Daniel M. Spielman

In vivo spectroscopic quantification of the N-acetyl moiety, creatine, and choline from large volumes of brain gray and white matter: effects of normal aging.

Volumetric proton magnetic resonance spectroscopic imaging (MRSI) was used to generate brain metabolite maps in 15 young and 19 elderly adult volunteers. All subjects also had structural MR scans, and a model, which took into account the underlying structural composition of the brain contributing to each metabolite voxel, was developed and used to estimate the concentration of the N‐acetyl‐moiety (NAc), creatine (Cr), and choline (Cho) in gray matter and white matter. NAc concentration (signal intensity per unit volume of brain) was higher in gray than white matter and did not differ between young and old subjects despite significant gray matter volume deficits in the older subjects. To the extent that NAc is an index of neuronal integrity, the available gray matter appears to be intact in these older healthy adults. Cr concentrations were much higher in gray than white matter and significantly higher in the old than young subjects. Cho concentration in gray matter was also significantly higher in old than young subjects. Independent determination of metabolite values rather than use of ratios is essential for characterizing age‐related changes in brain MRS metabolites. Magn Reson Med 41:276–284, 1999. Published 1999 Wiley‐Liss, Inc.

Decreased dorsolateral prefrontal N-acetyl aspartate in bipolar disorder.

Background: N-acetyl aspartate (NAA) is an amino acid present in high concentrations in neurons and is thus a putative neuronal marker. In vivo proton magnetic resonance spectroscopy (1H MRS) studies have shown lower NAA concentrations in patients with various neurodegenerative disorders, suggesting decreased neuronal number, size, or function. Dorsolateral prefrontal (DLPF) NAA has not been extensively assessed in bipolar disorder patients, but it could be decreased in view of consistent reports of decreased DLPF cerebral blood flow and metabolism in mood disorders. We measured DLPF NAA in patients with bipolar disorder and healthy control subjects using in vivo 1H MRS. Methods: We obtained ratios of NAA, choline, and myoinositol (mI) to creatine-phosphocreatine (Cr-PCr) in bilateral DLPF 8-mL voxels of 20 bipolar patients (10 Bipolar I, 10 Bipolar II) and 20 age- and gender-matched healthy control subjects using 1H MRS. Results: DLPF NAA/Cr-PCr ratios were lower on the right hemisphere(p < .03) and the left hemisphere (p < .003) in bipolar disorder patients compared with healthy control subjects. Conclusions: These preliminary data suggest that bipolar disorder patients have decreased DLPF NAA/Cr-PCr. This finding could represent decreased neuronal density or neuronal dysfunction in the DLPF region.

Regularized higher-order in vivo shimming

A regularized algorithm is presented for localized in vivo shimming. The technique uses first‐ (X,Y,Z), second‐ (Z2, ZX, ZY, X2‐Y2, XY), and third‐order (Z3) shim coils, and is robust when applied to arbitrarily‐shaped, as well as off‐center, regions of interest (ROIs). A single‐shot spiral pulse sequence is used for rapid field map acquisition, and a least‐squares calculation of the shim currents is performed to minimize the root‐mean‐square (RMS) value of the B0 inhomogeneity over a user‐selected ROI. The use of a singular value decomposition (SVD) in combination with a regularization algorithm significantly improves the numerical stability of the least‐squares fitting procedure. The fully automated shimming package is implemented on a 3 T GE Signa system and its robust performance is demonstrated in phantom and in vivo studies. Magn Reson Med 48:715–722, 2002.

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

In patients with Alzheimers 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.

Low N-acetyl-aspartate and high choline in the anterior cingulum of recently abstinent methamphetamine-dependent subjects: a preliminary proton MRS study

Studies based on animal models report that methamphetamine (MA) abuse diminishes dopamine (DA) and serotonin innervation in frontal brain regions. In this in vivo human study, we used proton magnetic resonance spectroscopy (MRS), which yields measures of N-acetyl-aspartate (NAA), a marker of living neurons, to examine frontal brain regions possibly affected by methamphetamine dependence (MD). We tested the hypothesis that MD subjects would exhibit abnormally low levels of NAA, referenced to creatine (Cr), in anterior cingulate gray matter. We further hypothesized that the primary visual cortex, which receives relatively less DA innervation than the frontal brain regions, would show normal NAA/Cr ratios in MD subjects. Subjects included nine MD men (mean+/-standard deviation (S.D.)=32.5+/-6.4 years) and nine age-matched control men (mean+/-S.D.=32.7+/-6.8 years). The MD subjects were MA-free for 4-13 weeks. Proton MRS metabolites were expressed as ratios of creatine; the absolute values of which did not distinguish controls and MD subjects. With regard to metabolite ratios, the MD men had significantly lower NAA/Cr in the cingulum (mean+/-standard error (S.E.): control=1.46+/-0.03; MD=1.30+/-0.03; Mann-Whitney P=0.01) but not in the visual cortex (mean+/-S.E.: control=1.64+/-0.06; MD=1.69+/-11; Mann-Whitney P=0.52) relative to controls. These results provide evidence for NAA/Cr deficit that is selective to the anterior cingulum, at least with respect to visual cortex, in MD subjects. The neuronal compromise that these changes reflect may contribute to the attentional deficits and dampened reward system in MD.

Simple analytic variable density spiral design.

Variable density spirals have been proposed in a variety of applications, including MR fluoroscopy, cardiac imaging, and MR spectroscopic imaging. In this work, a simple analytic solution for designing a flexible set of variable density spiral trajectory waveforms is presented. The method enables real‐time waveform prescription on scanners with limited computational power. Both slew rate‐limited and amplitude‐limited regimes are incorporated in the design process. Magn Reson Med 50:214–219, 2003.

Mapping of the prostate in endorectal coil-based MRI/MRSI and CT: a deformable registration and validation study.

The endorectal coil is being increasingly used in magnetic resonance imaging (MRI) and MR spectroscopic imaging (MRSI) to obtain anatomic and metabolic images of the prostate with high signal-to-noise ratio (SNR). In practice, however, the use of endorectal probe inevitably distorts the prostate and other soft tissue organs, making the analysis and the use of the acquired image data in treatment planning difficult. The purpose of this work is to develop a deformable image registration algorithm to map the MRI/MRSI information obtained using an endorectal probe onto CT images and to verify the accuracy of the registration by phantom and patient studies. A mapping procedure involved using a thin plate spline (TPS) transformation was implemented to establish voxel-to-voxel correspondence between a reference image and a floating image with deformation. An elastic phantom with a number of implanted fiducial markers was designed for the validation of the quality of the registration. Radiographic images of the phantom were obtained before and after a series of intentionally introduced distortions. After mapping the distorted phantom to the original one, the displacements of the implanted markers were measured with respect to their ideal positions and the mean error was calculated. In patient studies, CT images of three prostate patients were acquired, followed by 3 Tesla (3 T) MR images with a rigid endorectal coil. Registration quality was estimated by the centroid position displacement and image coincidence index (CI). Phantom and patient studies show that TPS-based registration has achieved significantly higher accuracy than the previously reported method based on a rigid-body transformation and scaling. The technique should be useful to map the MR spectroscopic dataset acquired with ER probe onto the treatment planning CT dataset to guide radiotherapy planning.

MELAS Clinical and pathologic correlations with MRI, xenon/CT, and MR spectroscopy

Article abstract-We describe the clinical, imaging, and pathologic findings in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). The patient experienced her first stroke-like episode at age forty-four. Brain MRI, obtained at symptom onset, at 3 weeks, and at 1 year, revealed migrating T2-weighted hyperintensities in the temporal/parietal and occipital cortices and later revealed atrophy. Abnormal cerebrovascular reserve was evident on xenon/CT four days after the first MRI. MR spectroscopy at 1 year revealed increased lactate in both the occipital and the temporal lobes. Histologic sections demonstrated spongy degeneration of the cortex that was most prominent at the crests of the gyri. Electron microscopy of the blood vessels showed increased numbers of abnormal mitochondria within the vascular smooth muscle and in endothelial cells. We hypothesize that the stroke-like episodes in MELAS may be due to impaired autoregulation secondary to the impaired metabolic activity of mitochondria in the endothelial and smooth muscle cells of blood vessels. NEUROLOGY 1996;46 223-227

Application of subsecond spiral chemical shift imaging to real-time multislice metabolic imaging of the rat in vivo after injection of hyperpolarized 13C1-pyruvate.

Dynamic nuclear polarization can create hyperpolarized compounds with MR signal‐to‐noise ratio enhancements on the order of 10,000‐fold. Both exogenous and normally occurring endogenous compounds can be polarized, and their initial concentration and downstream metabolic products can be assessed using MR spectroscopy. Given the transient nature of the hyperpolarized signal enhancement, fast imaging techniques are a critical requirement for real‐time metabolic imaging. We report on the development of an ultrafast, multislice, spiral chemical shift imaging sequence, with subsecond acquisition time, achieved on a clinical MR scanner. The technique was used for dynamic metabolic imaging in rats, with measurement of time‐resolved spatial distributions of hyperpolarized 13C1‐pyruvate and metabolic products 13C1‐lactate and 13C1‐alanine, with a temporal resolution of as fast as 1 s. Metabolic imaging revealed different signal time courses in liver from kidney. These results demonstrate the feasibility of real‐time, hyperpolarized metabolic imaging and highlight its potential in assessing organ‐specific kinetic parameters. Magn Reson Med, 2009.

Metabolic imaging in the anesthetized rat brain using hyperpolarized [1-13C] pyruvate and [1-13C] ethyl pyruvate.

Formulation, polarization, and dissolution conditions were developed to obtain a stable hyperpolarized solution of [1‐13C]‐ethyl pyruvate. A maximum tolerated concentration and injection rate were determined, and 13C spectroscopic imaging was used to compare the uptake of hyperpolarized [1‐13C]‐ethyl pyruvate relative to hyperpolarized [1‐13C]‐pyruvate into anesthetized rat brain. Hyperpolarized [1‐13C]‐ethyl pyruvate and [1‐13C]‐pyruvate metabolic imaging in normal brain is demonstrated and quantified in this feasibility and range‐finding study. Magn Reson Med 63:1137–1143, 2010.