Different signal intensity at Gd-EOB-DTPA compared with Gd-DTPA-enhanced MRI in hepatocellular carcinoma transgenic mouse model in delayed phase hepatobiliary imaging

Purpose:

To evaluate hyperintense Gd‐DTPA‐ compared with hyper‐ and hypointense Gd‐EOB‐DTPA‐enhanced magnet resonance imaging (MRI) in c‐myc/TGFα transgenic mice for detecting hepatocellular carcinoma (HCC).

Materials And Methods:

Twenty HCC‐bearing transgenic mice with overexpression of the protooncogene c‐myc and transforming growth factor‐alpha (TGF‐α) were analyzed. MRI was performed using a 3‐T MRI scanner and an MRI coil. The imaging protocol included Gd‐DTPA‐ and Gd‐EOB‐DTPA‐enhanced T1‐weighted images. The statistically evaluated parameters are signal intensity (SI), signal intensity ratio (SIR), contrast‐to‐noise ratio (CNR), percentage enhancement (PE), and signal‐to‐noise ratio (SNR).

Results:

On Gd‐DTPA‐enhanced MRI compared with Gd‐EOB‐DTPA‐enhanced MRI, the SI of liver was 265.02 to 573.02 and of HCC 350.84 to either hyperintense with 757.1 or hypointense with 372.55 enhancement. Evaluated parameters were SNR of HCC 50.1 to 56.5/111.5 and SNR of liver parenchyma 37.8 to 85.8, SIR 1.32 to 1.31/0.64, CNR 12.2 to 26.1/?30.08 and PE 42.08% to 80.5/?98.2%, (P < 0.05).

Conclusion:

Gd‐EOB‐DTPA is superior to Gd‐DTPA for detecting HCC in contrast agent‐enhanced MRI in the c‐myc/TGFα transgenic mouse model and there was no difference between the hyperintense or hypointense appearance of HCC. Either way, HCCs can easily be distinguished from liver parenchyma in mice. J. Magn. Reson. Imaging 2012;35:1397–1402. © 2012 Wiley Periodicals, Inc.

     

Chemical-shift-selective filter for the in vivo detection of J-coupled metabolites at 3T.

A chemical-shift-selective filter (CSSF) was applied to the detection of J-coupled metabolites in the human brain. This filter is an acquisition-based technique that requires the chemical shifts (CS's) of different metabolites, but not their whole multiplet structures, to be resolved. The sequence is based on the 2D constant-time spin-echo experiment, which yields pure CS spectra in the indirect dimension. Localization is achieved through point-resolved spectroscopy (PRESS). The method enables unequivocal detection of glutamate and myo-inositol, both in vitro and in vivo in the human brain, at 3T.     

Increased N-acetylaspartate in model mouse of Pelizaeus-Merzbacher disease

Purpose:

To evaluate the N‐acetylaspartate (NAA) and N‐acetylaspartylglutamate (NAAG) biochemical pathways in the brain of myelin synthesis‐deficient (msd) mouse, a model of Pelizaeus‐Merzbacher disease (PMD).

Materials and Methods:

We performed magnetic resonance imaging and proton magnetic resonance spectroscopy (¹H‐MRS) of the thalamus for msd and wildtype mice with a 7.0 T magnet. NAA and NAAG were independently measured by high‐performance liquid chromatography (HPLC). Immunohistochemical analysis using anti‐Mbp, Gfap, Ng2, and NeuN antibodies were also performed.

Results:

¹H‐MRS in msd mice revealed increased total NAA (tNAA, NAA+NAAG), creatine, glutamine, and glutamate and decreased choline (Cho). HPLC analysis revealed increases of both NAA and NAAG in the msd brains. Histologically, the msd brains revealed hypomyelination and astrogliosis. Oligodendrocyte progenitor cells and neurons were normal in number in the thalamus wherein ¹H‐MRS was obtained.

Conclusion:

The evidence suggests that the neurochemical derangement in the msd mice may be a primary increase of NAA resulting in a secondary increase of NAAG. Increased tNAA with decreased Cho detectable on ¹H‐MRS may be an important marker for PMD, and might be used to distinguish it from more common neurological disorders that have decreased tNAA. J. Magn. Reson. Imaging 2012;418‐425. © 2011 Wiley Periodicals, Inc.     

Loss of fine structure and edge sharpness in fast-spin-echo carotid wall imaging: measurements and comparison with multiple-spin-echo in normal and atherosclerotic subjects

Purpose:

To test whether the k‐space acquisition strategy used by fast‐spin‐echo (FSE) is a major source of blurring in carotid wall and plaque imaging, and investigate an alternative acquisition approach.

Materials and Methods:

The effect of echo train length (ETL) and T₂ on the amount of blurring was studied in FSE simulations of vessel images. Edge sharpness was measured in black‐blood T₁ and proton‐density weighted (T₁W and PDW) carotid images acquired from 5 normal volunteers and 19 asymptomatic patients using both FSE and multiple‐spin‐echo (Multi‐SE) sequences at 3 Tesla. Plaque images were classified and divided in group α (tissues' average T₂ ～40–70 ms) and group β (plaque components with shorter T₂).

Results:

Simulations predicted 26.9% reduction of vessel edge sharpness from Multi‐SE to FSE images (ETL = 9, T₂ = 60 ms). This agreed with in vivo measurements in normal volunteers (27.4%) and in patient group α (26.2%), while in group β the loss was higher (31.6%).

Conclusion:

FSE significantly reduced vessel edge sharpness along the phase‐encoding direction in T₁W and PDW images. Blurring was stronger in the presence of plaque components with short T₂ times. This study shows a limitation of FSE and the potential of Multi‐SE to improve the quality of carotid imaging. J. Magn. Reson. Imaging 2011;33:1136–1143. © 2011 Wiley‐Liss, Inc.     

In vivo MRI and histopathological assessment of tumor microenvironment in luminal-like and basal-like breast cancer xenografts

Purpose:

To explore tumor pathophysiology with special attention to the microenvironment in two molecular subtypes of human breast cancer using in vivo magnetic resonance imaging (MRI) and histopathology. The impact of tumor growth, size, and the influence of estradiol were also investigated.

Materials and Methods:

Two orthotopic and directly transplanted human breast cancer models representing luminal‐like and basal‐like molecular subtypes were characterized by dynamic contrast‐enhanced MRI and diffusion‐weighted MRI. Ex vivo measurements of vascularization, hypoxia, mitoses, and the level of VEGF activations were associated with the calculated in vivo MRI parameters of the tumors.

Results:

The vascular permeability and perfusion (K^trans) was significantly higher in basal‐like compared to luminal‐like tumors. These findings were confirmed by a 4‐fold higher proliferating microvessel density (pMVD) in basal‐like tumors, reflecting the difference in aggressiveness between the subtypes. No effect of tumor growth was observed during 6 days of growth in any of the models; however, large tumors had lower K^trans, higher extracellular extravascular volume fraction (v_e), and more hypoxia than medium‐sized tumors. Estradiol withdrawal induced increased K^trans, v_e, and tumor water diffusion (ADC) in luminal‐like tumors, corresponding to increased VEGFR2 activation, which is likely to cause increased tumor vessel permeability.

Conclusion:

These novel data confirm the potential of functional MRI methods to map histopathologically proven changes in breast tumor vasculature and microenvironment in vivo. J. Magn. Reson. Imaging 2012;35:1098‐1107. © 2011 Wiley Periodicals, Inc.     

In vivo monitoring of hepatic glutathione in anesthetized rats by 13C NMR.

A method for in vivo (13)C NMR monitoring of hepatic glutathione (GSH) in intact, anesthetized rats has been developed. Studies were conducted using a triple-tuned, surgically implanted surface coil designed for this animal model. The coil permitted complete decoupling and sufficient resolution in the (13)C NMR spectrum to monitor the time course of hepatic (13)C-metabolites of intravenously administered 2-(13)C-glycine, particularly GSH at 44.2 ppm and serine signals at 61.1 and 57.2 ppm, respectively. It further allowed concomitant monitoring of high-energy phosphagens and intracellular pH by (31)P NMR. To confirm in vivo NMR peak assignments, we compared high-resolution 2D (1)H[(13)C] heteronuclear multiple quantum coherence and 1D (13)C spectra of hepatic perchloric acid extracts to those of authentic standards. The fractional isotopic enrichment of hepatic (13)C-glycine increased exponentially at a rate of 1.68 h(-1) and reached its plateau level of 81% in 2 h. The (13)C fractional isotopic enrichment of GSH increased exponentially at a rate of 0.316 h(-1) and reached 55% after 4 h of 2-(13)C-glycine infusion, but without achieving a plateau. To confirm that the resonance at 44.2 ppm resulted from GSH, a rat was given an intravenous dose of 2-oxothiazolidine-4-carboxylic acid (OTC), a cysteine precursor that increases intracellular GSH. As expected, with OTC administration the hepatic (13)C GSH-to-glycine peak area increased more than sevenfold.     

Fast whole‐body magnetic resonance angiography in mice

High‐throughput magnetic resonance imaging (MRI) tools are required for the longitudinal investigation of vascular diseases in mouse models. Angiographic data from various anatomic regions may be needed in a single experiment. This study involves a three‐dimensional (3D) time‐of‐flight (TOF) magnetic resonance angiography (MRA) method using sequential acquisitions of four data sets corresponding to the head, the thorax, the abdomen, and the hind limbs of a mouse. After repositioning the animal, each anatomic region was acquired in 2 min, and the TOF effect was provided by the spatial selectivity of the radio frequency (RF) resonator. No slab selection was needed and whole‐body MRA was performed in a total experiment time of 10 min. The voxel size was equal to or greater than 131 × 195 × 188 μm³. To suppress the signal arising from stationary tissues, both inversion recovery and interspersed saturation, used as magnetization preparations, were compared from a theoretical and an experimental perspective. The arterial tree (carotid, aortic, iliac, renal, and smaller arteries) was well visualized by this method, both in control healthy mice and in mice with common carotid artery ligation. The potential interest of this method for evaluating arterial diseases is discussed. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Applicability of contrast‐enhanced ultrasound in the diagnosis of plantar fasciitis

Contrast‐enhanced ultrasound (CEUS) is used to visualize the microvascularization in various tissues. The purpose of this study was to investigate whether CEUS could be used to visualize the microvascular volume (MV) in the plantar fascia, and to compare the method to clinical symptoms and B‐mode ultrasound (US) in patients with plantar fasciitis (PF). Twenty patients with unilateral PF were included and were divided by US in insertional thickening (10), midsubstance thickening (5), and no US changes (5). The MV was measured simultaneously in both heels. Four areas in the plantar fascia and plantar fat pad were measured independently by two observers. Inter‐ and intra‐observer correlation analyses were performed. The asymptomatic heels showed a constantly low MV, and for the whole group of patients, a significantly higher MV was found in the symptomatic plantar fascia and plantar fat pad. Inter‐observer correlation as well as intra‐observer agreement was excellent. The MV in the plantar fascia and plantar fat pad can be measured reliably using CEUS, suggesting that it is a reproducible method to examine patients with plantar fasciitis.     

A quantitative pressure and microbubble‐size dependence study of focused ultrasound‐induced blood‐brain barrier opening reversibility in vivo using MRI

Focused ultrasound in conjunction with the systemic administration of microbubbles has been shown to open the blood‐brain barrier (BBB) selectively, noninvasively and reversibly. In this study, we investigate the dependence of the BBB opening's reversibility on the peak‐rarefactional pressure (0.30–0.60 MPa) as well as the microbubble size (diameters of 1–2, 4–5, or 6–8 μm) in mice using contrast‐enhanced T₁‐weighted (CE‐T₁) MR images (9.4 T). Volumetric measurements of the diffusion of Gd‐DTPA‐BMA into the brain parenchyma were used for the quantification of the BBB‐opened region on the day of sonication and up to 5 days thereafter. The volume of opening was found to increase with both pressure and microbubble diameter. The duration required for closing was found to be proportional to the volume of opening on the day of opening, and ranged from 24 h, for the smaller microbubbles, to 5 days at high peak‐rarefactional pressures. Overall, larger bubbles did not show significant differences. Also, the extent of BBB opening decreased radially towards the focal region until the BBB's integrity was restored. In the cases where histological damage was detected, it was found to be highly correlated with hyperintensity on the precontrast T₁ images. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.     

Scaling waist girth for differences in body size reveals a new improved index associated with cardiometabolic risk

Our aim was to examine whether a new ratio, waist divided by height^0.5 (WHT.5R), is both independent of stature and a stronger predictor of cardiometabolic risk (CMR) than other anthropometric indices. Subjects (4117 men and 646 women), aged 20–69 years, were assessed for stature (cm), mass (kg), waist, and hip girths (cm) from which body mass index (BMI), waist‐to‐hip ratio (WHR), waist‐to‐height ratio (WHTR), and two new indices, a body shape index (ABSI) and WHT.5R, were determined. We used the allometric power law, W = a.HT^b, to obtain a simple body shape index for waist girth (W) to be independent of stature (HT). Physical activity was determined using self‐report, and physical fitness was determined using the Bruce protocol. Glucose, total cholesterol, low‐density lipoprotein, high‐density lipoprotein, triglycerides, and TC/HDL ratio were determined from fasting venous blood samples. A single CMR composite score was derived from log‐transformed z‐scores of Triglycerides + average blood pressure ((diastolic + systolic)/2) + glucose + HDL (*?1). Results confirmed WHT.5R to be independent of stature and the strongest predictor of CMR, compared with BMI, WC, WHR, ABSI, and WHTR. We also found that CMR scores decline significantly with increasing fitness and physical activity, confirming that being fit and active can compensate for the adverse effects of being fat as measured by all other anthropometric indices. In conclusion, WHT.5R was the best anthropometric index associated with CMR, and being both physically fit and active has a protective effect on CMR, irrespective of weight status.     

Optimization of blood-myocardial contrast in 3D true FISP cardiac imaging at 1.5 T.

Three-dimensional (3D) steady-state free precession (SSFP) MRI sequences are often applied to visualize both intra- and extracardiac pathologies. In the present study the contrast behavior of 3D true fast imaging with steady precession (True-FISP) sequences for cardiac imaging was optimized in numerical simulations and compared with measurements obtained in eight healthy volunteers on a 1.5 T whole-body scanner. Two SS preparation schemes in combination with and without a T(2) preparation were assessed to improve contrast between blood and myocardium using a navigator-gated and ECG-triggered 3D True-FISP sequence. Numerical simulations and experimental studies in volunteers showed that an SS preparation using a constant flip angle (CFA) is preferable to a linear flip angle (LFA) preparation in terms of contrast between blood and myocardium. The optimized 3D True-FISP sequence provides a reliable, accurate, and time-efficient means of obtaining a morphological cardiac diagnosis.     

Reference-scan-free method for automated correction of Nyquist ghost artifacts in echoplanar brain images.

One of the most common artifacts for echo-planar imaging is the Nyquist ghost, typically overcome with the aid of a reference scan preceding the actual image acquisition. In this work, a nonlinear phase correction obviating the need for a reference scan is proposed. The method is based on computing the second moments of the even and odd subdomains of the phase-encoding k-space data to retrieve the phase disparities between even and odd echoes. The method's underlying assumption is that the images are dominated by their low frequency and symmetric part. In vivo data demonstrate the effectiveness of the algorithm showing ghost suppression comparable to that achievable with the reference-scan method.     

Quantitation of differential renal blood flow and renal function using dynamic contrast-enhanced MRI in rats.

A first-pass upslope approach was used to estimate differential renal blood flow (DRBF) and a Patlak-Rutland approach was used to estimate differential renal function (DRF) using Gd-DTPA-BMA-enhanced MRI. DRBF and DRF were estimated in rat kidneys under three different experimental conditions: 1) transient renal artery occlusion (TRAO); 2) partial unilateral ureteric obstruction (PUO); and 3) sham-operated control rats (SHAM). A bolus of Gd-DTPA-BMA was given intravenously during a dynamic single slice T1-weighted gradient echo sequence, which allowed calculation of concentration from signal intensity values. Calculations based on the raw signal intensity showed that DRBF was decreased in both PUO (44 +/- 1%; P < 0.05) and in TRAO (38 +/- 1%; P < 0.05) compared with SHAM (52 +/- 1%). Converting the signal intensity into a measure of Gd-DTPA-BMA concentration did not substantially alter these findings (PUO: 40 +/- 3%, P < 0.05; TRAO: 35 +/- 2%, P < 0.05; SHAM 49 +/- 1%). Likewise, DRF decreased in both PUO (43 +/- 4%; P < 0.05) and TRAO (39 +/- 3%; P < 0.05) compared with SHAM (48 +/- 2%). Converting the signal intensity into measurements of Gd-DTPA-BMA concentration revealed similar findings (PUO: 41 +/- 5%, P < 0.05; TRAO: 34 +/- 5%, P < 0.05; SHAM: 49 +/- 2%). Our results suggest that renal damage in rats may be demonstrated by an observed reduction of DRBF and DRF as estimated from single-slice Gd-DTPA-BMA enhanced signal intensity using time-activity curves with and without quantitation of Gd-concentration.     

On the influence of training data quality in k-t BLAST reconstruction.

This work investigated how the quality of prior information (i.e., data acquired during the training stage) influences k-t BLAST reconstruction. The impact of several factors, such as the amount of training data, the presence of spatial misregistration in the training data, and the effects of filtering, was investigated with simulations and in vivo data. It is shown that k-t BLAST outperforms sliding window reconstruction, even with very limited training data. By increasing the amount of training data, reconstruction error continues to decrease, albeit by a diminishing amount. However, an increased amount of training data also increases susceptibility to misregistration of the training data. Filtering of the training data with the goal of reducing truncation artifacts had only minor impact on reconstruction errors. Considering the balance among obtaining the most benefit from the training data, minimizing susceptibility to misregistration, and keeping data acquisition to a minimum, it is concluded that in cardiac imaging the training datasets should be limited to 10-20 profiles in k-space for a typical field of view. The training data may be acquired in a separate breathhold without much penalty, if care is taken to minimize misregistration, such as with a navigator.     

Effect of Gd-DTPA-BMA on choline signals of HT29 tumors detected by in vivo 1H MRS

Purpose

To study the impact of Gd‐DTPA‐BMA on choline signals of HT29 colon carcinomas determined by localized ¹H MRS in vivo at 4.7T.

Materials and Methods

PRESS ¹H MR spectra (2‐second repetition time and echo times of 20–272 msec) were acquired from HT29 xenografts prior to and following intravenous administration of 0.1 or 0.2 mmol/kg Gd‐DTPA‐BMA. The magnetic resonance spectroscopy (MRS) data were analyzed by 1) normalizing choline and water peak areas to their precontrast values; and 2) estimating absolute choline concentration relative to tissue water.

Results

Changes in the T₁ and T₂ of choline and water were apparent following administration of Gd‐DTPA‐BMA. Administration of 0.1 mmol/kg Gd‐DTPA‐BMA induced significant increases in the choline peak area, concomitant with enhancements of the water peak area, whereas 0.2 mmol/kg Gd‐DTPA‐BMA induced no enhancement of choline peak area but significant increases in water peak area at short echo times.

Conclusion

The effect of Gd‐DTPA‐BMA on estimation of tumor choline concentration varied with the dose of contrast agent, the echo time, and the time after contrast agent administration. These data highlight the potential pitfalls associated with the modulation of choline and water signals post‐Gd‐DTPA‐BMA and may account for the apparently contradictory results previously reported. J. Magn. Reson. Imaging 2008;28:1201–1208. © 2008 Wiley‐Liss, Inc.