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.

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.

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.

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.

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.

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.

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.

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.

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.

Simulating cardiac ultrasound image based on MR diffusion tensor imaging.

PURPOSE: Cardiac ultrasound simulation can have important applications in the design of ultrasound systems, understanding the interaction effect between ultrasound and tissue and setting the ground truth for validating quantification methods. Current ultrasound simulation methods fail to simulate the myocardial intensity anisotropies. New simulation methods are needed in order to simulate realistic ultrasound images of the heart. METHODS: The proposed cardiac ultrasound image simulation method is based on diffusion tensor imaging (DTI) data of the heart. The method utilizes both the cardiac geometry and the fiber orientation information to simulate the anisotropic intensities in B-mode ultrasound images. Before the simulation procedure, the geometry and fiber orientations of the heart are obtained from high-resolution structural MRI and DTI data, respectively. The simulation includes two important steps. First, the backscatter coefficients of the point scatterers inside the myocardium are processed according to the fiber orientations using an anisotropic model. Second, the cardiac ultrasound images are simulated with anisotropic myocardial intensities. The proposed method was also compared with two other nonanisotropic intensity methods using 50 B-mode ultrasound image volumes of five different rat hearts. The simulated images were also compared with the ultrasound images of a diseased rat heart in vivo. A new segmental evaluation method is proposed to validate the simulation results. The average relative errors (AREs) of five parameters, i.e., mean intensity, Rayleigh distribution parameter σ, and first, second, and third quartiles, were utilized as the evaluation metrics. The simulated images were quantitatively compared with real ultrasound images in both ex vivo and in vivo experiments. RESULTS: The proposed ultrasound image simulation method can realistically simulate cardiac ultrasound images of the heart using high-resolution MR-DTI data. The AREs of their proposed method are 19% for the mean intensity, 17.7% for the scale parameter of Rayleigh distribution, 36.8% for the first quartile of the image intensities, 25.2% for the second quartile, and 19.9% for the third quartile. In contrast, the errors of the other two methods are generally five times more than those of their proposed method. CONCLUSIONS: The proposed simulation method uses MR-DTI data and realistically generates cardiac ultrasound images with anisotropic intensities inside the myocardium. The ultrasound simulation method could provide a tool for many potential research and clinical applications in cardiac ultrasound imaging.

3D in vivo imaging of rat hearts by high frequency ultrasound and its application in myofiber orientation wrapping.

Cardiac ultrasound plays an important role in the imaging of hearts in basic cardiovascular research and clinical examinations. 3D ultrasound imaging can provide the geometry or motion information of the heart. Especially, the wrapping of cardiac fiber orientations to the ultrasound volume could supply useful information on the stress distributions and electric action spreading. However, how to acquire 3D ultrasound volumes of the heart of small animals in vivo for cardiac fiber wrapping is still a challenging problem. In this study, we provide an approach to acquire 3D ultrasound volumes of the rat hearts in vivo. The comparison between both in vivo and ex vivo geometries indicated 90.1% Dice similarity. In this preliminary study, the evaluations of the cardiac fiber orientation wrapping errors were 24.7° for the acute angle error and were 22.4° for the inclination angle error. This 3D ultrasound imaging and fiber orientation estimation technique have potential applications in cardiac imaging.

Spatio-temporal assessment of the neuroprotective effects of neuregulin-1 on ischemic stroke lesions using MRI.

The neuroprotective effects of neuregulin-1 (NRG-1) on stroke lesions were assessed longitudinally in rats with middle cerebral artery occlusion (MCAo) using MRI. Sprague-Dawley rats (n=16, 250±20g) underwent permanent MCAo surgery with cerebral blood flow (CBF) monitored by laser doppler flowmetry at ipsilateral side of bregma for 20min post-occlusion. A single 50µl bolus dose of NRG-1 or vehicle was administered into the left internal carotid artery immediately prior to MCAo. The expansion of the ischemic lesion into the cortex was attenuated by NRG-1 over a 48-hour (h) time span as measured by diffusion weighted imaging (DWI). The final infarct volumes of NRG-1 treated rats were significantly smaller than those of the vehicle treated rats at 48h (264.8±192.1 vs. 533.4±175.5mm(3), p<0.05). The NRG-1 treated rats were further subdivided into 2 subgroups according to their CBF reduction during stroke surgery: mild ischemia (<70% CBF reduction) or severe ischemia (>70% CBF reduction). In particular, ischemic infarction was not usually observed in the cortex of NRG-1 treated rats with mild ischemia at 3 and 48h post-occlusion. Histological results validated the imaging findings and demonstrated that NRG-1 treated rats had fewer injured neurons in peri-infarct areas 48h post-ischemia. In summary, the neuroprotective effect of NRG-1 in the pMCAo stroke model was demonstrated by prevention of ischemic lesion expansion, reduced infarct volume and protection of neurons from ischemic damage.

Temporal evolution of ischemic lesions in nonhuman primates: a diffusion and perfusion MRI study.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) and perfusion MRI were used to examine the spatiotemporal evolution of stroke lesions in adult macaques with ischemic occlusion. METHODS: Permanent MCA occlusion was induced with silk sutures through an interventional approach via the femoral artery in adult rhesus monkeys (n = 8, 10-21 years old). The stroke lesions were examined with high-resolution DWI and perfusion MRI, and T2-weighted imaging (T2W) on a clinical 3T scanner at 1-6, 48, and 96 hours post occlusion and validated with H&E staining. RESULTS: The stroke infarct evolved via a natural logarithmic pattern with the mean infarct growth rate = 1.38 ± 1.32 ml per logarithmic time scale (hours) (n = 7) in the hyperacute phase (1-6 hours). The mean infarct volume after 6 hours post occlusion was 3.6±2.8 ml (n = 7, by DWI) and increased to 3.9±2.9 ml (n = 5, by T2W) after 48 hours, and to 4.7±2.2ml (n = 3, by T2W) after 96 hours post occlusion. The infarct volumes predicted by the natural logarithmic function were correlated significantly with the T2W-derived lesion volumes (n = 5, r = 0.92, p = 0.01) at 48 hours post occlusion. The final infarct volumes derived from T2W were correlated significantly with those from H&E staining (r = 0.999, p < 0.0001, n = 4). In addition, the diffusion-perfusion mismatch was visible generally at 6 hours but nearly diminished at 48 hours post occlusion. CONCLUSION: The infarct evolution follows a natural logarithmic pattern in the hyperacute phase of stroke. The logarithmic pattern of evolution could last up to 48 hours after stroke onset and may be used to predict the infarct volume growth during the acute phase of ischemic stroke. The nonhuman primate model, MRI protocols, and post data processing strategy may provide an excellent platform for characterizing the evolution of acute stroke lesion in mechanistic studies and therapeutic interventions of stroke disease.

Register cardiac fiber orientations from 3D DTI volume to 2D ultrasound image of rat hearts.

Two-dimensional (2D) ultrasound or echocardiography is one of the most widely used examinations for the diagnosis of cardiac diseases. However, it only supplies the geometric and structural information of the myocardium. In order to supply more detailed microstructure information of the myocardium, this paper proposes a registration method to map cardiac fiber orientations from three-dimensional (3D) magnetic resonance diffusion tensor imaging (MR-DTI) volume to the 2D ultrasound image. It utilizes a 2D/3D intensity based registration procedure including rigid, log-demons, and affine transformations to search the best similar slice from the template volume. After registration, the cardiac fiber orientations are mapped to the 2D ultrasound image via fiber relocations and reorientations. This method was validated by six images of rat hearts ex vivo. The evaluation results indicated that the final Dice similarity coefficient (DSC) achieved more than 90% after geometric registrations; and the inclination angle errors (IAE) between the mapped fiber orientations and the gold standards were less than 15 degree. This method may provide a practical tool for cardiologists to examine cardiac fiber orientations on ultrasound images and have the potential to supply additional information for diagnosis of cardiac diseases.

Mapping Cardiac Fiber Orientations from High-Resolution DTI to High-Frequency 3D Ultrasound.

The orientation of cardiac fibers affects the anatomical, mechanical, and electrophysiological properties of the heart. Although echocardiography is the most common imaging modality in clinical cardiac examination, it can only provide the cardiac geometry or motion information without cardiac fiber orientations. If the patient's cardiac fiber orientations can be mapped to his/her echocardiography images in clinical examinations, it may provide quantitative measures for diagnosis, personalized modeling, and image-guided cardiac therapies. Therefore, this project addresses the feasibility of mapping personalized cardiac fiber orientations to three-dimensional (3D) ultrasound image volumes. First, the geometry of the heart extracted from the MRI is translated to 3D ultrasound by rigid and deformable registration. Deformation fields between both geometries from MRI and ultrasound are obtained after registration. Three different deformable registration methods were utilized for the MRI-ultrasound registration. Finally, the cardiac fiber orientations imaged by DTI are mapped to ultrasound volumes based on the extracted deformation fields. Moreover, this study also demonstrated the ability to simulate electricity activations during the cardiac resynchronization therapy (CRT) process. The proposed method has been validated in two rat hearts and three canine hearts. After MRI/ultrasound image registration, the Dice similarity scores were more than 90% and the corresponding target errors were less than 0.25 mm. This proposed approach can provide cardiac fiber orientations to ultrasound images and can have a variety of potential applications in cardiac imaging.