Naoki Ohno

Gd-EOB-DTPA-enhanced magnetic resonance imaging and alpha-fetoprotein predict prognosis of early-stage hepatocellular carcinoma

The survival of patients with hepatocellular carcinoma (HCC) is often individually different even after surgery for early‐stage tumors. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd‐EOB‐DTPA)‐enhanced magnetic resonance imaging (MRI) has been introduced recently to evaluate hepatic lesions with regard to vascularity and the activity of the organic anion transporter OATP1B3. Here we report that Gd‐EOB‐DTPA‐enhanced MRI (EOB‐MRI) in combination with serum alpha‐fetoprotein (AFP) status reflects the stem/maturational status of HCC with distinct biology and prognostic information. Gd‐EOB‐DTPA uptake in the hepatobiliary phase was observed in ∼15% of HCCs. This uptake correlated with low serum AFP levels, maintenance of hepatocyte function with the up‐regulation of OATP1B3 and HNF4A expression, and good prognosis. By contrast, HCC showing reduced Gd‐EOB‐DTPA uptake with high serum AFP levels was associated with poor prognosis and the activation of the oncogene FOXM1. Knockdown of HNF4A in HCC cells showing Gd‐EOB‐DTPA uptake resulted in the increased expression of AFP and FOXM1 and the loss of OATP1B3 expression accompanied by morphological changes, enhanced tumorigenesis, and loss of Gd‐EOB‐DTPA uptake in vivo. HCC classification based on EOB‐MRI and serum AFP levels predicted overall survival in a single‐institution cohort (n = 70), and its prognostic utility was validated independently in a multi‐institution cohort of early‐stage HCCs (n = 109). Conclusion: This noninvasive classification system is molecularly based on the stem/maturation status of HCCs and can be incorporated into current staging practices to improve management algorithms, especially in the early stage of disease. (Hepatology 2014;60:1674–1685)

Idiopathic Normal-Pressure Hydrocephalus: Temporal Changes in ADC during Cardiac Cycle

PURPOSE To determine whether temporal changes in apparent diffusion coefficient (ADC) over the cardiac cycle are different in patients with idiopathic normal-pressure hydrocephalus (INPH) as compared with patients with ex vacuo ventricular dilatation and healthy control subjects. MATERIALS AND METHODS This prospective study was approved by the institutional review board and was performed only after informed consent was obtained from each patient. At 1.5 T, electrocardiographically triggered single-shot diffusion echo-planar magnetic resonance imaging (b = 0 and 1000 sec/mm(2)) was performed with sensitivity encoding and half-scan techniques to minimize bulk motion. ΔADC was defined as the difference between maximum and minimum ADC on a pixel-by-pixel basis over 20 phases of the cardiac cycle. Mean ADC during the diastolic phase and ΔADC in the frontal white matter were determined in patients with INPH (n = 13), patients with ex vacuo ventricular dilatation (n = 8), and healthy volunteers (n = 10). Kruskal-Wallis tests were used to determine significance between groups. RESULTS Mean ΔADC in the INPH group was significantly higher than that in the ex vacuo ventricular dilatation and control groups (P < .01 for both). There was no significant difference in ΔADC between the ex vacuo ventricular dilatation and control groups (P = .86). There was no significant difference in mean ADC during the diastolic phase among groups (P > .05 for all). There was no significant correlation between ΔADC and mean ADC during the diastolic phase in any group. CONCLUSION Determination of fluctuation of ADC over the cardiac cycle may render it possible to noninvasively obtain new and more detailed information than that provided by standard ADC measurement in suspected INPH, potentially facilitating the diagnosis of this disease.

Triexponential function analysis of diffusion‐weighted MRI for diagnosing prostate cancer

To evaluate more detailed information noninvasively through on diffusion and perfusion in prostate cancer (PCa) using triexponential analysis of diffusion‐weighted imaging (DWI).

Apparent diffusion coefficient and fractional anisotropy in the vertebral bone marrow

To assess the state of cancellous tissue we analyzed the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in vertebral bone marrow.

Quantitative analysis of hepatic fat fraction by single-breath-holding MR spectroscopy with T 2 correction: phantom and clinical study with histologic assessment

The focus of this study was on the investigation of the accuracy of the fat fraction of the liver by use of single-breath-holding magnetic resonance spectroscopy (MRS) with T2 correction. Single-voxel proton MRS was performed with several TE values, and the fat fraction was determined with and without T2 correction. MRS was also performed with use of the point-resolved spectroscopy sequence in single breath holding. The T2 values of both water and fat were determined separately at the same time, and the effect of T2 on the fat fraction was corrected. In addition, MRS-based fat fractions were compared with the degree of hepatic steatosis (HS) by liver biopsy in human subjects. With T2 correction, the MRI-derived fat fractions were in good agreement with the fat fractions in all phantoms, but the fat fractions were overestimated without T2 correction. R2 values were in good agreement with the preset iron concentrations in the phantoms. The MRI-derived fat fraction was well correlated with the degree of HS. Iron deposited in the liver affects the signal strength when proton MRS is used for detection of the fat signal in the liver. However, the fat signal can be evaluated more accurately when the T2 correction is applied. Breath-holding MRS minimizes the respiratory motion, and it can be more accurate in the quantification of the hepatic fat fraction.

Modified triexponential analysis of intravoxel incoherent motion for brain perfusion and diffusion.

To noninvasively obtain more detailed information on brain perfusion and diffusion using modified triexponential analysis.

Acoustic Noise Transfer Function in Clinical MRI: A Multicenter Analysis

RATIONALE AND OBJECTIVES Acoustic noise both in terms of its magnitude and frequency during magnetic resonance imaging (MRI) scan is influenced by imaging parameters and pulse sequences. It varies because of many different factors such as structure, materials, and magnetic field strength. The purpose of our study is to evaluate the characteristics of acoustic noise independent of MRI scan protocol by measuring a gradient-pulse-to-acoustic-noise transfer function (GPAN-TF) at various MRI scanners. MATERIALS AND METHODS We measured sound pressure levels in the frequency domain in a 0.4-T, seven 1.5-T, and three 3.0-T clinical MRI systems when applying a simple narrower trapezoidal gradient pulse. We calculated a GPAN-TF [μPa/(mT/m)] in each gradient coil (ie, X, Y, and Z-axis) by the deconvolution process. RESULTS GPAN-TF at a high-frequency range (1000-10,000 Hz) was larger than that at low frequency for all MRI (P<0.01) scanners except for a low static field machine. For high frequency (>1000 Hz), the 3.0-T MRI scanner had a larger GPAN-TF than that of 0.4-T and 1.5-T (P < .01). MR scanner with a vacuum chamber reduced GPAN-TF at a lower frequency (P < .01), but this effect decreased at higher frequency. CONCLUSION GPAN-TF analysis makes it possible to obtain more detailed information on acoustic noise properties among MRI scanners.

Technical Note: Development of a cranial phantom for assessing perfusion, diffusion, and biomechanics

Purpose A novel cranial phantom was developed to simulate the relationships among factors such as blood perfusion, water diffusion, and biomechanics in intracranial tissue. Methods The cranial phantom consisted of a high‐density polypropylene filter (mimicking brain parenchyma) with intra‐ and extrafilter spaces (mimicking cerebral artery and vein, respectively), and a capacitor space (mimicking the cerebrospinal fluid space). Pulsatile and steady flow with different flow rates were applied to the cranial phantom using a programmable pump. On 3.0‐T MRI, the measurements of the internal pressure in the phantom, apparent diffusion coefficient (ADC) with monoexponential analysis in the filter, and total simulated cerebral blood flow (tSCBF) into the phantom were synchronized with the pulsatile flow. We obtained their maximum changes during the pulsation period (ΔP, ΔADC, and ΔtSCBF, respectively). Then, the compliance index (CI) was calculated by dividing the volume change (ΔV) by the ΔP in the phantom. Moreover, the same measurements were repeated after the compliance of the phantom was reduced by increasing the water volume in the capacitor space. Under steady flow conditions, we determined the regional SCBF (rSCBF) and perfusion‐related and restricted diffusion coefficients (D* and D, respectively) with biexponential analysis in the filter. Results The internal pressure, ADC, and tSCBF varied over the pulsation period depending on the input flow. Moreover, the ΔP, ΔADC, ΔtSCBF, and rSCBF increased with the input flow rate. Compared to the high compliance condition, in the low compliance condition, the ΔP and ΔADC were higher by factors of 2.5 and 1.3, respectively, and the CI was smaller by a factor of 2.7, whereas the ΔV was almost unchanged. The D* was strongly affected by the input flow. Conclusion Our original phantom models the relationships among the blood perfusion, water diffusion, and biomechanics of the intracranial tissue, potentially facilitating the validation of novel MRI techniques and optimization of imaging parameters.

Quantitative Assessment of Tissue Perfusion in Hepatocellular Carcinoma Using Perflubutane Dynamic Contrast-Enhanced Ultrasonography: A Preliminary Study.

Our purpose in this study was to assess the relationship between contrast signal intensity (CI) and concentration of perflubutane microbubbles in a phantom experiment, and to examine the feasibility of this technique for quantitative analysis of vascularity in hepatocellular carcinoma (HCC). Microbubble solutions of the perflubutane contrast agent were prepared by mixing with purified water. We examined the relationship between CI in dB units and the concentration. Moreover, seven HCC patients were examined using real-time dynamic contrast imaging. The perfusion index was calculated from time-intensity curves generated for both HCC and surrounding liver parenchyma. We observed a linear relationship between the CIdB and the concentration in the phantom study and a higher perfusion index in the HCC lesions relative to the surrounding liver parenchyma. Dynamic contrast-enhanced ultrasonography with perflubutane microbubbles, which exhibit linear and temporally stable characteristics under continuous ultrasound exposure, allows the collection of quantitative hemodynamic information regarding HCC.

Dynamic state of water molecular displacement of the brain during the cardiac cycle in idiopathic normal pressure hydrocephalus

The predictive accuracy of iNPH diagnoses could be increased using a combination of supplemental tests for iNPH. To evaluate the dynamic state of water displacement during the cardiac cycle in idiopathic normal pressure hydrocephalus (iNPH), we determined the change in water displacement using q-space analysis of diffusion magnetic resonance image. ECG-triggered single-shot diffusion echo planar imaging was used. Water displacement was obtained from the displacement probability profile calculated by Fourier transform of the signal decay fitted as a function of the reciprocal spatial vector q. Then maximum minus minimum displacement (delta-displacement), of all cardiac phase images was calculated. We assessed the delta-displacement in white matter in patients with iNPH and atrophic ventricular dilation (atrophic VD), and in healthy volunteers (control group). Delta-displacement in iNPH was significantly higher than those in the atrophic VD and control. This shows that water molecules of the white matter in iNPH are easily fluctuated by volume loading of the cranium during the cardiac cycle, due to the decrease in intracranial compliance. There was no significant correlation between delta-displacement and displacement. The delta-displacement and the displacement do not necessarily yield the same kind of information. Delta-displacement demonstrated to obtain biophysical information about fluctuation. This analysis may be helpful in the understanding physiology and pathological condition in iNPH and the assisting in the diagnosis.