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Reducing the echo time of magnetic resonance spectroscopy experiments is appealing because it increases the available signal and reduces J-evolution of coupled metabolites. In this manuscript a novel sequence, referred to as Ultrashort echo TimE, SPin ECho, full Intensity Acquired Localized (UTE-SPECIAL), is described which is able to achieve ultrashort echo times (4 ms) on a standard clinical 3 T MR system while recovering the entirety of the available magnetization. UTE-SPECIAL obtains full 3D spatial localization through a 2D adiabatic inversion pulse which is cycled "on" and "off" every other repetition, in combination with a slice-selective excitation pulse. In addition to an ultrashort echo time, UTE-SPECIAL has negligible chemical shift displacement artefact and, because it uses no slice-selective refocusing pulse, has no signal cancellation at the borders for J-coupled metabolites. Spectra with an ultrashort echo time of 4 ms are demonstrated in vivo at 3 T, as well as J-resolved spectra obtained in a phantom and a healthy volunteer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The first use of a surface coil to obtain a 31 P NMR spectrum from an intact rat by Ackerman and colleagues initiated a revolution in magnetic resonance imaging (MRI) and spectroscopy (MRS). Today, we take it for granted that one can detect signals in regions external to an RF coil; at the time, however, this concept was most unusual. In the approximately four decade long period since its introduction, this simple idea gave birth to an increasing number of innovations that has led to transformative changes in the way we collect data in an in vivo magnetic resonance experiment, particularly with MRI of humans. These innovations include spatial localization and/or encoding based on the non-uniform B 1 field generated by the surface coil, leading to new spectroscopic localization methods, image acceleration, and unique RF pulses that deal with B 1 inhomogeneities and even reduce power deposition. Without the surface coil, many of the major technological advances that define the extraordinary success of MRI in clinical diagnosis and in biomedical research, as exemplified by projects like the Human Connectome Project, would not have been possible., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To estimate the accuracy of predicting response to neoadjuvant chemotherapy (NACT) in patients with locally advanced breast cancer using MR spectroscopy (MRS) measurements made very early in treatment., Materials and Methods: This prospective Health Insurance Portability and Accountability Act (HIPAA)-compliant protocol was approved by the American College of Radiology and local-site institutional review boards. One hundred nineteen women with invasive breast cancer of ≥3 cm undergoing NACT were enrolled between September 2007 and April 2010. MRS measurements of the concentration of choline-containing compounds ([tCho]) were performed before the first chemotherapy regimen (time point 1, TP1) and 20-96 h after the first cycle of treatment (TP2). The change in [tCho] was assessed for its ability to predict pathologic complete response (pCR) and radiologic response using the area under the receiver operating characteristic curve (AUC) and logistic regression models., Results: Of the 119 subjects enrolled, only 29 cases (24%) with eight pCRs provided usable data for the primary analysis. Technical challenges in acquiring quantitative MRS data in a multi-site trial setting limited the capture of usable data. In this limited data set, the decrease in tCho from TP1 to TP2 had poor ability to predict either pCR (AUC = 0.53, 95% confidence interval [CI]: 0.27-0.79) or radiologic response (AUC = 0.51, 95% CI: 0.27-0.75)., Conclusion: The technical difficulty of acquiring quantitative MRS data in a multi-site clinical trial setting led to a low yield of analyzable data, which was insufficient to accurately measure the ability of early MRS measurements to predict response to NACT., Level of Evidence: 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:290-302., (© 2016 International Society for Magnetic Resonance in Medicine.)

Transplantation of macroencapsulated tissue-engineered grafts (TEGs) is being investigated as a treatment for type 1 diabetes, but there is a critical need to measure TEG viability both in vitro and in vivo. Oxygen deficiency is the most critical issue preventing widespread implementation of TEG transplantation and delivery of supplemental oxygen (DSO) has been shown to enhance TEG survival and function in vivo. In this study, we demonstrate the first use of oxygen-17 magnetic resonance spectroscopy ( 17 O-MRS) to measure the oxygen consumption rate (OCR) of TEGs and show that in addition to providing therapeutic benefits to TEGs, DSO with 17 O 2 can also enable measurements of TEG viability. Macroencapsulated TEGs containing βTC3 murine insulinoma cells were prepared with three fractional viabilities and provided with 17 O 2 . Cellular metabolism of 17 O 2 into nascent mitochondrial water (H 2 17 O) was monitored by 17 O-MRS and, from the measured data, OCR was calculated. For comparison, OCR was simultaneously measured on a separate, but equivalent sample of cells with a well-established stirred microchamber technique. OCR measured by 17 O-MRS agreed well with measurements made in the stirred microchamber device. These studies confirm that 17 O-MRS can quantify TEG viability noninvasively. Biotechnol. Bioeng. 2017;114: 1118-1121. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Techniques to monitor the oxygen partial pressure (pO 2 ) within implanted tissue-engineered grafts (TEGs) are critically necessary for TEG development, but current methods are invasive and inaccurate. In this study, we developed an accurate and noninvasive technique to monitor TEG pO 2 utilizing proton ( 1 H) or fluorine ( 19 F) magnetic resonance spectroscopy (MRS) relaxometry. The value of the spin-lattice relaxation rate constant (R 1 ) of some biocompatible compounds is sensitive to dissolved oxygen (and temperature), while insensitive to other external factors. Through this physical mechanism, MRS can measure the pO 2 of implanted TEGs. We evaluated six potential MRS pO 2 probes and measured their oxygen and temperature sensitivities and their intrinsic R 1 values at 16.4 T. Acellular TEGs were constructed by emulsifying porcine plasma with perfluoro-15-crown-5-ether, injecting the emulsion into a macroencapsulation device, and cross-linking the plasma with a thrombin solution. A multiparametric calibration equation containing R 1 , pO 2 , and temperature was empirically generated from MRS data and validated with fiber optic (FO) probes in vitro. TEGs were then implanted in a dorsal subcutaneous pocket in a murine model and evaluated with MRS up to 29 days postimplantation. R 1 measurements from the TEGs were converted to pO 2 values using the established calibration equation and these in vivo pO 2 measurements were simultaneously validated with FO probes. Additionally, MRS was used to detect increased pO 2 within implanted TEGs that received supplemental oxygen delivery. Finally, based on a comparison of our MRS data with previously reported data, ultra-high-field (16.4 T) is shown to have an advantage for measuring hypoxia with 19 F MRS. Results from this study show MRS relaxometry to be a precise, accurate, and noninvasive technique to monitor TEG pO 2 in vitro and in vivo., Competing Interests: Statement No competing financial interests exist.

Purpose: Iron-oxide nanoparticles (IONPs) have proven utility as contrast agents in many MRI applications. Previous quantitative IONP mapping has been performed using mainly T2 * mapping methods. However, in applications requiring high IONP concentrations, such as magnetic nanoparticles based thermal therapies, conventional pulse sequences are unable to map T2 * because the signal decays too rapidly. In this article, sweep imaging with Fourier transformation (SWIFT) sequence is combined with the Look-Locker method to map T1 of IONPs in high concentrations., Methods: T1 values of agar containing IONPs in different concentrations were measured with the SWIFT Look-Locker method and with inversion recovery spectroscopy. Precisions of Look-Locker and variable flip angle (VFA) methods were compared in simulations., Results: The measured R1 (=1/T1 ) has a linear relationship with IONP concentration up to 53.6 mM of Fe. This concentration exceeds concentrations measured in previous work by almost an order of magnitude. Simulations show SWIFT Look-Locker method is also much less sensitive to B1 inhomogeneity than the VFA method., Conclusion: SWIFT Look-Locker can accurately measure T1 of IONP concentrations ≤53.6 mM. By mapping T1 as a function of IONP concentration, IONP distribution maps might be used in the future to plan effective magnetic nanoparticle hyperthermia therapy., (Copyright © 2014 Wiley Periodicals, Inc.)

Despite the enormous public health impact of Alzheimer's disease (AD), no disease-modifying treatment has yet been proven to be efficacious in humans. A rate-limiting step in the discovery of potential therapies for humans is the absence of efficient non-invasive methods of evaluating drugs in animal models of disease. Magnetic resonance spectroscopy (MRS) provides a non-invasive way to evaluate the animals at baseline, at the end of treatment, and serially to better understand treatment effects. In this study, MRS was assessed as potential outcome measure for detecting disease modification in a transgenic mouse model of AD. Passive immunization with two different antibodies, which have been previously shown to reduce plaque accumulation in transgenic AD mice, was used as intervention. Treatment effects were detected by MRS, and the most striking finding was attenuation of myo-inositol (mIns) increases in APP-PS1 mice with both treatments. Additionally, a dose-dependent effect was observed with one of the treatments for mIns. MRS appears to be a valid in vivo measure of anti-Aβ therapeutic efficacy in pre-clinical studies. Because it is noninvasive, and can detect treatment effects, use of MRS-based endpoints could substantially accelerate drug discovery., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)

Purpose: T1 quantification of contrast agents, such as super-paramagnetic iron oxide nanoparticles, is a challenging but important task inherent to many in vivo applications in magnetic resonance imaging. In this work, a sweep imaging with Fourier transformation using variable flip angles (VFAs-SWIFT) method was proposed to measure T1 of aqueous super-paramagnetic iron oxide nanoparticle suspensions., Methods: T1 values of various iron concentrations (from 1 to 7 mM) were measured using VFA-SWIFT and three-dimensional spoiled gradient-recalled echo with VFAs (VFA-SPGR) sequences on a 7 T MR scanner. For validation, T1 values were also measured using a spectroscopic inversion-recovery sequence on a 7 T spectrometer., Results: VFA-SWIFT demonstrated its advantage for quantifying T1 of highly concentrated aqueous super-paramagnetic iron oxide nanoparticle suspensions, but VFA-SPGR failed at the higher end of iron concentrations. Both VFA-SWIFT and VFA-SPGR yielded linear relationships between the relaxation rate and iron concentrations, with relaxivities of 1.006 and 1.051 s(-1) mM(-1) at 7 T, respectively, in excellent agreement with the spectroscopic measurement of 1.019 s(-1) mM(-1) ., Conclusion: VFA-SWIFT is able to achieve accurate T1 quantification of aqueous super-paramagnetic iron oxide nanoparticle suspensions up to 7 mM., (© 2013 Wiley Periodicals, Inc.)

Muscle (1)H magnetic resonance spectroscopy noninvasively measures intramyocellular lipid levels, which correlate with obesity, insulin resistance, and type 2 diabetes. The appearance of muscle magnetic resonance spectra is influenced by bulk magnetic susceptibility and residual dipolar couplings which depend on the angle between the muscle fibers and the main magnetic field. This study used a 4 T magnet to examine the influence of foot orientation on the appearance and quantification of muscle magnetic resonance spectra from the soleus and the vastus lateralis. For each individual, intramyocellular lipid, extramyocellular lipid, and creatine concentrations were quantified in the soleus and the vastus lateralis during one session. Foot orientation was found to influence the appearance of muscle spectra from the soleus but not from the vastus lateralis. It was concluded that quantifying intramyocellular lipid by the standard LCModel using a water reference may be more appropriate than using a creatine reference in the presence of residual dipolar couplings., (Copyright © 2012 Wiley Periodicals, Inc.)

This work describes our first efforts to implement SWIFT (SWeep Imaging with Fourier Transformation) in continuous mode for imaging and spectroscopy. We connected a standard quadrature hybrid with a quad coil and acquired NMR signal during continuous radiofrequency excitation. We utilized a chirped radiofrequency pulse to minimize the instantaneous radiofrequency field during excitation of the spin system for the target flip angle and bandwidth. Due to the complete absence of "dead time", continuous SWIFT has the potential to extend applications of MRI and spectroscopy in studies of spin systems having extremely fast relaxation or broad chemical shift distributions beyond the range of existing MRI sequences., (Copyright © 2012 Elsevier Inc. All rights reserved.)

At the high field strength of 7 T, in vivo spectra of the human brain with exceptional spectral quality sufficient to quantify 16 metabolites have been obtained previously only in the occipital lobe. However, neurochemical abnormalities associated with many brain disorders are expected to occur in brain structures other than the occipital lobe. The purpose of the present study was to obtain high-quality spectra from various brain regions at 7 T and to quantify the concentrations of different metabolites. To obtain concentrations of metabolites within four different regions of the brain, such as the occipital lobe, motor cortex, basal ganglia and cerebellum, the T(2) relaxation times of the singlets and J-coupled metabolites in these regions were measured for the first time at 7 T. Our results demonstrate that high-quality, quantifiable spectra can be obtained in regions other than the occipital lobe at 7 T utilizing a 16-channel transceiver coil and B(1)(+) shimming., (Copyright © 2011 John Wiley & Sons, Ltd.)

In this work, we investigated the frequency-offset dependence of the rotating frame longitudinal (R(1ρ)) and transverse (R(2ρ)) relaxation rate constants when using hyperbolic-secant adiabatic full passage pulses or continuous-wave spin-lock irradiation. Phantom and in vivo measurements were performed to validate theoretical predictions of the dominant relaxation mechanisms existing during adiabatic full passage pulses when using different settings of the frequency offset relative to the carrier. In addition, adiabatic R(1ρ) and R(2ρ) values of total creatine and N-acetylaspartate were measured in vivo from the human brain at 4 T. When the continuous-wave pulse power was limited to safe specific absorption rates for humans, simulations revealed a strong dependence of R(1ρ) and R(2ρ) values on the frequency offset for both dipolar interactions and anisochronous exchange mechanisms. By contrast, theoretical and experimental results showed adiabatic R(1ρ) and R(2ρ) values to be practically invariant within the large subregion of the bandwidth of the hyperbolic-secant pulse where complete inversion was achieved. However, adiabatic R(1ρ) and R(2ρ) values of the methyl protons of total creatine (at 3.03 ppm) were almost doubled when compared with those of the methyl protons of N-acetylaspartate (at 2.01 ppm) in spite of the fact that these resonances were in the flat region of the inversion band of the adiabatic full passage pulses. We conclude that differences in adiabatic R(1ρ) and R(2ρ) values of human brain metabolites are not a result of their chemical shifts, but instead reflect differences in dynamics., (Copyright © 2011 John Wiley & Sons, Ltd.)

We report initial results with single voxel spectroscopy (SVS) using diffusion weighting and localization by adiabatic selective refocusing (LASER) in breast tumors to measure the apparent diffusion coefficient of water (ADCw). This is a quick (30 s) and relatively easy method to implement compared with image-based diffusion measurements, and is insensitive to lipid signal contamination. The ADCw and concentration of total choline containing compounds [tCho] were evaluated for associations with each other and final pathologic diagnosis in 25 subjects. The average (+/- SD) ADCw in benign and malignant lesions was 1.96 +/- 0.47 mm(2)/s and 1.26 +/- 0.29 x 10(-3) mm(2)/s, respectively, P< 0.001. Receiver operating characteristic curve analysis showed an area under the curve of 0.92. Analysis of the single voxel (SV) ADCw and [tCho] showed significant correlation with a R(2) of 0.56, P< 0.001. Compared with more commonly used image-based methods of measuring water ADC, SV-ADCw is faster, more robust, insensitive to fat, and potentially easier to implement on standard clinical systems., ((c) 2009 Wiley-Liss, Inc.)

Purpose: This study was designed to test whether metabolic characterization of intact, unaltered human rectal adenocarcinoma specimens is possible using the high-resolution magic angle spinning proton (1H) magnetic resonance spectroscopy technique., Methods: The study included 23 specimens from five patients referred for ultrasonographic staging of suspected rectal cancer. Multiple biopsies of macroscopically malignant rectal tumors and benign rectal mucosa were obtained from each patient for a total of 14 malignant and 9 benign samples. Unaltered tissue samples were spectroscopically analyzed. Metabolic profiles were established from the spectroscopy data and correlated with histopathologic findings., Results: Metabolomic profiles represented by principle components of metabolites measured from spectra differentiated between malignant and benign samples and correlated with the volume percent of cancer (P = 0.0065 and P = 0.02, respectively) and benign epithelium (P = 0.0051 and P = 0.0255, respectively), and with volume percent of stroma, and inflammation., Conclusions: Magnetic resonance spectroscopy of rectal biopsies has the ability to metabolically characterize samples and differentiate between pathological features of interest. Future studies should determine its utility in in vivo applications for non-invasive pathologic evaluations of suspicious rectal lesions.

In vivo 1H MRS is rapidly developing as a clinical tool for diagnosing and characterizing breast cancers. Many in vivo and in vitro experiments have demonstrated that alterations in concentrations of choline-containing metabolites are associated with malignant transformation. In recent years, considerable efforts have been made to evaluate the role of 1H MRS measurements of total choline-containing compounds in the management of patients with breast cancer. Current technological developments, including the use of high-field MR scanners and quantitative spectroscopic analysis methods, promise to increase the sensitivity and accuracy of breast MRS. This article reviews the literature describing in vivo MRS in breast cancer, with an emphasis on the development of high-field MR scanning and quantitative methods. Potential applications of these technologies for diagnosing suspicious lesions and monitoring response to chemotherapy are discussed.

In NMR spectroscopy, volume selection can be advantageously achieved using adiabatic pi pulses, which enable high bandwidth and B(1) insensitivity. In order to avoid the generation of non-linear phase profiles and the subsequent signal loss caused by incoherent averaging, adiabatic pi pulses are usually used in pairs for volume selection in each spatial dimension. Alternatively, when performing spectroscopic imaging (SI), a high enough spatial resolution results in negligible phase dispersion within each pixel. This allows using only one pulse per selected spatial dimension, resulting in a reduced echo-time and reduced power deposition. In this work, the feasibility of such an approach is explored theoretically and numerically, allowing the derivation of explicit conditions to obtain SI images without artifact. Adequate spatial and spectral post-processing procedures are described to compensate for the effect of non-linear phase profiles. These developments are applied to SI in the rat brain at 9.4 T, using a new adiabatic sequence named Pseudo-LASER.

The problem of the relaxation of identical spins 1/2 induced by chemical exchange between spins with different chemical shifts in the presence of time-dependent RF irradiation (in the first rotating frame) is considered for the fast exchange regime. The solution for the time evolution under the chemical exchange Hamiltonian in the tilted doubly rotating frame (TDRF) is presented. Detailed derivation is specified to the case of a two-site chemical exchange system with complete randomization between jumps of the exchanging spins. The derived theory can be applied to describe the modulation of the chemical exchange relaxation rate constants when using a train of adiabatic pulses, such as the hyperbolic secant pulse. Theory presented is valid for quantification of the exchange-induced time-dependent rotating frame longitudinal T1rho,ex and transverse T2rho,ex relaxations in the fast chemical exchange regime.

The aim of this study was to compare the diffusion characteristic of lactate and alanine in a brain tumor model to that of normal brain metabolites known to be mainly intracellular such as N-acetylaspartate or creatine. The diffusion of (13)C-labeled metabolites was measured in vivo with localized NMR spectroscopy at 9.4 T (400 MHz) using a previously described localization and editing pulse sequence known as ACED-STEAM ('adiabatic carbon editing and decoupling'). (13)C-labeled glucose was administered and the apparent diffusion coefficients of the glycolytic products, {(1)H-(13)C}-lactate and {(1)H-(13)C}-alanine, were determined in rat intracerebral 9L glioma. To obtain insights into {(1)H-(13)C}-lactate compartmentation (intra- versus extracellular), the pulse sequence used very large diffusion weighting (50 ms/microm(2)). Multi-exponential diffusion attenuation of the lactate metabolite signals was observed. The persistence of a lactate signal at very large diffusion weighting provided direct experimental evidence of significant intracellular lactate concentration. To investigate the spatial distribution of lactate and other metabolites, (1)H spectroscopic images were also acquired. Lactate and choline-containing compounds were consistently elevated in tumor tissue, but not in necrotic regions and surrounding normal-appearing brain. Overall, these findings suggest that lactate is mainly associated with tumor tissue and that within the time-frame of these experiments at least some of the glycolytic product ([(13)C] lactate) originates from an intracellular compartment.

Purpose: To determine whether the addition of in vivo quantitative hydrogen 1 (1H) magnetic resonance (MR) spectroscopy can improve the radiologist's diagnostic accuracy in interpreting breast MR images to distinguish benign from malignant lesions., Materials and Methods: The study was approved by the institutional review board and, where appropriate, was compliant with the Health Insurance Portability and Accountability Act. All patients provided written informed consent. Fifty-five breast MR imaging cases-one lesion each in 55 patients aged 24-66 years with biopsy-confirmed findings-were retrospectively evaluated by four radiologists. Patients were examined with contrast material-enhanced fat-suppressed T1-weighted 4.0-T MR imaging. The concentration of total choline-containing compounds (tCho) was quantified by using single-voxel 1H MR spectroscopy. For each case, the radiologists were asked to give the percentage probability of malignancy, the Breast Imaging and Reporting Data System category, and a recommendation for patient treatment. Two interpretations were performed for each case: The initial interpretation was based on the lesion's morphologic features and time-signal intensity curve, and the second interpretation was based on the lesion's morphologic features, time-signal intensity curve, and tCho concentration. Receiver operating characteristic (ROC), Wilcoxon signed rank, kappa statistic, and accuracy (based on the area under the ROC curve) analyses were performed., Results: Of the 55 lesions evaluated, 35 were invasive carcinomas and 20 were benign. The addition of 1H MR spectroscopy resulted in higher sensitivity, specificity, accuracy, and interobserver agreement for all four radiologists. More specifically, two of the four radiologists achieved a significant improvement in sensitivity (P=.03, P=.03), and all four radiologists achieved a significant improvement in accuracy (P = .01, P = .05, P = .009, P < .001)., Conclusion: Current study results suggest that the addition of quantitative 1H MR spectroscopy to the breast MR imaging examination may help to improve the radiologist's ability to distinguish benign from malignant breast lesions.

Magnetic resonance spectroscopic imaging (MRSI) has proven to be a powerful tool for the metabolic characterization of prostate cancer in patients before and following therapy. The metabolites that are of particular interest are citrate and choline because an increased choline-to-citrate ratio can be used as a marker for cancer. High-field systems offer the advantage of improved spectral resolution as well as increased magnetization. Initial attempts at extending MRSI methods to 3 T have been confounded by the J-modulation of the citrate resonances. A new pulse sequence is presented that controls the J-modulation of citrate at 3 T such that citrate is upright, with high amplitude, at a practical echo time. The design of short (14 ms) spectral-spatial refocusing pulses and trains of nonselective refocusing pulses are described. Phantom studies and simulations showed that upright citrate with negligible sidebands is observed at an echo time of 85 ms. Studies in a human subject verified that this behavior is reproduced in vivo and demonstrated that the water and lipid suppression of the new pulse sequence are sufficient for application in prostate cancer patients., (Copyright 2005 Wiley-Liss, Inc.)

A novel single-shot spectral editing technique for in vivo proton NMR is proposed to recover resonances of low-concentration metabolites obscured by very strong resonances. With this new method, editing is performed by transferring transverse magnetization to J-coupled spins from selected coupling partners using a homonuclear Hartmann-Hahn polarization transfer with adiabatic pulses. The current implementation uses 1D-TOCSY with single-voxel localization based on LASER to recover the H1 proton of beta-glucose at 4.63 ppm from under water and the lactate methyl resonances from beneath a strong lipid signal. The method can be extended to further spin systems where conventional editing methods are difficult to perform., (Copyright 2005 Wiley-Liss, Inc.)

Transverse relaxation in the rotating frame (T(2rho)) is the dominant relaxation mechanism during an adiabatic Carr-Purcell (CP) spin-echo pulse sequence when no delays are used between pulses in the CP train. The exchange-induced and dipolar interaction contributions (T(2rho,ex) and T(2rho,dd)) depend on the modulation functions of the adiabatic pulses used. In this work adiabatic pulses having different modulation functions were utilized to generate T(2rho) contrast in images of the human occipital lobe at magnetic field of 4 T. T(2rho) time constants were measured using an adiabatic CP pulse sequence followed by an imaging readout. For these measurements, adiabatic full passage pulses of the hyperbolic secant HSn (n = 1 or 4) family having significantly different amplitude-and frequency-modulation functions were used with no time delays between pulses. A dynamic averaging (DA) mechanism (e.g., chemical exchange and diffusion in the locally different magnetic susceptibilities) alone was insufficient to fully describe differences in brain tissue water proton T(2rho) time constants. Measurements of the apparent relaxation time constants (T(2) (dagger)) of brain tissue water as a function of the time between centers of pulses (tau(cp)) at 4 and 7 T permitted separation of the DA contribution from that of dipolar relaxation. The methods presented assess T(2rho) relaxation influenced by DA in tissue and provide a means to generate T(2rho) contrast in MRI., (Copyright 2005 Wiley-Liss, Inc.)

A technique called in vivo magnetic resonance spectroscopy (MRS) can be performed along with magnetic resonance imaging (MRI) to obtain information about the chemical content of breast lesions. This information can be used for several clinical applications, such as monitoring the response to cancer therapies and improving the accuracy of lesion diagnosis. Initial MRS studies of breast cancer show promising results, and a growing number of research groups are incorporating the technique into their breast MRI protocols. This article introduces 1H-MRS of the breast, reviews the literature, discusses current methods and technical issues, and describes applications for treatment monitoring and lesion diagnosis.

Respiratory motion is well known to cause artifacts in magnetic resonance spectroscopy (MRS). In MRS of the breast, the dominant artifact is not due to motion of the breast itself, but rather it is produced by B0 field distortions associated with respiratory motion of tissues in the chest and abdomen. This susceptibility artifact has been reported to occur in the brain, but it is more apparent in the breast due to the anatomic proximity of the lungs. In the breast, these B0 distortions cause shot-to-shot frequency shifts, which vary an average of 24 Hz during a typical 1H MRS scan at 4 T. This variation can be corrected retrospectively by frequency shifting individual spectra prior to averaging. If not corrected, these shifts reduce spectral resolution and increase peak fitting errors. This work demonstrates the artifact, describes a method for correcting it, and evaluates its impact on quantitative spectroscopy. When the artifact is not corrected, quantification errors increase by an average of 28%, which dramatically impacts the ability to measure metabolite resonances at low signal-to-noise ratios., ((c) 2004 Wiley-Liss, Inc.)

Purpose: To determine if changes in the concentration of choline-containing compounds (tCho) from before primary systemic therapy (PST) to within 24 hours after the first treatment enable prediction of clinical response in patients with locally advanced breast cancer., Materials and Methods: Sixteen women with biopsy-confirmed locally advanced breast cancer scheduled to undergo doxorubicin-based PST were recruited. Magnetic resonance (MR) imaging and spectroscopy were performed at 4 T prior to treatment, within 24 hours after the first dose, and after the fourth dose. Lesion size was assessed by using gadolinium-enhanced MR imaging. Lesion tCho concentration was quantified by using single-voxel hydrogen 1 MR spectroscopy. Statistical analysis was performed by using the Pearson correlation coefficient and the Wilcoxon rank sum test., Results: Fourteen of 16 patients completed the protocol. In one patient, the level of tCho was not measurable because of unfavorable lesion morphology for MR spectroscopy voxel placement. Of the remaining 13 patients, four had inflammatory breast cancer, six had invasive ductal carcinoma, two had invasive lobular carcinoma, and one had mixed invasive ductal and lobular carcinoma. On the basis of the Response Evaluation Criteria in Solid Tumors, eight of 13 patients had an objective response and five had no response. The change in concentration of tCho from baseline to within 24 hours after the first dose of PST showed significant positive correlation with the change in lesion size (R = 0.79, P = .001). Change in tCho concentration within 24 hours after first dose was significantly different between patients with objective response and those with no response (P = .007)., Conclusion: These results suggest that the change in tCho concentration between baseline and 24 hours after the first dose of PST can serve as an indicator for predicting clinical response to doxorubicin-based chemotherapy in locally advanced breast cancer.

On-resonance longitudinal relaxation time in the rotating frame (T1rho) has been shown to provide unique information during the early minutes of acute stroke. In the present study, the contributions of the different relaxation mechanisms to on-resonance T1rho relaxation were assessed by determining relaxation rates (R1rho) in both protein phantoms and in rat brain at 2.35, 4.7, and 9.4 T. Similar to transverse relaxation rate (R2), R1rho increased substantially with increasing magnetic field strength (B0). The B0 dependence was more pronounced at weak spin-lock fields. In contrast to R1rho, longitudinal relaxation rate (R1) decreased as a function of increasing B0 field. The present data argue that dipole-dipole interaction forms only one pathway for T1rho relaxation and the contributions from other physicochemical factors need to be considered., (Copyright 2003 Wiley-Liss, Inc.)

This work describes a methodology for quantifying levels of total choline-containing compounds (tCho) in the breast using in vivo (1)H MR spectroscopy (MRS) at high field (4 Tesla). Water is used as an internal reference compound to account for the partial volume of adipose tissue. Peak amplitudes are estimated by fitting one peak at a time over a narrow frequency band to allow measurement of small metabolite resonances in spectra with large lipid peaks. This quantitative method significantly improves previously reported analysis methods by accounting for the variable sensitivity of breast (1)H MRS measurements. Using this technique, we detected and quantified a tCho peak in 214 of 500 in vivo spectra. tCho levels were found to be significantly higher in malignancies than in benign abnormalities and normal breast tissues, which suggests that this technique could be used to diagnose suspicious lesions and monitor response to cancer treatments., (Copyright 2003 Wiley-Liss, Inc.)

Detecting metabolites in breast lesions by in vivo (1)H MR spectroscopy can be difficult due to the abundance of mobile lipids in the breast which can produce spurious sidebands that interfere with the metabolite signals. Two-dimensional J-resolved spectroscopy has been demonstrated in the brain as a means to eliminate these artifacts from a large water signal; coherent sidebands are resolved at their natural frequencies, leaving the noncoupled metabolite resonances in the zero-frequency trace of the 2D spectrum. This work demonstrates that using the zero-frequency trace-or equivalently the average of spectra acquired with different echo times-can be used to separate noncoupled metabolite signals from the lipid-induced sidebands. This technique is demonstrated with simulations, phantom studies, and in several breast lesions. Compared to the conventional approach using a single echo time, echo time averaging provides increased sensitivity for the study of small and irregularly shaped lesions., (Copyright 2002 Wiley-Liss, Inc.)

Frequency-modulated (FM) pulses that function according to adiabatic principles are becoming increasingly popular in many areas of NMR. Often adiabatic pulses can extend experimental capabilities and minimize annoying experimental imperfections. Here, adiabatic principles and some of the current methods used to create these pulses are considered. The classical adiabatic rapid passage, which is a fundamental element upon which all adiabatic pulses and sequences are based, is analyzed using vector models in different rotating frames of reference. Two methods to optimize adiabaticity are described, and ways to tailor modulation functions to best satisfy specific experimental needs are demonstrated. Finally, adiabatic plane rotation pulses and frequency-selective multiple spin-echo sequences are considered.

A technique is described for performing frequency-selective signal suppression with a high degree of tolerance to RF field inhomogeneity. The method is called B1-insensitive train to obliterate signal (BISTRO). BISTRO consists of multiple amplitude- and frequency-modulated (FM) pulses interleaved with spoiler gradients. BISTRO was developed for the purpose of accomplishing band-selective signal removal, as in water suppression and outer-volume suppression (OVS), in applications requiring the use of an inhomogeneous RF transmitter, such as a surface coil. In the present work, Bloch simulations were used to illustrate the principles and theoretical performance of BISTRO. Its performance for OVS was evaluated experimentally using MRI and spectroscopic imaging of phantoms and in vivo animal and human brain. By using FM pulses featuring offset-independent adiabaticity, BISTRO permitted high-quality, broadband suppression with one (or two) discrete borders demarcating the edge(s) of the suppression band. Simulations and experiments demonstrated the ability to operate BISTRO with reasonably attainable peak RF power levels and with average RF energy deposition similar to other multipulse OVS techniques., (Copyright 2001 Wiley-Liss, Inc.)

Many types of NMR experiments demand the use of frequency-selective pulses to invert magnetization within discrete frequency limits. For certain experiments, only one side of the inversion band must be sharply demarcated, in which case this transition bandwidth can be narrowed when using an asymmetric adiabatic full passage. In the present study, a highly efficient asymmetric adiabatic full passage was created from a combination of two adiabatic half passages which used different modulation functions (HS12 and tanh/tan). Each adiabatic half passage occupied a different amount of time in the total pulse and performed one-half of the inversion. On one side, HS12 produced a sharp transition between inverted and noninverted states which was approximately 2.5 times narrower than the transition bandwidth afforded by a symmetric hyperbolic secant pulse of equal length. On the other side of the narrow transition band, the tanh/tan pulse achieved broadband inversion. These asymmetric pulses were applied to select NH groups immediately adjacent to the water signal in water-flip-back HSQC experiments using a double spin echo for the reverse INEPT step., (Copyright 1999 Academic Press.)

Magnetic resonance spectroscopy (MRS) measurements of the lactate methyl proton in rat brain C6 glioma tissue acquired in the presence of an off-resonance irradiation field, analyzed using coupled Bloch equation formalism assuming two spin pools, demonstrated the occurrence of magnetization transfer. Quantitative analysis revealed that a very small fraction of lactate (f = 0.0012) is rotationally immobilized despite a large magnetization transfer effect. Off-resonance rotating frame spin-lattice relaxation studies demonstrated that deuterated lactate binds to bovine serum albumin and the proteins present in human plasma, thereby providing a possible physical basis for the observed magnetization transfer effect. These results demonstrate that partial or complete saturation of the motionally restricted lactate pool (as well as other metabolites) by the application of an off-resonance irradiation field, such as that used for water presaturation, can lead to a substantial decrease in resonance intensity by way of magnetization transfer effects, resulting in quantitation errors.

The measurement of cerebral metabolites using highly homologous localization techniques and similar shimming methods was performed in the human brain at 1.5 and 4 T as well as in the dog and rat brain at 9.4 T. In rat brain, improved resolution was achieved by shimming all first- and second-order shim coils using a fully adiabatic FASTMAP sequence. The spectra showed a clear improvement in spectral resolution for all metabolite resonances with increased field strength. Changes in cerebral glutamine content were clearly observed at 4 T compared to 1.5 T in patients with hepatic encephalopathy. At 9.4 T, glutamine H4 at 2.46 ppm was fully resolved from glutamate H4 at 2.37 ppm, as was the potential resonance from gamma-amino-butyric acid at 2.30 ppm and N-acetyl-aspartyl-glutamate at 2.05 ppm. Singlet linewidths were found to be as low as 6 Hz (0.015 ppm) at 9.4 T, indicating a substantial decrease in ppm linewidth with field strength. Furthermore, the methylene peak of creatine was partially resolved from phosphocreatine, indicating a close to 1:1 relationship in gray matter. We conclude that increasing the magnetic field strength increases spectral resolution also for 1H NMR, which can lead to more than linear sensitivity gains., (Copyright 1998 Academic Press.)

Water suppression is typically performed in vivo by exciting the longitudinal magnetization in combination with dephasing, or by using frequency-selective coherence generation. MEGA, a frequency-selective refocusing technique, can be placed into any pulse sequence element designed to generate a Hahn spin-echo or stimulated echo, to dephase transverse water coherences with minimal spectral distortions. Water suppression performance was verified in vivo using stimulated echo acquisition mode (STEAM) localization, which provided water suppression comparable with that achieved with four selective pulses in 3,1-DRYSTEAM. The advantage of the proposed method was exploited for editing J-coupled resonances. Using a double-banded pulse that selectively inverts a J-coupling partner and simultaneously suppresses water, efficient metabolite editing was achieved in the point resolved spectroscopy (PRESS) and STEAM sequences in which MEGA was incorporated. To illustrate the efficiency of the method, the detection of gamma-aminobutyric acid (GABA) was demonstrated, with minimal contributions from macromolecules and overlying singlet peaks at 4 T. The estimated occipital GABA concentration was consistent with previous reports, suggesting that editing for GABA is efficient when based on MEGA at high field strengths.

Despite the advantages of compensation for resonance offset and B1 inhomogeneity, adiabatic pulses are not yet in general use in high-resolution NMR, often because of the conception that these pulses require longer time or increased power to perform. We show that adiabatic pulses with tangential frequency sweeps and other frequency-modulation functions can be optimized to accomplish 13C and 1H broadband inversion using pulse lengths of 192 and 64 micro(s), respectively, at B1 strengths available with modern high-resolution probes., (Copyright 1998 Academic Press.)

Adiabatic pulses are sometimes considered to be mysterious and exotic entities which are difficult to understand, complex to generate and impractical to implement. This work is an attempt to bring familiarity and to fulfill the preliminary needs of anyone interested in learning more about this subject. The response of magnetization to stimuli produced by adiabatic pulses is analyzed using vector representations in a frequency modulated rotating frame. The first section deals with basic principles of amplitude and frequency modulated pulses and a vector representation in a second rotating frame is used to explain how the adiabatic condition can be satisfied. The subsequent section explains the principles of offset independent adiabaticity. These principles are then used to design optimal functions for the amplitude, frequency, and magnetic field gradient modulations for adiabatic inversion pulses. The last section considers some practical aspects for those who want to develop methodologies involving adiabatic pulses.

The use of surface coils in magnetic resonance imaging offers significant improvements in the signal-to-noise ratio over volume coils for many applications. However, the inhomogeneous reception profile of surface coils hampers their usefulness by introducing significant nonuniformities or intensity variations which can vary by greater than six-fold across the sample. In this study, we evaluated an automatic technique for retrospective correction of intensity variations observed in a high-resolution surface coil MR image of the rat brain obtained using an adiabatic magnetic resonance imaging sequence. The images are shown to have a coefficient of variation less than 12% following application of this correction algorithm. This image intensity correction technique can be applied retrospectively to all data sets and corrects both sample/patient dependent effects (e.g. attenuation of overlying tissue) or sample independent effects (e.g. coil geometry or position). This approach should also prove valuable in improving regions of interest analysis, volume histograms and thresholding techniques.

A technique for single-shot, localized, water-suppressed in vivo 1H NMR with high immunity to B1 inhomogeneities is described. The single-shot localization is based on complete outer-volume suppression which is achieved with optimized, adiabatic BIR-4 pulses in combination with BO gradient modulation. B1-insensitive water suppression is achieved with BISTRO, a train of selective adiabatic full-passage pulses interleaved with BO gradient crushers. Computer simulations based on the Bloch equations, experimental images of the localized volume, and in vivo 1H spectroscopy experiments demonstrate the excellent spatial localization and water suppression.

Measurement of the resonances of glucose between 3.2 and 3.9 ppm in 1H NMR spectra from the human brain is difficult due to spectral overlap with peaks from more concentrated metabolites. The H1 resonance of alpha-D-glucose at 5.23 ppm is resolved from other metabolite peaks, but potentially overlaps with the intense water signal at 4.72 ppm. This paper demonstrates that the increased resolution at 4 Tesla permits to suppress the water signal sufficiently to reliably detect glucose directly at 5.23 ppm by 1H MRS and the estimated peak intensity is consistent with previous 13C NMR quantification.

An adiabatic pulse has been developed to accomplish uniform slice-selective excitation with a spatially inhomogeneous B1. This new pulse can generate a uniform, arbitrary flip angle that is determined by four adjustable phase shifts in the pulse. Self-refocused slice selection is achieved by modulating a B(O) gradient in concert with the pulse frequency (or phase) modulation. B1-compensated, self-refocused slice selection is demonstrated in computer simulations and phantom experiments using a surface transmitter/receiver coil. This adiabatic pulse can provide optimal performance in multislice MRI and localized spectroscopy when transmitting with an inhomogeneous B1.

Amplitude- and frequency-modulated pulses, known as adiabatic pulses, can induce uniform flip angles in the presence of extreme B1 inhomogeneity, which makes them advantageous for in vivo surface-coil studies. This paper describes the conversion of conventional (square pulse-based) spectral-editing sequences into their adiabatic counterparts. Eight adiabatic homo- and heteronuclear sequences are experimentally evaluated for lactate editing. For homonuclear lactate editing, gradient-enhanced multiple-quantum-coherence filtering provides the best overall performance (100% signal recovery with excellent water and lipid suppression in a single acquisition). For heteronuclear [3-(13)C]lactate editing, gradient-enhanced heteronuclear multiple-quantum-coherence filtering provides the best suppression of unwanted signals in a single acquisition, whereas J-modulated spin-echo sequences yield maximum sensitivity.

A new method is described for accomplishing localized spectroscopy with an adiabatic pulse, BIR-4. The method has advantages similar to previously described combinations of outer-volume suppression (OVS) and ISIS, with the additional advantages that localization is achieved with only three radiofrequency pulses and the localization remains accurate even in the presence of intense signals with short relaxation times. This new localization pulse sequence is referred to as integrated OVS-ISIS. Computer simulations, experimental images of the localized volumes, and in vivo 1H spectroscopy measurements demonstrate the high degree of localization achievable with integrated OVS-ISIS.

Purpose: To quantify lithium in the human brain., Methods: A 7Li MR spectroscopy method was developed with special features for high precision including: a) sampling a large cerebral volume to maximize the signal-to-noise ratio; b) adiabatic excitation pulses to ensure uniform spin mutation; c) morphometric analysis of the MR images of the sampled cerebrum; d) a mathematical model derived from empirical data to correct for receiver inhomogeneity effects; and e) a long interpulse delay, to eliminate errors arising from uncertain T1 values., Results: A theoretical precision of 5.2% and an accuracy of better than 7.2% in someone with a brain lithium level of 1.0 mEq per liter of cerebral volume and precision and accuracy of 6.8 and 8.6%, respectively, in someone with 0.5 mEq/L brain lithium was calculated. This level of precision was surpassed in phantoms and patients. Brain lithium in 10 patients treated with lithium carbonate varied from 0.52 to 0.87 mEq/L (mean = 0.58 mEq/L; SD = 0.17 mEq/L). Brain-to-serum lithium ratios varied from 0.50 to 0.97 mEq/L (mean = 0.77 mEq/L; SD = 0.14 mEq/L). Substantial variation in brain lithium was observed in patients with similar serum lithium., Conclusions: A highly reliable method to quantify human brain lithium by 7Li MR spectroscopy has been implemented. Unexpected variability in brain versus serum levels of lithium was detected in patients with bipolar disease.

In vivo 1H MRS can be used to detect and quantify the lactate resonance at 1.3 ppm provided that overlapping lipid resonances are eliminated. A homonuclear spectral editing method was developed to acquire uncontaminated 1H spectra of lactate with adiabatic pulses. An advantage of the adiabatic pulse sequence is the ability to induce uniform flip angles and to maximize sensitivity in applications employing surface coil transmitters which produce highly inhomogeneous B1. Glycolytic activity in an intracerebral C6 glioma in rats was monitored by using adiabatic editing sequences to observe [3-13C]lactate produced from infused [1-13C]glucose. Acute hyperglycemia (serum glucose > 22 mM, n = 10) had no significant effect (P = 0.08) on the total ([12C] + [13C]) tumor lactate signal intensity.

Surface coil MRI combined with spatially localized spectroscopy was used to noninvasively detect 1H signals from metabolites within an intracerebral malignant glioma in rats. The MRS pulse sequence was based upon two-dimensional ISIS, which restricted 1H signals to a column-shaped volume, combined with one-dimensional spectroscopic imaging, which further resolved the signals into 8 or 16 slices along the major axis of the column. All experiments were executed with adiabatic pulses which induced uniform spin excitation despite the inhomogeneous radiofrequency field distribution produced by the surface coil transmitter. Surface coil MRI and MRS experiments were performed on phantom samples, normal rat brains, and rat brains harboring malignant gliomas. Spatially resolved in vivo 1H spectra of intracerebral gliomas revealed significantly decreased concentrations of N-acetyl-aspartate and creatine and increased lactic acid (or lipids) as compared to the contralateral hemisphere. These results demonstrate that metabolic abnormalities in intracerebral rat gliomas can be spatially resolved in a noninvasive manner using localized in vivo 1H MRS.

Spatially resolved 31P magnetic resonance spectroscopy (MRS) at 4.7 T was applied to noninvasively assess liver phosphorus metabolites in a biochemically well-characterized model of hepatotoxicity induced by injection of a sublethal dose of D-galactosamine (galN). A newly developed hybrid method based on spectral localization with B0 and B1 gradients was employed to obtain multivoxel spectra in intact anesthesized rats. Spatially localized in vivo spectra were recorded 0 to 26 h after galN injection of female rats. In response to galN exposure, diphosphodiester peaks ascribed to UDP-hexosamines became detectable by 4 h and persisted up to 26 h. A metabolite coresonating with inorganic phosphate increased rapidly in intensity by 2 h after galN and returned to baseline by 18 h; this resonance was shown not to be Pi and was assigned to galN-1-phosphate by subsequent high resolution MRS experiments on extracts prepared from these livers. These results confirmed in vivo the metabolic perturbations described previously for this model of hepatotoxicity following biochemical studies based on classical extraction methods. Unlike the in vitro studies, however, these noninvasive experiments provided additional information on the time course of metabolic alterations on the same animal.