Can magnetic resonance spectroscopy predict neurodevelopmental outcome in very low birth weight preterm infants?

OBJECTIVE: To determine if metabolite ratios at near-term age predict outcome in very low birth weight preterm infants at 18 to 24 months adjusted age. STUDY DESIGN: Thirty-six infants (birth weight

Optimization of fast spiral chemical shift imaging using least squares reconstruction: application for hyperpolarized (13)C metabolic imaging.

A least-squares-based optimization and reconstruction algorithm has been developed for rapid metabolic imaging in the context of hyperpolarized (13)C. The algorithm uses a priori knowledge of resonance frequencies, J-coupling constants, and T(2)* values to enable acquisition of high-quality metabolic images with imaging times of approximately 100 ms for an 8-cm field of view (FOV) and 0.5 cm isotropic resolution. A root-mean-square error (rMSE) analysis is introduced to optimize metabolic image quality by appropriate choice of pulse sequence parameters, echo times, and signal model. By performing the reconstruction in k-space, the algorithm also allows the inclusion of the effect of chemical shift evolution during the readout period. Single-interleaf multiecho spiral chemical shift imaging (spCSI) is analyzed in detail as an illustrative example for the use of the new reconstruction and optimization algorithm. Simulation of the in vivo spectrum following the bolus injection of hyperpolarized (13)C(1) pyruvate shows that single-interleaf spiral spectroscopic imaging can achieve image quality in 100 ms, comparable to the performance of a 13-s phase-encoded chemical shift imaging (FIDCSI) experiment. Single-interleaf spCSI was also tested at a 3-T MR scanner using a phantom containing approximately 0.5-M solutions of alanine, lactate, and a pyruvate-pyruvate hydrate C(1)-C(2) ester at thermal equilibrium polarization, all enriched to 99% (13)C in the C(1) carbonyl positions. Upon reconstruction using the k-space-based least-squares technique, metabolite ratios obtained using the spCSI method were comparable to those obtained using a reference FIDCSI acquisition.

Temporal lobe magnetic resonance spectroscopic imaging following selective amygdalohippocampectomy for treatment-resistant epilepsy.

OBJECTIVES: Magnetic resonance spectroscopic imaging (MRSI) may show circumscribed or extensive decreased brain N-acetyl aspartate (NAA)/creatine and phosphocreatine (Cr) in epilepsy patients. We compared temporal lobe MRSI in patients seizure-free (SzF) or with persistent seizures (PSz) following selective amygdalohippocampectomy (SAH) for medically intractable mesial temporal lobe epilepsy (mTLE). We hypothesized that PSz patients had more extensive temporal lobe metabolite abnormalities than SzF patients. MATERIALS AND METHODS: MRSI was used to study six regions of interest (ROI) in the bilateral medial and lateral temporal lobes in 14 mTLE patients following SAH and 11 controls. RESULTS: PSz patients had more temporal lobe ROI with abnormally low NAA/Cr than SzF patients, including the unoperated hippocampus and ipsilateral lateral temporal lobe. CONCLUSION: Postoperative temporal lobe MRSI abnormalities are more extensive if surgical outcome following SAH is poor. MRSI may be a useful tool to improve selection of appropriate candidates for SAH by identifying patients requiring more intensive investigation prior to epilepsy surgery. Future prospective studies are needed to evaluate the utility of MRSI, a predictor of successful outcome following SAH.

Zero-quantum filter offering single-shot lipid suppression and simultaneous detection of lactate, choline, and creatine resonances.

A zero-quantum (ZQ) filter offering single-shot lipid suppression and providing for simultaneous detection of the lactate methyl doublet (1.3 ppm) and nonoverlapping singlets including choline (Cho, 3.2 ppm) and creatine (Cr, 3.0 ppm) is described. Filtering is provided by soft mixing and reading pulses (RF(mix), RF(rd)) that are selective for the lactate methine quartet (4.1 ppm), Cho, and Cr resonances but exclude the 1.3 ppm lactate component and overlapping lipids. Surrounding RF(mix) and RF(rd) are magnetic field gradient pulses of equal magnitude but opposite signs to enable the rephasing of the zero-quantum lactate coherence and the creation of a stimulated echo for singlets within the pulse passbands. The sequence is designed to retain half the original lactate and singlet signal intensities. Theoretical predictions were confirmed experimentally at 1.5T using phantom acquisitions. The lipid suppression factor was measured to be over 10(3).

Effects of forced diving on the spleen and hepatic sinus in northern elephant seal pups.

In phocid seals, an increase in hematocrit (Hct) accompanies diving and periods of apnea. The variability of phocid Hct suggests that the total red cell mass is not always in circulation, leading researchers to speculate on the means of blood volume partitioning. The histology and disproportionate size of the phocid spleen implicates it as the likely site for RBC storage. We used magnetic resonance imaging on Northern elephant seals to demonstrate a rapid contraction of the spleen and a simultaneous filling of the hepatic sinus during forced dives (P < 0.0001, R(2) = 0.97). The resulting images are clear evidence demonstrating a functional relationship between the spleen and hepatic sinus. The transfer of blood from the spleen to the sinus provides an explanation for the disparity between the timing of diving-induced splenic contraction ( approximately 1-3 min) and the occurrence of peak Hct (15-25 min). Facial immersion was accompanied by an immediate and profound splenic contraction, with no further significant decrease in splenic volume after min 2 (Tukey-Kramer HSD, P = 0.05). At the conclusion of the dive, the spleen had contracted to 16% of its predive volume (mean resting splenic volume = 3,141 ml +/- 68.01 ml; 3.54% of body mass). In the postdive period, the spleen required 18-22 min to achieve resting volume, indicating that this species may not have sufficient time to refill the spleen when routinely diving at sea, which is virtually continuous with interdive surface intervals between 1 and 3 min.

Longitudinal decline of the neuronal marker N-acetyl aspartate in Alzheimer's disease.

In patients with Alzheimer's disease, but not in health controls, longitudinal magnetic resonance spectroscopy shows a striking decline in the neuronal marker, N-acetyl aspartate, despite little decline in underlying grey-matter volume.

Optimal voxel size for measuring global gray and white matter proton metabolite concentrations using chemical shift imaging.

Quantification of gray and white matter levels of spectroscopically visible metabolites can provide important insights into brain development and pathological conditions. Chemical shift imaging offers a gain in efficiency for estimation of global gray and white matter metabolite concentrations compared to single voxel methods. In the present study, the optimal voxel size is calculated from segmented human brain data and accompanying field maps. The optimal voxel size is found to be approximately 8 cc, but a wide range of values, 4-64 cc, can be chosen with little increase in estimated concentration error (<15%). Magn Reson Med 44:10-18, 2000.

Motion correction and lipid suppression for 1H magnetic resonance spectroscopy.

Spectral/spatial spin-echo pulses with asymmetric excitation profiles were incorporated into a PRESS-based localization sequence to provide lipid suppression while retaining a sufficient amount of water to allow for correction of motion-induced shot-to-shot phase variations. 1H magnetic resonance spectroscopy data were acquired at 1.5 Tesla from a motion phantom and in vivo from the human liver, kidney, and breast. The results demonstrated that lipids in the chemical shift stopband were completely suppressed and that full metabolite signal intensity was maintained after implementation of a regularization algorithm based on phasing the residual water signal. Liver and kidney spectra contained a large resonance at 3.2 ppm that was ascribed to trimethylammonium moieties (betaine plus choline) and a weaker signal at 3.7 ppm that may result from glycogen. A breast spectrum from a histologically proven invasive ductal carcinoma displayed a highly elevated choline signal (3.2 ppm) relative to that from a normal volunteer.

In vivo 1H MR spectroscopy of human head and neck lymph node metastasis and comparison with oxygen tension measurements.

BACKGROUND AND PURPOSE: Current diagnostic methods for head and neck metastasis are limited for monitoring recurrence and assessing oxygenation. 1H MR spectroscopy (1H MRS) provides a noninvasive means of determining the chemical composition of tissue and thus has a unique potential as a method for localizing and characterizing cancer. The purposes of this investigation were to measure 1H spectral intensities of total choline (Cho), creatine (Cr), and lactate (Lac) in vivo in human lymph node metastases of head and neck cancer for comparison with normal muscle tissue and to examine relationships between metabolite signal intensities and tissue oxygenation status. METHODS: Volume-localized Lac-edited MRS at 1.5 T was performed in vivo on the lymph node metastases of 14 patients whose conditions were untreated and who had primary occurrences of squamous cell carcinoma. MRS measurements were acquired also from the neck muscle tissue of six healthy volunteers and a subset of the patients. Peak areas of Cho, Cr, and Lac were calculated. Tissue oxygenation (pO2) within the abnormal lymph nodes was measured independently using an Eppendorf polarographic oxygen electrode. RESULTS: Cho:Cr ratios were significantly higher in the nodes than in muscle tissue (node Cho:Cr = 2.9 +/- 1.6, muscle Cho:Cr = 0.55 +/- 0.21, P = .0006). Lac was significantly higher in cancer tissue than in muscle (P = .01) and, in the nodes, showed a moderately negative correlation with median pO2 (r = -.76) over a range of approximately 0 to 30 mm Hg. Nodes with oxygenation values less than 10 mm Hg had approximately twice the Lac signal intensity as did nodes with oxygenation values greater than 10 mm Hg (P = .01). Cho signal intensity was not well correlated with pO2 (r = -.46) but seemed to decrease at higher oxygenation levels (>20 mm Hg). CONCLUSION: 1H MRS may be useful for differentiating metastatic head and neck cancer from normal muscular tissue and may allow for the possibility of assessing oxygenation. Potential clinical applications include the staging and monitoring of treatment.

Reduced spatial side lobes in chemical-shift imaging.

Density-weighted k-space sampling with spiral trajectories is used to reduce spatial side lobes in chemical-shift imaging (CSI). In this method, more time is spent collecting data at the center of k space and less time at the edges of k space in order to make the sampling density proportional to a given apodization function, subject to constraints imposed by gradient performance and Nyquist sampling. The efficient k-space coverage of spiral-based trajectories enables good control over the sampling density within practical in vivo scan times. The density-weighted acquisition is compared to a conventional, nonweighted spiral sampling without the application of a window function. For a fixed voxel size and imaging time, the noise variance is observed to be the same for both cases, while spatial side lobes are greatly reduced with the variable-density sampling. This method is demonstrated on a normal volunteer by imaging of brain metabolites at 1.5 T with both single slice CSI and volumetric CSI. Magn Reson Med 42:314-323, 1999.

Spatially resolved two-dimensional spectroscopy.

A method is presented to collect spatially resolved two-dimensional spectra on a conventional clinical scanner. Time-varying gradients during the readout period rapidly sample data simultaneously for two spatial and two spectral dimensions. The k-space trajectories are based on spiral paths that make efficient use of the gradient hardware. A gridding algorithm is used for reconstruction. With the spiral-based readout gradients, current single-voxel two-dimensional techniques can be extended to spatially resolved volumetric acquisitions. The method is demonstrated with a two-dimensional J-resolved acquisition of a phantom with separate compartments of lactic acid and ethyl alcohol in water. Data were acquired with a spatial resolution of 18 x 18 pixels over a 24 cm field of view, 400 Hz spectral bandwidth in the chemical shift dimension with a 3.8 Hz resolution, and 50 Hz spectral bandwidth in the second frequency dimension with a 1.56 Hz resolution.

Feasibility study of lactate imaging of head and neck tumors.

A proton spectroscopic imaging sequence was used to investigate the feasibility of lactate imaging in head and neck tumors. The sequence employs a two-shot lactate editing method with inversion recovery for additional lipid suppression, and a restricted field of view to suppress motion artifacts. Variations in acquisition parameters and two different receive coils were investigated on twelve patients. Elevated lactate was detected in three patients, no lactate was observed in seven patients, and two studies were inconclusive because of severe motion or inhomogeneity artifacts. Best results were obtained with an anterior/posterior neck coil at a 288 ms echo time (TE).

Strategy for lipid suppression in lactate imaging using STIR-DQCT: a study of hypoxic-ischemic brain injury.

In vivo lactate detection using gradient enhanced double quantum coherence transfer (DQCT) was significantly improved by addition of short-time-inversion-recovery (STIR). Phantom studies demonstrated lipid suppression down to the background noise level with 33% loss of lactate signal. In vivo studies using a rabbit model of hypoxic and unilateral-ischemic brain injury showed reduction down to 29 +/- 11% in lipids with inversion times between 140 and 170 ms. Lactate signals on the ischemic side were 51 +/- 53% higher than the nonischemic side at the peak of hypoxia. STIR-DQCT can be a useful robust method of obtaining metabolic maps of lactate in vivo.

Quantitative assessment of improved homogeneity using higher-order shims for spectroscopic imaging of the brain.

Magnetic field homogeneity is of major concern for in vivo spectroscopy, and with the increased use of volumetric chemical shift imaging (CSI) techniques, the ability to shim over a large volume of tissue is now one of the primary limiting constraints in performing these studies. In vivo shimming is routinely performed using linear shim correction terms, and although many scanners are also equipped with additional resistive shim supplies that can provide second and third-order shim fields, they are often not used due to the additional effort and scan time required. The question as to how much improvement can be achieved using additional higher-order shims compared with the linear shims alone was quantitatively addressed. Performance measures for both intervoxel B0 uniformity and intravoxel T2* line broadening were evaluated for 15 normal volunteers. The analysis tools developed in this study, along with the summarized data, can be useful in deciding if a given application warrants the additional time, effort, and expense (if additional hardware needs to be purchased) of implementing higher-order shimming routines. For CSI studies of the brain, the use of the higher-order shims, compared with linear terms alone, yielded approximately 30% greater volume of brain tissue that could be shimmed within typical constraints for intervoxel B0 shifts and intravoxel T2* linebroadening. In addition, a regional analysis shows significant improvement in the homogeneity within specific areas of the brain, particularly those near the skull.

Volumetric spectroscopic imaging with spiral-based k-space trajectories.

Spiral-based k-space trajectories were applied in a spectroscopic imaging sequence with time-varying readout gradients to collect volumetric chemical shift information. In addition to spectroscopic imaging of low signal-to-noise ratio (SNR) brain metabolites, the spiral trajectories were used to rapidly collect reference signals from the high SNR water signal to automatically phase the spectra and to aid the reconstruction of metabolite maps. Spectral-spatial pulses were used for excitation and water suppression. The pulses were designed to achieve stable phase profiles in the presence of up to 20% variation in the radiofrequency field. A gridding algorithm was used to resample the data onto a rectilinear grid before fast Fourier transforms. This method was demonstrated by in vivo imaging of brain metabolites at 1.5 T with 10 slices of 18 x 18 pixels each. Nominal voxel size was 1.1 cc, spectral bandwidth was 400 Hz, scan time was 18 min for the metabolite scan and 3 min for the reference scan.

Impaired cerebrovascular autoregulation after hypoxic-ischemic injury in extremely low-birth-weight neonates: detection with power and pulsed wave Doppler US.

PURPOSE: To evaluate regional cerebral blood flow with power and pulsed wave Doppler ultrasound (US) in extremely low-birth-weight neonates with periventricular leukomalacia (PVL), germinal matrix hemorrhage (GMH), or both. MATERIALS AND METHODS: The lenticulostriate arteries of 17 preterm neonates (birth weight < or = 1,100 g) were assessed daily with Doppler US during the first 5-6 days of life. The mean arterial pressure and bilateral peak velocity, resistive index, coronal vascular cross-sectional area, and product of the peak velocity and vascular cross-sectional area were measured. RESULTS: Five neonates developed PVL, GMH, or both; results of follow-up examinations in 11 patients were normal. One neonate with severe intrauterine growth retardation and renal tubular acidosis was excluded. Neonates with PVL, GMH, or both showed significantly greater mean values and more variable values of vascular cross-sectional area and product of peak velocity and cross-sectional area than neonates without PVL or GMH (P < .025). Mean resistive index was significantly lower in neonates with PVL, GMH, or both than in neonates without (P < .01). There were no significant differences between mean arterial pressure in neonates with and those without PVL, GMH, or both. CONCLUSION: By enabling the detection of autoregulatory fluctuations in cerebral blood flow associated with hypoxic-ischemic injury, power and pulsed wave Doppler US may enable identification of preterm neonates who are at risk of developing PVL, GMH, or both during the 1st week of life.

Estimating NAA in cortical gray matter with applications for measuring changes due to aging.

N-acetylaspartic acid (NAA), a prominent peak in the proton spectrum, is an amino acid thought to be present almost exclusively in neurons and their dendritic and axonal extensions. While 1H MRS studies are showing promise in identifying NAA deficits in different patient groups, unwanted lipid signal from subcutaneous fat surrounding the skull, and necessarily large voxels have limited investigators' ability to assess NAA in cortical gray matter. Here we report a technique developed to derive estimates of NAA signal from cortical gray matter. This approach uses an inversion recovery imaging pulse sequence with a long TE to suppress lipid signal from the scalp and information from concurrently obtained structural MR images to determine the CSF, white and gray matter composition of each spectroscopic voxel. A regression analysis is then used to estimate what NAA levels would be in "pure" white and gray matter voxels. This technique has been applied to demonstrate reduced NAA gray/white levels in the brains of five healthy older compared with five healthy younger women.

A model for detecting early metabolic changes in neonatal asphyxia by 1H-MRS.

In newborn rabbits, the early cerebral metabolic changes caused by hypoxic-ischemic (H-I) insult was examined by using volume localized 1H-MRS (STEAM). Partial ischemia was caused by unilateral carotid artery ligation, and hypoxia was induced by 10% oxygen inspiration for 150 minutes. Lactate immediately increased after hypoxia induction and almost disappeared 120 to 150 minutes after removal of hypoxia in both H-I and hypoxia-only experiments. Lactate production correlated well with decrease of the blood oxygen saturation. More lactate was produced on ischemic side 50 minutes post-hypoxia induction in H-I study. Ischemia alone did not cause any significant lactate production. Lactate caused by hypoxia can be dynamically monitored by localized 1H-MRS. Existence of regional ischemia can induce greater anaerobic glycolysis and may affect the pattern of brain injury under hypoxia. 1H-MRS is a sensitive tool to detect the acute metabolic change caused by H-I insult.

Magnetic resonance imaging of human brain function.

BACKGROUND: Previously the exclusive domain of the technology of positron emission tomography, functional MRI is now proving capable of mapping functional regions of the human cortex in near real time during specific task activations or in response to any hemodynamic stress. Of particular interest is the opportunity to observe secondary cortical responses, activation due to imagined tasks, memory function, time-resolved pathways through cortical regions, and activation in sub-cortical structures. METHODS AND RESULTS: One method of functional MRI uses blood oxygenation changes, which can be imaged continuously while functional centers are being stimulated. Image intensity can become darker if there is more deoxygenated blood and brighter if more oxygenated blood enters the brain. This concepts works in all perfused tissues in the body, and allows use of the blood oxygenation mechanism to image neuronal activation. A second method takes advantage of the fact that the protons within the MRI slice are always partially saturated by the rapid rate of imaging. As blood flow delivers unsaturated blood water protons into an imaged slice, these arterially-delivered protons will appear very bright in the image. Visualization of this effect is accomplished by simple image subtraction or by comparison of intensity changes as a function of the paradigm application frequency. Using either approach leads directly to a functional map. CONCLUSIONS: At present, clinical applications are rapidly moving toward routine non-invasive mapping of distortions of the functional motor and somatosensory cortex and other cortical regions as a result of brain tumors. Other clinical applications include the observation of the effect of degenerative diseases such as multiple sclerosis. Alzheimer's disease, stroke, migraine, epilepsy, and other diseases causing neuronal loss and Parkinsonism. Functional MRI and its applications will continue to grow exponentially throughout the decade.