Ajania pacifica (Nakai) K. Bremer and Humphries Extract Limits MYC Expression to Induce Apoptosis in Diffuse Large B Cell Lymphoma.

The proto-oncogene MYC is frequently dysregulated in patients with diffuse large B-cell lymphoma (DLBCL) and plays a critical role in disease progression. To improve the clinical outcomes of patients with DLBCL, the development of strategies to target MYC is crucial. The use of medicinal plants for developing anticancer drugs has garnered considerable attention owing to their diverse mechanisms of action. In this study, 100 plant extracts of flora from the Republic of Korea were screened to search for novel agents with anti-DLBCL effects. Among them, Ajania pacifica (Nakai) K. Bremer and Humphries extract (APKH) efficiently suppressed the survival of DLBCL cells, while showing minimal toxicity toward normal murine bone marrow cells. APKH suppressed the expression of anti-apoptotic BCL2 family members, causing an imbalance between the pro-apoptotic and anti-apoptotic BCL2 members. This disrupted mitochondrial membrane potential, cytochrome c release, and pro-caspase-3 activation and eventually led to DLBCL cell death. Importantly, MYC expression was markedly downregulated by APKH and ectopic expression of MYC in DLBCL cells abolished the pro-apoptotic effects of APKH. These results demonstrate that APKH exerts anti-DLBCL effects by inhibiting MYC expression. Moreover, when combined with doxorubicin, an essential component of the CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone), APKH synergistically enhanced the therapeutic effect of doxorubicin. This indicates that APKH may overcome drug resistance, which is common in patients with refractory/relapsed DLBCL. To identify compounds with anti-DLBCL activities in APKH, the chemical profile analysis of APKH was performed using UPLC-QTOF/MSe analysis and assessed for its anticancer activity. Based on the UPLC-QTOF/MSe chemical profiling, it is conceivable that APKH may serve as a novel agent targeting MYC and sensitizing drug-resistant DLBCL cells to CHOP chemotherapy. Further studies to elucidate how the compounds in APKH exert tumor-suppressive role in DLBCL are warranted.

Measurement and evaluation of specific absorption rate and temperature elevation caused by an artificial hip joint during MRI scanning.

A primary safety concern in a magnetic resonance imaging environment is heating of metallic implants by absorbing radiofrequency (RF) energy during MRI scanning. Experimental measurement in conjunction with computational modeling was used to evaluate the risk of biological tissue injury from the RF heating of artificial hip joints by obtaining both specific absorption rate (SAR) and temperature elevation at 1.5 T and 3 T MRI systems. Simulation result showed that high SAR and high temperature appeared near both head and tail sections of the artificial hip joints. For five different 1.5 T and 3 T MRI systems, measured temperature location showed that high temperature rises occurred near both head and tail regions of the metallic hip joints. Measured SAR value of 24.6 W/kg and the high temperature rise (= 4.22 °C) occurred in the tail region of the hip joint at 1.5 T, which was higher than the limits for temperature required by the international electrotechnical commission 60601-2-33. We have demonstrated the feasibility of evaluating RF heating of metallic hip joints during MRI scans.

Reduction of bias in the evaluation of fractional anisotropy and mean diffusivity in magnetic resonance diffusion tensor imaging using region-of-interest methodology.

Accurate quantification of fractional anisotropy (FA) and mean diffusivity (MD) in MR diffusion tensor imaging (DTI) requires adequate signal-to-noise ratio (SNR) especially in low FA areas of the brain, which necessitates clinically impractical long image acquisition times. We explored a SNR enhancement strategy using region-of-interest (ROI)-based diffusion tensor for quantification. DTI scans from a healthy male were acquired 15 times and combined into sets with different number of signal averages (NSA = 1-4, 15) at one 1.5-T Philips and three 3-T (Philips, Siemens and GE) scanners. Equivalence test was performed to determine NSA thresholds for bias-free FA and MD quantifications by comparison with reference values derived from images with NSA = 15. We examined brain areas with low FA values including caudate nucleus, globus pallidus, putamen, superior temporal gyrus, and substructures within thalamus (lateral dorsal, ventral anterior and posterior nuclei), where bias-free FA is difficult to obtain using a conventional approach. Our results showed that bias-free FA can be obtained with NSA = 2 or 3 in some cases using ROI-based analysis. ROI-based analysis allows reliable FA and MD quantifications in various brain structures previously difficult to study with clinically feasible data acquisition schemes.

Correcting B0 Field Distortions in MRI Caused by Stainless Steel Orthodontic Appliances at 1.5 T Using Permanent Magnets - A Head Phantom Study.

Susceptibility artifacts caused by stainless steel orthodontic appliances (braces) pose significant challenges in clinical brain MRI examinations. We introduced field correction device (FCD) utilizing permanent magnets to cancel the induced B0 inhomogeneity and mitigate geometric distortions in MRI. We evaluated a prototype FCD using a 3D-printed head phantom in this proof of concept study. The phantom was compartmented into anterior frontal lobe, temporal lobe, fronto-parieto-occipital lobe, basal ganglia and thalami, brain stem, and cerebellum and had built-in orthogonal gridlines to facilitate the quantification of geometric distortions and volume obliterations. Stainless steel braces were mounted on dental models of three different sizes with total induced magnetic moment 0.15 to 0.17 A·m2. With braces B0 standard deviation (SD) ranged from 2.8 to 3.7 ppm in the temporal and anterior frontal lobes vs. 0.2 to 0.3 ppm without braces. The volume of brain regions in diffusion weighted imaging was obliterated by 32-38% with braces vs. 0% without braces in the cerebellum. With the FCD the SD of B0 ranged from 0.3 to 1.2 ppm, and obliterated volume ranged from 0 to 6% in the corresponding brain areas. These results showed that FCD can effectively decrease susceptibility artifacts from orthodontic appliances.

Early detection of neonatal hypoxic-ischemic white matter injury: an MR diffusion tensor imaging study.

The purpose of this study was to compare diffusion tensor metrics in normal age-matched neonates with survivors of hypoxic-ischemic encephalopathy (HIE) and extracorporeal membrane oxygenation (ECMO). Thirty-five normal, 27 HIE, and 13 ECMO infants underwent MRI at 3 T. Neurodevelopmental assessments were performed. Fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) of the inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, anterior commissure, genu corpus callosum and splenium of the corpus callosum, anterior and posterior limb of the internal capsule, superior longitudinal fasciculus, and the centrum semiovale were analyzed with tract-based spatial statistics modified for use in neonates. Linear regression analysis was performed, and 95% confidence intervals were created for age effects on the tensor metrics with the control patients. Two-sample t-test was done to determine whether there was a difference in the tensor metrics between the normal and patient cohort. There was a statistically significant age effect on the FA and RD in the selected regions of the brain (F<0.05) and a group difference in the FA and RD between the normal and the HIE group (P<0.05). The group difference in the FA and RD between the normal and ECMO groups was seen in the anterior commissure, genu corpus callosum, right inferior longitudinal fasciculus, fronto-occipital fasciculus, centrum semiovale, and superior longitudinal fasciculus (P<0.05). Patients who were outside the 95% confidence intervals of the FA, AD, and RD overlapped with those with abnormalities clinically and on the conventional MRI. In conclusion, diffusion tensor imaging can play a significant role in detecting infants with early indications of hypoxic-ischemic brain injury.

MRI scanner-independent specific absorption rate measurements using diffusion coefficients.

OBJECTIVE: The purpose of this study was to measure specific absorption rate (SAR) during MRI scanning using a human torso phantom through quantification of diffusion coefficients independently of those reported by the scanner software for five 1.5 and 3 T clinical MRI systems from different vendors. METHODS: A quadrature body coil transmitted the RF power and a body array coil received the signals. With diffusion tensor imaging, SAR values for three MRI sequences were measured on the five scanners and compared to the nominal values calculated by the scanners. RESULTS: For the GE 1.5 T MRI system, the MRI scanner-reported SAR value was 1.58 W kg-1 and the measured SAR value was 1.38 W kg-1 . For the Philips 1.5 T MRI scanner, the MRI system-reported SAR value was 1.48 W kg-1 and the measured value was 1.39 W kg-1 . For the Siemens 3 T MRI system, the reported SAR value was 2.5 W kg-1 and the measured SAR value was 1.96 W kg-1 . For two Philips 3 T MRI scanners, the reported SAR values were 1.5 W kg-1 and the measured values were 1.94 and 1.96 W kg-1 . The percentage differences between the measured and reported SAR values on the GE 1.5 T, Philips 1.5 T, Siemens 3 T, and Philips 3 T were 13.5, 6.3, 24.2, 25.6, and 26.6% respectively. CONCLUSION: The scanner-independent SAR measurements using diffusion coefficients described in this study can play a significant role in estimating accurate SAR values as a standardized method.

Assessment of diffusion tensor image quality across sites and vendors using the American College of Radiology head phantom.

The purpose of this study was to explore the feasibility of assessing quality of diffusion tensor imaging (DTI) from multiple sites and vendors using American College of Radiology (ACR) phantom. Participating sites (Siemens (n = 2), GE (n= 2), and Philips (n = 4)) reached consensus on parameters for DTI and used the widely available ACR phantom. Tensor data were processed at one site. B0 and eddy current distortions were assessed using grid line displacement on phantom Slice 5; signal-to-noise ratio (SNR) was measured at the center and periphery of the b = 0 image; fractional anisotropy (FA) and mean diffusivity (MD) were assessed using phantom Slice 7. Variations of acquisition parameters and deviations from specified sequence parameters were recorded. Nonlinear grid line distortion was higher with linear shimming and could be corrected using the 2nd order shimming. Following image registration, eddy current distortion was consistently smaller than acquisi-tion voxel size. SNR was consistently higher in the image periphery than center by a factor of 1.3-2.0. ROI-based FA ranged from 0.007 to 0.024. ROI-based MD ranged from 1.90 × 10-3 to 2.33 × 10-3 mm2/s (median = 2.04 × 10-3 mm2/s). Two sites had image void artifacts. The ACR phantom can be used to compare key qual-ity measures of diffusion images acquired from multiple vendors at multiple sites.

Diffusion tensor imaging metrics in neonates-a comparison of manual region-of-interest analysis vs. tract-based spatial statistics.

BACKGROUND: Diffusion tensor data can be analyzed using region-of-interest (ROI) analysis and tract-based spatial statistics (TBSS). There is essentially no literature validating or comparing these techniques in the neonate. OBJECTIVE: The purpose of this study was to perform a direct comparison of fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) derived using manual ROI analysis and TBSS modified for use in neonates. MATERIALS AND METHODS: This study was IRB-approved. Thirty-nine infants, 32-49 weeks post-conception age, underwent MRI at 3 T. FA, AD and RD of the callosal genu (CG) and splenium (CS) and posterior limbs of both internal capsules (PLIC) were determined using both techniques. Pearson correlation (r) was used to estimate the concordance of tensor metrics derived from these techniques. RESULTS: The r value for FA in the CG, CS and left and right PLIC was 0.88, 0.75, 0.78 and 0.35, respectively. The r value for axial/radial diffusivity in the CG, CS and left and right PLIC was 0.62/0.72, 0.76/0.64, 0.68/0.9 and 0.3/0.72, respectively. The variable concordance results from problems with spatial correspondence of ROI masks between the native space and the FA skeleton. CONCLUSION: Direct comparison between these methodologies shows tensor metrics varied with location and by degree, suggesting the two techniques do not provide consistently comparable results.

Minimum SNR and acquisition for bias-free estimation of fractional anisotropy in diffusion tensor imaging - a comparison of two analytical techniques and field strengths.

Although it is known that low signal-to-noise ratio (SNR) can affect tensor metrics, few studies reporting disease or treatment effects on fractional anisotropy (FA) report SNR; the implicit assumption is that SNR is adequate. However, the level at which low SNR causes bias in FA may vary with tissue FA, field strength and analytical methodology. We determined the SNR thresholds at 1.5 T vs. 3 T in regions of white matter (WM) with different FA and compared FA derived using manual region-of-interest (ROI) analysis to tract-based spatial statistics (TBSS), an operator-independent whole-brain analysis tool. Using ROI analysis, SNR thresholds on our hardware-software magnetic resonance platforms were 25 at 1.5 T and 20 at 3 T in the callosal genu (CG), 40 at 1.5 and 3 T in the anterior corona radiata (ACR), and 50 at 1.5 T and 70 at 3 T in the putamen (PUT). Using TBSS, SNR thresholds were 20 at 1.5 T and 3 T in the CG, and 35 at 1.5 T and 40 at 3 T in the ACR. Below these thresholds, the mean FA increased logarithmically, and the standard deviations widened. Achieving bias-free SNR in the PUT required at least nine acquisitions at 1.5 T and six acquisitions at 3 T. In the CG and ACR, bias-free SNR was achieved with at least three acquisitions at 1.5 T and one acquisition at 3 T. Using diffusion tensor imaging (DTI) to study regions of low FA, e.g., basal ganglia, cerebral cortex, and WM in the abnormal brain, SNR should be documented. SNR thresholds below which FA is biased varied with the analytical technique, inherent tissue FA and field strength. Studies using DTI to study WM injury should document that bias-free SNR has been achieved in the region of the brain being studied as part of quality control.

Magnetic resonance thermal imaging combined with SMASH navigators in the presence of motion.

This study develops and tests an MR thermometry method combined with SMASH navigators in phantom experiments mimicking human liver motion with the purpose of detecting and correcting motion artifacts in thermal MR images. Experimental data were acquired on a 3T MRI scanner. Motion artifacts of mobile phantoms mimicking human liver motion were detected and corrected using the SMASH navigators and then MR temperature maps were obtained using a proton resonant frequency (PRF) shift method with complex image subtraction. Temperature acquired by MR thermal imaging was compared to that measured via thermocouples. MR thermal imaging combined with the SMASH navigator technique resulted in accurate temperature maps of the mobile phantoms compared to temperatures measured using the thermocouples. The differences between the obtained and measured temperatures varied from 8.2°C to 14.2°C and 2.2°C to 4.9°C without and with motion correction, respectively. Motion correction improved the temperature acquired by MR thermal imaging by > 55%. The combination of the MR thermal imaging and SMASH navigator technique will enable monitoring and controlling heat distribution and temperature change in tissues during thermal therapies and will be a very important tool for cancer treatment in mobile organs.

A quality assurance protocol for diffusion tensor imaging using the head phantom from American College of Radiology.

PURPOSE: To propose a quality assurance procedure for routine clinical diffusion tensor imaging (DTI) using the widely available American College of Radiology (ACR) head phantom. METHODS: Analysis was performed on the data acquired at 1.5 and 3.0 T on whole body clinical MRI scanners using the ACR phantom and included the following: (1) the signal-to-noise ratio (SNR) at the center and periphery of the phantom, (2) image distortion by EPI readout relative to spin echo imaging, (3) distortion of high-b images relative to the b= 0 image caused by diffusion encoding, and (4) determination of fractional anisotropy (FA) and mean diffusivity (MD) measured with region-of-interest (ROI) and pixel-based approaches. Reproducibility of the measurements was assessed by five repetitions of data acquisition on each scanner. RESULTS: The SNR at the phantom center was approximately half of that near the periphery at both 1.5 and 3 T. The image distortion by the EPI readout was up to 7 mm at 1.5 T and 10 mm at 3 T. The typical distortion caused by eddy currents from diffusion encoding was on the order of 0.5 mm. The difference between ROI-based and pixel-based MD quantification was 1.4% at 1.5 T and 0.3% at 3 T. The ROI-based MD values were in close agreement (within 2%) with the reference values. The ROI-based FA values were approximately a factor of 10 smaller than pixel-based values and less than 0.01. The measurement reproducibility was sufficient for quality assurance (QA) purposes. CONCLUSIONS: This QA approach is simple to perform and evaluates key aspects of the scanner performance for DTI data acquisition using a widely available phantom.

Age-related variations in white matter anisotropy in school-age children.

BACKGROUND: Determination of diffusion tensor metrics in typically developing school-age children shows that maturational increases in fractional anisotropy (FA) vary across the brain and that age effects on FA are to increases in axial diffusivity in some regions, to decreases in radial diffusivity in some, and to both increases in axial and decreases in radial diffusivity in others. OBJECTIVE: When studying developing white matter (WM) using diffusion tensor imaging (DTI), knowledge of age-related normative tensor metrics is important, as normal variations can mask or mimic disease effects. MATERIALS AND METHODS: Right-handed English-speaking children (n = 32) 6-18 years old (mean 11.0) were studied over 31 months, 7 longitudinally. Anisotropy data were analyzed using tract-based spatial statistics; 43 regions showing significant (P < 0.05) age effects on fractional anisotropy (FA) were analyzed for age effects (r), coefficient of variability (CV), and FA, axial and radial diffusivity. This study was IRB-approved. RESULTS: The callosal genu and splenium showed the highest FA values, smallest age effects, and lowest between-subject variability. Mean FA was lower and age effects were greatest in the dorsal callosal body. The highest age effects on FA were in the cingulum, centrum semiovale, right corticospinal tract, and right temporal WM. The dorsal callosal body, calcarine WM, superior frontal and temporal gyri, and right corticospinal tract showed the highest CV. Radial diffusivity decreased while axial diffusivity increased in the cingulum, decreased in the optic tracts, and showed minimal or no age effects in most other regions. CONCLUSION: Age effects on FA and variability in FA are location-dependant in developing WM.

Magnetic resonance temperature mapping of microwave-fried chicken fingers.

The main objective of this study was to compare the heating patterns of chicken fingers deep-fried conventionally and using a microwave. Two dimensional internal temperature maps of fried chicken fingers with rectangular geometry were measured post frying using magnetic resonance imaging (MRI). Frying was performed in a microwave oven at 365 W power level for 0.5 and 1.5 min after bringing the oil temperature to 180 +/- 1 degrees C. Samples were also fried in a conventional fryer at 180 degrees C for 2 and 5 min for comparison. Variations in internal temperature distribution increased proportionally to frying time in both microwave and conventional frying. Internal thermal equilibrium is reached in all samples after 13 min of holding time. Internal structural changes, void formation, were also visualized in the images. Void formation did not significantly impact cooling rates.