Siamak Nejad-Davarani | Henry Ford Health System (original) (raw)

Papers by Siamak Nejad-Davarani

Research paper thumbnail of Comparison of Neurite Density Measured by MRI and Histology after TBI

PLoS ONE, 2013

Background: Functional recovery after brain injury in animals is improved by marrow stromal cells... more Background: Functional recovery after brain injury in animals is improved by marrow stromal cells (MSC) which stimulate neurite reorganization. However, MRI measurement of neurite density changes after injury has not been performed. In this study, we investigate the feasibility of MRI measurement of neurite density in an animal model of traumatic brain injury (TBI) with and without MSC treatment.

Research paper thumbnail of An extended vascular model for less biased estimation of permeability parameters in DCE-T1 images

NMR in biomedicine, 2017

One of the key elements in dynamic contrast enhanced (DCE) image analysis is the arterial input f... more One of the key elements in dynamic contrast enhanced (DCE) image analysis is the arterial input function (AIF). Traditionally, in DCE studies a global AIF sampled from a major artery or vein is used to estimate the vascular permeability parameters; however, not addressing dispersion and delay of the AIF at the tissue level can lead to biased estimates of these parameters. To find less biased estimates of vascular permeability parameters, a vascular model of the cerebral vascular system is proposed that considers effects of dispersion of the AIF in the vessel branches, as well as extravasation of the contrast agent (CA) to the extravascular-extracellular space. Profiles of the CA concentration were simulated for different branching levels of the vascular structure, combined with the effects of vascular leakage. To estimate the permeability parameters, the extended model was applied to these simulated signals and also to DCE-T1 (dynamic contrast enhanced T1 ) images of patients with g...

Research paper thumbnail of A parametric model of the brain vascular system for estimation of the arterial input function (AIF) at the tissue level

NMR in biomedicine, 2017

In this paper, we introduce a novel model of the brain vascular system, which is developed based ... more In this paper, we introduce a novel model of the brain vascular system, which is developed based on laws of fluid dynamics and vascular morphology. This model is used to address dispersion and delay of the arterial input function (AIF) at different levels of the vascular structure and to estimate the local AIF in DCE images. We developed a method based on the simplex algorithm and Akaike information criterion to estimate the likelihood of the contrast agent concentration signal sampled in DCE images belonging to different layers of the vascular tree or being a combination of different signal levels from different nodes of this structure. To evaluate this method, we tested the method on simulated local AIF signals at different levels of this structure. Even down to a signal to noise ratio of 5.5 our method was able to accurately detect the branching level of the simulated signals. When two signals with the same power level were combined, our method was able to separate the base signa...

Research paper thumbnail of Optimization of a novel large field of view distortion phantom for MR-only treatment planning

Journal of applied clinical medical physics, Jan 12, 2017

MR-only treatment planning requires images of high geometric fidelity, particularly for large fie... more MR-only treatment planning requires images of high geometric fidelity, particularly for large fields of view (FOV). However, the availability of large FOV distortion phantoms with analysis software is currently limited. This work sought to optimize a modular distortion phantom to accommodate multiple bore configurations and implement distortion characterization in a widely implementable solution. To determine candidate materials, 1.0 T MR and CT images were acquired of twelve urethane foam samples of various densities and strengths. Samples were precision-machined to accommodate 6 mm diameter paintballs used as landmarks. Final material candidates were selected by balancing strength, machinability, weight, and cost. Bore sizes and minimum aperture width resulting from couch position were tabulated from the literature (14 systems, 5 vendors). Bore geometry and couch position were simulated using MATLAB to generate machine-specific models to optimize the phantom build. Previously deve...

Research paper thumbnail of Diffusion-derived MRI Measures of Longitudinal Microstructural Remodeling Induced by Marrow Stromal Cell Therapy after TBI

Journal of Neurotrauma, 2016

Using magnetic resonance imaging (MRI) and an animal model of traumatic brain injury (TBI), we in... more 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 hours or 1 week post-injury, these rats were intravenously injected with 1 ml of saline (at 6 hours or 1 week, n=5/group) or with hMSCs in suspension (3x106 hMSCs, at 6 hours or 1 week, n=10/group). In vivo MRI measurements and sensorimotor function estimates were performed on all animals pre-injury, 1 day, and weekly for 3 weeks post-injury. Bielshowsky'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 to the therapy carried out at 1 week post-TBI, cell intervention executed at 6 hours expedites the brain remodeling process and results in an earlier functional recovery. While 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 FA, in probing the structural alterations in the tissue areas with complex fiber patterns.

Research paper thumbnail of Cell Treatment for Stroke in Type Two Diabetic Rats Improves Vascular Permeability Measured by MRI

PloS one, 2016

Treatment of stroke with bone marrow stromal cells (BMSC) significantly enhances brain remodeling... more Treatment of stroke with bone marrow stromal cells (BMSC) significantly enhances brain remodeling and improves neurological function in non-diabetic stroke rats. Diabetes is a major risk factor for stroke and induces neurovascular changes which may impact stroke therapy. Thus, it is necessary to test our hypothesis that the treatment of stroke with BMSC has therapeutic efficacy in the most common form of diabetes, type 2 diabetes mellitus (T2DM). T2DM was induced in adult male Wistar rats by administration of a high fat diet in combination with a single intraperitoneal injection (35mg/kg) of streptozotocin. These rats were then subjected to 2h of middle cerebral artery occlusion (MCAo). T2DM rats received BMSC (5x106, n = 8) or an equal volume of phosphate-buffered saline (PBS) (n = 8) via tail-vein injection at 3 days after MCAo. MRI was performed one day and then weekly for 5 weeks post MCAo for all rats. Compared with vehicle treated control T2DM rats, BMSC treatment of stroke in...

Research paper thumbnail of White matter changes after stroke in type 2 diabetic rats measured by diffusion magnetic resonance imaging

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, Jan 18, 2015

Diffusion-related magnetic resonance imaging parametric maps may be employed to characterize whit... more Diffusion-related magnetic resonance imaging parametric maps may be employed to characterize white matter of brain. We hypothesize that entropy of diffusion anisotropy may be most effective for detecting therapeutic effects of bone marrow stromal cell treatment of ischemia in type 2 diabetes mellitus rats. Type 2 diabetes mellitus was induced in adult male Wistar rats. These rats were then subjected to 2 h of middle cerebral artery occlusion, and received bone marrow stromal cell (5 × 10(6), n = 8) or an equal volume of saline (n = 8) via tail vein injection at three days after middle cerebral artery occlusion. Magnetic resonance imaging was performed on day one and then weekly for five weeks post middle cerebral artery occlusion. The diffusion metrics complementarily permitted characterization of axons and axonal myelination. All six magnetic resonance imaging diffusion metrics, confirmed by histological measures, demonstrated that bone marrow stromal cell treatment significantly (...

Research paper thumbnail of Patterns and dynamics of subventricular zone neuroblast migration in the ischemic striatum of the adult mouse

Journal of Cerebral Blood Flow and Metabolism Official Journal of the International Society of Cerebral Blood Flow and Metabolism, May 1, 2009

The migratory behavior of neuroblasts after a stroke is poorly understood. Using time-lapse micro... more The migratory behavior of neuroblasts after a stroke is poorly understood. Using time-lapse microscopy, we imaged migration of neuroblasts and cerebral vessels in living brain slices of adult doublecortin (DCX, a marker of neuroblasts) enhanced green fluorescent protein (eGFP) transgenic mice that were subjected to 7 days of stroke. Our results show that neuroblasts originating in the subventricular zone (SVZ) of adult mouse brain laterally migrated in chains or individually to reach the ischemic striatum. The chains were initially formed at the border between the SVZ and the striatum by neuroblasts in the SVZ and then extended to the striatum. The average speed of DCX-eGFP-expressing cells within chains was 28.67±1.04 μm/h, which was significantly faster (P < 0.01) than the speed of the cells in the SVZ (17.98±0.57 μm/h). Within the ischemic striatum, individual neuroblasts actively extended or retracted their processes, suggestive of probing the immediate microenvironment. The neuroblasts close to cerebral blood vessels exhibited multiple processes. Our data suggest that neuroblasts actively interact with the microenvironment to reach the ischemic striatum by multiple migratory routes.

Research paper thumbnail of Stroke increases neural stem cells and angiogenesis in the neurogenic niche of the adult mouse

PloS one, 2014

The unique cellular and vascular architecture of the adult ventricular-subventricular zone (V/SVZ... more The unique cellular and vascular architecture of the adult ventricular-subventricular zone (V/SVZ) neurogenic niche plays an important role in regulating neural stem cell function. However, the in vivo identification of neural stem cells and their relationship to blood vessels within this niche in response to stroke remain largely unknown. Using whole-mount preparation of the lateral ventricle wall, we examined the architecture of neural stem cells and blood vessels in the V/SVZ of adult mouse over the course of 3 months after onset of focal cerebral ischemia. Stroke substantially increased the number of glial fibrillary acidic protein (GFAP) positive neural stem cells that are in contact with the cerebrospinal fluid (CSF) via their apical processes at the center of pinwheel structures formed by ependymal cells residing in the lateral ventricle. Long basal processes of these cells extended to blood vessels beneath the ependymal layer. Moreover, stroke increased V/SVZ endothelial cel...

Research paper thumbnail of Perfusion and Diffusion Abnormalities of Multiple Sclerosis Lesions and Relevance of Classified Lesions to Disease Status

Journal of neurology & neurophysiology, 2014

Hemodynamic abnormality and disruption of white matter (WM) integrity are significant components ... more Hemodynamic abnormality and disruption of white matter (WM) integrity are significant components in the pathophysiology of multiple sclerosis (MS) lesions. However, the roles of stratified lesions with distinct degrees of hemodynamic and structural injury in disease states remain to be explored. We tested the hypothesis that hemodynamic and structural impairment, as assessed by cerebral blood volume (CBV) and fractional anisotropy (FA), respectively, characterizes the extent of tissue injury, and the load of lesion with substantial tissue destruction would reflect the disease status and therefore, would be related to clinical disability. Seven relapsing-remitting MS patients and seven healthy controls underwent perfusion, diffusion and conventional MRI scans. Based on T2-FLAIR and T1-weighted image, WM plaques were classified. After image coregistration, values of CBV and FA were estimated in three distinct lesion types (active, T1-hypointense and T1-isointense lesion) and compared ...

Research paper thumbnail of <title>A microfabricated phantom for diffusion tensor imaging</title>

Medical Imaging 2010: Biomedical Applications in Molecular, Structural, and Functional Imaging, 2010

A microfabricated phantom with application in diffusion tensor imaging (DTI) is presented. Using ... more A microfabricated phantom with application in diffusion tensor imaging (DTI) is presented. Using lithography technique, we have the capability of creating microchannels in the same scale as actual neural fibers (few to tens of microns in diameter). The method is flexible in generating different geometrical patterns. Neural bundles were simulated by designing a large number of microchannels, running parallel to

Research paper thumbnail of Comparison of Neurite Density Measured by MRI and Histology after TBI

PLoS ONE, 2013

Functional recovery after brain injury in animals is improved by marrow stromal cells (MSC) which... more Functional recovery after brain injury in animals is improved by marrow stromal cells (MSC) which stimulate neurite reorganization. However, MRI measurement of neurite density changes after injury has not been performed. In this study, we investigate the feasibility of MRI measurement of neurite density in an animal model of traumatic brain injury (TBI) with and without MSC treatment. Fifteen male Wistar rats, were treated with saline (n = 6) or MSCs (n = 9) and were sacrificed at 6 weeks after controlled cortical impact (CCI). Healthy non-CCI rats (n = 5), were also employed. Ex-vivo MRI scans were performed two days after the rats were sacrificed. Multiple-shell hybrid diffusion imaging encoding scheme and spherical harmonic expansion of a two-compartment water diffusion displacement model were used to extract neurite related parameters. Bielshowski and Luxol Fast blue was used for staining axons and myelin, respectively. Modified Morris water maze and neurological severity score (mNSS) test were performed for functional evaluation. The treatment effects, the correlations between neurite densities measured by MRI and histology, and the correlations between MRI and functional variables were calculated by repeated measures analysis of variance, the regression correlation analysis tests, and spearman correlation coefficients. Neurite densities exhibited a significant correlation (R(2)&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.80, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;1E-20) between MRI and immuno-histochemistry measurements with 95% lower bound of the intra-correlation coefficient (ICC) as 0.86. The conventional fractional anisotropy (FA) correlated moderately with histological neurite density (R(2) = 0.59, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;1E-5) with 95% lower bound of ICC as 0.76. MRI data revealed increased neurite reorganization with MSC treatment compared with saline treatment, confirmed by histological data from the same animals. mNSS were significantly correlated with MRI neurite density in the hippocampus region. The present studies demonstrated that neurite density can be estimated by MRI after TBI and MRI measurement of neurite density is a sensitive marker to MSC treatment response.

Research paper thumbnail of MRI detects brain reorganization after human umbilical tissue-derived cells (hUTC) treatment of stroke in rat

PloS one, 2012

Human umbilical tissue-derived cells (hUTC) represent an attractive cell source and a potential t... more Human umbilical tissue-derived cells (hUTC) represent an attractive cell source and a potential technology for neurorestoration and improvement of functional outcomes following stroke. Male Wistar rats were subjected to a transient middle cerebral artery occlusion (tMCAo) and were intravenously administered hUTC (N = 11) or vehicle (N = 10) 48 hrs after stroke. White matter and vascular reorganization was monitored over a 12-week period using MRI and histopathology. MRI results were correlated with neurological functional and histology outcomes to demonstrate that MRI can be a useful tool to measure structural recovery after stroke. MRI revealed a significant reduction in the ventricular volume expansion and improvement in cerebral blood flow (CBF) in the hUTC treated group compared to vehicle treated group. Treatment with hUTC resulted in histological and functional improvements as evidenced by enhanced expression of vWF and synaptophysin, and improved outcomes on behavioral tests....

Research paper thumbnail of Blood-Brain-Barrier Imaging in Brain Tumors: Concepts and Methods

Neurographics, 2012

Malignant gliomas are often very heterogeneous tumors with complex vasculature, frequently exhibi... more Malignant gliomas are often very heterogeneous tumors with complex vasculature, frequently exhibiting angiogenesis and increased vascular permeability. In vivo measurement of the tumor vessel permeability can serve as a potential imaging biomarker to assess tumor grade and aggressiveness. It can also be used to study the response of tumors to various therapies, especially antiangiogenic therapy. Central to the concept of permeability is a thorough knowledge of the BBB and its role in brain tumors and angiogenesis. Much work has been done in the past to understand the structural/molecular composition of the BBB and the role it plays in various pathologic processes, including brain tumors. Various imaging techniques have also been used to evaluate BBB leakiness in brain tumors because higher tumor vascular leakiness is known to be associated with higher grade and malignant potential of the tumor and hence poor patient prognosis. These imaging techniques range from routine postcontrast T1-weighted images to measurement of vascular permeability using various quantitative or semiquantitative indices based on multicompartment pharmacokinetic models. The purpose of this article is to discuss BBB anatomy; various clinically available imaging techniques to evaluate tumor vascular leakiness (perfusion imaging), including their advantages and limitations; as well as a brief discussion of the clinical utility of measuring vascular permeability in brain tumors. We will also discuss the various permeability-related indices along with the pharmacokinetic models to simplify the "nomenclature soup."

Research paper thumbnail of Characterizing Brain Structures and Remodeling after TBI Based on Information Content, Diffusion Entropy

PLoS ONE, 2013

Background: To overcome the limitations of conventional diffusion tensor magnetic resonance imagi... more Background: To overcome the limitations of conventional diffusion tensor magnetic resonance imaging resulting from the assumption of a Gaussian diffusion model for characterizing voxels containing multiple axonal orientations, Shannon's entropy was employed to evaluate white matter structure in human brain and in brain remodeling after traumatic brain injury (TBI) in a rat.

Research paper thumbnail of MRI of Neuronal Recovery after Low-Dose Methamphetamine Treatment of Traumatic Brain Injury in Rats

PLoS ONE, 2013

We assessed the effects of low dose methamphetamine treatment of traumatic brain injury (TBI) in ... more We assessed the effects of low dose methamphetamine treatment of traumatic brain injury (TBI) in rats by employing MRI, immunohistology, and neurological functional tests. Young male Wistar rats were subjected to TBI using the controlled cortical impact model. The treated rats (n = 10) received an intravenous (iv) bolus dose of 0.42 mg/kg of methamphetamine at eight hours after the TBI followed by continuous iv infusion for 24 hrs. The control rats (n = 10) received the same volume of saline using the same protocol. MRI scans, including T2-weighted imaging (T2WI) and diffusion tensor imaging (DTI), were performed one day prior to TBI, and at 1 and 3 days post TBI, and then weekly for 6 weeks. The lesion volumes of TBI damaged cerebral tissue were demarcated by elevated values in T 2 maps and were histologically identified by hematoxylin and eosin (H&E) staining. The fractional anisotropy (FA) values within regions-of-interest (ROI) were measured in FA maps deduced from DTI, and were directly compared with Bielschowsky's silver and Luxol fast blue (BLFB) immunohistological staining. No therapeutic effect on lesion volumes was detected during 6 weeks after TBI. However, treatment significantly increased FA values in the recovery ROI compared with the control group at 5 and 6 weeks after TBI. Myelinated axons histologically measured using BLFB were significantly increased (p,0.001) in the treated group (25.8461.41%) compared with the control group (17.0562.95%). Significant correlations were detected between FA and BLFB measures in the recovery ROI (R = 0.54, p,0.02). Methamphetamine treatment significantly reduced modified neurological severity scores from 2 to 6 weeks (p,0.05) and foot-fault errors from 3 days to 6 weeks (p,0.05) after TBI. Thus, the FA data suggest that methamphetamine treatment improves white matter reorganization from 5 to 6 weeks after TBI in rats compared with saline treatment, which may contribute to the observed functional recovery.

Research paper thumbnail of Model selection for DCE-T1 studies in glioblastoma

Magnetic Resonance in Medicine, 2012

Dynamic contrast enhanced T 1 -weighted MRI using the contrast agent gadopentetate dimeglumine (G... more Dynamic contrast enhanced T 1 -weighted MRI using the contrast agent gadopentetate dimeglumine (Gd-DTPA) was performed on 10 patients with glioblastoma. Nested models with as many as three parameters were used to estimate plasma volume or plasma volume and forward vascular transfer constant (K trans ) and the reverse vascular transfer constant (k ep ). These constituted models 1, 2, and 3, respectively. Model 1 predominated in normal nonleaky brain tissue, showing little or no leakage of contrast agent. Model 3 predominated in regions associated with aggressive portions of the tumor, and model 2 bordered model 3 regions, showing leakage at reduced rates. In the patient sample, v p was about four times that of white matter in the enhancing part of the tumor. K trans varied by a factor of 10 between the model 2 (1.9 $ 10 23 min 21 ) and model 3 regions (1.9 $ 10 22 min 21 ). The mean calculated interstitial space (model 3) was 5.5%. In model 3 regions, excellent curve fits were obtained to summarize concentration-time data (mean R 2 5 0.99). We conclude that the three parameters of the standard model are sufficient to fit dynamic contrast enhanced T 1 data in glioblastoma under the conditions of the experiment. Magn Reson Med 000:000-000,

Research paper thumbnail of Measurement of rat brain tumor kinetics using an intravascular MR contrast agent and DCE-MRI nested model selection

Journal of Magnetic Resonance Imaging, 2014

Purpose: Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in a rat glioma mod... more Purpose: Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in a rat glioma model, and nested model selection (NMS), to compare estimates of the pharmacokinetic parameters v p , K trans , and v e for two different contrast agents (CAs)-gadofosveset, which reversibly binds to human serum albumin, and gadopentetate dimeglumine, which does not.

Research paper thumbnail of MRI measurement of angiogenesis and the therapeutic effect of acute marrow stromal cell administration on traumatic brain injury

Journal of Cerebral Blood Flow & Metabolism, 2012

Using magnetic resonance imaging (MRI), the present study was undertaken to investigate the thera... more Using magnetic resonance imaging (MRI), the present study was undertaken to investigate the therapeutic effect of acute administration of human bone marrow stromal cells (hMSCs) on traumatic brain injury (TBI) and to measure the temporal profile of angiogenesis after the injury with or without cell intervention. Male Wistar rats (300 to 350 g, n=18) subjected to controlled cortical impact TBI were intravenously injected with 1 mL of saline (n=9) or hMSCs in suspension (n=9, 3 × 10(6) hMSCs) 6 hours after TBI. In-vivo MRI acquisitions of T2-weighted imaging, cerebral blood flow (CBF), three-dimensional (3D) gradient echo imaging, and blood-to-brain transfer constant (Ki) of contrast agent were performed on all animals 2 days after injury and weekly for 6 weeks. Sensorimotor function and spatial learning were evaluated. Volumetric changes in the trauma-induced brain lesion and the lateral ventricles were tracked and quantified using T2 maps, and hemodynamic alteration and blood-brain barrier permeability were monitored by CBF and Ki, respectively. Our data show that transplantation of hMSCs 6 hours after TBI leads to reduced cerebral atrophy, early and enhanced cerebral tissue perfusion and improved functional outcome compared with controls. The hMSC treatment increases angiogenesis in the injured brain, which may promote neurologic recovery after TBI.

Research paper thumbnail of Magnetic resonance imaging investigation of axonal remodeling and angiogenesis after embolic stroke in sildenafil-treated rats

Journal of Cerebral Blood Flow & Metabolism, 2008

Interaction between angiogenesis and axonal remodeling after stroke was dynamically investigated ... more Interaction between angiogenesis and axonal remodeling after stroke was dynamically investigated by MRI in rats with or without sildenafil treatments. Male Wistar rats were subjected to embolic stroke and treated daily with saline (n = 10) or with sildenafil (n = 11) initiated at 24 h and subsequently for 7 days after onset of ischemia. -weighted imaging, cerebral blood flow (CBF), and diffusion tensor imaging (DTI) measurements were performed from 24 h to 6 weeks after embolization. and fractional anisotropy (FA) maps detected angiogenesis and axonal remodeling after stroke, respectively, starting from 1 week in sildenafil-treated rats. Areas demarcated by MRI with enhanced angiogenesis, elevated local CBF, and augmented axonal remodeling were spatially and temporally matched, and FA values were significantly correlated with the corresponding CBF values (R = 0.66, P <4×10 −5 ) at 6 weeks after stroke. Axonal projections were reorganized along the ischemic boundary after stroke. These MRI measurements, confirmed by histology, showed that sildenafil treatment simultaneously enhanced angiogenesis and axonal remodeling, which were MRI detectable starting from 1 week after stroke in rats. The spatial and temporal consistency of MRI metrics and the correlation between FA and local CBF suggest that angiogenesis, by elevating local CBF, promotes axonal remodeling after stroke.

Research paper thumbnail of Comparison of Neurite Density Measured by MRI and Histology after TBI

PLoS ONE, 2013

Background: Functional recovery after brain injury in animals is improved by marrow stromal cells... more Background: Functional recovery after brain injury in animals is improved by marrow stromal cells (MSC) which stimulate neurite reorganization. However, MRI measurement of neurite density changes after injury has not been performed. In this study, we investigate the feasibility of MRI measurement of neurite density in an animal model of traumatic brain injury (TBI) with and without MSC treatment.

Research paper thumbnail of An extended vascular model for less biased estimation of permeability parameters in DCE-T1 images

NMR in biomedicine, 2017

One of the key elements in dynamic contrast enhanced (DCE) image analysis is the arterial input f... more One of the key elements in dynamic contrast enhanced (DCE) image analysis is the arterial input function (AIF). Traditionally, in DCE studies a global AIF sampled from a major artery or vein is used to estimate the vascular permeability parameters; however, not addressing dispersion and delay of the AIF at the tissue level can lead to biased estimates of these parameters. To find less biased estimates of vascular permeability parameters, a vascular model of the cerebral vascular system is proposed that considers effects of dispersion of the AIF in the vessel branches, as well as extravasation of the contrast agent (CA) to the extravascular-extracellular space. Profiles of the CA concentration were simulated for different branching levels of the vascular structure, combined with the effects of vascular leakage. To estimate the permeability parameters, the extended model was applied to these simulated signals and also to DCE-T1 (dynamic contrast enhanced T1 ) images of patients with g...

Research paper thumbnail of A parametric model of the brain vascular system for estimation of the arterial input function (AIF) at the tissue level

NMR in biomedicine, 2017

In this paper, we introduce a novel model of the brain vascular system, which is developed based ... more In this paper, we introduce a novel model of the brain vascular system, which is developed based on laws of fluid dynamics and vascular morphology. This model is used to address dispersion and delay of the arterial input function (AIF) at different levels of the vascular structure and to estimate the local AIF in DCE images. We developed a method based on the simplex algorithm and Akaike information criterion to estimate the likelihood of the contrast agent concentration signal sampled in DCE images belonging to different layers of the vascular tree or being a combination of different signal levels from different nodes of this structure. To evaluate this method, we tested the method on simulated local AIF signals at different levels of this structure. Even down to a signal to noise ratio of 5.5 our method was able to accurately detect the branching level of the simulated signals. When two signals with the same power level were combined, our method was able to separate the base signa...

Research paper thumbnail of Optimization of a novel large field of view distortion phantom for MR-only treatment planning

Journal of applied clinical medical physics, Jan 12, 2017

MR-only treatment planning requires images of high geometric fidelity, particularly for large fie... more MR-only treatment planning requires images of high geometric fidelity, particularly for large fields of view (FOV). However, the availability of large FOV distortion phantoms with analysis software is currently limited. This work sought to optimize a modular distortion phantom to accommodate multiple bore configurations and implement distortion characterization in a widely implementable solution. To determine candidate materials, 1.0 T MR and CT images were acquired of twelve urethane foam samples of various densities and strengths. Samples were precision-machined to accommodate 6 mm diameter paintballs used as landmarks. Final material candidates were selected by balancing strength, machinability, weight, and cost. Bore sizes and minimum aperture width resulting from couch position were tabulated from the literature (14 systems, 5 vendors). Bore geometry and couch position were simulated using MATLAB to generate machine-specific models to optimize the phantom build. Previously deve...

Research paper thumbnail of Diffusion-derived MRI Measures of Longitudinal Microstructural Remodeling Induced by Marrow Stromal Cell Therapy after TBI

Journal of Neurotrauma, 2016

Using magnetic resonance imaging (MRI) and an animal model of traumatic brain injury (TBI), we in... more 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 hours or 1 week post-injury, these rats were intravenously injected with 1 ml of saline (at 6 hours or 1 week, n=5/group) or with hMSCs in suspension (3x106 hMSCs, at 6 hours or 1 week, n=10/group). In vivo MRI measurements and sensorimotor function estimates were performed on all animals pre-injury, 1 day, and weekly for 3 weeks post-injury. Bielshowsky&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;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 to the therapy carried out at 1 week post-TBI, cell intervention executed at 6 hours expedites the brain remodeling process and results in an earlier functional recovery. While 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 FA, in probing the structural alterations in the tissue areas with complex fiber patterns.

Research paper thumbnail of Cell Treatment for Stroke in Type Two Diabetic Rats Improves Vascular Permeability Measured by MRI

PloS one, 2016

Treatment of stroke with bone marrow stromal cells (BMSC) significantly enhances brain remodeling... more Treatment of stroke with bone marrow stromal cells (BMSC) significantly enhances brain remodeling and improves neurological function in non-diabetic stroke rats. Diabetes is a major risk factor for stroke and induces neurovascular changes which may impact stroke therapy. Thus, it is necessary to test our hypothesis that the treatment of stroke with BMSC has therapeutic efficacy in the most common form of diabetes, type 2 diabetes mellitus (T2DM). T2DM was induced in adult male Wistar rats by administration of a high fat diet in combination with a single intraperitoneal injection (35mg/kg) of streptozotocin. These rats were then subjected to 2h of middle cerebral artery occlusion (MCAo). T2DM rats received BMSC (5x106, n = 8) or an equal volume of phosphate-buffered saline (PBS) (n = 8) via tail-vein injection at 3 days after MCAo. MRI was performed one day and then weekly for 5 weeks post MCAo for all rats. Compared with vehicle treated control T2DM rats, BMSC treatment of stroke in...

Research paper thumbnail of White matter changes after stroke in type 2 diabetic rats measured by diffusion magnetic resonance imaging

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, Jan 18, 2015

Diffusion-related magnetic resonance imaging parametric maps may be employed to characterize whit... more Diffusion-related magnetic resonance imaging parametric maps may be employed to characterize white matter of brain. We hypothesize that entropy of diffusion anisotropy may be most effective for detecting therapeutic effects of bone marrow stromal cell treatment of ischemia in type 2 diabetes mellitus rats. Type 2 diabetes mellitus was induced in adult male Wistar rats. These rats were then subjected to 2 h of middle cerebral artery occlusion, and received bone marrow stromal cell (5 × 10(6), n = 8) or an equal volume of saline (n = 8) via tail vein injection at three days after middle cerebral artery occlusion. Magnetic resonance imaging was performed on day one and then weekly for five weeks post middle cerebral artery occlusion. The diffusion metrics complementarily permitted characterization of axons and axonal myelination. All six magnetic resonance imaging diffusion metrics, confirmed by histological measures, demonstrated that bone marrow stromal cell treatment significantly (...

Research paper thumbnail of Patterns and dynamics of subventricular zone neuroblast migration in the ischemic striatum of the adult mouse

Journal of Cerebral Blood Flow and Metabolism Official Journal of the International Society of Cerebral Blood Flow and Metabolism, May 1, 2009

The migratory behavior of neuroblasts after a stroke is poorly understood. Using time-lapse micro... more The migratory behavior of neuroblasts after a stroke is poorly understood. Using time-lapse microscopy, we imaged migration of neuroblasts and cerebral vessels in living brain slices of adult doublecortin (DCX, a marker of neuroblasts) enhanced green fluorescent protein (eGFP) transgenic mice that were subjected to 7 days of stroke. Our results show that neuroblasts originating in the subventricular zone (SVZ) of adult mouse brain laterally migrated in chains or individually to reach the ischemic striatum. The chains were initially formed at the border between the SVZ and the striatum by neuroblasts in the SVZ and then extended to the striatum. The average speed of DCX-eGFP-expressing cells within chains was 28.67±1.04 μm/h, which was significantly faster (P < 0.01) than the speed of the cells in the SVZ (17.98±0.57 μm/h). Within the ischemic striatum, individual neuroblasts actively extended or retracted their processes, suggestive of probing the immediate microenvironment. The neuroblasts close to cerebral blood vessels exhibited multiple processes. Our data suggest that neuroblasts actively interact with the microenvironment to reach the ischemic striatum by multiple migratory routes.

Research paper thumbnail of Stroke increases neural stem cells and angiogenesis in the neurogenic niche of the adult mouse

PloS one, 2014

The unique cellular and vascular architecture of the adult ventricular-subventricular zone (V/SVZ... more The unique cellular and vascular architecture of the adult ventricular-subventricular zone (V/SVZ) neurogenic niche plays an important role in regulating neural stem cell function. However, the in vivo identification of neural stem cells and their relationship to blood vessels within this niche in response to stroke remain largely unknown. Using whole-mount preparation of the lateral ventricle wall, we examined the architecture of neural stem cells and blood vessels in the V/SVZ of adult mouse over the course of 3 months after onset of focal cerebral ischemia. Stroke substantially increased the number of glial fibrillary acidic protein (GFAP) positive neural stem cells that are in contact with the cerebrospinal fluid (CSF) via their apical processes at the center of pinwheel structures formed by ependymal cells residing in the lateral ventricle. Long basal processes of these cells extended to blood vessels beneath the ependymal layer. Moreover, stroke increased V/SVZ endothelial cel...

Research paper thumbnail of Perfusion and Diffusion Abnormalities of Multiple Sclerosis Lesions and Relevance of Classified Lesions to Disease Status

Journal of neurology & neurophysiology, 2014

Hemodynamic abnormality and disruption of white matter (WM) integrity are significant components ... more Hemodynamic abnormality and disruption of white matter (WM) integrity are significant components in the pathophysiology of multiple sclerosis (MS) lesions. However, the roles of stratified lesions with distinct degrees of hemodynamic and structural injury in disease states remain to be explored. We tested the hypothesis that hemodynamic and structural impairment, as assessed by cerebral blood volume (CBV) and fractional anisotropy (FA), respectively, characterizes the extent of tissue injury, and the load of lesion with substantial tissue destruction would reflect the disease status and therefore, would be related to clinical disability. Seven relapsing-remitting MS patients and seven healthy controls underwent perfusion, diffusion and conventional MRI scans. Based on T2-FLAIR and T1-weighted image, WM plaques were classified. After image coregistration, values of CBV and FA were estimated in three distinct lesion types (active, T1-hypointense and T1-isointense lesion) and compared ...

Research paper thumbnail of <title>A microfabricated phantom for diffusion tensor imaging</title>

Medical Imaging 2010: Biomedical Applications in Molecular, Structural, and Functional Imaging, 2010

A microfabricated phantom with application in diffusion tensor imaging (DTI) is presented. Using ... more A microfabricated phantom with application in diffusion tensor imaging (DTI) is presented. Using lithography technique, we have the capability of creating microchannels in the same scale as actual neural fibers (few to tens of microns in diameter). The method is flexible in generating different geometrical patterns. Neural bundles were simulated by designing a large number of microchannels, running parallel to

Research paper thumbnail of Comparison of Neurite Density Measured by MRI and Histology after TBI

PLoS ONE, 2013

Functional recovery after brain injury in animals is improved by marrow stromal cells (MSC) which... more Functional recovery after brain injury in animals is improved by marrow stromal cells (MSC) which stimulate neurite reorganization. However, MRI measurement of neurite density changes after injury has not been performed. In this study, we investigate the feasibility of MRI measurement of neurite density in an animal model of traumatic brain injury (TBI) with and without MSC treatment. Fifteen male Wistar rats, were treated with saline (n = 6) or MSCs (n = 9) and were sacrificed at 6 weeks after controlled cortical impact (CCI). Healthy non-CCI rats (n = 5), were also employed. Ex-vivo MRI scans were performed two days after the rats were sacrificed. Multiple-shell hybrid diffusion imaging encoding scheme and spherical harmonic expansion of a two-compartment water diffusion displacement model were used to extract neurite related parameters. Bielshowski and Luxol Fast blue was used for staining axons and myelin, respectively. Modified Morris water maze and neurological severity score (mNSS) test were performed for functional evaluation. The treatment effects, the correlations between neurite densities measured by MRI and histology, and the correlations between MRI and functional variables were calculated by repeated measures analysis of variance, the regression correlation analysis tests, and spearman correlation coefficients. Neurite densities exhibited a significant correlation (R(2)&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;0.80, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;1E-20) between MRI and immuno-histochemistry measurements with 95% lower bound of the intra-correlation coefficient (ICC) as 0.86. The conventional fractional anisotropy (FA) correlated moderately with histological neurite density (R(2) = 0.59, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;1E-5) with 95% lower bound of ICC as 0.76. MRI data revealed increased neurite reorganization with MSC treatment compared with saline treatment, confirmed by histological data from the same animals. mNSS were significantly correlated with MRI neurite density in the hippocampus region. The present studies demonstrated that neurite density can be estimated by MRI after TBI and MRI measurement of neurite density is a sensitive marker to MSC treatment response.

Research paper thumbnail of MRI detects brain reorganization after human umbilical tissue-derived cells (hUTC) treatment of stroke in rat

PloS one, 2012

Human umbilical tissue-derived cells (hUTC) represent an attractive cell source and a potential t... more Human umbilical tissue-derived cells (hUTC) represent an attractive cell source and a potential technology for neurorestoration and improvement of functional outcomes following stroke. Male Wistar rats were subjected to a transient middle cerebral artery occlusion (tMCAo) and were intravenously administered hUTC (N = 11) or vehicle (N = 10) 48 hrs after stroke. White matter and vascular reorganization was monitored over a 12-week period using MRI and histopathology. MRI results were correlated with neurological functional and histology outcomes to demonstrate that MRI can be a useful tool to measure structural recovery after stroke. MRI revealed a significant reduction in the ventricular volume expansion and improvement in cerebral blood flow (CBF) in the hUTC treated group compared to vehicle treated group. Treatment with hUTC resulted in histological and functional improvements as evidenced by enhanced expression of vWF and synaptophysin, and improved outcomes on behavioral tests....

Research paper thumbnail of Blood-Brain-Barrier Imaging in Brain Tumors: Concepts and Methods

Neurographics, 2012

Malignant gliomas are often very heterogeneous tumors with complex vasculature, frequently exhibi... more Malignant gliomas are often very heterogeneous tumors with complex vasculature, frequently exhibiting angiogenesis and increased vascular permeability. In vivo measurement of the tumor vessel permeability can serve as a potential imaging biomarker to assess tumor grade and aggressiveness. It can also be used to study the response of tumors to various therapies, especially antiangiogenic therapy. Central to the concept of permeability is a thorough knowledge of the BBB and its role in brain tumors and angiogenesis. Much work has been done in the past to understand the structural/molecular composition of the BBB and the role it plays in various pathologic processes, including brain tumors. Various imaging techniques have also been used to evaluate BBB leakiness in brain tumors because higher tumor vascular leakiness is known to be associated with higher grade and malignant potential of the tumor and hence poor patient prognosis. These imaging techniques range from routine postcontrast T1-weighted images to measurement of vascular permeability using various quantitative or semiquantitative indices based on multicompartment pharmacokinetic models. The purpose of this article is to discuss BBB anatomy; various clinically available imaging techniques to evaluate tumor vascular leakiness (perfusion imaging), including their advantages and limitations; as well as a brief discussion of the clinical utility of measuring vascular permeability in brain tumors. We will also discuss the various permeability-related indices along with the pharmacokinetic models to simplify the "nomenclature soup."

Research paper thumbnail of Characterizing Brain Structures and Remodeling after TBI Based on Information Content, Diffusion Entropy

PLoS ONE, 2013

Background: To overcome the limitations of conventional diffusion tensor magnetic resonance imagi... more Background: To overcome the limitations of conventional diffusion tensor magnetic resonance imaging resulting from the assumption of a Gaussian diffusion model for characterizing voxels containing multiple axonal orientations, Shannon's entropy was employed to evaluate white matter structure in human brain and in brain remodeling after traumatic brain injury (TBI) in a rat.

Research paper thumbnail of MRI of Neuronal Recovery after Low-Dose Methamphetamine Treatment of Traumatic Brain Injury in Rats

PLoS ONE, 2013

We assessed the effects of low dose methamphetamine treatment of traumatic brain injury (TBI) in ... more We assessed the effects of low dose methamphetamine treatment of traumatic brain injury (TBI) in rats by employing MRI, immunohistology, and neurological functional tests. Young male Wistar rats were subjected to TBI using the controlled cortical impact model. The treated rats (n = 10) received an intravenous (iv) bolus dose of 0.42 mg/kg of methamphetamine at eight hours after the TBI followed by continuous iv infusion for 24 hrs. The control rats (n = 10) received the same volume of saline using the same protocol. MRI scans, including T2-weighted imaging (T2WI) and diffusion tensor imaging (DTI), were performed one day prior to TBI, and at 1 and 3 days post TBI, and then weekly for 6 weeks. The lesion volumes of TBI damaged cerebral tissue were demarcated by elevated values in T 2 maps and were histologically identified by hematoxylin and eosin (H&E) staining. The fractional anisotropy (FA) values within regions-of-interest (ROI) were measured in FA maps deduced from DTI, and were directly compared with Bielschowsky's silver and Luxol fast blue (BLFB) immunohistological staining. No therapeutic effect on lesion volumes was detected during 6 weeks after TBI. However, treatment significantly increased FA values in the recovery ROI compared with the control group at 5 and 6 weeks after TBI. Myelinated axons histologically measured using BLFB were significantly increased (p,0.001) in the treated group (25.8461.41%) compared with the control group (17.0562.95%). Significant correlations were detected between FA and BLFB measures in the recovery ROI (R = 0.54, p,0.02). Methamphetamine treatment significantly reduced modified neurological severity scores from 2 to 6 weeks (p,0.05) and foot-fault errors from 3 days to 6 weeks (p,0.05) after TBI. Thus, the FA data suggest that methamphetamine treatment improves white matter reorganization from 5 to 6 weeks after TBI in rats compared with saline treatment, which may contribute to the observed functional recovery.

Research paper thumbnail of Model selection for DCE-T1 studies in glioblastoma

Magnetic Resonance in Medicine, 2012

Dynamic contrast enhanced T 1 -weighted MRI using the contrast agent gadopentetate dimeglumine (G... more Dynamic contrast enhanced T 1 -weighted MRI using the contrast agent gadopentetate dimeglumine (Gd-DTPA) was performed on 10 patients with glioblastoma. Nested models with as many as three parameters were used to estimate plasma volume or plasma volume and forward vascular transfer constant (K trans ) and the reverse vascular transfer constant (k ep ). These constituted models 1, 2, and 3, respectively. Model 1 predominated in normal nonleaky brain tissue, showing little or no leakage of contrast agent. Model 3 predominated in regions associated with aggressive portions of the tumor, and model 2 bordered model 3 regions, showing leakage at reduced rates. In the patient sample, v p was about four times that of white matter in the enhancing part of the tumor. K trans varied by a factor of 10 between the model 2 (1.9 $ 10 23 min 21 ) and model 3 regions (1.9 $ 10 22 min 21 ). The mean calculated interstitial space (model 3) was 5.5%. In model 3 regions, excellent curve fits were obtained to summarize concentration-time data (mean R 2 5 0.99). We conclude that the three parameters of the standard model are sufficient to fit dynamic contrast enhanced T 1 data in glioblastoma under the conditions of the experiment. Magn Reson Med 000:000-000,

Research paper thumbnail of Measurement of rat brain tumor kinetics using an intravascular MR contrast agent and DCE-MRI nested model selection

Journal of Magnetic Resonance Imaging, 2014

Purpose: Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in a rat glioma mod... more Purpose: Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in a rat glioma model, and nested model selection (NMS), to compare estimates of the pharmacokinetic parameters v p , K trans , and v e for two different contrast agents (CAs)-gadofosveset, which reversibly binds to human serum albumin, and gadopentetate dimeglumine, which does not.

Research paper thumbnail of MRI measurement of angiogenesis and the therapeutic effect of acute marrow stromal cell administration on traumatic brain injury

Journal of Cerebral Blood Flow & Metabolism, 2012

Using magnetic resonance imaging (MRI), the present study was undertaken to investigate the thera... more Using magnetic resonance imaging (MRI), the present study was undertaken to investigate the therapeutic effect of acute administration of human bone marrow stromal cells (hMSCs) on traumatic brain injury (TBI) and to measure the temporal profile of angiogenesis after the injury with or without cell intervention. Male Wistar rats (300 to 350 g, n=18) subjected to controlled cortical impact TBI were intravenously injected with 1 mL of saline (n=9) or hMSCs in suspension (n=9, 3 × 10(6) hMSCs) 6 hours after TBI. In-vivo MRI acquisitions of T2-weighted imaging, cerebral blood flow (CBF), three-dimensional (3D) gradient echo imaging, and blood-to-brain transfer constant (Ki) of contrast agent were performed on all animals 2 days after injury and weekly for 6 weeks. Sensorimotor function and spatial learning were evaluated. Volumetric changes in the trauma-induced brain lesion and the lateral ventricles were tracked and quantified using T2 maps, and hemodynamic alteration and blood-brain barrier permeability were monitored by CBF and Ki, respectively. Our data show that transplantation of hMSCs 6 hours after TBI leads to reduced cerebral atrophy, early and enhanced cerebral tissue perfusion and improved functional outcome compared with controls. The hMSC treatment increases angiogenesis in the injured brain, which may promote neurologic recovery after TBI.

Research paper thumbnail of Magnetic resonance imaging investigation of axonal remodeling and angiogenesis after embolic stroke in sildenafil-treated rats

Journal of Cerebral Blood Flow & Metabolism, 2008

Interaction between angiogenesis and axonal remodeling after stroke was dynamically investigated ... more Interaction between angiogenesis and axonal remodeling after stroke was dynamically investigated by MRI in rats with or without sildenafil treatments. Male Wistar rats were subjected to embolic stroke and treated daily with saline (n = 10) or with sildenafil (n = 11) initiated at 24 h and subsequently for 7 days after onset of ischemia. -weighted imaging, cerebral blood flow (CBF), and diffusion tensor imaging (DTI) measurements were performed from 24 h to 6 weeks after embolization. and fractional anisotropy (FA) maps detected angiogenesis and axonal remodeling after stroke, respectively, starting from 1 week in sildenafil-treated rats. Areas demarcated by MRI with enhanced angiogenesis, elevated local CBF, and augmented axonal remodeling were spatially and temporally matched, and FA values were significantly correlated with the corresponding CBF values (R = 0.66, P <4×10 −5 ) at 6 weeks after stroke. Axonal projections were reorganized along the ischemic boundary after stroke. These MRI measurements, confirmed by histology, showed that sildenafil treatment simultaneously enhanced angiogenesis and axonal remodeling, which were MRI detectable starting from 1 week after stroke in rats. The spatial and temporal consistency of MRI metrics and the correlation between FA and local CBF suggest that angiogenesis, by elevating local CBF, promotes axonal remodeling after stroke.