Xiaohong Joe Zhou

High-resolution diffusion tensor imaging in the substantia nigra of de novo Parkinson disease

Background: In the midbrain of patients with Parkinson disease (PD), there is a selective loss of dopaminergic neurons in the ventrolateral and caudal substantia nigra (SN). In a mouse model of PD, investigators have administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and found that measures derived using diffusion tensor imaging (DTI) were correlated with the number of dopamine neurons lost following intoxication. Methods: Twenty-eight subjects (14 with early stage, untreated PD and 14 age- and gender-matched controls) were studied with a high-resolution DTI protocol at 3 Tesla using an eight-channel phase array coil and parallel imaging to study specific segments of degeneration in the SN. Regions of interest were drawn in the rostral, middle, and caudal SN by two blinded and independent raters. Results: Fractional anisotropy (FA) was reduced in the SN of subjects with PD compared with controls (p < 0.001). Post hoc analysis identified that reduced FA for patients with PD was greater in the caudal compared with the rostral region of interest (p < 0.00001). A receiver operator characteristic analysis in the caudal SN revealed that sensitivity and specificity were 100% for distinguishing patients with PD from healthy subjects. Findings were consistent across both raters. Conclusions: These findings provide evidence that high resolution diffusion tensor imaging in the substantia nigra distinguishes early stage, de novo patients with Parkinson disease (PD) from healthy individuals on a patient by patient basis and has the potential to serve as a noninvasive early biomarker for PD.

Diffusion Tensor Imaging Study of White Matter Fiber Tracts in Pediatric Bipolar Disorder and Attention-Deficit/Hyperactivity Disorder

BACKGROUND To investigate microstructure of white matter fiber tracts in pediatric bipolar disorder (PBD) and attention-deficit/hyperactivity disorder (ADHD). METHODS A diffusion tensor imaging (DTI) study was conducted at 3 Tesla on age- and IQ-matched children and adolescents with PBD (n = 13), ADHD (n = 13), and healthy control subjects (HC) (n = 15). Three DTI parameters, fractional anisotropy (FA), apparent diffusion coefficient (ADC), and regional fiber coherence index (r-FCI), were examined in eight fiber tracts: anterior corona radiata (ACR), anterior limb of the internal capsule (ALIC), superior region of the internal capsule (SRI), posterior limb of the internal capsule (PLIC), superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), cingulum (CG), and splenium (SP). RESULTS Significantly lower FA was observed in ACR in both PBD and ADHD relative to HC. In addition, FA and r-FCI values were significantly lower in ADHD relative to PBD and HC in both the ALIC and the SRI. Further, ADC was significantly greater in ADHD relative to both the PBD and HC in ACR, ALIC, PLIC, SRI, CG, ILF, and SLF. CONCLUSIONS Decreased FA in ACR implies an impaired fiber density or reduced myelination in both PBD and ADHD in this prefrontal tract. These abnormalities, together with the reduced fiber coherence, extended to corticobulbar tracts in ADHD. Increased ADC across multiple white matter tracts in ADHD indicates extensive cellular abnormalities with less diffusion restriction in ADHD relative to PBD.

Association of Cerebral Deficits With Clinical Symptoms in Antipsychotic-Naive First-Episode Schizophrenia: An Optimized Voxel-Based Morphometry and Resting State Functional Connectivity Study

OBJECTIVE The purpose of the present study was to characterize the association between clinical symptoms and anatomical and functional cerebral deficits in a relatively large sample of antipsychotic-naive first-episode schizophrenia patients using optimized voxel-based morphometry and resting state functional connectivity analysis. METHOD Participants were 68 antipsychotic-naive first-episode schizophrenia patients and 68 matched healthy comparison subjects. Both patients and healthy comparison subjects were scanned using a volumetric three-dimensional spoiled gradient recall sequence and a gradient-echo echo-planar imaging sequence. Psychopathology of first-episode schizophrenia patients was evaluated using the Positive and Negative Syndrome Scale (PANSS). Optimized voxel-based morphometry was used to characterize gray matter deficits in schizophrenia patients. The clinical significance of regional volume reduction was investigated by examining its association with symptoms in patients with first-episode schizophrenia and with alterations in resting state functional connectivity when brain regions with gray matter volume reduction were used as seed areas. RESULTS Significantly decreased gray matter volume was observed in schizophrenia patients in the right superior temporal gyrus (Brodmanns area 41), right middle temporal gyrus (Brodmanns area 21), and right anterior cingulate gyrus (Brodmanns area 32). Decreased gray matter volume in these brain regions was related to greater disturbance as shown on PANSS scores for positive symptoms, general psychopathology symptoms, thought disturbance, activation, paranoia, and impulsive aggression as well as total PANSS scores. A positive correlation was observed between PANSS scores for thought disturbance and temporo-putamen connectivity, and negative correlations were found between temporo-precuneus connectivity and total PANSS scores as well as scores for negative symptoms and anergia. CONCLUSIONS The findings revealed volume loss in the right superior temporal gyrus, right middle temporal gyrus, and right anterior cingulate gyrus among antipsychotic-naive first-episode schizophrenia patients. In addition, the functional networks involving the right superior temporal gyrus and middle temporal gyrus were associated with clinical symptom severity. No abnormalities were observed in resting state connectivity with regions of identified gray matter deficits.

Thalamic integrity underlies executive dysfunction in traumatic brain injury

Objective: To quantify the effects of traumatic brain injury on integrity of thalamocortical projection fibers and to evaluate whether damage to these fibers accounts for impairments in executive function in chronic traumatic brain injury. Methods: High-resolution (voxel size: 0.78 mm × 0.78 mm × 3 mm3) diffusion tensor MRI of the thalamus was conducted on 24 patients with a history of single, closed-head traumatic brain injury (TBI) (12 each of mild TBI and moderate to severe TBI) and 12 age- and education-matched controls. Detailed neuropsychological testing with an emphasis on executive function was also conducted. Fractional anisotropy was extracted from 12 regions of interest in cortical and corpus callosum structures and 7 subcortical regions of interest (anterior, ventral anterior, ventral lateral, dorsomedial, ventral posterior lateral, ventral posterior medial, and pulvinar thalamic nuclei). Results: Relative to controls, patients with a history of brain injury showed reductions in fractional anisotropy in both the anterior and posterior corona radiata, forceps major, the body of the corpus callosum, and fibers identified from seed voxels in the anterior and ventral anterior thalamic nuclei. Fractional anisotropy from cortico-cortico and corpus callosum regions of interest did not account for significant variance in neuropsychological function. However, fractional anisotropy from the thalamic seed voxels did account for variance in executive function, attention, and memory. Conclusions: The data provide preliminary evidence that traumatic brain injury and resulting diffuse axonal injury results in damage to the thalamic projection fibers and is of clinical relevance to cognition.

CEST signal at 2ppm (CEST@2ppm) from Z-spectral fitting correlates with creatine distribution in brain tumor.

In general, multiple components such as water direct saturation, magnetization transfer (MT), chemical exchange saturation transfer (CEST) and aliphatic nuclear Overhauser effect (NOE) contribute to the Z‐spectrum. The conventional CEST quantification method based on asymmetrical analysis may lead to quantification errors due to the semi‐solid MT asymmetry and the aliphatic NOE located on a single side of the Z‐spectrum. Fitting individual contributors to the Z‐spectrum may improve the quantification of each component. In this study, we aim to characterize the multiple exchangeable components from an intracranial tumor model using a simplified Z‐spectral fitting method. In this method, the Z‐spectrum acquired at low saturation RF amplitude (50 Hz) was modeled as the summation of five Lorentzian functions that correspond to NOE, MT effect, bulk water, amide proton transfer (APT) effect and a CEST peak located at +2 ppm, called CEST@2ppm. With the pixel‐wise fitting, the regional variations of these five components in the brain tumor and the normal brain tissue were quantified and summarized. Increased APT effect, decreased NOE and reduced CEST@2ppm were observed in the brain tumor compared with the normal brain tissue. Additionally, CEST@2ppm decreased with tumor progression. CEST@2ppm was found to correlate with the creatine concentration quantified with proton MRS. Based on the correlation curve, the creatine contribution to CEST@2ppm was quantified. The CEST@2ppm signal could be a novel imaging surrogate for in vivo creatine, the important bioenergetics marker. Given its noninvasive nature, this CEST MRI method may have broad applications in cancer bioenergetics. Copyright

Analytical error propagation in diffusion anisotropy calculations.

To develop an analytical formalism describing how noise and selection of diffusion‐weighting scheme propagate through the diffusion tensor imaging (DTI) computational chain into variances of the diffusion tensor elements, and errors in the relative anisotropy (RA) and fractional anisotropy (FA) indices.

White matter microstructure in untreated first episode bipolar disorder with psychosis: Comparison with schizophrenia

Lu LH, Zhou XJ, Keedy SK, Reilly JL, Sweeney JA. White matter microstructure in untreated first episode bipolar disorder with psychosis: comparison with schizophrenia. Bipolar Disord 2011: 13: 604–613.

Concomitant gradient field effects in spiral scans.

Maxwells equations imply that imaging gradients are accompanied by higher order spatially varying fields (concomitant fields) that can cause artifacts in MR imaging. The lowest order concomitant fields depend quadratically on the imaging gradient amplitude and inversely on the static field strength. Time‐varying concomitant fields that accompany the readout gradients of spiral scans cause unwanted phase accumulation during the readout, resulting in spatially dependent blurring. Concomitant field phase errors are independent of echo time and, therefore, cannot be detected using Dixon‐type field map measurements that are normally used to deblur spiral scan images. Data acquisition methods that reduce concomitant field blurring increase off‐resonant spin blurring, and vice versa. Blurring caused by concomitant fields can be removed by variations of image reconstruction methods developed to correct for spatially dependent resonance offsets with nonrectangular k‐space trajectories. Magn Reson Med 41:103‐112, 1999.

Diffusion Tensor Imaging of Parkinson's Disease, Atypical Parkinsonism, and Essential Tremor

Diffusion tensor imaging could be useful in characterizing movement disorders because it noninvasively examines multiple brain regions simultaneously. We report a multitarget imaging approach focused on the basal ganglia and cerebellum in Parkinsons disease, parkinsonian variant of multiple system atrophy, progressive supranuclear palsy, and essential tremor and in healthy controls. Seventy‐two subjects were studied with a diffusion tensor imaging protocol at 3 Tesla. Receiver operating characteristic analysis was performed to directly compare groups. Sensitivity and specificity values were quantified for control versus movement disorder (92% sensitivity, 88% specificity), control versus parkinsonism (93% sensitivity, 91% specificity), Parkinsons disease versus atypical parkinsonism (90% sensitivity, 100% specificity), Parkinsons disease versus multiple system atrophy (94% sensitivity, 100% specificity), Parkinsons disease versus progressive supranuclear palsy (87% sensitivity, 100% specificity), multiple system atrophy versus progressive supranuclear palsy (90% sensitivity, 100% specificity), and Parkinsons disease versus essential tremor (92% sensitivity, 87% specificity). The brain targets varied for each comparison, but the substantia nigra, putamen, caudate, and middle cerebellar peduncle were the most frequently selected brain regions across classifications. These results indicate that using diffusion tensor imaging of the basal ganglia and cerebellum accurately classifies subjects diagnosed with Parkinsons disease, atypical parkinsonism, and essential tremor and clearly distinguishes them from control subjects.

Effects of aging on the ventral and dorsal substantia nigra using diffusion tensor imaging

Dopaminergic neurons in the substantia nigra produce dopamine for the nigrostriatal pathway that facilitates motor function. Postmortem examinations demonstrate an age-related loss of cells in the substantia nigra, with most of the cell loss focused on the dorsal substantia nigra compared with the ventral substantia nigra. The current study used diffusion tensor imaging (DTI) to provide the first in vivo assessment of age-related degeneration in specific segments of the substantia nigra of humans. Measures extracted from DTI of 16 young adults (19-27 years) and 15 older adults (55-71 years) showed that in the dorsal substantia nigra, fractional anisotropy was reduced and radial diffusivity was increased with age. In the ventral substantia nigra and red nucleus, there were no differences across age for the DTI measures. DTI provides a noninvasive technique that accurately reflects the established pattern of age-related cell loss in the dorsal and ventral substantia nigra, further suggesting the robust potential for using DTI to characterize degeneration in the nigrostriatal pathway in both health and disease.