The factors that determine symptom penetrance in inherited disease are poorly understood. Increasingly, magnetic resonance diffusion tensor imaging (DTI) and PET are used to separate alterations in brain structure and function that are linked to disease symptomatology from those linked to gene carrier status. One example is DYT1 dystonia, a dominantly inherited movement disorder characterized by sustained muscle contractions, postures, and/or involuntary movements. This form of dystonia is caused by a 3-bp deletion (i.e., ΔE) in the TOR1A gene that encodes torsinA. Carriers of the DYT1 dystonia mutation, even if clinically nonpenetrant, exhibit abnormalities in cerebellothalamocortical (CbTC) motor pathways. However, observations in human gene carriers may be confounded by variability in genetic background and age. To address this problem, we implemented a unique multimodal imaging strategy in a congenic line of DYT1 mutant mice that contain the ΔE mutation in the endogenous mouse torsinA allele (i.e., DYT1 knock-in). Heterozygous knock-in mice and littermate controls underwent microPET followed by ex vivo high-field DTI and tractographic analysis. Mutant mice, which do not display abnormal movements, exhibited significant CbTC tract changes as well as abnormalities in brainstem regions linking cerebellar and basal ganglia motor circuits highly similar to those identified in human nonmanifesting gene carriers. Moreover, metabolic activity in the sensorimotor cortex of these animals was closely correlated with individual measures of CbTC pathway integrity. These findings further link a selective brain circuit abnormality to gene carrier status and demonstrate that DYT1 mutant torsinA has similar effects in mice and humans.
Abstract A theoretical framework is presented for designing birdcage resonators for MRI and MR spectroscopy. The analogy between the birdcage problem and the phonon problem in solid‐state physics is used to achieve multiple tuning. Allowing that the capacitances in the columns of the cage assume unequal values, it is possible to achieve multiple tuning and simultaneously preserve the sinusoidal current distribution necessary to set a homogeneous magnetic field. Given the physical dimensions of the columns and branches of the cage as well as the desired resonant frequencies, the corresponding values of the capacitances can be calculated exactly. Closed‐form expressions for the capacitances are given in terms of the mutual inductances and the desired resonant frequencies. A detailed analysis for a symmetrical low‐pass birdcage is presented. The expressions for the resonant frequencies reduce to those given by other authors when only nearestneighbor mutual inductances are included.
Aims : Evaluation of the average brain diffusion constant in Fabry disease. Introduction : Fabry disease is an X‐linked recessive lysosomal storage disorder secondary to deficiency of α‐galactosidase A and resulting in excess tissue globotriaosylceramide, particularly in cerebral blood vessels. This has been associated with cerebral hyperperfusion. Increased tissue perfusion should increase interstitial water by the Starling relationship. This hypothesis was examined by measuring the average CNS diffusion constant (D av ) in patients with Fabry disease using diffusion‐weighted magnetic resonance imaging (DWI). Methods : Axial DWI was performed at b = 1000 seconds/mm 2 and b = 1000 seconds/mm 2 (TR (pulse repetition time), 10 000; TE (time to echo), 100; FOV (field of view), 22 cm; 3 mm interleaved slices; image matrix, 128 × 128; GE Signa, 1.5T). Eight healthy male volunteers (age range, 21–47 years) and 17 hemizygous patients with Fabry disease (age range, 19–49 years) were examined. Following DWI acquisition, the trace image and the diffusion distribution map were calculated. The diffusion distribution curve was then fitted by a multi‐modal Gaussian curve, allowing estimation of D av . Results : The D av was 0.743 ±; 0.024 ±; 10 ‐5 cm 2 /second (mean ±; SD) for patients with Fabry disease and 0.726 ±; 0.014 ±; 10 ‐5 cm 2 /second for the control group. D av was significantly increased in the patients with Fabry disease compared with the controls ( p = 0.029) Conclusions : The elevated D av indicates increased brain tissue water diffusivity in patients with Fabry disease, a finding consistent with increased extracellular water and increased cerebral blood flow.
It is crucial to detect the locations of brain tumors for the diagnosis. The aim of this study was the generation and comparison of the high and low-grade probabilistic brain tumor maps to present the tumor observance frequencies in the brain tissue. T1-weighted, pre-operated data from 162 brain tumor patients are examined during the study. Although most of high-grade tumors are located around the superior and right lateral regions of sub-ventricular zone, low-grade gliomas are mostly observed in the posterior part of the sub-ventricular zone. Moreover, since all types of tumors are gathered close to the sub-ventricular zone, our results support the theory proposing that there is a relation between gliomas and sub-ventricular zone, which is the origin of glial cells.
Diffusion tensor imaging an emerging MR imaging modality which has started to be used in clinical setting. Here, we are describing use of quantitative DTI in diagnosis of upper motor neuron diseases: amyotropic lateral sclerosis and primary lateral sclerosis. Upper motor neuron diseases are difficult to diagnose using imaging means. Currently, diagnosis is usually one of exclusion requiring careful clinical examination and series of tests to rule out diseases that may mimic upper motor neuron diseases. Upper motor neuron diseases present with progressive degeneration of corticospinal tract. The relentless disease progression ultimately leads to severe spastic spinobulbar paresis. Since diffusion tensor imaging is sensitive to the changes in tissue microstructure, it is an ideal tool to use in diagnosis of upper motor neuron diseases where the damage in corticospinal tract is microscopic.
Professional boxing is associated with chronic, repetitive head blows that may cause brain injuries. Diffusion-weighted imaging is sensitive to microscopic changes and may be a useful tool to quantify the microstructural integrity of the brain. In this study, we sought to quantify microscopic alterations associated with chronic traumatic brain injury in professional boxers.MR and diffusion-weighted imaging were performed in 24 boxers and in 14 age- and sex-matched control subjects with no history of head trauma. Using distribution analysis, the average diffusion constant of the entire brain (BD(av)) and diffusion distribution width (sigma) were calculated for each subject; findings in professional boxers were compared with those of control subjects. In the boxer group, correlations between diffusion changes and boxing history and diffusion changes and MR imaging findings were assessed.The measured diffusion values in the boxer group were significantly higher than those measured in the control group (BD(av), P <.0001; sigma, P <.01). In the boxer group, a robust correlation was found between increased BD(av) and frequency of hospitalization for boxing injuries (r = 0.654, P <.05). The most common MR finding in the boxer group was volume loss inappropriate to age followed by cavum septum pellucidum, subcortical white matter disease, and periventricular white matter disease.Boxers had higher diffusion constants than those in control subjects. Our data suggest that microstructural damage of the brain associated with chronic traumatic brain injury may elevate whole-brain diffusion. This global elevation can exist even when routine MR findings are normal.
To investigate the value of objective biomarkers for upper (UMN) and lower (LMN) motor neuron involvement in ALS.We prospectively studied 64 patients with ALS and its subsets using clinical measures, proton MR spectroscopic imaging ((1)H MRSI), diffusion tensor imaging, transcranial magnetic stimulation, and the motor unit number estimation (MUNE) at baseline and every 3 months for 15 months and compared them with control subjects.(1)H MRSI measures of the primary motor cortex N-acetyl-aspartate (NAA) concentration were markedly reduced in ALS (p = 0.009) and all UMN syndromes combined (ALS, familial ALS [fALS], and primary lateral sclerosis; p = 0.03) vs control values. Central motor conduction time to the tibialis anterior was prolonged in ALS (p < 0.0005) and combined UMN syndromes (p = 0.001). MUNE was lower in ALS (p < 0.0005) and all LMN syndromes combined (ALS, fALS, and progressive muscular atrophy; p = 0.001) vs controls. All objective markers correlated well with the ALS Functional Rating Scale-Revised, finger and foot tapping, and strength testing, suggesting these markers related to disease activity. Regarding changes over time, MUNE changed rapidly, whereas neuroimaging markers changed more slowly and did not significantly differ from baseline.(1)H MR spectroscopic imaging measures of the primary motor cortex N-acetyl-aspartate (NAA) concentration and ratio of NAA to creatine, central motor conduction time to the tibialis anterior, and motor unit number estimation significantly differed between ALS, its subsets, and control subjects, suggesting they have potential to provide insight into the pathobiology of these disorders.
