Relationships of Radiation Dose Indices with Body Size Indices in Adult Body Computed Tomography.

We investigated the relationships between radiation dose indices and body size indices in adult body computed tomography (CT). A total of 3200 CT scans of the thoracic, abdominal, abdominopelvic, or thoraco-abdominopelvic regions performed using one of four CT scanners were analyzed. Volume CT dose index (CTDIvol) and dose length product (DLP) were compared with various body size indices derived from CT images (water-equivalent diameter, WED; effective diameter, ED) and physical measurements (weight, weight/height, body mass index, and body surface area). CTDIvol showed excellent positive linear correlations with WED and ED. CTDIvol also showed high linear correlations with physical measurement-based indices, whereas the correlation coefficients were lower than for WED and ED. Among the physical measurement-based indices, weight/height showed the strongest correlations, followed by weight. Compared to CTDIvol, the correlation coefficients with DLP tended to be lower for WED, ED, and weight/height and higher for weight. The standard CTDIvol values at 60 kg and dose increase ratios with increasing weight, estimated using the regression equations, differed among scanners. Radiation dose indices closely correlated with body size indices such as WED, ED, weight/height, and weight. The relationships between dose and body size differed among scanners, indicating the significance of dose management considering body size.

SIZE-SPECIFIC DOSE ESTIMATES IN PEDIATRIC BRAIN CT IN RELATION TO AGE AND WEIGHT.

The size-specific dose estimate (SSDE) is used for radiation dose management in computed tomography (CT) and represents patient's absorbed dose more accurately than volume CT dose index. The relationship between SSDE and age or weight was investigated using 980 pediatric brain CT scans. Monolinear, power, and bilinear functions were fitted to the plots of SSDE against age or weight, and SSDE was estimated using the obtained functions. SSDE showed a biphasic increase with increasing age and weight: a rapid initial increase and subsequent a slow increase. Bilinear and power functions were successfully fitted to the plots, and mean estimation errors were close to 0, irrespective of the age or weight group. The standard SSDE values estimated from the obtained functions agreed well with the median values for each age or weight group. The curve-fitting method is expected to aid radiation dose management for pediatric brain CT using SSDE.

Age-Dependent Changes in Effective Dose in Pediatric Brain CT: Comparisons of Estimation Methods.

The effective dose (ED) in computed tomography (CT) may be calculated by multiplying the dose-length product (DLP) by a conversion factor. As children grow, automatic exposure control increases the DLP, while the conversion factor decreases; these two changes affect the ED in opposite ways. The aim of this study was to investigate the methods of ED estimation according to age in pediatric brain CT. We retrospectively analyzed 980 brain CT scans performed for various clinical indications in children. The conversion factor at each age, in integer years, was determined based on the values at 0, 1, 5, and 10 years provided by the International Commission on Radiological Protection (ICRP), using a curve (curve method) or lines (linear method). In the simple method, the ED was estimated using the ICRP conversion factor for the closest age. We also analyzed the ED estimated by a radiation dose management system. Although the median DLP at each age increased with age, the median ED estimated by the curve method was highest at 0 years, decreased with age, and then plateaued at 9 years. The linear method yielded mildly different results, especially at 2 and 3 years. The ED estimated by the simple method or the radiation dose management system showed inconsistent, up-and-down changes with age. In conclusion, the ED in pediatric brain CT decreases with age despite increased DLP. Determination of the conversion factor at each age using a curve is expected to contribute to estimating the ED in pediatric CT according to age.

Automatic Exposure Control Attains Radiation Dose Modulation Matched with the Head Size in Pediatric Brain CT.

We investigated the relationship between the head size and radiation dose in pediatric brain computed tomography (CT) to evaluate the validity of automatic exposure control (AEC). Phantom experiments were performed to assess image noise with and without AEC, and indicated that AEC decreased differences in noise between slices of different section sizes. Retrospective analysis was conducted on 980 pediatric brain CT scans where the tube current was determined using AEC. The water equivalent diameter (WED) was employed as an index of the head size, and mean WED for each image set (WEDmean) and WED for each slice (WEDslice) were used for analysis. For the image-set-based analysis, volume CT dose index (CTDIvol) was compared to WEDmean. For the slice-based analysis, the tube current was compared to WEDslice using 20 of the 980 sets. Additionally, CTDIvol and WEDmean were compared between male and female patients matched for age, weight, or WEDmean. CTDIvol increased with increasing WEDmean, and an exponential curve was closely fitted to the relationship. Tube current changed similarly to the change in WEDslice for each image set, and an exponential curve was well-fitted to the plots of tube current against WEDslice when data from the 20 sets were pooled together. Although CTDIvol and WEDmean were slightly but significantly larger for male than female patients after matching for age or weight, a sex-dependent difference in CTDIvol was not found after matching for WEDmean. This study indicated successful dose modulation using AEC according to the head size for each patient and each slice location. The application of AEC to pediatric brain CT is recommended for radiation dose optimization.

Sample Size and Estimation of Standard Radiation Doses for Pediatric Brain CT.

Estimation of the standard radiation dose at each imaging facility is required for radiation dose management, including establishment and utilization of the diagnostic reference levels. We investigated methods to estimate the standard dose for pediatric brain computed tomography (CT) using a small number of data. From 980 pediatric brain CT examinations, 25, 50, and 100 examinations were randomly extracted to create small, medium, and large datasets, respectively. The standard dose was estimated by applying grouping and curve-fitting methods for 20 datasets of each sample size. For the grouping method, data were divided into groups according to age or body weight, and the standard dose was defined as a median value in each group. For the curve-fitting methods, logarithmic, power, and bilinear functions were fitted to plots of radiation dose against age or weight, and the standard dose was calculated at the designated age or weight using the derived equation. When the sample size was smaller, the random variations of the estimated standard dose were larger. Better estimation of the standard dose was achieved with the curve-fitting methods than with the grouping method. Power fitting appeared to be more effective than logarithmic and bilinear fittings for suppressing random variation. Determination of the standard dose for pediatric brain CT by the curve-fitting method is recommended to improve radiation dose optimization at facilities performing the imaging procedure infrequently.

Radiation Dose Management in Pediatric Brain CT According to Age and Weight as Continuous Variables.

The diagnostic reference levels (DRLs) for pediatric brain computed tomography (CT) are provided for groups divided according to age. We investigated the relationships of radiation dose indices (volume CT dose index and dose length product) with age and weight, as continuous variables, in pediatric brain CT. In a retrospective analysis, 980 pediatric brain CT examinations were analyzed. Curve fitting was performed for plots of the CT dose indices versus age and weight, and equations to estimate age- and weight-dependent standard dose indices were derived. Standard dose indices were estimated using the equations, and the errors were calculated. The results showed a biphasic increase in dose indices with increasing age and weight, characterized by a rapid initial and subsequent slow increase. Logarithmic, power, and bilinear functions were well fitted to the plots, allowing estimation of standard dose indices at an arbitrary age or weight. Error analysis suggested that weight was mildly better than age and that the best results were obtained with the bilinear function. Curve fitting of the relationship between CT dose indices and age or weight facilitates the determination of standard dose indices in pediatric brain CT at each facility and is expected to aid the establishment and application of the DRLs.

SUBOPTIMAL MODULATION OF RADIATION DOSE IN THE COMPUTED TOMOGRAPHY COMPONENT OF WHOLE-BODY POSITRON EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY.

Radiation exposure in computed tomography (CT) is automatically modulated by automatic exposure control (AEC) mainly based on scout images. To simulate the whole-body positron emission tomography/CT, CT images of a phantom were obtained using the posteroanterior scout image alone (PA scout) or the posteroanterior and lateral images (PA + Lat scout). Old and new versions of the AEC software were compared. Using the old version of the software and the PA scout, a markedly high dose at the top of the head was observed, which varied depending on the position of the phantom. This issue was resolved in the new version of the software. Radiation dose in the shoulder region was much higher using the PA scout than using the PA + Lat scout, even with the new version of the software. AEC may cause unreasonably high radiation exposure locally, and the appropriateness of the dose modulation pattern should be examined at each facility.

Effects of scout radiographic imaging conditions on tube current modulation in chest computed tomography.

For the optimisation of radiation dose in computed tomography (CT), dose reduction is attempted while preserving diagnostic performance. To reduce the overall radiation dose related to CT, the dose from scout radiography may be reduced by decreasing the tube voltage and tube current. We evaluated the effects of scout imaging conditions on CT radiation dose. An anthropomorphic chest phantom was imaged on two CT scanners (scanners A and B) from different vendors, manipulating the scout imaging conditions in terms of imaging direction, tube voltage and tube current, and assessed the tube current modulation in subsequent CT and pixel values in scout radiographs. The direction of the scout radiography influenced the shape of the tube current modulation curve and total radiation dose in subsequent CT. When compared with the use of the lateral projection, use of the posteroanterior or anteroposterior projection alone increased the radiation dose substantially on scanner A, but did not change, or mildly decreased, the dose on scanner B. When imaged using the lateral scout on scanner A, reduction in tube voltage and tube current for scout radiography decreased the CT dose in the cranial part of the scan range and, to a lesser degree, the total radiation dose. On the low-voltage, low-current lateral radiograph, the image contrast was impaired and pixel values were underestimated around the lung apex. Without the use of the lateral radiograph, neither the tube voltage nor tube current for scout radiography influenced the CT dose. On scanner B, reduced tube voltage for scout radiography increased the CT dose. In conclusion, reduced tube voltage and tube current may affect scout radiographs, resulting in alteration of the tube current modulation pattern and total radiation dose in subsequent CT. These effects vary depending on the CT scanners and scout direction.

ESTIMATION OF RADIATION DOSE IN CT VENOGRAPHY OF THE LOWER EXTREMITIES: PHANTOM EXPERIMENTS USING DIFFERENT AUTOMATIC EXPOSURE CONTROL SETTINGS AND SCAN RANGES.

We performed phantom experiments to assess radiation dose in computed tomography (CT) venography of the lower extremities. CT images of a whole-body phantom were acquired using different automatic exposure control settings and scan ranges, simulating CT venography. Tube current decreased in the lower extremities compared to the trunk. The scout direction and dose modulation strength affected tube current, dose length product (DLP) and effective dose. The middle and distal portions of the lower extremities contributed substantially to DLP but not to effective dose. When effective dose was estimated by multiplying DLP by a single conversion factor, overestimation was evident; this became more pronounced as the scan range narrowed. In CT venography of the lower extremities, the scout direction and modulation strength affect radiation dose. Use of DLP severely overestimates radiation dose and underestimates effects of scan range narrowing.

Feature visualization of Raman spectrum analysis with deep convolutional neural network.

We demonstrate a recognition and feature visualization method that uses a deep convolutional neural network for Raman spectrum analysis. The visualization is achieved by calculating important regions in the spectra from weights in pooling and fully-connected layers. The method is first examined for simple Lorentzian spectra, then applied to the spectra of pharmaceutical compounds and numerically mixed amino acids. We investigate the effects of the size and number of convolution filters on the extracted regions for Raman-peak signals using the Lorentzian spectra. It is confirmed that the Raman peak contributes to the recognition by visualizing the extracted features. A near-zero weight value is obtained at the background level region, which appears to be used for baseline correction. Common component extraction is confirmed by an evaluation of numerically mixed amino acid spectra. High weight values at the common peaks and negative values at the distinctive peaks appear, even though the model is given one-hot vectors as the training labels (without a mix ratio). This proposed method is potentially suitable for applications such as the validation of trained models, ensuring the reliability of common component extraction from compound samples for spectral analysis.

BCPP compounds, PET probes for early therapeutic evaluations, specifically bind to mitochondrial complex I.

BCPP compounds have been developed as PET imaging probes for neurodegenerative diseases in the living brain. 18F-BCPP-EF identifies damaged neuronal areas based on the lack of MC-I; however, its underlying mechanisms of action and specificity for MC-I remain unclear. We herein report the effects of BCPP-BF, -EF, -EM on MC-I in respiratory chain complexes using cardiomyocyte SMP. BCPP compounds inhibited the binding of 3H-dihydrorotenone to MC-I and the proton pumping activity of MC-I in a concentration-dependent manner in vitro. These results suggest that BCPP compounds are MC-I selective inhibitors, and, thus, these radiolabeled compounds are useful for the quantitative imaging of MC-I using PET.

EFFECTS OF THE SCAN RANGE ON RADIATION DOSE IN THE COMPUTED TOMOGRAPHY COMPONENT OF ONCOLOGY POSITRON EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY.

We performed phantom experiments to investigate radiation dose in the computed tomography component of oncology positron emission tomography/computed tomography in relation to the scan range. Computed tomography images of an anthropomorphic whole-body phantom were obtained from the head top to the feet, from the head top to the proximal thigh or from the skull base to the proximal thigh. Automatic exposure control using the posteroanterior and lateral scout images offered reasonable tube current modulation corresponding to the body thickness. However, when the posteroanterior scout alone was used, unexpectedly high current was applied in the head and upper chest. When effective dose was calculated on a region-by-region basis, it did not differ greatly irrespective of the scan range. In contrary, when effective dose was estimated simply by multiplying the scanner-derived dose-length product by a single conversion factor, estimates increased definitely with the scan range, indicating severe overestimation in whole-body imaging.

CT dose modulation using automatic exposure control in whole-body PET/CT: effects of scout imaging direction and arm positioning.

Automatic exposure control (AEC) modulates tube current and consequently X-ray exposure in CT. We investigated the behavior of AEC systems in whole-body PET/CT. CT images of a whole-body phantom were acquired using AEC on two scanners from different manufactures. The effects of scout imaging direction and arm positioning on dose modulation were evaluated. Image noise was assessed in the chest and upper abdomen. On one scanner, AEC using two scout images in the posteroanterior (PA) and lateral (Lat) directions provided relatively constant image noise along the z-axis with the arms at the sides. Raising the arms increased tube current in the head and neck and decreased it in the body trunk. Image noise increased in the upper abdomen, suggesting excessive reduction in radiation exposure. AEC using the PA scout alone strikingly increased tube current and reduced image noise in the shoulder. Raising the arms did not substantially influence dose modulation and decreased noise in the abdomen. On the other scanner, AEC using the PA scout alone or Lat scout alone resulted in similar dose modulation. Raising the arms increased tube current in the head and neck and decreased it in the trunk. Image noise was higher in the upper abdomen than in the middle and lower chest, and was not influenced by arm positioning. CT dose modulation using AEC may vary greatly depending on scout direction. Raising the arms tended to decrease radiation exposure; however, the effect depends on scout direction and the AEC system.

Measurement of Renal Depth in Dynamic Renal Scintigraphy Using Ultralow-Dose CT.

PURPOSE: Renal depths predicted using predefined formulas are commonly used for camera-based evaluation of renal function. We investigated the feasibility and utility of renal depth measurement using ultralow-dose CT images acquired in conjunction with dynamic renal scintigraphy. METHODS: Dynamic renal scintigraphy with Tc-MAG3 was performed in 117 patients (225 kidneys) using a SPECT/CT scanner, and ultralow-dose CT (estimated effective dose of 0.17 mSv) was performed during free breathing immediately before tracer injection. The clarity of the renal contour on the CT images was evaluated visually. The renal depths were measured by 2 methods and compared with depths predicted by 2 previously reported methods. The accuracy of camera-based clearance using predicted and measured depths was evaluated using a single-sample method as a standard. RESULTS: The clarity of the renal contour was poor in 18 of 225 kidneys, and 12 of 117 patients were considered ineligible for depth measurement. The measurement for eligible patients showed excellent intraobserver and interobserver repeatabilities. Although mean depths were similar among the 2 CT measurement methods and 2 prediction methods, absolute differences of more than 1 cm were observed in approximately 20% of kidneys between CT measurement and prediction. CT measurement of renal depth failed to improve the accuracy of camera-based clearance evaluation. CONCLUSION: Ultralow-dose CT allowed measurement of renal depth in most patients. Substantial differences in renal depth between prediction and CT measurement indicated potential usefulness of CT measurement, although no actual improvement in the accuracy of clearance estimation was demonstrated in this study.

Iejimalide C is a potent V-ATPase inhibitor, and induces actin disorganization.

Iejimalides (IEJLs) A-D are 24-membered macrolides isolated from a tunicate Eudistoma cf. rigida, and exhibit potent cytotoxicity in vitro and antitumor activity in vivo. We previously reported that the molecular target of IEJL-A and -B was the vacuolar-type H(+)-ATPases (V-ATPases). However IEJL-C and -D, which are sulfonylated IEJL-A and -B, respectively, show more potent antitumor activity, and their molecular targets remain to be discovered. Here, we report that IEJL-C is also a potent V-ATPase inhibitor by binding in a site similar to the bafilomycin-binding site. Two-hour treatment with IEJL-C resulted in the complete disappearance of acidic organelles in HeLa cells. Interestingly, after 24-h treatment, small actin aggregates were observed instead of actin fibers. The same actin reorganization was also observed in cells treated with another V-ATPase inhibitor, bafilomycin A1. Because IEJLs did not inhibit actin polymerization in vitro, these results suggest that the primary target of IEJL-C, as well as IEJL-A and -B, is V-ATPase, and actin reorganizations are probably caused by the disruption of pH homeostasis via V-ATPase inhibition.

Non-surgical treatment of canine oral malignant melanoma: A case study of the application of complementary alternative medicine.

This report describes a dog with a clinical stage III oral malignant melanoma that was treated with complementary alternative medicine (CAM). The CAM included high temperature hyperthermia, dendritic cell therapy and lupeol injections. Surgery, radiation and chemotherapy were not performed. Two months after the start of treatment, the tumor disappeared and after six months, the follow-up examinations revealed no recurrence or metastasis of the tumor. Quality of life (QOL) of the dog was maintained; therefore, the application of CAM may be an effective treatment for canine oral malignant melanoma. The effective application of CAM has the potential to prolong life and maintain an excellent QOL for pets.

Neither helix in the coiled coil region of the axle of F1-ATPase plays a significant role in torque production.

F(1)-ATPase is an ATP-driven rotary molecular motor in which the central gamma-subunit rotates inside the cylinder made of alpha(3)beta(3) subunits. The amino and carboxy termini of the gamma-subunit form the axle, an alpha-helical coiled coil that deeply penetrates the stator cylinder. We previously truncated the axle step by step, starting with the longer carboxy terminus and then cutting both termini at the same levels, resulting in a slower yet considerably powerful rotation. Here we examine the role of each helix by truncating only the carboxy terminus by 25-40 amino-acid residues. Longer truncation impaired the stability of the motor complex severely: 40 deletions failed to yield rotating the complex. Up to 36 deletions, however, the mutants produced an apparent torque at nearly half of the wild-type torque, independent of truncation length. Time-averaged rotary speeds were low because of load-dependent stumbling at 120 degrees intervals, even with saturating ATP. Comparison with our previous work indicates that half the normal torque is produced at the orifice of the stator. The very tip of the carboxy terminus adds the other half, whereas neither helix in the middle of the axle contributes much to torque generation and the rapid progress of catalysis. None of the residues of the entire axle played a specific decisive role in rotation.

Temperature dependence of the rotation and hydrolysis activities of F1-ATPase.

F(1)-ATPase, a water-soluble portion of the enzyme ATP synthase, is a rotary molecular motor driven by ATP hydrolysis. To learn how the kinetics of rotation are regulated, we have investigated the rotational characteristics of a thermophilic F(1)-ATPase over the temperature range 4-50 degrees C by attaching a polystyrene bead (or bead duplex) to the rotor subunit and observing its rotation under a microscope. The apparent rate of ATP binding estimated at low ATP concentrations increased from 1.2 x 10(6) M(-1) s(-1) at 4 degrees C to 4.3 x 10(7) M(-1) s(-1) at 40 degrees C, whereas the torque estimated at 2 mM ATP remained around 40 pN.nm over 4-50 degrees C. The rotation was stepwise at 4 degrees C, even at the saturating ATP concentration of 2 mM, indicating the presence of a hitherto unresolved rate-limiting reaction that occurs at ATP-waiting angles. We also measured the ATP hydrolysis activity in bulk solution at 4-65 degrees C. F(1)-ATPase tends to be inactivated by binding ADP tightly. Both the inactivation and reactivation rates were found to rise sharply with temperature, and above 30 degrees C, equilibrium between the active and inactive forms was reached within 2 s, the majority being inactive. Rapid inactivation at high temperatures is consistent with the physiological role of this enzyme, ATP synthesis, in the thermophile.

Axle-less F1-ATPase rotates in the correct direction.

F1-adenosine triphosphatase (ATPase) is an ATP-driven rotary molecular motor in which the central gamma subunit rotates inside a cylinder made of three alpha and three beta subunits alternately arranged. The rotor shaft, an antiparallel alpha-helical coiled coil of the amino and carboxyl termini of the gamma subunit, deeply penetrates the central cavity of the stator cylinder. We truncated the shaft step by step until the remaining rotor head would be outside the cavity and simply sat on the concave entrance of the stator orifice. All truncation mutants rotated in the correct direction, implying torque generation, although the average rotary speeds were low and short mutants exhibited moments of irregular motion. Neither a fixed pivot nor a rigid axle was needed for rotation of F1-ATPase.

Coupling of rotation and catalysis in F(1)-ATPase revealed by single-molecule imaging and manipulation.

F(1)-ATPase is a rotary molecular motor that proceeds in 120 degrees steps, each driven by ATP hydrolysis. How the chemical reactions that occur in three catalytic sites are coupled to mechanical rotation is the central question. Here, we show by high-speed imaging of rotation in single molecules of F(1) that phosphate release drives the last 40 degrees of the 120 degrees step, and that the 40 degrees rotation accompanies reduction of the affinity for phosphate. We also show, by single-molecule imaging of a fluorescent ATP analog Cy3-ATP while F(1) is forced to rotate slowly, that release of Cy3-ADP occurs at approximately 240 degrees after it is bound as Cy3-ATP at 0 degrees . This and other results suggest that the affinity for ADP also decreases with rotation, and thus ADP release contributes part of energy for rotation. Together with previous results, the coupling scheme is now basically complete.