional RF pulses, off-resonance/continuous wave saturation, or selective inversion, which are essential in the one-dimensional 1H MR exchange spectroscopy. Even though the TM-crusher dephased single- and higher-order multiple-quantum coherences, the zero-quantum coherences were indistinguishable from the longitudinal magnetization leading to J-coupled 2D cross peaks similar to COSY. With TM of 300 ms, two different exchange cross peaks were recorded in human calf muscle: a first peak, between the mobile tissue water and total creatine pools, and a second peak, possibly between the olefinic and magnetically equivalent poly methylene protons of unsaturated lipids. Our preliminary results demonstrate that the intermolecular and intramolecular chemical exchange mechanisms can be monitored noninvasively in human calf muscle using 2D L-EXSY. Magn Reson Med 53:495-502, 2005. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Purpose To evaluate a two-dimensional localized chemical shift correlated spectroscopy (L-COSY) sequence in elderly patients with major depression. Materials and Methods A total of 33 healthy elderly subjects and 15 elderly patients with major depression were investigated. A voxel size of 3 × 3 × 3 cm3 was chosen in the dorsolateral prefrontal region with predominantly white matter, with the use of three slice-selective radiofrequency (RF) pulses (90°, 180°, and 90°). A chemical shift-selective (CHESS) sequence was used prior to volume localization for the presaturation of water. The two-dimensional raw data matrix consisted of 1024 complex points along the detection period (t2), and 100 increments along the evolution period (t1), resulting in a total acquisition time of approximately 27 minutes per acquisition. The metabolite ratios were calculated using the two-dimensional peak volumes with respect to the diagonal peak volume of total creatine (Cr) at 3.0 ppm. Results In the 33 elderly subjects, the mean ratio of choline (Cho) to Cr was 10% higher in men compared to women ( P < 0.05), consistent with earlier findings obtained by one-dimensional MRS. When the metabolite ratios were compared in a subsample of 16 elderly female controls and 12 depressed female patients, the depressed geriatric patients had higher levels of myoinositol (mI), phosphoethanolamine (PE), and glutamate/glutamine (Glx) than the controls, although the differences were not statistically significant. Conclusion Our pilot study shows the feasibility of performing two-dimensional L-COSY successfully in elderly subjects and patients with late-life mood disorders. These findings are consistent with and expand on our earlier findings in major depressive disorder (MDD) detected with one-dimensional MRS. J. Magn. Reson. Imaging 2004;20:1039-1045. © 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]