Comparison of manual and semi-automatic measuring techniques in MSCT scans of patients with lymphoma: a multicentre study.

OBJECTIVES: Multicentre evaluation of the precision of semi-automatic 2D/3D measurements in comparison to manual, linear measurements of lymph nodes regarding their inter-observer variability in multi-slice CT (MSCT) of patients with lymphoma. METHODS: MSCT data of 63 patients were interpreted before and after chemotherapy by one/two radiologists in five university hospitals. In 307 lymph nodes, short (SAD)/long (LAD) axis diameter and WHO area were determined manually and semi-automatically. Volume was solely calculated semi-automatically. To determine the precision of the individual parameters, a mean was calculated for every lymph node/parameter. Deviation of the measured parameters from this mean was evaluated separately. Statistical analysis entailed intraclass correlation coefficients (ICC) and Kruskal-Wallis tests. RESULTS: Median relative deviations of semi-automatic parameters were smaller than deviations of manually assessed parameters, e.g. semi-automatic SAD 5.3 vs. manual 6.5 %. Median variations among different study sites were smaller if the measurement was conducted semi-automatically, e. g. manual LAD 5.7/4.2 % vs. semi-automatic 3.4/3.4 %. Semi-automatic volumetry was superior to the other parameters (2.8 %). CONCLUSIONS: Semi-automatic determination of different lymph node parameters is (compared to manually assessed parameters) associated with a slightly greater precision and a marginally lower inter-observer variability. These results are with regard to the increasing mobility of patients among different medical centres and in relation to the quality management of multicentre trials of importance. KEY POINTS: • In a multicentre setting, semi-automatic measurements are more accurate than manual assessments. • Lymph node volumetry outperforms all other semi-automatically and manually performed measurements. • Use of semi-automatic lymph node analyses can reduce the inter-observer variability.

Therapy response evaluation of malignant lymphoma in a multicenter study: comparison of manual and semiautomatic measurements in CT.

PURPOSE: Comparison of manual one-/bi-dimensional measurements versus semi-automatically derived one-/bi-dimensional and volumetric measurements for therapy response evaluation of malignant lymphoma during CT follow-up examinations in a multicenter setting. MATERIALS AND METHODS: MSCT data sets of patients with malignant lymphoma were evaluated before (baseline) and after two cycles of chemotherapy (follow-up) at radiological centers of five university hospitals. The long axis diameter (LAD), the short axis diameter (SAD) and the bi-dimensional WHO of 307 target lymph nodes were measured manually and semi-automatically using dedicated software. Lymph node volumetry was performed semi-automatically only. The therapeutic response was evaluated according to lymphoma-adapted RECIST. RESULTS: Based on a single lymph node, semi-automatically derived multidimensional parameters allowed for significantly more accurate therapy response classification than the manual or the semi-automatic unidimensional parameters. Incorrect classifications were reduced by up to 9.6%. Compared to the manual approach, the influence of the study center on correct therapy classification is significantly less relevant when using semi-automatic measurements. CONCLUSION: Semi-automatic volumetry and bi-dimensional WHO significantly reduce the number of incorrectly classified lymphoma patients by approximately 9.6% in the multicenter setting in comparison to linear parameters. Semi-automatic quantitative software tools may help to significantly reduce wrong classifications that are associated with the manual assessment approach. KEY POINTS: ► Semi-automatic volumetry and bi-dimensional WHO significantly reduce the number of incorrectly classified lymphoma patients ► Manual lymph node evaluation with uni-dimensional parameters is inferior to semi-automatic analysis in a multicenter setting ► Semi-automatic quantitative software tools should be introduced in clinical study evaluation.

Effect of kernels used for the reconstruction of MDCT datasets on the semi-automated segmentation and volumetry of liver lesions.

PURPOSE: To evaluate the effect of different reconstruction kernels on the semi-automated segmentation of liver lesions in MDCT. MATERIALS AND METHODS: A total 62 liver lesions were measured by three independent radiologists with the semi-automated segmentation software Oncology-Prototype (Fraunhofer MEVIS, Siemens Healthcare, Germany) using MDCT datasets (3-mm slice thickness, 2-mm increment) reconstructed with standard, soft and detailed kernels (Philips B, A and D). To ensure objective measurements, only lesions with satisfactory initial segmentation were included, and manual correction was not used. The effective diameter and volume were recorded for each lesion. Segmentation in the soft and detailed kernel datasets was performed by copying the initial seed's position from the standard kernel dataset. RESULTS: The mean effective lesion diameter was 19.9 ±â€Š9.7 mm using the standard kernel. Comparing the three kernels, no significant differences were found. The mean difference was 1% ±â€Š6% for the standard kernel compared to the soft kernel, 3% ±â€Š13% for the standard kernel vs. the detailed kernel and 2% ±â€Š9% for the soft kernel compared to the detailed kernel. The intra-class correlation coefficients were > 0.96 in all cases. CONCLUSION: The semi-automated segmentation and volumetry of liver lesions shows reliable measurements regardless of the kernel used for reconstruction of the MDCT dataset. KEY POINTS: ► Semi-automated segmentation and volumetry of liver lesions is reliable regardless of the kernel used for reconstruction of the MDCT dataset. ► Until today the gold standard for the evaluation of tumor response has been unidimensional manual measurement. ► Volumetric measurements could improve the assessment of tumor growth.

Clinical lymph node staging--influence of slice thickness and reconstruction kernel on volumetry and RECIST measurements.

PURPOSE: Therapy response evaluation in oncological patient care requires reproducible and accurate image evaluation. Today, common standard in measurement of tumour growth or shrinkage is one-dimensional RECIST 1.1. A proposed alternative method for therapy monitoring is computer aided volumetric analysis. In lung metastases volumetry proved high reliability and accuracy in experimental studies. High reliability and accuracy of volumetry in lung metastases has been proven. However, other metastatic lesions such as enlarged lymph nodes are far more challenging. The aim of this study was to investigate the reproducibility of semi-automated volumetric analysis of lymph node metastases as a function of both slice thickness and reconstruction kernel. In addition, manual long axis diameters (LAD) as well as short axis diameters (SAD) were compared to automated RECIST measurements. MATERIALS AND METHODS: Multislice-CT of the chest, abdomen and pelvis of 15 patients with lymph node metastases of malignant melanoma were included. Raw data were reconstructed using different slice thicknesses (1-5 mm) and varying reconstruction kernels (B20f, B40f, B60f). Volume and RECIST measurements were performed for 85 lymph nodes between 10 and 60 mm using Oncology Prototype Software (Fraunhofer MEVIS, Siemens, Germany) and were compared to a defined reference volume and diameter by calculating absolute percentage errors (APE). Variability of the lymph node sizes was computed as relative measurement differences, precision of measurements was computed as relative measurement deviation. RESULTS: Mean absolute percentage error (APE) for volumetric analysis varied between 3.95% and 13.8% and increased significantly with slice thickness. Differences between reconstruction kernels were not significant, however, a trend towards middle soft tissue kernel could be observed.. Between automated and manual short axis diameter (SAD, RECIST 1.1) and long axis diameter (LAD, RECIST 1.0) no significant differences were found. The most unsatisfactory segmentation results occurred in higher slice thickness (3 and 5 mm) and sharp tissue kernel. CONCLUSION: Volumetric analysis of lymph nodes works satisfying in a clinical setting. Thin slice reconstructions (≤3 mm) and a middle soft tissue reconstruction kernel are recommended. LAD and SAD did not show significant differences regarding APE. Automated RECIST measurement showed lower APE than manual measurement in trend.

Semi-automated volumetric analysis of artificial lymph nodes in a phantom study.

PURPOSE: Quantification of tumour burden in oncology requires accurate and reproducible image evaluation. The current standard is one-dimensional measurement (e.g. RECIST) with inherent disadvantages. Volumetric analysis is discussed as an alternative for therapy monitoring of lung and liver metastases. The aim of this study was to investigate the accuracy of semi-automated volumetric analysis of artificial lymph node metastases in a phantom study. MATERIALS AND METHODS: Fifty artificial lymph nodes were produced in a size range from 10 to 55mm; some of them enhanced using iodine contrast media. All nodules were placed in an artificial chest phantom (artiCHEST®) within different surrounding tissues. MDCT was performed using different collimations (1-5 mm) at varying reconstruction kernels (B20f, B40f, B60f). Volume and RECIST measurements were performed using Oncology Software (Siemens Healthcare, Forchheim, Germany) and were compared to reference volume and diameter by calculating absolute percentage errors. RESULTS: The software performance allowed a robust volumetric analysis in a phantom setting. Unsatisfying segmentation results were frequently found for native nodules within surrounding muscle. The absolute percentage error (APE) for volumetric analysis varied between 0.01 and 225%. No significant differences were seen between different reconstruction kernels. The most unsatisfactory segmentation results occurred in higher slice thickness (4 and 5 mm). Contrast enhanced lymph nodes showed better segmentation results by trend. CONCLUSION: The semi-automated 3D-volumetric analysis software tool allows a reliable and convenient segmentation of artificial lymph nodes in a phantom setting. Lymph nodes adjacent to tissue of similar density cause segmentation problems. For volumetric analysis of lymph node metastases in clinical routine a slice thickness of ≤3mm and a medium soft reconstruction kernel (e.g. B40f for Siemens scan systems) may be a suitable compromise for semi-automated volumetric analysis.

Semi-automated volumetric analysis of lymph node metastases during follow-up--initial results.

OBJECTIVE: Quantification of tumour burden in oncology requires accurate and reproducible evaluation. The current standard is RECIST measurement with its inherent disadvantages. Volumetric analysis is an alternative for therapy monitoring. The aim of this study was to evaluate the feasibility of volumetric analysis of lymph node metastases using a software prototype in a follow-up setting. METHODS: MSCT was performed in 50 patients covering the chest, abdomen and pelvis. A total of 174 suspicious lymph nodes were evaluated by two radiologists regarding short axis diameters and volumetric analysis using semi-automated software. Quality of segmentation, time, maximum diameter and volume were documented. Variability of the derived change rates was computed as the standard deviation of the difference of the obtained respective change rates. RESULTS: The software performance provides robust volumetric analysis. Quality of segmentation was rated acceptable to excellent in 76-79% by each reader. Mean time spent per lesion was 38 s. The variability of change in effective diameters was 10.6%; for change rates of RECIST maximum diameter variability was 27.5%. CONCLUSION: Semi-automated volumetric analysis allows fast and convenient segmentation of most lymph node metastases. Compared with RECIST the inter-observer-variability in baseline and follow-up is reduced. This should principally allow subtle changes to be subclassified within the RECIST stable range as minor response [-15% to +10%].

Rapid image recognition of body parts scanned in computed tomography datasets.

AIM: Automatic CT dataset classification is important to efficiently create reliable database annotations, especially when large collections of scans must be analyzed. METHOD: An automated segmentation and labeling algorithm was developed based on a fast patient segmentation and extraction of statistical density class features from the CT data. The method also delivers classifications of image noise level and patient size. The approach is based on image information only and uses an approximate patient contour detection and statistical features of the density distribution. These are obtained from a slice-wise analysis of the areas filled by various materials related to certain density classes and the spatial spread of each class. The resulting families of curves are subsequently classified using rules derived from knowledge about features of the human anatomy. RESULTS: The method was successfully applied to more than 5,000 CT datasets. Evaluation was performed via expert visual inspection of screenshots showing classification results and detected characteristic positions along the main body axis. Accuracy per body region was very satisfactory in the trunk (lung/liver >99.5% detection rate, presence of abdomen >97% or pelvis >95.8%) improvements are required for zoomed scans. CONCLUSION: The method performed very reliably. A test on 1,860 CT datasets collected from an oncological trial showed that the method is feasible, efficient, and is promising as an automated tool for image post-processing.

Linear and volume measurements of pulmonary nodules at different CT dose levels - intrascan and interscan analysis.

PURPOSE: To compare the interobserver variability of the unidimensional diameter and volume measurements of pulmonary nodules in an intrascan and interscan analysis using semi-automated segmentation software on ultra-low-dose computed tomography (ULD-CT) and standard dose CT (SD-CT) data. MATERIALS AND METHODS: In 33 patients with pulmonary nodules, two chest multi-slice CT (MSCT) datasets (1 mm slice thickness; 20 % reconstruction overlap) had been consecutively acquired with an ultra-low dose (120 kV, 5 mAs) and standard dose technique (120 kV, 75 mAs). MSCT data was retrospectively analyzed using the segmentation software OncoTREAT (MeVis, Bremen, Germany, version 1.3). The volume of 229 solid pulmonary nodules included in the analysis as well as the largest diameter according to RECIST (Response Evaluation Criteria for Solid Tumors) were measured by two radiologists. Interobserver variability was calculated and SD-CT and ULD-CT data compared in an intrascan and interscan analysis. RESULTS: The median nodule diameter (n = 229 nodules) was registered with 8.2 mm (range: 2.8 to 43.6 mm, mean: 10.8 mm). The nodule volume ranged between 0.01 and 49.1 ml (median 0.1 ml, mean 1.5 ml). With respect to interobserver variability, the intrascan analysis did not reveal statistically significant differences (p > 0.05) between ULD-CT and SD-CT with broader limits of agreement for relative differences of RECIST measurements (-31.0 % + 27.0 % mean -2.0 % for SD-CT; -27.0 % + 38.6 %, mean 5.8 % for ULD-CT) than for volume measurements (-9.4 %, 8.0 %, mean 0.7 % for SD-CT; -13 %, 13 %, mean 0.0 % for ULD-CT). The interscan analysis showed broadened 95 % confidence intervals for volume measurements (-26.5 % 29.1 % mean 1.3 %, and -25.2 %, 29.6 %, mean 2.2 %) but yielded comparable limits of agreement for RECIST measurements. CONCLUSION: The variability of nodule volumetry assessed by semi-automated segmentation software as well as nodule size determination by RECIST appears to be independent of the acquisition dose in the CT source dataset. This is particularly important regarding size determination of pulmonary nodules in screening trials using low-dose CT data for follow-up imaging.

Semi-automated volumetric analysis of lymph node metastases in patients with malignant melanoma stage III/IV--a feasibility study.

Therapy monitoring in oncological patient care requires accurate and reliable imaging and post-processing methods. RECIST criteria are the current standard, with inherent disadvantages. The aim of this study was to investigate the feasibility of semi-automated volumetric analysis of lymph node metastases in patients with malignant melanoma compared to manual volumetric analysis and RECIST. Multislice CT was performed in 47 patients, covering the chest, abdomen and pelvis. In total, 227 suspicious, enlarged lymph nodes were evaluated retrospectively by two radiologists regarding diameters (RECIST), manually measured volume by placement of ROIs and semi-automated volumetric analysis. Volume (ml), quality of segmentation (++/--) and time effort (s) were evaluated in the study. The semi-automated volumetric analysis software tool was rated acceptable to excellent in 81% of all cases (reader 1) and 79% (reader 2). Median time for the entire segmentation process and necessary corrections was shorter with the semi-automated software than by manual segmentation. Bland-Altman plots showed a significantly lower interobserver variability for semi-automated volumetric than for RECIST measurements. The study demonstrated feasibility of volumetric analysis of lymph node metastases. The software allows a fast and robust segmentation in up to 80% of all cases. Ease of use and time needed are acceptable for application in the clinical routine. Variability and interuser bias were reduced to about one third of the values found for RECIST measurements.

Influence of food on bioavailability of amdinocillin pivoxil.

The bioavailability of amdinocillin was not altered when amdinocillin pivoxil was ingested 1 h before a standard breakfast, and it increased by 20% when amdinocillin pivoxil was ingested with or 1 h after a standard breakfast. Amdinocillin pivoxil would be convenient for patients since it may be taken with or without food.

Influence of food on midazolam absorption.

The influence of food on the absorption of midazolam, a new benzodiazepine derivative, was investigated in 18 healthy volunteers in a four-way, randomized, crossover study with a one-week washout period between treatments. Single 15-mg oral doses of midazolam were administered one hour before, with, and one hour after a standard meal as well as under fasting conditions (control). Following serial blood sampling over the next 24-hour period, midazolam plasma concentrations were determined by gas chromatography and mass spectrometry for pharmacokinetic evaluation. The maximum plasma concentration (Cmax), time of maximum concentration (tmax), lag time prior to absorption (tlag), area under the plasma concentration-time curve (AUC), and elimination rate constant of midazolam and 1-hydroxymethylmidazolam were determined. Significant changes in these parameters were not found when midazolam was taken one hour before or with a meal as compared with the control condition. Significant changes in the Cmax, tmax, and AUC parameters for both midazolam and its metabolite were seen when midazolam was ingested one hour after a meal: There was a delayed and reduced rate of absorption as well as a small reduction in the extent of absorption. Thus, ingestion of midazolam within one hour after a meal may result in a delay in the onset of the pharmacologic effect. These changes may be of some clinical significance in that they may potentially delay the onset of sleep.

Pharmacokinetics of intravenous amdinocillin in healthy subjects and patients with renal insufficiency.

Five healthy volunteers and 31 patients with various degrees of renal impairment received a 10-mg/kg intravenous dose of amdinocillin by infusion over 15 min to establish the disposition profile of the drug in plasma and urine. Both clearance from plasma and elimination rate constant showed a linear relationship with creatinine clearance. It was noted that in subjects with creatinine clearances of greater than 50 ml/min, the elimination half-life remained relatively constant; however, as the creatinine clearance decreased from 50 to 5 ml/min, there was a progressive rise in the elimination half-life. Despite the removal of the drug by hemodialysis (32 to 72% of the dose), concentrations of amdinocillin in plasma remained in the therapeutic range. In patients undergoing peritoneal dialysis, less than 4.0% of the infused dose was removed by dialysis during the hourly exchanges over a 14- to 18-h period. Although the clearance from plasma and the half-life of amdinocillin were altered up to fourfold in patients with creatinine clearances of less than 15 ml/min, the amdinocillin dosage per se may not need to be reduced for these patients if the frequency of dosing is reduced from six to three or four times daily. This is based on drug accumulation estimates of 56% from a regimen of 10 mg/kg every 8 h in these patients as compared with less than 10% from a regimen of 10 mg/kg every 4 h in subjects with normal renal function. In addition, supplemental doses may not be necessary during or at the end of hemodialysis for patients undergoing hemodialysis.

Dose dependent pharmacokinetics of midazolam.

The pharmacokinetics of midazolam and 1-hydroxymethylmidazolam were investigated following oral administration of 7.5, 15 and 30 mg doses of midazolam in solution to 12 healthy subjects. Compared to the 7.5 mg dose, the Cmax and AUC parameters of both midazolam and 1-hydroxymethylmidazolam increased proportionally after the 15 mg dose and more than proportionally after the 30 mg dose. The t1/2 for midazolam remained relatively constant between the 7.5 and 15 mg doses whereas it increased slightly but significantly after the 30 mg dose. These data indicated that the pharmacokinetics of midazolam and 1-hydroxymethylmidazolam were linear between the 7.5 and 15 mg oral dose range. However, after the 30 mg dose, the systemic availability of midazolam and the AUC for 1-hydroxymethylmidazolam appeared to be greater than that anticipated from the lower doses, possibly due to saturation of midazolam first-pass metabolism. This is not expected to have any clinical significance under the conditions of therapeutic use.

Intravenous and intramuscular pharmacokinetics of recombinant leukocyte A interferon.

Interferon is currently being evaluated for the treatment of disseminated cancer and viral diseases. Alpha interferons have shown to be effective in the treatment of a number of malignancies. Recombinant leukocyte A interferon (rIFN-alpha A) is an alpha interferon produced by recombinant DNA techniques. A kinetic evaluation of rIFN-alpha A following intravenous and intramuscular administration has not been adequately defined. The present study was designed to evaluate the kinetics of rIFN-alpha A following intravenous and intramuscular administration of 3, 9 or 18 X 10(6) units to patients with disseminated cancer. A preliminary report of this study was presented at the meeting of the American Society for Clinical Pharmacology and Therapeutics in San Diego, March 1983 (1).

Pharmacokinetic model to describe the disposition of lead in the rat.

A pharmacokinetic model was developed to describe the disposition of lead in the rat. The model can be used to predict the effect of acute high-dose as well as low-dose exposure to lead. These results suggest that the model should be able to predict the effect of chronic low-dose exposures as well. Plasma, bone, liver, and bile profiles were generated from this model using previously published data. The results obtained supported the existing theory that lead demonstrates a dose-dependent pharmacokinetic profile in the rat.