A radiographic and physical analysis of factors affecting seat belt position in sitting car seat.

The characteristic subcutaneous hemorrhage along the seat belt in motor vehicle accidents is called the seat belt sign (SBS). The risk of organ injuries is especially high when abdominal SBS is located above the anterior superior iliac spine (ASIS). The purpose of this study analyzed the physical and radiographic factors of healthy volunteers sit on car seat that affect initial position of abdominal seat belt, namely "lap belt", related to the seat belt injury. This study was examined prospectively relation between physical characteristics of one hundred healthy volunteers and lap belt position sitting the car seat. Physical findings were clarified age, sex, height, body mass index (BMI), and waist circumference. Radiographical findings were measured lumber lordosis (LL), sacral slope (SS), and initial lap belt position by marking with lead tape for the center and ASIS of the lap belt installed on the driver's car seat. In the lateral X-ray image, we measured the horizontal distance (X-value) and vertical distance (Z-value) from the ASIS to the central marker. The lap belt angle was determined to measure the angle between the horizontal line and the straight line connecting the upper edges of the markers. Statistical analysis of the relationships between physical characteristics and radiological findings was performed. X-value and Z-value were positively correlated with body weight, BMI, and waist circumference, while the lap belt angle was negatively correlated with body weight, BMI, and waist circumference. The relationship between physical characteristics and the initial position of seat belt was analyzed. Since the lap belt is positioned higher than the ASIS in occupants with a high BMI, it is likely to cause seat belt injury. This analysis can help to develop safer seat belts and to enlighten car occupants.

Clostridium butyricum MIYAIRI 588 as Adjunctive Therapy for Treatment-Resistant Major Depressive Disorder: A Prospective Open-Label Trial.

AIM: Up to 60% of depressed patients do not obtain sufficient relief from a course of antidepressant therapy, and these treatment-resistant major depressive disorder (TRD) patients are at increased risk for relapse, chronicity, persistent psychosocial impairments, and suicide. Probiotics actively participate in treatment of neuropsychiatric disorders. However, the role of gut microbiota in brain disorders and depression remains unclear. We performed a prospective study to evaluate the effects of Clostridium butyricum MIYAIRI 588 (CBM588). METHODS: This was an 8-week open-label study to evaluate the efficacy and safety of CBM588 in combination with antidepressants in adult patients diagnosed with TRD according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Forty antidepressant-treated inpatients were included. Patients were randomized to adjuvant treatment with CBM588 (n = 20) or control (n = 20). The primary endpoint was the change in the 17-item Hamilton Depression Rating Scale score from baseline to week 8. Secondary end points were changes in the Beck Depression Inventory and the Beck Anxiety Inventory scale scores from baseline to week 8. The Systematic Assessment of Treatment Emergent Events-General Inquiry was used to assess adverse effects. RESULTS: CBM588 (60 mg/d) in combination with antidepressants (flvoxamine, paroxetine, escitalopram, duroxetine, and sertraline) provided significant improvement in depression. All patients completed the trial, and 70% responded to treatment; the remission rate was 35.0%. No serious adverse events occurred. CONCLUSIONS: These preliminary data suggest that CBM588 in combination with antidepressants is effective and well tolerated in the treatment of TRD. Further studies using a larger, double-blind, parallel-group design are warranted to confirm these findings.

Clinical assessment of coiled fiducial markers as internal surrogates for hepatocellular carcinomas during gated stereotactic body radiotherapy with a real-time tumor-tracking system.

BACKGROUND AND PURPOSE: To report the clinical usefulness of coiled fiducial markers as an internal surrogate in gated stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) using a real-time tumor-tracking radiotherapy (RTRT) system. MATERIALS AND METHODS: Seventeen HCC patients with Child-Pugh (CP) scores of A or B received gated SBRT (45-50Gy in 5-10 fractions) using an RTRT system and Visicoil markers. Local control (LC), progression-free (PFS), and overall survival (OS) rates were assessed using the Kaplan-Meier method. Toxicities were assessed using the Common Terminology Criteria for Adverse Events, Version 4.0. RESULTS: Of the 17 patients, 14 had a CP score A. The mean planning target volume was 54.6cc. Only 1 patient developed pneumothorax after marker implantation. Visicoil tracking during SBRT was possible in all cases. With a median follow-up of 16months, 1-year LC, PFS, and OS rates were 100%, 53%, and 82%, respectively. Grade≥2 late toxicity was observed in 2 patients (grade 2 duodenal ulcer and grade 3 temporary transaminase elevation). CONCLUSIONS: Using an RTRT system and Visicoil markers, gated SBRT was well tolerated in patients with HCC. This can be considered a safe treatment strategy with potential for delivering favorable outcomes.

Evaluation of a combined respiratory-gating system comprising the TrueBeam linear accelerator and a new real-time tumor-tracking radiotherapy system: a preliminary study.

A combined system comprising the TrueBeam linear accelerator and a new real-time, tumor-tracking radiotherapy system, SyncTraX, was installed in our institution. The goals of this study were to assess the capability of SyncTraX in measuring the position of a fiducial marker using color fluoroscopic images, and to evaluate the dosimetric and geometric accuracy of respiratory-gated radiotherapy using this combined system for the simple geometry. For the fundamental evaluation of respiratory-gated radiotherapy using SyncTraX, the following were performed:1) determination of dosimetric and positional characteristics of sinusoidal patterns using a motor-driven base for several gating windows; 2) measurement of time delay using an oscilloscope; 3) positional verification of sinusoidal patterns and the pattern in the case of a lung cancer patient; 4) measurement of the half-value layer (HVL in mm AL), effective kVp, and air kerma, using a solid-state detector for each fluoroscopic condition, to determine the patient dose. The dose profile in a moving phantom with gated radiotherapy having a gating window ≤ 4 mm was in good agreement with that under static conditions for each photon beam. The total time delay between TrueBeam and SyncTraX was < 227 ms for each photon beam. The mean of the positional tracking error was < 0.4 mm for sinusoidal patterns and for the pattern in the case of a lung cancer patient. The air-kerma rates from one fluoroscopy direction were 1.93 ± 0.01, 2.86 ± 0.01, 3.92 ± 0.04, 5.28 ± 0.03, and 6.60 ± 0.05 mGy/min for 70, 80, 90, 100, and 110 kV X-ray beams at 80 mA, respectively. The combined system comprising TrueBeam and SyncTraX could track the motion of the fiducial marker and control radiation delivery with reasonable accuracy; therefore, this system provides significant dosimetric improvement. However, patient exposure dose from fluoroscopy was not clinically negligible.

Evaluation of the incident directional dependence of radiochromic film by use of Monte Carlo simulation and measurement.

In high-precision radiotherapy, absolute and relative doses are evaluated for patient-specific intensity-modulated radiation therapy (IMRT) quality assurance (QA). In our institution, we use GAFCHROMIC EBT3 (EBT3) for relative dose evaluation in IMRT QA. We usually use two directional film configurations, which are in the axial and sagittal planes. The QA in our institution shows some differences between the gamma pass rates in the axial and sagittal directions. The purpose of this study was to evaluate the incident directional dependence of EBT3 by using the percent depth dose (PDD) and the off-center ratio (OCR) between EBT3 films positioned perpendicular to the beam axis and along the beam axis. Furthermore, we compared the PDD in EBT3 films positioned perpendicular to the beam axis and the PDD by using an ionization chamber. In addition, PDDs in water phantoms with and without EBT3 films were calculated by Monte Carlo simulation. The results showed that the PDD in EBT3 films positioned perpendicular to the beam axis increased with the depth from the phantom surface. Monte Carlo simulation showed the same trend as did the film measurements. The OCR results were slightly different at dose levels below 20 %. The OCR in EBT3 films positioned along the beam axis was higher than that perpendicular to the beam axis. Thus, we conclude that EBT3 film has incident directional dependence. In IMRT QA, the gamma analysis results may be affected by the incident directional dependence of EBT3 film.

The low attenuation area on dual-energy perfusion CT: correlation with the pulmonary function tests and quantitative CT measurements.

PURPOSE: To retrospectively investigate the distribution of the low attenuation area (LAA) on dual energy perfusion CT (DEpCT) in comparison with the results of pulmonary function tests (PFTs) and quantitative CT measurements. MATERIALS AND METHODS: Twenty-eight patients (15 male and 13 female; mean age: 62.21 years) underwent DEpCT and PFTs within a 1-month interval. The ranges of the LAA on DEpCT were classified into six groups with attenuation values of 0-3, 0-5, 0-8, 0-10, 0-13 and 0-15 HU and the ratios of LAA in each group were compared with the percentage of forced expiratory volume in the 1st second (%FEV(1.0)), FEV(1.0)/forced vital capacity (FEV(1.0)/FVC) and the relative area of the lung with attenuation coefficients lower than -950 HU (RA(-950)). RESULTS: The LAAs on the DEpCT images were significantly correlated with the RA(-950), %FEV(1.0) and FEV(1.0)/FVC, and the regression analysis showed that the best values of LAA on DEpCT were 0-10 HU with RA(-950) (r=0.63), 0-8 HU with %FEV(1.0) (r=-0.52) and 0-8HU with FEV(1.0)/FVC (r=-0.61) per patient. CONCLUSION: The iodine disturbance on DEpCT had a moderate correlation with the results of the PFTs and RA(-950), but further examination would be needed for evaluation of iodine distribution.

Correction of liver displacement due to irregular respiration for SPECT images obtained using a multiple short-time acquisition with breath-holding technique.

Recently, a new method for acquiring single photon emission computed tomography (SPECT) data during breath-holding with a high-speed rotation (HSR-SPECT) technique was applied to hepatic-function scintigraphy. This technique can suppress motion artifact caused by respiration. However, it is challenging to apply this technique to patients with respiratory problems. Our purpose in this study was to analyze projection data and correct liver displacement due to irregular respiration during technetium-99m-diethylenetriaminepentaacetic acid galactosyl human serum albumin ((99m)Tc-GSA) liver SPECT scans. We calculated cross-correlation functions (CCFs) for both intra- and inter-projections to correct irregular projections by shifting them in the longitudinal direction enough to maximize the CCFs. We integrated all of the shifted projections and created a synthesis projection which was used to reconstruct SPECT images. To confirm the effectiveness of our method, we did both a phantom study and a clinical retrospective review. In the phantom study, blurring artifacts due to displacement were reduced using our method. Post-processing using our method showed improvements in the normalized mean square error values ranging from 0.18 to 0.06. Furthermore, our method showed no disadvantage or miss-correction if we applied our method to data without displacement. In the clinical review, our method improved the image clarity for patients who could not repeat consistent respiration. In both the phantom simulation and the clinical application, the results showed the usefulness of our method. The efficiency of our method has the potential to reduce the displacement problem caused by respiration and provides excellent matching SPECT/CT fusion images.

Assessment of cross-sectional lung ventilation-perfusion imbalance in primary and passive pulmonary hypertension with automated V/Q SPECT.

PURPOSE: Cross-sectional lung ventilation (V)-perfusion (Q) imbalance in primary pulmonary arterial hypertension (PAH) and passive pulmonary hypertension (PH) was characterized by automated V/Q single-photon emission computed tomography (SPECT). MATERIALS AND METHODS: Technegas/macro-aggregated albumin SPECT-derived V/Q SPECT and V/Q profile were automatically built to characterize cross-sectional lung V-Q imbalance in 12 patients with primary (idiopathic or familial) PAH and 15 patients with passive PH associated with left ventricular dysfunction or failure. The abnormality of V/Q distribution in these patients was correlated with PaO2 and pulmonary arterial pressure and with lung morphologic changes on computed tomography (CT). RESULTS: Markedly low V/Q ratios (reverse V-Q mismatch) in the background lungs with heterogeneous V/Q distribution was seen in 12 of the 12 (100%) patients with primary PAH and in 10 of the 15 (66%) patients with passive PH, which were predominantly seen in the upper lung zone. Including these regions with reverse V-Q mismatch, the V/Q profile frequently showed flattened peaks with asymmetric and broadened V/Q distribution in all patients, with significant correlation between the standard deviation of V/Q ratios in the entire lungs and PaO2 and mean pulmonary arterial pressure (both; P<0.01). At the regions of the lungs with reverse V-Q mismatch, bronchial lumens compressed by dilated pulmonary arteries and heterogeneous lung attenuations were frequently seen on CT. CONCLUSION: Patients with primary PAH and passive PH seem to characteristically have a high prevalence of reverse V-Q mismatch indicative of an inadequate hypoxic vasoconstriction reflex on V/Q SPECT, frequently accompanied with heterogeneous lung attenuations and compressed airways on CT.

Characteristic crescentic subpleural lung zones with high ventilation (V)/perfusion (Q) ratios in interstitial pneumonia on V/Q quotient SPECT.

OBJECTIVE: Nonspecific interstitial pneumonia (NSIP) and usual IP (UIP) preferentially involve subpleural lung zones (SPLZ), and may result in characteristic regional lung function impairment. The aim of this study was to characterize cross-sectional lung ventilation (V)-perfusion (Q) imbalance in these disorders on automated V/Q quotient single photon emission computed tomography (SPECT). METHODS: 99mTc-technegas/macroaggregated albumin SPECT-derived V/Q quotient SPECT and V/Q profile were automatically built for assessment of cross-sectional lung V-Q imbalance in 38 patients with NSIP or UIP. The findings of V/Q quotient SPECT were correlated with lung CT morphology. The results were compared with 12 healthy nonsmoker controls and 48 patients with chronic obstructive pulmonary disease. RESULTS: V/Q quotient SPECT showed 81 crescentic SPLZ with high V/Q ratios in 32 patients (84%) with NSIP or UIP, which were not observed in controls and patients with chronic obstructive pulmonary disease. Sixty-three (77.7%) of them were located at high-attenuation areas (reticular and/or ground-glass opacities) with or without small cystic air spaces (honeycombing and/or traction bronchiectasis) on CT, and 12 (14.8%) at normal lung areas. V/Q profile at the lung sections with crescentic SPLZ with high V/Q ratios showed flattened peaks with broadened V/Q ratio distribution compared with controls, and standard deviation of V/Q ratios in the entire lungs was significantly correlated with partial oxygen arterial blood pressure (P = 0.0009) and predicted diffusing capacity of the lungs for carbon monoxide (P = 0.0139). Five of eight patients with NSIP or UIP and with worsening of hypoxemia showed an extension of SPCZ with high V/Q ratios on follow-up V/Q quotient SPECT, without significant changes on CT. CONCLUSION: A high prevalence of crescentic SPLZ with high V/Q ratios is a characteristic feature of lung V-Q imbalance causing alveolar gas exchange impairment in NSIP and UIP.

[Study of high speed rotation SPECT acquisition method with breath-hold -comparison between dual-head system and triple-head system-].

BACKGROUND: Because lung perfusion Tc-99m MAA of SPECT is generally acquired under the non-breath-hold condition, SPECT image quality is degraded for respiratory lung motion. To solve this problem, a new acquisition mode would need to be developed. We suggest that the acquisition mode is the detector rotating at high speed during the deep breath-hold condition and 20 sec. This acquisition method is known as high-speed detector rotation-multiplied projection single photon emission computed tomography (HSRMP-SPECT). Detail is reconstructed from projection data added while projection data are acquired several times under deep breath-hold sets. PURPOSE: The HSRMP-SPECT technique has been developed under the triple-head system. However, the triple-head system is a small field of view. Thus a description of the entire lung area was impossible under the deep breath-hold condition. The HSRMP-SPECT technique seems needed to make the shift to dual-head system, because the generally dual-head system has a large field of view. We were compared triple-head system with dual-head system, and researched some parameter. RESULT: With lung perfusion HSRMP-SPECT using the dual-head system, description of the entire lung area possible. The triple-head system of 5 projection data sets and dual-head system of 6 projection data sets nearly equaled the total count, and also the coefficient of variation is nearly same. Therefore, we were able to make the triple-head system to the dual-head system the shift on HSRMP-SPECT.

Application of breath-holding SPECT with high-speed-rotation technique in hepatic-function scintigraphy.

Recently, a new method for acquiring SPECT data in deep inspiratory breath hold with a high-speed rotation (HSR-SPECT) technique was developed for pulmonary perfusion scintigraphy. Our purpose in this study was to apply this method to hepatic-function scintigraphy. A phantom study was performed for determining data acquisition times. The coefficient of variation (CV) value was used for evaluating nonuniformity of radioactivity in the liver area. Data acquisition times were determined based on the CV value. According to the results of the phantom study, this method needs at least ten projection data sets for acquiring sufficient counts for a proper diagnosis. Under clinical conditions, breath-holding HSR-SPECT can suppress the respiratory motion effects, better than the conventional method can. In addition, the fusion images made from breath-holding HSR-SPECT images match excellently with CT images.

Infrared absorption change in single-walled carbon nanotubes observed by combination spectroscopy of synchrotron radiation and laser.

The Drude tail due to photo-excited carriers in single-walled carbon nanotubes (SWNTs) has been observed in the mid-infrared region by using combination spectroscopy of synchrotron radiation and Ti:sapphire laser. It is found that the density of photo-excited carriers increases as the sample temperature is raised from 12 to 300 K, and their lifetime is of the order of minutes at 300 K. These facts suggest that the movement of photo-excited carriers is largely affected by some extrinsic defect, thus resulting in the long-lasting Drude reflection in SWNTs.

[Examination of three-detector high-speed-rotation SPECT acquisition under breathhold in body: clinical application of 99mTc-MAA].

In traditional pulmonary perfusion single photon emission computed tomography (SPECT), respiratory lung motion and cyclically varying changes in lung volume during image acquisition inherently degrade the image sharpness of ill-defined perfusion defects. However, because of the lack of an adequate fast imaging technique, perfusion SPECT has never been acquired under breathhold conditions, whereas breathhold images are commonly used for pulmonary magnetic resonance (MR) and computed tomographic (CT) images. Although a high-speed imaging technique combined with a multidetector SPECT system may enable SPECT images to be obtained during a short period of breathholding, image quality would be degraded owing to decreased radioactivity counts and increased statistical noise. To resolve this problem, we developed an innovative SPECT imaging technique using a triple-head SPECT system and the high-speed-detector rotation-multiplied projection (HSRMP) technique, where a single SPECT image was reconstructed from multiple respiratory dimensional breathhold projection data obtained at the same angle. HSRMP provided noiseless high-quality perfusion SPECT images by compensating for decreased radioactivity counts caused by high-speed imaging, and significantly improved image quality and perfusion defect clarity compared with traditional non-breathhold SPECT images.

Assessment of the hepatic and intestinal first-pass metabolism of midazolam in a CYP3A drug-drug interaction model rats.

In the current study, to understand the characteristics of dexamethasone (DEX)-treated female rats as an animal model for drug-drug interactions, a double-cannulation method was applied and separately assessed for the intestinal and hepatic first-pass metabolism of midazolam. Midazolam was administered intravenously or orally to the animals, and midazolam concentrations in the portal and systemic plasma were simultaneously determined. Next, the rates of elimination from the intestine and liver were estimated using the AUC values. After oral administration of midazolam, the entire drug was absorbed without intestinal first-pass metabolism, and 93% of the administered midazolam was extracted in the liver of the DEX-treated female rats. Seven per cent of the midazolam administered reached the systemic circulation. When ketoconazole was given orally to the animals, in conjunction with midazolam, the extraction ratio in the liver decreased from 93% to 77% in the control rats, and the bioavailability of midazolam increased to 23%. On the other hand, after intravenous administration, the elimination half-life of midazolam was not changed by ketoconazole pretreatment. These results indicated that midazolam is only extracted in the liver of DEX-treated female rats and that ketoconazole inhibits the hepatic first-pass metabolism, but not the systemic metabolism. In conclusion, DEX-treated female rats can be used as a drug-drug interaction model via CYP3A4 enzyme inhibition, especially for the hepatic first-pass metabolism of orally administered drugs.

Mechanism of the drug interaction between valproic acid and carbapenem antibiotics in monkeys and rats.

The Ministry of Health and Welfare, Japan banned coadministration of carbapenems, such as panipenem/betamipron (PAPM), meropenem (MEPM), and valproic acid (VPA) because clinical reports have indicated that the coadministration caused seizures in epileptic patients due to lowered plasma levels of VPA. In this study, we have clarified the mechanism of the drug-drug interaction using PAPM, MEPM, and doripenem [S-4661; (+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-[[(3S,5S)-5-[(sulfamoylamino)methyl]-3-pyrrolidinyl]thio]-1-azabicyclo[3.2.0]hept-2-ene-2-caboxylic acid monohydrate], a newly synthesized carbapenem. In vitro experiments using monkey liver slices suggested that the apparent synthetic rate of VPA glucuronide (VPA-G) increased in the presence of carbapenems. However, no such increase was observed in the experiment using monkey liver microsomes. Although no increase of uridine 5'-diphosphate D-glucuronic acid was found in monkey liver slices in the presence of carbapenems, potent inhibitory activity of carbapenems for the hydrolysis of VPA-G was found in monkey and rat liver homogenate. In vivo hydrolysis of VPA-G was clearly shown by the existence of VPA in plasma after dosing of VPA-G to rats, and its inhibition by carbapenems was also clearly shown by the negligible levels of VPA in rat plasma after coadministration of carbapenems and VPA-G. These results clearly indicate one of the important causes of drug interaction as follows: carbapenems would inhibit the hydrolytic enzyme, which is involved in the hydrolysis of VPA-G to VPA, resulting in a decrease of plasma concentration of VPA.

Study on the practical use of quantitative whole-body auto-radioluminography.

The practical use of quantitative radioluminography (RLG) using reading system BAS 2000 (Fuji Photo Film Ltd., Tokyo, Japan) and STORM 820 (Molecular Dynamics, USA) was examined using a chemical matrix as an internal standard, which offers the benefits of being preservative, inexpensive, and easy to handle. The results were as follows: 1. As the water content is within the range of 65-80% for most organs and tissues, we selected a chemical matrix, Tissue-TEK containing 85% water, as a base for the preparation of a standard curve. 2. The calibration curve prepared using Tissue-Tek as the internal standard was compared with the calibration curve using liver paste preparations as the internal standard. The results showed good linearity in both cases, with almost no difference in the slopes of the two calibration curves. 3. The PSL-BG or MD counts/pixel-BG values of the lowest radioactivity concentration measured for small areas of the region of interest (ROI) showed large fluctuations with both BAS 2000 and STORM 820, but the fluctuation became less than 15% at above 25 mm(2) of ROI. 4. The value of dpm/g calculated using the calibration curve prepared from Tissue-Tex internal standards showed a very good correlation with the values of dpm/g obtained by scraping off the tissue from the remaining block and conducting measurements with a liquid scintillation counter.

[Significance of the visual evaluation method using the two-visit method (two-sample preference test suggested by Ferris)].

To increase the accuracy of the visual evaluation method, we studied the significance of the two-sample preference test using the two-visit method, as proposed by Ferris. Advantages of this method include not only its ability to estimate whether the image quality of the sample is statistically the same but also its ability to distinguish the difference between samples more clearly than when using the conventional two-sample preference test or paired-comparison method. However, a disadvantage is that this method involves two observations of the same sample. When using chest images, even if a difference between the samples is not recognizable by the conventional method, a significant difference can be elicited with this method. The data obtained by this method can be evaluated with the paired-comparison method, so some samples may be ranked as well. Therefore, we verified that the two-sample preference test, which Ferris formulated, is useful in visual evaluations.

Liver-specific distribution of rosuvastatin in rats: comparison with pravastatin and simvastatin.

Rosuvastatin is a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. The liver is the target organ for the lipid-regulating effect of rosuvastatin; therefore liver-selective uptake of this drug is a desirable property. The aim of this study was to investigate, and compare with pravastatin and simvastatin, the tissue-specific distribution of rosuvastatin. Bolus intravenous doses (5 mg/kg) of radiolabeled rosuvastatin, pravastatin, and simvastatin were administered to rats, and initial uptake clearance (CL(uptake)) in various tissues was calculated. Hepatic CL(uptake) of rosuvastatin (0.885 ml/min/g tissue) was significantly (p < 0.001) larger than that of pravastatin (0.703 ml/min/g tissue), and rosuvastatin was taken up by the hepatic cells more selectively and efficiently than pravastatin. Hepatic CL(uptake) of simvastatin (1.24 ml/min/g tissue) was significantly larger than that of rosuvastatin (p < 0.01) and pravastatin (p < 0.001). However, adrenal CL(uptake) of simvastatin (1.55 ml/min/g tissue) was larger than hepatic CL(uptake), and simvastatin was distributed to other tissues more easily than rosuvastatin. Microautoradiography of the liver, spleen, and adrenal was undertaken 5 min after administration of the study drugs; distribution was quantified by counting the number of silver grains. After administration of rosuvastatin and pravastatin, silver grains were distributed selectively in the intracellular space of the liver, but more rosuvastatin (3.3 +/- 1.0 x 10(5) particles/mm(2)) than pravastatin (2.0 +/- 0.3 x 10(5) particles/mm(2)) tended to distribute to the liver. Simvastatin was less liver-specific (it also distributed to the spleen and adrenal). The results of this study indicated that rosuvastatin was taken up by hepatic cells more selectively and more efficiently than pravastatin and simvastatin.