Assessment of dynamic susceptibility contrast cerebral blood flow response to amphetamine challenge: a human pharmacological magnetic resonance imaging study at 1.5 and 4 T.

Pharmacological MRI (phMRI) techniques can be used to monitor the neurophysiological effects of central nervous system (CNS) active drugs. In this study, we investigated whether dynamic susceptibility contrast (DSC) perfusion imaging employing the use of superparamagnetic iron oxide nanoparticles (Resovist) could be used to measure hemodynamic response to d-amphetamine challenge in human subjects at both 1.5 and 4 T. Significant changes in cerebral blood flow (CBF) were found in focal regions associated with the nigrostriatal circuit and mesolimbic and mesocortical dopaminergic pathways. More significant CBF responses were found at higher field strength, mainly within striatal structures. The results from this study indicate that DSC perfusion imaging using Resovist can be used to assess the efficacy of CNS-active drugs and may play a role in the development of novel psychiatric therapies at the preclinical level.     

Application of image-guided surface coil P-31 MR spectroscopy to human liver, heart, and kidney

Localized phosphorus-31 magnetic resonance (MR) spectroscopy in humans has previously been accomplished with surface coils by means of depth-resolved surface coil spectroscopy or rotating frame experiments, in which the extent of tissue sampled critically depends on surface coil placement. The authors' goal was to modify the surface coil image-selected in vivo spectroscopy (ISIS) experiment to accomplish three-dimensional volume selection through application of selective pulses in the presence of B0 gradients. Advantages of ISIS include the ability to use proton images to define the volume of interest (VOI) and reduced dependence on exact positioning of the surface coil. However, rapid replication of the surface coil ISIS experiment can cause spectral contamination from signals originating outside the VOI. A modified version of the ISIS experiment was developed to alleviate contamination under conditions of rapid replication. Applications of localized P-31 MR spectroscopy for observation of high-energy phosphorus metabolites are presented in human liver, heart, and transplanted and normal kidney.     

Pearls and pitfalls of magnetic resonance imaging of the upper extremity

Magnetic resonance imaging (MRI) is capable of producing images in any anatomical plane, visualizing and analyzing a variety of tissue characteristics, as well as quantifying blood flow and metabolic functions. Although MRI details of compact bone and calcium are poor when compared to those taken with plain radiography or computed tomography, its high soft tissue contrast discrimination and multiplanar imaging capabilities are significant advantages. Musculoskeletal anatomy and neurovascular bundles are well delineated. The advent of MRI has revolutionized the clinician's ability to confirm a proper diagnosis for musculoskeletal problems, which has led to more directed, specific rehabilitative protocols. However, the value of MRI to rehabilitative professionals has been even greater in its ability to identify serious, more uncommon pathologies, such as in those with underlying infection, fracture, or tumor, that require immediate care and are considered to be beyond their scope of practice. Furthermore, MRI, with its precise delineation of fat, muscle, and bone, is an ideal candidate for imaging of muscle disease or injury and has emerged as the method of choice for the detection of early cartilage wear in young patients, such as osteoarthritis. Finally, this imaging modality can avoid radiation exposure in a predominantly younger patient cohort commonly affected by musculoskeletal diseases. The aim of this paper is to consider how physical therapists may take advantage of the diagnostic value of MRI of the upper limb, while avoiding the pitfalls of misinterpretation of images as a result of technical issues, pathological changes, or normal variants.     

Comparison of two-dimensional speckle and tissue velocity based strain and validation with harmonic phase magnetic resonance imaging

Two-dimensional (2-D) strain (epsilon2-D) on the basis of speckle tracking is a new technique for strain measurement. This study sought to validate epsilon2-D and tissue velocity imaging (TVI)-based strain (epsilonTVI) with tagged harmonic-phase (HARP) magnetic resonance imaging (MRI). Thirty patients (mean age 62 +/- 11 years) with known or suspected ischemic heart disease were evaluated. Wall motion (wall motion score index 1.55 +/- 0.46) was assessed by an expert observer. Three apical images were obtained for longitudinal strain (16 segments) and 3 short-axis images for radial and circumferential strain (18 segments). Radial epsilonTVI was obtained in the posterior wall. HARP MRI was used to measure principal strain, expressed as maximal length change in each direction. Values for epsilon2-D, epsilonTVI, and HARP MRI were comparable for all 3 strain directions and were reduced in dysfunctional segments. The mean difference and correlation between longitudinal epsilon2-D and HARP MRI (2.1 +/- 5.5%, r = 0.51, p <0.001) were similar to those between longitudinal epsilonTVI and HARP MRI (1.1 +/- 6.7%, r = 0.40, p <0.001). The mean difference and correlation were more favorable between radial epsilon2-D and HARP MRI (0.4 +/- 10.2%, r = 0.60, p <0.001) than between radial epsilonTVI and HARP MRI (3.4 +/- 10.5%, r = 0.47, p <0.001). For circumferential strain, the mean difference and correlation between epsilon2-D and HARP MRI were 0.7 +/- 5.4% and r = 0.51 (p <0.001), respectively. In conclusion, the modest correlations of echocardiographic and HARP MRI strain reflect the technical challenges of the 2 techniques. Nonetheless, epsilon2-D provides a reliable tool to quantify regional function, with radial measurements being more accurate and feasible than with TVI. Unlike epsilonTVI, epsilon2-D provides circumferential measurements.     

Diffusion indices on magnetic resonance imaging and neuropsychological performance in amnestic mild cognitive impairment

Background

Magnetic resonance diffusion tensor imaging (DTI) shows promise in the early detection of microstructural pathophysiological changes in the brain.

Objectives

To measure microstructural differences in the brains of participants with amnestic mild cognitive impairment (MCI) compared with an age‐matched control group using an optimised DTI technique with fully automated image analysis tools and to investigate the correlation between diffusivity measurements and neuropsychological performance scores across groups.

Methods

34 participants (17 participants with MCI, 17 healthy elderly adults) underwent magnetic resonance imaging (MRI)‐based DTI. To control for the effects of anatomical variation, diffusion images of all participants were registered to standard anatomical space. Significant statistical differences in diffusivity measurements between the two groups were determined on a pixel‐by‐pixel basis using gaussian random field theory.

Results

Significantly raised mean diffusivity measurements (p<0.001) were observed in the left and right entorhinal cortices (BA28), posterior occipital–parietal cortex (BA18 and BA19), right parietal supramarginal gyrus (BA40) and right frontal precentral gyri (BA4 and BA6) in participants with MCI. With respect to fractional anisotropy, participants with MCI had significantly reduced measurements (p<0.001) in the limbic parahippocampal subgyral white matter, right thalamus and left posterior cingulate. Pearson''s correlation coefficients calculated across all participants showed significant correlations between neuropsychological assessment scores and regional measurements of mean diffusivity and fractional anisotropy.

Conclusions

DTI‐based diffusivity measures may offer a sensitive method of detecting subtle microstructural brain changes associated with preclinical Alzheimer''s disease.Substantial effort is currently being focused towards improving the diagnosis of early Alzheimer''s disease. The term mild cognitive impairment (MCI) is often used to describe the transitional stage between normal ageing and dementia. Owing to the heterogeneity of MCI, not all participants with MCI will have predementia Alzheimer''s disease.¹ Peterson et al² suggested the criteria for a subtype of MCI, so‐called amnestic MCI, which is presumed to present a typical prodrome of dementia in Alzheimer''s disease. People with amnestic MCI have a 10–15% annual conversion rate to Alzheimer''s disease compared with 1–2% in the normal elderly population.² Neuroimaging studies conducted on participants with MCI using magnetic resonance imaging (MRI) morphological analysis have consistently reported atrophic changes primarily in the medial temporal lobe and, to a lesser extent, in the thalamus and cingulate gyrus.^3,4,5 Furthermore, the degree of atrophy in temporal lobe structures correlates with performance on memory tasks³ and with density of neurofibrillar tangles at autopsy.⁶ These findings support the concept that MRI‐based neuroimaging studies together with neuropsychological assessment may enable identification of participants with MCI which may progress to Alzheimer''s disease, and evaluation of the efficacy of novel treatments.Recent studies using diffusion tensor magnetic resonance imaging (DTI) have shown microstructural changes in the hippocampus of participants with MCI that may not be apparent using standard anatomical imaging.^7,8,9 DTI measures the random motion of bulk water in cerebral tissue. When the random motion of water is restricted preferentially in one direction when compared with the orthogonal planes, such as occurs in white matter, diffusion is referred to as anisotropic; in contradistinction, bulk water motion in the cerebrospinal fluid is equal in all directions and is thus referred to as isotropic. Fractional anisotropy, a quantitative measurement of the degree of anisotropy, can be used to probe the integrity of white matter fibre tracts.¹⁰ The mean diffusivity is a quantitative measurement of the bulk mean motion of water considered in all directions and is used to interrogate pathological changes in cerebral tissue, such as ischaemia in patients with stroke.¹⁰ DTI studies in patients with MCI have shown raised mean diffusivity in the hippocampus and other temporal lobe regions, using manually traced regions of interest (ROI).^7,8,9 Although the precise neural correlates of altered mean diffusivity measurements are uncertain, increased mean diffusivity most likely results from loss of neurones, axons and dendrites, resulting in an increase in extracellular space and raised water diffusivity in these regions.⁷ It is unknown whether such microstructural changes, detectable by DTI, are due to amyloid or neurofibrillar tangle formation or some other neuropathological process in Alzheimer''s disease. However, the finding of a negative correlation between hippocampal diffusivity and volume in people with MCI indicates that both measurements are sensitive to early Alzheimer''s disease neuropathology.⁷ Using manually defined ROI analyses, a recent study has identified marked changes in volume, mean diffusivity and fractional anisotropy indices in the hippocampus in participants with MCI compared with age‐matched controls.⁹ Specifically, compared with volume measurements, raised left hippocampal mean diffusivity was found to be a strong independent predictor of poor verbal memory performance in both controls and participants with MCI.In this study, we investigated whether mean diffusivity and fractional anisotropy measurements differed between participants with MCI and age‐matched controls, using an optimised DTI protocol¹¹ and a fully automated voxel‐by‐voxel method of data analysis. This approach assesses the entire brain, rather than just one structure, and circumvents any operator‐introduced errors in the manual selection of ROI for analysis. In addition, we investigated the relationship between measurements of water diffusivity and performance on memory and other cognitive tasks across participants.     

Dopamine transporter genotype predicts behavioural and neural measures of response inhibition

The ability to inhibit unwanted actions is a heritable executive function that may confer risk to disorders such as attention deficit hyperactivity disorder (ADHD). Converging evidence from pharmacology and cognitive neuroscience suggests that response inhibition is instantiated within frontostriatal circuits of the brain with patterns of activity that are modulated by the catecholamines dopamine and noradrenaline. A total of 405 healthy adult participants performed the stop-signal task, a paradigmatic measure of response inhibition that yields an index of the latency of inhibition, termed the stop-signal reaction time (SSRT). Using this phenotype, we tested for genetic association, performing high-density single-nucleotide polymorphism mapping across the full range of autosomal catecholamine genes. Fifty participants also underwent functional magnetic resonance imaging to establish the impact of associated alleles on brain and behaviour. Allelic variation in polymorphisms of the dopamine transporter gene (SLC6A3: rs37020; rs460000) predicted individual differences in SSRT, after corrections for multiple comparisons. Furthermore, activity in frontal regions (anterior frontal, superior frontal and superior medial gyri) and caudate varied additively with the T-allele of rs37020. The influence of genetic variation in SLC6A3 on the development of frontostriatal inhibition networks may represent a key risk mechanism for disorders of behavioural inhibition.