Anterior mediastinal solid tumours in adults: characterisation using dynamic contrast-enhanced MRI, diffusion-weighted MRI, and FDG-PET/CT.

AIM: To find significant parameters to characterise anterior mediastinal solid tumours in adults using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), diffusion-weighted MRI (DWI), and combined 2-[(18)F]-fluoro-2-deoxy-d-glucose positron-emission tomography/computed tomography (FDG-PET/CT). MATERIALS AND METHODS: Forty-eight histologically confirmed anterior mediastinal solid tumours in 48 patients (24 men, 24 women; age range 21-83 years, mean 50.7 years) were examined. The parameters analysed were maximal diameter, presence of capsule/septa on T2-weighted images, time-signal intensity curves (TICs), apparent diffusion coefficient (ADC), and maximum standardised uptake value (SUVmax). Also examined was whether any differences between histological types could be seen in these parameters. In a validation study, 42 anterior mediastinal solid tumours in 42 patients were examined consecutively. RESULTS: The washout pattern on TIC was seen only in thymic epithelial tumours (20/32). SUVmax of lymphoma (mean, 17.9), malignant germ cell tumours (14.2), and thymic carcinomas (15.6) were significantly higher than that of thymomas (6.1). The mean maximal diameter of thymic epithelial tumours was significantly smaller than that of lymphomas (p<0.01) and malignant germ cell tumours (p<0.05). The validation study also yielded high accuracy (38/42, 91%) in differentiation among the anterior mediastinal solid tumours. CONCLUSION: The SUVmax, TIC pattern on DCE-MRI, and maximal diameter might be useful to differentiate anterior mediastinal solid tumours in adults.

Low-dose CT screening using hybrid iterative reconstruction: confidence ratings of diagnoses of simulated lesions other than lung cancer.

OBJECTIVE: To evaluate the confidence ratings of diagnoses of simulated lesions other than lung cancer on low-dose screening CT with hybrid iterative reconstruction (IR). METHODS: Simulated lesions (emphysema, mediastinal masses and interstitial pneumonia) in a chest phantom were scanned by a 320-row area detector CT. The scans were performed by 64-row and 160-row helical scans at various dose levels and were reconstructed by filtered back projection (FBP) and IR. Emphysema, honeycombing and reticular opacity were visually scored on a four-point scale by six thoracic radiologists. The ground-glass opacity as a percentage of total lung volume (%GGO), CT value and contrast-to-noise ratio (CNR) of mediastinal masses were calculated. These scores and values were compared between FBP and IR. Wilcoxon's signed-rank test was used (p < 0.05). Interobserver agreements were evaluated by κ statistics. RESULTS: There were no significant differences in visual assessment. Interobserver agreement was almost perfect. CT values were almost equivalent between FBP and IR, whereas CNR with IR was significantly higher than that with FBP. %GGO significantly increased at low-dose levels with FBP; however, IR suppressed the elevation. CONCLUSION: The confidence ratings of diagnoses of simulated lesions other than lung cancer on low-dose CT screening were not degraded with hybrid IR compared with FBP. ADVANCES IN KNOWLEDGE: Hybrid IR did not degrade the confidence ratings of diagnoses on visual assessment and differential diagnoses based on CT value of mediastinal masses, and it showed the advantage of higher GGO conspicuity at low-dose level. Radiologists can analyse images of hybrid IR alone on low-dose CT screening for lung cancer.

Changes of the apparent diffusion coefficient in brain diffusion-weighted images due to subject positioning: A simulation study.

BACKGROUND AND PURPOSE: The purpose of this work was to investigate whether the cortical apparent diffusion coefficient (ADC) values derived from brain diffusion-weighted images vary with changes in the position of the subject against a static magnetic field. MATERIALS AND METHODS: To focus on the variations in ADC due to the change of subject positioning, a simulation was performed using a digital brain phantom. The magnetic field inhomogeneities in the digital phantom were calculated for each subject position while changing the angle between the direction of the static field and the head of the digital phantom. The angle was changed from 0 to 40 degrees at 10-degree intervals. For each angle, the diffusion-weighted images were simulated based on magnetic resonance physics in which the magnetic field inhomogeneity was taken into account. The relative differences of average ADC values between the tilt angles were calculated to evaluate the variations in ADC. The Wilcoxon rank-sum test was used for comparisons of ADC values between the tilt angles for each cortical region. RESULTS: In the cortical regions distorted by magnetic field inhomogeneities, the average ADC values differed significantly according to the position of the subject (P < 0.05). The range of the relative differences in average ADC values in relation to the differences in subject positioning was approximately 1% to 12%. CONCLUSION: Our results suggest that subject positioning against a static field is one of the factors affecting the accuracy of cortical ADC measurements derived from brain diffusion-weighted images.

Detectability of simulated interstitial pneumonia on chest radiographs: comparison between irradiation side sampling indirect flat-panel detector and computed radiography.

OBJECTIVE: To compare the detectability of simulated interstitial pneumonia on chest radiographs between an irradiation side sampling indirect flat-panel detector (ISS-FPD) and computed radiography (CR). METHODS: Simulated interstitial pneumonia findings (ground-glass opacity, reticular opacity and honeycomb lung) were superimposed on an anthropomorphic chest phantom. Chest radiographs were acquired under three exposure levels (4.0, 3.2 and 2.0 mAs) with an ISS-FPD and with CR. 5 thoracic radiologists evaluated 72 images for the presence or absence of a lesion over each of 6 areas. A total of 1296 observations were analysed in a receiver-operating characteristic analysis. A jackknife method was used for the statistical analysis. RESULTS: The areas under the curves (AUCs) for the detection of simulated honeycomb lung obtained with the ISS-FPD were significantly larger than those obtained with CR at all exposure conditions. For the detection of simulated ground-glass opacity and reticular opacity, there were no significant differences between the two systems. In addition, the AUCs for the detectability of simulated honeycomb lung obtained with the ISS-FPD at all exposure levels were significantly larger than those obtained with CR at 4 mAs. CONCLUSION: The ISS-FPD was superior to CR for the detection of simulated honeycomb lung. Provided that the chosen model is representative of interstitial pneumonia, the use of an ISS-FPD might reduce a patient's exposure dose during the detection of interstitial pneumonia. ADVANCES IN KNOWLEDGE: The ISS-FPD has shown its advantage compared with CR in the detection of honeycombing, one sign of interstitial pneumonia.

Evaluation of the extent of ground-glass opacity on high-resolution CT in patients with interstitial pneumonia associated with systemic sclerosis: comparison between quantitative and qualitative analysis.

AIM: To verify whether quantitative analysis of the extent of ground-glass opacity (GGO) on high-resolution computed tomography (HRCT) could show a stronger correlation with the therapeutic response of interstitial pneumonia (IP) associated with systemic sclerosis (SSc) compared with qualitative analysis. MATERIALS AND METHODS: Seventeen patients with IP associated with SSc received autologous peripheral blood stem cell transplantation (auto-PBSCT) and were followed up using HRCT and pulmonary function tests. Two thoracic radiologists assessed the extent of GGO on HRCT using a workstation. Therapeutic effect was assessed using the change of vital capacity (VC) and diffusing capacity of the lung for carbon monoxide (DLco) before and 12 months after PBSCT. Interobserver agreement was assessed using Spearman's rank correlation coefficient and the Bland-Altman method. Correlation with the therapeutic response between quantitative and qualitative analysis was assessed with Pearson's correlation coefficients. RESULTS: Spearman's rank correlation coefficient showed good agreement, but Bland-Altman plots showed that proportional error could be suspected. Quantitative analysis showed stronger correlation than the qualitative analysis based on the relationships between the change in extent of GGO and VC, and change in extent of GGO and DLco. CONCLUSION: Quantitative analysis of the change in extent of GGO showed stronger correlation with the therapeutic response of IP with SSc after auto-PBSCT than with the qualitative analysis.

SU-E-I-59: Investigation of the Usefulness of a Standard Deviation and Mammary Gland Density as Indexes for Mammogram Classification.

PURPOSE: To investigate the usefulness of the standard deviation of pixel values in a whole mammary glands region and the percentage of a high- density mammary glands region to a whole mammary glands region as features for classification of mammograms into four categories based on the ACR BI-RADS breast composition. METHODS: We used 36 digital mediolateral oblique view mammograms (18 patients) approved by our IRB. These images were classified into the four categories of breast compositions by an experienced breast radiologist and the results of the classification were regarded as a gold standard. First, a whole mammary region in a breast was divided into two regions such as a high-density mammary glands region and a low/iso-density mammary glands region by using a threshold value that was obtained from the pixel values corresponding to a pectoral muscle region. Then the percentage of a high-density mammary glands region to a whole mammary glands region was calculated. In addition, as a new method, the standard deviation of pixel values in a whole mammary glands region was calculated as an index based on the intermingling of mammary glands and fats. Finally, all mammograms were classified by using the combination of the percentage of a high-density mammary glands region and the standard deviation of each image. RESULTS: The agreement rates of the classification between our proposed method and gold standard was 86% (31/36). This result signified that our method has the potential to classify mammograms. CONCLUSIONS: The combination of the standard deviation of pixel values in a whole mammary glands region and the percentage of a high-density mammary glands region to a whole mammary glands region was available as features to classify mammograms based on the ACR BI- RADS breast composition.

SU-E-I-62: Investigation of Dominant Factors Affecting Fatigue in Image Reading of Radiologists.

PURPOSE: To investigate dominant factors affecting fatigue in image reading of radiologists. METHODS: Two kinds of fatigue were assessed in this study. One was fatigue in the central nervous system evaluated by the critical fusion frequency (CFF). The other was eye fatigue evaluated by a score determined from a questionnaire based on the oculomotor strain subscale from the Simulator Sickness Questionnaire (SSQ). When fatigue increases, the CFF and the SSQ score indicate low and high values, respectively. The fatigue of seventeen radiologists was assessed before and after their daily image reading. The reading times and the numbers of images were different among the assessments, and ranged about 1.5 - 5.0 hours and 1,000 - 12,000 images, respectively. The assessments of fatigue were repeated four times for each radiologist on different days. Finally, the measurements of the two kinds of fatigue were analyzed in terms of years of experience, age, sleeping time the previous night, ambient light conditions, reading time, and the numbers of interpreted images, series, and cases. RESULTS: The CFF and SSQ score after image reading were significantly lower and higher than those measured before image reading, respectively. Younger and less experienced radiologists indicated a higher level of fatigue than older and more experienced radiologists in both the CFF and the SSQ score. When radiologists interpreted clinical images for longer hours, the SSQ score tended to be higher. On the other hand, there was little incremental difference in the CFF among different lengths of reading time. No obvious differences were observed in the other items. CONCLUSIONS: Less experience with reading images, a younger age, and a longer reading time could be dominant factors affecting fatigue in image reading.

Imaging findings of neurogenic tumours in the head and neck region.

OBJECTIVE: The aim of this study was to describe the CT, MRI and ultrasonography findings of five cases of neurogenic tumours in the head and neck region. METHODS: Five neurogenic tumours were analysed with respect to their CT value, the presence of cystic change, target sign, lobulation, connection to the nerve and vascularity. RESULTS: The contrast-enhanced CT (ECT) of the schwannomas demonstrated either a mass with low enhancement (two out of three cases), which reflected the predominant Antoni B components, or a mass with cystic changes, which was an Antoni A-based schwannoma displaying cystic changes (one out of three cases). On MRI, all tumours showed homogeneous and isointense signals for muscle on T1 weighted images (T1 WIs). T2 weighted images (T2 WIs) and gadolinium (Gd)-enhanced T1 WIs demonstrated target sign in both schwannomas. Ultrasound examination showed a well-defined, ovoid or round hypoechoic mass. The direct connection to the nerve was demonstrated in two of the five cases. Lobulation was observed in only one of the five cases and cystic changes were observed in one of the five cases. In all of the cases, no vascularity was seen in power Doppler images (PDIs) obtained percutaneously. CONCLUSIONS: Low-enhanced areas on ECTs can be specific for schwannomas, which suggests the predominance of Antoni B components. The target sign on T2 WIs and Gd-enhanced T1 WIs can be specific, which can be used to differentiate the two different components (Antoni A and Antoni B). The direct connection to the nerve can be a specific finding for neurogenic tumours; however, at present the sensitivity is 40%.

Apparent diffusion coefficient calculated with relatively high b-values correlates with local failure of head and neck squamous cell carcinoma treated with radiotherapy.

BACKGROUND AND PURPOSE: Few studies have investigated the relationship between ADC and clinical outcome in HNSCC. Our hypothesis has that relatively high pretreatment ADC would correlate with local failure of HNSCC treated with radiation therapy. MATERIALS AND METHODS: This includes prospective and validation studies. Seventeen patients treated with radiation therapy for primary HNSCC completed the prospective study. Variables considered to affect local failure including MR imaging-related parameters such as ADC and its change ratio were compared between patients with local failure and controls, and those showing difference or association with local failure were further tested by survival analysis. Furthermore, variables were analyzed in 40 patients enrolled in the validation study. RESULTS: Relatively high ADC calculated with b-values (300, 500, 750, and 1000 s/mm(2)) before treatment, high ADC increase ratio, and treatment method (chemoradiotherapy versus radiation therapy alone) revealed significant difference between patients with local failure and controls or association with local failure. In Cox proportional hazard testing, high ADC before treatment alone showed significant association with local failure (P = .0186). In the validation study, tumor volume before treatment, high ADC before treatment, T stage (T12 versus T34), and treatment method showed significance. Tumor volume before treatment (P = .0217) and high ADC before treatment (P = .0001) revealed significant association with local failure in Cox proportional hazard testing. High ADC before treatment was superior to tumor volume before treatment regarding association with local failure. CONCLUSIONS: These results suggest pretreatment ADC obtained at high b-values as well as tumor volume correlate with local failure of HNSCC treated with radiation therapy.

Size and orientation of masticatory muscles in patients with mandibular laterognathism.

Size measurements of jaw muscles reflect their force capabilities and correlate with facial morphology. Using MRI, we examined the size and orientation of jaw muscles in patients with mandibular laterognathism in comparison with a control group. We hypothesized that the muscles of the deviated side would be smaller than those of the non-deviated side, and that the muscles of both sides would be smaller than in controls. In patients, a comparison of deviated and non-deviated sides showed, in orientation, differences for masseter and medial pterygoid muscles, but, in size, differences only for the masseter muscle. Nevertheless, muscle sizes in patients were much smaller than in controls. Lateral displacement of the mandible can explain the orientation differences, but not the smaller muscle size, in patients. It is possible that the laterodeviation initiates an adaptive process in the entire jaw system, resulting in extensive atrophy of the jaw muscles.

Multiple splicing variants of two new human ATP-binding cassette transporters, ABCC11 and ABCC12.

Two new human ABC transporters, ABCC11 and ABCC12, were cloned from a cDNA library of human adult liver. ABCC11 and ABCC12 genes consist of 30 and 29 exons, respectively, and they are tandemly located in a tail-to-head orientation on human chromosome 16q12.1. The predicted amino acid sequences of both gene products show a high similarity with ABCC5. The transcripts of ABCC11 and ABCC12 genes were detected by PCR in various adult human tissues, including liver, lung, and kidney, and also in several fetal tissues. By searching cDNA libraries from various human tissues, we have identified alternative splicing variants of ABCC11 and ABCC12 genes at significantly high frequencies. One splice variant lacking the exon 28 corresponded to about 25% of total ABCC11 gene transcripts. Furthermore, four splicing variants encoding putatively short peptides were predominant in ABCC12 gene transcripts. Those splicing variants may represent diverse biological functions of these ABC transporter genes.

Nonfunctioning adrenal rest tumor of the liver: radiologic appearance.

We describe the radiologic features of an adrenal rest tumor of the liver. The adrenal rest tumor appeared on ultrasound as a round, well defined, heterogeneous, solid mass in the posterior aspect of the liver, on angiography as a homogeneous hypervascular mass, and on dynamic CT as a mass containing components of both fat density and soft tissue density and showing early fill-in and early fill-out. Adrenal rest tumors should be included in the lists of hypervascular or fat-containing masses in the liver.

p-aminohippuric acid transport at renal apical membrane mediated by human inorganic phosphate transporter NPT1.

Organic anions are secreted into urine via organic anion transporters across the renal basolateral and apical membranes. However, no apical membrane transporter for organic anions such as p-aminohippuric acid (PAH) has yet been identified. In the present study, we showed that human NPT1, which is present in renal apical membrane, mediates the transport of PAH. The K(m) value for PAH uptake was 2.66 mM and the uptake was chloride ion sensitive. These results are compatible with those reported for the classical organic anion transport system at the renal apical membrane. PAH transport was inhibited by various anionic compounds. Human NPT1 also accepted uric acid, benzylpenicillin, faropenem, and estradiol-17beta-glucuronide as substrates. Considering its chloride ion sensitivity, Npt1 is expected to function for secretion of PAH from renal proximal tubular cells. This is the first molecular demonstration of an organic anion transport function for PAH at the renal apical membrane.

Faropenem transport across the renal epithelial luminal membrane via inorganic phosphate transporter Npt1.

We previously showed that the mouse inorganic phosphate transporter Npt1 operates in the hepatic sinusoidal membrane transport of anionic drugs such as benzylpenicillin and mevalonic acid. In the present study, the mechanism of renal secretion of penem antibiotics was examined by using a Xenopus oocyte expression system. Faropenem (an oral penem antibiotic) was transported via Npt1 with a Michaelis-Menten constant of 0.77 +/- 0.34 mM in a sodium-independent but chloride ion-sensitive manner. When the concentration of chloride ions was increased, the transport activity of faropenem by Npt1 was decreased. Since the concentration gradient of chloride ions is in the lumen-to-intracellular direction, faropenem is expected to be transported from inside proximal tubular cells to the lumen. So, we tested the release of faropenem from Xenopus oocytes. The rate of efflux of faropenem from Npt1-expressing oocytes was about 9.5 times faster than that from control water-injected Xenopus oocytes. Faropenem transport by Npt1 was significantly inhibited by beta-lactam antibiotics such as benzylpenicillin, ampicillin, cephalexin, and cefazolin to 24.9, 40. 5, 54.4, and 26.2% of that for the control, respectively. Zwitterionic beta-lactam antibiotics showed lesser inhibitory effects on faropenem uptake than anionic derivatives, indicating that Npt1 preferentially transports anionic compounds. Other anionic compounds, such as indomethacin and furosemide, and the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid significantly inhibited faropenem uptake mediated by Npt1. In conclusion, our results suggest that Npt1 participates in the renal secretion of penem antibiotics.

High-resolution CT characteristics of poorly differentiated adenocarcinoma of the peripheral lung: comparison with well differentiated adenocarcinoma.

OBJECTIVE: The purpose of this study was to elucidate the characteristic high-resolution CT (HRCT) findings of poorly differentiated adenocarcinoma (PDA) in comparison with those of well differentiated adenocarcinoma (WDA). MATERIALS AND METHODS: We investigated the HRCT features of surgically resected PDAs (n=21) and WDAs (n=31). We analyzed the margin, CT attenuation, and internal architecture of the tumor and findings in the surrounding lung field, comparing them with the corresponding pathologic findings. RESULTS: Smoothness of the greater part (full-1/2 round) of the tumor and solid appearance were more prevalent in PDAs than WDAs (81% vs. 32%, 100% vs. 35%) [p<0.01]. Air-bronchogram was prevalent in WDAs (58%), but was never seen in PDAs [p<0.01]. Ground-glass opacity in PDAs pathologically corresponded to inflammation and edema in the alveolar space. CONCLUSIONS: Smoothness of the tumor margin and solid appearance without air-bronchogram were more commonly found in PDA than in WDA. HRCT may predict the histological differentiation of adenocarcinoma in selected cases in which differentiation is inconclusive by sputum cytology and transbronchial or CT-guided biopsy.

Hepatocellular carcinoma with ring calcification: report of two cases.

Two cases of hepatocellular carcinoma (HCC) with ring calcification are reported together with their CT findings. HCC in both cases showed little early enhancement followed by delayed enhancement on dynamic CT. The pathologic specimen in one case showed HCC with fairly abundant fibrosis, and calcification was noted underneath the thick fibrous capsule, which might explain the enhancement pattern on CT.

Immunohistochemical and functional characterization of pH-dependent intestinal absorption of weak organic acids by the monocarboxylic acid transporter MCT1.

The participation of the monocarboxylic acid transporter MCT1 in the intestinal absorption of weak organic acids has been clarified by functional characterization, by use of stably transfected cells, and by immunohistochemical location of the transporter in intestinal tissues. Immunohistochemical analysis by use of the anti-MCT1 antibody showed that MCT1 is distributed throughout the upper and lower intestines, especially in the basolateral membrane and, to a lesser extent, in the brush-border membrane. When the transporter gene rat MCT1 was transfected into MDA-MB231 cells, transport of benzoic acid, a model weak organic acid that has been generally believed to be transported across the cell membranes by passive diffusion, and lactic acid in rat MCT1-transfected cells was significantly increased compared with transport in cells transfected with the expression vector pRc-CMV alone (mock cells). The observed transport was pH-dependent and activity increased between pH 7.5 and pH 5.5, whereas pH-dependence in mock cells was moderate. Rat MCT1-mediated benzoic acid uptake was saturable, with an apparent Km value of 3.05 mM. In addition, MCT1 increased the efflux of [14C]benzoic acid from the cells. Several weak organic acids were also transported by rat MCT1. These results show that pH-dependent intestinal absorption of weak organic acids, previously explained in terms of passive diffusion according to the pH-partition hypothesis, is at least partially accounted for by MCT1-mediated transport energized at acidic pH by utilization of the proton gradient as a driving force.

"Crazy paving appearance" on high resolution CT in various diseases.

PURPOSE: The purpose of this work was to demonstrate the variety of causes of crazy-paving appearance (CPA) on high resolution CT (HRCT). METHOD: To identify cases exhibiting CPA (ground-glass opacity with superimposed interlobular septal thickening and intralobular interstitial thickening) on HRCT, we prospectively searched for them over a period of 29 months. RESULTS: We identified 10 cases of CPA on HRCT, including 4 Pneumocystis carinii pneumonia, 1 alveolar proteinosis, 1 usual interstitial pneumonia, 1 pulmonary hemorrhage, 1 acute radiation pneumonitis, 1 adult respiratory distress syndrome, and 1 drug-induced pneumonitis. CONCLUSION: CPA can result from a variety of diseases. When we encounter CPA on HRCT, clinical information is necessary for differentiation of these entities.

Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance.

Carnitine deficiency, either primary or drug-induced, causes critical symptoms and is thought to involve alteration of active transport of carnitine across the plasma membrane of tissues as the underlying mechanism. Recently, we showed that human organic cation transporter, hOCTN2, cloned as a member of the organic cation transporter family, is a physiologically important Na(+)-dependent high-affinity carnitine transporter in humans. In this study, we further characterized the functional properties of hOCTN2 and examined the interaction between hOCTN2-mediated carnitine transport and clinically used drugs to assess possible toxicological effects. When expressed in human embryonic kidney (HEK)293 cells, hOCTN2 showed low but significant stereospecific transport activity: D-carnitine was transported with lower affinity (K(m) = 10.9 microM) than the L-isomer (K(m) = 4.3 microM). One Na(+) appeared to be associated with the transport of one carnitine molecule. hOCTN2-mediated transport of acetyl-L-carnitine was also Na(+)-dependent and of high affinity, with a K(m) value of 8.5 microM. To examine the transport activity for organic cations other than carnitine and the possible relationship of drug-induced carnitine deficiency with hOCTN2, the inhibitory effect of several drugs on hOCTN2-mediated L-carnitine transport was examined. Many zwitterionic drugs, such as cephaloridine, and many cationic drugs, such as quinidine and verapamil, exhibited significant inhibitory effects. Among these inhibitors, tetraethylammonium, pyrilamine, quinidine, verapamil, and valproate were found to be transported by hOCTN2. The results suggest that the carnitine deficiency-related toxicological effects by long-term treatment with such drugs might be ascribed to a functional alteration of hOCTN2-mediated carnitine transport.