Reliability of mean transit time obtained using perfusion-weighted MR imaging; comparison with positron emission tomography

The purpose of this project was to assess the reliability of the cerebral mean transit time (MTT) obtained using perfusion-weighted MR imaging by comparing it with the MTT obtained when performing positron emission tomography (PET). Ten patients with chronic occlusive cerebrovascular disease were investigated. They had either unilateral internal carotid artery occlusion or middle cerebral artery occlusion. The regions-of-interest were placed in non-infarcted areas within the territory of the middle cerebral artery on the affected side. Control regions-of-interest were placed in mirrored regions of the contralateral side. Linear regression analyses were performed using the parameters of the MTT obtained with perfusion-weighted MR imaging and the MTT, cerebral blood flow, vascular reactivity, and oxygen extraction fraction obtained with PET. The respective MTTs of the affected and non-affected sides obtained with perfusion-weighted MR imaging versus those with PET were 7.3 +/- 2.2 s and 6.0 +/- 1.2 s versus 8.2 +/- 3.0 s and 6.4 +/- 1.7 s. The MTT obtained using perfusion-weighted MR imaging and PET demonstrated statistically significant correlation (r = 0.87, p < 0.0001). The MTT obtained with perfusion-weighted MR imaging correlated statistically with cerebral blood flow (r = -0.74, p < 0.001), vascular reactivity (r = -0.73, p < 0.001) and oxygen extraction fraction (r = 0.61, p < 0.01). Similarly, the MTT obtained using PET statistically correlated with cerebral blood flow (r = -0.78, p < 0.0001), vascular reactivity (r = -0.51, p < 0.05) and oxygen extraction fraction (r = 0.68, p < 0.01). The reliability of the MTT obtained using perfusion-weighted MR imaging appears to be approximately equal to that obtained with positron emission tomography.     

Phosphorus-31 MR spectroscopic imaging (MRSI) of normal and pathological human brains.

The goals of this study were to evaluate 31P MR spectroscopic imaging (MRSI) for clinical studies and to survey potentially significant spatial variations of 31P metabolite signals in normal and pathological human brains. In normal brains, chemical shifts and metabolite ratios corrected for saturation were similar to previous studies using single-volume localization techniques (n = 10; pH = 7.01 +/- 0.02; PCr/Pi = 2.0 +/- 0.4; PCr/ATP = 1.4 +/- 0.2; ATP/Pi = 1.6 +/- 0.2; PCr/PDE = 0.52 +/- 0.06; PCr/PME = 1.3 +/- 0.2; [Mg2+]free = 0.26 +/- 0.02 mM.) In 17 pathological case studies, ratios of 31P metabolite signals between the pathological regions and normal-appearing (usually homologous contralateral) regions were obtained. First, in subacute and chronic infarctions (n = 9) decreased Pi (65 +/- 12%), PCr (38 +/- 6%), ATP (55 +/- 6%), PDE (47 +/- 9%), and total 31P metabolite signals (50 +/- 8%) were observed. Second, regions of decreased total 31P metabolite signals were observed in normal pressure hydrocephalus (NPH, n = 2), glioblastoma (n = 2), temporal lobe epilepsy (n = 2), and transient ischemic attacks (TIAs, n = 2). Third, alkalosis was detected in the NPH periventricular tissue, glioblastoma, epilepsy ipsilateral ictal foci, and chronic infarction regions; acidosis was detected in subacute infarction regions. Fourth, in TIAs with no MRI-detected infarction, regions consistent with transient neurological deficits were detected with decreased Pi, ATP, and total 31P metabolite signals. These results demonstrate an advantage of 31P MRSI over single-volume 31P MRS techniques in that metabolite information is derived simultaneously from multiple regions of brain, including those outside the primary pathological region of interest. These preliminary findings also suggest that abnormal metabolite distributions may be detected in regions that appear normal on MR images.     

MRI based diffusion and perfusion predictive model to estimate stroke evolution.

In this study we present a novel automated strategy for predicting infarct evolution, based on MR diffusion and perfusion images acquired in the acute stage of stroke. The validity of this methodology was tested on novel patient data including data acquired from an independent stroke clinic. Regions-of-interest (ROIs) defining the initial diffusion lesion and tissue with abnormal hemodynamic function as defined by the mean transit time (MTT) abnormality were automatically extracted from DWI/PI maps. Quantitative measures of cerebral blood flow (CBF) and volume (CBV) along with ratio measures defined relative to the contralateral hemisphere (r(a)CBF and r(a)CBV) were calculated for the MTT ROIs. A parametric normal classifier algorithm incorporating these measures was used to predict infarct growth. The mean r(a)CBF and r(a)CBV values for eventually infarcted MTT tissue were 0.70 +/- 0.19 and 1.20 +/- 0.36. For recovered tissue the mean values were 0.99 +/- 0.25 and 1.87 +/- 0.71, respectively. There was a significant difference between these two regions for both measures (p < 0.003 and p < 0.001, respectively). Mean absolute measures of CBF (ml/100g/min) and CBV (ml/100g) for the total infarcted territory were 33.9 +/- 9.7 and 4.2 +/- 1.9. For recovered MTT tissue, the mean values were 41.5 +/- 7.2 and 5.3 +/- 1.2, respectively. A significant difference was also found for these regions (p < 0.009 and p < 0.036, respectively). The mean measures of sensitivity, specificity, positive and negative predictive values for modeling infarct evolution for the validation patient data were 0.72 +/- 0.05, 0.97 +/- 0.02, 0.68 +/- 0.07 and 0.97 +/- 0.02. We propose that this automated strategy may allow possible guided therapeutic intervention to stroke patients and evaluation of efficacy of novel stroke compounds in clinical drug trials.     

3-D echo planar (1)HMRS imaging in MS: metabolite comparison from supratentorial vs. central brain

To determine if metabolite ratios as measured by 3-dimensional echo planar spectroscopy imaging (3D-EPSI) from central brain regions of interest (ROI) centered at the corpus callosum reflect imaging metrics of large volumes of supratentorial brain (STB) from patients with multiple sclerosis. METHODS: 48 MS patients with relapsing-remitting, secondary progressive, and primary progressive disease underwent a 3D-EPSI sequence covering large volumes of STB. Metabolite ratios were first estimated from all voxels within a STB mask using a linear regression of N-acetylaspartate (NAA) over Creatine (Cr), NAA over choline (Cho) and Cho over Cr. Secondly, spectroscopic voxels from a central brain (CB) ROI centered at the corpus callosum were selected within the STB. Ratios were compared using Bland-Altman regression analysis and Spearman's correlation coefficients between STB versus central brain. Ratios from studied ROIs were correlated with the EDSS and compared to normal controls. RESULTS: Very strong correlations ranging from 0.884 and 0.938 (p < 0.0001) were found for all metabolite ratios between STB versus central brain. NAA/Cr ratios were similarly and negatively correlated with the EDSS across all ROIs, trends ranging from -0.257 to -0.314 (p < 0.1). NAA/Cr from all MS patients was similarly decreased compared to controls across all ROIs (p < 0.01). CONCLUSION: Metabolite ratios from a central brain ROI were statistically equivalent and highly correlated with ratios from the STB. The study of NAA/Cr using (1)HMRS from a central brain ROI centered at the corpus callosum seems to be representative of brainwide axonal changes in patients with MS.     

Biexponential characterization of prostate tissue water diffusion decay curves over an extended b-factor range

Detailed measurements of water diffusion within the prostate over an extended b-factor range were performed to assess whether the standard assumption of monoexponential signal decay is appropriate in this organ. From nine men undergoing prostate MR staging examinations at 1.5 T, a single 10-mm-thick axial slice was scanned with a line scan diffusion imaging sequence in which 14 equally spaced b factors from 5 to 3,500 s/mm(2) were sampled along three orthogonal diffusion sensitization directions in 6 min. Due to the combination of long scan time and limited volume coverage associated with the multi-b-factor, multidirectional sampling, the slice was chosen online from the available T2-weighted axial images with the specific goal of enabling the sampling of presumed noncancerous regions of interest (ROIs) within the central gland (CG) and peripheral zone (PZ). Histology from prescan biopsy (n=9) and postsurgical resection (n=4) was subsequently employed to help confirm that the ROIs sampled were noncancerous. The CG ROIs were characterized from the T2-weighted images as primarily mixtures of glandular and stromal benign prostatic hyperplasia, which is prevalent in this population. The water signal decays with b factor from all ROIs were clearly non-monoexponential and better served with bi- vs. monoexponential fits, as tested using chi(2)-based F test analyses. Fits to biexponential decay functions yielded intersubject fast diffusion component fractions in the order of 0.73+/-0.08 for both CG and PZ ROIs, fast diffusion coefficients of 2.68+/-0.39 and 2.52+/-0.38 microm(2)/ms and slow diffusion coefficients of 0.44+/-0.16 and 0.23+/-0.16 um(2)/ms for CG and PZ ROIs, respectively. The difference between the slow diffusion coefficients within CG and PZ was statistically significant as assessed with a Mann-Whitney nonparametric test (P<.05). We conclude that a monoexponential model for water diffusion decay in prostate tissue is inadequate when a large range of b factors is sampled and that biexponential analyses are better suited for characterizing prostate diffusion decay curves.     

Spectroscopic imaging of radiation-induced effects in the white matter of glioma patients

External radiation therapy of brain tumors may cause adverse effects on normal brain tissue, resulting in severe neuropsychological and cognitive impairment. We investigated the late delayed radiation effects in the white matter (WM) using (1)H magnetic resonance spectroscopic imaging ((1)HMRSI). Nine glioma patients with local radiation-induced signal abnormalities in the T(2)-weighted MR images were studied with nine age- and sex-matched controls. The metabolite ratios in the radiation-induced hyper intensity area (RIHA) and in the normal appearing white matter (NAWM) of the patients were compared with respective WM areas of the controls. In RIHA, choline/creatine (Cho/Cr) was 17% decreased (1.22 +/- 0.13 vs 1.47 +/- 0.16, p = 0.0027, significant (s), unpaired Student's t test with Bonferroni correction) in the patients compared to the controls, while there was no difference in N-acetyl aspartate/Cr (NAA/Cr) (2.49 +/- 0.57 vs 2.98 +/- 0.32, p = 0.039) or NAA/Cho (2. 03 +/- 0.40 vs 2.04 +/- 0.17, p = 0.95). In NAWM, Cho/Cr was 24% decreased (1.21 +/- 0.15 vs 1.59 +/- 0.13, p < 0.0001, s) and NAA/Cho was 20% increased (2.49 +/- 0.49 vs 1.98 +/- 0.15, p = 0. 0082, s) in the patients compared to the controls, while there was no difference in NAA/Cr (2.99 +/- 0.46 vs 3.16 +/- 0.32, p = 0.38). NAA(RIHA)/NAA(NAWM) was 25% decreased (0.75 +/- 0.20 vs 1.00 +/- 0. 12, p = 0.0043, s) and Cr(RIHA)/Cr(NAWM) was 16% decreased (0.89 +/- 0.15 vs 1.06 +/- 0.10, p = 0.013, s) in the patients compared to the controls, while there was no difference in Cho(RIHA)/Cho(NAWM) (0.92 +/- 0.23 vs 0.98 +/- 0.10, p = 0.47). (1)HMRSI reveals widespread chemical changes in the WM after radiation therapy. In RIHA, there is loss of NAA, Cho, and Cr implying axonal and membrane damage and in NAWM, there is loss of Cho, reflecting membrane damage.     

原子吸收法检测脑梗塞患者头发中锌、铜、镁、锰

用原子吸收分光光度法测定脑梗塞患者 4 5例及健康对照者 2 0例头发中微量元素Zn ,Cu ,Mg ,Mn的含量。结果表明 ,脑梗塞组头发中Zn ,Cu ,Mg元素含量均显著低于正常对照组 (P <0 0 1) ,Mn元素的含量显著高于对照组 (P <0 0 1) ,揭示体内Zn ,Cu ,Mg ,Mn元素含量与脑梗塞发病存在一定关系。     

Differentiation between acutely ischemic myocardium and zones of completed infarction in dogs on the basis of frequency-dependent backscatter

The goal of this work was to determine whether the frequency dependence of apparent backscatter coefficient (not corrected for attenuation within the myocardium) could differentiate completed, remote infarction from acute myocardial injury in vivo. Myocardial infarcts were produced in six dogs by coronary artery occlusion. One to 12 months later, acute ischemic injury was induced in each dog by ligation of a coronary artery that supplied a region of myocardium adjacent to the established infarct. Infarct, ischemic, and normal regions were interrogated with a 5-MHz, circular, 0.5-in. diam, broadband, focused, piezoelectric transducer mounted in a water-filled stand-off device placed against the exposed, beating heart. Apparent backscatter coefficients were measured over the range of frequencies from 3-7 MHz. The frequency dependence was obtained from the slope of log apparent backscatter coefficient versus log frequency. No significant difference in frequency dependence was found between normal and acutely ischemic myocardium for periods of up to 2 h of ischemia. In contrast, frequency dependence in regions of remote infarct (1.8 +/- 0.1, mean +/- standard error) was significantly lower than that in acutely ischemic or nonischemic regions (2.3 +/- 0.1) (p less than 0.01). These results suggest that remote myocardial infarction can be differentiated from acutely injured but still potentially salvageable myocardium in vivo on the basis of the frequency dependence of backscatter.     

Whole-body T2* mapping at 1.5 T

This study investigated the feasibility of an MRI protocol providing whole-body T2* maps at 1.5 T. Seven healthy volunteers (mean age=30.1+/-3.7, three women and four men) and two patients (both male, 53 and 46 years old) affected by transfusion-dependent anemias participated in the study. Coronally oriented images of five subsequent body levels were acquired using a fat-suppressed multiecho 2D gradient-echo sequence (12 echo times ranging from 4.8 to 76.3 ms were selected) and afterwards composed. Parametrical T2* maps of the whole body were reconstructed on a pixel-by-pixel basis. For both, healthy volunteers and patients, representative T2* values were computed from extended regions of interest (ROIs). Good-quality whole-body T2* maps were computed in all volunteers and patients. In healthy volunteers, T2* values were assessed in the cerebral white (58.5+/-4.2 ms) and gray (81.4+/-5.5 ms) matter, liver (34.3+/-7.0 ms), spleen (63.5+/-3.3 ms), kidneys (65.4+/-10.3 ms) and skeletal muscles (~30 ms). The liver presented faster relaxation rates in males as compared to females. One patient (serum ferritin concentration=927 microg/dl) showed shortened T2* values in liver (3.6+/-5.5 ms), spleen (3.1+/-4.8 ms), kidneys (11.1+/-7.1 ms) and muscles (25.1+/-3.4 ms). The second patient (serum ferritin concentration=346 microg/dl) presented reduced T2* values in liver (3.9+/-7.3 ms), spleen (20.1+/-9.8 ms) and kidneys (24.6+/-7.7 ms). The presented technique may find clinical application in the assessment of the iron burden in the entire body, and in monitoring of chelation therapies in patients treated with frequent blood transfusions.     

The influence of hyperoxia on regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV) and cerebral blood flow velocity in the middle cerebral artery (CBFVMCA) in human volunteers

Conflicting results reported on the effects of hyperoxia on cerebral hemodynamics have been attributed mainly to methodical and species differences. In the present study contrast-enhanced magnetic resonance imaging (MRI) perfusion measurement was used to analyze the influence of hyperoxia (fraction of inspired oxygen (FiO2) = 1.0) on regional cerebral blood flow (rCBF) and regional cerebral blood volume (rCBV) in awake, normoventilating volunteers (n = 19). Furthermore, the experiment was repeated in 20 volunteers for transcranial Doppler sonography (TCD) measurement of cerebral blood flow velocity in the middle cerebral artery (CBFV(MCA)). When compared to normoxia (FiO2 = 0.21), hyperoxia heterogeneously influenced rCBV (4.95 +/- 0.02 to 12.87 +/- 0.08 mL/100g (FiO2 = 0.21) vs. 4.50 +/- 0.02 to 13.09 +/- 0.09 mL/100g (FiO2 = 1.0). In contrast, hyperoxia diminished rCBF in all regions (68.08 +/- 0.38 to 199.58 +/- 1.58 mL/100g/min (FiO2 = 0.21) vs. 58.63 +/- 0.32 to 175.16 +/- 1.51 mL/100g/min (FiO2 = 1.0)) except in parietal and left frontal gray matter. CBFV(MCA) remained unchanged regardless of the inspired oxygen fraction (62 +/- 9 cm/s (FiO2 = 0.21) vs. 64 +/- 8 cm/s (FiO2 = 1.0)). Finding CBFV(MCA) unchanged during hyperoxia is consistent with the present study's unchanged rCBF in parietal and left frontal gray matter. In these fronto-parietal regions predominantly fed by the middle cerebral artery, the vasoconstrictor effect of oxygen was probably counteracted by increased perfusion of foci of neuronal activity controlling general behavior and arousal.     

Magnetic resonance imaging in patients with unstable angina: comparison with acute myocardial infarction and normals

The role of magnetic resonance imaging in characterizing normal, ischemic and infarcted segments of myocardium was examined in 8 patients with unstable angina, 11 patients with acute myocardial infarction, and 7 patients with stable angina. Eleven normal volunteers were imaged for comparison. Myocardial segments in short axis magnetic resonance images were classified as normal or abnormal on the basis of perfusion changes observed in thallium-201 images in 22 patients and according to the electrocariographic localization of infarction in 4 patients. T2 relaxation time was measured in 57 myocardial segments with abnormal perfusion (24 with reversible and 33 with irreversible perfusion changes) and in 25 normally perfused segments. T2 measurements in normally perfused segments of patients with acute myocardial infarction, unstable angina and stable angina were within normal range derived from T2 measurements in 48 myocardial segments of 11 normal volunteers (42 +/- 10 ms). T2 in abnormal myocardial segments of patients with stable angina also was not significantly different from normal. T2 of abnormal segments in patients with unstable angina (64 +/- 14 in reversibly ischemic and 67 +/- 21 in the irreversibly ischemic segments) was prolonged when compared to normal (p less than 0.0001) and was not significantly different from T2 in abnormal segments of patients with acute myocardial infarction (62 +/- 18 for reversibly and 66 +/- 11 for irreversibly ischemic segments). The data indicate that T2 prolongation is not specific for acute myocardial infarction and may be observed in abnormally perfused segments of patients with unstable angina.(ABSTRACT TRUNCATED AT 250 WORDS)     

Identification of human myocardial infarction in vitro based on the frequency dependence of ultrasonic backscatter.

It has been reported previously that acute and mature myocardial infarction in dogs can be differentiated in vitro and in vivo by ultrasonic tissue characterization based on measurement of the frequency dependence of ultrasonic backscatter. To characterize human infarction with an index of the frequency dependence of backscatter that could be obtained in patients, cylindrical biopsy specimens from 7 normal regions and 12 regions of infarction of 6 fixed, explanted human hearts in 2-deg steps around their entire circumference with a 5-MHz broadband transducer were insonified. One to six consecutive transmural levels were studied for each specimen. The dependence of apparent (uncompensated for attenuation or beam width) backscatter, /B(f)/2, on frequency (f) was computed from spectral analyses of radio-frequency data as /B(f)/2 = afn, where from theoretical considerations the magnitude of n decreases as scatterer size increases. Apparent integrated backscatter was computed as the average of /B(f)/2 from 3 to 7 MHz. The average value for n for normal tissue (0.9 +/- 0.1) exceeded that for tissue from regions of infarction (0.6 +/- 0.1; p less than 0.05). Infarct manifested a significant decrease of n from epicardial to endocardial levels (epi----mid----endo: 0.9----0.7----0.2; p less than 0.05) whereas normal tissue manifested similar values for n at each transmural level (0.8----1.1----0.9; p = NS). Average integrated backscatter across all transmural levels for infarct was significantly greater than for normal tissue (-48.3 +/- 0.5 vs -53.4 +/- 0.4 dB, infarct versus normal; p less than 0.05). The presence of fibrosis was associated with smaller values of n and greater integrated backscatter.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebral tissue water spin-spin relaxation times in human neonates at 2.4 tesla: methodology and the effects of maturation

Using a 4-echo spin-echo sequence, cerebral T2 was measured in specific anatomic regions in eleven healthy newborn infants, whose gestational plus postnatal ages (GPAs) lay between 37 and 42 weeks. For a region in the pons, T2 was 141+/-9 ms (mean +/- standard deviation), and no significant dependence upon GPA was seen. In the thalamus mean T2 was 136+/-13 ms, and T2 demonstrated a significant negative linear dependence upon age (r = 0.690; p < 0.02). In periventricular and frontal regions, mean T2 were 217+/-33, and 228+/-32 ms respectively, and more marked negative linear correlations with age were observed (r = 0.833; p < 0.001 and r = 0.722; p < 0.02). For these regions, the rate of T2 decrease with age appeared to be related to known patterns of myelination. For the parietal region studied, mean T2 was 204+/-34 ms, no significant dependence upon GPA being seen. T2 shows promise as an objective measure of cerebral development in the perinatal period.     

MR-visible brain water content in human acute stroke

Quantification of metabolite concentrations by proton magnetic resonance spectroscopy (1H-MRS) in the human brain using water as an internal standard is based on the assumption that water content does not change significantly in pathologic brain tissue. To test this, we used 1H-MRS to estimate brain water content during the course of cerebral infarction. Measurements were performed serially in the acute, subacute, and chronic phase of infarction. Fourteen patients with acute cerebral infarction were examined as well as 9 healthy controls. To correlate with regional cerebral blood flow (rCBF) SPECT-scanning using 99mTc-HMPAO as flow tracer was performed in the patients. Mean water content (SD) in the infarct area was 37.7 (5.1); 41.8 (4.8); 35.2 (5.4); and 39.3 (5.1) mol x [kg wet weight](-1) at 0-3; 4-7; 8-21; and >180 days after stroke, respectively. Water content increased between Day 0-3 and Day 4-7 (p = 0.034) and decreased from Day 0-3 to Day 8-21 (p = 0.028). Water content at Day 4-7 was significantly higher than in controls (p < or = 0.05). At the same time intervals, mean rCBF (SD) was 76 (23); 94 (31); 106 (35); and 64 (26)%, respectively. There was a significant increase in rCBF from Day 0-3 to Day 4-7 (p = 0.050) and from Day 0-3 to Day 8-21 (p = 0.028). No correlation between rCBF and water content was found. Water content in ischemic brain tissue increased significantly between Day 4-7 after stroke. This should be considered when performing quantitative 1H-MRS using water as an internal standard in stroke patients.     

The accuracy of whole brain N-acetylaspartate quantification

A non-localizing pulse sequence to quantify the total amount of N-acetylaspartate (NAA) in the whole brain (WBNAA) was introduced recently [Magn. Reson. Med. 40, 684–689 (1998)]. However, it is known that regional magnetic field inhomogeneities, ΔB₀s, arising from susceptibility differences at tissue interfaces, shift and broaden local resonances to outside the integration window, leading to an underestimation of the true amount of NAA in the entire brain. To quantify the upper limit of this loss, the whole-head proton MR spectrum (¹H-MRS) of the water was integrated over the same frequency width as the NAA. The ratio of this area/total-water-line was 75 ± 5% in 5 volunteers. The procedure was repeated with the brain-only water peak, obtained by summing signals only from voxels within that organ from a three-dimensional chemical-shift-imaging (3D CSI) set. It indicated that <10% of the water signal loss occurred in the brain. Therefore, by analogy, WBNAA accounts for >90% of that metabolite.     

Experimental hypoxic–ischemic encephalopathy: comparison of apparent diffusion coefficients and proton magnetic resonance spectroscopy

This study aims to compare the apparent diffusion coefficients (ADCs) and proton magnetic resonance spectroscopy (¹H-MRS) in the first 24 h of acute hypoxic-ischemic brain damage (HIBD) in piglets. Twenty-five 7-day-old piglets were subjected to transient bilateral common carotid artery occlusion followed by ventilation with 4% oxygen for 1 h. Diffusion-weighted imaging (DWI) and ¹H-MRS were performed on cessation of the insult or at 3, 6, 12 or 24 h after resuscitation (all n=5). ADCs, N-acetylaspartate/choline (NAA/Cho), NAA/creatine (NAA/Cr), lactate/NAA (Lac/NAA), Lac/Cho and Lac/Cr were calculated. Cerebral injury was evaluated by pathological study and Hsp70 immunohistochemical analysis. On cessation of the insult, ADCs, NAA/Cho and NAA/Cr reduced, Lac/NAA, Lac/Cho and Lac/Cr increased. From 3 to 12 h after resuscitation, ADCs, Lac/NAA, Lac/Cho and Lac/Cr recovered, NAA/Cho and NAA/Cr reduced. Twenty-four hours after resuscitation, ADCs reduced once more, Lac/NAA, Lac/Cho and Lac/Cr increased again, whereas NAA/Cho and NAA/Cr decreased continuously. Pathological study revealed mild cerebral edema on cessation of the insult and more and more severe cerebral injury after resuscitation. No Hsp70-positive cells were detected on cessation of the insult. From 3 to 12 hours after resuscitation, Hsp70-positive cells gradually increased. Twenty-four hours after resuscitation, Hsp70-positive cells decreased. Throughout the experiment, changes in NAA/Cho and pathology had the best correlation (R=–0.729). In conclusion, NAA/Cho is the most precise ratio to reflect the pathological changes of early HIBD. Transient ADCs and Lac ratios recovery do not predict the reversal of histological damage of early HIBD. Reducing astrocytic swelling is of great clinical significance.     

Serial Precision of Metabolite Peak Area Ratios and Water Referenced Metabolite Peak Areas in Proton MR Spectroscopy of the Human Brain

The precision of cerebral proton magnetic resonance spectroscopy (MRS) measurements is critical both in the clinical setting and for research purposes. Marshall et al. have recently concluded that “disappointing in vivo repeatability…is likely to limit” the ability of MRS to detect modest changes. We present here a comprehensive study of the precision of short- and long-term metabolite peak area ratios and water referenced metabolite peak areas for long echo time point resolved spectroscopy (PRESS) spectra (repetition time (TR) = 2000 ms, echo time (TE) = 136 ms) acquired from the occipital lobes of normal volunteers and a phantom using a conventional whole body 1.5 T MR system and conventional acquisition and analysis protocols. Short-term in vitro precision determined by five repeat scans on five occasions was excellent as measured by a mean coefficient of variation (NAA/Cho = 1.3%, NAA/Cr + PCr = 1.0%, Cho/Cr + PCr = 1.6%, NAA/H₂O = 0.5%, Cho/H₂O = 1.2%, Cr + PCr/H₂O = 0.8%). Long term in vitro precision using 100 spectra acquired over 2 years was also very good (NAA/Cho = 2.7%, NAA/Cr + PCr = 1.4%, Cho/Cr + PCr = 2.2%, NAA/H₂O = 1.5%, Cho/H₂O = 2.4%, Cr + PCr/H₂O = 1.5%). Short-term in vivo precision determined by five repeat scans in a single scanning session on eight subjects was also excellent (NAA/Cho = 5.2%, NAA/Cr + PCr = 3.0%, Cho/Cr + PCr = 6.6%, NAA/H₂O = 1.4%, Cho/H₂O = 4.9%, Cr + PCr/H₂O = 2.7%) and only worsened slightly for long-term in vivo precision determined by five repeat scans on eight subjects over 3 months (NAA/Cho = 5.2%, NAA/Cr + PCr = 4.8%, Cho/Cr + PCr = 7.7%, NAA/H₂O = 2.5%, Cho/H₂O = 6.4%, Cr + PCr/H₂O = 3.8%). We attribute the excellent precision reported here to the use of highly automated techniques for voxel shimming, water suppression and peak area measurements. These results allow us to repudiate Marshall’s assertion regarding disappointing repeatability of in vivo MRS.     

In vivo quantification of the metabolites in normal brain and brain tumors by proton MR spectroscopy using water as an internal standard

Metabolite concentrations in normal adult brains and in gliomas were quantitatively analyzed by in vivo proton magnetic resonance spectroscopy (MRS) using the fully relaxed water signal as an internal standard. Between January 1998 and October 2001, 28 healthy volunteers and 18 patients with gliomas were examined by in vivo proton MRS. Single voxel spectra were acquired using the point-resolved spectroscopic pulse sequence with a 1.5-T scanner (TR/TE/Ave = 3000 ms/30 ms/64). The calculated concentrations of N-acetyl-aspartate (NAA), creatine (Cre), choline (Cho), and water (H2O) in the normal hemispheric white matter were 23.59 +/- 2.62 mM (mean +/- SD), 13.06 +/- 1.8 mM, 4.28 +/- 0.8 mM, and 47280.96 +/- 5414.85 mM, respectively. The metabolite concentrations were not necessarily uniform in different parts of the brain. The concentrations of NAA and Cre decreased in all gliomas (p < 0.001). The NAA/Cho and NAA/H2O ratios can distinguish the normal brain from gliomas, and low-grade astrocytoma from high-grade group (p < 0.001). The concentration of taurine (Tau) in medulloblastomas was 29.64 +/- 5.76 mM. This is the first quantitative analysis of Tau in medulloblastoma in vivo and confirms earlier in vitro findings.     

High-field localized 1H NMR spectroscopy in the anesthetized and in the awake monkey

Localized cerebral in vivo ¹H NMR spectroscopy (MRS) was performed in the anesthetized as well as the awake monkey using a novel vertical 7 T/60 cm MR system. The increased sensitivity and spectral dispersion gained at high field enabled the quantification of up to 16 metabolites in 0.1- to 1-ml volumes. Quantification was accomplished by using simulations of 18 metabolite spectra and a macromolecule (MM) background spectrum consisting of 12 components. Major cerebral metabolites (concentrations >3 mM) such as glutamate (Glu), N-acetylaspartate (NAA), creatine (Cr)/phosphocreatine (PCr) and myo-inositol (Ins) were identified with an error below 3%; most other metabolites were quantified with errors in the order of 10%. Metabolite ratios were 1.39:1 for total NAA, 1.38:1 for glutamate (Glu)/glutamine (Gln) and 0.09:1 for cholines (Cho) relative to total Cr. Taurine (Tau) was detectable at concentrations lower than 1 mM, while lactate (Lac) remained below the detection limit. The spectral dispersion was sufficient to separate metabolites of similar spectral patterns, such as Gln and Glu, N-acetylaspartylglutamate (NAAG) and NAA, and PCr–Cr. MRS in the awake monkey required the development and refinement of acquisition and correction strategies to minimize magnetic susceptibility artifacts induced by respiration and movement of the mouth or body. Periods with major motion artifacts were rejected, while a frequency/phase correction was performed on the remaining single spectra before averaging. In resting periods, both spectral amplitude and line width, that is, the voxel shim, were unaffected permitting reliable measurements. The corrected spectra obtained from the awake monkey afforded the reliable detection of 6–10 cerebral metabolites of 1-ml volumes.     

In vivo quantification of the metabolites in normal brain and brain tumors by proton MR spectroscopy using water as an internal standard

Metabolite concentrations in normal adult brains and in gliomas were quantitatively analyzed by in vivo proton magnetic resonance spectroscopy (MRS) using the fully relaxed water signal as an internal standard. Between January 1998 and October 2001, 28 healthy volunteers and 18 patients with gliomas were examined by in vivo proton MRS. Single-voxel spectra were acquired using the point-resolved spectroscopic (PRESS) pulse sequence with a 1.5 T scanner (TR/TE/Ave = 3000 ms/30 ms/64). The calculated concentrations of N-acetyl-aspartate (NAA), creatine (Cre), choline (Cho), and water(H(2)O) in the normal hemispheric white matter were 23.59 +/- 2.62 mM (mean +/- SD), 13.06 +/- 1.8 mM, 4.28 +/- 0.8 mM, and 47280.96 +/- 5414.85 mM, respectively. The metabolite concentrations were not necessarily uniform in different parts of the brain. The concentrations of NAA and Cre decreased in all gliomas (p < 0.001). The NAA/Cho and NAA/H(2)O ratios can distinguish the normal brain from gliomas and low-grade from high-grade astrocytoma (p < 0.001). The concentration of taurine (Tau) in medulloblastomas was 29.64 +/- 5.76 mM. This is the first quantitative analysis of Tau in medulloblastoma in vivo and confirms earlier in vitro findings.