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.

Correlation of serum level of high mobility group box 1 with the burden of granulomatous inflammation in granulomatosis with polyangiitis (Wegener's).

OBJECTIVES: To investigate the correlation of serum levels of high mobility group box 1 (HMGB1) with the extent of granulomatous inflammation in granulomatosis with polyangiitis (GPA). METHODS: From 169 patients with GPA, 17 patients with granulomatous inflammation, without evidence of vasculitis were identified and 36 patients without measurable 'granuloma' formation. HMGB1 serum levels were determined and compared between the two groups, using a Mann-Whitney U test. Serum levels of 26 healthy individuals served as controls. In a further 21 patients with GPA with a pulmonary granulomatous manifestation from the study population, CT volumetry of 'granuloma' was performed. Volumes were compared with serum levels of HMGB1 (Spearman rank order test). RESULTS: Serum levels of HMGB1 were significantly higher in patients with predominant granulomatous disease than in patients without measurable 'granuloma' manifestations (6.44 ± 4.53 ng/ml vs 3.85 ± 2.88 ng/ml; p=0.0107). In both groups, levels of HMGB1 were significantly higher than in controls (2.34 ± 2.01 ng/ml; p<0.01). A positive correlation of HMGB1 serum levels with volumes of pulmonary 'granuloma' (r=0.761, p<0.0017) was seen. CONCLUSIONS: HMGB1 serum levels are significantly higher in GPA with predominant granulomatous manifestations and correlate with volumes of pulmonary 'granuloma'. HMGB1 may be used as a marker of the burden of granulomatous inflammation in GPA.

MRI of respiratory dynamics with 2D steady-state free-precession and 2D gradient echo sequences at 1.5 and 3 Tesla: an observer preference study.

To compare the image quality of dynamic lung MRI with variations of steady-state free-precession (SSFP) and gradient echo (GRE) cine techniques at 1.5 T and 3 T. Ventilated porcine lungs with simulated lesions inside a chest phantom and four healthy human subjects were assessed with SSFP (TR/TE=2.9/1.22 ms; 3 ima/s) and GRE sequences (TR/TE=2.34/0.96 ms; 8 ima/s) as baseline at 1.5 and 3 T. Modified SSFPs were performed with nine to ten images/s (parallel imaging factors 2 and 3). Image quality for representative structures and artifacts was ranked by three observers independently. At 1.5 T, standard SSFP achieved the best image quality with superior spatial resolution and signal, but equal temporal resolution to GRE. SSFP with improved temporal resolution was ranked second best. Further acceleration (PI factor 3) was of no benefit, but increased artifacts. At 3 T, GRE outranged SSFP imaging with high lesion signal intensity, while artifacts on SSFP images increased visibly. At 1.5 T, a modified SSFP with moderate parallel imaging (PI factor 2) was considered the best compromise of temporal and spatial resolution. At 3 T, GRE sequences remain the best choice for dynamic lung MRI.

[Investigation of respiratory-dependent movements of pulmonary space-occupying lesions with MRI]. / Untersuchung der atemabhängigen Bewegungen pulmonaler Raumforderungen mit der MRT.

Parallel imaging and echo sharing techniques have markedly reduced the acquisition times for MRI of large volumes. Dynamic 2 and 3-dimensional data sets of the chest with high temporal resolution (up to 10 images/s with single slice and 2 volume/s) allow an analysis of respiratory motion of the lungs and tumors. Time-resolved 2D series in preselected planes can be used to observe respiratory motion during free breathing or after respiratory commands, e.g. to exclude chest wall invasion by a tumor or for diagnosing impairment of respiratory mechanics. Time-resolved 3D-series (4D-MRI) allow monitoring of the spatial displacement of the lungs and tumors as a whole volume. Present limitations such as an overestimation of tumor size and an underestimation of displacement due to a limited temporal resolution are expected to be overcome with further technical developments. However, 4D-MRI already appears to be the appropriate tool to select patients for motion-adapted radiotherapy. In addition 4D-MRI is available for a broad spectrum of scientific applications, as it allows repeated and prolonged series of measurements without radiation exposure.

Four-dimensional magnetic resonance imaging for the determination of tumour movement and its evaluation using a dynamic porcine lung phantom.

A method of four-dimensional (4D) magnetic resonance imaging (MRI) has been implemented and evaluated. It consists of retrospective sorting and slice stacking of two-dimensional (2D) images using an external signal for motion monitoring of the object to be imaged. The presented method aims to determine the tumour trajectories based on a signal that is appropriate for monitoring the movement of the target volume during radiotherapy such that the radiation delivery can be adapted to the movement. For evaluation of the 4D-MRI method, it has been applied to a dynamic lung phantom, which exhibits periodic respiratory movement of a porcine heart-lung explant with artificial pulmonary nodules. Anatomic changes of the lung phantom caused by respiratory motion have been quantified, revealing hysteresis. The results demonstrate the feasibility of the presented method of 4D-MRI. In particular, it enables the determination of trajectories of periodically moving objects with an uncertainty in the order of 1 mm.

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.

Volumetric response classification in metastatic solid tumors on MSCT: initial results in a whole-body setting.

PURPOSE: To examine technical parameters of measurement accuracy and differences in tumor response classification using RECIST 1.1 and volumetric assessment in three common metastasis types (lung nodules, liver lesions, lymph node metastasis) simultaneously. MATERIALS AND METHODS: 56 consecutive patients (32 female) aged 41-82 years with a wide range of metastatic solid tumors were examined with MSCT for baseline and follow up. Images were evaluated by three experienced radiologists using manual measurements and semi-automatic lesion segmentation. Institutional ethics review was obtained and all patients gave written informed consent. Data analysis comprised interobserver variability operationalized as coefficient of variation and categorical response classification according to RECIST 1.1 for both manual and volumetric measures. Continuous data were assessed for statistical significance with Wilcoxon signed-rank test and categorical data with Fleiss kappa. RESULTS: Interobserver variability was 6.3% (IQR 4.6%) for manual and 4.1% (IQR 4.4%) for volumetrically obtained sum of relevant diameters (p<0.05, corrected). 4-8 patients' response to therapy was classified differently across observers by using volumetry compared to standard manual measurements. Fleiss kappa revealed no significant difference in categorical agreement of response classification between manual (0.7558) and volumetric (0.7623) measurements. CONCLUSION: Under standard RECIST thresholds there was no advantage of volumetric compared to manual response evaluation. However volumetric assessment yielded significantly lower interobserver variability. This may allow narrower thresholds for volumetric response classification in the future.

Inter-observer reproducibility of semi-automatic tumor diameter measurement and volumetric analysis in patients with lung cancer.

OBJECTIVES: Therapy monitoring in oncologic patient requires precise measurement methods. In order to improve the precision of measurements, we used a semi-automated generic segmentation algorithm to measure the size of large lung cancer tumors. The reproducibility of computer-assisted measurements were assessed and compared with manual measurements. METHODS: CT scans of 24 consecutive lung cancer patients who were referred to our hospital over a period of 6 months were analyzed. The tumor sizes were measured manually by 3 independent radiologists, according to World Health Organization (WHO) and the Revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. At least 10 months later, measurements were repeated semi-automatically on the same scans by the same radiologists. The inter-observer reproducibility of all measurements was assessed and compared between manual and semi-automated measurements. RESULTS: Manual measurements of the tumor longest diameter were significantly (p < 0.05) smaller compared with the semi-automated measurements. The intra-rater correlations coefficients were significantly higher for measurements of longest diameter (intra-class correlation coefficients: 0.998 vs. 0.986; p < 0.001) and area (0.995 vs. 0.988; p = 0.032) using semi-automated compared with manual method. The variation coefficient for manual measurement of the tumor area (WHO guideline, 15.7% vs. 7.3%) and the longest diameter (RECIST guideline, 7.7% vs. 2.7%) was 2-3 times that of semi-automated measurement. CONCLUSIONS: By using computer-assisted size assessment in primary lung tumor, interobserver-variability can be reduced to about half to one-third compared to standard manual measurements. This indicates a high potential value for therapy monitoring in lung cancer patients.

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.

MRI of the lung (2/3). Why when how?

BACKGROUND: Among the modalities for lung imaging, proton magnetic resonance imaging (MRI) has been the latest to be introduced into clinical practice. Its value to replace X-ray and computed tomography (CT) when radiation exposure or iodinated contrast material is contra-indicated is well acknowledged: i.e. for paediatric patients and pregnant women or for scientific use. One of the reasons why MRI of the lung is still rarely used, except in a few centres, is the lack of consistent protocols customised to clinical needs. METHODS: This article makes non-vendor-specific protocol suggestions for general use with state-of-the-art MRI scanners, based on the available literature and a consensus discussion within a panel of experts experienced in lung MRI. RESULTS: Various sequences have been successfully tested within scientific or clinical environments. MRI of the lung with appropriate combinations of these sequences comprises morphological and functional imaging aspects in a single examination. It serves in difficult clinical problems encountered in daily routine, such as assessment of the mediastinum and chest wall, and even might challenge molecular imaging techniques in the near future. CONCLUSION: This article helps new users to implement appropriate protocols on their own MRI platforms. Main Messages • MRI of the lung can be readily performed on state-of-the-art 1.5-T MRI scanners. • Protocol suggestions based on the available literature facilitate its use for routine • MRI offers solutions for complicated thoracic masses with atelectasis and chest wall invasion. • MRI is an option for paediatrics and science when CT is contra-indicated.

Lung, liver and lymph node metastases in follow-up MSCT: comprehensive volumetric assessment of lesion size changes.

PURPOSE: To investigate measurement accuracy in terms of precision and inter-rater variability in the simultaneous volumetric assessment of lung, liver and lymph node metastasis size change over time in comparison to RECIST 1.1. MATERIALS AND METHODS: Three independent readers evaluated multislice CT data from clinical follow-up studies (chest/abdomen) in 50 patients with metastases. A total of 117 lung, 77 liver and 97 lymph node metastases were assessed manually (RECIST 1.1) and by volumetry with semi-automated software. The quality of segmentation and need for manual adjustments were recorded. Volumes were converted to effective diameters to allow comparison to RECIST. For statistical assessment of precision and interobserver agreement, the Wilcoxon-signed rank test and Bland-Altman plots were utilized. RESULTS: The quality of segmentation after manual correction was acceptable to excellent in 95 % of lesions and manual corrections were applied in 21 - 36 % of all lesions, most predominantly in lymph nodes. Mean precision was 2.6 - 6.3 % (manual) with 0.2 - 1.5 % (effective) relative measurement deviation (p <.001). Inter-reader median variation coefficients ranged from 9.4 - 12.8 % (manual) and 2.9 - 8.2 % (volumetric) for different lesion types (p < .001). The limits of agreement were ± 9.8 to ± 11.2 % for volumetric assessment. CONCLUSION: Superior precision and inter-rater variability of volumetric over manual measurement of lesion change over time was demonstrated in a whole body setting.

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.

Lung nodule assessment in computed tomography: precision of attenuation measurement based on computer-aided volumetry.

PURPOSE: To compare the reproducibility (r) of CT value measurement of pulmonary nodules using volumetry software (LungCare, LC) and manual ROIs (mROI). MATERIALS AND METHODS: 54 artificial nodules in a chest phantom were scanned three times with CT. CT values were measured with LC and mROI. The intrascan-r was assessed with three measurements in the first scan, and the interscan-r with measurements in three consecutive scans (one observer). Intrascan-r und interobserver-r (two obs.) were assessed in the first scan and in contrast-enhanced CT of 51 nodules from 15 patients (kernels b50f and b80f). Intrascan-r and interscan-r were described as the mean range and interobserver-r as the mean difference of CT values. The significance of differences was tested using t-test and sign test. RESULTS: Reproducibility was significantly higher for volumetry-based measurements in both artificial and patient nodules (range 0.11 vs. 6.16 HU for intrascan-r, 2.22 vs. 7.03 HU for interscan-r, difference 0.11 vs. 18.42 HU for interobserver-r; patients: 1.78 vs. 13.19 HU (b50f-Kernel) and 1.88 vs. 27.4 HU (b80f-Kernel) for intrascan-r, 3.71 vs. 22.43 HU for interobserver-r). Absolute CT values differed significantly between convolution kernels (pat./mROI: 29.3 [b50f] and 151.9 HU [b80f] pat./LC: 5 [b50f] and 147 HU [b80f]). CONCLUSION: The reproducibility of volumetry-based measurements of CT values in pulmonary nodules is significantly higher and should therefore be recommended, e. g. in dynamic chest CT protocols. Reproducibility does not depend on absolute CT values.

[Automated procedure for volumetric measurement of metastases: estimation of tumor burden]. / Automatisierte Verfahren zur Volumetrie von Metastasen: Ermittlung der Tumorlast.

Cancer is a common and increasing disease worldwide. Therapy monitoring in oncologic patient care requires accurate and reliable measurement methods for evaluation of the tumor burden. RECIST (response evaluation criteria in solid tumors) and WHO criteria are still the current standards for therapy response evaluation with inherent disadvantages due to considerable interobserver variation of the manual diameter estimations. Volumetric analysis of e.g. lung, liver and lymph node metastases, promises to be a more accurate, precise and objective method for tumor burden estimation.

Image-based evaluation of tumor response to treatment: where is radiology today?

Oncological patient care requires long term follow-up in order to estimate effectiveness of existing and new treatment choices. Image-based assessment of whole body tumour burden is commonly used for that purpose. The WHO response criteria were established in 1979 proposing bi-dimensional tumor measurements. New RECIST guidelines appeared in 2000 relying on only the longest diameter (uni-dimensional) measurements. Obviously, a change in tumour size is only one potential surrogate for therapy response which not necessarily reflects the biologic activity of the tumour or the effect of particular therapy. Thus, the evaluation of biological, metabolic or molecular properties of a tumor and its changes might be an attractive means to assess the response to therapy sensitively and early.

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.