Development and Evaluation of a Short-time Imaging Method for the Clinical Study of the Apparent Diffusion Coefficient Subtraction Method.

The apparent diffusion coefficient subtraction method (ASM) was developed as a new restricted diffusionweighted imaging technique for magnetic resonance imaging (MRI). The usefulness of the ASM has been established by in vitro basic research using a bio-phantom, and clinical research on the application of the ASM for the human body is needed. Herein, we developed a short-time sequence for ASM imaging of the heads of healthy volunteers (n=2), and we investigated the similarity between the obtained ASM images and diffusion kurtosis (DK) images to determine the utility of the ASM for clinical uses. This study appears to be the first to report ASM images of the human head. We observed that the short-time sequence for the ASM imaging of the head can be scanned in approx. 3 min at 1.5T MRI. The noise reduction effect of median filter processing was confirmed on the ASM images scanned by this sequence. The obtained ASM images showed a weak correlation with the DK images, indicating that the ASM images are restricted diffusion-weighted images. The new shorttime imaging sequence could thus be used in clinical studies applying the ASM.

Evaluation of Fast Diffusion Kurtosis Imaging Using New Software Designed for Widespread Clinical Use.

Clinical research using restricted diffusion-weighted imaging, especially diffusion kurtosis (DK) imaging, has been progressing, with reports on its effectiveness in the diagnostic imaging of cerebral infarctions, neurodegenerative diseases, and tumors, among others. However, the application of DK imaging in daily clinical practice has not spread because of the long imaging time required and the use of specific software for image creation. Herein, with the aim of promoting clinical research using DK imaging at any medical facility, we evaluated fast DK imaging using a new software program. We developed a new macro program that produces DK images using general-purpose, inexpensive software (Microsoft Excel and ImageJ), and we evaluated fast DK imaging using bio-phantoms and a healthy volunteer in clinical trials. The DK images created by the new software with diffusion-weighted images captured with short-time imaging sequences were similar to the original DK images captured with long-time imaging sequences. The DK images using three b-values, which can reduce the imaging time by 43%, were equivalent to the DK images using five b-values. The DK imaging technique developed herein might allow any medical facility to increase its daily clinical use of DK imaging and easily conduct clinical research.

Evaluation of the Imaging Process for a Novel Subtraction Method Using Apparent Diffusion Coefficient Values.

Diffusion-weighted imaging may be used to obtain the apparent diffusion coefficient (ADC), which aids the diagnosis of cerebral infarction and tumors. An ADC reflects elements of free diffusion. Diffusion kurtosis imaging (DKI) has attracted attention as a restricted diffusion imaging technique. The ADC subtraction method (ASM) was developed to visualize restricted diffusion with high resolution by using two ADC maps taken with different diffusion times. We conducted the present study to provide a bridge between the reported basic ASM research and clinical research. We developed new imaging software for clinical use and evaluated its performance herein. This software performs the imaging process automatically and continuously at the pixel level, using ImageJ software. The new software uses a macro or a plugin which is compatible with various operating systems via a Java Virtual Machine. We tested the new imaging software's performance by using a Jurkat cell bio-phantom, and the statistical evaluation of the performance clarified that the ASM values of 99.98% of the pixels in the bio-phantom and physiological saline were calculated accurately (p<0.001). The new software may serve as a useful tool for future clinical applications and restricted diffusion imaging research.

[Usefulness of Respiratory Suppression for Abdominal Using EPI Sequences].

The upper abdomen was imaged with diffusion weighted images for free breathing and respiratory suppression using single shot-echo planar imaging (SS-EPI) and readout segmented-EPI (RS-EPI). We examined the usefulness of respiratory suppression imaging for the subject of healthy volunteers. Motion artifacts, apparent diffusion coefficient (ADC) values, and organs movement distances were evaluated. As a result, motion artifacts and organs movement distances were reduced in respiratory suppression than free breathing. The ADC values did not change. Respiratory suppression was simple and useful. In addition, it was found that RS-EPI imaging could be used for imaging the upper abdomen in the same way as SS-EPI by respiratory suppression.

Evaluation of Setup Errors at the Skin Surface Position for Whole Breast Radiotherapy of Breast Cancer Patients.

We used image-processing software to analyze the setup errors at the skin surface position of breast cancer patients (n=66) who underwent post-operative whole breast irradiation at our hospital in 2014-2015. The sixty-six digital reconstructed radiographs (DRR) were created at the treatment planning for each patient. The lineacgraphies (n=377) were taken after the patients' setup during radiotherapy. The lineacgraphies and DRR were superimposed at the skin surface position for each patient with the image-processing software. We measured the deviations of the isocenters for the nipple-lung (X) direction and craniocaudal (Y) direction and the deviation of the rotation angle of the XY axes between the lineacgraphy and DRR on the superimposed images. The systematic error (µ, Σ) and random error (σ) were calculated from the X and Y deviations and rotation angle deviation. The µ of X, Y, and rotation angle were 0.01 mm, -1.2 mm, and 0.05°, respectively. The Σ of X, Y, and rotation angle were 1.8 mm, 1.5 mm, and 0.9°, respectively. The σ of X, Y, and rotation angle were 2.0 mm, 1.5 mm, and 1.0°, respectively. Our analyses thus revealed that evaluations using image-processing software at the skin surface position in routine breast radiotherapy result in sufficiently small setup errors.

The Usefulness of Readout-Segmented Echo-Planar Imaging (RESOLVE) for Bio-phantom Imaging Using 3-Tesla Clinical MRI.

Readout-segmented echo-planar imaging (RESOLVE) is a multi-shot echo-planar imaging (EPI) modality with k-space segmented in the readout direction. We investigated whether RESOLVE decreases the distortion and artifact in the phase direction and increases the signal-to-noise ratio (SNR) in phantoms image taken with 3-tesla (3T) MRI versus conventional EPI. We used a physiological saline phantom and subtraction mapping and observed that RESOLVE's SNR was higher than EPI's. Using RESOLVE, the combination of a special-purpose coil and a large-loop coil had a higher SNR compared to using only a head/neck coil. RESOLVE's image distortioas less than EPI's. We used a 120 mM polyethylene glycol phantom to examine the phase direction artifact.vThe range where the artifact appeared in the apparent diffusion coefficient (ADC) image was shorter with RESOLVE compared to EPI. We used RESOLVE to take images of a Jurkat cell bio-phantom: the cell-region ADC was 856×10-6mm2/sec and the surrounding physiological saline-region ADC was 2,951×10-6mm2/sec. The combination of RESOLVE and the 3T clinical MRI device reduced image distortion and improved SNR and the identification of accurate ADC values due to the phase direction artifact reduction. This combination is useful for obtaining accurate ADC values of bio-phantoms.

[Measurement Accuracy of Fat and Iron Deposits in the Liver Using 1H-MRS (HISTO)].

1H-MRS, which is a method of measuring fat and iron deposits in the liver, has a single voxel spectroscopy imaging method called high-speed T2-corrected multiecho (HISTO) based on the STEAM method. If HISTO measurement accuracy is high, it will be one of the biomarkers, so the measurement accuracy was examined. We imaged a self-made phantom simulating a known amount of fat and iron deposition in the liver. A regression analysis of HISTO-measured values for hepatic fat phantom was performed. In addition, regression analysis was performed on the hepatic iron phantom for the R2 values obtained from the T2 values measurement and the actually measured value of the HISTO. From the regression analysis, the correlation coefficients were 0.999, 0.992 and 0.977, respectively. The measurement accuracy of HISTO is high, and the reliability of the obtained fat and iron deposit value is high.

[Evaluation of Image Quality of Readout Segmented EPI with Readout Partial Fourier Technique].

Readout segmented EPI (readout segmentation of long variable echo-trains: RESOLVE) segmented k-space in the readout direction. By using the partial Fourier method in the readout direction, the imaging time was shortened. However, the influence on image quality due to insufficient data sampling is concerned. The setting of the partial Fourier method in the readout direction in each segment was changed. Then, we examined signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and distortion ratio for changes in image quality due to differences in data sampling. As the number of sampling segments decreased, SNR and CNR showed a low value. In addition, the distortion ratio did not change. The image quality of minimum sampling segments is greatly different from full data sampling, and caution is required when using it.

Enhancing Diagnostic Precision: Evaluation of Preprocessing Filters in Simple Diffusion Kurtosis Imaging for Head and Neck Tumors.

Background: Our initial clinical study using simple diffusion kurtosis imaging (SDI), which simultaneously produces a diffusion kurtosis image (DKI) and an apparent diffusion coefficient map, confirmed the usefulness of SDI for tumor diagnosis. However, the obtained DKI had noticeable variability in the mean kurtosis (MK) values, which is inherent to SDI. We aimed to improve this variability in SDI by preprocessing with three different filters (Gaussian [G], median [M], and nonlocal mean) of the diffusion-weighted images used for SDI. Methods: The usefulness of filter parameters for diagnosis was examined in basic and clinical studies involving 13 patients with head and neck tumors. Results: The filter parameters, which did not change the median MK value, but reduced the variability and significantly homogenized the MK values in tumor and normal tissues in both basic and clinical studies, were identified. In the receiver operating characteristic curve analysis for distinguishing tumors from normal tissues using MK values, the area under curve values significantly improved from 0.627 without filters to 0.641 with G (σ = 0.5) and 0.638 with M (radius = 0.5). Conclusions: Thus, image pretreatment with G and M for SDI was shown to be useful for improving tumor diagnosis in clinical practice.

[Examination of Reacquisition Mode in Readout-segmented EPI during the Body Motion].

Readout-segmented echo planar imaging has a reacquisition mode in case of body motion. The phantom was moved and imaged to characterize the reacquisition mode. The counts, angle, and terms of continuous body motion and the terms and counts of intermittent body motion were changed. Then, we investigated the effect on the image quality and the improvement effect of the reacquisition mode. We compared the signal intensity of each pixel in images without body motion and images with and without the reacquisition mode using Spearman's correlation coefficient. The correlation coefficient decreased with increasing counts of body motion. There was no difference by angle. The correlation coefficient was high for body motion immediately after the start of imaging and decreased thereafter. The correlation coefficient was high when the counts of body motion were decreased and even when the terms of body motion increased. In all cases, the correlation coefficient was improved by the reacquisition mode.

Evaluation of calculation processes of apparent diffusion coefficient subtraction method (ASM) imaging.

A number of restricted diffusion (RD) imaging techniques, such as diffusion kurtosis (DK) imaging and Q space imaging, have been developed and proven to be useful for the diagnosis of diseases, including cerebral gliomas and cerebrovascular infarction. In particular, apparent diffusion coefficient (ADC) subtraction method (ASM) imaging has become available recently as a novel RD imaging technique. ASM is based on the difference between the ADC values in an image pair of two ADC maps, ADC basic (ADCb) and ADC modify (ADCm), which are created from diffusion-weighted images taken using short and long effective diffusion times, respectively. The present study aimed to assess the potential of different types of ASM imaging by comparing them with DK imaging which is the gold-standard RD imaging technique. In the present basic study using both polyethylene glycol phantom and cell-containing bio-phantom, three different types of ASM images were created using different calculation processes. ASM/A is an image calculated by dividing the absolute difference between ADCb and ADCm by ADCb several times. By contrast, ASM/S is an image created by dividing the absolute difference between ADCb and ADCm by the standard deviation of ADCb several times. As for positive ASM/A image (PASM/A), the positive image, which was resultant after subtracting ADCb from ADCm, was divided by ADCb several times. A comparison was made between the types of ASM and DK images. The results showed the same tendency between ASM/A in addition to both ASM/S and PASM/A. By increasing the number of divisions by ADCb from three to five times, ASM/A images transformed from DK-mimicking to more RD-sensitive images compared with DK images. These observations suggest that ASM/A images may prove useful for future clinical applications in RD imaging protocols for the diagnosis of diseases.

Development of a novel phantom using polyethylene glycol for the visualization of restricted diffusion in diffusion kurtosis imaging and apparent diffusion coefficient subtraction method.

The present study aimed to investigate whether polyethylene glycol (PEG) phantoms have the potential to be used as standard phantoms for magnetic resonance imaging (MRI) in order to visualize restricted diffusion in diffusion kurtosis imaging (DKI), the ADC subtraction method (ASM) and the apparent diffusion coefficient (ADC). Diffusion-weighted images of 0-120 mM PEG phantoms were captured to create ADC, DKI and ASM images with post-processing. ASM is a recently developed method for restricted diffusion imaging using the readout segmentation of long variable echo-train sequences. As the PEG concentration increases, the ADC value decreases. Conversely, an increase in DKI and ASM values is associated with increasing PEG concentration. Formulae were constructed to represent the association between PEG concentrations and ADC, DKI and ASM values. These formulae can be used to determine the required PEG concentrations to mimic arbitrary ADC, DKI and ASM values of certain diseases, including tumors and infarctions. Validation experiments were conducted using bio-phantoms and clarified that the PEG phantoms cover the range of ADC and DKI values reported in previous clinical research using 3T MRI. PEG phantoms may be useful for future MRI research involving restricted diffusion.

Development of a novel method for visualizing restricted diffusion using subtraction of apparent diffusion coefficient values.

In order to visualize restricted diffusion, the present study developed a novel method called 'apparent diffusion coefficient (ADC) subtraction method (ASM)' and compared it with diffusion kurtosis imaging (DKI). The diffusion-weighted images of physiological saline, in addtion to bio-phatoms of low cell density and the highest cell density were obtained using two sequences with different effective diffusion times. Then, the calculated ADC values were subtracted. The mean values and standard deviations (SD) of the ADC values of physiological saline, low cell density and the highest cell density phantoms were 2.95±0.08x10­3, 1.90±0.35x10­3 and 0.79±0.05x10­3 mm2/sec, respectively. The mean kurtosis values and SD of DKI were 0.04±0.01, 0.44±0.13 and 1.27±0.03, respectively. The ASM and SD values were 0.25±0.20x104, 0.51±0.41x104 and 4.80±4.51x104 (sec/mm2)2, respectively. Using bio­phantoms, the present study demonstrated that DKI exhibits restricted diffusion in the extracellular space. Similarly, ASM may reflect the extent of restricted diffusion in the extracellular space.