Synbiotics Combined with Glutamine Stimulate Brain Development and the Immune System in Preterm Pigs

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.

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A Correlational Study between Microstructural White Matter Properties and Macrostructural Gray Matter Volume Across Normal Ageing: Conjoint DTI and VBM Analysis

Magnetic Resonance Insights ◽

10.1177/1178623x18799926 ◽

2018 ◽

Vol 11 ◽

pp. 1178623X1879992 ◽

Cited By ~ 4

Author(s):

Vikas Pareek ◽

VP Subramanyam Rallabandi ◽

Prasun K Roy

Keyword(s):

White Matter ◽

Life Span ◽

Fractional Anisotropy ◽

Gray Matter ◽

Healthy Aging ◽

Gray Matter Volume ◽

Mean Diffusivity ◽

Radial Diffusivity ◽

Axial Diffusivity ◽

Matter Volume

We investigate the relationship between Gray matter’s volume vis-a-vis White matter’s integrity indices, such Axial diffusivity, Radial diffusivity, Mean diffusivity, and Fractional anisotropy, in individuals undergoing healthy aging. We investigated MRI scans of 177 adults across 20 to 85 years. We used Voxel-based morphometry, and FDT-FSL analysis for estimation of Gray matter volume and White matter’s diffusion indices respectively. Across the life span, we observed an inter-relationship between the Gray matter and White matter, namely that both Axial diffusivity and Mean Diffusivity show strong correlation with Gray matter volume, along the aging process. Furthermore, across all ages the Fractional anisotropy and Mean diffusivity are found to be significantly reduced in females when compared to males, but there are no significant gender differences in Axial Diffusivity and Radial diffusivity. We conclude that for both genders across all ages, the Gray matter’s Volume is strongly correlated with White matter’s Axial Diffusivity and Mean Diffusivity, while being weakly correlated with Fractional Anisotropy. Our study clarifies the multi-scale relationship in brain tissue, by elucidating how the White matter’s micro-structural parameters influences the Gray matter’s macro-structural characteristics, during healthy aging across the life-span.

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White matter differences between essential tremor and Parkinson disease

Neurology ◽

10.1212/wnl.0000000000006694 ◽

2018 ◽

Vol 92 (1) ◽

pp. e30-e39 ◽

Cited By ~ 5

Author(s):

Meher R. Juttukonda ◽

Giulia Franco ◽

Dario J. Englot ◽

Ya-Chen Lin ◽

Kalen J. Petersen ◽

...

Keyword(s):

White Matter ◽

Parkinson Disease ◽

Essential Tremor ◽

Fractional Anisotropy ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

Superior Cerebellar Peduncle ◽

Radial Diffusivity ◽

Cerebellar Peduncles ◽

Cerebellar Peduncle

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.

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Discrimination of epileptogenic lesions and perilesional white matter using diffusion tensor magnetic resonance imaging

The Neuroradiology Journal ◽

10.1177/1971400918813991 ◽

2018 ◽

Vol 32 (1) ◽

pp. 10-16

Author(s):

Alexander Rau ◽

Elias Kellner ◽

Niels A Foit ◽

Niklas Lützen ◽

Dieter H Heiland ◽

...

Keyword(s):

White Matter ◽

Fractional Anisotropy ◽

Diffusion Tensor ◽

Focal Cortical Dysplasia ◽

Mean Diffusivity ◽

Area Under The Curve ◽

P Value ◽

Radial Diffusivity ◽

Normal Appearing White Matter ◽

Diffusion Parameters

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.

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

The Neuroradiology Journal ◽

10.1177/1971400917733431 ◽

2018 ◽

Vol 31 (2) ◽

pp. 168-176 ◽

Cited By ~ 3

Author(s):

Jonathan Y Li ◽

Dana M Middleton ◽

Steven Chen ◽

Leonard White ◽

Carley R Corado ◽

...

Keyword(s):

Fractional Anisotropy ◽

Diffusion Tensor ◽

Region Of Interest ◽

Internal Capsule ◽

Canine Model ◽

Krabbe Disease ◽

Radial Diffusivity ◽

Centrum Semiovale ◽

Pelvic Limb ◽

Normal Controls

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.

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Early postsurgical diffusivity metrics for prognostication of long-term pain relief after Gamma Knife radiosurgery for trigeminal neuralgia

Journal of Neurosurgery ◽

10.3171/2018.3.jns172936 ◽

2019 ◽

Vol 131 (2) ◽

pp. 539-548 ◽

Cited By ~ 4

Author(s):

Sarasa Tohyama ◽

Peter Shih-Ping Hung ◽

Jidan Zhong ◽

Mojgan Hodaie

Keyword(s):

Pain Relief ◽

Trigeminal Neuralgia ◽

Fractional Anisotropy ◽

Gamma Knife ◽

Trigeminal Nerve ◽

Gamma Knife Radiosurgery ◽

Mean Diffusivity ◽

Clinical Effectiveness ◽

Radial Diffusivity

OBJECTIVEGamma Knife radiosurgery (GKRS) is an important treatment modality for trigeminal neuralgia (TN). Current longitudinal assessment after GKRS relies primarily on clinical diagnostic measures, which are highly limited in the prediction of long-term clinical benefit. An objective, noninvasive, predictive tool would be of great utility to advance the clinical management of patients. Using diffusion tensor imaging (DTI), the authors’ aim was to determine whether early (6 months post-GKRS) target diffusivity metrics can be used to prognosticate long-term pain relief in patients with TN.METHODSThirty-seven patients with TN treated with GKRS underwent 3T MRI scans at 6 months posttreatment. Diffusivity metrics of fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity were extracted bilaterally from the radiosurgical target of the affected trigeminal nerve and its contralateral, unaffected nerve. Early (6 months post-GKRS) diffusivity metrics were compared with long-term clinical outcome. Patients were identified as long-term responders if they achieved at least 75% reduction in preoperative pain for 12 months or longer following GKRS.RESULTSTrigeminal nerve diffusivity at 6 months post-GKRS was predictive of long-term clinical effectiveness, where long-term responders (n = 19) showed significantly lower fractional anisotropy at the radiosurgical target of their affected nerve compared to their contralateral, unaffected nerve and to nonresponders. Radial diffusivity and mean diffusivity, correlates of myelin alterations and inflammation, were also significantly higher in the affected nerve of long-term responders compared to their unaffected nerve. Nonresponders (n = 18) did not exhibit any characteristic diffusivity changes after GKRS.CONCLUSIONSThe authors demonstrate that early postsurgical target diffusivity metrics have a translational, clinical value and permit prediction of long-term pain relief in patients with TN treated with GKRS. Importantly, an association was found between the footprint of radiation and clinical effectiveness, where a sufficient level of microstructural change at the radiosurgical target is necessary for long-lasting pain relief. DTI can provide prognostic information that supplements clinical measures, and thus may better guide the postoperative assessment and clinical decision-making for patients with TN.

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Segmental Diffusion Properties of the Corticospinal Tract and Motor Outcome in Hemiparetic Children With Perinatal Stroke

Journal of Child Neurology ◽

10.1177/0883073817696815 ◽

2017 ◽

Vol 32 (6) ◽

pp. 550-559 ◽

Cited By ~ 14

Author(s):

Jacquie Hodge ◽

Bradley Goodyear ◽

Helen Carlson ◽

Xing-Chang Wei ◽

Adam Kirton

Keyword(s):

Diffusion Tensor Imaging ◽

Fractional Anisotropy ◽

Corticospinal Tract ◽

Diffusion Tensor ◽

Model Development ◽

Structural Connectivity ◽

Mean Diffusivity ◽

Radial Diffusivity ◽

Perinatal Stroke ◽

Motor Outcomes

Perinatal stroke injures developing motor systems, resulting in hemiparetic cerebral palsy. Diffusion tensor imaging can explore structural connectivity. We used diffusion tensor imaging to assess corticospinal tract diffusion in hemiparetic children with perinatal stroke. Twenty-eight children (6-18 years) with unilateral stroke underwent diffusion tensor imaging. Four corticospinal tract assessments included full tract, partial tract, minitract and region of interest. Diffusion characteristics (fractional anisotropy, mean, axial, and radial diffusivity) were calculated. Ratios (lesioned/nonlesioned) were compared across segments and to validated long-term motor outcomes (Pediatric Stroke Outcome Measure, Assisting Hand Assessment, Melbourne Assessment). Fractional anisotropy and radial diffusivity ratios decreased as tract size decreased, while mean diffusivity showed consistent symmetry. Poor motor outcomes were associated with lower fractional anisotropy in all segments and radial diffusivity correlated with both Assisting Hand Assessment and Melbourne Assessment. Diffusion imaging of segmented corticospinal tracts is feasible in hemiparetic children with perinatal stroke. Correlations with disability support clinical relevance and utility in model development for personalized rehabilitation.

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Diffusion tensor imaging and arterial tissue: establishing the influence of arterial tissue microstructure on fractional anisotropy, mean diffusivity and tractography

Scientific Reports ◽

10.1038/s41598-020-77675-x ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

B. Tornifoglio ◽

A. J. Stone ◽

R. D. Johnston ◽

S. S. Shahid ◽

C. Kerskens ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

Fractional Anisotropy ◽

Diffusion Tensor ◽

Ex Vivo ◽

Mean Diffusivity ◽

Tissue Microstructure ◽

Highly Sensitive ◽

Arterial Tissue ◽

Porcine Carotid Artery ◽

Diffusion Tensor Imaging Dti

AbstractThis study investigates diffusion tensor imaging (DTI) for providing microstructural insight into changes in arterial tissue by exploring how cell, collagen and elastin content effect fractional anisotropy (FA), mean diffusivity (MD) and tractography. Five ex vivo porcine carotid artery models (n = 6 each) were compared—native, fixed native, collagen degraded, elastin degraded and decellularised. Vessels were imaged at 7 T using a DTI protocol with b = 0 and 800 s/mm2 and 10 isotopically distributed directions. FA and MD were evaluated in the vessel media and compared across models. FA values measured in native (p < 0.0001), fixed native (p < 0.0001) and collagen degraded (p = 0.0018, p = 0.0016, respectively) were significantly higher than those in elastin degraded and decellularised arteries. Native and fixed native had significantly lower MD values than elastin degraded (p < 0.0001) and decellularised tissue (p = 0.0032, p = 0.0003, respectively). Significantly lower MD was measured in collagen degraded compared with the elastin degraded model (p = 0.0001). Tractography yielded helically arranged tracts for native and collagen degraded vessels only. FA, MD and tractography were found to be highly sensitive to changes in the microstructural composition of arterial tissue, specifically pointing to cell, not collagen, content as the dominant source of the measured anisotropy in the vessel wall.

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Diffusion tensor imaging and arterial tissue: establishing the influence of arterial tissue microstructure on fractional anisotropy, mean diffusivity and tractography

10.1101/2020.05.20.104711 ◽

2020 ◽

Author(s):

B. Tornifoglio ◽

A. J. Stone ◽

R. D. Johnston ◽

S. S. Shahid ◽

C. Kerskens ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

Fractional Anisotropy ◽

Diffusion Tensor ◽

Ex Vivo ◽

Mean Diffusivity ◽

Cell Content ◽

Tissue Microstructure ◽

Highly Sensitive ◽

Arterial Tissue ◽

Tissue Models

AbstractIn this study we investigated the potential of diffusion tensor imaging (DTI) for providing insight into microstructural changes in arterial tissue by exploring the influence that cell, collagen and elastin content have on fractional anisotropy (FA), mean diffusivity (MD) and tractography. Five ex vivo porcine carotid artery models (n = 6 vessels each) – native, fixed native, collagen degraded, elastin degraded and decellularised – were developed to selectively remove components of arterial microstructure. Intact vessels were imaged at 7 T using a DTI protocol with b = 0 and 800 s/mm2 and 10 isotopically distributed directions. FA and MD values were evaluated in the medial layer of vessels and compared across tissue models. FA values measured in native and fixed native vessels were significantly higher (p<0.0001) than those in the elastin degraded and decellularised arteries. Collagen degraded vessels had a significantly higher (p<0.01) FA than elastin degraded and decellularised vessels. Native and fixed vessels had significantly lower (p<0.0001) MD values than elastin degraded, while the MD in decellularised arteries was significantly higher than that in both native (p<0.01) and fixed (p<0.005) tissue. Significantly lower (p<0.005) MD was measured in collagen degraded compared with the elastin degraded model. Tractography results yielded similar helically arranged tracts for native and collagen degraded vessels, whilst elastin degraded and decellularised vessels showed no consistent tracts. FA, MD and tractography were found to be highly sensitive to changes in the microstructural composition of arterial tissue, with cell content being a dominant source of the measured anisotropy in the vessel wall.

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Diffuse axonal injury in mild traumatic brain injury: a diffusion tensor imaging study

Journal of Neurosurgery ◽

10.3171/jns.2005.103.2.0298 ◽

2005 ◽

Vol 103 (2) ◽

pp. 298-303 ◽

Cited By ~ 375

Author(s):

Matilde Inglese ◽

Sachin Makani ◽

Glyn Johnson ◽

Benjamin A. Cohen ◽

Jonathan A. Silver ◽

...

Keyword(s):

Diffusion Tensor Imaging ◽

Mr Imaging ◽

Fractional Anisotropy ◽

Diffusion Tensor ◽

Axonal Injury ◽

Diffuse Axonal Injury ◽

Mean Diffusivity ◽

Internal Capsule ◽

Content Type ◽

Fine Print

Object. Diffuse axonal injury (DAI) is a major complication of traumatic brain injury (TBI) that leads to functional and psychological deficits. Although DAI is frequently underdiagnosed by conventional imaging modalities, it can be demonstrated using diffusion tensor imaging. The aim of this study was to assess the presence and extent of DAI in patients with mild TBI. Methods. Forty-six patients with mild TBI and 29 healthy volunteers underwent a magnetic resonance (MR) imaging protocol including: dual—spin echo, fluid-attenuated inversion recovery, T2-weighted gradient echo, and diffusion tensor imaging sequences. In 20 of the patients, MR imaging was performed at a mean of 4.05 days after injury. In the remaining 26, MR imaging was performed at a mean of 5.7 years after injury. In each case, mean diffusivity and fractional anisotropy were measured using both whole-brain histograms and regions of interest analysis. No differences in any of the histogram-derived measures were found between patients and control volunteers. Compared with controls, a significant reduction of fractional anisotropy was observed in patients' corpus callosum, internal capsule, and centrum semiovale, and there were significant increases of mean diffusivity in the corpus callosum and internal capsule. Neither histogram-derived nor regional diffusion tensor imaging metrics differed between the two groups. Conclusions. Although mean diffusivity and fractional anisotropy abnormalities in these patients with TBI were too subtle to be detected with the whole-brain histogram analysis, they are present in brain areas that are frequent sites of DAI. Because diffusion tensor imaging changes are present at both early and late time points following injury, they may represent an early indicator and a prognostic measure of subsequent brain damage.

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Breast milk exposure is associated with cortical maturation in preterm infants

10.1101/2022.01.04.22268723 ◽

2022 ◽

Author(s):

Gemma Sullivan ◽

Kadi Vaher ◽

Manuel Blesa ◽

Paola Galdi ◽

David Q Stoye ◽

...

Keyword(s):

Preterm Birth ◽

Breast Milk ◽

Fractional Anisotropy ◽

Preterm Infants ◽

Gestational Age ◽

Brain Mri ◽

Mean Diffusivity ◽

Brain Morphology ◽

Radial Diffusivity ◽

Nutritional Data

Breast milk exposure is associated with improved neurocognitive outcomes following preterm birth but the neural substrates linking nutrition with outcome are uncertain. By combining nutritional data with brain MRI, we tested the hypothesis that high versus low breast milk exposure in preterm infants during neonatal care results in a cortical morphology that more closely resembles that of infants born at term. We studied 135 preterm (mean gestational age 30+2 weeks, range 22+1 to 32+6) and 77 term-born infants (mean gestational age 39+4 weeks, range 36+3 to 42+1). Nutritional data was collected from birth until hospital discharge to identify the proportion of days preterm infants received exclusive breast milk. Structural and diffusion MRI were performed at term-equivalent age. Cortical indices (volume, thickness, surface area, gyrification index, sulcal depth, curvature) and water diffusion parameters (fractional anisotropy, mean diffusivity, radial diffusivity, axial diffusivity, neurite density index, orientation dispersion index) were compared between preterm infants who received exclusive breast milk for <75% of inpatient days (n=68), preterm infants who received exclusive breast milk for ≥75% of inpatient days (n=67) and term-born controls (n=77). High breast milk exposure was associated with reduced cortical gray matter volume (d=0.47, p=0.014), thickness (d=0.42, p=0.039) and radial diffusivity (d=0.38, p=0.039), and increased fractional anisotropy (d=0.38, p=0.037) after adjustment for age at MRI. High versus low breast milk exposure in the weeks following preterm birth is associated with a cortical imaging phenotype that more closely resembles the brain morphology of healthy infants born at term.

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