A Mathematical Model for Predicting Patient Responses to Combined Radiotherapy with CTLA-4 Immune Checkpoint Inhibitors.

The purpose of this study was to develop a cell-cell interaction model that could predict a tumor's response to radiotherapy (RT) combined with CTLA-4 immune checkpoint inhibition (ICI) in patients with hepatocellular carcinoma (HCC). The previously developed model was extended by adding a new term representing tremelimumab, an inhibitor of CTLA-4. The distribution of the new immune activation term was derived from the results of a clinical trial for tremelimumab monotherapy (NCT01008358). The proposed model successfully reproduced longitudinal tumor diameter changes in HCC patients treated with tremelimumab (complete response = 0%, partial response = 17.6%, stable disease = 58.8%, and progressive disease = 23.6%). For the non-irradiated tumor control group, adding ICI to RT increased the clinical benefit rate from 8% to 32%. The simulation predicts that it is beneficial to start CTLA-4 blockade before RT in terms of treatment sequences. We developed a mathematical model that can predict the response of patients to the combined CTLA-4 blockade with radiation therapy. We anticipate that the developed model will be helpful for designing clinical trials with the ultimate aim of maximizing the efficacy of ICI-RT combination therapy.

Neurodegenerative Changes in the Brains of the 5xFAD Alzheimer's Disease Model Mice Investigated by High-Field and High-Resolution Magnetic Resonance Imaging and Multi-Nuclei Magnetic Resonance Spectroscopy.

This study aimed to investigate morphological and metabolic changes in the brains of 5xFAD mice. Structural magnetic resonance imaging (MRI) and 1H magnetic resonance spectroscopy (MRS) were obtained in 10- and 14-month-old 5xFAD and wild-type (WT) mice, while 31P MRS scans were acquired in 11-month-old mice. Significantly reduced gray matter (GM) was identified by voxel-based morphometry (VBM) in the thalamus, hypothalamus, and periaqueductal gray areas of 5xFAD mice compared to WT mice. Significant reductions in N-acetyl aspartate and elevation of myo-Inositol were revealed by the quantification of MRS in the hippocampus of 5xFAD mice, compared to WT. A significant reduction in NeuN-positive cells and elevation of Iba1- and GFAP-positive cells supported this observation. The reduction in phosphomonoester and elevation of phosphodiester was observed in 11-month-old 5xFAD mice, which might imply a sign of disruption in the membrane synthesis. Commonly reported 1H MRS features were replicated in the hippocampus of 14-month-old 5xFAD mice, and a sign of disruption in the membrane synthesis and elevation of breakdown were revealed in the whole brain of 5xFAD mice by 31P MRS. GM volume reduction was identified in the thalamus, hypothalamus, and periaqueductal gray areas of 5xFAD mice.

Quantitative Assessment of the Restoration of Original Anatomy after 3D Virtual Reduction of Long Bone Fractures.

Background: The purpose of this study was to demonstrate the usefulness of 3D image-based virtual reduction by validating the evaluation criteria according to guidelines suggested by the AO Surgery Reference. Methods: For this experiment, 19 intact radial ORTHObones (ORTHObones radius, 3B Scientific, Germany, Hamburg) without any fractures were prepared. All ORTHObones with six cortical marking holes (three points on the distal part and three points on the proximal part) were scanned using a CT scanner twice (before/after intentional fracture of the ORTHObone). After the virtual reduction of all 19 ORTHObones, accuracy evaluations using the four criteria (length variation, apposition variation, alignment variation, Rotation Variation) suggested in the AO Surgery Reference were performed. Results: The mean (M) length variation was 0.42 mm, with 0.01 mm standard deviation (SD). The M apposition variation was 0.48 mm, with 0.40 mm SD. The M AP angulation variation (for alignment variation) was 3.24°, with 2.95° SD. The M lateral angulation variation (for alignment variation) was 0.09°, with 0.13° SD. The M angle of axial rotation was 1.27° with SD: 1.19°. Conclusions: The method of accuracy evaluation used in this study can be helpful in establishing a reliable plan.

Fabrication and evaluation of bilateral Helmholtz radiofrequency coil for thermo-stable breast image with reduced artifacts.

PURPOSE: The positron emission tomography (PET)-magnetic resonance (MR) system is a newly emerging technique that yields hybrid images with high-resolution anatomical and metabolic information. With PET-MR imaging, a definitive diagnosis of breast abnormalities will be possible with high spatial accuracy and images will be acquired for the optimal fusion of anatomic locations. Therefore, we propose a PET-compatible two-channel breast MR coil with minimal disturbance to image acquisition which can be used for simultaneous PET-MR imaging in patients with breast cancer. MATERIALS AND METHODS: For coil design and construction, the conductor loops of the Helmholtz coil were tuned, matched, and subdivided with nonmagnetic components. Element values were optimized with an electromagnetic field simulation. Images were acquired on a GE 600 PET-computed tomography (CT) and GE 3.0 T MR system. For this study, we used the T1-weighted image (volunteer; repetition time (TR), 694 ms; echo time (TE), 9.6 ms) and T2-weighted image (phantom; TR, 8742 ms; TE, 104 ms) with the fast spin-echo sequence. RESULTS: The results of measuring image factors with the proposed radiofrequency (RF) coil and standard conventional RF coil were as follows: signal-to-noise ratio (breast; 207.7 vs. 175.2), percent image uniformity (phantom; 89.22%-91.27% vs. 94.63%-94.77%), and Hounsfield units (phantom; -4.51 vs. 2.38). CONCLUSIONS: Our study focused on the feasibility of proposed two-channel Helmholtz loops (by minimizing metallic components and soldering) for PET-MR imaging and found the comparable image quality to the standard conventional coil. We believe our work will help significantly to improve image quality with the development of a less metallic breast MR coil.

Development of a new advanced animal cradle for small animal multiple imaging modalities: acquisition and evaluation of high-throughput multiple-mouse imaging.

The physiological conditions of small animals are an essential component to be considered when acquiring images for pre-clinical studies, and they play a vital role in the overall results of a study. However, several previous studies did not consider these conditions. In this study, a new animal cradle that can be modified and adjusted to suit multiple imaging modalities such as positron emission tomography (PET)/computed tomography (CT) and magnetic resonance imaging (MRI) was developed. Unlike previous cradles where only one mouse can be imaged at a time, a total of four mice can be imaged simultaneously using this new cradle. Additionally, fusion images with high-throughput multiple-mouse imaging (MMI) of PET/MRI and PET/CT images can be acquired using this newly developed cradle. The dynamic brain images were also acquired simultaneously by applying PET dynamic imaging technology to high-throughput MMI methods. The results of this study suggest that the newly developed small animal cradle can be widely used in pre-clinical studies.

An in vivo proton magnetic resonance spectroscopy study with optimized echo-time technique for concurrent quantification and T2 measurement targeting glutamate in the rat brain.

OBJECTIVE: The present study applied in vivo proton magnetic resonance spectroscopy (1H MRS) to concurrently measure the concentration and T2 relaxation time of glutamate with the concept of optimized-for-quantification-and-T2-measurement-of-glutamate (OpQT2-Glu). MATERIALS AND METHODS: 7T MRS scans of the OpQT2-Glu were acquired from the prefrontal cortex of five rats. The echo-time-(TE)-specific J-modulation of glutamate was investigated by spectral simulations and analyses for selecting the eight TEs appropriate for T2 estimation of glutamate. The OpQT2-Glu results were compared to those of the typical short-TE MRS and T2 measurements. RESULTS: No significant differences were observed between the OpQT2-Glu and typical short-TE MRS (p > 0.050). The estimated glutamate T2 (67.75 ms) of the OpQT2-Glu was similar to the multiple TE MRS for the T2 measurement (71.58 ms) with enhanced signal-to-noise ratio and reliability. DISCUSSION: The results revealed that the quantification reliability of the OpQT2-Glu was comparable to that of the single short-TE MRS and its estimation reliability for the T2 relaxation time of glutamate was enhanced compared to the multiple TE MRS for T2 measurement. Despite certain limitations, the quantification and T2 estimation of glutamate can be concurrently performed within an acceptable scan time via high-field in vivo 1H MRS with the OpQT2-Glu.

Development of a hybrid magnetic resonance/computed tomography-compatible phantom for magnetic resonance guided radiotherapy.

The purpose of the present study was to develop a hybrid magnetic resonance/computed tomography (MR/CT)-compatible phantom and tissue-equivalent materials for each MR and CT image. Therefore, the essential requirements necessary for the development of a hybrid MR/CT-compatible phantom were determined and the development process is described. A total of 12 different tissue-equivalent materials for each MR and CT image were developed from chemical components. The uniformity of each sample was calculated. The developed phantom was designed to use 14 plugs that contained various tissue-equivalent materials. Measurement using the developed phantom was performed using a 3.0-T scanner with 32 channels and a Somatom Sensation 64. The maximum percentage difference of the signal intensity (SI) value on MR images after adding K2CO3 was 3.31%. Additionally, the uniformity of each tissue was evaluated by calculating the percent image uniformity (%PIU) of the MR image, which was 82.18 ±1.87% with 83% acceptance, and the average circular-shaped regions of interest (ROIs) on CT images for all samples were within ±5 Hounsfield units (HU). Also, dosimetric evaluation was performed. The percentage differences of each tissue-equivalent sample for average dose ranged from -0.76 to 0.21%. A hybrid MR/CT-compatible phantom for MR and CT was investigated as the first trial in this field of radiation oncology and medical physics.

Analysis of ovarian volume of Korean children and adolescents at magnetic resonance imaging.

BACKGROUND: Knowledge of ovarian volume is important for diagnostic evaluations; however, normal ovarian volume studies on children and adolescents are lacking. OBJECTIVE: This study aimed to analyze age-specific ovarian volume and identify the diverse factors that contribute to ovarian diagnoses. MATERIALS AND METHODS: We retrospectively enrolled 180 patients (0-18 years of age) with normal ovaries who underwent magnetic resonance imaging (MRI) between 2010 and 2018. MRI sequences included coronal and axial T2-weighted turbo spin echo (TSE) images and coronal T1-weighted TSE images. Ovarian volume was calculated by the standard ellipsoid formula. Age-specific ovarian volume, height, weight, height-adjusted total ovarian volume and body mass index were obtained. Linear regression analysis was used to predict ovarian volume. RESULTS: Six age groups (infant; early and late child, and early, middle and late adolescent) were described. The early adolescent group (10-12 years) had the highest rate of increase. In the middle adolescent period (13-15 years), the curve of ovarian volume appeared flat. CONCLUSION: Our findings provide age-specific references for ovarian volume.

Metal artifacts with dental implants: Evaluation using a dedicated CT/MR oral phantom with registration of the CT and MR images.

The aims of this study were to develop a computed tomography/magnetic resonance (CT/MR) oral phantom with insertable dental implants and to register CT/MR images to generate artifact-free MR images for patients undergoing teeth restorations. All measurements were done using a human MR scanner with spin echo (SE) and gradient echo (GRE) sequences image scan together with CT image. The metal regions and normal teeth parts are extracted with a suitable threshold from an initial image reconstructed with artifact from the CT images. Corrected metal projection regions of MR images and CT images are fused to produce artifact-free MR image that include dental restorations. After CT/MR registration, artifact size presented differences on the x- (SE, 12.0 mm; GRE, 18.0 mm) and y- (SE, 24.0 mm; GRE, 36.6 mm). When comparing the dental restoration with normal teeth, the structural similarity index metric (SSIM) of GRE 50 was lower than for the GRE 8 sequence and the SSIM of SE 145 shown higher than for the SE 490 sequence. The dedicated phantom provides a useful tool in head and neck research for multi-modality images. Therefore, CT/MR image-based approach for ground truth and registration offers visualization in diagnostic system and radiation treatment planning system.

Investigating the metabolic alterations in a depressive-like rat model of chronic forced swim stress: An in vivo proton magnetic resonance spectroscopy study at 7T.

Although recent investigations of major depressive disorder (MDD) have focused on the monoaminergic system, accumulating evidences suggest that alternative pathophysiological models of MDD and treatment options for patients with MDD are needed. Animals subjected to chronic forced swim stress (CFSS) develop behavioral despair. The purpose of this study was to investigate the in vivo effects of CFSS on systems other than the monoamine system in the rat prefrontal cortex (PFC) with 7T and short-echo-time (16.3 ms) proton magnetic resonance spectroscopy (1H MRS). Ten male Wistar rats underwent 14 days of CFSS, and in vivo1H MRS and forced swim tests were performed before and after CFSS. Point-resolved spectroscopy was used to quantify metabolite levels in the rat PFC. To investigate spectral overlap in glutamate and glutamine, spectral analyses in the spectra obtained in the in vivo1H MRS, parametrically matched spectral simulation, and in vitro experiments were performed. The results of the spectral analyses showed that the glutamate/glutamine spectral overlap was not critical, which suggested that in vivo1H MRS can be used to reliably assess the glutamate system. The rats showed significantly increased immobility times and decreased climbing times in the FST after CFSS, which suggested that the rats developed behavioral despair. The pre-CFSS and post-CFSS glutamate and glutamine levels did not significantly differ (p > 0.050). The levels of myo-inositol, total choline, and N-acetylaspartate, myo-inositol/creatine, and total choline/creatine increased significantly (p < 0.050). Similar findings have been reported in patients with MDD. Taken together, these results suggest that the CFSS-induced metabolic alterations were similar to those found in patients and that high-field and short-echo-time in vivo1H MRS can be used to investigate depression-induced metabolic alterations. Such investigations might provide alternative insights into the nonmonoaminergic pathophysiology and treatment of depression.

Metabolic effects of light deprivation in the prefrontal cortex of rats with depression-like behavior: In vivo proton magnetic resonance spectroscopy at 7T.

Recent evidence suggests that the glutamate system plays an important role in the pathogenesis of major depressive disorder (MDD). The aim of this study was to investigate the effects of light deprivation (LD) in the prefrontal cortex (PFC) of animals with depression-like behavior, targeting the glutamate system, using in vivo proton magnetic resonance spectroscopy (1H MRS). Male Sprague-Dawley rats were housed in constant darkness for six weeks (n = 12; LD group), while controls (n = 8) were housed under normal light cycles. The animals were assessed with forced swim tests. Point-resolved spectroscopy was used to quantify metabolite levels in the PFC. To substantiate the validity of the use of in vivo1H MRS in this study, the spectra obtained in the in vivo1H MRS, parametrically matched spectral simulation, and in vitro experiments were analyzed. The results of the spectral analyses showed that the quantification of glutamate and glutamine was not significantly affected by spectral overlaps. Thus, these results suggested that in vivo1H MRS can be used to reliably investigate the glutamate system. The results of the forced swim test showed LD-induced behavioral despairs in the animals. The levels of glutamate, myo-inositol, phosphocreatine, and total creatine were found significantly (p < 0.010) increased in the PFC of the LD animals compared with the controls. These results suggested that the LD-induced metabolic changes were consistent with the previous findings in patients with MDD and that short-echo-time in vivo1H MRS can be used to effectively measure depression-induced alterations in glutamate systems.

Improved quantitative fatty acid values with correction of T2 relaxation time in terminal methyl group: In vivo proton magnetic resonance spectroscopy at ultra high field in hepatic steatosis.

Proton magnetic resonance spectroscopy (MRS) with optimized relaxation time is an effective method to quantify hepatic fatty acid values and characterize steatosis. The aim of this study is to quantify the difference in hepatic lipid content with metabolic changes during the progression of steatosis by using localized MRS sequence with T2 relaxation time determination. Fatty liver disease was induced in C57BL/6N mice through a high-fat diet (HFD) of pellets containing 60% fat, 20% protein, and 20% carbohydrates. We used stimulated echo acquisition mode (repetition time: 3500 ms; mixing time: 10 ms; echo time: 20 ms) sequence. Using enhanced and mono exponential curve-fitting methods, the lipid relaxation time in mice was estimated at a fixed repetition time of 5000 ms and echo time ranging from 20 to 70 ms. The calculated lipid contents with incorrect and correct relaxation times were as follows: total saturated fatty acid (4.00 ±â€¯2.90 vs 6.74 ±â€¯2.25, p < 0.05 at week 0; 15.23 ±â€¯9.94 vs 25.53 ±â€¯10.49, p < 0.05 at week 4); total unsaturated fatty acid (0.40 ±â€¯0.49 vs 0.56 ±â€¯0.47, p < 0.05 at week 4; 0.33 ±â€¯0.26 vs 0.60 ±â€¯0.21, p < 0.01 at week 7); total unsaturated bond (0.48 ±â€¯0.52 vs 1.05 ±â€¯0.58, p < 0.05 at week 10). Furthermore, we determined that the correct relaxation times of triglycerides between 0 and 10 weeks were significantly altered in the resonances (∼2.03 ppm: 31.07 ±â€¯1.00 vs 27.62 ±â€¯1.20, p < 0.01; ∼2.25 ppm: 29.10 ±â€¯1.52 vs 26.39 ±â€¯1.08, p < 0.05; ∼2.78 ppm: 37.67 ±â€¯2.92 vs 29.37 ±â€¯2.64, p < 0.001). The work presented focused on the significance of the J-coupling effect. The selection of an appropriate relaxation time considering the J-coupling effect provides an effective method for quantifying lipid contents and characterizing hepatic steatosis.

High-fat diet-induced hyperglutamatergic activation of the hippocampus in mice: A proton magnetic resonance spectroscopy study at 9.4T.

The aim of this study was to investigate the long-term neurochemical alterations in the hippocampus of mice fed a high-fat diet (HFD) while plasma leptin and corticosterone levels were monitored. Although metabolic disturbances induced by the excess intake of fat are assumed to cause depression, the relationship underlying dysfunctional adipose tissue, stress hormone release, and excitatory metabolism has not been fully understood yet. Four-week-old male C57BL/6 mice were separated into a HFD-fed group (n = 8) and low-fat diet-fed group (n = 8). Proton magnetic resonance spectroscopy was used to measure the long-term changes in neurochemicals in the hippocampus at 0, 5, and 10 weeks and blood samples were taken at the same time to assess plasma hormones levels. At the end of the experiment, magnetic resonance imaging was performed to quantify abdominal fat accumulation. At 10 weeks, corticosterone and leptin levels were significantly increased in the HFD group compared with the low-fat diet group. In addition, aspartate, glutamate, total choline, and N-acetylaspartic acid levels were significantly increased, but glutamine/glutamate ratios were substantially decreased at 10 weeks in the HFD group. These results were compatible with HFD-induced acute stress responses and changes in N-methyl-d-aspartate receptor-induced plasticity. These findings demonstrated that the long-term ingestion of a HFD induced hyperglutamatergic metabolism and altered glutamine-glutamate cycling. Therfore, it is suggested that hypothalamic-pituitary-adrenal dysfunction and hyperglutamatergic activation in the hippocampus resulting from the HFD.

Decreased Glutamatergic Activity in the Frontal Cortex of Single Prolonged Stress Model: In vivo and Ex Vivo Proton MR Spectroscopy.

Single prolonged stress (SPS) is one of the preclinical models of posttraumatic stress disorder (PTSD) in humans. Not every traumatized person develops PTSD and the onset of the disease varies from months to many years after exposure to life-threatening events. The pathogenetic neurometabolites in PTSD have not been investigated to date, and could provide a means for therapeutic interventions. Therefore the present study aimed to evaluate neurochemical changes in the frontal cortex in the SPS model during time-dependent sensitization using in vivo and ex vivo proton magnetic spectroscopy (1H-MRS). Twenty-one male Sprague-Dawley rats (200-220 g) were randomly assigned into two groups (Control, n = 10; SPS, n = 11). SPS consists of three consecutive stressors (restraint, forced swimming, and ether exposure) followed by 7 days without disturbance. In vivo 1H-MRS scans were conducted at baseline, immediately after SPS, and 3 and 7 days after SPS to quantify time-dependent alterations in the frontal cortex. On day 7, all animals were sacrificed and ex vivo 1H-MRS was performed. After SPS exposure, the SPS group showed signs of excitatory activities (glutamate) and cellular membrane turnover (choline and total choline) for 7 days. After the time-sensitization period, the SPS group showed lower glutamate and creatine levels and higher choline and lactate levels than the control group. These results indicate that SPS induces sustained adaptation of glutamatergic neuronal activity in the frontal cortex. Therefore, we conclude that SPS-induced stress reduces glutamatergic metabolism in the frontal cortex.

Effects of repeated dizocilpine treatment on glutamatergic activity in the prefrontal cortex in an animal model of schizophrenia: An in vivo proton magnetic resonance spectroscopy study at 9.4T.

Repeated exposure to dizocilpine (MK-801) can be used as a model of schizophrenia that incorporates disease progression. Proton magnetic resonance spectroscopy (1H MRS) has been widely used to investigate schizophrenia-related alterations in glutamate (Glu). The purpose of this study was to investigate metabolic alterations in the prefrontal cortex (PFC) in an animal model of schizophrenia by using in vivo 1H MRS. Because of the spectral overlap of Glu and glutamine (Gln), high-field 1H MRS with short echo time (TE) was used. A point-resolved spectroscopy sequence was used to measure the levels of Glu and Gln, and the brain metabolites in a volume of interest (22.5µL) located in the PFC region of rats (n=13) before and after 6days of MK-801 (0.5mg/kg) treatment. Analysis of the spectra showed that the cross-contamination of Glu and Gln can be considered to comparably low. No metabolic parameters were altered (p>0.05). However, differences in Glu and N-acetylaspartate (NAA) levels between two times were significantly correlated (p<0.01). The results showed both decreased (in 6 of the 13 rats) and increased (7 of the 13 rats) levels of Glu and NAA, which suggested that these opposite metabolic alterations reflect two stage of disease progression. The results suggest that high-field and short TE in vivo 1H MRS can quantify Glu and Gln with reliably low level of cross-contamination and that repeated exposure to MK-801 induces the progressive development of schizophrenia.

Glutamine and Glutamate Complex, as Measured by Functional Magnetic Resonance Spectroscopy, Alters During Face-Name Association Task in Patients with Mild Cognitive Impairment and Alzheimer's Disease.

BACKGROUND: The metabolite response during a memory task in Alzheimer's disease (AD) patients is unknown. OBJECTIVE: To investigate the metabolite changes in subjects with AD, amnestic mild cognitive impairment (aMCI), and cognitively normal (CN) elderly during a memory task using functional magnetic resonance spectroscopy (fMRS). METHODS: This study involved 23 young normal controls (YC), 24 CN elderly, 24 aMCI, and 24 mild and probable AD individuals. fMRS data were acquired at the precuneus and posterior cingulate brain regions during a face-name association task. Statistical analyses of quantified metabolites were performed to evaluate differences of the metabolite values between the stimulation conditions and among the four subject groups. Receiver operating curve analysis was performed to evaluate whether the metabolic changes after functional activations can differentiate the subject groups. RESULT: Glutamine and glutamate complex (Glx) was statistically significantly different between the fixation and repeat conditions in aMCI (p = 0.0492) as well as between the fixation and the novel conditions in the AD (p = 0.0412) group. The total N-acetylaspartate (tNAA) was statistically significantly different among the four subject groups in the fixation condition (DF = 3, F = 7.673, p <  0.001), the novel condition (DF = 3, F = 6.945, p <  0.001), and the repeat condition (DF = 3, F = 7.127, p <  0.001). tNAA, tCr, and mIns could be used to differentiate CN from aMCI. Furthermore, tNAA, tCr, Glx, and Glu could also differentiate CN from AD, and aMCI from AD. CONCLUSION: Glx was altered during a stimulation that may be used to evaluate neuronal dysfunction in a demented patient. tNAA and tCr were reduced in patients with AD.

Dosimetric Effects of Magnetic Resonance Imaging-assisted Radiotherapy Planning: Dose Optimization for Target Volumes at High Risk and Analytic Radiobiological Dose Evaluation.

Based on the assumption that apparent diffusion coefficients (ADCs) define high-risk clinical target volume (aCTVHR) in high-grade glioma in a cellularity-dependent manner, the dosimetric effects of aCTVHR-targeted dose optimization were evaluated in two intensity-modulated radiation therapy (IMRT) plans. Diffusion-weighted magnetic resonance (MR) images and ADC maps were analyzed qualitatively and quantitatively to determine aCTVHR in a high-grade glioma with high cellularity. After confirming tumor malignancy using the average and minimum ADCs and ADC ratios, the aCTVHR with double- or triple-restricted water diffusion was defined on computed tomography images through image registration. Doses to the aCTVHR and CTV defined on T1-weighted MR images were optimized using a simultaneous integrated boost technique. The dosimetric benefits for CTVs and organs at risk (OARs) were compared using dose volume histograms and various biophysical indices in an ADC map-based IMRT (IMRTADC) plan and a conventional IMRT (IMRTconv) plan. The IMRTADC plan improved dose conformity up to 15 times, compared to the IMRTconv plan. It reduced the equivalent uniform doses in the visual system and brain stem by more than 10% and 16%, respectively. The ADC-based target differentiation and dose optimization may facilitate conformal dose distribution to the aCTVHR and OAR sparing in an IMRT plan.

Design of a fused phantom for quantitative evaluation of brain metabolites and enhanced quality assurance testing for magnetic resonance imaging and spectroscopy.

BACKGROUND: Magnetic resonance imaging and spectroscopy (MRI-MRS) is a useful tool for the identification and evaluation of chemical changes in anatomical regions. Quality assurance (QA) is performed in either images or spectra using QA phantom. Therefore, consistent and uniform technical MRI-MRS QA is crucial. NEW METHOD: Here we developed an MRI-MRS fused phantom along with the inserts for metabolite quantification to simultaneously optimize QA parameters for both MRI and MRS. T1- and T2-weighted images were obtained and MRS was performed with point-resolved spectroscopy. RESULTS: Using the fused phantom, the results of measuring MRI factors were: geometric distortion, <2% and ± 2 mm; image intensity uniformity, 83.09 ± 1.33%; percent-signal ghosting, 0.025 ± 0.004; low-contrast object detectability, 27.85 ± 0.80. In addition, the signal-to-noise ratio of N-acetyl-aspartate was consistently high (42.00 ± 5.66). COMPARISON WITH EXISTING METHODS: In previous studies, MR phantoms could not obtain information from both images and spectra in the MR scanner simultaneously. Here we designed and developed a phantom for accurate and consistent QA within the acceptance range. It is important to take into account variations in the QA value using the MRI-MRS phantom, when comparing to other clinical or research MR scanners. CONCLUSIONS: The MRI-MRS QA factors obtained simultaneously using the phantom can facilitate evaluation of both images and spectra, and provide guidelines for obtaining MRI and MRS QA factors simultaneously.

In vivo proton magnetic resonance spectroscopy of liver metabolites in non-alcoholic fatty liver disease in rats: T2 relaxation times in methylene protons.

The aim of this study was to evaluate the transverse relaxation time of methylene resonance as compared to other lipid resonances. The examinations were performed using a 3.0 T scanner with a point-resolved spectroscopy (PRESS) sequence. Lipid relaxation time in a lipid phantom filled with canola oil was estimated with a repetition time (TR) of 6000ms and echo time (TE) of 40-550ms. For in vivo proton magnetic resonance spectroscopy ((1)H-MRS), eight male Sprague-Dawley rats were given free access to a normal-chow (NC) and another eight male Sprague-Dawley rats were given free access to a high-fat (HF) diet. Both groups drank water ad libitum. T2 measurements in the rats' livers were conducted at a fixed TR of 6000ms and TE of 40-220ms. Exponential curve fitting quality was calculated through the coefficients of determination (R(2)). Chemical analyses of the phantom and livers were not performed, but T2 decay curves were acquired. The T2 relaxation time of methylene resonance was estimated as follows: NC rats, 37.1±4.3ms; HF rats, 31.4±1.8ms (p<0.05). The extrapolated M0 values were higher in HF rats than in NC rats (p<0.005). This study of (1)H MRS led to sufficient spectral resolution and signal-to-noise ratio differences to characterize the T2 relaxation times of methylene resonance. (1)H MRS relaxation times may be useful for quantitative characterization of various liver diseases, including fatty liver disease.