Assessment of a combined spin- and gradient-echo (SAGE) DSC-MRI method for preclinical neuroimaging

The goal of this study was to optimize and validate a combined spin- and gradient-echo (SAGE) sequence for dynamic susceptibility-contrast magnetic resonance imaging to obtain hemodynamic parameters in a preclinical setting. The SAGE EPI sequence was applied in phantoms and in vivo rat brain (normal, tumor, and stroke tissue). Partial and full Fourier encoding schemes were implemented and characterized. Maps of cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), vessel size index (VSI), volume transfer constant (K^trans), and volume fraction of the extravascular extracellular space (v_e) were obtained. Partial Fourier encoding provided shortened echo times with acceptable signal-to-noise ratio and temporal stability, thus enabling reliable characterization of T₂, T₂^? and T₁ in both phantoms and rat brain. The hemodynamic parameters CBV, CBF, and MTT for gradient-echo and spin-echo contrast were determined in tumor and stroke; VSI, K^trans, and v_e were also computed in tumor tissue. The SAGE EPI sequence allows the acquisition of multiple gradient- and spin-echoes, from which measures of perfusion, permeability, and vessel size can be obtained in a preclinical setting. Partial Fourier encoding can be used to minimize SAGE echo times and reliably quantify dynamic T₂ and T₂^? changes. This acquisition provides a more comprehensive assessment of hemodynamic status in brain tissue with vascular and perfusion abnormalities.     

Proton spectroscopy of human stroke: Assessment of transverse relaxation times and partial volume effects in single volume STEAM MRS

Proton T₂ relaxation times were measured in 13 stroke patients and 13 aged-matched normal subjects at 2.1 T. Spectra were acquired from an 8-cc volume using the STEAM sequence with echo times (TE) of 30.4 ms and 270.0 ms and repetition time of 2.8 s. Transverse relaxation times were estimated using two-point calculations. Percentage volume of infarct in the STEAM voxel was measured on spin-echo MRI encompassing the infarct and correlated with the peak amplitude of N-acetylated compounds (NA). T₂ values of NA, creatine, and choline resonances showed no significant difference between patients and controls. T₂ for lactate in patients was 780 ± 257 ms, respectively (mean ± SE, n = 7). In stroke patients, high inverse correlation was found between the absolute NA signal and partial volume of normal brain contributing to each spectrum (p < .001, r = 0.97). Together with unchanged T₂, this suggests that NAA largely disappears from infarcted tissue within 24 hr postinfarct.     

Adaptive total linear least square method for quantification of mean transit time in brain perfusion MRI

Absolute quantification of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) are of great relevance for clinical applications. One of the widely used methods for quantification of these parameters is gamma-variate fitting. Traditional nonlinear regression methods for gamma-variate fitting are inaccurate and computationally demanding. In this study, we developed an adaptive total least square method (ATSSL) to fit a gamma-variate function to the delayed concentration-time course. For each concentration-time curve, the beginning and ending time point of the curve are adaptively determined online. After the curves were fitted, a robust method for automatically determination of arterial input function (AIF) from whole and region of interest (ROI) was developed. Using the obtained AIF and fitted gamma-variate concentration-time curve, the MTT, CBV, and CBF were calculated by utilizing singular value decomposition algorithm. Computer simulations show that the suggested method is adaptive, reliable, and insensitive to noise. Comparison with the traditional nonlinear regression method indicated that the presented method is more accurate and faster to determine the CBV, CBF and MTT.     

Quantitative perfusion imaging in carotid artery stenosis using dynamic susceptibility contrast-enhanced magnetic resonance imaging

Quantitative, multislice dynamic susceptibility contrast-enhanced MRI perfusion measurements were used to determine the patterns of cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and normalized first moment of the tissue deltaR2-time curve (N) in 11 subjects with carotid artery occlusion or stenosis. MTT correlated with degree of carotid stenosis, whereas a range of alterations in CBF and CBV were found presumably reflecting variables degrees of collateral flow. There was no significant correlation between MRI and SPET flow perfusion measurements, with increasing disparity between the two techniques at higher inter-hemispheric flow ratios. The effect of obtaining the arterial input function (AIF) from the middle cerebral artery (MCA) ipsilateral or contralateral to the stenosis was determined. Despite the use of an AIF from the MCA, which is distal to the circle of Willis, and hence the major sources of collateral supply, there was still some extra dispersion of the contrast agent bolus due to differences in arrival time.     

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.     

Quantification of cerebral blood flow by bolus tracking and artery spin tagging methods

This study deals with perfusion quantification in healthy volunteers using two types of dynamic magnetic resonance imaging (MRI) methods. Absolute cerebral blood flow (CBF) measurements were performed in 11 subjects by applying both bolus tracking of exogenous contrast agent and non-invasive arterial spin labeling MRI techniques. Both methods produced CBF images with good tissue contrast and CBF values are in good agreement with literature data. The correlation between cerebral blood volume (CBV) and CBF is also discussed.     

Effect of hyperosmotic mannitol on magnetic resonance relaxation parameters in reperfused canine myocardial infarction

To determine how administration of a hyperosmotic agent alters regional nuclear magnetic resonance (NMR) relaxation parameters and imaging characteristics in ischemic-reperfused myocardium, 7 dogs were infused with mannitol for 15 minutes before and after the release of a 3 hour left anterior descending coronary artery (LAD) occlusion. Nine control animals received normal saline during the 3 hour occlusion and 1 hour reperfusion periods. Normal posterior left ventricular (LV) wall and the ischemic anterior LV wall (risk area) myocardium was sampled for calculation of segmental microsphere myocardial blood flow, % tissue water content, NMR relaxation times (T1, T2) and myocyte ultrastructure using electron microscopy. Mean infarct T1 values were 14% greater than normal segments in saline-treated controls, but only 5% greater after mannitol. The difference in tissue water content between infarcted and normal segments was 4% in saline-treated (83 vs. 79%) compared to 2% in mannitol-treated dogs (79 vs. 77%). T1, T2 and % water content of control infarct segments were greater than treated infarcts (p less than 0.01). T1 and T2 rose as occlusion flow fell below 0.5 ml/min/g in control hearts but did not rise until flows were reduced to 0.1 ml/min/g in mannitol-treated hearts. Areas of increased signal in T1 and T2 NMR images correlated well with histochemical infarct volume (r = 0.98, SEE = 1.1 cc) in mannitol-treated dogs, but infarct borders were qualitatively less well-defined than in controls. We concluded that mannitol (1) diminishes tissue edema and reduces NMR relaxation parameters (T1, T2) in infarcted myocardium; and (2) attenuates the rise in T1 and T2 and ultrastructural myocyte injury in ischemic-reperfused myocardium.     

Differences between arterial occlusive and cortical photothrombosis stroke models with magnetic resonance imaging and microtubule-associated protein-2 immunoreactivity

The differences between two models of cerebral ischemia [middle cerebral arterial transection (MCAT) and cortical photothrombosis (PT)] were explored with multiparametric MRI of apparent diffusion coefficient trace (ADCtr), cerebral blood flow (CBF) and T1. Microtubule-associated protein-2 (MAP2) immunoreactivity sections aligned with the MR images in the same coronal plane were used to map the infarct and to guide region-of-interest selection. In ischemic cortex, the larger T1 increase in PT versus MCAT (42+/-7% vs. 16+/-5%) is related to the different character of edema between these models; yet, neither CBF nor ADCtr discriminated between them at 3.5 h, suggesting that different mechanisms of ischemic damage to the brain cells resulted in the same ADCtr value. CBF and ADCtr were depressed in immediately adjacent ischemic border by 27+/-7% and 47+/-10%, respectively, in MCAT but not in PT, suggesting marginal perfusion in MCAT. CBF in homotopic normal cortex in the opposite hemisphere was higher for PT compared with MCAT (199+/-20 and 134+/-10 ml/100 g/min, respectively). Different pathological processes in the two models affect CBF, ADCtr and T1 in a unique, regionally specific manner. The PT model differs substantially from the MCAT and is not a model of cortical ischemia with an appreciable border zone.     

Visualization of myocardial infarction and subsequent coronary reperfusion with MRI using a dog model

Twelve anesthetized mongrel dogs underwent left thoracotomy with placement of a removable ligature around the left circumflex coronary artery. Following a 3 to 6 hour delay, ECG-gated spin-echo MRI was performed. The ligature was then removed reperfusing the heart, and after a 10-15 min period, MRI repeated. Finally, post-sacrifice images were obtained, and the hearts chemically stained for infarct evaluation. The MR images were subjectively and quantitatively evaluated for visibility of the endocardial border and of the injured myocardium, and for changes after reperfusion. The injured tissue was variably visible in vivo, the major limitation a result of motion blurring and artifact. The abnormal tissue was easily visible on MRI in 11 animals, and not clearly visible in one. The endocardial border was easily seen in 10 animals. The variation of calculated relaxation times was high for both normal and ischemic/infarcted myocardium in the beating hearts (normal: T1 = 566 +/- 288, T2 = 38 +/- 6; injured myocardium: T1 = 637 +/- 250, T2 = 41 +/- 12) in contrast, relatively stationary skeletal muscle measured in the same images had narrower ranges (T1 = 532 +/- 199, T2 = 28 +/- 2). Changes with reperfusion were seen, but not reliably. The infarcted or ischemic zones were easily visible on post-sacrifice images in all animals imaged. Post-sacrifice relaxation times were T1 = 564 +/- 69 msec, T2 = 39 +/- 3 msec for normal heart muscle, and 725 +/- 114, T2 = 47 +/- 5 for ischemic/infarcted tissue.(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)     

Assessment of clinical data of nonlinear stochastic deconvolution versus block-circulant singular value decomposition for quantitative dynamic susceptibility contrast magnetic resonance imaging

Dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) allows the noninvasive assessment of brain hemodynamics alterations by quantifying, via deconvolution, the cerebral blood flow (CBF) and mean transit time (MTT). Singular value decomposition (SVD) and block-circulant SVD (cSVD) are the most widely adopted deconvolution method, although they bear some limitations, including unphysiological oscillations in the residue function and bias in the presence of delay and dispersion between the tissue and the arterial input function. A nonlinear stochastic regularization (NSR) has been proposed, which performs better than SVD and cSVD on simulated data both in the presence and absence of dispersion. Moreover, NSR allows to quantify the dispersion level. Here, cSVD and NSR are compared for the first time on a group of nine patients with severe atherosclerotic unilateral stenosis of internal carotid artery before and after carotid stenting to investigate the effect of arterial dispersion. According to region of interest-based analysis, NSR characterizes the pathologic tissue more accurately than cSVD, thus improving the quality of the information provided to physicians for diagnosis. In fact, in 7 (78%) of the 9 subjects, CBF and MTT maps provided by NSR allow to correctly identify the pathologic hemisphere to the physician. Moreover, by emphasizing the difference between pathologic and healthy tissues, NSR may be successfully used to monitor the subject's recovery after the treatment and/or surgery. NSR also generates dispersion level and non-dispersed CBF and MTT maps. The dispersion level provides information on CBF and MTT estimates reliability and may also be used as a clinical indicator of pathological tissue state complementary to CBF and MTT, thus increasing the clinical information provided by DSC-MRI analysis.     

Anisotropy of the backscatter coefficient of formalin-fixed ovine myocardium

The objective of this study was to measure the backscatter coefficient of formalin-fixed myocardial tissue as a function of angle of insonification relative to the myocardial fiber direction. Backscatter measurements were performed on eight cylindrical formalin-fixed lamb myocardial specimens and compensated for attenuation and diffraction effects to determine the backscatter coefficient. The backscatter coefficient at 5 MHz was found to be maximum for insonification perpendicular to the predominant myofiber orientation and minimum for parallel insonification, with values of (17+/-14) and (1.2+/-0.7) x 10(-4) cm(-1) sr(-1) (mean+/-standard deviation), respectively.     

Correcting the effects of background microcirculation in the measurement of arterial input functions using dynamic susceptibility contrast MRI of the brain

In dynamic susceptibility contrast MRI, the shape of the arterial input function (AIF) is commonly obtained in the near vicinity of the middle cerebral artery (MCA). However, the tissue regions where the AIF is sampled also have significant perfusion, which contributes to T(2)* changes. We investigate whether correction of this effect will introduce significant changes in the measurement of the AIF and, subsequently, the assessment of the mean transit time (MTT). Clinical dynamic susceptibility data from 13 patients with brain tumors were analyzed. Patients received either single or double doses of Magnevist followed by a saline flush through a power injector. In the correction procedure, DeltaR(2)* was sampled in a region of gray matter approximately 1-2 cm away from the MCA and then subtracted from the DeltaR(2)* sampled in the immediate vicinity of the MCA. We demonstrate that in the brain, this correction of DeltaR(2)* due to tissue perfusion leads to a narrower width of the AIF curve obtained with DeltaR(2)* (mean+/-S.D.=7.3+/-2.0 and 6.4+/-1.7 s, before and after correction, respectively, P<.001 using a two-tailed paired t-test). Furthermore, the peak of the AIF also moved to a slightly earlier time relative to the time of arrival (mean+/-S.D.=4.7+/-0.9 and 4.3+/-0.8 s, before and after correction, with P<.001). With the use of the corrected AIF, the measured MTT had increased values in areas of both gray and white matter.     

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.     

Direct measurement of oxygen extraction with fMRI using 6% CO2 inhalation

The blood-oxygenation-level-dependent (BOLD) signal is an indirect hemodynamic signal that is sensitive to cerebral blood flow (CBF), cerebral blood volume (CBV) and cerebral metabolic rate of oxygen. Therefore, the BOLD signal amplitude and dynamics cannot be interpreted unambiguously without additional physiological measurements, and thus, there remains a need for a functional magnetic resonance imaging (fMRI) signal, which is more closely related to the underlying neuronal activity. In this study, we measured CBF with continuous arterial spin labeling, CBV with an exogenous contrast agent and BOLD combined with intracortical electrophysiological recording in the primary visual cortex of the anesthetized monkey. During inhalation of 6% CO2, it was observed that CBF and CBV are not further increased by a visual stimulus, although baseline CBF for 6% CO2 is below the maximal value of CBF. In contrast, the electrophysiological response to the stimulation was found to be preserved during hypercapnia. As a consequence, the simultaneously measured BOLD signal responds negatively to a visual stimulation for 6% CO2 inhalation in the same voxels responding positively during normocapnia. These observations suggest that the fMRI response to a sensory stimulus for 6% CO2 inhalation occurs in the absence of a hemodynamic response, and it therefore directly reflects oxygen extraction into the tissue.     

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.     

基于NIRS-ICG的脑血流量无创测量

临床上脑血流量(cerebral blood flow, CBF)等脑血管血流动力学参数是脑血氧水平及脑血管储备功能诊断依据,现有检测手段存在技术复杂及相应试剂或设备不适用于所有诊断人群等缺点。为解决以上问题,利用近红外光谱技术(NIRS)结合吲哚青绿(indocyanine green, ICG)脉搏色素浓度法,研究了一种无创、快速、可重复测量的脑血流量床旁检测方法NIRS-ICG。该方法根据静脉注射ICG后脑组织及脑动脉血流中三种主要吸光色团氧合血红蛋白(oxygenated hemoglobin, HbO₂)、还原血红蛋白(reduced hemoglobin, HbR)及ICG的浓度变化情况,建立脑组织及脑动脉血流中ICG积累量及引入量模型,以获得脑血氧及CBF等脑血流动力学参数。为验证该方法的可行性,将NIRS-ICG应用于血碳酸正常及高碳酸血症病理模型的实验猪的脑血流情况检测。具体方法是：分别对四组实验猪用按0%,3%,6%,9%比例调制的CO₂和空气混合气体施行机械通气,静脉快速推注ICG后,利用NIRS-ICG方法测量CBF、脑动脉血氧饱和度(cerebral arterial oxygen saturation, SaO₂)及脑血管管床平均循环时间(mean transit time, MTT)。实验结果表明,NIRS-ICG测得的CBF随CO₂比率升高而升高,SaO₂随着CO₂比例的升高而降低,MTT并无显著变化,与生理变化一致。因此,该方法可为脑血氧及脑血管储备功能诊断提供可靠依据。     

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.     

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.     

Apparent diffusion coefficient (ADC) measurements may be more reliable and reproducible than lesion volume on diffusion-weighted images from patients with acute ischaemic stroke-implications for study design

Early ischemic change after stroke can be demonstrated with diffusion-weighted imaging (DWI) and quantified by measuring the apparent diffusion coefficient (ADC) and/or lesion volume. We examined the reliability and reproducibility of lesion volume and ADC measurement on DWI images, and discuss the implications for clinical studies. Using 38 DWI scans from 15 stroke patients, two observers (a physicist and a neuroscience graduate) blind to each other, recorded the lesion volume on DWI sequences, measured the ADC values in this volume and calculated the ratio of ischemic: control ADC (ADCr). One observer repeated his measurements blind to his first, and also examined the effect on lesion volume and ADC of deliberately varying by only one pixel, the outline of the visible boundary of the lesion. The inter and intra-rater reliability were worse for lesion volume than ADC or ADCr measurements: lesion volume, inter-rater coefficient of variation (CoV) 85 +/- 130%, intra-rater CoV 20+/-SD80% (p < 0.05); ADC inter-rater CoV 7.7 +/- SD 19%, intra-rater CoV 0.2 +/- SD 12% (p = NS); and ADCr inter-rater CoV 8 +/- SD27%, intra-rater CoV 0.8 +/- SD73% (p = NS). Altering the position of the outline tracing of the lesion boundary by one pixel altered the measured volumes by 22 +/- SD25% (p < 0.05), but ADC values were altered by only 2.9 +/- SD4.9% and ADCr by 2.7 +/- SD4.8% (p = NS). ADC and ADCr values are more reliable and reproducible than DWI lesion size in acute ischemic stroke because altering where the lesion boundary is measured has a much greater impact on lesion volume than on the ADC or ADCr. This effect is greatest in large lesions.