Motion and temporal B0 shift corrections for quantitative susceptibility mapping (QSM) and R2* mapping using dual-echo spiral navigators and conjugate-phase reconstruction.

PURPOSE: To develop an efficient navigator-based motion and temporal B0 shift correction technique for 3D multi-echo gradient-echo (ME-GRE) MRI for quantitative susceptibility mapping (QSM) and R2* mapping. THEORY AND METHODS: A dual-echo 3D spiral navigator was designed to interleave with the Cartesian ME-GRE acquisitions, allowing the acquisition of both low- and high-echo time signals. We additionally designed a novel conjugate-phase based reconstruction method for the joint correction of motion and temporal B0 shifts. We performed both numerical simulation and in vivo human scans to assess the performance of the methods. RESULTS: Numerical simulation and human brain scans demonstrated that the proposed technique successfully corrected artifacts induced by both head motions and temporal B0 changes. Efficient B0-change correction with conjugate-phase reconstruction can be performed on less than 10 clustered k-space segments. In vivo scans showed that combining temporal B0 correction with motion correction further reduced artifacts and improved image quality in both R2* and QSM images. CONCLUSION: Our proposed approach of using 3D spiral navigators and a novel conjugate-phase reconstruction method can improve susceptibility-related measurements using MR.

Early Detection and Staging of Lung Fibrosis Enabled by Collagen-Targeted MRI Protein Contrast Agent.

Chronic lung diseases, such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD), are major leading causes of death worldwide and are generally associated with poor prognoses. The heterogeneous distribution of collagen, mainly type I collagen associated with excessive collagen deposition, plays a pivotal role in the progressive remodeling of the lung parenchyma to chronic exertional dyspnea for both IPF and COPD. To address the pressing need for noninvasive early diagnosis and drug treatment monitoring of pulmonary fibrosis, we report the development of human collagen-targeted protein MRI contrast agent (hProCA32.collagen) to specifically bind to collagen I overexpressed in multiple lung diseases. When compared to clinically approved Gd3+ contrast agents, hProCA32.collagen exhibits significantly better r1 and r2 relaxivity values, strong metal binding affinity and selectivity, and transmetalation resistance. Here, we report the robust detection of early and late-stage lung fibrosis with stage-dependent MRI signal-to-noise ratio (SNR) increase, with good sensitivity and specificity, using a progressive bleomycin-induced IPF mouse model. Spatial heterogeneous mapping of usual interstitial pneumonia (UIP) patterns with key features closely mimicking human IPF, including cystic clustering, honeycombing, and traction bronchiectasis, were noninvasively detected by multiple MR imaging techniques and verified by histological correlation. We further report the detection of fibrosis in the lung airway of an electronic cigarette-induced COPD mouse model, using hProCA32.collagen-enabled precision MRI (pMRI), and validated by histological analysis. The developed hProCA32.collagen is expected to have strong translational potential for the noninvasive detection and staging of lung diseases, and facilitating effective treatment to halt further chronic lung disease progression.

Quantitative Evaluation of Oxygen Extraction Fraction Changes in the Monkey Brain during Acute Stroke by Using Quantitative Susceptibility Mapping.

BACKGROUND: The oxygen extraction fraction (OEF) indicates the brain's oxygen consumption and can be estimated by using the quantitative susceptibility mapping (QSM) MRI technique. Recent studies have suggested that OEF alteration following stroke is associated with the viability of at-risk tissue. In the present study, the temporal evolution of OEF in the monkey brain during acute stroke was investigated using QSM. METHODS: Ischemic stroke was induced in adult rhesus monkeys (n = 8) with permanent middle cerebral artery occlusion (pMCAO) by using an interventional approach. Diffusion-, T2-, and T2*-weighted images were conducted on day 0, day 2, and day 4 post-stroke using a clinical 3T scanner. Progressive changes in magnetic susceptibility and OEF, along with their correlations with the transverse relaxation rates and diffusion indices, were examined. RESULTS: The magnetic susceptibility and OEF in injured gray matter of the brain significantly increased during the hyperacute phase, and then decreased significantly on day 2 and day 4. Moreover, the temporal changes of OEF in gray matter were moderately correlated with mean diffusivity (MD) (r = 0.52; p = 0.046) from day 0 to day 4. Magnetic susceptibility in white matter progressively increased (from negative values to near zero) during acute stroke, and significant increases were seen on day 2 (p = 0.08) and day 4 (p = 0.003) when white matter was significantly degenerated. However, significant reduction of OEF in white matter was not seen until day 4 post-stroke. CONCLUSION: The preliminary results demonstrate that QSM-derived OEF is a robust approach to examine the progressive changes of gray matter in the ischemic brain from the hyperacute phase to the subacute phase of stroke. The changes of OEF in gray matter were more prominent than those in white matter following stroke insult. The findings suggest that QSM-derived OEF may provide complementary information for understanding the neuropathology of the brain tissue following stroke and predicting stroke outcomes.

Non-invasive detection and complementary diagnosis of liver metastases via chemokine receptor 4 imaging.

Noninvasive detection of early-stage liver metastases from different primary cancers is a pressing unmet medical need. The lack of both molecular biomarkers and the sensitive imaging methodology makes the detection challenging. In this study, we observed the elevated expression of chemokine receptor 4 (CXCR4) in uveal melanoma (UM) patient liver tissues, and high CXCR4 expression in liver metastases of UM murine models, regardless of the expression levels in the primary tumors. Based on these findings, we identified CXCR4 as an imaging biomarker and exploited a CXCR4-targeted MRI contrast agent ProCA32.CXCR4 for molecular MRI imaging. ProCA32.CXCR4 has strong CXCR4 binding affinity, high metal selectivity, and r1 and r2 relaxivities, which enables the sensitive detection of liver micrometastases. The MRI imaging capacity for detecting liver metastases was demonstrated in three UM models and one ovarian cancer model. The imaging results were validated by histological and immunohistochemical analysis. ProCA32.CXCR4 has strong potential clinical application for non-invasive diagnosis of liver metastases.

Improving delineation of the corticospinal tract in the monkey brain scanned with conventional DTI by using a compressed sensing based algorithm.

Background: The corticospinal tract (CST) is a major tract for motor function. It can be impaired by stroke. Its degeneration is associated with stroke outcome. Diffusion tensor imaging (DTI) tractography plays an important role in assessing fiber bundle integrity. However, it is limited in detecting crossing fibers in the brain. The crossing fiber angular resolution of intra-voxel structure (CFARI) algorithm shows potential to resolve complex fibers in the brain. The objective of the present study was to improve delineation of CST pathways in monkey brains scanned by conventional DTI. Methods: Healthy rhesus monkeys were scanned by diffusion MRI with 128 diffusion encoding directions to evaluate the CFARI algorithm. Four monkeys with ischemic occlusion were also scanned with DTI (b = 1000 s/mm2, 30 diffusion directions) at 6, 48, and 96 hours post stroke. CST fibers were reconstructed with DTI and CFARI-based tractography and evaluated. A two-way repeated MANOVA was used to determine significances of changes in DTI indices, tract number, and volumes of the CST between hemispheres or post-stroke time points. Results: CFARI algorithm revealed substantially more fibers originated from the ventral premotor cortex in healthy and stroke monkey brains than DTI tractography. In addition, CFARI showed better sensitivity in detecting CST abnormality than DTI tractography following stroke. Conclusion: CFARI significantly improved delineation of the CST in the brain scanned by DTI with 30 gradient directions. It showed better sensitivity in detecting abnormity of the CST following stroke. Preliminary results suggest that CFARI could facilitate prediction of function outcomes after stroke.

Investigation of white matter and grey matter alteration in the monkey brain following ischemic stroke by using diffusion tensor imaging.

Background: Investigation of stroke lesion has mostly focused on grey matter (GM) in previous studies and white matter (WM) degeneration during acute stroke is understudied. In the present study, monkeys were utilized to investigate the alterations of GM and WM in the brain following ischemic occlusion using diffusion tensor imaging (DTI). Methods: Permanent middle cerebral artery occlusion (pMCAO) was induced in rhesus monkeys (n=6) with an interventional approach. Serial DTI was conducted on a clinical 3T in the hyperacute phase (2-6 hours), 48, and 96 hours post occlusion. Regions of interest in GM and WM of lesion areas were selected for data analysis. Results: Mean diffusivity (MD), radial diffusivity (RD), and axial Diffusivity (AD) in WM decreased substantially during hyperacute stroke, as similar as those seen in GM. No obvious fractional anasotropy (FA) changes were seen in GM and WM during hyper acute phase. until 48 hours post stroke when significant fiber losses were oberved also. Pseudo-normalization of MD, AD, and RD was seen at 96 hours. Pathological changes of WM and GM were observed in ischemic areas at 8, 48, and 96 hours post stroke. Relative changes of MD, AD and RD of WM were correlated negatively with infarction volumes at 6 hours post stroke. Conclusion: The present study revealed the microstructural changes in gray matter and white matter of monkey brains during acute stroke by using DTI. The preliminary results suggest axial and radial diffusivity (AD and RD) may be sensitive surrogate markers to assess specific microstructural changes in white matter during hyper-acute stroke.

Development of fast multi-slice apparent T1 mapping for improved arterial spin labeling MRI measurement of cerebral blood flow.

PURPOSE: To develop fast multi-slice apparent T1 (T1app ) mapping for accurate cerebral blood flow (CBF) quantification with arterial spin labeling (ASL) MRI. METHODS: Fast multi-slice T1app was measured using a modified inversion recovery echo planar imaging (EPI) sequence with simultaneous application of ASL tagging radiofrequency (RF) and gradient pulses. The fast multi-slice T1app measurement was compared with the single-slice T1app imaging approach, repeated per slice. CBF was assessed in healthy adult Wistar rats (N = 5) and rats with acute stroke 24 hours after a transient middle cerebral artery occlusion (N = 5). RESULTS: The fast multi-slice T1app measurement was in good agreement with that of a single-slice T1app imaging approach (Lin's concordance correlation coefficient = 0.92). CBF calculated using T1app reasonably accounted for the finite labeling RF duration, whereas the routine T1 -normalized ASL MRI underestimated the CBF, particularly at short labeling durations. In acute stroke rats, the labeling time and the CBF difference (ΔCBF) between the contralateral normal area and the ischemic lesion were significantly correlated when using T1 -normalized perfusion calculation (R = 0.844, P = .035). In comparison, T1app -normalized ΔCBF had little labeling time dependence based on the linear regression equation of ΔCBF = -0.0247*τ + 1.579 mL/g/min (R = -0.352, P = .494). CONCLUSIONS: Our study found fast multi-slice T1app imaging improves the accuracy and reproducibility of CBF measurement.

Chemokine receptor 4 targeted protein MRI contrast agent for early detection of liver metastases.

Liver metastases often progress from primary cancers including uveal melanoma (UM), breast, and colon cancer. Molecular biomarker imaging is a new non-invasive approach for detecting early stage tumors. Here, we report the elevated expression of chemokine receptor 4 (CXCR4) in liver metastases in UM patients and metastatic UM mouse models, and development of a CXCR4-targeted MRI contrast agent, ProCA32.CXCR4, for sensitive MRI detection of UM liver metastases. ProCA32.CXCR4 exhibits high relaxivities (r 1 = 30.9 mM-1 s-1, r 2 = 43.2 mM-1 s-1, 1.5 T; r 1 = 23.5 mM-1 s-1, r 2 = 98.6 mM-1 s-1, 7.0 T), strong CXCR4 binding (K d = 1.10 ± 0.18 µM), CXCR4 molecular imaging capability in metastatic and intrahepatic xenotransplantation UM mouse models. ProCA32.CXCR4 enables detecting UM liver metastases as small as 0.1 mm3. Further development of the CXCR4-targeted imaging agent should have strong translation potential for early detection, surveillance, and treatment stratification of liver metastases patients.

Improved MR fingerprinting for relaxation measurement in the presence of semisolid magnetization transfer.

PURPOSE: To characterize and minimize the magnetization transfer (MT) effect in MR fingerprinting (MRF) relaxation measurements with a 2-pool (2P) MT model of multiple tissue types. THEORY AND METHODS: Semisolid MT effect in MRF was modeled using 2P Bloch-McConnell equations. The combinations of MT parameters of multiple tissues (white [WM] and gray matter [GM]) were used to build the MRF dictionary. Both 1-pool (1P) and 2P models were simulated to characterize the dependence on MT. Relaxations measured using MRF with spin-echo saturation-recovery (SR) or inversion-recovery preparations were compared with conventional SR-prepared T1 and multiple spin-echo T2 measurements. The simulations results were validated with phantoms and brain tissue samples. RESULTS: The MRF signal was different from the 1P and 2P models. 1P MRF produced significantly (P < .05) underestimated T1 in WM (20-30%) and GM (7-10%), while 2P MRF measured consistent T1 and T2 in both WM and GM with conventional measurements (pairwise test P > .1; correlated P < .05). Simulations showed that SR-prepared MRF measuring T1 had much less errors against the variation of the macromolecular fraction. Compared with inversion-recovery preparation, SR-prepared MRF produced higher relaxation correlations (R > 0.9) with conventional measurements in both WM and GM across samples, suggesting that SR-prepared MRF was less sensitive to the compositive effect of multiple MT parameters variations. CONCLUSIONS: 2P MRF using a combination of MT parameters for multiple tissue types can measure consistent relaxations with conventional methods. With the 2P models, SR-prepared MRF would provide an option for robust relaxation measurement under heterogeneous MT.

Diffusion tensor imaging reveals microstructural alterations in corpus callosum and associated transcallosal fiber tracts in adult macaques with neonatal hippocampal lesions.

To investigate the effects of neonatal hippocampal lesions on the microstructural integrity of the corpus callosum (CC) in adulthood, macaque monkeys (n = 5) with neonatal bilateral neurotoxic hippocampal lesion (Neo-Hibo) and sham-operated controls (Neo-C, n = 5) were scanned using magnetic resonance diffusion tensor imaging (DTI) technique at 8-10 years old. CC was segmented into seven regionsgrouped into anterior CC (rostrum, genu, rostral body and anterior midbody) and posterior CC (posterior midbody, isthmus and splenium) for data analysis. Associated transcallosal fiber tracts were delineated using probabilistic tractography and evaluated with tract-based spatial statistics (TBSS). Neo-Hibo lesions resulted in significant increased diffusivity indices (mean, axial and radial diffusivity) in CC posterior segments. Also, significant decreased fractional anisotropy (FA) and increased diffusivity indices were seen in the associated transcallosal fiber tracts proximal to motor, posterior parietal and retrosplenial cortices. In Neo-Hibo animals, increased mean diffusivity (MD) in posterior midbody negatively correlated with reduction of CC surface areaand the magnitude of their memory impairments was significantly correlated with FA in transcallosal fiber tracts across splenium. Although no microstructural changes were observed in CC anterior segments, changes in FA values and diffusivity indices were observed in the white matter fibers of the ventromedial prefrontal cortex. Thus, Neo-H lesions resulted in enduring degradation in transcallosal fibers proximal to parietal and retrosplenial cortices, and hemispheric connections through posterior CC. The findings may provide complementary information for understanding the neural substrate of behavioral and cognitive deficits observed in patients with early insult to the hippocampus.

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.

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.

Developmental Whole Brain White Matter Alterations in Transgenic Huntington's Disease Monkey.

Transgenic Huntington's disease monkey (HD monkey) model provides great opportunity for studying disease progression that could lead to new insight for developing biomarker, early intervention and novel therapeutics. Whole brain white matter integrity of HD-monkeys was examined longitudinally from 6 to 48 months using diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS). Progressive developmental white matter alterations in HD monkeys were widespread and were observed not only in fiber bundles connecting cortical areas to the striatum (e.g. striatal bundle and external capsule), but also in long association fiber pathways, commissural fibers, and subcortical fiber bundle. In all fiber tracts, the data indicate an arrest in white matter development around 23 months followed by slight decline until adulthood in HD monkeys. The microstructural changes parallel the progressive motor, memory and cognitive decline previously reported as HD monkeys aged. The findings revealed the widespread progressive temporal-spatial microstructural changes in HD monkey brains from infancy to adulthood, suggesting differentiated degenerations across different brain areas during brain development.

Estimating cardiac fiber orientations in pig hearts using registered ultrasound and MR image volumes.

Heart fiber mechanics can be important predictors in current and future cardiac function. Accurate knowledge of these mechanics could enable cardiologists to provide a diagnosis before conditions progress. Magnetic resonance diffusion tensor imaging (MR-DTI) has been used to determine cardiac fiber orientations. Ultrasound is capable of providing anatomical information in real time, enabling a physician to quickly adjust parameters to optimize image scans. If known fiber orientations from a template heart measured using DTI can be accurately deformed onto a cardiac ultrasound volume, fiber orientations could be estimated for the patient without the need for a costly MR scan while still providing cardiologists valuable information about the heart mechanics. In this study, we apply the method to pig hearts, which are a close representation of human heart anatomy. Experiments from pig hearts show that the registration method achieved an average Dice similarity coefficient (DSC) of 0.819 ± 0.050 between the ultrasound and deformed MR volumes and that the proposed ultrasound-based method is able to estimate the cardiac fiber orientation in pig hearts.

Decreased functional connectivity in dorsolateral prefrontal cortical networks in adult macaques with neonatal hippocampal lesions: Relations to visual working memory deficits.

Neonatal hippocampal lesions in monkeys impairs normal performance on both relational and working memory tasks, suggesting that the early lesions have impacted the normal development of prefrontal-hippocampal functional interactions necessary for normal performance on these tasks. Given that working memory processes engage distributed neuronal networks associated with the prefrontal cortex, it is critical to explore the integrity of distributed neural networks of dorsolateral prefrontal cortex (dlPFC) following neonatal hippocampal lesions in monkeys. We used resting-state functional MRI to assess functional connectivity of dlPFC networks in monkeys with neonatal neurotoxic hippocampal lesion (Neo-Hibo, n=4) and sham-operated control animals (Neo-C, n=4). Significant differences in the patterns of dlPFC functional networks were found between Groups Neo-Hibo and Neo-C. The within-group maps and the between-group comparisons yielded a highly coherent picture showing altered interactions of core regions of the working memory network (medial prefrontal cortex and posterior parietal cortex) as well as the dorsal (fundus of superior temporal area and superior temporal cortex) and ventral (V4 and infero-temporal cortex) visual processing areas in animals with Neo-Hibo lesions. Correlations between functional connectivity changes and working memory impairment in the same animals were found only between the dlPFC and visual cortical areas (V4 and infero-temporal cortex). Thus, the impact of the neonatal hippocampal lesions extends to multiple cortical areas interconnected with the dlPFC.

Transcallosal connectivity changes from infancy to late adulthood: an ex vivo diffusion spectrum imaging study of macaque brains.

Interhemispheric communication plays a critical role to ensure normal brain functions in cognition and behavior. Since non-human primate (NHP) brains resemble most aspects of the human brain, a thorough knowledge of interhemispheric cortical connectivity changes in NHP brains throughout the developmental and aging periods may provide valuable insights for translational and clinical research. In this study, formalin-fixed rhesus monkey brains aged from 1 to 24 years were utilized to examine transcallosal connectivity changes using diffusion spectrum imaging (DSI). It was found that the transcallosal connectivity for most frontal cortical areas, including dorso- and ventro-lateral prefrontal, premotor, and motor cortices, demonstrated pronounced age-related alterations. However, such a pattern was less obvious in temporal, posterior parietal, and visual cortices. The DSI results reveal the age-related evolution pattern of transcallosal connectivity in various cortical areas of macaque brains from infancy to late adulthood, and may have implications for assessing the functional defects or alterations in the associated cortical areas during brain development and aging in humans.

Alterations of hippocampal projections in adult macaques with neonatal hippocampal lesions: a Diffusion Tensor Imaging study.

Neuropsychological and brain imaging studies have demonstrated persistent deficits in memory functions and structural changes after neonatal neurotoxic hippocampal lesion in monkeys. However, the relevant microstructural changes in the white matter of affected brain regions following this early insult remain unknown. This study assessed white matter integrity in the main hippocampal projections of adult macaque monkeys with neonatal hippocampal lesions, using diffusion tensor imaging (DTI). Data analysis was performed using tract-based spatial statistics (TBSS) and compared with volume of interest statistics. Alterations of fractional anisotropy (FA) and diffusivity indices were observed in fornix, temporal stem, ventromedial prefrontal cortex and optical radiations. To further validate the lesion effects on the prefrontal cortex, probabilistic diffusion tractography was used to examine the integrity of the fiber connections between hippocampus and ventromedial prefrontal cortex, and alterations were found in these connections. In addition, increased radial diffusivity in the left ventromedial prefrontal cortex correlated negatively with the severity of deficits in working memory in the same monkeys. The findings revealed microstructural changes due to neonatal hippocampal lesion, and confirmed that neonatal neurotoxic hippocampal lesions resulted in significant and enduring functional alterations in the hippocampal projection system.

In vivo diffusion spectrum imaging of non-human primate brain: initial experience in transcallosal fiber examination.

In comparison with conventional diffusion tensor imaging (DTI) technique, diffusion spectrum imaging (DSI) allows for delineating crossing and touching fibers in the brain and has been explored in clinical and preclinical studies. Non-human primates (NHPs) resemble most aspects of human and are widely employed in various neuroscience researches and pharmaceutical development. In the present study, a parallel imaging-based DSI protocol was implemented for in vivo fiber tracking of macaque monkey brains on a 3.0 T clinical scanner. Transcallosal fiber tracts of adult macaque brains were examined with DSI and compared with those from a a conventional DTI protocol. The results demonstrate that DSI can reveal the transcallosal fiber bundles much more extensively than the conventional DTI. The preliminary results suggest that DSI may provide a feasible and robust approach for characterizing the fiber pathways in various disease models of NHPs.

Acute toxicity of zinc oxide nanoparticles to the rat olfactory system after intranasal instillation.

With the increased applications of zinc oxide (ZnO) nanoparticles (NPs), the toxicity of ZnO NPs arouses great concerns from the nano community and the general public. In this study, we report the toxicity of ZnO NPs (30 nm) to the rat olfactory system after intranasal instillation revealed by non-invasive magnetic resonance imaging (MRI). MRI scans were performed on a 4.7-T scanner at 1, 2, 3 and 7 days post-exposure, and the histological changes of the rat olfactory epithelium were evaluated. The influences of chemical component and dispersant of the NPs were also investigated. In addition, an olfactory behavior test was performed. The MRI and histological results indicated that ZnO NPs induced significant damages to the olfactory epithelium, including disruption of the olfactory epithelial structures and inflammation. The destruction of mitochondria in epithelial cells was observed under transmission electron microscopy (TEM), suggesting that the possible toxicological mechanism might involve cellular energy metabolic dysfunction. Further, the lesion of the olfactory epithelium disturbed sniffing behaviors of the treated animals. The results suggest that MRI is potentially useful as a screening tool to assess the consequence of occupational exposure of ZnO NPs. Caution should therefore be taken during the use and disposal of ZnO NPs to prevent the unintended public health impacts.

Simultaneous measurement of cerebral blood flow and transit time with turbo dynamic arterial spin labeling (Turbo-DASL): application to functional studies.

A turbo dynamic arterial spin labeling method (Turbo-DASL) was developed to simultaneously measure cerebral blood flow (CBF) and blood transit time with high temporal resolution. With Turbo-DASL, images were repeatedly acquired with a spiral readout after small-angle excitations during pseudocontinuous arterial spin labeling and control periods. Turbo-DASL experiments at 9.4 T without and with diffusion gradients were performed on rats anesthetized with isoflurane or α-chloralose. We determined blood transit times from carotid arteries to cortical arterial vessels (TT(a) ) from data obtained without diffusion gradients and to capillaries (TT(c) ) from data obtained with diffusion gradients. Cerebral arterial blood volume (CBV(a) ) was also calculated. At the baseline condition, both CBF and CBV(a) in the somatosensory cortical area were 40-50% less in rats with α-chloralose than in rats with isoflurane, while TT(a) and TT(c) were similar for both anesthetics. Absolute CBF and CBV(a) were positively correlated, while CBF and TT(c) were slightly negatively correlated. During forepaw stimulation, CBF increase was 15 ± 3% (n = 7) vs. 60 ± 7% (n = 5), and CBV(a) increase was 19 ± 9% vs. 46 ± 17% under isoflurane vs. α-chloralose anesthesia, respectively; CBF vs. CBV(a) changes were highly correlated. However, TT(a) and TT(c) were not significantly changed during stimulation. Our results support that arterial CBV increase plays a major role in functional CBF changes.