[show abstract][hide abstract] ABSTRACT: RTT, caused by mutations in the methyl CPG binding protein 2 (MeCP2) gene, is a disorder of neuronal maturation and connections. Our aim was to prospectively examine FA by DTI and correlate this with certain clinical features in patients with RTT.
Thirty-two patients with RTT underwent neurologic assessments and DTI. Thirty-seven age-matched healthy female control subjects were studied for comparison. With use of a 1.5T MR imaging unit, DTI data were acquired, and FA was evaluated to investigate multiple regional tract-specific abnormalities in patients with RTT.
In RTT, significant reductions in FA were noted in the genu and splenium of the corpus callosum and external capsule, with regions of significant reductions in the cingulate, internal capsule, posterior thalamic radiation, and frontal white matter. In contrast, FA of visual pathways was similar to control subjects. FA in the superior longitudinal fasciculus, which is associated with speech, was equal to control subjects in patients with preserved speech (phrases and sentences) (P = .542), whereas FA was reduced in those patients who were nonverbal or speaking only single words (P < .001). No correlations between FA values for tracts and clinical features such as seizures, gross or fine motor skills, and head circumference were identified.
DTI, a noninvasive technique to assess white matter tract pathologic features, may add specificity to the assessment of RTT clinical severity that is presently based on the classification of MeCP2 gene mutation and X-inactivation.
American Journal of Neuroradiology 10/2009; 31(2):295-9. · 3.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: Conventional MR imaging shows evidence of brain injury and/or maldevelopment in 70%-90% of children with cerebral palsy (CP), though its capability to identify specific white matter tract injury is limited. The great variability of white matter lesions in CP already demonstrated by postmortem studies is thought to be one of the reasons why response to treatment is so variable. Our hypothesis is that diffusion tensor imaging (DTI) is a suitable technique to provide in vivo characterization of specific white matter tract lesions in children with CP associated with periventricular leukomalacia (PVL).
In this study, 24 children with CP associated with PVL and 35 healthy controls were evaluated with DTI. Criteria for identification of 26 white matter tracts on the basis of 2D DTI color-coded maps were established, and a qualitative scoring system, based on visual inspection of the tracts in comparison with age-matched controls, was used to grade the severity of abnormalities. An ordinal grading system (0=normal, 1=abnormal, 2=severely abnormal or absent) was used to score each white matter tract.
There was marked variability in white matter injury pattern in patients with PVL, with the most frequent injury to the retrolenticular part of the internal capsule, posterior thalamic radiation, superior corona radiata, and commissural fibers.
DTI is a suitable technique for in vivo assessment of specific white matter lesions in patients with PVL and, thus, a potentially valuable diagnostic tool. The tract-specific evaluation revealed a family of tracts that are highly susceptible in PVL, important information that can potentially be used to tailor treatment options in the future.
American Journal of Neuroradiology 09/2007; 28(7):1213-22. · 3.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: While holding vast potential, diffusion tensor imaging (DTI) with single-excitation protocols still faces serious challenges. Limited spatial resolution, susceptibility to magnetic field inhomogeneity, and low signal-to-noise ratio (SNR) may be considered the most prominent limitations. It is demonstrated that all of these shortcomings can be effectively mitigated by the transition to parallel imaging technology and high magnetic field strength. Using the sensitivity encoding (SENSE) technique at 3 T, brain DTI was performed in nine healthy volunteers. Despite enhanced field inhomogeneity, parallel acquisition permitted both controlling geometric distortions and enhancing spatial resolution up to 0.8 mm in-plane. Heightened SNR requirements were met in part by high base sensitivity at 3 T. A further significant increase in SNR efficiency was accomplished by SENSE acquisition, exploiting enhanced encoding speed for echo time reduction. Based on the resulting image data, high-resolution tensor mapping is demonstrated.
Magnetic Resonance in Medicine 03/2004; 51(2):230-6. · 3.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: The authors used diffusion-tensor imaging to examine central white matter pathways in two children with spastic quadriplegic cerebral palsy. Corticospinal tracts projecting from cortex to brainstem resembled controls. In contrast, posterior regions of the corpus callosum, internal capsule, and corona radiata were markedly reduced, primarily in white matter fibers connected to sensory cortex. These findings suggest that the motor impairment in periventricular leukomalacia may, in part, reflect disruption of sensory connections outside classic pyramidal motor pathways.
[show abstract][hide abstract] ABSTRACT: Neuroimaging is a key instrument for determining structural and in vivo functional status of the brain, non-invasively. Multiple approaches can now determine aspects of anatomic and neurochemical changes in brain, and have been utilized effectively in Rett Syndrome patients to understand the biological basis of this neurodevelopmental disorder. Studies performed at our institute include volumetric analyses of MRI, magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), cerebral blood flow measurements with MRI, and positron emission tomography scans (PET). These studies have provided considerable insight into mechanisms underlying the clinical features of this disease. Volumetric analyses suggest that decreased brain volume in RS results from global reductions in both gray and white matter of the brain. A selective vulnerability of the frontal lobes is evidenced by the preferential reduction of blood flow, increased choline and reduced n-acetyl aspartate (NAA) by MRS, and increased glucose uptake in these same regions as shown by ((18)F)-fluorodeoxyglucose (FDG) PET scans. We hypothesize that the increased glucose uptake relates to increased glutamate cycling in synapses. The resulting neuroexcitotoxic injury to the developing brain contributes to the seizures, behavioral disturbance and respiratory irregularities commonly seen in phases 1 and 2 of this disorder.
Brain and Development 01/2002; 23 Suppl 1:S62-71. · 1.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: It is shown that diffusion tensor MR imaging (DTI) can discretely delineate the microstructure of white matter and gray matter in embryonic and early postnatal mouse brains based on the existence and orientation of ordered structures. This order was found not only in white matter but also in the cortical plate and the periventricular zone, which are precursors of the cerebral cortex. This DTI-based information could be used to accomplish the automated spatial definition of the cortical plate and various axonal tracts. The DTI studies also revealed a characteristic evolution of diffusion anisotropy in the cortex of the developing brain. This ability to detect changes in the organization of the brain during development will greatly enhance morphological studies of transgenic and knockout models of cortical dysfunction. Magn Reson Med 46:18-23, 2001.
Magnetic Resonance in Medicine 08/2001; 46(1):18-23. · 3.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: MRI studies using mouse brain models of ischemia are becoming a valuable tool for understanding the mechanism of stroke, since transgenic models are now available. However, the small size of the mouse brain and the surgical complexity of creating ischemia in mice make it technically challenging to obtain high-quality MRI data. Therefore, there are few reports of MRI studies in murine cerebral ischemia. In this project a newly developed rapid 3D diffusion-weighted imaging (DWI) technique was applied to study experimental stroke in a mouse model of reversible middle cerebral artery occlusion (MCAO). Ischemic volumes were successfully delineated using this 3D whole-brain imaging technique with high spatial (0.34 x 0.5 x 1.0 mm(3) before zero-filling) and temporal (7 min) resolution. The 3D observation revealed the characteristic evolution of stroke after transient MCAO. There was a temporarily high diffusion constant in the cortex during early reperfusion, followed by a secondary energy failure in the cortex and caudate-putamen at 6 and 21 h of reperfusion. Magn Reson Med 46:183-188, 2001.
Magnetic Resonance in Medicine 08/2001; 46(1):183-8. · 3.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: Brain diffusion tensor MRI of 11 boys with X-linked adrenoleukodystrophy was performed. The authors determined quantitative isotropic apparent diffusion coefficient (ADC(i)) and fractional anisotropy (FA) values in the white matter. ADC(i) and FA values in the affected white matter were significantly different from those in normal-appearing white matter. Zonal ADC(i) and FA gradations, which might originate from well-established histopathologic zonal changes, existed within affected white matter.
[show abstract][hide abstract] ABSTRACT: The in situ assessment of axonal projections of the brain has been severely limited by the lack of noninvasive techniques to study this type of anatomy. We show here that in vivo three-dimensional (3D) reconstruction of axonal projections can be achieved using a rapid 3D high-resolution diffusion-weighted imaging technique combined with a recently designed fiber reconstruction algorithm. As a first example, neuronal pathways in the rat brain were probed. Eight well-known fiber projections; genu and splenium of corpus callosum, internal and external capsule, fimbria, anterior commissure, optic tract, and stria terminalis were tracked and shown to be in agreement with the location of these known axonal projections. The experiment took 2 hr and shorter times should be possible in the clinical situation. By combining anisotropy information with fiber tracking, the anisotropy of individual projections was also documented. Magn Reson Med 42:1123-1127, 1999.
Magnetic Resonance in Medicine 01/2000; 42(6):1123-7. · 3.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: Diffusion magnetic resonance imaging (MRI) is one of the most rapidly evolving techniques in the MRI field. This method exploits the random diffusional motion of water molecules, which has intriguing properties depending on the physiological and anatomical environment of the organisms studied. We explain the principles of this emerging technique and subsequently introduce some of its present applications to neuroimaging, namely detection of ischemic stroke and reconstruction of axonal bundles and myelin fibers.
[show abstract][hide abstract] ABSTRACT: The relationship between brain structure and complex behavior is governed by large-scale neurocognitive networks. The availability of a noninvasive technique that can visualize the neuronal projections connecting the functional centers should therefore provide new keys to the understanding of brain function. By using high-resolution three-dimensional diffusion magnetic resonance imaging and a newly designed tracking approach, we show that neuronal pathways in the rat brain can be probed in situ. The results are validated through comparison with known anatomical locations of such fibers.
Annals of Neurology 03/1999; 45(2):265-9. · 11.19 Impact Factor
[show abstract][hide abstract] ABSTRACT: It is shown that the flow-sensitive alternating inversion recovery (FAIR) technique is complicated by the effect of radiation damping, leading to problems in calibrating this method on phantoms and to inaccuracies in measured flows. A modified scheme called FAIRER (FAIR excluding radiation damping) is proposed, which suppresses the damping effects by employing very weak magnetic field gradients (0.06 G/cm) during the inversion recovery, spin-echo, and predelay periods. Results on phantoms and in vivo on cat brain are presented that demonstrate that FAIRER effectively solves these problems.
Magnetic Resonance in Medicine 12/1998; 40(5):712-9. · 3.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: In this paper, a series of diffusion-weighted fast spin-echo (FSE) sequences with a new motion correction scheme are introduced. This correction scheme is based on the navigator echo technique. Unlike conventional spin-echo imaging, motion correction for FSE is complicated by the phase oscillation between odd-numbered and even-numbered echoes and the complex phase relationship between spin echo and stimulated echo components. In our approach, incoherent phase shifting due to motion is monitored by consecutive acquisition of two navigator echoes, which provide information on both inter-echo and intra-echo train phase shifts. Applications to both phantom and in vivo studies are presented.
Magnetic Resonance in Medicine 11/1998; 40(4):511-6. · 3.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: It is shown that the effect of pH changes can be measured in proton NMR spectra through the pH sensitivity of the signal intensities of metabolite protons exchanging with water. To observe this phenomenon, pulse sequences must be used that can sensitively observe these exchangeable protons under physiological conditions, which is achieved by avoiding magnetization transfer signal losses due to water saturation for solvent suppression purposes. These methods provide an order-of-magnitude enhancement of many signals between 5 and 10 ppm, containing both N-bound protons as well as aromatic C-H protons coupled to them, the intensity of which is influenced by exchange-relayed saturation. As a first application, the effects of pH change on these resonances are studied ex vivo (perfused cells) and in vivo (cat brain).
Magnetic Resonance in Medicine 08/1998; 40(1):36-42. · 3.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: Measurement of exchange rates between water and NH protons by magnetization transfer methods is often complicated by artifacts, such as intramolecular NOEs, and/or TOCSY transfer from C alpha protons coincident with the water frequency, or exchange-relayed NOEs from fast exchanging hydroxyl or amine protons. By applying the Phase-Modulated CLEAN chemical EXchange (CLEANEX-PM) spin-locking sequence, 135 degrees (x) 120 degrees (-x) 110 degrees (x) 110 degrees (-x) 120 degrees (x) 135 degrees (-x) during the mixing period, these artifacts can be eliminated, revealing an unambiguous water-NH exchange spectrum. In this paper, the CLEANEX-PM mixing scheme is combined with Fast-HSQC (FHSQC) detection and used to obtain accurate chemical exchange rates from the initial slope analysis for a sample of 15N labeled staphylococcal nuclease. The results are compared to rates obtained using Water EXchange filter (WEX) II-FHSQC, and spin-echo-filtered WEX II-FHSQC measurements, and clearly identify the spurious NOE contributions in the exchange system.
Journal of Biomolecular NMR 03/1998; 11(2):221-6. · 2.85 Impact Factor
[show abstract][hide abstract] ABSTRACT: The rates of hydrogen exchange were measured in a "physiological" denatured state of staphylococcal nuclease using a NMR magnetization transfer experiment suitable for the measurement of exchange rates faster than 0.5 s-1. The results are compared with predicted exchange rates (kex) for the random coil state (Bai et al., Proteins 17:75-86, 1993). No protection factors (= predicted rate/measured rate) larger than 2.4 were observed, consistent with other NMR data which strongly suggest only small amounts of residual secondary structure in this denatured state. Systematically low protection factors (0.51 +/- 0.23) were found for Asp and Glu residues, while high protection factors were observed for Gly (1.60 +/- 0.60). We conclude that the predicted exchange rates (kex) may have an uncertainty of 2- to 3-fold. Thus, for denatured proteins only protection factors with a value of 5 or larger can be assigned structural significance. These results also demonstrate that multidimensional magnetization transfer NMR techniques are powerful tools in this research field due to its ability to measure rapidly exchanging protons (> 05 s-1) with high accuracy.
Proteins Structure Function and Bioinformatics 07/1997; 28(3):325-32. · 3.34 Impact Factor
[show abstract][hide abstract] ABSTRACT: It is shown that a repetitive pulse sequence consisting of two 90 degrees pulses and gradients in a 1:2 ratio around the second 90 degrees pulse generates interscan shifted stimulated echoes (SSTEs) and intrascan multiple spin echoes (MSEs). Separation of these two types of signals is accomplished using specific gradient crusher schemes. The intensity of the SSTEs is an order of magnitude larger than that of the MSEs and determines the signal contrast if both effects are selected simultaneously. The SSTE sequence generates improved contrast between gray and white matter, even at high field, which is explained in terms of increased inverse T1-weighting for the interscan echo. The MSE image has low signal to noise and no detectable contrast. The effect of interscan diffusion weighting is also discussed.
Magnetic Resonance in Medicine 04/1997; 37(3):336-40. · 3.27 Impact Factor