Diffusion tensor imaging in multiple sclerosis at different final outcomes.

OBJECTIVES: Methods to evaluate the relative contributions of demyelination vs axonal degeneration over the long-term course of MS are urgently needed. We used magnetic resonance diffusion tensor imaging (DTI) to estimate degrees of demyelination and axonal degeneration in the corpus callosum (CC) in cases of MS with different final outcomes. MATERIALS AND METHODS: We determined DTI measures mean diffusivity (MD), fractional anisotropy (FA), and axial (AD) and radial (RD) diffusivities in the CC of 31 MS patients, of whom 13 presented a secondary progressive course, 11 a non-progressive course, and seven a monophasic course. The study participants were survivors from an incidence cohort of 254 attack-onset MS patients with 50 years of longitudinal follow-up. As reference, we included five healthy individuals without significant morbidity. RESULTS: In patients with secondary progression, compared to all other groups, the corpus callosum showed increased RD and reduced FA, but no change in AD. None of the parameters exhibited differences among non-progressive and monophasic course groups and controls. CONCLUSION: Increased RD was observed in secondary progressive MS, indicating significant myelin loss. Normal RD values observed in the clinically isolated syndrome and non-progressive groups confirm their benign nature. AD was not a characterizing parameter for long-term outcome. Demyelination revealed by increased RD is a distinguishing trait for secondary progression.

Forensic application of postmortem diffusion-weighted and diffusion tensor MR imaging of the human brain in situ.

BACKGROUND AND PURPOSE: DWI and DTI of the brain have proved to be useful in many neurologic disorders and in traumatic brain injury. This prospective study aimed at the evaluation of the influence of the PMI and the cause of death on the ADC and FA for the application of DWI and DTI in forensic radiology. MATERIALS AND METHODS: DWI and DTI of the brain were performed in situ in 20 deceased subjects with mapping of the ADC and FA. Evaluation was performed in different ROIs, and the influence of PMI and cause of death was assessed. RESULTS: Postmortem ADC values of the brain were decreased by 49%-72% compared with healthy living controls. With increasing PMI, ADCs were significantly reduced when considering all ROIs together and, particularly, GM regions (all regions, P < .05; GM, P < .01), whereas there was no significant effect in WM. Concerning the cause of death, ADCs were significantly lower in mechanical and hypoxic brain injury than in brains from subjects having died from heart failure (traumatic brain injury, P < .005; hypoxia, P < .001). Postmortem FA was not significantly different from FA in living persons and showed no significant influence of PMI or cause of death. CONCLUSIONS: Performing postmortem DWI and DTI of the brain in situ can provide valuable information for application in forensic medicine. ADC could be used as an indicator of PMI and could help in the assessment of the cause of death.

Convection-enhanced drug delivery of interleukin-4 Pseudomonas exotoxin (PRX321): increased distribution and magnetic resonance monitoring.

Convection-enhanced drug delivery (CED) enables achieving a drug concentration within brain tissue and brain tumors that is orders of magnitude higher than by systemic administration. Previous phase I/II clinical trials using intratumoral convection of interleukin-4 Pseudomonas exotoxin (PRX321) have demonstrated an acceptable safety and toxicity profile with promising signs of therapeutic activity. The present study was designed to assess the distribution efficiency and toxicity of this PRX321 using magnetic resonance imaging (MRI) and to test whether reformulation with increased viscosity could enhance drug distribution. Convection of low- [0.02% human serum albumin (HSA)] and high-viscosity (3% HSA) infusates mixed with gadolinium-diethylenetriamine pentaacetic acid and PRX321 were compared with low- and high-viscosity infusates without the drug, in normal rat brains. MRI was used for assessment of drug distribution and detection of early and late toxicity. Representative brain samples were subjected to histological examination. Distribution volumes calculated from the magnetic resonance images showed that the average distribution of 0.02% HSA was larger than that of 0.02% HSA with PRX321 by a factor of 1.98 (p < 0.02). CED of 3.0% HSA, with or without PRX321, tripled the volume of distribution compared with 0.02% HSA with PRX321 (p < 0.015). No drug-related toxicity was detected. These results suggest that the impeded convection of the PRX321 infusate used in previous clinical trials can be reversed by increasing infusate viscosity and lead to tripling of the volume of distribution. This effect was not associated with any detectable toxicity. A similar capability to reverse impeded convection was also demonstrated in a CED model using acetic acid. These results will be implemented in an upcoming phase IIb PRX321 CED trial with a high-viscosity infusate.

Line-scan diffusion tensor imaging of the posttraumatic brain stem: changes with neuropathologic correlation.

Following trauma, imaging of brain stem lesions is often inconclusive. In a man who suffered a lethal accident, postmortem MR diffusion tensor (DT) imaging of the brain and neuropathologic examination were performed. DT imaging showed a disorganization of fibers in the brain stem that was not found in 2 controls and corresponded to changes on neuropathologic correlation. Diffusion tensor imaging provides an insight into the organization of myelinated structures of the CNS, potentially allowing diagnosis of traumatic fiber tract rupture.

DTI and MTR abnormalities in schizophrenia: analysis of white matter integrity.

Diffusion tensor imaging (DTI) studies in schizophrenia demonstrate lower anisotropic diffusion within white matter due either to loss of coherence of white matter fiber tracts, to changes in the number and/or density of interconnecting fiber tracts, or to changes in myelination, although methodology as well as localization of such changes differ between studies. The aim of this study is to localize and to specify further DTI abnormalities in schizophrenia by combining DTI with magnetization transfer imaging (MTI), a technique sensitive to myelin and axonal alterations in order to increase specificity of DTI findings. 21 chronic schizophrenics and 26 controls were scanned using Line-Scan-Diffusion-Imaging and T1-weighted techniques with and without a saturation pulse (MT). Diffusion information was used to normalize co-registered maps of fractional anisotropy (FA) and magnetization transfer ratio (MTR) to a study-specific template, using the multi-channel daemon algorithm, designed specifically to deal with multidirectional tensor information. Diffusion anisotropy was decreased in schizophrenia in the following brain regions: the fornix, the corpus callosum, bilaterally in the cingulum bundle, bilaterally in the superior occipito-frontal fasciculus, bilaterally in the internal capsule, in the right inferior occipito-frontal fasciculus and the left arcuate fasciculus. MTR maps demonstrated changes in the corpus callosum, fornix, right internal capsule, and the superior occipito-frontal fasciculus bilaterally; however, no changes were noted in the anterior cingulum bundle, the left internal capsule, the arcuate fasciculus, or inferior occipito-frontal fasciculus. In addition, the right posterior cingulum bundle showed MTR but not FA changes in schizophrenia. These findings suggest that, while some of the diffusion abnormalities in schizophrenia are likely due to abnormal coherence, or organization of the fiber tracts, some of these abnormalities may, in fact, be attributed to or coincide with myelin/axonal disruption.

Dairy cream as a phantom material for biexponential diffusion decay.

Commercially available aliquots of dairy cream are shown to have diffusion decay curves characterized by biexponential functions when studied over a wide range of b-factors. The fast and slow diffusion components responsible for the biexponential decay are attributed to water and lipid protons, respectively. The fast diffusion coefficient and relative fast and slow diffusion component fractions obtained from biexponential fits of cream phantoms over a wide range of b-factors up to 3,000 s/mm2 are similar to those obtained previously for brain. The slow diffusion coefficient from lipid protons is smaller than that found in the brain. Overall, however, the results suggest that dairy cream can serve as a widely available phantom material for testing software and hardware components designed to perform quantitative, biexponential diffusion decay studies.

Processing and visualization for diffusion tensor MRI.

This paper presents processing and visualization techniques for Diffusion Tensor Magnetic Resonance Imaging (DT-MRI). In DT-MRI, each voxel is assigned a tensor that describes local water diffusion. The geometric nature of diffusion tensors enables us to quantitatively characterize the local structure in tissues such as bone, muscle, and white matter of the brain. This makes DT-MRI an interesting modality for image analysis. In this paper we present a novel analytical solution to the Stejskal-Tanner diffusion equation system whereby a dual tensor basis, derived from the diffusion sensitizing gradient configuration, eliminates the need to solve this equation for each voxel. We further describe decomposition of the diffusion tensor based on its symmetrical properties, which in turn describe the geometry of the diffusion ellipsoid. A simple anisotropy measure follows naturally from this analysis. We describe how the geometry or shape of the tensor can be visualized using a coloring scheme based on the derived shape measures. In addition, we demonstrate that human brain tensor data when filtered can effectively describe macrostructural diffusion, which is important in the assessment of fiber-tract organization. We also describe how white matter pathways can be monitored with the methods introduced in this paper. DT-MRI tractography is useful for demonstrating neural connectivity (in vivo) in healthy and diseased brain tissue.

Slab scan diffusion imaging.

For maximum robustness of a diffusion-weighted MR imaging sequence, it is desirable to use a single-shot imaging method. This article introduces a new single-shot imaging approach that combines the advantages of multiple spin-echoes with the technique of line scan diffusion imaging. A slab volume, which can be spatially encoded with fewer phase encodes than a regular field of view, is selected with 2D selective pulses. With the shorter echo train, the sensitivity to field inhomogeneities and chemical shift is thus greatly diminished. Further reduction is achieved by interleaving short gradient echo trains with refocusing spin-echo pulses. Optimized slice-selective RF pulses that produce flip angles close to 180 degrees are used to minimize the stimulated echo component. Motion-related phase shifts, which change polarity with each spin-echo excitation, will give rise to artifacts that are avoidable by processing even and odd spin-echoes separately. As with line scan diffusion imaging, the complete field of view is acquired by sequential scanning. Since with each shot several lines of data are collected, a considerable improvement over line scan diffusion imaging in terms of scanning speed is achieved. Diffusion data obtained in phantoms and normal subjects demonstrate the feasibility of this novel approach.

Biexponential apparent diffusion coefficient parametrization in adult vs newborn brain.

The decay of brain water signal with b-factor in adult and newborn brains has been measured over an extended b-factor range. Measurements of the apparent diffusion coefficient (ADC) decay curves were made at 16 b-factors from 100 to 5000 s/mm(2) along three orthogonal directions using a line scan diffusion imaging (LSDI) sequence to acquire data from 0.09 ml voxels in a mid-brain axial slice. Regions-of-interest (ROIs) in cortical gray (CG) and white matter in the internal capsule (IC) were selected for ADC decay curve analyses using a biexponential fitting model over this extended b-factor range. Measures of the fast and slow ADC component amplitudes and the traces of the fast and slow diffusion coefficients were obtained from CG and IC ROIs in both adults and newborns. The ADC decay curves from the newborn brain regions were found to have a significantly higher fraction of the fast diffusion ADC component than corresponding regions in the adult brain. The results demonstrate that post-natal brain development has a profound affect on the biexponential parameters which characterize the decay of water signal over an extended b-factor range in both gray and white matter.

Monitoring response to convection-enhanced taxol delivery in brain tumor patients using diffusion-weighted magnetic resonance imaging.

Convection-enhanced drug delivery (CEDD) is a novel approach to enhance the delivery of drugs directly into brain tumors. We have used diffusion-weighted MRI (DWMRI) to monitor the effects of intratumoral CEDD in three brain tumor patients treated with Taxol. Clear changes in the images and the water diffusion parameters were observed shortly after the initiation of treatment. Initially, a bright area corresponding to decreased diffusion appeared, followed by the appearance of a dark area of increased diffusion within the bright area. The time to appearance of the dark area varied among the patients, suggesting different response rates. In this work, we have demonstrated the feasibility of using DWMRI as a noninvasive tool to achieve unique early tissue characterization not attainable by other conventional imaging methods.

Line scan diffusion tensor MRI of the cervical spinal cord in preterm infants.

Line scan diffusion tensor magenetic resonance imaging (DT-MRI) of the cervical spinal cord was demonstrated in vivo for unsedated preterm (gestational age 24-30 weeks at birth), very low birthweight (birthweight 620-1300 g) infants at postmenstrual ages from 29-40 weeks. Scalar invariant measures of diffusion [apparent diffusion coefficient (ADC) and relative anisotropy (RA)] determined from a cervical cord region of interest in each case are reported, characterizing the maturational status of the normal third trimester and newborn spinal cord. Mean ADC of 11 infants was 1.2 +/- 0.1 microm(2)/msec and the mean RA was 24.3 +/- 4.9%. Normal infant cord neural fiber tract morphology was visualized using a mapping of the predominant diffusion tensor eigenvector. Potential clinical applications of line scan DT-MRI of the spinal cord of preterm and term newborns for assessment of spinal cord injury are discussed. J. Magn. Reson. Imaging 2001;13:949-953.

Normal brain and brain tumor: multicomponent apparent diffusion coefficient line scan imaging.

Magnetic resonance line scan diffusion imaging of the brain, with diffusion weighting between 5 and 5,000 sec/mm(2), was performed in healthy subjects and patients with a 1.5-T machine. For each voxel, biexponential signal decay fits produced two apparent diffusion constants and respective signal amplitudes. Images based on these parameters show potential for use in the differentiation of gray and white matter, edema, and tumor.

Regional differences in cell loss associated with binge-like alcohol exposure during the first two trimesters equivalent in the rat.

Women who abuse alcohol during pregnancy may deliver offspring who could be diagnosed with fetal alcohol syndrome (FAS) or a less severe deficit involving cognitive and behavioral disorders. The severity of the deficits may involve the interaction of several known risk factors, such as alcohol consumption pattern or duration, the timing of alcohol consumption relative to critical windows of vulnerability, or the inherent differential vulnerability among the various brain regions to alcohol-induced brain injury. In this study, we explore the vulnerability of the different brain regions by making cell counts from multiple brain regions. Specifically, we used stereological cell-counting techniques to estimate the total cell numbers in the cerebellum (Purkinje and granule cells), olfactory bulb (mitral and granule cells), hippocampus (CA1 and CA3 cells), and dentate gyrus (granule cells). Groups of timed-pregnant Sprague-Dawley rats were assigned to one of five treatments: alcohol by intragastric intubation (2.25, 4.5, or 6.5 g/kg/day), nutritional control [pairfed and intubated=Pairfed) and intubated], and normal control (Chow). Treatments began on embryonic day 1 (E1) and continued through E20. On E33 (usually postnatal day 10), all offspring were perfused intracardially with saline followed by fixatives. Representative forebrains, cerebella, and olfactory bulb from each group were processed for cell counting. The optical dissector was used to obtain cell densities, while Cavalieri's principle was used to calculate the reference volume. The product of density and volume gave unbiased estimates of the total neuronal number within each brain region. Overall peak BACs (regardless of sampling day) for the three alcohol groups averaged 136, 290, and 422 mg/dl for the 2.25-, 4.5-, and 6.5-g/kg groups, respectively. The total number of cerebellar Purkinje cells was reduced in the 6.5-g/kg group relative to controls, while the total number of olfactory bulb mitral cells and hippocampal CA1 and CA3 pyramidal cells from all alcohol-treated groups was not different from controls. Total numbers of granule neurons were reduced in the cerebellum and olfactory bulb of offspring exposed to 4.5 or 6.5 g/kg/day, but granule cell numbers in the dentate gyrus were not affected by the prenatal alcohol treatment. Taken together with previous findings, these data demonstrate that prenatal alcohol exposure results in regional vulnerability of various brain structures and underscores the variability of deleterious effects of alcohol on brain development.

Microstructural brain development after perinatal cerebral white matter injury assessed by diffusion tensor magnetic resonance imaging.

OBJECTIVE: Brain injury in premature infants is characterized predominantly by perinatally acquired lesions in the cerebral white matter (WM). The impact of such injury on the subsequent development of cerebral WM is not clear. This study uses diffusion tensor magnetic resonance imaging (MRI) to evaluate the effects of cerebral WM injury on subsequent microstructural brain development in different WM areas of the brain. METHODS: Twenty premature infants (gestational age: 29.1 +/- 1.9 weeks) were studied by conventional MRI within the first 3 weeks of life and again at term, with the addition at the latter time of diffusion tensor MRI. Ten of the preterm infants had cerebral WM injury identified by the early MRI and were matched with 10 premature infants of similar gestational age and neonatal course but with normal neonatal MRI scans. Diffusion tensor MRI at term was acquired in coronal and axial planes and used to determine the apparent diffusion coefficient, a measure of overall restriction to water diffusion, and the relative anisotropy (RA), a measure of preferred directionality of diffusion, in central WM, anterior frontal WM, occipital WM, temporal WM, and the posterior limb of the internal capsule. Diffusion vector maps were generated from the diffusion tensor analysis to define the microstructural architecture of the cerebral WM regions. RESULTS: At term, the diffusion tensor MRI revealed no difference in apparent diffusion coefficient among preterm infants with or without perinatal WM lesions. By contrast, RA, the measure of preferred directionality of diffusion and thereby dependent on development of axonal fibers and oligodendroglia, was 25% lower in central WM, the principal site of the original WM injury. However, RA was unaffected in relatively uninjured WM areas, such as temporal, anterior frontal, and occipital regions. Notably, RA values in the internal capsule, which contains fibers that descend from the injured cerebral WM, were 20% lower in the infants with WM injury versus those without. Diffusion vector maps showed striking alterations in the size, orientation, and organization of fiber tracts in central WM and in those descending to the internal capsule. CONCLUSIONS: Perinatal cerebral WM injury seems to have major deleterious effects on subsequent development of fiber tracts both in the cerebral WM and more distally. The ultimate impact of brain injury in the newborn should be considered as a function not only of tissue destruction, but also of impaired subsequent brain development.

Intraoperative diffusion imaging on a 0.5 Tesla interventional scanner.

Intraoperative line scan diffusion imaging (LSDI) on a 0.5 Tesla interventional MRI was performed during neurosurgery in three patients. Diffusion trace images were obtained in acute ischemic cases. Scan time per slice was 46 seconds and 94 seconds, respectively, for diffusion tensor images. Diagnosis of acutely developed vascular occlusion was confirmed with follow-up scans. White matter tracts were displayed with the principal eigenvectors and provided guidance for the tumor surgery. In all cases, the diagnostic utility of LSDI was established. J. Magn. Reson. Imaging 2001;13:115-119.

Motion robust imaging for continuous intraoperative MRI.

The sensitivity of MR imaging to motion and susceptibility normally requires that the physician using intraoperative MRI cease surgical activity while image data sets are acquired. We demonstrate that line scan imaging allows the physician to continue operating without the delays caused by imaging. Consequently, patient anesthesia, surgery, and operating room time can be reduced. J. Magn. Reson. Imaging 2001;13:158-161.

Drinking patterns and alcohol-related birth defects.

The consequences of maternal alcohol use during pregnancy on the outcome of offspring depend, among other factors, on the amount and pattern of alcohol consumption. Animal studies found that bingelike drinking patterns, in which the fetus is exposed to high blood alcohol concentrations (BACs) over relatively short periods of time, are particularly harmful, even if the overall alcohol amount consumed is less than those of more continuous drinking patterns. Long-term studies in humans have confirmed that children of binge-drinking mothers exhibited especially severe cognitive and behavioral deficits. Binge drinking may be particularly harmful because it results in high BACs, may occur during critical periods of brain development, and may be associated with repeated withdrawal episodes.

MR line-scan diffusion imaging of the spinal cord in children.

Diffusion imaging has been widely used in the brain, but its application in the spinal cord has been limited. Using line-scan diffusion imaging (LSDI), a technique that is less sensitive to magnetic susceptibility and motion artifacts than are other diffusion techniques, we have successfully imaged the spinal cord in children. The apparent diffusion coefficient and relative diffusion anisotropy of the normal spinal cord were measured. LSDI was compared with echo-planar diffusion imaging of the spine in three patients.

Multi-component apparent diffusion coefficients in human brain: relationship to spin-lattice relaxation.

In vivo measurements of the human brain tissue water signal decay with b-factor over an extended b-factor range up to 6,000 s/mm(2) reveal a nonmonoexponential decay behavior for both gray and white matter. Biexponential parametrization of the decay curves from cortical gray (CG) and white matter voxels from the internal capsule (IC) of healthy adult volunteers describes the decay process and serves to differentiate between these two tissues. Inversion recovery experiments performed in conjunction with the extended b-factor signal decay measurements are used to make separate measurements of the spin-lattice relaxation times of the fast and slow apparent diffusion coefficient (ADC) components. Differences between the spin-lattice relaxation times of the fast and slow ADC components were not statistically significant in either the CG or IC voxels. It is possible that the two ADC components observed from the extended b-factor measurements arise from two distinct water compartments with different intrinsic diffusion coefficients. If so, then the relaxation results are consistent with two possibilities. Either the spin-lattice relaxation times within the compartments are similar or the rate of water exchange between compartments is "fast" enough to ensure volume averaged T(1) relaxation yet "slow" enough to allow for the observation of biexponential ADC decay curves over an extended b-factor range. Magn Reson Med 44:292-300, 2000.

Phase-velocity cine magnetic resonance imaging measurement of pulsatile blood flow in children and young adults: in vitro and in vivo validation.

Quantification of blood flow in vessels provides valuable information that aids management decisions in a variety of cardiac conditions. Current flow measurement techniques are often limited by accuracy, time resolution, convenience, or anatomic localization. This study examined the accuracy of a commercially available phase-velocity cine magnetic resonance imaging (PVC MRI) technique to quantify flow rate in a pulsatile flow phantom. In addition, the equivalence of PVC MRI measurements of pulmonary and systemic flow was evaluated in children and adults without any pathologic shunt. Using a pulsatile flow phantom, volume flow rates measured by PVC MRI were compared to those by a transit-time ultrasound flowmeter over a range of flow rates (1.25-3.5 L/min, 13 trials). Close agreement was found between these techniques (y = 1.02x - 0.02, r = 0.99, Bland-Altman bias = -0.045 L/min, 95% limits of agreement = -0. 19-0.10 L/min). Twenty subjects (median age 12.8 years, range 0.7-49 years) with no pathologic shunt underwent PVC MRI measurement of blood flow in the main pulmonary artery (Q(p)) and the ascending aorta (Q(s)). Data processing time for each location was 20 minutes. The Q(p)/Q(s) ratio closely approximated unity (mean = 0.99, SD = 0. 10, range 0.85-1.19). Interobserver agreement was excellent (Bland-Altman bias = 0.09 L/min, 95% limits of agreement = 0.15-0.33 L/min). PVC MRI is an accurate technique to quantify pulsatile blood flow at a specific location. It can be used to noninvasively calculate Q(p) and Q(s) under normal flow conditions.