Fast three‐dimensional proton spectroscopic imaging of the human brain at 3 T by combining spectroscopic missing pulse steady‐state free precession and echo planar spectroscopic imaging

The combination of the principles of two fast spectroscopic imaging (SI) methods, spectroscopic missing pulse steady‐state free precession and echo planar SI (EPSI) is described as an approach toward fast 3D SI. This method, termed missing pulse steady‐state free precession echo planar SI, exhibits a considerably reduced minimum total measurement time T_min, allowing a higher temporal resolution, a larger spatial matrix size, and the use of k‐space weighted averaging and phase cycling, while maintaining all advantages of the original spectroscopic missing pulse steady‐state free precession sequence. The minor signal‐to‐noise ratio loss caused by using oscillating read gradients can be compensated by applying k‐space weighted averaging. The missing pulse steady‐state free precession echo planar SI sequence was implemented on a 3 T head scanner, tested on phantoms and applied to healthy volunteers. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.     

MR spectroscopy of the human brain with enhanced signal intensity at ultrashort echo times on a clinical platform at 3T and 7T

Recently, the spin‐echo full‐intensity acquired localized (SPECIAL) spectroscopy technique was proposed to unite the advantages of short TEs on the order of milliseconds (ms) with full sensitivity and applied to in vivo rat brain. In the present study, SPECIAL was adapted and optimized for use on a clinical platform at 3T and 7T by combining interleaved water suppression (WS) and outer volume saturation (OVS), optimized sequence timing, and improved shimming using FASTMAP. High‐quality single voxel spectra of human brain were acquired at TEs below or equal to 6 ms on a clinical 3T and 7T system for six volunteers. Narrow linewidths (6.6 ± 0.6 Hz at 3T and 12.1 ± 1.0 Hz at 7T for water) and the high signal‐to‐noise ratio (SNR) of the artifact‐free spectra enabled the quantification of a neurochemical profile consisting of 18 metabolites with Cramér‐Rao lower bounds (CRLBs) below 20% at both field strengths. The enhanced sensitivity and increased spectral resolution at 7T compared to 3T allowed a two‐fold reduction in scan time, an increased precision of quantification for 12 metabolites, and the additional quantification of lactate with CRLB below 20%. Improved sensitivity at 7T was also demonstrated by a 1.7‐fold increase in average SNR (= peak height/root mean square [RMS]‐of‐noise) per unit‐time. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

RF shimming for spectroscopic localization in the human brain at 7 T

Spectroscopic imaging of the human head at short echo times (≤15 ms) typically requires suppression of signals from extracerebral tissues. However, at 7 T, decreasing efficiency in B generation (hertz/watt) and increasing spectral bandwidth result in dramatic increases in power deposition and increased chemical shift registration artifacts for conventional gradient‐based in‐plane localization. In this work, we describe a novel method using radiofrequency shimming and an eight‐element transceiver array to generate a B field distribution that excites a ring about the periphery of the head and leaves central brain regions largely unaffected. We have used this novel B distribution to provide in‐plane outer volume suppression (>98% suppression of extracerebral lipids) without the use of gradients. This novel B distribution is used in conjunction with a double inversion recovery method to provide suppression of extracerebral resonances with T₁s greater than 400 ms, while having negligible effect on metabolite ratios of cerebral resonances with T₁s > 1000 ms. Despite the use of two adiabatic pulses, the high efficiency of the ring distribution allows radiofrequency power deposition to be limited to 3‐4 W for a pulse repetition time of 1.5 sec. The short echo time enabled the acquisition of images of the human brain, displaying glutamate, glutamine, macromolecules, and other major cerebral metabolites. Magn Reson Med, 2010. © 2009 Wiley‐Liss, Inc.     

2D 1H spectroscopic imaging of the human brain at 4.1 T

A two-dimensional spectroscopic imaging sequence consisting of an inversion recovery pulse, a plane selective prefocused pulse, and a semiselective water suppression pulse has been used to create ¹H spectroscopic images of the human brain with nominal voxels of 0.5 cc. Due to the excellent lipid suppression provided by the inversion recovery pulse and subsequent delay, only planar volume selection is required enabling the entire brain within the slice to be imaged without contamination from extracerebral lipids in the brain voxels. The use of a semiselective refocusing pulse for water suppression permits any echo evolution time to be used, minimizing J-modulation and T₂ losses, while retaining full sensitivity in the lactate resonance. Using this sequence we have visualized the lactate elevation in the peri-infarct region about a 6-week-old stroke.     

Proton echo-planar spectroscopic imaging of J-coupled resonances in human brain at 3 and 4 Tesla.

In this multicenter study, 2D spatial mapping of J-coupled resonances at 3T and 4T was performed using short-TE (15 ms) proton echo-planar spectroscopic imaging (PEPSI). Water-suppressed (WS) data were acquired in 8.5 min with 1-cm(3) spatial resolution from a supraventricular axial slice. Optimized outer volume suppression (OVS) enabled mapping in close proximity to peripheral scalp regions. Constrained spectral fitting in reference to a non-WS (NWS) scan was performed with LCModel using correction for relaxation attenuation and partial-volume effects. The concentrations of total choline (tCho), creatine + phosphocreatine (Cr+PCr), glutamate (Glu), glutamate + glutamine (Glu+Gln), myo-inositol (Ins), NAA, NAA+NAAG, and two macromolecular resonances at 0.9 and 2.0 ppm were mapped with mean Cramer-Rao lower bounds (CRLBs) between 6% and 18% and approximately 150-cm(3) sensitive volumes. Aspartate, GABA, glutamine (Gln), glutathione (GSH), phosphoethanolamine (PE), and macromolecules (MMs) at 1.2 ppm were also mapped, although with larger mean CRLBs between 30% and 44%. The CRLBs at 4T were 19% lower on average as compared to 3T, consistent with a higher signal-to-noise ratio (SNR) and increased spectral resolution. Metabolite concentrations were in the ranges reported in previous studies. Glu concentration was significantly higher in gray matter (GM) compared to white matter (WM), as anticipated. The short acquisition time makes this methodology suitable for clinical studies.     

Quantitative proton spectroscopic imaging of the neurochemical profile in rat brain with microliter resolution at ultra-short echo times.

Proton spectroscopy allows the simultaneous quantification of a high number of metabolite concentrations termed the neurochemical profile. The spin echo full intensity acquired localization (SPECIAL) scheme with an echo time of 2.7 ms was used at 9.4T for excitation of a slab parallel to a home-built quadrature surface coil in conjunction with phase encoding in the two remaining spatial dimensions to yield an effective spatial resolution of 1.7 microL. The absolute concentrations of at least 10 metabolites were calculated from the spectra of individual voxels using LCModel analysis. The calculated concentrations were used for constructing quantitative metabolic maps of the neurochemical profile in normal and pathological rat brain. Summation of individual spectra was used to assess the neurochemical profile of unique brain regions, such as corpus callosum, in rat for the first time. Following focal ischemia in rat pups, imaging the neurochemical profile indicated increased choline groups in the ischemic core and increased glutamine in the penumbra, which is proposed to reflect glutamate excitotoxicity. We conclude that it is feasible to achieve a sensitivity that is sufficient for quantitative mapping of the neurochemical profile at microliter spatial resolution.     

Short echo time proton magnetic resonance spectroscopic imaging of macromolecule and metabolite signal intensities in the human brain

A novel approach is presented for imaging macromolecule and metabolite signals in brain by proton magnetic resonance spectroscopic imaging. The method differentiates between metabolites and macromolecules by T₁ weighting using an inversion pulse followed by a variable inversion recovery time before localization and spectroscopic imaging. In healthy subjects, the major macromolecule resonances at 2.05 and 0.9 ppm were mapped at a nominal spatial resolution of 1 × 1 × 1.5 cm³ and were demonstrated to be highly reproducible between subjects. In subacute stroke patients, a highly elevated macromolecule resonance at 1.3 ppm was mapped to infarcted brain regions, suggesting potential applications for studying pathological conditions.     

Proton MR spectroscopic imaging of rhesus macaque brain in vivo at 7T

Due to the overall similarity of their brains' structure and physiology to its human counterpart, nonhuman primates provide excellent model systems for the pathogenesis of neurological diseases and their response to treatments. Its much smaller size, 80 versus 1250 cm(3), however, requires proportionally higher spatial resolution to study, nondestructively, as many analogous regions as efficiently as possible in anesthetized animals. The confluence of these requirements underscores the need for the highest sensitivity, spatial coverage, resolution, and exam speed. Accordingly, we demonstrate the feasibility of 3D multi-voxel, proton ((1)H) MRSI at (0.375 cm)(3)=0.05 cm(3) isotropic spatial resolution over 21 cm(3) (approximately 25%) of the anesthetized rhesus macaques brain at 7T in 25 min. These voxels are x10(2)-10(1) times smaller than the 8-1 cm(3) common to (1)H-MRS in humans, retaining similar proportions between the macaque and human brain. The spectra showed a signal-to-noise-ratio (SNR) approximately 9-10 for the major metabolites and the interanimal SNR spatial distribution reproducibility was in the +/-10% range for the standard error of their means (SEMs). Their metabolites' linewidths, 9+/-2 Hz, yield excellent spectral resolution as well. These results indicate that 3D (1)H-MRSI can be integrated into comprehensive MR studies in primates at such high fields.     

Out-and-in spiral spectroscopic imaging in rat brain at 7 T.

With standard spectroscopic imaging, high spatial resolution is achieved at the price of a large number of phase-encoding steps, leading to long acquisition times. Fast spatial encoding methods reduce the minimum total acquisition time. In this article, a k-space scanning scheme using a continuous series of growing and shrinking, or "out-and-in," spiral trajectories is implemented and the feasibility of spiral spectroscopic imaging for animal models at high B(0) field is demonstrated. This method was applied to rat brain at 7 T. With a voxel size of about 8.7 microl (as calculated from the point-spread function), a 30 x 30 matrix, and a spectral bandwidth of 11 kHz, the minimum scan time was 9 min 20 sec for a signal-to-noise ratio of 7.1 measured on the N-acetylaspartate peak.     

Fast proton spectroscopic imaging of human brain using multiple spin-echoes

We introduce a multi-echo multi-slice MR proton spectroscopic imaging method, which allows for a dramatic reduction of the measurement time by acquiring multiple spin-echoes within a single repetition time. In the multi-echo multi-slice experiment discussed in this paper, a threefold reduction in measurement time is obtained by sacrificing some spectral resolution. Signal-to-noise ratio and spatial resolution are preserved. Metabolite images of N-acetyl aspartate, and total choline + total creatine from multiple slices through the human brain are presented and compared with images obtained with a conventional single-echo multi-slice method.     

Fast (13)C-glucose metabolite mapping in rat brain using (1)H echo planar spectroscopic imaging technique at 2T

For fast (13)C metabolite mapping in rat brains, (1)H-detected (13)C NMR spectroscopy using gradient-enhanced heteronuclear multiple-quantum coherence and (1)H echo planar spectroscopic imaging were combined. (13)C glucose and 3-/4-(13)C-Glu/Gln images of rat brain were successfully constructed with 35-minute temporal resolution under a 2T magnetic field. In the ischemic region of the suture middle cerebral artery occlusion model, glucose and Glu/Gln signals decreased and lactate signals appeared. J. Magn. Reson. Imaging 2001;13:787-791.     

Spin‐echo magnetic resonance spectroscopic imaging at 7 T with frequency‐modulated refocusing pulses

Two approaches to high‐resolution SENSE‐encoded magnetic resonance spectroscopic imaging (MRSI) of the human brain at 7 Tesla (T) with whole‐slice coverage are described. Both sequences use high‐bandwidth radiofrequency pulses to reduce chemical shift displacement artifacts, SENSE‐encoding to reduce scan time, and dual‐band water and lipid suppression optimized for 7 T. Simultaneous B₀ and transmit B₁ mapping was also used for both sequences to optimize field homogeneity using high‐order shimming and determine optimum radiofrequency transmit level, respectively. One sequence (“Hahn‐MRSI”) used reduced flip angle (90°) refocusing pulses for lower radiofrequency power deposition, while the other sequence used adiabatic fast passage refocusing pulses for improved sensitivity and reduced signal dependence on the transmit‐B₁ level. In four normal subjects, adiabatic fast passage‐MRSI showed a signal‐to‐noise ratio improvement of 3.2 ± 0.5 compared to Hahn‐MRSI at the same spatial resolution, pulse repetition time, echo time, and SENSE‐acceleration factor. An interleaved two‐slice Hahn‐MRSI sequence is also demonstrated to be experimentally feasible. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

31P-{1H} echo-planar spectroscopic imaging of the human brain in vivo.

Echo-planar spectroscopic imaging (EPSI) is one of the fastest spectroscopic imaging (SI) methods. It has been applied to (1)H MR spectroscopy (MRS) studies of the human brain in vivo. However, to our knowledge, EPSI with detection of the (31)P nucleus to monitor phosphorus-containing neurometabolites has not yet been considered. In this work, eight different (31)P-{(1)H} EPSI sequence versions with spectral widths ranging from 313 Hz to 2.27 kHz were implemented on a clinical 1.5T whole-body MR tomograph. The sequence versions utilized the heteronuclear nuclear Overhauser effect (NOE) for (31)P signal enhancement. The sensitivity observed in experiments with model solutions was in good agreement with theoretical predictions. In vivo measurements performed on healthy volunteers (N = 16) demonstrated the feasibility of performing two-dimensional (2D) (31)P-{(1)H} EPSI in the human brain, and the technique enabled fast acquisition of well-resolved localized spectra.     

Quantitative mapping of total choline in healthy human breast using proton echo planar spectroscopic imaging (PEPSI) at 3 Tesla

Purpose:

To quantitatively measure tCho levels in healthy breasts using Proton‐Echo‐Planar‐Spectroscopic‐Imaging (PEPSI).

Materials and Methods:

The two‐dimensional mapping of tCho at 3 Tesla across an entire breast slice using PEPSI and a hybrid spectral quantification method based on LCModel fitting and integration of tCho using the fitted spectrum were developed. This method was validated in 19 healthy females and compared with single voxel spectroscopy (SVS) and with PRESS prelocalized conventional Magnetic Resonance Spectroscopic Imaging (MRSI) using identical voxel size (8 cc) and similar scan times (～7 min).

Results:

A tCho peak with a signal to noise ratio larger than 2 was detected in 10 subjects using both PEPSI and SVS. The average tCho concentration in these subjects was 0.45 ± 0.2 mmol/kg using PEPSI and 0.48 ± 0.3 mmol/kg using SVS. Comparable results were obtained in two subjects using conventional MRSI. High lipid content in the spectra of nine tCho negative subjects was associated with spectral line broadening of more than 26 Hz, which made tCho detection impossible. Conventional MRSI with PRESS prelocalization in glandular tissue in two of these subjects yielded tCho concentrations comparable to PEPSI.

Conclusion:

The detection sensitivity of PEPSI is comparable to SVS and conventional PRESS‐MRSI. PEPSI can be potentially used in the evaluation of tCho in breast cancer. A tCho threshold concentration value of ～0.7 mmol/kg might be used to differentiate between cancerous and healthy (or benign) breast tissues based on this work and previous studies. J. Magn. Reson. Imaging 2012;36:1113–1123. © 2012 Wiley Periodicals, Inc.     

Long and short echo time proton magnetic resonance spectroscopic imaging of the healthy aging brain

PURPOSE: To investigate the relationship between subject age and white matter brain metabolite concentrations and R(2) relaxation rates in a cross-sectional study of human brain. MATERIALS AND METHODS: Long- and short-echo proton spectroscopic imaging were used to investigate concentrations and R2 relaxation rates of N-acetyl aspartate (NAA) + N-acetyl aspartyl glutamate (NAAG), choline (Cho), creatine (Cr), and myoinositol (mI) in the white matter of the centrum semiovale of 106 healthy volunteers aged 50-90 years; usable data were obtained from 79 subjects. A major aim was to identify which parameters were most sensitive to changes with age. Spectra were analyzed using the LCModel method. RESULTS: The apparent R2 of NAA and the LCModel concentration of Cr at short echo time were significantly correlated with age after multiplicity correction. Large lipid resonances were observed in the brain midline of some subjects, the incidence increasing significantly with age. We believe this to result from lipid deposits in the falx cerebri. CONCLUSION: Since only short-echo spectroscopy showed a robust relationship between Cr and subject age, and detects more metabolites than long echo time, we conclude that short-echo is superior to long-echo for future aging studies. Future studies could usefully determine whether the Cr-age relationship is due to changes in concentration, T1, or both.     

Evaluation of cerebral gray and white matter metabolite differences by spectroscopic imaging at 4.1T

Using a 4.1 T whole body system, we have acquired ¹H spectroscopic imaging (SI) data of N-acetyl (NA) compounds, creatine (CR), and choline (CH) with nominal voxel sizes of 0.5 cc (1.15 cc after filtering). We have used the SI data to estimate differences in cerebral metabolites of human gray and white matter. To evaluate the origin of an increased CWNA and CWNA ratios in gray matter relative to white matter, we measured the T₁ and T₂ of CR, NA, and CH in gray and white matter using moderate resolution SI imaging. In white matter the T₂s of NA, CR, and CH were 233 ± 27,141 ± 18, and 167 ± 20 ms, respectively, and 227 ± 27,140 ± 16, and 189 ± 25 ms in gray matter. The T, values for NA, CR, and CH were 1267 ±141, 1487 ± 146, and 1111 ± 136 ms in gray matter and 1260 ± 154, 1429 & 233, and 1074 ± 146 ms in white matter. After correcting for T₁ and T₂ losses, creatine content was significantly lower in white matter than gray (P < e 0.01, t-test), with a white/gray content ratio of 0.8, in agreement with biopsy and in vivo measurements at 1.5 and 2.0T.