scholarly journals Quantitative DTI metrics in a canine model of Krabbe disease: comparisons versus age-matched controls across multiple ages

2018 ◽  
Vol 31 (2) ◽  
pp. 168-176 ◽  
Author(s):  
Jonathan Y Li ◽  
Dana M Middleton ◽  
Steven Chen ◽  
Leonard White ◽  
Carley R Corado ◽  
...  

Purpose The purpose of this study was to compare quantitative diffusion tensor imaging metrics in dogs affected with a model of Krabbe disease to age-matched normal controls. We hypothesized that fractional anisotropy would be decreased and radial diffusivity would be increased in the Krabbe dogs. Methods We used a highly reproducible region-of-interest interrogation technique to measure fractional anisotropy and radial diffusivity in three different white matter regions within the internal capsule and centrum semiovale in four Krabbe affected brains and three age-matched normal control brains. Results Despite all four Krabbe dogs manifesting pelvic limb paralysis at the time of death, age-dependent differences in DTI metrics were observed. In the 9, 12, and 14 week old Krabbe dogs, FA values unexpectedly increased and RD values decreased. FA values were generally higher and RD values generally lower in both regions of the internal capsule in the Krabbe brains during this period. FA values in the brain from the 16 week old Krabbe dog decreased and were lower than in control brains and RD values increased and were higher than in control brain. Conclusion Our findings suggest that FA and RD in the internal capsule and centrum semiovale are affected differently at different ages, despite disease having progressed to pelvic limb paralysis in all dogs evaluated. In 9, 12, and 14 week old Krabbe dogs, higher FA values and lower RD values are seen in the internal capsule. However, in the 16 week old Krabbe dog, lower FA and higher RD values are seen, consistent with previous observations in Krabbe dogs, as well as observations in human Krabbe patients.

2020 ◽  
Vol 133 (2) ◽  
pp. 573-579 ◽  
Author(s):  
Matthew S. Willsey ◽  
Kelly L. Collins ◽  
Erin C. Conrad ◽  
Heather A. Chubb ◽  
Parag G. Patil

OBJECTIVETrigeminal neuralgia (TN) is an uncommon idiopathic facial pain syndrome. To assist in diagnosis, treatment, and research, TN is often classified as type 1 (TN1) when pain is primarily paroxysmal and episodic or type 2 (TN2) when pain is primarily constant in character. Recently, diffusion tensor imaging (DTI) has revealed microstructural changes in the symptomatic trigeminal root and root entry zone of patients with unilateral TN. In this study, the authors explored the differences in DTI parameters between subcategories of TN, specifically TN1 and TN2, in the pontine segment of the trigeminal tract.METHODSThe authors enrolled 8 patients with unilateral TN1, 7 patients with unilateral TN2, and 23 asymptomatic controls. Patients underwent DTI with parameter measurements in a region of interest within the pontine segment of the trigeminal tract. DTI parameters were compared between groups.RESULTSIn the pontine segment, the radial diffusivity (p = 0.0049) and apparent diffusion coefficient (p = 0.023) values in TN1 patients were increased compared to the values in TN2 patients and controls. The DTI measures in TN2 were not statistically significant from those in controls. When comparing the symptomatic to asymptomatic sides in TN1 patients, radial diffusivity was increased (p = 0.025) and fractional anisotropy was decreased (p = 0.044) in the symptomatic sides. The apparent diffusion coefficient was increased, with a trend toward statistical significance (p = 0.066).CONCLUSIONSNoninvasive DTI analysis of patients with TN may lead to improved diagnosis of TN subtypes (e.g., TN1 and TN2) and improve patient selection for surgical intervention. DTI measurements may also provide insights into prognosis after intervention, as TN1 patients are known to have better surgical outcomes than TN2 patients.


2017 ◽  
Vol 30 (5) ◽  
pp. 454-460
Author(s):  
Dana M Middleton ◽  
Jonathan Y Li ◽  
Steven D Chen ◽  
Leonard E White ◽  
Patricia I Dickson ◽  
...  

Purpose We compared fractional anisotropy and radial diffusivity measurements between pediatric canines affected with mucopolysaccharidosis I and pediatric control canines. We hypothesized that lower fractional anisotropy and higher radial diffusivity values, consistent with dysmyelination, would be present in the mucopolysaccharidosis I cohort. Methods Six canine brains, three affected with mucopolysaccharidosis I and three unaffected, were euthanized at 7 weeks and imaged using a 7T small-animal magnetic resonance imaging system. Average fractional anisotropy and radial diffusivity values were calculated for four white-matter regions based on 100 regions of interest per region per specimen. A 95% confidence interval was calculated for each mean value. Results No difference was seen in fractional anisotropy or radial diffusivity values between mucopolysaccharidosis affected and unaffected brains in any region. In particular, the 95% confidence intervals for mucopolysaccharidosis affected and unaffected canines frequently overlapped for both fractional anisotropy and radial diffusivity measurements. In addition, in some brain regions a large range of fractional anisotropy and radial diffusivity values were seen within the same cohort. Conclusion The fractional anisotropy and radial diffusivity values of white matter did not differ between pediatric mucopolysaccharidosis affected canines and pediatric control canines. Possible explanations include: (a) a lack of white matter tissue differences between mucopolysaccharidosis affected and unaffected brains at early disease stages; (b) diffusion tensor imaging does not detect any existing differences; (c) inflammatory processes such as astrogliosis produce changes that offset the decreased fractional anisotropy values and increased radial diffusivity values that are expected in dysmyelination; and (d) our sample size was insufficient to detect differences. Further studies correlating diffusion tensor imaging findings to histology are warranted.


Neurology ◽  
2018 ◽  
Vol 92 (1) ◽  
pp. e30-e39 ◽  
Author(s):  
Meher R. Juttukonda ◽  
Giulia Franco ◽  
Dario J. Englot ◽  
Ya-Chen Lin ◽  
Kalen J. Petersen ◽  
...  

ObjectiveTo assess white matter integrity in patients with essential tremor (ET) and Parkinson disease (PD) with moderate to severe motor impairment.MethodsSedated participants with ET (n = 57) or PD (n = 99) underwent diffusion tensor imaging (DTI) and fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity values were computed. White matter tracts were defined using 3 well-described atlases. To determine candidate white matter regions that differ between ET and PD groups, a bootstrapping analysis was applied using the least absolute shrinkage and selection operator. Linear regression was applied to assess magnitude and direction of differences in DTI metrics between ET and PD populations in the candidate regions.ResultsFractional anisotropy values that differentiate ET from PD localize primarily to thalamic and visual-related pathways, while diffusivity differences localized to the cerebellar peduncles. Patients with ET exhibited lower fractional anisotropy values than patients with PD in the lateral geniculate body (p < 0.01), sagittal stratum (p = 0.01), forceps major (p = 0.02), pontine crossing tract (p = 0.03), and retrolenticular internal capsule (p = 0.04). Patients with ET exhibited greater radial diffusivity values than patients with PD in the superior cerebellar peduncle (p < 0.01), middle cerebellar peduncle (p = 0.05), and inferior cerebellar peduncle (p = 0.05).ConclusionsRegionally, distinctive white matter microstructural values in patients with ET localize to the cerebellar peduncles and thalamo-cortical visual pathways. These findings complement recent functional imaging studies in ET but also extend our understanding of putative physiologic features that account for distinctions between ET and PD.


2018 ◽  
Vol 32 (1) ◽  
pp. 10-16
Author(s):  
Alexander Rau ◽  
Elias Kellner ◽  
Niels A Foit ◽  
Niklas Lützen ◽  
Dieter H Heiland ◽  
...  

The aim of this study was to evaluate whether ganglioglioma (GGL), dysembryoplastic neuroepithelial tumour (DNET) and FCD (focal cortical dysplasia) are distinguishable through diffusion tensor imaging. Additionally, it was investigated whether the diffusion measures differed in the perilesional (pNAWM) and in the contralateral normal appearing white matter (cNAWM). Six GGLs, eight DNETs and seven FCDs were included in this study. Quantitative diffusion measures, that is, axial, radial and mean diffusivity and fractional anisotropy, were determined in the lesion identified on isotropic T2 or FLAIR-weighted images and in pNAWM and cNAWM, respectively. DNET differed from FCD in mean diffusivity, and GGL from FCD in radial diffusivity. Both types of glioneuronal tumours were different from pNAWM in fractional anisotropy and radial diffusivity. For identifying the tumour edges, threshold values for tumour-free tissue were investigated with receiver operating characteristic analyses: tumour could be separated from pNAWM at a threshold ≤ 0.32 (fractional anisotropy) or ≥ 0.56 (radial diffusivity) *10–3 mm2/s (area under the curve 0.995 and 0.990 respectively). While diffusion parameters of FCDs differed from cNAWM (radial diffusivity (*10–3 mm/s2): 0.74 ± 0.19 vs. 0.43 ± 0.05; corrected p-value < 0.001), the pNAWM could not be differentiated from the FCD.


2019 ◽  
Vol 149 (1) ◽  
pp. 36-45 ◽  
Author(s):  
Anders D Andersen ◽  
Duc Ninh Nguyen ◽  
Louise Langhorn ◽  
Ingrid B Renes ◽  
Ruurd M van Elburg ◽  
...  

ABSTRACT Background Preterm infants are born with an immature gut, brain, and immune system, predisposing them to short- and long-term complications. Objective We hypothesized that a milk diet supplemented with pre- and probiotics (i.e. synbiotics) and glutamine would improve gut, brain, and immune maturation in preterm neonates, using preterm pigs as a model. Methods Preterm pigs (Landrace x Yorkshire x Duroc, n = 40, delivered by c-section at 90% of gestation) were reared individually until day 23 after birth under highly standardized conditions. Piglets in the intervention group (PPG, n = 20) were fed increasing volumes of bovine milk supplemented with prebiotics (short-chain galacto- and long chain fructo-oligosaccharides 9:1, 4–12 g/L), probiotics (Bifidobacterium breve M16-V, 3 × 109 CFU/d) and l-glutamine [0.15–0.30 g/(kg · d)], and compared with pigs fed bovine milk with added placebo compounds as control (CON, n = 20). Clinical, gastrointestinal, immunological, cognitive, and neurological endpoints were measured. Results The PPG pigs showed more diarrhea but weight gain, body composition, and gut parameters were similar between the groups. Cognitive performance, assessed in a T-maze, was significantly higher in PPG pigs (P < 0.01), whereas motor function and exploratory interest were similar between the groups. Using ex vivo diffusion imaging, the orientation dispersion index in brain cortical gray matter was 50% higher (P = 0.04), and fractional anisotropy value was 7% lower (P = 0.05) in PPG pigs compared with CON pigs, consistent with increased dendritic branching in PPG. In associative fibers, radial diffusivity was lower and fractional anisotropy was higher in PPG pigs compared with CON pigs (all P < 0.05), while measures in the internal capsule showed a tendency towards reduced radial diffusivity and mean diffusivity (both P = 0.09). On day 23 pigs in the PPG group showed higher blood leukocyte numbers (+43%), neutrophil counts (+100%), and phagocytic rates (+24%), relative to CON, all P < 0.05. Conclusion Preterm pigs supplemented with Bifidobacterium breve, galacto- and fructo-oligosaccharides, and l-glutamine showed enhanced neuronal and immunological development. The findings indicate the potential for targeted nutritional interventions after preterm birth, to support development of important systems such as immunity and brain.


2019 ◽  
Vol 25 (09) ◽  
pp. 950-960 ◽  
Author(s):  
Douglas P. Terry ◽  
Catherine M. Mewborn ◽  
L. Stephen Miller

AbstractObjective: Multiple concussions sustained in youth sport may be associated with later-life brain changes and worse cognitive outcomes. We examined the association between two or more concussions during high school football and later-life white matter (WM) microstructure (i.e., 22–47 years following football retirement) using diffusion tensor imaging (DTI). Method: Forty former high school football players aged 40–65 who received 2+ concussions during high school football (N = 20), or denied concussive events (N = 20) were recruited. Participants underwent neurocognitive testing and DTI scanning. Results: Groups did not statistically differ on age, education, or estimated pre-morbid intelligence. Tract-based Spatial Statistics (TBSS) correcting for Family-Wise Error (FWE)(p &lt; .05) did not yield differences between groups at the whole-brain level. Region of interest analyses showed higher mean diffusivity (MD) in the anterior limb of the internal capsule (ALIC) in the concussed group compared to the non-concussed former players. More liberal analyses (i.e., p &lt; .001, uncorrected for multiple comparisons, ≥8 voxels) also revealed that former players endorsing 2+ concussions had higher MD in the ALIC. Analyses that covaried for age did not reveal differences at either threshold. Concussive histories were not associated with worse cognitive functioning, nor did it impact the relationship between neuropsychological scores and DTI metrics. Discussion: Results suggest only minimal neuroanatomical brain differences in former athletes many years following original concussive injuries compared to controls.


2020 ◽  
Author(s):  
Sascha Gill ◽  
Meng Wang ◽  
Pauline Mouches ◽  
Deepthi Rajashekar ◽  
Tolulope Sajobi ◽  
...  

Abstract Background: Agitation and aggression are common in dementia and pre-dementia. The dementia risk syndrome mild behavioral impairment (MBI) includes these symptoms in the impulse dyscontrol domain. However, the neural circuitry associated with impulse dyscontrol in neurodegenerative disease is not well understood. The aim of this work is to investigate if regional micro- and macro-structural brain properties are associated with impulse dyscontrol symptoms in older adults with normal cognition, mild cognitive impairment, and Alzheimer’s disease. Methods: Clinical, neuropsychiatric, and T1-weighted and diffusion-tensor MRI (DTI) data from 80 individuals with and 123 individuals without impulse dyscontrol, were obtained from the Alzheimer’s Disease Neuroimaging Initiative. Linear mixed effect (LME) models were used to assess if impulse dyscontrol was related to regional DTI and volumetric parameters. Results: Impulse dyscontrol was present in 17% of participants with NC, 43% with MCI, and 66% with AD. Impulse dyscontrol was associated with: 1) lower fractional anisotropy, and greater mean, axial, and radial diffusivity in the fornix; 2) lesser fractional anisotropy, and greater radial diffusivity in the superior fronto-occipital fasciculus; 3) greater axial diffusivity in the cingulum; 4) grey matter atrophy, specifically, lower cortical thickness and greater surface area in the parahippocampal gyrus. Conclusion: Our findings provide evidence that well-established atrophy patterns of AD are prominent in the presence of impulse dyscontrol, even when disease status is controlled for, and possibly in advance of dementia. Our findings support the growing evidence base for impulse dyscontrol symptoms as an early manifestation of Alzheimer’s disease.


2019 ◽  
Vol 98 (Suppl) ◽  
pp. 13-13
Author(s):  
Mario Minor Murakami Junior ◽  
Fabio Luiz Franceschi Godinho ◽  
Paula Ricci Arantes ◽  
Eberval Gadelha Figueiredo ◽  
Rubens Gisbert Cury ◽  
...  

Introduction: Obsessive-compulsive disorder (OCD) is a common, chronic and long-lasting mental disorder. The current first-line therapy for OCD is high doses of selective serotonin reuptake inhibitor (SSRI) and cognitive-behavioral psychotherapy. For patients with refractory symptoms, studies demonstrated that they may respond well to Deep Brain Stimulation (DBS), a technique that can modulate altered neuronal activity. Some stimulation sites are currently being used as targets to DBS and showed good response, but further analyses are necessary to improve the location of the electrodes since some patients demonstrated a poor outcome. Neuroimaging that assess white matter such as diffusion tensor image and tractography can evaluate the quality of the targets and assess the tracts that are affected by the electric field of the electrodes used in the surgery. Our hypothesis is that the patient outcome depends on the trajectory of the tracts that are affected by the electric field.Objectives: Our aim is to investigate which tracts connected with the stimulation sites contribute to clinical improvement effects and weather is possible to predict the outcomes based on connectivity.Methodology: We analyzed 4 patients (2 female) with treatment-refractory obsessive-compulsive disorder undergoing deep brain stimulation targeting the anterior limb of the internal capsule/ nucleus accumbens (ALIC). We will perform tractography analysis of the fibers using the volume of active tissue (VTA) as the region of interest. We will relate the alteration in OCD symptom severity on Yale-Brown obsessive-compulsive scale (Y-BOCS) between the condition before surgery and one-year follow-up with the tracts involved with the stimulation sites using DTI data such as fractal anisotropy and mean diffusivity.Partial Results: Half of the patients did show great improvement and the other two maintained a bad outcome. We found that active stimulation of the ALIC more lateral and posterior of the nucleus was associated with a better outcome. Currently, the description of the tracts involved in patients with better outcomes is performed. The tracts involved with this result will be determined by analysis of DTI and tractography.Discussion and Conclusion: For a future perspective, the results will be important to improve the stimulation sites in DBS surgery resulting in better outcomes.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Timothy T. Griffiths ◽  
Robert Flather ◽  
Irvin Teh ◽  
Hamied A. Haroon ◽  
David Shelley ◽  
...  

AbstractCubital tunnel syndrome (CuTS) is the 2nd most common compressive neuropathy. To improve both diagnosis and the selection of patients for surgery, there is a pressing need to develop a reliable and objective test of ulnar nerve ‘health’. Diffusion tensor imaging (DTI) characterises tissue microstructure and may identify differences in the normal ulnar from those affected by CuTS. The aim of this study was to compare the DTI metrics from the ulnar nerves of healthy (asymptomatic) adults and patients with CuTS awaiting surgery. DTI was acquired at 3.0 T using single-shot echo-planar imaging (55 axial slices, 3 mm thick, 1.5 mm2 in-plane) with 30 diffusion sensitising gradient directions, a b-value of 800 s/mm2 and 4 signal averages. The sequence was repeated with the phase-encoding direction reversed. Data were combined and corrected using the FMRIB Software Library (FSL) and reconstructed using generalized q-sampling imaging in DSI Studio. Throughout the length of the ulnar nerve, the fractional anisotropy (FA), quantitative anisotropy (QA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were extracted, then compared using mixed-effects linear regression. Thirteen healthy controls (8 males, 5 females) and 8 patients with CuTS (6 males, 2 females) completed the study. Throughout the length of the ulnar nerve, diffusion was more isotropic in patients with CuTS. Overall, patients with CuTS had a 6% lower FA than controls, with the largest difference observed proximal to the cubital tunnel (mean difference 0.087 [95% CI 0.035, 0.141]). Patients with CuTS also had a higher RD than controls, with the largest disparity observed within the forearm (mean difference 0.252 × 10–4 mm2/s [95% CI 0.085 × 10–4, 0.419 × 10–4]). There were no significant differences between patients and controls in QA, MD or AD. Throughout the length of the ulnar nerve, the fractional anisotropy and radial diffusivity in patients with CuTS are different to healthy controls. These findings suggest that DTI may provide an objective assessment of the ulnar nerve and potentially, improve the management of CuTS.


Sign in / Sign up

Export Citation Format

Share Document