April M. Chow

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 300 s/mm2 and 6 diffusion gradient directions was performed at 7 T 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 1000 s/mm2 to estimate true diffusion coefficient (Dtrue) and perfusion fraction (Pfraction) using a bi‐compartmental model. ADC of injured renal cortex (1.69 ± 0.24 × 10−3 mm2/s) was significantly lower (p < 0.01) than that of contralateral intact cortex (2.03 ± 0.35 × 10−3 mm2/s). Meanwhile, both ADC and FA of IR‐injured medulla (1.37 ± 0.27 × 10−3 mm2/s and 0.28 ± 0.04, respectively) were significantly less (p < 0.01) than those of contralateral intact medulla (2.01 ± 0.38 × 10−3 mm2/s and 0.36 ± 0.04, 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).

Enhancement of gas-filled microbubble R2* by iron oxide nanoparticles for MRI.

Gas‐filled microbubbles have the potential to become a unique intravascular MR contrast agent due to their magnetic susceptibility effect, biocompatibility, and localized manipulation via ultrasound cavitation. However, microbubble susceptibility effect is relatively weak when compared with other intravascular MR susceptibility contrast agents. In this study, enhancement of microbubble susceptibility effect by entrapping monocrystalline iron oxide nanoparticles (MIONs) into polymeric microbubbles was investigated at 7 T in vitro. Apparent T2 enhancement (ΔR2*) induced by microbubbles was measured to be 79.2 ± 17.5 sec−1 and 301.2 ± 16.8 sec−1 for MION‐free and MION‐entrapped polymeric microbubbles at 5% volume fraction, respectively. ΔR2* and apparent transverse relaxivities (r2*) for MION‐entrapped polymeric microbubbles and MION‐entrapped solid microspheres (without gas core) were also compared, showing the synergistic effect of the gas core with MIONs. This is the first experimental demonstration of microbubble susceptibility enhancement for MRI application. This study indicates that gas‐filled polymeric microbubble susceptibility effect can be substantially increased by incorporating iron oxide nanoparticles into microbubble shells. With such an approach, microbubbles can potentially be visualized with higher sensitivity and lower concentrations by MRI. Magn Reson Med, 2010.

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.

Microbubbles as a novel contrast agent for brain MRI

Gas-filled microbubbles have the potential to become a unique MR contrast agent due to their magnetic susceptibility effect, biocompatibility and localized manipulation via ultrasound cavitation. In this study, two types of microbubbles, custom-made albumin-coated microbubbles (A-MB) and a commercially available lipid-based clinical ultrasound contrast agent (SonoVue), were investigated with in vivo dynamic brain MRI in Sprague-Dawley rats at 7 T. Microbubble suspensions (A-MB: 0.2 mL of approximately 4% volume fraction; SonoVue: 0.2 mL of approximately 3.5% volume fraction) were injected intravenously. Transverse relaxation rate enhancements (DeltaR(2)(*)) of 2.49+/-1.00 s(-1) for A-MB and 2.41+/-1.18 s(-1) for SonoVue were observed in the brain (N=5). Brain DeltaR(2)(*) maps were computed, yielding results similar to the cerebral blood volume maps obtained with a common MR blood pool contrast agent. Microbubble suspension DeltaR(2)(*) was measured for different volume fractions. These results indicate that gas-filled microbubbles can serve as an intravascular contrast agent for brain MRI at high field. Such capability has the potential to lead to real-time MRI guidance in various microbubble-based drug delivery and therapeutic applications in the central nervous system.

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.

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.

Magnetic resonance spectroscopy of the brain under mild hypothermia indicates changes in neuroprotection-related metabolites

Brain hypothermia has demonstrated pronounced neuroprotective effect in patients with cardiac arrest, ischemia and acute liver failure. However, its underlying neuroprotective mechanisms remain to be elucidated in order to improve therapeutic outcomes. Single voxel proton magnetic resonance spectroscopy ((1)H-MRS) was performed using a 7 Tesla MRI scanner on normal Sprague-Dawley rats (N=8) in the same voxel under normothermia (36.5 degrees C) and 30min mild hypothermia (33.5 degrees C). Levels of various brain proton metabolites were compared. The level of lactate (Lac) and myo-inositol (mI) increased in the cortex during hypothermia. In the thalamus, taurine (Tau), a cryogen in brain, increased and choline (Cho) decreased. These metabolic alterations indicated the onset of a number of neuroprotective processes that include attenuation of energy metabolism, excitotoxic pathways, brain osmolytes and thermoregulation, thus protecting neuronal cells from damage. These experimental findings demonstrated that (1)H-MRS can be applied to investigate the changes of specific metabolites and corresponding neuroprotection mechanisms in vivo noninvasively, and ultimately improve our basic understanding of hypothermia and ability to optimize its therapeutic efficacy.