Cell layers and neuropil: contrast‐enhanced MRI of mouse brain in vivo

Contrast‐enhanced T₁‐ and T₂‐weighted MRI at 9.4 T and in‐plane resolutions of 25 and 30 µm has been demonstrated to differentiate between neural tissues in mouse brain in vivo, including granule cell layers, principal cell layers, general neuropil, specialized neuropil and white matter. In T₁‐weighted MRI of the olfactory bulb, hippocampus and cerebellum, contrast obtained by the intracranial administration of gadopentetate dimeglumine (Gd‐DTPA) reflects the extra‐ and intracellular spaces of gray matter in agreement with histological data. General neuropil areas are highlighted, whereas other tissues present with lower signal intensities. The induced contrast is similar to that in plain T₂‐weighted MRI, but offers a 16–30‐fold higher contrast‐to‐noise ratio. Systemic administration of manganese chloride increases the signal‐to‐noise ratio in T₁‐weighted MRI to a significantly greater extent in principal cell layers and specialized neuropil than in granule cell layers, whereas gadolinium‐enhanced MRI indicates no larger intracellular spaces in these tissues. Granule cell layers are enhanced no more than general neuropil by manganese, whereas gadolinium‐enhanced MRI indicates significantly larger intracellular spaces in the cell layers. These discrepancies suggest that the signal increase after manganese administration reflects cellular activity which is disproportionate to the intracellular space. As a result, principal cell layers and specialized neuropil become highlighted, whereas granule cell layers, general neuropil and white matter present with lower signal intensities. Copyright © 2013 John Wiley & Sons, Ltd.     

Manganese threonine chelate—a new enteric contrast agent for MRI: a pilot study on rats

Enteric contrast agents are important in gastrointestinal MRI. However, no currently available agent is well established as the standard of care. In this study, in vitro relaxivities of manganese threonine chelate (Mn‐Thr), a common nutritional food supplement, were measured at 1.5 T and 3 T with further investigation of its efficacy and safety in vivo as an enteric contrast agent. According to the calculated relaxivities, T₁W and T₂W TSE sequences of Mn‐Thr solutions at different concentrations were acquired, and the optimal concentration for dark lumen imaging on both T₁W and T₂W images was determined in vitro. To validate the optimal concentration in vivo, eight Sprague‐Dawley rats were randomly divided into two groups. Each group received rectal injection of either 2.00 g/L (about 3.80 mM) Mn‐Thr or saline as an enteric contrast agent and underwent MRI. After a time interval of one week, the same procedures were repeated with the alternative contrast agent. Animals were sacrificed after the second MRI. Tissue manganese quantification and histopathological examination were obtained. Qualitative MR image quality assessments were performed and compared between Mn‐Thr and saline. Measured T₁ and T₂ relaxivities of Mn‐Thr were significantly higher than those of MnCl₂ in vitro (p < 0.05). At the concentration of 2.00 g/L (about 3.80 mM), Mn‐Thr produced a dark lumen on T₁W and T₂W images both in vitro and in vivo. Compared with saline, Mn‐Thr showed significantly more homogenous luminal signal and increased bowel wall conspicuity in image quality assessments. Tissue manganese concentrations were not significantly different between two groups. Histopathological examinations were normal in both groups. Our data suggest that Mn‐Thr possesses favorable paramagnetic properties and can create a homogenous dark lumen on T₁W and T₂W images without obvious side effects in healthy rats. As a commercially available nutritional food supplement, Mn‐Thr appears to be a promising enteric contrast agent for MRI.     

Manganese‐enhanced MRI visualizes V1 in the non‐human primate visual cortex

MRI at 7 Tesla has been used to investigate the accumulation of manganese in the occipital cortex of common marmoset monkeys (Callithrix jacchus) after administering four fractionated injections of 30 mg/kg MnCl₂ · 4H₂O in the tail vein. We found a statistically significant decrease in T₁ in the primary (V1) and secondary (V2) areas of the visual cortex caused by an accumulation of manganese. The larger T₁ shortening in V1 (ΔT₁ = 640 ms) relative to V2 (ΔT₁ = 490 ms) allowed us to robustly detect the V1/V2 border in vivo using heavily T₁‐weighted MRI. Furthermore, the dorso‐medial (DM) and middle‐temporal (MT) areas of the visual pathway could be identified by their T₁‐weighted enhancement. We showed by comparison to histological sections stained for cytochrome oxidase (CO) activity that the extent of V1 is accurately identified throughout the visual cortex by manganese‐enhanced MRI (MEMRI). This provides a means of visualizing functional cortical regions in vivo and could be used in longitudinal studies of phenomena such as cortical plasticity, and for non‐destructive localization of cortical regions to guide in the implementation of functional techniques. Published in 2009 by John Wiley & Sons, Ltd.     

Rapid simultaneous acquisition of T1 and T2 mapping images using multishot double spin‐echo EPI and automated variations of TR and TE (ms‐DSEPI‐T12)

A rapid method of simultaneous T₁ and T₂ measurement is presented which uses a segmented echo‐planar readout with varying repetition times (TR) and echo times (TE). This method is useful in T₁ mapping for analysis of dynamic contrast enhanced MRI (DCE‐MRI), where T₁ can be used to estimate contrast agent concentration. In the application of this method to dynamic imaging, the equilibrium magnetization is measured on pre‐contrast images and incorporated into post‐contrast T₁ calculations for improved accuracy. Simultaneous T₂ measurement allows correction of T₂ effects in the T₁ map which may occur at high contrast agent concentrations, and is performed without significant imaging time penalty. Phantom and in vivo results show the usefulness of this technique for analysis of contrast enhancement kinetics. Accurate rapid contrast agent concentration measurement may be useful for analyzing the distribution and kinetics of contrast agents or labeled pharmaceuticals. Copyright © 2009 John Wiley & Sons, Ltd.     

Simultaneous evaluation of vascular morphology,blood volume and transvascular permeability using SPION‐based,dual‐contrast MRI: imaging optimization and feasibility test

Exploiting ultrashort‐T_E (UTE) MRI, T₁‐weighted positive contrast can be obtained from superparamagnetic iron oxide nanoparticles (SPIONs), which are widely used as a robust T₂‐weighted, negative contrast agent on conventional MR images. Our study was designed (a) to optimize the dual‐contrast MRI method using SPIONs and (b) to validate the feasibility of simultaneously evaluating the vascular morphology, blood volume and transvascular permeability using the dual‐contrast effect of SPIONs. All studies were conducted using 3 T MRI. According to numerical simulation, 0.15 mM was the optimal blood SPION concentration for visualizing the positive contrast effect using UTE MRI (T_E = 0.09 ms), and a flip angle of 40° could provide sufficient SPION‐induced enhancement and acceptable measurement noise for UTE MR angiography. A pharmacokinetic study showed that this concentration can be steadily maintained from 30 to 360 min after the injection of 29 mg/kg of SPIONs. An in vivo study using these settings displayed image quality and CNR of SPION‐enhanced UTE MR angiography (image quality score 3.5; CNR 146) comparable to those of the conventional, Gd‐enhanced method (image quality score 3.8; CNR 148) (p > 0.05). Using dual‐contrast MR images obtained from SPION‐enhanced UTE and conventional spin‐ and gradient‐echo methods, the transvascular permeability (water exchange index 1.76–1.77), cerebral blood volume (2.58–2.60%) and vessel caliber index (3.06–3.10) could be consistently quantified (coefficient of variation less than 9.6%; Bland–Altman 95% limits of agreement 0.886–1.111) and were similar to the literature values. Therefore, using the optimized setting of combined SPION‐based MRI techniques, the vascular morphology, blood volume and transvascular permeability can be comprehensively evaluated during a single session of MR examination. Copyright © 2015 John Wiley & Sons, Ltd.     

Manganese‐enhanced MRI detection of impaired calcium regulation in a mouse model of cardiac hypertrophy

The aim of this study was to use manganese (Mn)‐enhanced MRI (MEMRI) to detect changes in calcium handling associated with cardiac hypertrophy in a mouse model, and to determine whether the impact of creatine kinase ablation is detectable using this method. Male C57BL/6 (C57, n = 11) and male creatine kinase double‐knockout (CK‐M/Mito^–/–, DBKO, n = 12) mice were imaged using the saturation recovery Look–Locker T₁ mapping sequence before and after the development of cardiac hypertrophy. Hypertrophy was induced via subcutaneous continuous 3‐day infusion of isoproterenol, and sham mice not subjected to cardiac hypertrophy were also imaged. During each scan, the contrast agent Mn was administered and the resulting change in R₁ (=1/T₁) was calculated. Two anatomical regions of interest (ROIs) were considered, the left‐ventricular free wall (LVFW) and the septum, and one ROI in an Mn‐containing standard placed next to the mouse. We found statistically significant (p < 0.05) decreases in the uptake of Mn in both the LVFW and septum following the induction of cardiac hypertrophy. No statistically significant decreases were detected in the standard, and no statistically significant differences were found among the sham mice. Using a murine model, we successfully demonstrated that changes in Mn uptake as a result of cardiac hypertrophy are detectable using the functional contrast agent and calcium mimetic Mn. Our measurements showed a decrease in the relaxivity (R₁) of the myocardium following cardiac hypertrophy compared with normal control mice. Copyright © 2014 John Wiley & Sons, Ltd.     

Improved visibility of brain tumors in synthetic MP‐RAGE anatomies with pure T1 weighting

Conventional MRI for brain tumor diagnosis employs T₂‐weighted and contrast‐enhanced T₁‐weighted sequences. Non‐enhanced T₁‐weighted images provide improved anatomical details for precise tumor location, but reduced tumor‐to‐background contrast as elevated T₁ and proton density (PD) values in tumor tissue affect the signal inversely. Radiofrequency (RF) coil inhomogeneities may further mask tumor and edema outlines. To overcome this problem, the aims of this work were to employ quantitative MRI techniques to create purely T₁‐weighted synthetic anatomies which can be expected to yield improved tissue and tumor‐to‐background contrasts, to compare the quality of conventional and synthetic anatomies, and to investigate optical contrast and visibility of brain tumors and edema in synthetic anatomies. Conventional magnetization‐prepared rapid acquisition of gradient echoes (MP‐RAGE) anatomies and maps of T₁, PD and RF coil profiles were acquired in comparable and clinically feasible times. Three synthetic MP‐RAGE anatomies (PD T₁ weighting both with and without RF bias; pure T₁ weighting) were calculated for healthy subjects and 32 patients with brain tumors. In healthy subjects, the PD T₁‐weighted synthetic anatomies with RF bias precisely matched the conventional anatomies, yielding high signal‐to‐noise (SNR) and contrast‐to‐noise (CNR) ratios. Pure T₁ weighting yielded lower SNR, but high CNR, because of increased optical contrasts. In patients with brain tumors, synthetic anatomies with pure T₁ weighting yielded significant increases in optical contrast and improved visibility of tumor and edema in comparison with anatomies reflecting conventional T₁ contrasts. In summary, the optimized purely T₁‐weighted synthetic anatomy with an isotropic resolution of 1 mm, as proposed in this work, considerably enhances optical contrast and visibility of brain tumors and edema. Copyright © 2015 John Wiley & Sons, Ltd.     

Difference in the intratumoral distributions of extracellular‐fluid and intravascular MR contrast agents in glioblastoma growth

Contrast enhancement by an extracellular‐fluid contrast agent (CA) (Gd‐DOTA) depends primarily on the blood–brain‐barrier permeability (bp ), and transverse‐relaxation change caused by intravascular T₂ CA (superparamagnetic iron oxide nanoparticles, SPIONs) is closely associated with the blood volume (BV). Pharmacokinetic (PK) vascular characterization based on single‐CA‐using dynamic contrast‐enhanced MRI (DCE‐MRI) has shown significant measurement variation according to the molecular size of the CA. Based on this recognition, this study used a dual injection of Gd‐DOTA and SPIONs for tracing the changes of bp and BV in C6 glioma growth (Days 1 and 7 after the tumor volume reached 2 mL). bp was quantified according to the non‐PK parameters of Gd‐DOTA‐using DCE‐MRI (wash‐in rate, maximum enhancement ratio and initial area under the enhancement curve (IAUC)). BV was estimated by SPION‐induced ΔR₂* and ΔR₂. With validated measurement reliability of all the parameters (coefficients of variation ≤10%), dual‐contrast MRI demonstrated a different region‐oriented distribution between Gd‐DOTA and SPIONs within a tumor as follows: (a) the BV increased stepwise from the tumor center to the periphery; (b) the tumor periphery maintained the augmented BV to support continuous tumor expansion from Day 1 to Day 7; (c) the internal tumor area underwent significant vascular shrinkage (i.e. decreased ΔR₂ and ΔR₂) as the tumor increased in size; (d) the tumor center showed greater bp ‐indicating parameters, i.e. wash‐in rate, maximum enhancement ratio and IAUC, than the periphery on both Days 1 and 7 and (e) the tumor center showed a greater increase of bp than the tumor periphery in tumor growth, as suggested to support tumor viability when there is insufficient blood supply. In the MRI–histologic correlation, a prominent BV increase in the tumor periphery seen in MRI was verified with increased fluorescein isothiocyanate–dextran signals and up‐regulated immunoreactivity of CD31–VEGFR. In conclusion, the spatiotemporal alterations of BV and bp in glioblastoma growth, i.e. augmented BV in the tumor periphery and increased bp in the center, can be sufficiently evaluated by MRI with dual injection of extracellular‐fluid Gd chelates and intravascular SPION.     

Characterization of a rat orthotopic pancreatic head tumor model using three‐dimensional and quantitative multi‐parametric MRI

The purpose of this study was to investigate the reliability of 3D isotropic MRI and quantitative multi‐parametric MRI characterization on an orthotopic pancreatic head tumor model in rats. 3D isotropic T₂‐weighted MRI was performed as a routine for tumor longitudinal follow‐up and volume estimation. Common bile duct diameter was measured from 3D multiplanar reconstruction. Quantitative multi‐parametric measurements including pixel‐wise T₂, T₁ relaxivity, apparent diffusion coefficient (ADC) and apparent diffusion kurtosis mapping were performed twice throughout tumor growth. Semi‐quantitative and quantitative analyses based on an extended Tofts model were applied to region‐of‐interest‐based dynamic contrast‐enhanced imaging, followed by contrast ratio measurement on standard contrast‐enhanced imaging. Moreover, low‐level texture‐based analysis was inspected for T₂, T₁, ADC and contrast ratio measurements. Results indicated that multi‐parametric MRI showed good reproducibility for tumor characterization; the measurements were not affected by tumor growth. Tumor growth was further confirmed with histology examinations. To conclude, state‐of‐the‐art clinical MRI techniques were translated to this preclinical tumor model with high reliability, and have paved the way for translational oncology studies on this tumor model.     

Comparison of different MRI sequences in lesion detection and early response evaluation of diffuse large B‐cell lymphoma – a whole‐body MRI and diffusion‐weighted imaging study

To compare different MRI sequences for the detection of lesions and the evaluation of response to chemotherapy in patients with diffuse large B‐cell lymphoma (DLBCL), 18 patients with histology‐confirmed DLBCL underwent 3‐T MRI scanning prior to and 1 week after chemotherapy. The MRI sequences included T₁‐weighted pre‐ and post‐contrast, T₂‐weighted with and without fat suppression, and a single‐shot echo‐planar diffusion‐weighted imaging (DWI) with two b values (0 and 800 s/mm²). Conventional MRI sequence comparisons were performed using the contrast ratio between tumor and normal vertebral body instead of signal intensity. The apparent diffusion coefficient (ADC) of the tumor was measured directly on the parametric ADC map. The tumor volume was used as a reference for the evaluation of chemotherapy response. The mean tumor volume was 374 mL at baseline, and decreased by 65% 1 week after chemotherapy (p < 0.01). The T₂‐weighted image with fat suppression showed a significantly higher contrast ratio compared with images from all other conventional MRI sequences, both before and after treatment (p < 0.01, respectively). The contrast ratio of the T₂‐weighted image with fat suppression decreased significantly (p < 0.01), and that of the T₁‐weighted pre‐contrast image increased significantly (p < 0.01), after treatment. However, there was no correlation between the change in contrast ratio and tumor volume. The mean ADC value was 0.68 × 10^–3 mm²/s at baseline; it increased by 89% after chemotherapy (p < 0.001), and the change in ADC value correlated with the change in tumor volume (r = 0.66, p < 0.01). The baseline ADC value also correlated inversely with the percentage change in ADC after treatment (r = ?0.62, p < 0.01). In conclusion, this study indicates that T₂‐weighted imaging with fat suppression is the best conventional sequence for the detection of lesions and evaluation of the efficacy of chemotherapy in DLBCL. DWI with ADC mapping is an imaging modality with both diagnostic and prognostic value that could complement conventional MRI. Copyright © 2013 John Wiley & Sons, Ltd.     

Orotracheal manganese‐enhanced MRI (MEMRI): An effective approach for lung tumor detection

Lung cancer is a primary cause of cancer deaths worldwide. Timely detection of this pathology is necessary to delay or interrupt lung cancer progression, ultimately resulting in a possible better prognosis for the patient. In this context, magnetic resonance imaging (MRI) is especially promising. Ultra‐short echo time (UTE) MRI sequences, in combination with gadolinium‐based contrast agents, have indeed shown to be especially adapted to the detection of lung neoplastic lesions at submillimeter precision. Manganese‐enhanced MRI (MEMRI) increasingly appears to be a possible effective alternative to gadolinium‐enhanced MRI. In this work, we investigated whether low‐dose MEMRI can effectively target non‐small‐cell lung cancer in rodents, whilst minimizing the potential toxic effect of manganese. Both systemic and orotracheal administration modalities allowed the identification of tumors of submillimeter size, as confirmed by bioluminescence imaging and histology. Equivalent tumor signal enhancements and contrast‐to‐noise ratios were observed with orotracheal administration using 20 times lower doses compared with the more conventional systemic route. This finding is of crucial importance as it supports the observation that higher performances of contrast agents can be obtained using an orotracheal administration route when targeting lung diseases. As a consequence, lower concentrations of contrast media can be employed, reducing the dose and potential safety issues. The non‐detectable accumulation of ionic manganese in the brain and liver following orotracheal administration observed in vivo is extremely encouraging with regard to the safety of the orotracheal protocol with low‐dose Mn²⁺ administration. To our knowledge, this is the first time that a study has clearly allowed the high‐precision detection of lung tumor and its contours via the synergic employment of a strongly T₁‐weighted MRI UTE sequence and ionic manganese, an inexpensive contrast agent. Overall, these results support the growing interest in drug and contrast agent delivery via the airways to target and diagnose several diseases of the lungs.     

Challenges towards MR imaging of the peripheral inflammatory response in the subacute and chronic stages of transient focal ischemia

Intravenous administration of iron oxide nanoparticles after experimental stroke has been shown to produce focal signal intensity changes in the ischemic boundary on MRI images. These changes have been attributed to the influx of iron‐laden blood‐borne macrophages, although it has been suggested that this effect might not always be completely specific to inflammatory cells. The aim of the present study was to investigate this phenomenon in a subacute time frame that is more relevant to the peripheral inflammatory response. Imaging experiments (T₂‐, T₂*‐ and T₁‐weighted sequences) were acquired in Wistar rats 6 days after transient middle cerebral artery occlusion (MCAO). Animals were intravenously infused with different doses of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles (300, 600 or 1000 µmol Fe/kg), or saline and gadolinium, and imaged again 24 h later. Tissue was immediately processed for immunohistochemistry with the macrophage marker ED‐1, in combination with Prussian blue for iron. Ischemic tissue exhibited a large increase in T₂ values, and overall contrast enhancement was apparent in the brain and surrounding muscle. In contrast with previous reports, there were no regions of focal signal intensity changes in the ischemic territory in any of the images, although a region of interest analysis revealed a trend towards iron accumulation in the ischemic hemisphere, particularly in the cortex of T₂* images. However, histological examination revealed that, despite extensive ED‐1‐positive macrophage accumulation in the entire ischemic territory, none of these cells were Prussian blue positive, except in the meninges of one animal that received a high dose of USPIO nanoparticles. These results imply that the observed trend is a result of the presence of contrast agent in the blood, or meninges, and not iron‐containing inflammatory cells. Copyright © 2010 John Wiley & Sons, Ltd.     

Monitoring dynamic alterations in calcium homeostasis by T1‐mapping manganese‐enhanced MRI (MEMRI) in the early stage of small intestinal ischemia–reperfusion injury

Manganese‐enhanced MRI studies have proven to be useful in monitoring physiological activities associated with calcium ions (Ca²⁺) due to the paramagnetic property of the manganese ion (Mn²⁺), which makes it an excellent probe of Ca²⁺. In this study, we developed a method in which a Mn²⁺‐enhanced T₁‐map MRI could enable the monitoring of Ca²⁺ influx during the early stages of intestinal ischemia–reperfusion (I/R) injury. The Mn²⁺ infusion protocol was optimized by obtaining dose‐dependent and time‐course wash‐out curves using a Mn²⁺‐enhanced T₁‐map MRI of rabbit abdomens following an intravenous infusion of 50 mmol/l MnCl₂ (5–10 nmol/g body weight (BW)). In the rabbit model of intestinal I/R injury, T₁ values were derived from the T₁ maps in the intestinal wall region and revealed a relationship between the dose of the infused MnCl₂ and the intestinal wall relaxation time. Significant Mn²⁺ clearance was also observed over time in control animals after the infusion of Mn²⁺ at a dose of 10 nmol/g BW. This technique was also shown to be sensitive enough to monitor variations in calcium ion homeostasis in vivo after small intestinal I/R injury. The T₁ values of the intestinal I/R group were significantly lower (P < 0.05) than that of the control group at 5, 10, and 15 min after Mn²⁺ infusion. Our data suggest that MnCl₂ has the potential to be an MRI contrast agent that can be effectively used to monitor changes in intracellular Ca²⁺ homeostasis during the early stages of intestinal I/R injury. Copyright © 2015 John Wiley & Sons, Ltd.     

Triple‐echo steady‐state T2 relaxometry of the human brain at high to ultra‐high fields

Quantitative MRI techniques, such as T₂ relaxometry, have demonstrated the potential to detect changes in the tissue microstructure of the human brain with higher specificity to the underlying pathology than in conventional morphological imaging. At high to ultra‐high field strengths, quantitative MR‐based tissue characterization benefits from the higher signal‐to‐noise ratio traded for either improved resolution or reduced scan time, but is impaired by severe static (B₀) and transmit (B₁) field heterogeneities. The objective of this study was to derive a robust relaxometry technique for fast T₂ mapping of the human brain at high to ultra‐high fields, which is highly insensitive to B₀ and B₁ field variations. The proposed method relies on a recently presented three‐dimensional (3D) triple‐echo steady‐state (TESS) imaging approach that has proven to be suitable for fast intrinsically B₁‐insensitive T₂ relaxometry of rigid targets. In this work, 3D TESS imaging is adapted for rapid high‐ to ultra‐high‐field two‐dimensional (2D) acquisitions. The achieved short scan times of 2D TESS measurements reduce motion sensitivity and make TESS‐based T₂ quantification feasible in the brain. After validation in vitro and in vivo at 3 T, T₂ maps of the human brain were obtained at 7 and 9.4 T. Excellent agreement between TESS‐based T₂ measurements and reference single‐echo spin‐echo data was found in vitro and in vivo at 3 T, and T₂ relaxometry based on TESS imaging was proven to be feasible and reliable in the human brain at 7 and 9.4 T. Although prominent B₀ and B₁ field variations occur at ultra‐high fields, the T₂ maps obtained show no B₀‐ or B₁‐related degradations. In conclusion, as a result of the observed robustness, TESS T₂ may emerge as a valuable measure for the early diagnosis and progression monitoring of brain diseases in high‐resolution 2D acquisitions at high to ultra‐high fields. Copyright © 2014 John Wiley & Sons, Ltd.     

Lateral diffusion of manganese in the rat brain determined by T<Subscript>1</Subscript> relaxation time measured by <Superscript>1</Superscript>H MRI

In order to optimize manganese ion-enhanced MRI in thalamic and hypothalamic nuclei, we analyzed the diffusion of manganese in the brain followed by the intra-cerebroventricular application of manganese-bicine (Mn-bicine). T₁-weighted MRI intensities, with 9-pixel ROIs in the hypothalamus perpendicular to the third ventricle, were measured during continuous infusion of Mn-bicine solution in the lateral cerebroventricle. Using a relationship between the image intensity of T₁-weighted MRI and T₁ relaxation time, the image intensity was converted into the concentration of manganese. Assuming a simple diffusion process, the apparent diffusion coefficient (D _ap) of manganese (4.2 × 10⁻⁵ mm² s⁻¹) is much lower than that of water (6 × 10⁻⁴ mm² s⁻¹), and the D _ap tended to decrease when the distance from the third ventricle increased. These results suggest (1) the Mn²⁺ ion is trapped by neural cells during diffusion and (2) the manganese efflux is discharged from the brain via veins.     

Simultaneous multi‐slice spin‐ and gradient‐echo dynamic susceptibility‐contrast perfusion‐weighted MRI of gliomas

Although combined spin‐ and gradient‐echo (SAGE) dynamic susceptibility‐contrast (DSC) MRI can provide perfusion quantification that is sensitive to both macrovessels and microvessels while correcting for T₁‐shortening effects, spatial coverage is often limited in order to maintain a high temporal resolution for DSC quantification. In this work, we combined a SAGE echo‐planar imaging (EPI) sequence with simultaneous multi‐slice (SMS) excitation and blipped controlled aliasing in parallel imaging (blipped CAIPI) at 3 T to achieve both high temporal resolution and whole brain coverage. Two protocols using this sequence with multi‐band (MB) acceleration factors of 2 and 3 were evaluated in 20 patients with treated gliomas to determine the optimal scan parameters for clinical use. ΔR₂*(t) and ΔR₂(t) curves were derived to calculate dynamic signal‐to‐noise ratio (dSNR), ΔR₂*‐ and ΔR₂‐based relative cerebral blood volume (rCBV), and mean vessel diameter (mVD) for each voxel. The resulting SAGE DSC images acquired using MB acceleration of 3 versus 2 appeared visually similar in terms of image distortion and contrast. The difference in the mean dSNR from normal‐appearing white matter (NAWM) and that in the mean dSNR between NAWM and normal‐appearing gray matter were not statistically significant between the two protocols. ΔR₂*‐ and ΔR₂‐rCBV maps and mVD maps provided unique contrast and spatial heterogeneity within tumors.     

CEST MRI of sepsis‐induced acute kidney injury

Sepsis‐induced acute kidney injury (SAKI) is a major complication of kidney disease associated with increased mortality and faster progression. Therefore, the development of imaging biomarkers to detect septic AKI is of great clinical interest. In this study, we aimed to characterize the endogenous chemical exchange saturation transfer (CEST) MRI contrast in the lipopolysaccharide (LPS)‐induced SAKI mouse model and to investigate the use of CEST MRI for detecting such injury. We used a SAKI mouse model that was generated by i.p. injection of 10 mg/kg LPS. The resulting kidney injury was confirmed by the elevation of serum creatinine and histology. MRI assessments were performed 24 h after LPS injection, including CEST MRI at different B₁ strengths (1, 1.8 and 3 μT), T₁ mapping, T₂ mapping and conventional magnetization transfer contrast (MTC) MRI. The CEST MRI results were analyzed using Z‐spectra, in which the normalized water signal saturation (S_sat/S₀) is measured as a function of saturation frequency. Substantial decreases in CEST contrast were observed at both 3.5 and ? 3.5 ppm frequency offset from water at all B₁ powers, with the most significant difference obtained at a B₁ of 1.8 μT. The average S_sat/S₀ differences between injured and normal kidneys were 0.07 (0.55 ± 0.04 versus 0.62 ± 0.04, P = 0.0028) and 0.07 (0.50 ± 0.04 versus 0.57 ± 0.03, P = 0.0008) for 3.5 and ? 3.5 ppm, respectively. In contrast, the T₁ and T₂ relaxation times and MTC contrast in the injured kidneys did not show a significant change compared with the normal control. Our results showed that CEST MRI is more sensitive to the pathological changes in injured kidneys than the changes in T₁, T₂ and MTC effect, indicating its potential clinical utility for molecular imaging of renal diseases.     

Relationship between blood and myocardium manganese levels during manganese‐enhanced MRI (MEMRI) with T1 mapping in rats

Manganese ions (Mn²⁺) enter viable myocardial cells via voltage‐gated calcium channels. Because of its shortening of T₁ and its relatively long half‐life in cells, Mn²⁺ can serve as an intracellular molecular contrast agent to study indirect calcium influx into the myocardium. One major concern in using Mn²⁺ is its sensitivity over a limited range of concentrations employing T₁‐weighted images for visualization, which limits its potential in quantitative techniques. Therefore, this study assessed the implementation of a T₁ mapping method for cardiac manganese‐enhanced MRI to enable a quantitative estimate of the influx of Mn²⁺ over a wide range of concentrations in male Sprague‐Dawley rats. This MRI method was used to compare the relationship between T₁ changes in the heart as a function of myocardium and blood Mn²⁺ levels. Results showed a biphasic relationship between ΔR₁ and the total Mn²⁺ infusion dose. Nonlinear relationships were observed between the total Mn²⁺ infusion dose versus blood levels and left ventricular free wall ΔR₁. At low blood levels of Mn²⁺, there was proportionally less cardiac enhancement seen than at higher levels of blood Mn²⁺. We hypothesize that Mn²⁺ blood levels increase as a result of rate‐limiting excretion by the liver and kidneys at these higher Mn²⁺ doses. Copyright © 2010 John Wiley & Sons, Ltd.     

Fluorescent Magnetic Nanoparticles with Specific Targeting Functions for Combinded Targeting,Optical Imaging and Magnetic Resonance Imaging

Abstract

Superparamagnetic iron oxides nanoparticles possess specific magnetic properties to be an efficient contrast agent for magnetic resonance imaging (MRI) to enhance the detection and characterization of tissue lesions within the body. To endow specific properties to nanoparticles that can target cancer cells and prevent recognition by the reticuloendothelial system (RES), the surface of the nanoparticles was modified with folic-acid-conjugated poly(ethylene glycol) (FA-PEG). In this study, we investigated the multifunctional fluorescent magnetic nanoparticles (IOPFC) that can specifically target cancer cells and be monitored by both MRI and optical imaging. IOPFC consists of an iron oxide superparamagnetic nanoparticle conjugated with a layer of PEG, which was terminal modified with either Cypher5E or folic acid molecules. The core sizes of IOPFC nanoparticles are around 10 nm, which were visualized by transmission electron microscope (TEM). The hysteresis curves, generated with superconducting quantum interference device (SQUID) magnetometer analysis, demonstrated that IOPFC nanoparticles are superparamagnetic with insignificant hysteresis. IOPFC displays higher intracellular uptake into KB and MDA-MB-231 cells due to the over-expressed folate receptor. This result is confirmed by laser confocal scanning microscopy (LCSM) and atomic flow cytometry. Both in vitro and in vivo MRI studies show better IOPFC uptake by the KB cells (folate positive) than the HT1080 cells (folate negative) and, hence, stronger T ₂-weighted signals enhancement. The in vivo fluorescent image recorded at 20 min post injection show strong fluorescence from IOPFC which can be observed around the tumor region. This multifunctional nanoparticle can assess the potential application of developing a magnetic nanoparticle system that combines tumor targeting, as well as MRI and optical imaging.     

ZTE imaging with long‐T2 suppression

Three‐dimensional radial zero echo time (ZTE) imaging enables efficient direct MRI of tissues with rapid transverse relaxation. Yet, the feature of capturing signals with a wide range of T₂ and T₂* values is accompanied by a lack of contrast between the corresponding tissues. In particular, the targeted short‐T₂ tissues may not be easily identified, and various approaches have been proposed to generate T₂ contrast by reducing the long‐T₂ signal of water and/or fat. The aim of this work was to provide efficient long‐T₂ suppression for selective direct MRI of short‐T₂ tissues using the ZTE technique. For magnetization preparation, suppression pulses for water and fat were designed to provide both good T₂ selectivity and off‐resonance performance. To obtain high efficiency at short TRs, the pulses were applied in a segmented sequence scheme with minimized timing overhead, thus leading to a quasi‐steady state of magnetization. The sequence timing was adjusted for optimal tissue contrast in musculoskeletal applications by means of simulations and experiments, incorporating both T₂ and T₁ of the involved tissues. The developed technique was employed for imaging of a lamb joint sample at 4.7 T. ZTE images were obtained with effective suppression of signals from tissues with long‐T2 water, such as muscle or articular spaces, and fat. Hence, primarily short‐T₂ tissues were visible, such as bone and tendon. The MR image intensity of bone showed strong similarity with bone density imaged with micro‐computed tomography. Copyright © 2014 John Wiley & Sons, Ltd.