Sj Fan

Liver fibrosis: an intravoxel incoherent motion (IVIM) study.

To characterize longitudinal changes in molecular water diffusion, blood microcirculation, and their contributions to the apparent diffusion changes using intravoxel incoherent motion (IVIM) analysis in an experimental mouse model of liver fibrosis.

Diffusion tensor imaging of renal ischemia reperfusion injury in an experimental model

Renal ischemia reperfusion injury (IRI) is a major cause of acute renal failure. It occurs in various clinical settings such as renal transplantation, shock and vascular surgery. Serum creatinine level has been used as an index for estimating the degree of renal functional loss in renal IRI. However, it only evaluates the global renal function. In this study, diffusion tensor imaging (DTI) was used to characterize renal IRI in an experimental rat model. Spin‐echo echo‐planar DTI with b‐value of 300u2009s/mm2 and 6 diffusion gradient directions was performed at 7u2009T in 8 Sprague‐Dawley (SD) with 60‐min unilateral renal IRI and 8 normal SD rats. Apparent diffusion coefficient (ADC), directional diffusivities and fractional anisotropy (FA) were measured at the acute stage of IRI. The IR‐injured animals were also examined by diffusion‐weighted imaging with 7 b‐values up to 1000u2009s/mm2 to estimate true diffusion coefficient (Dtrue) and perfusion fraction (Pfraction) using a bi‐compartmental model. ADC of injured renal cortex (1.69u2009±u20090.24u2009×u200910−3u2009mm2/s) was significantly lower (pu2009<u20090.01) than that of contralateral intact cortex (2.03u2009±u20090.35u2009×u200910−3u2009mm2/s). Meanwhile, both ADC and FA of IR‐injured medulla (1.37u2009±u20090.27u2009×u200910−3u2009mm2/s and 0.28u2009±u20090.04, respectively) were significantly less (pu2009<u20090.01) than those of contralateral intact medulla (2.01u2009±u20090.38u2009×u200910−3u2009mm2/s and 0.36u2009±u20090.04, respectively). The bi‐compartmental model analysis revealed the decrease in Dtrue and Pfraction in the IR‐injured kidneys. Kidney histology showed widespread cell swelling and erythrocyte congestion in both cortex and medulla, and cell necrosis/apoptosis and cast formation in medulla. These experimental findings demonstrated that DTI can probe both structural and functional information of kidneys following renal IRI. Copyright

Diffusion tensor imaging of liver fibrosis in an experimental model.

To characterize changes in diffusion properties of liver using diffusion tensor imaging (DTI) in an experimental model of liver fibrosis.

In vivo DTI assessment of hepatic ischemia reperfusion injury in an experimental rat model

To investigate hepatic ischemia reperfusion injury (IRI) using diffusion tensor imaging (DTI).

Measurement of liver T1 and T2 relaxation times in an experimental mouse model of liver fibrosis

To characterize changes in relaxation times of liver using quantitative magnetic resonance imaging (MRI) in an experimental mouse model of liver fibrosis. Quantitative MRI is a potentially robust method to characterize liver fibrosis. However, correlation between relaxation times and fibrosis stage has been controversial.

Metabolic changes in visual cortex of neonatal monocular enucleated rat: a proton magnetic resonance spectroscopy study.

Neonatal monocular enucleation (ME) is often employed to study the developmental mechanisms underlying visual perception and the cross‐modal changes in the central nervous system caused by early loss of the visual input. However, underlying biochemical or metabolic mechanisms that accompany the morphological, physiological and behavioral changes after ME are not fully understood. Male Sprague‐Dawley rats (N = 14) were prepared and divided into 2 groups. The enucleated group (N = 8) underwent right ME (right eye removal) at postnatal day 10, while the normal group (N = 6) was intact and served as a control. Three weeks after ME, single voxel proton magnetic resonance spectroscopy (1H MRS) was performed over the visual cortex of each hemisphere in all animals with a point‐resolved spectroscopy (PRESS) sequence at 7 T. The taurine (Tau) and N‐acetylaspartate (NAA) levels were found to be significantly lower in the left visual cortex (contralateral to enucleated eye) for enucleated animals. Such metabolic changes measured in vivo likely reflected the cortical degeneration associated with the reduction of neurons, axon terminals and overall neuronal activity. This study also demonstrated that 1H MRS approach has the potential to characterize neonatal ME and other developmental neuroplasticity models noninvasively for the biochemical and metabolic processes involved.

Long-Term Effects of Neonatal Hypoxia-Ischemia on Structural and Physiological Integrity of the Eye and Visual Pathway by Multimodal MRI

PURPOSEnNeonatal hypoxia-ischemia is a major cause of brain damage in infants and may frequently present visual impairments. Although advancements in perinatal care have increased survival, the pathogenesis of hypoxic-ischemic injury and the long-term consequences to the visual system remain unclear. We hypothesized that neonatal hypoxia-ischemia can lead to chronic, MRI-detectable structural and physiological alterations in both the eye and the brains visual pathways.nnnMETHODSnEight Sprague-Dawley rats underwent ligation of the left common carotid artery followed by hypoxia for 2 hours at postnatal day 7. One year later, T2-weighted MRI, gadolinium-enhanced MRI, chromium-enhanced MRI, manganese-enhanced MRI, and diffusion tensor MRI (DTI) of the visual system were evaluated and compared between opposite hemispheres using a 7-Tesla scanner.nnnRESULTSnWithin the eyeball, systemic gadolinium administration revealed aqueous-vitreous or blood-ocular barrier leakage only in the ipsilesional left eye despite comparable aqueous humor dynamics in the anterior chamber of both eyes. Binocular intravitreal chromium injection showed compromised retinal integrity in the ipsilesional eye. Despite total loss of the ipsilesional visual cortex, both retinocollicular and retinogeniculate pathways projected from the contralesional eye toward ipsilesional visual cortex possessed stronger anterograde manganese transport and less disrupted structural integrity in DTI compared with the opposite hemispheres.nnnCONCLUSIONSnHigh-field, multimodal MRI demonstrated in vivo the long-term structural and physiological deficits in the eye and brains visual pathways after unilateral neonatal hypoxic-ischemic injury. The remaining retinocollicular and retinogeniculate pathways appeared to be more vulnerable to anterograde degeneration from eye injury than retrograde, transsynaptic degeneration from visual cortex injury.

In Vivo Lipid Profiling Using Proton Magnetic Resonance Spectroscopy in an Experimental Liver Fibrosis Model

RATIONALE AND OBJECTIVESnThe aim of this study was to characterize early hepatic lipid changes in an experimental model of liver fibrosis using proton ((1)H) magnetic resonance spectroscopy (MRS) at high magnetic field in vivo.nnnMATERIALS AND METHODSnLiver fibrosis was induced in 12 Sprague-Dawley rats by twice-weekly carbon tetrachloride (CCl(4)) administration up to 4 weeks. Eight normal rats were used as controls. Single-voxel (1)H MRS experiments were performed at 7 Tesla to measure signal integrals of various lipid peaks including -CH(3), (-CH(2)-)(n), -CH(2)-C=C-CH(2)-, =C-CH(2)-C= and -CH=CH- at 0.9, 1.3, 2.0, 2.8, and 5.3 ppm, respectively, and peak from choline-containing compounds (CCC) at 3.2 ppm. Total lipid, total saturated fatty acid, total unsaturated fatty acid, total unsaturated bond, polyunsaturated bond, and CCC indices were quantified.nnnRESULTSnSignificant increases (P < .01) in total lipid and total saturated fatty acid indices were found in animals with CCl(4)-induced fibrosis as compared with normal animals. In addition, total unsaturated bond and polyunsaturated bond indices of animals at 4 weeks after CCl(4) insult were significantly higher than (P < .01 and P < .05, respectively) those of normal animals and animals at 2 weeks following insult; whereas there was only significant increase (P < .01) in total unsaturated fatty acid index in animals with 4-week CCl(4) insult as compared with normal animals.nnnCONCLUSIONnThe hepatic lipid changes in CCl(4)-induced experimental fibrosis model were documented in vivo and longitudinally using (1)Hxa0MRSxa0at 7 Tesla. The experimental findings suggested that total saturated fatty acid increase contributed mainly to the total lipid increase in animals with CCl(4) insult. This study also demonstrated the potential value of high field MRS to resolve lipid composition and alterations in liver fibrosis.

Molecular MRI of liver fibrosis by a peptide-targeted contrast agent in an experimental mouse model.

ObjectivesCyclic decapeptide CGLIIQKNEC (CLT1) has been demonstrated to target fibronectin-fibrin complexes in the extracellular matrix of different tumors and tissue lesions. Although liver fibrosis is characterized by an increased amount of extracellular matrix consisting of fibril-forming collagens and matrix glycoconjugates such as fibronectin, we aimed to investigate the feasibility of detecting and characterizing liver fibrosis using CLT1 peptide-targeted nanoglobular contrast agent (Gd-P) with dynamic contrast-enhanced magnetic resonance imaging in an experimental mouse model of liver fibrosis at 7 T. Materials and MethodsGd-P, control peptide KAREC conjugated nanoglobular contrast agent (Gd-CP), and control nontargeting nanoglobular contrast agent (Gd-C) were synthesized. Male adult C57BL/6N mice (22–25 g; N = 54) were prepared and were divided into fibrosis (n = 36) and normal (n = 18) groups. Liver fibrosis was induced in the fibrosis group through subcutaneous injection of 1:3 mixture of carbon tetrachloride (CCl4) in olive oil at a dose of 4 &mgr;L/g of body weight twice a week for 8 weeks. Dynamic contrast-enhanced MRI was performed in all animals. Dynamic contrast-enhanced magnetic resonance imaging was analyzed to yield postinjection &Dgr;R1(t) maps for quantitative measurements. Histological analysis was also performed. ResultsDifferential enhancements were observed and characterized between the normal and fibrotic livers using Gd-P at 0.03 mmol/kg, when compared with nontargeted controls (Gd-CP and Gd-C). For Gd-P injection, both the peak and steady-state &Dgr;R1 of the normal livers were significantly lower than those after 4 and 8 weeks of CCl4 dosing. Liver fibrogenesis with increased amount of fibronectin in the extracellular space in insulted livers were confirmed by histological observations. ConclusionsThese results indicated that dynamic contrast-enhanced magnetic resonance imaging with CLT1 peptide-targeted nanoglobular contrast agent can detect and stage liver fibrosis by probing the accumulation of fibronectin in fibrotic livers.

Auditory midbrain processing is differentially modulated by auditory and visual cortices: An auditory fMRI study.

The cortex contains extensive descending projections, yet the impact of cortical input on brainstem processing remains poorly understood. In the central auditory system, the auditory cortex contains direct and indirect pathways (via brainstem cholinergic cells) to nuclei of the auditory midbrain, called the inferior colliculus (IC). While these projections modulate auditory processing throughout the IC, single neuron recordings have samples from only a small fraction of cells during stimulation of the corticofugal pathway. Furthermore, assessments of cortical feedback have not been extended to sensory modalities other than audition. To address these issues, we devised blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) paradigms to measure the sound-evoked responses throughout the rat IC and investigated the effects of bilateral ablation of either auditory or visual cortices. Auditory cortex ablation increased the gain of IC responses to noise stimuli (primarily in the central nucleus of the IC) and decreased response selectivity to forward species-specific vocalizations (versus temporally reversed ones, most prominently in the external cortex of the IC). In contrast, visual cortex ablation decreased the gain and induced a much smaller effect on response selectivity. The results suggest that auditory cortical projections normally exert a large-scale and net suppressive influence on specific IC subnuclei, while visual cortical projections provide a facilitatory influence. Meanwhile, auditory cortical projections enhance the midbrain response selectivity to species-specific vocalizations. We also probed the role of the indirect cholinergic projections in the auditory system in the descending modulation process by pharmacologically blocking muscarinic cholinergic receptors. This manipulation did not affect the gain of IC responses but significantly reduced the response selectivity to vocalizations. The results imply that auditory cortical gain modulation is mediated primarily through direct projections and they point to future investigations of the differential roles of the direct and indirect projections in corticofugal modulation. In summary, our imaging findings demonstrate the large-scale descending influences, from both the auditory and visual cortices, on sound processing in different IC subdivisions. They can guide future studies on the coordinated activity across multiple regions of the auditory network, and its dysfunctions.