MRI evaluation of axonal reorganization after bone marrow stromal cell treatment of traumatic brain injury

Jiang, Quan; Qu, Changsheng; Chopp, Michael; Ding, Guangliang; Nejad-Davarani, Siamak P.; Helpern, Joseph A.; Jensen, Jens H.; Zhang, Zheng Gang; Li, Lian; Lü, Mei; Kaplan, David L.; Hu, Jiani; Shen, Yimin; Kou, Zhifeng; Li, Qingjiang; Wang, Shiyang; Mahmood, Asim

doi:10.1002/nbm.1667

Cited by 55 publications

(72 citation statements)

References 59 publications

(96 reference statements)

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“…14,20,26,56,57 In agreement with these findings, our dynamic image data showed that FA in particular brain areas spontaneously increased after TBI, which was accompanied with an improvement of functional recovery as measured by mNSS. In addition, similarly to some sites in the brain that are particularly vulnerable to diffuse axonal injury following TBI, 27,58 there seem to be brain regions that are more prone to structural remodeling.…”

Section: Fig 2 Sets Of T2 (A-c G-i M-o)supporting

confidence: 88%

“…20,24,26,[53][54][55] As an alternative approach, entropy provides a measure of anisotropy of diffusion based on information theory. 31,32 Without restriction, diffusion of water molecules is isotropic.…”

Section: Fig 2 Sets Of T2 (A-c G-i M-o)mentioning

confidence: 99%

“…These structural alterations within the injured brain can be revealed by magnetic resonance imaging (MRI), especially diffusion measurements. [16][17][18][19][20][21] By exploiting the anisotropic properties of water diffusion in white matter (WM), diffusion imaging technology provides new insights into the microstructural organization of the central nervous system. As a noninvasive tool capable of characterizing the major diffusion direction of fiber tracts, diffusion-tensor imaging (DTI) 22 maps the orientational architecture of neural tissue in vivo.…”

Section: Introductionmentioning

confidence: 99%

“…Fractional anisotropy (FA), one of the DTI-derived indices, describes the degree of directionality of tissue water diffusion. 23 Because of its ability to capture the alteration of WM integrity, FA is widely used in experimental study 20,24,25 and clinical research 16,21,26 to quantify the extent of structural pathology or therapeutic benefit following brain insult. Although DTI holds value as an excellent imaging modality for identifying axonal injury as well as neuroplasticity that occur in the injured brain 18,27,28 it has a well-known inherent limitation, stemming from the constraints of the tensor model, which prevent DTI from adequately resolving intravoxel fiber crossing.…”

Section: Introductionmentioning

confidence: 99%

“…20 The advent of advanced model-free estimate MRI, such as diffusion entropy, 30,31 raises the exciting possibility that brain structural reorganization evoked by the therapeutic intervention could be revealed, which may add to our understanding of the role of structural remodeling as underlying functional recovery. However, quite limited data exist regarding the use of entropy to dynamically monitor structural changes, particularly for cell-induced neural remodeling in TBI.…”

Section: Introductionmentioning

confidence: 99%

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Diffusion-Derived Magnetic Resonance Imaging Measures of Longitudinal Microstructural Remodeling Induced by Marrow Stromal Cell Therapy after Traumatic Brain Injury

Chopp

Ding

et al. 2017

Journal of Neurotrauma

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Using magnetic resonance imaging (MRI) and an animal model of traumatic brain injury (TBI), we investigated the capacity and sensitivity of diffusion-derived measures, fractional anisotropy (FA), and diffusion entropy, to longitudinally identify structural plasticity in the injured brain in response to the transplantation of human bone marrow stromal cells (hMSCs). Male Wistar rats (300-350g, n = 30) were subjected to controlled cortical impact TBI. At 6 h or 1 week postinjury, these rats were intravenously injected with 1 mL of saline (at 6 h or 1 week, n = 5/group) or with hMSCs in suspension (*3 · 10 6 hMSCs, at 6 h or 1 week, n = 10/group). In vivo MRI measurements and sensorimotor function estimates were performed on all animals pre-injury, 1 day post-injury, and weekly for 3 weeks post-injury. Bielschowsky's silver and Luxol fast blue staining were used to reveal the axon and myelin status, respectively, with and without cell treatment after TBI. Based on image data and histological observation, regions of interest encompassing the structural alterations were made and the values of FA and entropy were monitored in these specific brain regions. Our data demonstrate that administration of hMSCs after TBI leads to enhanced white matter reorganization particularly along the boundary of contusional lesion, which can be identified by both FA and entropy. Compared with the therapy performed at 1 week post-TBI, cell intervention executed at 6 h expedites the brain remodeling process and results in an earlier functional recovery. Although FA and entropy present a similar capacity to dynamically detect the microstructural changes in the tissue regions with predominant orientation of fiber tracts, entropy exhibits a sensitivity superior to that of FA, in probing the structural alterations in the tissue areas with complex fiber patterns.

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Section: Fig 2 Sets Of T2 (A-c G-i M-o)supporting

confidence: 88%

Section: Fig 2 Sets Of T2 (A-c G-i M-o)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Diffusion-Derived Magnetic Resonance Imaging Measures of Longitudinal Microstructural Remodeling Induced by Marrow Stromal Cell Therapy after Traumatic Brain Injury

Chopp

Ding

et al. 2017

Journal of Neurotrauma

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White Matter Alterations in Military Service Members With Remote Mild Traumatic Brain Injury

Kim,

Ollinger,

Song

et al. 2024

JAMA Netw Open

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ImportanceMild traumatic brain injury (mTBI) is the signature injury experienced by military service members and is associated with poor neuropsychiatric outcomes. Yet, there is a lack of reliable clinical tools for mTBI diagnosis and prognosis.ObjectiveTo examine the white matter microstructure and neuropsychiatric outcomes of service members with a remote history of mTBI (ie, mTBI that occurred over 2 years ago) using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI).Design, Setting, and ParticipantsThis case-control study examined 98 male service members enrolled in a study at the National Intrepid Center of Excellence. Eligible participants were active duty status or able to enroll in the Defense Enrollment Eligibility Reporting system, ages 18 to 60 years, and had a remote history of mTBI; controls were matched by age.ExposuresRemote history of mTBI.Main Outcomes and MeasuresWhite matter microstructure was assessed using a region-of-interest approach of skeletonized diffusion images, including DTI (fractional anisotropy, mean diffusivity, radial diffusivity and axial diffusivity) and NODDI (orientation dispersion index [ODI], isotropic volume fraction, intra-cellular volume fraction). Neuropsychiatric outcomes associated with posttraumatic stress disorder (PTSD) and postconcussion syndrome were assessed.ResultsA total of 65 male patients with a remote history of mTBI (mean [SD] age, 40.5 [5.0] years) and 33 age-matched male controls (mean [SD] age, 38.9 [5.6] years) were included in analysis. Compared with the control cohort, the 65 service members with mTBI presented with significantly more severe PTSD-like symptoms (mean [SD] PTSD CheckList-Civilian [PCL-C] version scores: control, 19.0 [3.8] vs mTBI, 41.2 [11.6]; P &lt; .001). DTI and NODDI metrics were altered in the mTBI group compared with the control, including intra-cellular volume fraction of the right cortico-spinal tract (β = −0.029, Cohen d = 0.66; P &lt; .001), ODI of the left posterior thalamic radiation (β = −0.006, Cohen d = 0.55; P &lt; .001), and ODI of the left uncinate fasciculus (β = 0.013, Cohen d = 0.61; P &lt; .001). In service members with mTBI, fractional anisotropy of the left uncinate fasciculus was associated with postconcussion syndrome (β = 5.4 × 10−3; P = .003), isotropic volume fraction of the genu of the corpus callosum with PCL-C (β = 4.3 × 10−4; P = .01), and ODI of the left fornix and stria terminalis with PCL-C avoidance scores (β = 1.2 × 10−3; P = .02).Conclusions and RelevanceIn this case-control study of military-related mTBI, the results suggest that advanced magnetic resonance imaging techniques using NODDI can reveal white matter microstructural alterations associated with neuropsychiatric symptoms in the chronic phase of mTBI. Diffusion trends observed throughout widespread white matter regions-of-interest may reflect mechanisms of neurodegeneration as well as postinjury tissue scarring and reorganization.

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Traumatic white matter injury and glial activation: From basic science to clinics

Kou

VandeVord

2014

Glia

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An improved understanding and characterization of glial activation and its relationship with white matter injury will likely serve as a novel treatment target to curb post injury inflammation and promote axonal remyelination after brain trauma. Traumatic brain injury (TBI) is a significant public healthcare burden and a leading cause of death and disability in the United States. Particularly, traumatic white matter (WM) injury or traumatic axonal injury has been reported as being associated with patients' poor outcomes. However, there is very limited data reporting the importance of glial activation after TBI and its interaction with WM injury. This article presents a systematic review of traumatic WM injury and the associated glial activation, from basic science to clinical diagnosis and prognosis, from advanced neuroimaging perspective. It concludes that there is a disconnection between WM injury research and the essential role of glia which serve to restore a healthy environment for axonal regeneration following WM injury. Particularly, there is a significant lack of non-invasive means to characterize the complex pathophysiology of WM injury and glial activation in both animal models and in humans. An improved understanding and characterization of the relationship between glia and WM injury will likely serve as a novel treatment target to curb post injury inflammation and promote axonal remyelination.

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MRI evaluation of axonal reorganization after bone marrow stromal cell treatment of traumatic brain injury

Cited by 55 publications

References 59 publications

Diffusion-Derived Magnetic Resonance Imaging Measures of Longitudinal Microstructural Remodeling Induced by Marrow Stromal Cell Therapy after Traumatic Brain Injury

Diffusion-Derived Magnetic Resonance Imaging Measures of Longitudinal Microstructural Remodeling Induced by Marrow Stromal Cell Therapy after Traumatic Brain Injury

White Matter Alterations in Military Service Members With Remote Mild Traumatic Brain Injury

Traumatic white matter injury and glial activation: From basic science to clinics

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