3-Deazaadenosine prevents smooth muscle cell proliferation and neointima formation by interfering with Ras signaling.

3-Deazaadenosine (c3Ado) is a potent inhibitor of S-adenosylhomocysteine hydrolase, which regulates cellular methyltransferase activity. In the present study, we sought to determine the effect of c3Ado on vascular smooth muscle cell (VSMC) function and neointima formation in vivo. c3Ado dose-dependently prevented the proliferation and migration of human coronary VSMCs in vitro. This was accompanied by an increased expression of the cyclin-dependent kinase inhibitors p21(WAF1/Cip1), p27(Kip1), a decreased expression of G(1)/S phase cyclins, and a lack of retinoblastoma protein hyperphosphorylation. In accordance with these findings, fluorescence-activated cell-sorting analysis of propidium iodide-stained cells indicated a cell cycle arrest in the G(0)/G(1) phase. Importantly, c3Ado did not affect the number of viable (trypan blue exclusion) or apoptotic cells (TUNEL). Mechanistically, c3Ado prevented FCS-induced Ras carboxyl methylation and membrane translocation and activity by inhibiting isoprenylcysteine carboxyl methyltransferase and reduced FCS-induced extracellular signal-regulated kinase (ERK)1/2 and Akt phosphorylation in a dose-dependent manner. Conversely, rescuing signal transduction by overexpression of a constitutive active Ras mutant abrogated c3Ado's effect on proliferation. For in vivo studies, the femoral artery of C57BL/6 mice was dilated and mice were fed a diet containing 150 microg of c3Ado per day. c3Ado prevented dilation-induced Ras activation, as well as ERK1/2 and Akt phosphorylation in vivo. At day 21, VSMC proliferation (proliferating-cell nuclear antigen [PCNA]-positive cells), as well as the neointima/media ratio (0.7+/-0.2 versus 1.6+/-0.4; P<0.05) were significantly reduced, without any changes in the number of apoptotic cells. Our data indicate that c3Ado interferes with Ras methylation and function and thereby with mitogenic activation of ERK1/2 and Akt, preventing VSMC cell cycle entry and proliferation and neointima formation in vivo. Thus, therapeutic inhibition of S-adenosylhomocysteine hydrolase by c3Ado may represent a save and effective novel approach to prevent vascular proliferative disease.

Effectiveness of therapeutic lymphography on lymphatic leakage.

BACKGROUND: The number of conventional lymphographies has declined markedly since the introduction of cross-sectional imaging techniques. Nevertheless, lymphography has a high potential as a reliable method to visualize and directly occlude lymphatic leaks. When used as a distinct radiological procedure with the intention to treat, this application can be described as therapeutic lymphography. PURPOSE: To investigate if therapeutic lymphography is a reliable method to treat lymphatic leakage when conservative treatment fails and to investigate which parameters influence the success rate. MATERIAL AND METHODS: Between August 1995 and January 2008, 50 patients with lymphatic leakage in form of chylothorax, chylous ascites, lymphocele, and lymphatic fistulas underwent conventional therapeutic lymphography after failure of conservative therapy. Of these 50 patients, seven could not be statistically evaluated in our retrospective study: one patient died of cancer 1 day after lymphography, and six were excluded due to various technical problems. The remaining 43 patients were evaluated. Therapeutic success was evaluated and correlated to the volume of lymphatic leakage (more or less than 500 mL/day), as assessed by drainage. RESULTS: In nearly 79% of patients, the location of the leak could be detected, and surgical intervention could be planned when therapeutic lymphography failed. Due to the irrigating effect of the contrast medium (lipiodol), the lymphatic leak could be completely occluded in 70% of patients when the lymphatic drainage volume was less than 500 mL/day. Even when lymphatic drainage was higher than 500 mL/day, therapeutic lymphography was still successful in 35% of the patients. The overall success rate in patients with failed conservative treatment was 51%. Success did not depend on other factors such as age and sex, cause of lymph duct damage, or time elapsed between lymphatic injury and intervention. CONCLUSION: Therapeutic lymphography is an effective method in the treatment of lymphatic leakage when conservative therapy fails. The volume of lymphatic drainage per day is a significant predictor of the therapeutical success rate.

MRI and MRCP findings of the pancreas in patients with diabetes mellitus: compared analysis with pancreatic exocrine function determined by fecal elastase 1.

GOALS: To review magnetic resonance imaging and magnetic resonance cholangiopancreatography (MRCP) findings in patients with diabetes mellitus (DM), with pancreatic exocrine insufficiency, and with combined pancreatic exocrine insufficiency and DM. STUDY: MRI/MRCP findings of 82 consecutive patients with DM (n=28), pancreatic exocrine insufficiency (n=25), and combination of both (n=29) were evaluated and compared with MRI/MRCP findings of 21 healthy volunteers with normal pancreatic exocrine function. Pancreatic exocrine function was determined by fecal elastase 1. MRCP images were evaluated according to the Cambridge classification. MRI of the pancreas was assessed for pancreatic size, signal intensity ratio (SIR), and arterial/venous enhancement ratio (A/V). RESULTS: On MRI, significant difference was present in terms of mean values of pancreatic size (P<0.0001), A/V (P<0.02), and SIR (P<0.005) between the control group and groups of patients with DM, pancreatic exocrine insufficiency, and combined DM and pancreatic exocrine insufficiency. No significant difference was observed between groups of patients with DM and pancreatic exocrine function alone in terms of pancreatic size, A/V, and SIR. Chronic pancreatitis MRCP findings were present with increasing frequency in groups of DM, pancreatic exocrine insufficiency, and combination of both. CONCLUSIONS: MRI/MRCP findings suggesting chronic pancreatitis may exist in patients with DM comparable to patients with pancreatic exocrine insufficiency. The frequency and severity of MRI/MRCP findings increase when the patients have combined DM and pancreatic exocrine insufficiency.

Role of computed tomography voxel size in detection and discrimination of calcium and iron deposits in atherosclerotic human coronary artery specimens.

OBJECTIVE: This study evaluated the influence of voxel size on its ability to discriminate calcium from iron deposits in ex vivo coronary arteries. METHODS: Postmortem human coronary arteries underwent multislice computed tomographic scan at (600-microm) voxel size to provide an index of computed tomography (CT) image noise and synchrotron-based micro-CT at (4-microm) voxel size to provide data for generating a range of voxel sizes 4 to (600-microm) after grayscale noise was added to the projection images before reconstruction so as to mimic the effect of retaining the same radiation exposure involved in the multislice computed tomographic scan. RESULTS: At voxel sizes of (20-microm) or smaller, iron deposits could be identified based on CT grayscale value. Voxels of (100-microm) or larger cannot resolve nor distinguish iron deposits from calcifications by virtue of CT grayscale value. CONCLUSIONS: Clinical CT scanners cannot be expected to discriminate iron deposits from calcifications by their CT value alone in the arterial wall.

Hepatobiliary and pancreatic MRI and MRCP findings in patients with HIV infection.

OBJECTIVE: The purpose of this article is to describe the spectrum of MRI and MR cholangiopancreatography (MRCP) findings of hepatic, pancreatic, and biliary manifestations in patients with HIV infection. CONCLUSION: The spectrum of MRI and MRCP findings in HIV-infected patients includes acute or chronic hepatitis (or both), pancreatitis, cholangitis, acalculous cholecystitis, and biliary strictures that may resemble primary sclerosing cholangitis. The presence of segmental extrahepatic biliary strictures is characteristic of AIDS cholangiopathy.

Correlation of vasa vasorum neovascularization and plaque progression in aortas of apolipoprotein E(-/-)/low-density lipoprotein(-/-) double knockout mice.

OBJECTIVE: We hypothesized that apolipoprotein E (apoE)(-/-)/low-density lipoprotein (LDL)(-/-) double knockout mice might develop vasa vasorum (VV) in association with advanced lesion formation. METHODS AND RESULTS: Aortas from apoE(-/-)/LDL(-/-) mice aged 16, 18, 20, or 80 weeks were infused in situ with Microfil, harvested, and scanned with micro-computed tomography (CT). We characterized plaque volume and CT "density" as well as VV luminal volume along the aorta using Analyze 6.0 software. Results were complemented by a detailed histological plaque classification according to American Heart Association guidelines. From 16 to 80 weeks, plaque volume and VV opacified lumen volume increased with age (P<0.001). The 3-dimensional micro-CT images of arterial and venous VV trees allowed perfusion territories to be delineated. The spatial location and magnitude of VV density and adventitial inflammation were strongly correlated in advanced atherosclerotic lesions (r=0.91) and identified as an independent correlate to advanced lesions. At age 80 weeks, VV luminal volume was increased 20-fold compared with animals at age 16 weeks (P<0.001). Micro-CT showed that adventitial VV communicate with intraplaque microvessels. CONCLUSIONS: Our results show that apoE(-/-)/LDL(-/-) double knockout mice develop VV and advanced atheromas along the aorta. Lesion volume was closely associated with amount of neovascularization in advanced atheromas.

High-resolution MRI of basal cell carcinomas of the face using a microscopy coil.

OBJECTIVE: The objective of this article is to evaluate the diagnostic accuracy of high-resolution MRI using a microscopy surface coil to stage basal cell carcinomas of the face. CONCLUSION: High-resolution MRI using a microscopy surface coil is a promising method to determine the extension of basaliomas of the facial region and to exclude infiltration of bone by the tumor.

Effect of i.v. injection of radiographic contrast media on human renal blood flow.

OBJECTIVE: The purpose of our study was to assess the effect of an i.v. injection of iodinated radiographic contrast medium on human renal blood flow using cine phase-contrast MRI. SUBJECTS AND METHODS: We examined 12 healthy adult volunteers. Blood flow in one renal artery was measured using cine phase-contrast imaging (1.5-T MR system). Each volunteer received 120 mL of isotonic sodium chloride on study day 1 and 120 mL of a low-osmolar, nonionic, iodinated contrast medium (iomeprol, 400 mg I/mL) on study day 2. Repetitive measurements were performed before (up to five measurements in 5 minutes) and after (up to 13 measurements in 30 minutes) the injection was started. RESULTS: Mean basal renal artery blood flow was 664 mL/min. In response to the injection of the test substances, we found a significantly larger decrease in average renal blood flow for contrast medium than for sodium chloride (31.9 mL/min vs 18.3 mL/min, p = 0.0481). Furthermore, in analyzing the measurements at early time points, we found a significant decrease (11.4% +/- 4.7% [SD]; Bonferroni-corrected, p < 0.05) in renal blood flow 2 minutes after the injection of the contrast medium was started. Sodium chloride did not produce a significant effect at any time. CONCLUSION: Cine phase-contrast MRI can measure a decrease in renal blood flow in humans in response to an i.v. injection of iodinated radiographic contrast medium. Therefore, cine phase-contrast MRI can be a helpful and noninvasive tool for further investigations of contrast media-induced changes in human renal blood flow and their possible impact on the development of contrast-induced nephropathy.

Split renal function measured by triphasic helical CT.

PURPOSE: To present a method for calculating split renal function solely from routine triphasic helical computed tomography (CT). SUBJECTS AND METHODS: We retrospectively included 26 adult patients who received renal scintigraphy and triphasic CT within 4 weeks in the years 2003 and 2004. All scans were performed using a standard abdominal protocol. Split renal function was calculated as relative single-kidney glomerular filtration rate (GFR) using a simplified "two-point Patlak plot" technique. As a reference method, split renal function was determined from renal scintigraphy using the standard technique. RESULTS: Linear correlation between the two methods was r=0.91, split renal function (CT)=0.0266+0.9573 x split renal function (scintigraphy). CONCLUSION: Split renal function can be measured accurately by minimally extended triphasic CT.

Informatics in radiology (infoRAD): new tools for computer assistance in thoracic CT. Part 1. Functional analysis of lungs, lung lobes, and bronchopulmonary segments.

Owing to the rapid development of scanner technology, thoracic computed tomography (CT) offers new possibilities but also faces enormous challenges with respect to the quality of computer-assisted diagnosis and therapy planning. In the framework of the Virtual Institute for Computer Assistance in Clinical Radiology cooperative research project, a prototypical software application was developed to assist the radiologist in functional analysis of thoracic CT data. By identifying the anatomic compartments of the lungs, the software application enables assessment of established functional CT parameters for each individual lung, pulmonary lobe, and pulmonary segment. Such region-based assessment allows a more localized diagnosis of lung diseases such as emphysema and more accurate estimation of regional lung function from CT data. With close cooperation between computer scientists and radiologists, the software application was tested and optimized to achieve a high degree of usability. Several clinical studies were carried out, the results of which indicated that the software application improves quantification in diagnosis, therapy planning, and therapy monitoring with respect to accuracy and time required.

Sonography of the common bile duct and the gallbladder during ceruletid infusion.

In the present study, we investigated a new sonographic test to confirm or exclude partial common bile duct (CBD) obstruction, hereinafter called "dynamic cholangio-cholecysto sonography (DCCS)." Healthy controls (6) and patients with low- to intermediate probability for partial CBD obstruction (17) were investigated. DCCS started with three baseline masurements of gallbladder volume and CBD diameter, which were then repeated every 2 to 3 min for 45 min during a 30-min infusion of ceruletid. According to CBD diameter change during gallbladder contraction, DCCS was considered positive (> 1 mm), negative (< 0.5 mm) or equivocal (remainder). After DCCS, all patients underwent endoscopic retrograde cholangiography (ERCP) and all but one patient had endoscopic sphincterotomy (EST). A follow-up examination was performed at least 4 weeks after ERCP. Based on these results, an outcome score was calculated to classify the patients as having a flow-relevant CBD obstruction or not. DCCS was true positive in 4 patients (sensitivity 66%, positive predictive value 100%). DCCS was false-negative in 1 patient and equivocal in another patient. DCCS was true-negative in 9 patients (specifity 82%, negative predictive value 90%). Two patients without flow-relevant CBD obstruction had equivocal DCCS test results. DCCS might be used as a noninvasive test for further workup of patients with low- to intermediate probability of flow relevant CBD obstruction, helping to avoid unnecessary ERCP and to serve as an additional indication for ERCP and EST.

Lopromide one-sample clearance as a measure of glomerular filtration rate.

OBJECTIVE: The pharmacokinetics of iopromide were analysed using a two-compartment model. The optimal point of time for blood withdrawal for calculation of a one-sample clearance was determined. METHODS: Plasma concentration of iodine was measured up to 8 h postinjection (p.i.) in 62 adult patients who received 120 ml iopromide for computed tomography (CT). A two exponential function was fitted by a weighted least error square method. As reference method, clearance was calculated from this function and the injected amount of iodine. Empirical parameters for calculation of one-sample clearance were determined. This one-sample clearance was compared with one-sample clearance calculated according to formulas developed for Tc99m-DTPA by Jacobsson as well as a two sample method. RESULTS: Total distribution volume of iopromide was calculated as 0.242 Lkg(-1)+/- 5.9%. A high correlation of all one-sample method and the two-sample method with reference to clearance was found. Best estimation of iopromide plasma clearance was achieved by determining one-sample clearance 270 or 285 min p. i. with SD(y.x) of 5.8 ml min(-1). CONCLUSIONS: After administration of 120 ml iopromide, one-sample plasma clearance can be calculated with low estimation error taking one blood sample at an appropriate time point. Late phase pharmacokinetics of iopromide found in the present study showed to be virtually identical to results published for iohexol and Tc99m-DTPA.

Fine structure of breast tissue on micro computed tomography a feasibility study.

RATIONALE AND OBJECTIVES: To evaluate the feasibility of micro computed tomography (CT) to assess the fine structure of breast tissue. METHODS AND MATERIALS: Breast core needle biopsy specimens (0.8 to 1.2 mm diameter) from fifteen women with clustered microcalcifications were examined using micro CT with isotropic voxels of 8.4 µm. Reconstructed two- and three-dimensional images were compared with the corresponding histological slices. Gray-scale measurements were performed in adipose tissue, fibroglandular tissue, fibrous tissue, microcalcifications, and tumor. The Tukey-Kramer method was applied to test the statistically significant differences between gray-scale attenuation values of breast tissue components. RESULTS: Soft-tissue architecture appearance at micro CT closely approximated that obtained by light microscopy at low power field. The Tukey-Kramer method revealed statistically significant differences for attenuation values for all combinations of breast tissue components with the exception of fibroglandular tissue versus fibrous tissue. CONCLUSIONS: Micro CT is feasible for the differentiation of breast tissue components from core needle specimens.

Contrast enhanced MR angiography with parallel imaging in the early period after renal transplantation.

PURPOSE: To evaluate renal allograft vessels in the early period after kidney transplantation with three-dimensional (3D) contrast-enhanced MR angiography (3D CE MRA) using a parallel imaging technique. MATERIALS AND METHODS: Sixty-three consecutive patients were examined with 3D CE MRA and integrated SENSE technique (Sensitivity Encoding) 2 to 21 days after renal transplantation. MR angiography studies were analyzed for the presence of arterial stenosis. The degree of renal transplant artery stenosis was graded qualitatively as <50% = mild, 50-70% = moderate, 70-99% = severe, and occlusion. Four patients (6.3%) with moderate (n = 1) or severe (n = 3) arterial stenoses on CE MRA underwent selective intra-arterial digital subtraction angiography. In two patients, selective intravenous digital subtraction angiography (DSA) was performed. RESULTS: Twenty-seven (42.9%) of the 63 patients had normal CE MR angiograms, 29 (46%) showed mild, 3 patients (4.8%) moderate, and 4 patients (6.3%) severe stenoses of the donor artery. In three patients, the severe stenosis of the graft artery was confirmed by surgery or intra-arterial DSA. One patient with suspicion of severe arterial stenosis on MRA had moderate vessel narrowing on DSA. Twelve months after kidney transplantation, serum creatinine levels were not significantly different in patients with mild and moderate stenoses from those without (P > 0.19) but significantly different from those with severe stenoses (P < 0.05). CONCLUSION: The incidence of mild and moderate vessel narrowing at the arterial anastomosis is unexpectedly high in the early period after kidney transplantation and is most likely due to surgery-related tissue edema.

Evaluation of angiogenesis using micro-computed tomography in a xenograft mouse model of lung cancer.

Quantitative evaluation of lung tumor angiogenesis using immunohistochemical techniques has been limited by difficulties in generating reproducible data. To analyze intrapulmonary tumor angiogenesis, we used high-resolution micro-computed tomography (micro-CT) of lung tumors of mice inoculated with mouse Lewis lung carcinoma (LLC1) or human adenocarcinoma (A549) cell lines. The lung vasculature was filled with the radiopaque silicone rubber, Microfil, through the jugular vein (in vivo application) or pulmonary artery (ex vivo application). In addition, human adenocarcinoma lung tumor-bearing mice treated site-specifically with humanized monoclonal antibody (bevacizumab) against vascular endothelial growth factor. Quantitative analysis of lung tumor microvessels imaged with micro-CT showed that more vessels (mainly small, <0.02 mm(2)) were filled using the in vivo (5.4%) compared with the ex vivo (2.1%) method. Furthermore, bevacizumab-treated lung tumor-bearing mice showed significantly reduced lung tumor volume and lung tumor angiogenesis compared with untreated mice as assessed by micro-CT. Interestingly, microvascularization of mainly the smaller vessels (<0.02 mm(2)) was reduced after bevacizumab treatment. This observation with micro-CT was nicely correlated with immunohistochemical measurement of microvessels. Therefore, micro-CT is a novel method for investigating lung tumor angiogenesis, and this might be considered as an additional complementary tool for precise quantification of angiogenesis.

Magnetic resonance imaging and magnetic resonance cholangiopancreatography findings compared with fecal elastase 1 measurement for the diagnosis of chronic pancreatitis.

OBJECTIVES: To correlate magnetic resonance cholangiopancreatography (MRCP) and magnetic resonance imaging (MRI) findings of the pancreas with the pancreatic exocrine function determined by fecal elastase 1 concentration. METHODS: Magnetic resonance imaging and MRCP findings of 81 consecutive patients with clinically suspected chronic pancreatitis and 21 healthy volunteers were evaluated. All subjects underwent MRI/MRCP and fecal elastase 1 testing within 1 to 4 weeks' interval. Magnetic resonance cholangiopancreatography images were evaluated according to Cambridge classification. Magnetic resonance imaging of the pancreas was assessed for pancreatic size, signal, and arterial enhancement. RESULTS: All volunteers had normal fecal elastase 1 levels (>200 microg/g) and normal MRI/MRCP findings. Thirty-one of 56 patients revealed MRI and/or MRCP findings despite normal fecal elastase 1 concentration. Four of 25 patients revealed normal MRI and MRCP findings despite low fecal elastase 1 concentration (<200 microg/g). Magnetic resonance imaging findings of size (P = 0.00001), arterial enhancement (P = 0.00001), and parenchymal signal (P = 0.001) were significantly different among the control group, patients with normal fecal elastase 1 levels, and patients with low fecal elastase 1 levels. Magnetic resonance cholangiopancreatography findings (P = 0.00001), pancreatic size (P = 0.00001), arterial enhancement (P = 0.014), and parenchymal signal (P = 0.004) on MRI correlated with the fecal elastase 1 concentration. CONCLUSIONS: Magnetic resonance imaging/MRCP findings correlate with fecal elastase 1 concentration and may precede pancreatic exocrine insufficiency in the early stages of chronic pancreatitis.

Three-dimensional imaging and morphometric analysis of alveolar tissue from microfocal X-ray-computed tomography.

We evaluated microfocal X-ray-computed tomography (micro-CT) as a method to visualize lung architecture two and three dimensionally and to obtain morphometric data. Inflated porcine lungs were fixed by formaldehyde ventilation. Tissue samples (8-mm diameter, 10-mm height) were stained with osmium tetroxide, and 400 projection images (1,024 x 1,024 pixel) were obtained. Continuous isometric micro-CT scans (voxel size 9 microm) were acquired to reconstruct two- and three-dimensional images. Tissue samples were sectioned (8-microm thickness) for histological analysis. Alveolar surface density and mean linear intercept were assessed by stereology-based morphometry in micro-CT scans and corresponding histological sections. Furthermore, stereology-based morphometry was compared with morphometric semi-automated micro-CT analysis within the same micro-CT scan. Agreement of methods was assessed by regression and Bland-Altman analysis. Comparing histology with micro-CT, alveolar surface densities (35.4 +/- 2.4 vs. 33.4 +/- 1.9/mm, P < 0.05) showed a correlation (r = 0.72; P = 0.018) with an agreement of 2 +/- 1.6/mm; the mean linear intercept (135.7 +/- 14.5 vs. 135.8 +/- 15 microm) correlated well (r = 0.97; P < 0.0001) with an agreement of -0.1 +/- 3.4 microm. Semi-automated micro-CT analysis resulted in smaller alveolar surface densities (33.4 +/- 1.9 vs. 30.5 +/- 1/mm; P < 0.01) with a correlation (r = 0.70; P = 0.023) and agreement of 2.9 +/- 1.4/mm. Non-destructive micro-CT scanning offers the advantage to visualize the spatial tissue architecture of small lung samples two and three dimensionally.

Glomerular filtration rate measured using the Patlak plot technique and contrast-enhanced dynamic MRI with different amounts of gadolinium-DTPA.

We determined the optimum gadolinium (Gd)-DTPA dose and time window for calculating the glomerular filtration rate (GFR) using contrast-enhanced (CE) dynamic MRI and the Patlak plot technique. Twelve adult volunteers with healthy kidneys were included in the study. As a reference method the GFR was measured by iopromide plasma clearance. A three-dimensional gradient-echo (GRE) sequence with a flip angle of 50 degrees was used for MRI. Signal was measured using a body surface coil with four elements. Each volunteer was examined on four days using 2 mL, 4 mL, 8 mL, or 16 mL of Gd-DTPA 0.5 mmol/mL dissolved with sodium chloride (NaCl) 0.9% to a total of 60 mL. The injection rate was 1 mL/second. A Patlak plot was calculated from the kidney and aorta signals. The mean reference GFR was 133 mL/min (min-max, 116-153 mL/min). The best correlation of GFR calculated from MRI data compared to the reference method was found in a time window 30-90 seconds after aortic signal rise using 16 mL Gd-DTPA. Pearson's correlation coefficient was r = 0.83, and the standard deviation (SD) from the line of regression was 10.5 mL/minute. We found a significantly lower average GFR(MR) using 16 mL Gd-DTPA compared to 4 mL and 2 mL in the late time window 60-120 seconds post aortic rise. A dose of 16 mL Gd-DTPA was optimal for measuring GFR using dynamic MRI and the Patlak plot technique. The slope should be measured in a time window of 30-90 seconds post aortic rise.

Micro-CT of the human lung: imaging of alveoli and virtual endoscopy of an alveolar duct in a normal lung and in a lung with centrilobular emphysema--initial observations.

The appearance of human lung parenchyma at the structural level of alveoli was investigated by the use of micro-computed tomography (CT). Approval for use of autopsy lungs was given by the head of the pathology institute of the university, in accordance with the requirements of the State Ministry of Science and Arts and without the need for institutional review board approval. Two human lungs (one normal lung and one lung with centrilobular emphysema of a mild to moderate degree) were inflated and fixed with hot formalin vapor. Lung specimens excised from the superior segment of the left lower lobe (B6) were stained with silver nitrate in a vacuum and investigated at a volume of interest of 4 mm for each side with a voxel size of 14 mum. Normal-size and enlarged alveoli became visible. A three-dimensional reconstruction of the terminal airspaces made virtual endoscopy of the alveolar ducts possible.

A 22-year-old woman with lower limb arteriopathy. Buerger's disease, or methamphetamine- or cannabis-induced arteritis?

This case report describes a 22-year-old woman with severe arterial ischemia leading to claudication and ulceration of the feet, presumably due to long-term abuse of amphetamine derivates, such as "speed" or "ecstasy," and cannabis. Known causes for peripheral occlusive disease, such as atherosclerosis, vasculitis, or collagen vascular disease, were excluded. Laboratory test results did not show evidence of risk factors for thromboembolic diseases. Conventional angiography and magnetic resonance-angiography showed occlusions of medium- and small-sized arteries of both calves and feet. In the past, vasculitis-like arteriopathy was attributed to the abuse of amphetamines as well as of cannabis. However, amphetamines have been reported to be associated with necrotizing vasculitis mainly of cerebral arteries. Therefore, the abuse of methamphetamine or "ecstasy" also appears to play a role in the development of peripheral arterial occlusions and seems to have broad similarities with Buerger's disease.