Intensity warping for multisite MRI harmonization.

In multisite neuroimaging studies there is often unwanted technical variation across scanners and sites. These "scanner effects" can hinder detection of biological features of interest, produce inconsistent results, and lead to spurious associations. We propose mica (multisite image harmonization by cumulative distribution function alignment), a tool to harmonize images taken on different scanners by identifying and removing within-subject scanner effects. Our goals in the present study were to (1) establish a method that removes scanner effects by leveraging multiple scans collected on the same subject, and, building on this, (2) develop a technique to quantify scanner effects in large multisite studies so these can be reduced as a preprocessing step. We illustrate scanner effects in a brain MRI study in which the same subject was measured twice on seven scanners, and assess our method's performance in a second study in which ten subjects were scanned on two machines. We found that unharmonized images were highly variable across site and scanner type, and our method effectively removed this variability by aligning intensity distributions. We further studied the ability to predict image harmonization results for a scan taken on an existing subject at a new site using cross-validation.

Distinguishing Extravascular from Intravascular Ferumoxytol Pools within the Brain: Proof of Concept in Patients with Treated Glioblastoma.

BACKGROUND AND PURPOSE: Glioblastoma-associated macrophages are a major constituent of the immune response to therapy and are known to engulf the iron-based MR imaging contrast agent, ferumoxytol. Current ferumoxytol MR imaging techniques for localizing macrophages are confounded by contaminating intravascular signal. The aim of this study was to assess the utility of a newly developed MR imaging technique, segregation and extravascular localization of ferumoxytol imaging, for differentiating extravascular-from-intravascular ferumoxytol contrast signal at a delayed 24-hour imaging time point. MATERIALS AND METHODS: Twenty-three patients with suspected post-chemoradiotherapy glioblastoma progression underwent ferumoxytol-enhanced SWI. Segregation and extravascular localization of ferumoxytol imaging maps were generated as the voxelwise difference of the delayed (24 hours) from the early (immediately after administration) time point SWI maps. Continuous segregation and extravascular localization of ferumoxytol imaging map values were separated into positive and negative components. Image-guided biologic correlation was performed. RESULTS: Negative segregation and extravascular localization of ferumoxytol imaging values correlated with early and delayed time point SWI values, demonstrating that intravascular signal detected in the early time point persists into the delayed time point. Positive segregation and extravascular localization of ferumoxytol imaging values correlated only with delayed time point SWI values, suggesting successful detection of the newly developed extravascular signal. CONCLUSIONS: Segregation and extravascular localization of ferumoxytol MR imaging improves on current techniques by eliminating intrinsic tissue and intravascular ferumoxytol signal and may inform glioblastoma outcomes by serving as a more specific metric of macrophage content compared with uncorrected T1 and SWI techniques.

Magnetic resonance imaging of the proximal upper extremity musculature in boys with Duchenne muscular dystrophy.

There is a pressing need for biomarkers and outcomes that can be used across disease stages in Duchenne muscular dystrophy (DMD), to facilitate the inclusion of a wider range of participants in clinical trials and to improve our understanding of the natural history of DMD. Quantitative magnetic resonance imaging (qMRI) and spectroscopy (MRS) biomarkers show considerable promise in both the legs and forearms of individuals with DMD, but have not yet been examined in functionally important proximal upper extremity muscles such as the biceps brachii and deltoid. The primary objective of this study was to examine the feasibility of implementing qMRI and MRS biomarkers in the proximal upper extremity musculature, and the secondary objective was to examine the relationship between MR measures of arm muscle pathology and upper extremity functional endpoints. Biomarkers included MRS and MRI measures of fat fraction and transverse relaxation time (T 2). The MR exam was well tolerated in both ambulatory and non-ambulatory boys. qMR biomarkers differentiated affected and unaffected participants and correlated strongly with upper extremity function (r = 0.91 for biceps brachii T 2 versus performance of upper limb score). These qMR outcome measures could be highly beneficial to the neuromuscular disease community, allowing measurement of the quality of functionally important muscles across disease stages to understand the natural history of DMD and particularly to broaden the opportunity for clinical trial participation.

Characterizing the white matter hyperintensity penumbra with cerebral blood flow measures.

OBJECTIVE: White matter hyperintensities (WMHs) are common with age, grow over time, and are associated with cognitive and motor impairments. Mechanisms underlying WMH growth are unclear. We aimed to determine the presence and extent of decreased normal appearing white matter (NAWM) cerebral blood flow (CBF) surrounding WMHs to identify 'WM at risk', or the WMH CBF penumbra. We aimed to further validate cross-sectional finding by determining whether the baseline WMH penumbra CBF predicts the development of new WMHs at follow-up. METHODS: Sixty-one cognitively intact elderly subjects received 3 T MPRAGE, FLAIR, and pulsed arterial spin labeling (PASL). Twenty-four subjects returned for follow-up MRI. The inter-scan interval was 18 months. A NAWM layer mask, comprised of fifteen layers, 1 mm thick each surrounding WMHs, was generated for periventricular (PVWMH) and deep (DWMH) WMHs. Mean CBF for each layer was computed. New WMH and persistent NAWM voxels for each penumbra layer were defined from follow-up MRI. RESULTS: CBF in the area surrounding WMHs was significantly lower than the total brain NAWM, extending approximately 12 mm from both the established PVWMH and DWMH. Voxels with new WMH at follow-up had significantly lower baseline CBF than voxels that maintained NAWM, suggesting that baseline CBF can predict the development of new WMHs over time. CONCLUSIONS: A CBF penumbra exists surrounding WMHs, which is associated with future WMH expansion. ASL MRI can be used to monitor interventions to increase white matter blood flow for the prevention of further WM damage and its cognitive and motor consequences.

Loss of pons-to-hypothalamic white matter tracks in brainstem obesity.

Hyperphagia and obesity have been reported following damage to the hypothalamus in humans. Other brain sites are also postulated to be involved in the control of food intake and body weight regulation, such as the amygdala and brainstem. The brainstem, however, is thought to primarily integrate short-term meal-related signals but not affect long-term alterations in body weight, which is controlled by higher centers. The objective of this study was to identify structural pathways damaged in a patient with a brainstem cavernoma who experienced sudden onset of hyperphagia and >50 kg weight gain in <1 year following surgical drainage via a midline suboccipital craniotomy. Diffusion tensor imaging revealed loss of nerve fiber connections between her brainstem, hypothalamus and higher brain centers with preservation of motor tracks. Imaging and endocrine testing confirmed normal hypothalamic structure and function. Gastric bypass surgery restored normal appetite and body weight to baseline. This is the first report of 'brainstem obesity' and adds to the brain regions that can determine the long-term body weight set point in humans.

Comparison of 3 T MRI and CT for the measurement of visceral and subcutaneous adipose tissue in humans.

OBJECTIVE: CT is considered the gold standard imaging modality for measurement of visceral adipose tissue area. However, as CT imaging exposes subjects to ionising radiation, a comparable imaging technique without this exposure is desirable, such as MRI. Therefore, we compared the agreement of measures of visceral adipose tissue and subcutaneous adipose tissue area from single-slice images obtained at the umbilicus using a 3 T MRI scanner with single-slice images obtained via CT scan. METHODS: 64 images were obtained from 27 subjects who underwent MRI and CT scanning on the same day, after 10-12 hours of fasting. Visceral and subcutaneous adipose tissue depots were manually separated and quantified using a multimodality image-processing software program. RESULTS: We found good agreement between CT and MRI for the measurement of both visceral adipose tissue and subcutaneous adipose tissue. Bland-Altman difference analysis demonstrated a mean bias of -2.9% (as a portion of total abdominal area) for visceral adipose tissue and +0.4% for subcutaneous adipose tissue, as measured by MRI compared with CT. CONCLUSION: MRI is a safe, accurate and precise imaging modality for measuring both visceral and subcutaneous adipose tissue, making it a favourable alternative to CT for quantification of these adipose depots.

Neuroimaging features of neurodegeneration with brain iron accumulation.

NBIA characterizes a class of neurodegenerative diseases that feature a prominent extrapyramidal movement disorder, intellectual deterioration, and a characteristic deposition of iron in the basal ganglia. The diagnosis of NBIA is made on the basis of the combination of representative clinical features along with MR imaging evidence of iron accumulation. In many cases, confirmatory molecular genetic testing is now available as well. A number of new subtypes of NBIA have recently been described, with distinct neuroradiologic and clinical features. This article outlines the known subtypes of NBIA, delineates their clinical and radiographic features, and suggests an algorithm for evaluation.

Brain functional magnetic resonance imaging response to glucose and fructose infusions in humans.

AIMS: In animals, intracerebroventricular glucose and fructose have opposing effects on appetite and weight regulation. In humans, functional brain magnetic resonance imaging (fMRI) studies during glucose ingestion or infusion have demonstrated suppression of hypothalamic signalling, but no studies have compared the effects of glucose and fructose. We therefore sought to determine if the brain response differed to glucose vs. fructose in humans independently of the ingestive process. METHODS: Nine healthy, normal weight subjects underwent blood oxygenation level dependent (BOLD) fMRI measurements during either intravenous (IV) glucose (0.3 mg/kg), fructose (0.3 mg/kg) or saline, administered over 2 min in a randomized, double-blind, crossover study. Blood was sampled every 5 min during a baseline period and following infusion for 60 min in total for glucose, fructose, lactate and insulin levels. RESULTS: No significant brain BOLD signal changes were detected in response to IV saline. BOLD signal in the cortical control areas increased during glucose infusion (p = 0.002), corresponding with increased plasma glucose and insulin levels. In contrast, BOLD signal decreased in the cortical control areas during fructose infusion (p = 0.006), corresponding with increases of plasma fructose and lactate. Neither glucose nor fructose infusions significantly altered BOLD signal in the hypothalamus. CONCLUSION: In normal weight humans, cortical responses as assessed by BOLD fMRI to infused glucose are opposite to those of fructose. Differential brain responses to these sugars and their metabolites may provide insight into the neurologic basis for dysregulation of food intake during high dietary fructose intake.

Reanalysis of multislice (1)H MRSI in amyotrophic lateral sclerosis.

The goal of this work was to reexamine previously published (1) brain spectroscopy data of abnormal metabolite ratios in amyotrophic lateral sclerosis (ALS). Toward this goal, (1)H MR spectroscopic imaging data from 10 ALS and nine control subjects were reanalyzed using improved data analysis techniques, including automated curve fitting and tissue-volume correction. In the motor cortex of ALS, N-acetyl aspartate (NAA) was 23% (P = 0.004) lower than in controls, and in the posterior internal capsule of ALS choline compounds (Cho) were 20% (P = 0.02) higher. This demonstrates that the metabolite ratio changes in ALS were due to NAA loss in the motor cortex (as expected) and Cho increase in the posterior internal capsule (not expected). Magn Reson Med 45:513-516, 2001.

Resting brain metabolic activity in a 4 tesla magnetic field.

MRI is a major tool for mapping brain function; thus it is important to assess potential effects on brain neuronal activity attributable to the requisite static magnetic field. This study used positron emission tomography (PET) and (18)F-deoxyglucose ((18)FDG) to measure brain glucose metabolism (a measure of brain function) in 12 subjects while their heads were in a 4 T MRI field during the (18)FDG uptake period. The results were compared with those obtained when the subjects were in the earth's field (PET scanner), and when they were in a simulated MRI environment in the PET instrument that imitated the restricted visual field of the MRI experiment. Whole-brain metabolism, as well as metabolism in occipital cortex and posterior cingulate gyrus, was lower in the real (4 T) and simulated (0 T) MRI environments compared with the PET. This suggests that the metabolic differences are due mainly to the visual field differences characteristic of the MRI and PET instruments. We conclude that a static magnetic field of 4 T does not in itself affect this fairly sensitive measure of brain activity.

Determination of the MRI contrast agent concentration time course in vivo following bolus injection: effect of equilibrium transcytolemmal water exchange.

For bolus-tracking studies, it is commonly assumed that CR concentration bears a linear relationship with the measured (usually longitudinal) (1)H(2)O relaxation rate constant, R*(1) identical with(T(1) *)(-1). This requires that equilibrium transcytolemmal water exchange be in the fast exchange limit (FXL). However, though systems remain in fast exchange, the FXL will not usually obtain. Here, the consequences are considered: 1) the measurement of R(1) * itself can be affected, 2) the resultant non-linear [CR]-dependence causes significant error by assuming FXL, 3) the thermodynamic [CR] (based on the space in which CR is actually distributed) can be determined, 4) transcytolemmal water permeability may be estimated, and 5) the pharmacokinetic parameters can be factored. For a 30-sec, 0.17 mmol/kg dose of GdDTPA(2-), the FXL assumption underestimates the [CR] maximum in rat thigh muscle by a factor of almost two. Similar results are obtained for a rat brain GS-9L gliosarcoma tumor model.

4.0 T water proton T1 relaxation times in normal human brain and during acute ethanol intoxication.

BACKGROUND: It has been reported that acute ethanol intoxication decreases the brain water proton magnetic resonance T1 values, an effect that has been interpreted to indicate brain dehydration during this condition. Because water macromolecular interactions largely determine tissue water T1, another possible explanation for reduced brain water proton T1 values is that the interaction between water and brain macromolecules is altered by ethanol. METHODS: A 4.0 T magnetic resonance imaging (MRI) instrument was used to measure brain water proton T1 relaxation times before, during, and after ethanol intoxication (dose, 0.75 mg/kg) in healthy controls. RESULTS: The T1 relaxation times as assessed with MRI were highly reproducible. The mean, paired ethanol-induced differences in T1 were -0.004 +/- 0.007 sec (mean +/- standard deviation) for white matter and 0.010 +/- 0.015 sec for internal gray matter structures, neither of which was significant. CONCLUSIONS: This reasonably sensitive measurement does not support the view that tissue water content or water macromolecule interactions are significantly altered in the brain during acute alcohol intoxication in otherwise healthy subjects.

1H MRSI comparison of white matter and lesions in primary progressive and relapsing-remitting MS.

OBJECTIVE: To compare brain metabolite levels in patients with primary progressive (PP) and relapsing remitting (RR) MS and controls. HYPOTHESES: (1) creatine (Cr), a putative marker of gliosis, is elevated and N-acetylaspartate (NAA), a putative marker of axonal density and functional integrity, is reduced in PPMS lesions and normal appearing white matter (NAWM) compared to control white matter; (2) The pattern of metabolite change in PPMS is different than in RRMS. METHODS: MRI and proton magnetic resonance spectroscopic imaging (1H MRSI) were collected from 15 PPMS patients, 13 RRMS patients, and 20 controls. RESULTS: Cr was increased in PPMS NAWM compared to controls (P=0.035), and compared to RRMS NAWM (P=0.038). Cr was increased in focal MRI lesions from PPMS compared to lesions from RRMS (P=0.044) and compared to control white matter (P=0.041). NAA was similarly reduced in PPMS and RRMS NAWM compared to control. NAA was similarly reduced in PPMS and RRMS lesions, compared to control white matter. CONCLUSIONS: Creatine is higher in PPMS than RRMS NAWM and focal lesions. This observation is consistent with the notion that progressive disability in PPMS reflects increased gliosis and axonal loss whereas disability in RRMS reflects the cumulative effects of acute inflammatory lesions and axonal loss.

Intimate combination of low- and high-resolution image data: I. Real-space PET and (1)H(2)O MRI, PETAMRI.

Two different types of (co-registered) images of the same slice of tissue will generally have different spatial resolutions. The judicious pixel-by-pixel combination of their data can be accomplished to yield a single image exhibiting properties of both. Here, axial (18)FDG PET and (1)H(2)O MR images of the human brain are used as the low- and high-resolution members of the pair. A color scale is necessary in order to provide for separate intensity parameters from the two image types. However, not all color scales can accommodate this separability. The HSV color model allows one to choose a color scale in which the intensity of the low-resolution image type is coded as hue, while that of the high-resolution type is coded as value, a reasonably independent parameter. Furthermore, the high-resolution image must have high contrast and be quantitative in the same sense as the low-resolution image almost always is. Here, relaxographic MR images (naturally segmented quantitative (1)H(2)O spin-density components) are used. Their essentially complete contrast serves to effect an apparent editing function when encoded as the value of the color scale. Thus, the combination of (18)FDG PET images with gray-matter (GM) relaxographic (1)H(2)O images produces visually "GM-edited" (18)FDG PETAMR (positron emission tomography and magnetic resonance) images. These exhibit the high sensitivity to tracer amounts characteristic of PET along with the high spatial resolution of (1)H(2)O MRI. At the same time, however, they retain the complete quantitative measures of each of their basis images. Magn Reson Med 42:345-360, 1999. Published 1999 Wiley-Liss, Inc.

A serial study of new MS lesions and the white matter from which they arise.

OBJECTIVE: To compare MS normal-appearing white matter (NAWM) where new gadolinium-enhancing (Gd+) lesions do and do not arise. METHODS: A total of 22 relapsing-remitting MS patients and 11 healthy control subjects completed as many as 12 monthly brain MRI sessions. Quantitative measures of gadolinium enhancement (GDR), water proton density (PDN), water proton T2 relaxation time constants (T2), magnetization transfer ratio (MTR), and T1-weighted signal intensity (T1N) were followed serially in healthy control and MS NAWM. RESULTS: A total of 129 new Gd+ lesions were identified in 11 patients. PDN, T2, MTR, and T1N were diffusely abnormal in MS NAWM. NAWM regions in which new Gd+ lesions arose have increased GDR, PDN, and T2, and reduced MTR and T1N compared with contralateral homologous NAWM regions in which no new Gd+ lesions arose. Differences between these NAWM regions preceded lesion appearance for at least several months. After lesions became visible, GDR returned to baseline within 2 months, and PDN and MTR had larger residual abnormalities than T2 or T1N. CONCLUSIONS: Quantitative MRI measures are diffusely abnormal in MS NAWM. These measures are, on average, more abnormal in NAWM regions in which new Gd+ lesions arise. After the appearance of Gd+ lesions, measures of PDN and MTR may provide more appealing markers of relatively irreversible tissue damage than measures of T2 and T1N.

Reduced MTR in the corticospinal tract and normal T2 in amyotrophic lateral sclerosis.

The objective of this study was to test the hypothesis that magnetization transfer ratios (MTR) are decreased in the corticospinal tract of patients with amyotrophic lateral sclerosis (ALS); to determine if T2 is increased in corticospinal tract or reduced in motor cortex in ALS; to determine if corticospinal tract MTR correlates with a clinical measure of motor neuron function in ALS. Ten ALS patients and 17 age-matched controls were studied. Double spin echo MRI and 3D gradient echo MRI with and without off-resonance saturation were acquired on each subject. 3D data sets were coregistered and resliced to match the spin echo data set. MTR was calculated for corticospinal and non-corticospinal tract white matter. T2 was calculated for corticospinal and non-corticospinal tract white matter, motor cortex and non-motor cortex. MTR was reduced by 2.6% (p < .02) in corticospinal, but not in non-corticospinal, tract white matter in ALS. There was no difference in T2 in any brain region. The correlation between a clinical measure of motor neuron function and corticospinal tract MTR was statistically significant. These findings are consistent with the known pathology in ALS and suggest that MTR is more sensitive than T2 for detecting involvement of the corticospinal tract. Quantitative MTR of the corticospinal tract may be a useful, objective marker of upper motor neuron pathology in ALS.

Decreased N-acetylaspartate in motor cortex and corticospinal tract in ALS.

The primary objectives of this study were to test whether 1) N-acetylaspartate (NAA), a neuronal marker, is reduced in motor cortex and corticospinal-tract (CST) brain regions of ALS patients; and 2) motor cortex NAA correlates to a clinical measurement of upper motor neuron function in ALS patients. Ten probable or definite ALS patients and nine neurologically normal control subjects were studied. Three axial planes of two-dimensional 1H MRSI data were collected, using a single spin-echo multislice sequence (TE140/TR2000). Two of the 1H MRSI planes were positioned superior to the lateral ventricles, and one plane was positioned at the level of the internal capsule. Spectroscopy voxels were selected from motor cortex, frontal cortex, parietal cortex, medial gray matter, centrum semiovale white matter, anterior internal capsule, and posterior internal capsule. Peak integrals were obtained for the three major 1H MRSI singlet resonances, NAA, creatine and phosphocreatine (Cr), and cholines (Cho). Maximum finger-tap rate was used as a clinical measurement of upper motor neuron function. In ALS, brain NAA/(Cho+Cr) was reduced 19% (p=0.024) in the motor cortex and 16% (p=0.021) in the CST (centrum semiovale and posterior internal capsule) regions. NAA/ (Cho+Cr) was not reduced in frontal cortex, parietal cortex, medial gray matter, or anterior internal capsule. There was a significant relation between ALS motor cortex NAA/(Cho+Cr) and maximum finger-tap rate (r=0.80; p=0.014). NAA/(Cho+Cr) was reduced in motor cortex and CST regions and unchanged in other brain regions of ALS patients when compared with controls. These findings are consistent with the known distribution of neuronal loss in ALS. The positive correlation between motor cortex NAA/(Cho+Cr) and maximum finger-tap rate suggests that reduced NAA/(Cho+Cr) is a surrogate marker of motor cortex neuron loss in ALS. These findings support the study of 1H MRSI NAA measurement as an objective and quantitative measurement of upper motor neuron dysfunction in ALS.

Inorganic phosphate and coronary perfusion pressure mediate contractile dysfunction during mild ischemia.

During mild graded ischemia in perfused rat hearts, we (V.M. Figueredo, R. Brandes, M. W. Weiner, B. M. Massie, and S. A. Camacho. J. Clin. Invest 90: 1794-1802, 1992) previously found a relationship between decreased left ventricular developed pressure (LVDP) and increased Pi, in which intracellular pH, cytosolic Ca2+ concentration ([Ca2+]i), ATP, and free-energy change of ATP hydrolysis were not altered enough to affect contractility. However, the contribution of decreased coronary perfusion pressure (CPP) to decreased LVDP could not be determined. Thus, in the present study, graded hypoxia in perfused rat hearts (95-37.5% O2) was used to increase Pi to similar levels produced during mild ischemia without altering CPP and minimizing changes of other potential mediators of contractile dysfunction. 31P-magnetic resonance spectroscopy and indo 1 fluorescence were used to assess energy metabolites and [Ca2+]i, respectively. The relationship between LVDP and Pi during graded hypoxia was fit to a monoexponential (LVDP = 105 x e-0.04Pi). These data were compared with the relationship of LVDP and Pi during mild ischemia (LVDP = 106 x e-0.08Pi) (V. M. Figueredo, R. Brandes, M. W. Weiner, B. M. Massie, and S. A. Camacho. J. Clin. Invest 90: 1794-1802, 1992). The exponential constant, which describes the effect of Pi on LVDP, was 50% lower during graded hypoxia relative to mild ischemia. This suggests that another mediator, which accounted for approximately 50% of the decrease of LVDP during mild ischemia, was not present during hypoxia. Because CPP decreased during ischemia but not hypoxia, these data suggest that CPP and Pi contribute similarly in mediating contractile dysfunction during mild ischemia.

1H MRSI of normal appearing white matter in multiple sclerosis.

The primary goal of this study was to determine if differences in proton magnetic resonance spectroscopy signals exist between normal appearing white matter (NAWM) of multiple sclerosis (MS) patients and white matter of control subjects. Water suppressed proton magnetic resonance spectroscopic imaging was used to determine the signal intensities of N-acetylated moieties (NA, predominantly N-acetylaspartate (NAA) the putative neuronal marker), creatine and phosphocreatine (Cr), and cholines (Ch) in 19 MS patients (15 relapsing-remitting and four secondary progressive) and 19 age matched control subjects. NA/Cr was significantly reduced (P < 0.001) in MS NAWM (1.8 +/- 0.2; x +/- s.d.) distant from MRI detected lesion areas compared to white matter of control subjects (2.1 +/- 0.2). This reduction was due to an increase in Cr from 0.39 +/- 0.04 (arbitrary units) in controls to 0.45 +/- 0.05 in MS patients. There was no significant change in NA or Ch in MS NAWM compared to controls. NA/Cr, distant from MRI lesion, was negatively correlated with total brain lesion volume as measured from T2-weighted MRI. We interpret the reduced NA/Cr in MS NAWM to indicate diffuse microscopic disease.

Effects of severe global ischemia on N-acetylaspartate and other metabolites in the rat brain.

N-acetylaspartate (NAA) is found exclusively in neurons and their processes in the adult brain. Since the regional distribution of NAA may be imaged using magnetic resonance spectroscopic imaging (1H-MRSI), a regional measure of neuronal density may be noninvasively obtained. The technique may be particularly useful in the diagnosis of diseases where neurons are selectively injured, since these diseases do not result in definitive changes on conventional imaging studies. The goal of this study was to determine whether 1H-MRSI measurement of NAA defects neuronal loss following global ischemia. 1H-MRSI was performed in rats 24 h after global ischemia was induced by bilateral carotid occlusion plus hypotension. 1-H-MRSI showed that NAA was decreased by 28-74% in vulnerable regions, including the cortex, striatum, hippocampus, and, to a lesser extent, the thalamus. No change was observed in the brain stem or cerebellum. Regions where 1H-MRSI observed NAA was decreased also had histological evidence of selective neuronal necrosis and showed marked increase of lactate and alanine. These results show that 1H-MRSI detected loss of NAA in brain regions with selective neuronal loss, suggesting that 1H-MRSI measurements of NAA could detect neuronal loss in a variety of disease states where there is selective neuronal necrosis.