Radiation induced brain injury: assessment of white matter tracts in a pre-clinical animal model using diffusion tensor MR imaging.

We aim to study radiation induced white matter injury in a pre-clinical model using Diffusion tensor MR imaging (DTI). Nineteen 12-week old Sprague-Dawley rats were irradiated to the right hemisphere using a linear accelerator. The dose distribution map was coregistered to the DTI map to generate the actual radiation dose to each white matter tract. Rats underwent longitudinal DTI scans at five time points from 4 to 48 weeks post-radiation with histological evaluations. Fractional anisotropy (FA) of the external capsule, fornix, cerebral peduncle, anterior commissure, optic tract and optic nerve was evaluated. Radiation dose was highest at the ipsilateral external capsule and fornix (29.4 ± 1.3 and 29.8 ± 1.1 Gy, respectively). Optic nerve received 50 % dose to the external capsule and other white matter tracts received 80 % dose. Significantly lower FA was firstly found in the ipsilateral external capsule at 4 weeks post-radiation and in the ipsilateral fornix at 40 weeks post-radiation compared to the contralateral side. Significantly lower FA was found in contralateral optic nerve compared to ipsilateral optic nerve at 48 weeks post-radiation despite ipsilateral optic nerves receiving higher radiation dose than contralateral optic nerve (p = 0.021). No differences were found in other white matter regions until 48 weeks. Histology indicated demyelination, axonal degeneration and coagulative necrosis in all injured white matter. DTI can serve as a promising tool for assessment of radiation induced white matter injury and regional radiosensitivity of white matter tracts.

Growth properties of SF188/V+ human glioma in rats in vivo observed by magnetic resonance imaging.

SF188/V+ is a highly vascular human glioma model that is based on transfection of vascular endothelial growth factor (VEGF) cDNA into SF188/V- cells. This study aims to assess its growth and vascularity properties in vivo in a rat model. Thirty-two adult rats were inoculated with SF188/V+ tumor cells, and, for comparison, five were inoculated with SF188/V- tumor cells. Several conventional magnetic resonance imaging (MRI) sequences were acquired, and several quantitative structural (T(2) and T(1)), functional [isotropic apparent diffusion coefficient (ADC) and blood flow], and molecular [protein and peptide-based amide proton transfer (APT)] MRI parameters were mapped on a 4.7 T animal scanner. In rats inoculated with SF188/V+ tumor cells, conventional T(2)-weighted images showed a highly heterogeneous tumor mass, and post-contrast T(1)-weighted images showed a heterogeneous, strong enhancement of the mass. There were moderate increases in T(2), T(1), and ADC, and large increases in blood flow and APT in the tumor, compared to contralateral brain tissue. Microscopic examination revealed prominent vascularity and hemorrhage in the VEGF-secreting xenografts as compared to controls, and immunohistochemical staining confirmed increased expression of VEGF in tumor xenografts. Our results indicate that the SF188/V+ glioma model exhibits some MRI and histopathology features that closely resemble human glioblastoma.

Evaluation of radiation necrosis and malignant glioma in rat models using diffusion tensor MR imaging.

Standard MRI cannot distinguish between radiation necrosis and tumor progression; however, this distinction is critical in the assessment of tumor response to therapy. In this study, one delayed radiation necrosis model (dose, 40 Gy; radiation field, 10 × 10 mm(2); n = 13) and two orthotopic glioma models in rats (9L gliosarcoma, n =8; human glioma xenografts, n = 5) were compared using multiple diffusion tensor imaging (DTI) indices. A visible isotropic apparent diffusion coefficient (ADC) pattern was observed in the lesion due to radiation necrosis, which consisted of a hypointense central zone and a hyperintense peripheral zone. There were significantly lower ADC, parallel diffusivity, and perpendicular diffusivity in the necrotic central zone than in the peripheral zone (all P < 0.001). When radiation-induced necrosis was compared with viable tumor, radiation necrosis had significantly lower ADC than 9L gliosarcoma and human glioma xenografts (both P < 0.01) in the central zone, and significantly lower fractional anisotropy than 9L gliosarcoma (P = 0.005) and human glioma xenografts (P = 0.012) in the peripheral zone. Histological analysis revealed parenchymal coagulative necrosis in the central zone, and damaged vessels and reactive astrogliosis in the peripheral zone. These data suggest that qualitative and quantitative analysis of the DTI maps can provide useful information by which to distinguish between radiation necrosis and viable glioma.

Diffusion tensor magnetic resonance imaging of rat glioma models: a correlation study of MR imaging and histology.

INTRODUCTION: Diffusion tensor magnetic resonance (MR) imaging (DTI) can be used to characterize the microstructures of ordered biological tissues. This study was designed to assess histological features of gliomas and surrounding brain tissues in rats using DTI. METHODS: Three types of tumors, a 9L gliosarcoma (n = 8), a F98 glioma (n = 5), and a human glioblastoma xenograft (GBM22; n = 8) were incubated in rat brains and underwent conventional MRI and DTI scanning using a 4.7-T animal MRI system. Fractional anisotropy (FA), isotropic apparent diffusion coefficient, parallel diffusivity (λ//), and perpendicular diffusivity (λ⊥), as well as histological features within several regions of interest were analyzed. RESULTS: All tumor masses consisted of low-FA central zones (tumor center) and high-FA peripheral regions (tumor rim). Histological examination revealed the existence of highly coherent tumor organizations (circular for 9L and F98 or radial for GBM22) in the tumor rims. There were higher apparent diffusion coefficient, λ⊥, and λ// in the peritumoral edema compared to the contralateral gray matter. There were significantly lower FA and higher λ⊥ in the ipsilateral white matter than in the contralateral white matter for the GBM22 tumor, whereas there were no differences for the 9L and F98 tumors. Histologic examination showed GBM22 tumor infiltration into the ipsilateral damaged white matter. CONCLUSIONS: Quantitative analysis of DTI indices provides useful information for assessing tumor microstructure and tumor cell invasion into the adjacent gray matter and white matter.

Brain structural alterations detected by an automatic quantified tool as an indicator for MCI diagnosing in type 2 diabetes mellitus patients: A magnetic resonance imaging study.

Background and objectives: Type 2 diabetes mellitus (T2DM) is an important risk factors for mild cognitive impairment (MCI). Structural magnetic resonance imaging (sMRI) is an effective and widely used method to investigate brain pathomorphological injury in neural diseases. In present study, we aimed to determine the brain regional alterations that correlated to the incidence of MCI in T2DM patients. Materials and methods: Eighteen T2DM patients with and without MCI (DMCI/T2DM) respectively, and eighteen age/gender-matched healthy controls (HC) were recruited. Brain MRI imagines of all the individuals were subjected to automatic quantified brain sub-structure volume segmentation and measurement by Dr. brain ™ software. The relative volume of total gray matter (TGM), total white matter (TWM), and 68 pairs (left and right) of brain sub-structures were compared between the three groups. Cognitive function correlation analysis and receiver operating characteristic (ROC) curve analysis were conducted in the MCI-related brain regions in T2DM patients, and we utilized a machine learning method to classify the three group of subjects. Results: 10 and 27 brain sub-structures with significant relative volumetric alterations were observed in T2DM patients without MCI and T2DM patients with MCI, respectively (p < 0.05). Compared with T2DM patients without MCI, eight critical regions include right anterior orbital gyrus, right calcarine and cerebrum, left cuneus, left entorhinal area, left frontal operculum, right medial orbital gyrus, right occipital pole, left temporal pole had significant lower volumetric ratio in T2DM patients with MCI (p < 0.05). Among them, the decrease of volumetric ratio in several regions had a positive correlation with Montreal Cognitive Assessment (MoCA) scores and Mini-Mental State Examination (MMSE) scores. The classification results conducted based on these regions as features by random forest algorithm yielded good accuracies of T2DM/HC 69.4%, DMCI/HC 72.2% and T2DM/DMCI 69.4%. Conclusions: Certain brain regional structural lesions occurred in patients with T2DM, and this condition was more serious in T2DM patients combined with MCI. A systematic way of segmenting and measuring the whole brain has a potential clinical value for predicting the presence of MCI for T2DM patients.

Comparison of Two Software Packages for Perfusion Imaging: Ischemic Core and Penumbra Estimation and Patient Triage in Acute Ischemic Stroke.

Purpose: Automated postprocessing packages have been developed for managing acute ischemic stroke (AIS). These packages identify ischemic core and penumbra using either computed tomographic perfusion imaging (CTP) data or magnetic resonance imaging (MRI) data. Measurements of abnormal tissues and treatment decisions derived from different vendors can vary. The purpose of this study is to investigate the agreement of volumetric and decision-making outcomes derived from two software packages. Methods: A total of 594 AIS patients (174 underwent CTP and 420 underwent MRI) were included. Imaging data were accordingly postprocessed by two software packages: RAPID and RealNow. Volumetric outputs were compared between packages by performing intraclass correlation coefficient (ICC), Wilcoxon paired test and Bland-Altman analysis. Concordance of selecting patients eligible for mechanical thrombectomy (MT) was assessed based on neuroimaging criteria proposed in DEFUSE3. Results: In the group with CTP data, mean ischemic core volume (ICV)/penumbral volume (PV) was 14.9/81.1 mL via RAPID and 12.6/83.2 mL via RealNow. Meanwhile, in the MRI group, mean ICV/PV were 52.4/68.4 mL and 48.9/61.6 mL via RAPID and RealNow, respectively. Reliability, which was measured by ICC of ICV and PV in CTP and MRI groups, ranged from 0.87 to 0.99. The bias remained small between measurements (CTP ICV: 0.89 mL, CTP PV: -2 mL, MRI ICV: 3.5 mL and MRI PV: 6.8 mL). In comparison with CTP ICV with follow-up DWI, the ICC was 0.92 and 0.94 for RAPID and Realnow, respectively. The bias remained small between CTP ICV and follow-up DWI measurements (Rapid: -4.65 mL, RealNow: -3.65 mL). Wilcoxon paired test showed no significant difference between measurements. The results of patient triage were concordant in 159/174 cases (91%, ICC: 0.90) for CTP and 400/420 cases (95%, ICC: 0.93) for MRI. Conclusion: The CTP ICV derived from RealNow was more accurate than RAPID. The similarity in volumetric measurement between packages did not necessarily relate to equivalent patient triage. In this study, RealNow showed excellent agreement with RAPID in measuring ICV and PV as well as patient triage.

Dynamic contrast-enhanced MRI of primary rectal cancer: quantitative correlation with positron emission tomography/computed tomography.

PURPOSE: To assess the correlations between parameters measured on dynamic contrast-enhanced magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in rectal cancer. MATERIALS AND METHODS: To assess the correlations between parameters measured on dynamic contrast-enhanced MRI and FDG-PET in rectal cancer. RESULTS: Significant correlations were only demonstrated between k(ep) and SUVmax (r = 0.587, P = 0.001), and k(ep) and SUVmean (r = 0.562, P = 0.002). No significant differences were found in imaging parameters between well, moderately and poorly differentiated adenocarcinoma groups. However, there was a trend that higher imaging values were found in poorly differentiated adenocarcinomas. CONCLUSION: Positive correlations were found between k(ep) and SUV values in primary rectal adenocarcinomas suggesting an association between angiogenesis and metabolic activity and further reflecting that angiogenic activity in washout phase is better associated with tumor metabolism than the uptake phase.

MR imaging of high-grade brain tumors using endogenous protein and peptide-based contrast.

Amide proton transfer (APT) imaging is a novel MRI technique, in which the amide protons of endogenous proteins and peptides are irradiated to accomplish indirect detection using the bulk water signal. In this paper, the APT approach was added to a standard brain MRI protocol at 3T, and twelve patients with high-grade gliomas confirmed by histopathology were scanned. It is shown that all tumors, including one with minor gadolinium enhancement, showed heterogeneous hyperintensity on the APT images. The average APT signal intensities of the viable tumor cores were significantly higher than those of peritumoral edema and normal-appearing white matter (P<0.001). The average APT signal intensities were significantly lower in the necrotic regions than in the viable tumor cores (P=0.004). The APT signal intensities of the cystic cavities were similar to those of the viable tumor cores (P>0.2). The initial results show that APT imaging at the protein and peptide level may enhance non-invasive identification of tissue heterogeneity in high-grade brain tumors.

Hippocampal and Amygdalar Morphological Abnormalities in Alzheimer's Disease Based on Three Chinese MRI Datasets.

BACKGROUND: Early detection of Alzheimer's disease (AD) and its early stage, the mild cognitive impairment (MCI), has important scientific, clinical and social significance. Magnetic resonance imaging (MRI) based statistical shape analysis provides an opportunity to detect regional structural abnormalities of brain structures caused by AD and MCI. OBJECTIVE: In this work, we aimed to employ a well-established statistical shape analysis pipeline, in the framework of large deformation diffeomorphic metric mapping, to identify and quantify the regional shape abnormalities of the bilateral hippocampus and amygdala at different prodromal stages of AD, using three Chinese MRI datasets collected from different domestic hospitals. METHODS: We analyzed the region-specific shape abnormalities at different stages of the neuropathology of AD by comparing the localized shape characteristics of the bilateral hippocampi and amygdalas between healthy controls and two disease groups (MCI and AD). In addition to group comparison analyses, we also investigated the association between the shape characteristics and the Mini Mental State Examination (MMSE) of each structure of interest in the disease group (MCI and AD combined) as well as the discriminative power of different morphometric biomarkers. RESULTS: We found the strongest disease pathology (regional atrophy) at the subiculum and CA1 subregions of the hippocampus and the basolateral, basomedial as well as centromedial subregions of the amygdala. Furthermore, the shape characteristics of the hippocampal and amygdalar subregions exhibiting the strongest AD related atrophy were found to have the most significant positive associations with the MMSE. Employing the shape deformation marker of the hippocampus or the amygdala for automated MCI or AD detection yielded a significant accuracy boost over the corresponding volume measurement. CONCLUSION: Our results suggested that the amygdalar and hippocampal morphometrics, especially those of shape morphometrics, can be used as auxiliary indicators for monitoring the disease status of an AD patient.

Deep-Learning-Based Segmentation and Localization of White Matter Hyperintensities on Magnetic Resonance Images.

White matter magnetic resonance hyperintensities of presumed vascular origin, which could be widely observed in elderly people, and has significant importance in multiple neurological studies. Quantitative measurement usually relies heavily on manual or semi-automatic delineation and intuitive localization, which is time-consuming and observer-dependent. Current automatic quantification methods focus mainly on the segmentation, but the spatial distribution of lesions plays a vital role in clinical diagnosis. In this study, we implemented four segmentation algorithms and compared the performances quantitatively and qualitatively on two open-access datasets. The location-specific analysis was conducted sequentially on 213 clinical patients with cerebral ischemia and lacune. The experimental results suggest that our deep-learning-based model has the potential to be integrated into the clinical workflow.

Revealing hemodynamic heterogeneity of gliomas based on signal profile features of dynamic susceptibility contrast-enhanced MRI.

Dynamic susceptibility contrast enhanced magnetic resonance imaging (DSC MRI) is widely used for studying blood perfusion in brain tumors. While the time-dependent change of MRI signals related to the concentration of the tracer is used to derive the hemodynamic parameters such as regional blood volume and flow into tumors, the tissue-specific information associated with variations in profiles of signal time course is often overlooked. We report a new approach of combining model free independent component analysis (ICA) identification of specific signal profiles of DSC MRI time course data and extraction of the features from those time course profiles to interrogate time course data followed by calculating the region specific blood volume based on selected individual time courses. Based on the retrospective analysis of DSC MRI data from 38 patients with pathology confirmed low (n = 18) and high (n = 20) grade gliomas, the results reveal the spatially defined intra-tumoral hemodynamic heterogeneity of brain tumors based on features of time course profiles. The hemodynamic heterogeneity as measured by the number of independent components of time course data is associated with the tumor grade. Using 8 selected signal profile features, machine-learning trained algorithm, e.g., logistic regression, was able to differentiate pathology confirmed low intra-tumoral and high grade gliomas with an accuracy of 86.7%. Furthermore, the new method can potentially extract more tumor physiological information from DSC MRI comparing to the traditional model-based analysis and morphological analysis of tumor heterogeneity, thus may improve the characterizations of gliomas for better diagnosis and treatment decisions.

Traumatic Brain Injury Results in Dynamic Brain Structure Changes Leading to Acute and Chronic Motor Function Deficits in a Pediatric Piglet Model.

Traumatic brain injury (TBI) is a leading cause of death and disability in children. Pediatric TBI patients often suffer from crippling cognitive, emotional, and motor function deficits that have negative lifelong effects. The objective of this study was to longitudinally assess TBI pathophysiology using multi-parametric magnetic resonance imaging (MRI), gait analysis, and histological approaches in a pediatric piglet model. TBI was produced by controlled cortical impact in Landrace piglets. MRI data, including from proton magnetic resonance spectroscopy (MRS), were collected 24 hours and 12 weeks post-TBI, and gait analysis was performed at multiple time-points over 12 weeks post-TBI. A subset of animals was sacrificed 24 hours, 1 week, 4 weeks, and 12 weeks post-TBI for histological analysis. MRI results demonstrated that TBI led to a significant brain lesion and midline shift as well as microscopic tissue damage with altered brain diffusivity, decreased white matter integrity, and reduced cerebral blood flow. MRS showed a range of neurochemical changes after TBI. Histological analysis revealed neuronal loss, astrogliosis/astrocytosis, and microglia activation. Further, gait analysis showed transient impairments in cadence, cycle time, % stance, step length, and stride length, as well as long-term impairments in weight distribution after TBI. Taken together, this study illustrates the distinct time course of TBI pathoanatomic and functional responses up to 12 weeks post-TBI in a piglet TBI model. The study of TBI injury and recovery mechanisms, as well as the testing of therapeutics in this translational model, are likely to be more predictive of human responses and clinical outcomes compared to traditional small animal models.

Characterization of white matter injury in a hypoxic-ischemic neonatal rat model by diffusion tensor MRI.

BACKGROUND AND PURPOSE: We evaluate white matter (WM) injury after hypoxic-ischemic (HI) insult in a neonatal rat model using diffusion tensor imaging (DTI) to determine whether lambda(parallel) and lambda(perpendicular) are able to characterize type and severity of brain damage. METHODS: Eighteen 7-day-old Sprague-Dawley rats underwent unilateral ligation of left common carotid artery followed by 50 minutes (n=9) or 90 minutes (n=9) of hypoxia at 37 degrees C. Rats were divided into 2 groups, according to absence (group A, n=11) or presence (group B, n=7) of cystic lesions on D7 post-HI T2-weighted imaging. DTI was performed for all rats at D1 and for group A rats at D7 post-HI. Signal intensity of ipsilateral and contralateral external capsule (EC) on D1 was compared by paired t test, with histological correlation. RESULTS: Group A rats had significantly reduced FA, elevated trace, elevated lambda(perpendicular), and similar lambda(parallel) on D1 in the ipsilateral compared to contralateral EC, whereas group B rats had significant reduction in all parameters in the ipsilateral EC. Elevated trace normalized on D7 in group A rats. Histopathologic results demonstrated reduced myelination in group A noncystic HI and severe necrosis in group B cystic HI. CONCLUSIONS: Increased lambda(perpendicular) with no significant change in lambda(parallel) appears to characterize noncystic WM injury with reduced myelination, whereas reduction in both lambda(parallel) and lambda(perpendicular) characterize severe damage with loss of structural integrity and necrosis. Combining with FA and trace, lambda(parallel) and lambda(perpendicular) provide additional information which reflects type and severity of HI injury.

Evaluation of neuregulin-1's neuroprotection against ischemic injury in rats using diffusion tensor imaging.

Stroke is a devastating neurovascular disorder that results in damage to neurons and white matter tracts. It has been previously demonstrated that neuregulin-1 (NRG-1) protects neurons from ischemic injury following stroke. Here, diffusion tensor imaging (DTI) was utilized to characterize the effects of NRG-1 treatment on cererbral infarction and integrity of white matter after ischemic insult using a permanent middle celebral artery occlusion (pMCAo) rat model. In the present study, sixteen Sprague-Dawley rats underwent pMCAo surgery and received either a single intra-arterial bolus (20 µg/kg) dose of NRG-1 or saline immediately prior to pMCAo. MRI including T2-weighted imaging and DTI was performed in the first 3 h post stroke, and repeated 48 h later. It is found that the stroke infarction was significantly reduced in the NRG-1 treated group. Also, NRG-1 prevented the reduction of fractional anisotropy (FA) in white matter tracts of fornix and corpus callosum (CC), indicating its protection of CC and fornix white matter bundles from ischemia insult. As a conclusion, the present DTI results demonstrate that NRG-1 has significantly neuroprotective effects in both cerebral cortex and white matter including corpus callosum and fornix during acute stroke. In particular, NRG-1 is more effective on stroke lesion with mild ischemia. As CC and fornix white matter bundles play critical roles in transcallosal connectivity and hippocampal projections respectively in the central nervous system, the findings could provide complementary information for better understanding the biological mechanism of NRG-1's neuroprotection in ischemic tissues and neurobehavioral effects.

Metabolite Profile of Alzheimer's Disease in the Frontal Cortex as Analyzed by HRMAS 1H NMR.

Background: Investigation on neurochemical changes in the frontal cortex in individuals with Alzheimer's disease (AD) and different Apolipoprotein E (APOE) genotypes, using ex vivo solid-state high-resolution NMR analysis, may lead to a better understanding of the neurochemistry associated with AD as well as new AD-specific metabolite biomarkers that might potentially improve the clinical diagnosis of AD. Methods: Intact tissue samples of the frontal cortex were obtained from 11 patients and 11 age-matched non-demented controls. Metabolite profiles in all samples were analyzed ex vivo, using solid-state high-resolution magic angle spinning (HRMAS) 600 MHz 1H nuclear magnetic resonance (NMR). A logistic regression analysis was used to rank metabolites based on their level of contribution in differentiating the AD patient tissues and the controls, and different AD-associated APOE genotypes (APOE ε4 vs. APOE ε3). Results: Tissue samples from the AD patients showed significantly lower NAA/Cr (p = 0.011), Ace/Cr (p = 0.027), GABA/Cr (p = 0.005), Asp/Cr (p < 0.0001), mI/Cr (p < 0.0001), and Tau/Cr (p = 0.021), and higher PCho/Cr (p < 0.0001), GPCho/Cr (p < 0.0001), and α&ß-Glc/Cr (p < 0.0001) than the controls did. Specifically, a newly observed resonance at 3.71 ppm, referred to as α&ß-Glc, was observed in 90.9% of the AD samples (10/11). Samples with APOE ε4 also exhibited higher PCho/Cr (p = 0.0002), GPCho/Cr (p = 0.0001), α&ß-Glc/Cr (p < 0.0001), and lower Asp/Cr (p = 0.004) and GABA/Cr (p = 0.04) than the samples with APOE ε3 did. In the logistic regression analysis, PCho, GPCho, ASP, and α&ß-Glc were found to be the most relevant metabolites for differentiating the AD patient tissues and the controls, and different APOE genotypes. Conclusion: HRMAS 1H NMR with high spectral resolution and sensitivity offers a powerful tool to gain quantitative information on AD associated neurochemical changes. There are important neurochemical differences in the frontal cortex between the AD patient tissues and the controls, and between those with different APOE genotypes. The resonance (α&ß-Glc) found at 3.71 ppm in the AD patient tissues may be further investigated for its potential in the diagnosis and monitoring of AD.

Progressive Assessment of Ischemic Injury to White Matter Using Diffusion Tensor Imaging: A Preliminary Study of a Macaque Model of Stroke.

BACKGROUND: Previous Diffusion Tensor Imaging (DTI) studies have demonstrated the temporal evolution of stroke injury in grey matter and white matter can be characterized by DTI indices. However, it still remains not fully understood how the DTI indices of white matter are altered progressively during the hyperacute (first 6 hours) and acute stage of stroke (≤ 1 week). In the present study, DTI was employed to characterize the temporal evolution of infarction and white matter injury after stroke insult using a macaque model with permanent ischemic occlusion. METHODS AND MATERIALS: Permanent middle cerebral artery (MCA) occlusion was induced in rhesus monkeys (n=4, 10-21 years old). The brain lesion was examined longitudinally with DTI during the hyperacute phase (2-6 hours, n=4), 48 hours (n=4) and 96 hours (n=3) post-occlusion. RESULTS: Cortical infarction was seen in all animals. The Mean Diffusivity (MD) in lesion regions decreased substantially at the first time point (2 hours post stroke) (35%, p <0.05, compared to the contralateral side) and became pseudo-normalized at 96 hours. In contrast, evident FA reduction was seen at 48 hours (39%, p <0.10) post-stroke. MD reduction in white matter bundles of the lesion area was much less than that in the grey matter during the hyper-acute phase but significant change was observed 4 hours (4.2%, p < 0.05) post stroke . Also, MD pseudonormalisation was seen at 96 hours post stroke. There was a significant correlation between the temporal changes of MD in white matter bundles and those in whole lesion areas during the entire study period. Meanwhile, no obvious fractional anisotropy (FA) changes were seen during the hyper-acute phase in either the entire infarct region or white matter bundles. Significant FA alteration was observed in entire lesion areas and injured white matter bundles 48 and 96 hours post stroke. The stroke lesion in grey matter and white matter was validated by pathological findings. CONCLUSION: The temporal evolution of ischemic injury to the grey matter and white matter from 2 to 96 hours after stroke onset was characterized using a macaque model and DTI. Progressive MD changes in white matter bundles are seen from hyperacute phase to acute phase after permanent MCA occlusion and temporally correlated with the MD changes in entire infarction regions. MD reduction in white matter bundles is mild in comparison with that in the grey matter but significant and progressive, indicating it may be useful to detect early white matter degeneration after stroke.

Longitudinal MRI evaluation of neuroprotective effects of pharmacologically induced hypothermia in experimental ischemic stroke.

Pharmacologically induced hypothermia (PIH) shows promising neuroprotective effects after stroke insult. However, the dynamic evolution of stroke infarct during the hypothermic therapy has not been understood very well. In the present study, MRI was utilized to longitudinally characterize the infarct evolution in a mouse model of ischemic stroke treated by PIH using the neurotensin agonist HPI201. Adult male C57BL/6 mice underwent permanent occlusion of the right middle cerebra artery (MCA). Each animal received a vehicle or HPI201 intraperitoneal injection. The temporal changes of stroke lesion were examined using T2-weighted imaging and diffusion-weighted imaging (DWI) in the acute phase (1-3h) and 24h post stroke. Significantly reduced infarct and edema volumes were observed in PIH treated stroke mice, in agreement with TTC staining findings. Also, the TUNEL staining results indicated apoptotic cells were widely distributed among the ischemic cortex in control group but limited in PIH treated mice. Dramatically reduced growth rate of infarction was seen in PIH treated stroke mice. These results demonstrate HPI201 has strong neuroprotection effects during acute stroke. In particular, MRI with the numerical modelling of temporal infarct evolution could provide a unique means to examine and predict the dynamic response of the PIH treatment on infarct evolution.

Amyloid-Related Imaging Abnormalities in an Aged Squirrel Monkey with Cerebral Amyloid Angiopathy.

Amyloid-related imaging abnormalities (ARIA) in magnetic resonance imaging scans have emerged as indicators of potentially serious side effects in clinical trials of therapeutics for Alzheimer's disease. These anomalies include an edematous type (ARIA-E) that appears as hyperintense (bright) regions by T2-weighted MRI, and a type characterized by the deposition of hemosiderin (ARIA-H) that elicits a hypointense signal, especially in T2* susceptibility weighted images. ARIA in general has been linked to the presence of amyloid-ß (Aß)-type cerebral amyloid angiopathy, an accumulation of misfolded Aß protein in the vascular wall that impairs the integrity of brain blood vessels. However, the pathobiology of ARIA remains poorly understood, in part due to the absence of an animal model of the disorder that would enable a contemporaneous analysis of tissue integrity in the affected region. Here we describe both ARIA-E and ARIA-H in an aged squirrel monkey (Saimiri sciureus), a nonhuman primate model of naturally occurring cerebral amyloid angiopathy. Histopathologic examination of the anomalous region revealed reactive astrocytosis and microgliosis, infiltration of systemic inflammatory/immune cells, damage to axons and myelin, and hemosiderin deposition. The disruption of axons in particular suggests that ARIA-E could have functional consequences for affected regions. The squirrel monkey model can be useful for studying the pathogenesis and long-term effects of ARIA, and for testing the safety and efficacy of emerging therapies for Alzheimer's disease.

Genetic engineered molecular imaging probes for applications in cell therapy: emphasis on MRI approach.

Recent advances in stem cell-based regenerative medicine, cell replacement therapy, and genome editing technologies (i.e. CRISPR-Cas 9) have sparked great interest in in vivo cell monitoring. Molecular imaging promises a unique approach to noninvasively monitor cellular and molecular phenomena, including cell survival, migration, proliferation, and even differentiation at the whole organismal level. Several imaging modalities and strategies have been explored for monitoring cell grafts in vivo. We begin this review with an introduction describing the progress in stem cell technology, with a perspective toward cell replacement therapy. The importance of molecular imaging in reporting and assessing the status of cell grafts and their relation to the local microenvironment is highlighted since the current knowledge gap is one of the major obstacles in clinical translation of stem cell therapy. Based on currently available imaging techniques, we provide a brief discussion on the pros and cons of each imaging modality used for monitoring cell grafts with particular emphasis on magnetic resonance imaging (MRI) and the reporter gene approach. Finally, we conclude with a comprehensive discussion of future directions of applying molecular imaging in regenerative medicine to emphasize further the importance of correlating cell graft conditions and clinical outcomes to advance regenerative medicine.

Determining Cardiac Fiber Orientation Using FSL and Registered Ultrasound/DTI volumes.

Accurate extraction of cardiac fiber orientation from diffusion tensor imaging is important for determining heart structure and function. However, the acquisition of magnetic resonance (MR) diffusion tensor images is costly and time consuming. By comparison, cardiac ultrasound imaging is rapid and relatively inexpensive, but it lacks the capability to directly measure fiber orientations. In order to create a detailed heart model from ultrasound data, a three-dimensional (3D) diffusion tensor imaging (DTI) with known fiber orientations can be registered to an ultrasound volume through a geometric mask. After registration, the cardiac orientations from the template DTI can be mapped to the heart using a deformable transformation field. This process depends heavily on accurate fiber orientation extraction from the DTI. In this study, we use the FMRIB Software Library (FSL) to determine cardiac fiber orientations in diffusion weighted images. For the registration between ultrasound and MRI volumes, we achieved an average Dice similarity coefficient (DSC) of 81.6±2.1%. For the estimation of fiber orientations from the proposed method, we achieved an acute angle error (AAE) of 22.7±3.1° as compared to the direct measurements from DTI. This work provides a new approach to generate cardiac fiber orientation that may be used for many cardiac applications.