Quantitative Amyloid Imaging Using Image-Derived Arterial Input Function

Amyloid PET imaging is an indispensable tool widely used in the investigation, diagnosis and monitoring of Alzheimer’s disease (AD). Currently, a reference region based approach is used as the mainstream quantification technique for amyloid imaging. This approach assumes the reference region is amyloid free and has the same tracer influx and washout kinetics as the regions of interest. However, this assumption may not always be valid. The goal of this work is to evaluate an amyloid imaging quantification technique that uses arterial region of interest as the reference to avoid potential bias caused by specific binding in the reference region. 21 participants, age 58 and up, underwent Pittsburgh compound B (PiB) PET imaging and MR imaging including a time-of-flight (TOF) MR angiography (MRA) scan and a structural scan. FreeSurfer based regional analysis was performed to quantify PiB PET data. Arterial input function was estimated based on coregistered TOF MRA using a modeling based technique. Regional distribution volume (V_T) was calculated using Logan graphical analysis with estimated arterial input function. Kinetic modeling was also performed using the estimated arterial input function as a way to evaluate PiB binding (DVR_kinetic) without a reference region. As a comparison, Logan graphical analysis was also performed with cerebellar cortex as reference to obtain DVR_REF. Excellent agreement was observed between the two distribution volume ratio measurements (r>0.89, ICC>0.80). The estimated cerebellum V_T was in line with literature reported values and the variability of cerebellum V_T in the control group was comparable to reported variability using arterial sampling data. This study suggests that image-based arterial input function is a viable approach to quantify amyloid imaging data, without the need of arterial sampling or a reference region. This technique can be a valuable tool for amyloid imaging, particularly in population where reference normalization may not be accurate.     

Maximum-Entropy Three-Dimensional Reconstruction with Deconvolution of the Contrast Transfer Function: A Test Application with Adenovirus

We have developed an objective, quantitative, and general algorithm to improve the fidelity of three-dimensional reconstructions made from electron micrographs while at the same time filtering much of the noise present in the recorded data. The new technique is called constrained maximum entropy tomography (COMET). The essence of the method is that it will produce the most featureless reconstruction that fits the projection data within their observational accuracy. In particular, the COMET procedure will minimise the detrimental effects of errors in the measured data and deconvolute the effects of the contrast transfer function. An objective test has been performed using COMET on a conventional image reconstruction obtained from cryo-electron micrographs of adenovirus. The density for hexon, the major coat protein of the virus, which is known to high resolution from X-ray crystallography, provided a known high-resolution control. The COMET reconstruction is in considerably better agreement with the crystallographic electron density than the original reconstruction, throughout the entire resolution range.     

Dual Energy CT Angiography of Peripheral Arterial Disease: Feasibility of Using Lower Contrast Medium Volume

ObjectiveOne of the main drawbacks associated with Dual Energy Computed Tomography Angiography (DECTA) is the risk of developing contrast medium-induced nephropathy (CIN). The aim of the present study was firstly, to design an optimal CT imaging protocol by determining the feasibility of using a reduced contrast medium volume in peripheral arterial DECTA, and secondly, to compare the results with those obtained from using routine contrast medium volume.MethodsThirty four patients underwent DECTA for the diagnosis of peripheral arterial disease. They were randomly divided into two groups: Group 1 (routine contrast volume group) with n = 17, injection rate 4–5 ml/s, and 1.5 ml/kg of contrast medium, and Group 2 ((low contrast volume group), with n = 17, injection rate 4–5ml/s, and contrast medium volume 0.75 ml/kg. A fast kilovoltage—switching 64-slice CT scanner in the dual-energy mode was employed for the study. A total of 6 datasets of monochromatic images at 50, 55, 60, 65, 70 and 75 keV levels were reconstructed with adaptive statistical iterative reconstruction (ASIR) at 50%. A 4-point scale was the tool for qualitative analysis of results. The two groups were compared and assessed quantitatively for image quality on the basis of signal-to-noise ratio (SNR) and contrast-to-noise-ratio (CNR). Radiation and contrast medium doses were also compared.ResultsThe overall mean CT attenuation and mean noise for all lower extremity body parts was significantly lower for the low volume contrast group (p<0.001), and varied significantly between groups (p = 0.001), body parts (p<0.001) and keVs (p<0.001). The interaction between group body parts was significant with CT attenuation and CNR (p = 0.002 and 0.003 respectively), and marginally significant with SNR (p = 0.047), with minimal changes noticed between the two groups. Group 2 (low contrast volume group) displayed the lowest image noise between 65 and 70 keV, recorded the highest SNR and CNR at 65 keV, and produced significantly lower results with respect to contrast medium volume and duration of contrast injection (p<0.001). The effect of radiation dose was not statistically significant between the two groups.ConclusionsDECTA images created at 65 keV and 50% ASIR with low contrast medium volume protocol, yielded results that were comparable to routine contrast medium volume, with acceptable diagnostic images produced during the evaluation of peripheral arteries.     

Evaluation of Liver Ischemia-Reperfusion Injury in Rabbits Using a Nanoscale Ultrasound Contrast Agent Targeting ICAM-1

ObjectiveTo assess the feasibility of ultrasound molecular imaging in the early diagnosis of liver ischemia-reperfusion injury (IRI) using a nanoscale contrast agent targeting anti-intracellular adhesion molecule-1 (anti-ICAM-1).MethodsThe targeted nanobubbles containing anti-ICAM-1 antibody were prepared using the avidin-biotin binding method. Human hepatic sinusoidal endothelial cells (HHSECs) were cultured at the circumstances of hypoxia/reoxygenation (H/R) and low temperature. The rabbit liver IRI model (I/R group) was established using the Pringle’s maneuver. The time-intensity curve of the liver contrast ultrasonographic images was plotted and the peak intensity, time to peak, and time of duration were calculated.ResultsThe size of the targeted nanobubbles were 148.15 ± 39.75 nm and the concentration was 3.6–7.4 × 10⁹/ml, and bound well with the H/R HHSECs. Animal contrast enhanced ultrasound images showed that the peak intensity and time of duration of the targeted nanobubbles were significantly higher than that of common nanobubbles in the I/R group, and the peak intensity and time of duration of the targeted nanobubbles in the I/R group were also significantly higher than that in the SO group.ConclusionThe targeted nanobubbles have small particle size, stable characteristic, and good targeting ability, which can assess hepatic ischemia-reperfusion injury specifically, noninvasively, and quantitatively at the molecular level.     

Injection of the Arterial System of the Mouse

Cannulation of the aorta of the mouse through an incision in the left ventricle has permitted the introduction of various injection media into the arterial tree. Heparinized mice, sacrificed by ether, were exsanguinated and injected with latex, latex-thorotrast or vinyl acetate. The apparatus consists of a special cannula made by combining a 1 inch segment of a 23 gauge hypodermic needle and fine polyethylene tubing (PE 50, intramedic). Nearly all of the vascular tree was injected with this technic. Latex-thorotrast injections have the decided advantage of permitting combined X-ray and histologic study of the material. The procedure was devised in the course of an attempt to evaluate the relationship between circulatory changes and experimentally produced bone absorption and new bone formation in mice.     

Determination of the Optimal Dose Reduction Level via Iterative Reconstruction Using 640-Slice Volume Chest CT in a Pig Model

Aim

To determine the optimal dose reduction level of iterative reconstruction technique for paediatric chest CT in pig models.

Materials and Methods

27 infant pigs underwent 640-slice volume chest CT with 80kVp and different mAs. Automatic exposure control technique was used, and the index of noise was set to SD10 (Group A, routine dose), SD12.5, SD15, SD17.5, SD20 (Groups from B to E) to reduce dose respectively. Group A was reconstructed with filtered back projection (FBP), and Groups from B to E were reconstructed using iterative reconstruction (IR). Objective and subjective image quality (IQ) among groups were compared to determine an optimal radiation reduction level.

Results

The noise and signal-to-noise ratio (SNR) in Group D had no significant statistical difference from that in Group A (P = 1.0). The scores of subjective IQ in Group A were not significantly different from those in Group D (P>0.05). There were no obvious statistical differences in the objective and subjective index values among the subgroups (small, medium and large subgroups) of Group D. The effective dose (ED) of Group D was 58.9% lower than that of Group A (0.20±0.05mSv vs 0.48±0.10mSv, p <0.001).

Conclusions

In infant pig chest CT, using iterative reconstruction can provide diagnostic image quality; furthermore, it can reduce the dosage by 58.9%.     

Validating a Low Dose Gamma Irradiation Process for Sterilizing Allografts Using ISO 11137 Method 2B

This paper describes the validation of an allograft sterilization method specifically designed for the processing methods used at AlloSource in Centennial, CO. The methods used for this validation followed ISO Standard 11137, Method 2B. Three hundred allografts, collected from three defined production batches were dosed using a series of five incremental doses, beginning at 1 kGy and increasing by 1 kGy until 5 kGy was achieved. Following sterilization dosing, each allograft test article was analyzed using a sterility test to identify any viable microorganisms. The number of positive sterility samples was used to calculate the verification dose (1.27 kGy), which was then verified by an additional batch of 100 allografts. The results from this validation indicate that sterility (10⁻⁶ SAL) on human allograft tissue using gamma ⁶⁰Co radiation can be achieved when a dose of at least 9.2 kGy is employed.     

Relating Doses of Contrast Agent Administered to TIC and Semi-Quantitative Parameters on DCE-MRI: Based on a Murine Breast Tumor Model

Objective

To explore the changes in the time-signal intensity curve(TIC) type and semi-quantitative parameters of dynamic contrast-enhanced(DCE)imaging in relation to variations in the contrast agent(CA) dosage in the Walker 256 murine breast tumor model, and to determine the appropriate parameters for the evaluation ofneoadjuvantchemotherapy(NAC)response.

Materials and Methods

Walker 256 breast tumor models were established in 21 rats, which were randomly divided into three groups of7rats each. Routine scanning and DCE-magnetic resonance imaging (MRI) of the rats were performed using a 7T MR scanner. The three groups of rats were administered different dosages of the CA0.2mmol/kg, 0.3mmol/kg, and 0.5mmol/kg, respectively; and the corresponding TICs the semi-quantitative parameters were calculated and compared among the three groups.

Results

The TICs were not influenced by the CA dosage and presented a washout pattern in all of the tumors evaluated and weren’t influenced by the CA dose. The values of the initial enhancement percentage(E_first), initial enhancement velocity(V_first), maximum signal(S_max), maximum enhancement percentage(E_max), washout percentage(E_wash), and signal enhancement ratio(SER) showed statistically significant differences among the three groups (F = 16.952, p = 0.001; F = 69.483, p<0.001; F = 54.838, p<0.001; F = 12.510, p = 0.003; F = 5.248, p = 0.031; F = 9.733, p = 0.006, respectively). However, the values of the time to peak(T_peak), maximum enhancement velocity(V_max), and washout velocity(V_wash)did not differ significantly among the three dosage groups (F = 0.065, p = 0.937; F = 1.505, p = 0.273; χ2 = 1.423, p = 0.319, respectively); the washout slope(Slope_wash), too, was uninfluenced by the dosage(F = 1.654, p = 0.244).

Conclusion

The CA dosage didn’t affect the TIC type, T_peak, V_max, V_wash or Slope_wash. These dose-independent parameters as well as the TIC type might be more useful for monitoring the NAC response because they allow the comparisons of the DCE data obtained using different CA dosages.     

Same Advantages of Using Low Speed Centrifugation for the Purification of Rat Liver Mitochondria

Twelve strains of lactose-fermenting yeast isolated from raw milk were evaluated on β-galactosidase producing ability. The enzymes from the four strains (Tolulopsis versatilis M6, Tolulopsis sphaerica J28, Candida pseudotropicalis B57 and A60), selected by high productivity, showed very similar properties and were characterized by a pH optimum of 7.0 or 7.5 and a relatively low optimal temperature of 30°C. The molecular weights were estimated by gel filtration to be 200,000-233,000. The Km values for o-nitrophenyl-β-d-galactopyranoside were 3.45 mm, 2.09 mm, 3.45 mm and 2.82 mm for enzymes from M6, J28, B57 and A60, respectively. All enzymes were activated by Mn²⁺ and inhibited by Mg²⁺, Zn²⁺ and Ca²⁺. The enzymes are sulfhydryl dependent and were completely inhibited by Hg²⁺ and sulfhydryl reagents. The yeasts may be a potential source for the enzyme for industrial use.     

CT Angiography of the Head-and-Neck Vessels Acquired with Low Tube Voltage,Low Iodine,and Iterative Image Reconstruction: Clinical Evaluation of Radiation Dose and Image Quality

Objectives

We aimed to assess the effectiveness and feasibility of head-and-neck Computed Tomography Angiography (CTA) with low tube voltage and low concentration contrast media combined with iterative reconstruction algorithm.

Methods

92 patients were randomly divided into group A and B: patients in group A received a conventional scan with 120 kVp and contrast media of 320 mgI/ml. Patients in group B, 80 kVp and contrast media of 270 mgI/ml were used along with iterative reconstruction algorithm techniques. Image quality, radiation dose and the effectively consumed iodine amount between two groups were analyzed and compared.

Results

Image quality of CTA of head-and-neck vessels obtained from patients in group B was significantly improved quantitatively and qualitatively. In addition, CT attenuation values in group B were also significantly higher than that in group A (p<0.001). Furthermore, compared with the protocol whereby 120 kVp and 320 mgI/dl were administrated, the mean radiation dose and consumed iodine amount in protocol B were also reduced by 50% and 15.6%, respectively (p<0.001).

Conclusions

With the help of iterative reconstruction algorithm techniques, the head-and-neck CTA with diagnostic quality can be adequately acquired with low tube voltage and low concentration contrast media. This method could be potentially extended to include any part of the body to reduce the risks related to ionizing radiation.     

Three-Dimensional Reconstruction with Contrast Transfer Function Correction from Energy-Filtered Cryoelectron Micrographs: Procedure and Application to the 70SEscherichia coliRibosome

Cryoelectron microscopy provides the means of studying macromolecules in their native state. However, the contrast transfer function (CTF) makes the images and the three-dimensional (3D) maps derived from them difficult to interpret. We developed methods to determine the CTF from experimental data and to obtain a CTF-corrected 3D reconstruction. The CTF correction and 3D reconstruction accomplished in one step make it easy to combine different defocus data sets and decrease the error accumulation in the computation. These methods were applied to energy-filtered images of the 70SEscherichia coliribosome, resulting in a distortion-free 3D map of the ribosome at 1/24.5 Å⁻¹resolution, as determined by the differential phase residual resolution criterion.     

Executive Function Deficits and Social-Behavioral Abnormality in Mice Exposed to a Low Dose of Dioxin In Utero and via Lactation

An increasing prevalence of mental health problems has been partly ascribed to abnormal brain development that is induced upon exposure to environmental chemicals. However, it has been extremely difficult to detect and assess such causality particularly at low exposure levels. To address this question, we here investigated higher brain function in mice exposed to dioxin in utero and via lactation by using our recently developed automated behavioral flexibility test and immunohistochemistry of neuronal activation markers Arc, at the 14 brain areas. Pregnant C57BL/6 mice were given orally a low dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at a dose of either 0, 0.6 or 3.0 µg/kg on gestation day 12.5. When the pups reached adulthood, they were group-housed in IntelliCage to assess their behavior. As a result, the offspring born to dams exposed to 0.6 µg TCDD/kg were shown to have behavioral inflexibility, compulsive repetitive behavior, and dramatically lowered competitive dominance. In these mice, immunohistochemistry of Arc exhibited the signs of hypoactivation of the medial prefrontal cortex (mPFC) and hyperactivation of the amygdala. Intriguingly, mice exposed to 3.0 µg/kg were hardly affected in both the behavioral and neuronal activation indices, indicating that the robust, non-monotonic dose-response relationship. In conclusion, this study showed for the first time that perinatal exposure to a low dose of TCDD in mice develops executive function deficits and social behavioral abnormality accompanied with the signs of imbalanced mPFC-amygdala activation.     

Using Low Levels of Stochastic Vestibular Stimulation to Improve Balance Function

Low-level stochastic vestibular stimulation (SVS) has been associated with improved postural responses in the medio-lateral (ML) direction, but its effect in improving balance function in both the ML and anterior-posterior (AP) directions has not been studied. In this series of studies, the efficacy of applying low amplitude SVS in 0–30 Hz range between the mastoids in the ML direction on improving cross-planar balance function was investigated. Forty-five (45) subjects stood on a compliant surface with their eyes closed and were instructed to maintain a stable upright stance. Measures of stability of the head, trunk, and whole body were quantified in ML, AP and combined APML directions. Results show that binaural bipolar SVS given in the ML direction significantly improved balance performance with the peak of optimal stimulus amplitude predominantly in the range of 100–500 μA for all the three directions, exhibiting stochastic resonance (SR) phenomenon. Objective perceptual and body motion thresholds as estimates of internal noise while subjects sat on a chair with their eyes closed and were given 1 Hz bipolar binaural sinusoidal electrical stimuli were also measured. In general, there was no significant difference between estimates of perceptual and body motion thresholds. The average optimal SVS amplitude that improved balance performance (peak SVS amplitude normalized to perceptual threshold) was estimated to be 46% in ML, 53% in AP, and 50% in APML directions. A miniature patch-type SVS device may be useful to improve balance function in people with disabilities due to aging, Parkinson’s disease or in astronauts returning from long-duration space flight.     

小鼠低剂量辐射损伤模型的初步研究

目的:对小鼠低剂量辐射损伤模型进行初步研究并筛选敏感检测指标.方法:实验分7组,1组为正常组,其余6组用XHA600直线加速器射线照射,每组取一部分小鼠于照射后2、4、8、16h测定红细胞(RBC)、白细胞(WBC)、血小板(PLT)和血红蛋白(HGB)含量;测定小鼠肝脏和脾脏重量及其组织中的超氧化合物歧化酶(SOD)和丙二醛(MDA)含量;剩余小鼠于4周后观察骨髓切片中血细胞变化.结果:照射后4h测定血常规,发现累积辐射0.4Gy组小鼠RBC有降低趋势,WBC、HGB显著降低,PLT显著升高;肝脏、脾脏的湿质量显著降低;小鼠肝脏组织中MDA的含量显著升高、SOD的活力显著降低;4周后小鼠骨髓细胞的病理改变与单次照射剂量相关,单次较大剂量(如0.6Gy)照射对骨髓细胞影响较大,在4周观察期不能自身恢复,而多次累积照射对骨髓细胞病理改变较小.结论:小鼠低剂量辐射损伤模型的最佳造模剂量为累积照射0.4Gy即每次照射100mGy,间隔一天,连续照射4次.