Low hepatic lipase activity is a novel risk factor for coronary artery disease.

BACKGROUND: The crucial function of hepatic lipase (HL) in lipid metabolism has been well established, but the relationship between HL activity and coronary artery disease (CAD) is disputed. METHODS AND RESULTS: We measured HL activity in the postheparin plasma of 200 consecutive men undergoing elective coronary angiography and determined the degree of CAD with the extent score, which has been shown to be better correlated with known risk factors than other measures of CAD extent. We found a significant inverse correlation between HL activity and the extent of CAD (r=-0.19, P<0.01). This association was mainly due to patients with HDL levels >0.96 mmol/L (n=94, r=-0.30, P<0.005). HL activity was lower in 173 patients with CAD than in 40 controls with normal angiograms (286+/-106 versus 338+/-108 nmol. mL(-1). min(-1), P<0.01). To correct for potential confounding factors, we performed multivariate analyses that confirmed the independent association of HL activity with CAD extent. In addition, the presence of the T allele at position -514 in the HL promoter, which leads to a reduced HL promoter activity, was associated with lower HL activity (r=0.30, P<0.001) and higher CAD extent (42.2+/-20.8 versus 35.3+/-23.6 [extent score], P<0.05). In patients with heterozygous familial hypercholesterolemia, calcified lesions in ECG-gated spiral computed tomography were higher in patients with low HL activity (6.3+/-6.8 versus 1.5+/-3.1, P=0.01). CONCLUSIONS: Our data show that low HL activity is associated with CAD. Therefore, HL might be useful for CAD risk estimation and might be a target for pharmacological intervention.

Stereotactic single-dose radiation therapy of liver tumors: results of a phase I/II trial.

PURPOSE: To investigate the feasibility and the clinical response of a stereotactic single-dose radiation treatment for liver tumors. PATIENTS AND METHODS: Between April 1997 and September 1999, a stereotactic single-dose radiation treatment of 60 liver tumors (four primary tumors, 56 metastases) in 37 patients was performed. Patients were positioned in an individually shaped vacuum pillow. The applied dose was escalated from 14 to 26 Gy (reference point), with the 80% isodose surrounding the planning target volume. Median tumor size was 10 cm(3) (range, 1 to 132 cm(3)). The morbidity, clinical outcome, laboratory findings, and response as seen on computed tomography (CT) scan were evaluated. RESULTS: Follow-up data could be obtained from 55 treated tumors (35 patients). The median follow-up period was 5.7 months (range, 1.0 to 26.1 months; mean, 9.5 months). The treatment was well tolerated by all patients. There were no major side effects. Fifty-four (98%) of 55 tumors were locally controlled after 6 weeks at the initial follow-up based on the CT findings (22 cases of stable disease, 28 partial responses, and four complete responses). After a dose-escalating and learning phase, the actuarial local tumor control rate was 81% at 18 months after therapy. A total of 12 local failures were observed during follow-up. So far, the longest local tumor control is 26.1 months. CONCLUSION: Stereotactic single-dose radiation therapy is a feasible method for the treatment of singular inoperable liver metastases with the potential of a high local tumor control rate and low morbidity.

Extracranial stereotactic radiation therapy: set-up accuracy of patients treated for liver metastases.

PURPOSE: Patients with liver metastases might benefit from high-dose conformal radiation therapy. A high accuracy of repositioning and a reduction of target movement are necessary for such an approach. The set-up accuracy of patients with liver metastases treated with stereotactic single dose radiation was evaluated. METHODS AND MATERIALS: Twenty-four patients with liver metastases were treated with single dose radiation therapy on 26 occasions using a self-developed stereotactic frame. Liver movement was reduced by abdominal pressure. The effectiveness was evaluated under fluoroscopy. CT scans were performed on the planning day and directly before treatment. Representative reference marks were chosen and the coordinates were calculated. In addition, the target displacement was quantitatively evaluated after treatment. RESULTS: Diaphragmal movement was reduced to median 7 mm (range: 3-13 mm). The final set-up accuracy of the body was limited to all of median 1.8 mm in latero-lateral direction (range: 0.3-5.0 mm) and 2.0 mm in anterior-posterior direction (0.8-3.8 mm). Deviations of the body in cranio-caudal direction were always less than the thickness of one CT slice (<5 mm). However, a repositioning was necessary in 16 occasions. The final target shift was median 1.6 mm (0.2-7.0 mm) in latero-lateral and 2.3 mm in anterior-posterior direction (0.0-6.3 mm). The median shift in cranio-caudal direction was 4.4 mm (0.0-10.0 mm). CONCLUSIONS: In patients with liver metastases, a high set-up accuracy of the body and the target can be achieved. This allows a high-dose focal radiotherapy of these lesions. However, a control CT scan should be performed directly before therapy to confirm set-up accuracy and possibly prompt necessary corrections.

Noninvasive patient fixation for extracranial stereotactic radiotherapy.

PURPOSE: To evaluate the setup accuracy that can be achieved with a novel noninvasive patient fixation technique based on a body cast attached to a recently developed stereotactic body frame during fractionated extracranial stereotactic radiotherapy. METHODS AND MATERIALS: Thirty-one CT studies (> or = 20 slices, thickness: 3 mm) from 5 patients who were immobilized in a body cast attached to a stereotactic body frame for treatment of paramedullary tumors in the thoracic or lumbar spine were evaluated with respect to setup accuracy. The immobilization device consisted of a custom-made wrap-around body cast that extended from the neck to the thighs and a separate head mask, both made from Scotchcast. Each CT study was performed immediately before or after every second or third actual treatment fraction without repositioning the patient between CT and treatment. The stereotactic localization system was mounted and the isocenter as initially located stereotactically was marked with fiducials for each CT study. Deviation of the treated isocenter as compared to the planned position was measured in all three dimensions. RESULTS: The immobilization device can be easily handled, attached to and removed from the stereotactic frame and thus enables treatment of multiple patients with the same stereotactic frame each day. Mean patient movements of 1.6 mm+/-1.2 mm (laterolateral [LL]), 1.4 mm+/-1.0 mm (anterior-posterior [AP]), 2.3 mm+/-1.3 mm (transversal vectorial error [VE]) and < slice thickness = 3 mm (craniocaudal [CC]) were recorded for the targets in the thoracic spine and 1.4 mm+/-1.0 mm (LL), 1.2 mm+/-0.7 mm (AP), 1.8 mm+/-1.2 mm (VE), and < 3 mm (CC) for the lumbar spine. The worst case deviation was 3.9 mm for the first patient with the target in the thoracic spine (in the LL direction). Combining those numbers (mean transversal VE for both locations and maximum CC error of 3 mm), the mean three-dimensional vectorial patient movement and thus the mean overall accuracy can be safely estimated to be < or = 3.6 mm. CONCLUSION: The presented combination of a body cast and head mask system in a rigid stereotactic body frame ensures reliable noninvasive patient fixation for fractionated extracranial stereotactic radiotherapy and may enable dose escalation for less radioresponsive tumors that are near the spinal cord or otherwise critically located while minimizing the risk of late sequelae.

Digitally reconstructed radiographs from abdominal CT scans as a new tool for radiotherapy planning.

OBJECTIVE: Abdominal extended field radiotherapy requires exact field shaping. Conventional treatment planning is difficult to adapt to individual anatomy, whereas three-dimensional planning is time-consuming. The authors introduce a method with digitally reconstructed radiographs of spiral CT data to facilitate radiotherapy planning. METHODS: Twenty-two patients underwent imaging with a standardized CT protocol, and digitally reconstructed radiographs were calculated in central beam projection using a maximum intensity projection algorithm (MIP-DRR). For comparison, the expected error from parallel projection was calculated depending on object thickness and field length. RESULTS: The contrast-enhanced protocol used in spiral CT produces a good rendition of all relevant structures. The resulting MIP images have a geometry identical to standard simulation films and to the linear accelerator, whereas standard MIPs with parallel projection show significant distortion compared to the treatment process. CONCLUSIONS: Because of the integration of the geometry of the radiotherapy treatment, the described central beam projection method might be used as a new tool for abdominal radiotherapy planning. The CT protocol offers sufficient contrast enhancement in all relevant structures and provides all necessary anatomic information for individual beam shaping.

Usability of semiautomatic segmentation algorithms for tumor volume determination.

RATIONALE AND OBJECTIVES: Tumor volume is an important parameter for clinical decision making. At present, semiautomatic image segmentation is not a standard for tumor volumetry. The aim of this work was to investigate the usability of semiautomatic algorithms for tumor volume determination. METHODS: Semiautomatic region- and volume-growing, isocontour, snakes, hierarchical, and histogram-based segmentation algorithms were tested for accuracy, contour variability, and time performance. The test were performed on a newly developed organic phantom for the simulation of a human liver and liver metastases. The real tumor volumes were measured by water displacement. These measured volumes were used as the gold standard for determining the accuracy of the algorithms. RESULTS: Variability of the segmented volumes ranging from 3.9 +/- 3.2% (isocontour algorithm) to 11.5 +/- 13.9% (hierarchical segmentation) was observed. The segmentation time per slice varied between 32 (volume-growing) and 72 seconds (snakes) on an IBM/RS6000 workstation. CONCLUSIONS: Only the region-growing and isocontour algorithms have the potential to be used for tumor volumetry. However, further improvements of these algorithms are necessary before they can be placed into clinical use.

Changes of tumor vascularity during gene therapy monitored with color Doppler US.

Using contrast-enhanced color Doppler (CD) sonography, we assessed alterations of tumor blood flow induced in 25 murine Morris hepatomas transfected with a gancyclovir- (GCV-)sensitizing Herpes simplex virus thymidine kinase (HSVtk) suicide gene in combination with systemic GCV treatment and compared findings with a control tumor. CD measurements were quantified by the color pixel density (CPD) and the mean encoded flow velocity (mean color value, MCV), using computer-assisted image analysis, and compared with histologic arteriole counts. During 5 days, the tumor volume remained constant. In HSVtk-expressing tumors, the median CPD dropped from 16% at baseline to 5% on day 5 (p = 0.001), remaining constant in controls. The MCV decreased from 1.9 cm/s to 1.6 cm/s in the HSVtk-expressing tumors (p = 0.001) and rose from 1.8 cm/s to 2.0 cm/s in the controls (p = 0.002). In an accompanying histologic arteriole assay, we found no alterations attributable to treatment.

Prognostic significance of color Doppler findings in head and neck tumors.

We examined whether or not the degree of tumor vascularity in lymph node metastases as depicted by color Doppler is associated with a patient's prognosis. Cervical lymph node metastases in 25 patients with head and neck cancer were examined before combined accelerated radiotherapy and chemotherapy. The findings were quantified using a computer-assisted protocol that quantitatively describes color Doppler images by the relative color pixel density (CPD) and the color hues, which are numerically expressed by the mean color value (MCV). We found that, in the patient group with a CPD below median, the median survival was 958 days and, in the group with a higher CPD, it was 423 days (p = 0.05). The time to detection of distant metastases was 18 months with a low CPD, and 6 months with a high CPD (p = 0.05). However, the time to local or nodal progression was not different between the groups. The MCV was not correlated with prognostic data. These results indicate that, in patients with metastatic head and neck cancer, highly vascularized lymph nodes detected with color Doppler sonography may indicate a shorter survival and earlier occurrence of distant metastases.

Virtual planning of liver resections: image processing, visualization and volumetric evaluation.

Operability of a liver tumor depends on its three dimensional relation to the intrahepatic vascular trees as well as the volume ratio of healthy to tumorous tissue. Precise operation planning is complicated by anatomic variability and distortion of the vascular trees by the tumor or preceding liver resections. We have developed a computer based 3D virtual operation planning system which is ready to go in routine use. The main task of a system in this domain is a quantifiable patient selection by exact prediction of post-operative liver function. It provides the means to measure absolute and relative volumes of the organ structures and resected parenchyma. Another important step in the pre-operative phase is to visualize the relation between the tumor, the liver and the vessel trees for each patient. The new 3D operation planning system offers quantifiable liver resection proposals based on individualized liver anatomy. The results are presented as 3D movies or as interactive visualizations as well as in quantitative reports.

Technical aspects of virtual liver resection planning.

Operability of a liver tumor is depending on its three dimensional relation to the intrahepatic vascular trees which define autonomously functioning liver (sub-)segments. Precise operation planning is complicated by anatomic variability, distortion of the vascular trees by the tumor or preceding liver resections. Because of the missing possibility to track the deformation of the liver during the operation an integration of the resection planning system into an intra-operative navigation system is not feasible. So the main task of an operation planning system in this domain is a quantifiable patient selection by exact prediction of post-operative liver function and a quantifiable resection proposal. The system quantifies the organ structures and resection volumes by means of absolute and relative values. It defines resection planes depending on security margins and the vascular trees and presents the data in visualized form as a 3D movie. The new 3D operation planning system offers quantifiable liver resection proposals based on individualized liver anatomy. The results are visualized in digital movies as well as in quantitative reports.

[Septic focus in the retroperitoneum--iatrogenic foreign body of cotton (gossypiboma)]. / Septischer Herd im Retroperitoneum--Iatrogener Fremdkörper aus Baumwolle (Gossypibom).

Retained surgical towels (gossypiboma) present a diagnsotic problem if they remain asymptomatic for many years. We report on one 51 year old patient with repeated septic temperatures in the early post-operative phase after hemicolectomy. The contrast enhanced CT of the abdomen revealed a well-defined round soft-tissue mass with a dense, enhanced wall containing an internal high-density wavy and striped area. At laparotomy a secondary infected surgical sponge with abscess formation was found.

Comparison of steady state serum theophylline concentrations in healthy volunteers after dosing with Euphyllin retard and PulmiDur.

In a randomized cross-over study, theophylline serum levels were compared over a 12-h dosing interval after repeated administration of Euphyllin retard and PulmiDur to 18 healthy male volunteers. Although both preparations are sustained-release formulations they differ in the systems used and in the state of hydration of theophylline. Two tablets each of Euphyllin retard or one tablet PulmiDur plus one tablet PulmiDur forte were administered in an identical dosing scheme always before food intake. The mean value curves of theophylline serum levels obtained at steady state clearly demonstrate the marked sustained-release properties of both preparations. The relative bioavailability of Euphyllin retard vs. PulmiDur calculated from the individual ratios of the dose adjusted AUCs was 96(83-111)%, results being given as geometric mean and 95% confidence limits. Hence Euphyllin retard is equivalent to PulmiDur with regard to the extent of absorption.

[Stereotactic irradiation of liver metastases]. / Stereotaktische Bestrahlung von Lebermetastasen.

PURPOSE: A number of minimal-invasive methods have been developed for the treatment of non-resectable liver metastases. A focused high dose can be delivered to a liver tumor with sparing of surrounding normal liver tissue using non-invasive stereotactic techniques. METHODS: Sixty-six metastases were treated stereotactically in 43 patients during a phase 2 trial. RESULTS: There were no major side effects observed. The actuarial local control was 82% after 18 months. The median actuarial survival was 24 months. However, there was a significantly improved survival in patients without additional extrahepatic tumor manifestation at the time of treatment compared to those, who were treated in palliative intention (87% vs. 24% after 18 months, p = 0.001 (log-rank). CONCLUSION: Stereotactic single dose irradiation is a non-invasive and safe treatment option for patients with inoperable liver metastases. Phase III studies will further evaluate this new approach.

Detection of gunshot residues in routine CTs.

The forensic assessment of non-fatal gunshot wounds often proves to be difficult as wounds have usually been cleaned and protected with a sterile bandage by the time of the examination. The aim of our investigation was to test the possible application of computed tomography (CT) for the forensic assessment. Doing so raised the questions whether gunshot residues in the soft tissues, detected by means of 3-dimensional CT, can be used as evidence of a close-range shot and whether conclusions can be drawn pertaining to the range of the shot or the type of bullet used based on the distribution of the radiologically detectable material? In this experimental study 39 shots were fired at fresh pig skin and it was possible to distinguish shots fired from distances of more than 10 cm and contact shots independent of the type of bullet. For unjacketed lead bullets, radiopaque material could be seen in the depth of the entrance would for firing distances up to 10 cm. In individual cases, CT data and the 3-D reconstruction could provide valuable information in the forensic assessment of patients with gunshot wounds.

[The vascular patient--diagnosis and minimally invasive therapy. Which technique for what illness?]. / Der Gefässpatient--Diagnostik und minimalinvasive Therapie. Welche Technik für welche Erkrankung?

The non-invasive imaging modalities, color coded duplex sonography (CCDS), magnetic resonance tomography (MRT), and computed tomography (CT), have pushed conventional angiography out of most diagnostic fields. The experienced user will achieve fast, reliable answers with CCDS in dedicated clinical settings. MRT as well as CT are concurring imaging modalities for the most appropriate diagnostic answer. Not only pure image quality, but also patient management, and availability play a major role. Catheter based angiography will in the future still play a role in mesenteric ischemia (non occlusive disease) and for imaging of very small vessel pathology, e.g. on panarteritis nodosa. At the moment, peripheral leg run-offs are still best performed with conventional angiography, nevertheless, MR as well as CT seem to have the ability to perform diagnostic procedures. Ongoing studies will allow a solid judgement in the near future. The true value of catheter angiography is in the direct assessment, planning, and performance of interventional procedures, e.g. catheter based obliteration or revascularization. Implantation of stent devices and a whole range of different mechanical and pharmacological revascularization procedures have improved the interventional management of vascular stenoses and occlusions. The interventional radiologist is treating physician in the classical sense in this setting. Acute bleeding episodes, e.g. in the brain, thorax, abdomen, or pelvis, are best imaged with computed tomography. Conventional angiography still plays a major diagnostic and therapeutic role in bleeding into preformed cavities, such as the bile ducts or the intestine. In this setting, all available information including CT scans should be valued. For complex therapeutic regimens in oncology or in pure palliative situations, angiographic diagnosis followed by embolization and/or ablation therapy is established.

Spiral CT vs incremental CT: is spiral CT superior in imaging of the brain?

The aim of this study was to evaluate image quality of spiral CT of the brain as compared with incremental CT using identical scanning parameters. Incremental or spiral cranial CT was performed on 46 consecutive, randomized patients with non-traumatic disease of the brain on a Siemens (Erlangen, Germany) Somatom Plus 4. Evaluation was done in a randomized blinded way by two experienced radiologists. Different anatomical structures, image noise, and artifacts were scaled 1 (bad) to 4 (very good). Statistical analysis was done using the F-test of variance for partial sums of squares as well as Student's t-test. Incremental CT was superior to spiral CT for evaluation of the internal capsule, supratentorial artifacts, gray/white matter differentiation, and image noise. No statistically significant differences were seen for evaluation of the pons, infratentorial artifacts, and eye muscles. With identical scanning parameters incremental CT is superior to spiral CT in the assessment of small, complex structures in a low-contrast setting. No differences are seen for larger structures or small structures in a medium-contrast range. Artifacts localized close to the skull in spiral CT can easily mimic hemorrhage in traumatized patients. Spiral CT should therefore only be used for CT angiography and if 3D reconstructions are needed.

[Requirements for a teleradiology system. Experiences with the MEDICUS-2 field test]. / Anforderungen an ein Teleradiologiesystem. Erfahrungen aus dem MEDICUS-2-Feldtest.

During the Medicus field test we gained experience using the teleradiology system for almost daily teleconferences between a radiology department and clinics for internal medicine, urology, and gynecology. The existing system has a high degree of functionality. The full 12-bit data format is available using the DICOM protocol. A data security concept is implemented, ensuring data integrity, privacy and authentication of communication partners. This concept covers the areas of organization, technique, user training, and software implementation. A future system should be a general purpose radiology workstation covering viewing functionality, image manipulation, and digital archive access. Dedicated teleradiology features have to be a part. Specialized evaluation software, e.g. for dynamic MRI, should be integratable in a modular way. For data exchange with other systems and for the synchronization of teleconference sessions, the protocols should be independent of the network standard used (ISDN, Ethernet, ATM) and based on the DICOM protocol. Extensions of the existing standard are therefore necessary. Besides future technical developments, reimbursement for teleradiology must be accomplished.

[Optimizing temporal resolution in CT with retrospective ECG gating]. / Optimierung der Zeitauflösung in der CT mittels retrospektivem EKG-Gating.

PURPOSE: Spiral CT of the heart using the established ways of ECG synchronization is hampered by the relatively long acquisition times of 250 to 500 ms. This only allows to acquire diastolic images in patients with moderate heart rates. In this work, algorithms for time-optimized retrospective cardiac gating are presented, and their potential to improve temporal resolution is investigated. MATERIAL AND METHODS: These algorithms use data from multiple gantry rotations for image reconstruction, which is possible for multi-scans at fixed slice positions as well as for overlapping spiral scans. Temporal resolution was quantified using computer simulations and compared to experimental data from pigs. RESULTS: Using a conventional sub-second CT scanner, considerably higher temporal resolutions are possible with spiral scanning. A temporal resolution of 170 ms already provides systolic images with little motion artifacts. Higher temporal resolutions of up to 70 ms are demonstrated for multi-scans, which allows to depict ventricle wall movement over the complete cardiac cycle. DISCUSSION: The method of time-optimized retrospective cardiac gating broadens the spectrum of conventional spiral-CT for cardiac imaging. It can be directly transferred to multi-slice scanners. Here it can be used clinically because of reduced scan time. Potential applications are the determination of functional cardiac parameters like ejection fraction and the detection of disorders of ventricle wall movement.

[Radiologic diagnosis of the kidneys in dialysis patients]. / Radiologische Diagnostik der Nieren bei Dialysepatienten.

The kidneys of patients with chronic renal failure undergoing maintenance hemodialysis may show different variances or complications. Most common are secondarily acquired renal cysts, which may be found in as many as 92% of patients after 8 years of hemodialysis. Single (in 12.5% of patients) or multiple (8.3%) cysts with bleeding are common; additionally, hematuria or ruptured cysts may be found. Bleeding into cysts is more common in patients with autosomal dominant polycystic kidney disease. Due to the decreasing urinary production development of kidney stones is very uncommon, but calcifications in or around cysts can be found in 71% of patients. Kidney tumors occur 41 times more often in patients with chronic renal failure than in patients without kidney disease. We detected tumors in 4.2% of our patients on long-term dialysis. Diagnostic differentiation of the relatively slow growing and fairly late metastasizing malignant tumors from adenomas is not possible. Nevertheless, we screen our patients every 3-4 years. Computed tomography is superior to ultrasonography for this purpose, because ultrasonography lacks the necessary sensitivity in this group of patients.

[Thorotrast-induced liver cancer: results of the German thorotrast study]. / Thorotrast-induzierte tumoren der Leber. Ergebnisse der Deutschen Thorotraststudie.

AIMS: The X-ray contrast medium Thorotrast, used worldwide between 1930 to 1950 predominantly for arteriography, consisted of a colloidal solution of thorium dioxide. The radioactive thorium-232 (half-life 1.4x10(10) years) is stored lifelong in the organs of the reticulo-endothelial system after intravascular injection, causing chronic exposure to alpha radiation. The aim of the German Thorotrast study is the assessment of radiation late effects and the calculation of risk estimates. MATERIAL AND METHODS: The German Thorotrast study started in 1968 as a cohort study and comprises 2326 Thorotrast patients and 1890 patients of a matched control group. The Thorotrast patients who were still alive at the beginning of the study were examined by X-ray plain films of the upper abdomen and of the injection site of the contrast medium as well as by whole-body counter measurements. At the beginning we offered the patients ultrasound and later on CT and MRI at regular intervals for early detection of liver cancer. RESULTS: To date 454 primary liver cancers have been registered in the group of Thorotrast patients compared to 3 cases in the control group. With the help of modern imaging methods relatively small liver cancers were detected and could be surgically removed. DISCUSSION: There is a correlation between the mean accumulated dose to the liver and the incidence of liver cancer. The cumulative risk for liver malignancies is about 600 diseases per 10(4) persons whose liver was exposed to 1 Gy. Also the incidence of liver cirrhosis is correlated with the mean accumulated dose to the liver.