Christopher Kloth

CT imaging of bone and bone marrow infiltration in malignant melanoma—Challenges and limitations for clinical staging in comparison to 18FDG-PET/CT

Rationale of this study was the evaluation of the diagnostic value of computed tomography (CT) in the detection of bone marrow infiltration in comparison to PET/CT. Fifty patients (age 61 ± 15.12 years) with metastatic malignant melanoma underwent 18F-FDG-PET/CT, including contrast-enhanced CT. 2 readers evaluated the CT images in consensus for bone and bone marrow lesions focusing on lesion location, type and size. PET/CT was used as reference standard to estimate sensitivity, specificity, negative and positive predictive value. Moreover, the bone marrow density was estimated in the long bones and the sacral bone. Serum hamoglobin, thrombocyte level and S100 protein were correlated with the presence or absence of bone and bone marrow lesions. According to PET/CT as standard of reference, of 594 bone and medullary lesions 495 were considered malignant. Of these 77.8% were medullary, 20.4% lytic, 1% sclerotic and 0.8% mixed lytic/sclerotic. Contrast-enhanced CT yielded a lesion-based sensitivity of 36.8% and a specificity of 87.9% (PPV 93.8%; NPV 21.8%). Patient-based sensitivity and specificity were 78.8% and 82.4%, respectively. Of the missed lesions, most were medullary (95.8%). A disseminated bone marrow involvement (defined as >10 bone marrow lesions or diffuse infiltration of a whole body segment) was described in 11 cases, in 6 cases the disseminated involvement was underestimated or missed on CT. In cases with disseminated bone marrow involvement the bone marrow density was significantly higher in the humerus (p=0.04), but not in the femur or sacral bone (p=0.06). Multivariate analysis revealed no isolated effect of bone metastases on S100 serum and hemoglobin level, but both were significantly altered in patients with disseminated bone marrow involvement (p<0.05). In conclusion, the diagnostic value of computed tomography for the detection of bone marrow metastases in patients with melanoma, is limited. Especially in cases with disseminated bone marrow involvement about 50% of the cases were missed or underestimated.

Quantitative chest CT analysis in patients with systemic sclerosis before and after autologous stem cell transplantation: comparison of results with those of pulmonary function tests and clinical tests

OBJECTIVES The aim of this study was to evaluate the course of SSc-related pulmonary abnormalities following high-dose chemotherapy with autologous stem cell transplantation (SCT) by quantitative chest CT analysis and compare the results with those of pulmonary function tests and the response of cutaneous involvement. METHODS Chest CT quantification was performed before, directly after [0.49 years (sd 0.20)] and at a mean of 2.2 years (sd 2.1) following autologous SCT in 26 consecutive patients with SSc between March 2001 and March 2015. Quantitative CT used fully automated software to calculate inspiratory total lung volume, mean lung density, high attenuation value and their pulmonary distribution (core vs peel). All patients underwent pulmonary function tests. We additionally analysed parallels in the response of associated skin changes by using the modified Rodnan skin score (mRSS). RESULTS The forced vital capacity (FVC) course at 6 months was used to classify patients into responders [n = 20 (76.9%)] and non-responders [n = 6 (23.1%)]. FVC, forced expiratory volume in 1 s, vital capacity (VC) as well as single-breath diffusion capacity for carbon monoxide significantly improved (P = 0.03, 0.001, 0.001 and 0.013, respectively) in responders. At quantitative CT, total lung volume increased (P = 0.018), whereas mean lung density (P = 0.026) and high attenuation value decreased (P = 0.020) after autologous SCT in responders. Correspondingly, mRSS improved from 27.35 (sd 9.25) before to 10.81 (sd 8.64) after autologous SCT (P = 0.003) in responders. Changes in mRSS before autologous SCT and thereafter correlated significantly with those 24 months after autologous SCT (r = 0.575; P = 0.031). CONCLUSIONS CT quantification of lung volume and parenchymal attenuation in SSc patients presenting with alveolitis and fibrosis that undergo autologous SCT yields parameters that match well with those of pulmonary function and even clinical tests. It might therefore be used as a substitute marker in patients who are unable to adequately perform lung function tests.

Improved Follow-Up and Response Monitoring of Thoracic Cage Involvement in Multiple Myeloma Using a Novel CT Postprocessing Software: The Lessons We Learned

OBJECTIVE The purpose of this study is to evaluate the benefit of using novel CT postprocessing software that generates unfolded rib images for more-accurate evaluation of multiple myeloma (MM) at follow-up, response monitoring, and visualization of treatment-related bone changes. MATERIALS AND METHODS Between January 2012 and February 2015, 40 consecutive patients with MM underwent repeated whole-body reduced-dose CT at our institution. The results were retrospectively evaluated and compared with established hematologic markers. Unfolded rib reformatted images were compared with 5- and 1-mm-thick slices with regard to bone changes, bone marrow attenuation, and bone sclerosis. RESULTS Hematologic response categories at follow-up were complete response (CR; n = 2), very good partial response (VGPR; n = 1), partial response (PR; n = 9), stable disease (n = 9), and progressive disease (PD; n = 19). The number of lesions increased in 11 patients (all with PD), decreased in two patients (both with CR), and stayed unchanged in 27 patients. The size of the lesions increased in 14 patients (all with PD), decreased in five patients (two with CR, two with PR, and one with stable disease), and remained unchanged in 21 patients. There was a mean (± SD) difference of 27.99 ± 19.71 HU in bone marrow attenuation for patients with PD (p < 0.0001) and -31.24 ± 13.57 HU in the responders group (p = 0.002), whereas patients with stable disease showed stable bone marrow attenuation at follow-up (mean, -3.37 ± 10.55 HU). Increased bone sclerosis was detected in 12 patients (all of whom were receiving therapy). The sensitivity and specificity of unfolded rib images, 5-mm slices, and 1-mm slices were, respectively, 78.9% and 100%, 52.6% and 100%, and 63.2% and 100% for accurate bone response assessment; 100% and 95.2%, 94.74% and 42.9%, and 89.47% and 47.62% for bone marrow attenuation; and 100% and 100%, 58.3% and 100%, and 91.67% and 100% for sclerosis. CONCLUSION For therapy response assessment, unfolded rib reading is more accurate than transverse CT slices.

Improved Delineation of Pulmonary Embolism and Venous Thrombosis Through Frequency Selective Nonlinear Blending in Computed Tomography

Objective The aim of this study was to test the hypothesis that a novel frequency selective nonlinear blending (NLB) algorithm increases the delineation of pulmonary embolism and venous thrombosis in portal-venous phase whole-body staging computed tomography (CT). Materials and Methods A cohort of 67 patients with incidental pulmonary embolism and/or venous thrombosis in contrast-enhanced oncological staging CT were retrospectively selected. Computed tomography data sets were acquired 65 to 90 seconds after intravenous iodine contrast administration using state-of-the-art multi-detector CT scanners. A novel frequency selective NLB postprocessing technique was applied to reconstructed standard CT images. Two readers determined the most suitable settings to increase the delineation of pulmonary embolism and venous thrombosis. Outcome measure included region of interest and contrast-to-noise ratio (CNR) analyses, image noise, overall image quality, subjective delineation, as well as number and size of emboli and thrombi. Statistical testing included quantitative comparisons of Hounsfield units of thrombus and vessel, image noise and related CNR values and subjective image analyses of image noise, image quality and thrombus delineation, number and size in standard, and NLB images. Results Using frequency selective NLB settings with a center of 100 HU, delta of 40 HU, and a slope of 5, CNR values of pulmonary embolism (StandardCNR, 10 [6, 16]; NLBCNR, 22 [15, 30]; P < 0.001) and venous thrombosis (StandardCNR, 8 [5, 15]; NLBCNR, 12 [7, 19]; P = 0.0007) increased. Mean vascular enhancement using NLB was significantly higher than in standard images for pulmonary arteries (Standard, 138 [118, 191] HU; NLB, 269 [176, 329] HU; P < 0.0001) and veins (Standard, 120 [103, 162] HU; NLB, 169 [132, 217] HU; P < 0.0001), respectively. Image noise was not significantly different between standard and NLB images (P = 0.64-0.88). There was substantial to almost perfect interrater agreement as well as a significant increase of overall image quality (P < 0.004) and subjective delineation of the thrombotic material (P < 0.0001) in both subgroups. Nonlinear blending images revealed 8 additional segmental and 13 subsegmental emboli. Thrombus sizes were not significantly different, but subjective accuracy of the measurement could be significantly increased using NLB (P = 0.03). Conclusions Postprocessing of standard whole-body staging CT images with frequency selective NLB improves image quality and the delineation of pulmonary embolism and venous thrombosis.

Evaluation of Texture Analysis Parameter for Response Prediction in Patients with Hepatocellular Carcinoma Undergoing Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) Using Biphasic Contrast-enhanced CT Image Data: Correlation with Liver Perfusion CT

RATIONALE AND OBJECTIVES This study aimed to evaluate the potential role of computed tomography texture analysis (CTTA) of arterial and portal-venous enhancement phase image data for prediction and accurate assessment of response of hepatocellular carcinoma undergoing drug-eluting bead transarterial chemoembolization (TACE) by comparison to liver perfusion CT (PCT). MATERIALS AND METHODS Twenty-eight patients (27 male; mean age 67.2 ± 10.4) with 56 hepatocellular carcinoma-typical liver lesions were included. Arterial and portal-venous phase CT data obtained before and after TACE with a mean time of 39.93 ± 62.21 days between examinations were analyzed. TACE was performed within 48 hours after first contrast-enhanced CT. CTTA software was a prototype. CTTA analysis was performed blinded (for results) by two observers separately. Combined results of modified Response Evaluation Criteria In Solid Tumors (mRECIST) and PCT of the liver were used as the standard of reference. Time to progression was additionally assessed for all patients. CTTA parameters included heterogeneity, intensity, average, deviation, skewness, and entropy of co-occurrence. Each parameter was compared to those of PCT (blood flow [BF], blood volume, arterial liver perfusion [ALP], portal-venous perfusion, and hepatic perfusion index) measured before and after TACE. RESULTS mRECIST + PCT yielded 28.6% complete response (CR), 42.8% partial response, and 28.6% stable disease. Significant correlations were registered in the arterial phase in CR between changes in mean heterogeneity and BF (P = .004, r = -0.815), blood volume (P = .002, r = -0.851), and ALP (P = .002, r = -0.851), respectively. In the partial response group, changes in mean heterogeneity correlated with changes in ALP (P = .003) and to a lesser degree with hepatic perfusion index (P = .027) in the arterial phase. In the stable disease group, BF correlated with entropy of nonuniformity (P = .010). In the portal-venous phase, no statistically significant correlations were registered in all groups. Receiver operating characteristic analysis of CTTA parameters yielded predictive cutoff values for CR in the arterial contrast-enhanced CT phase for uniformity of skewness (sensitivity: 90.0%; specificity: 45.8%), and in the portal-venous phase for uniformity of heterogeneity (sensitivity: 92.3%; specificity: 81.8%). CONCLUSIONS Significant correlations exist between CTTA parameters and those derived from PCT both in the pre- and the post-TACE settings, and some of them have predictive value for TACE midterm outcome.

VEGFR-2 expression in HCC, dysplastic and regenerative liver nodules, and correlation with pre-biopsy Dynamic Contrast Enhanced CT

PURPOSE To evaluate whether VEGFR-2-expression in hepatocellular carcinoma (HCC), dysplastic (DLN) and regenerative liver nodules (RLN) correlates with pre-histology, in vivo Dynamic Contrast Enhanced-Computed Tomography (DCE-CT) data as VEGFR-2-expression affects prognosis and therapeutic options. MATERIALS AND METHODS 34 patients (63.6±8.9years, 7 females) underwent liver biopsy or surgery due to suspected HCC or dysplastic nodules after DCE-CT between 2009 and 2015 with no previous chemo- or interventional therapy. Immunohistochemistry staining for VEGFR-2 was performed using Immunoreactive-Remmele-Stegner-Score (IRS) for quantification. A 128-row CT-scanner was used for DCE-CT with assessment of perfusion parameters blood flow (BF), blood volume (BV), arterial liver perfusion (ALP), portal venous perfusion (PVP), and hepatic perfusion index (HPI). RESULTS Histology confirmed HCC (n=10), DLN (n=7) and RLN (n=34). Mean IRS for VEGFR-2 in HCCs was 9.1±3.0, 7.3±1.6 for DLN and 5.2±2.8 for RLN (p=0.0004 for HCC vs. RLN). Perfusion values varied significantly between all three groups for BF and HPI (p<0.001 and p<0.0001) and for BV in HCC vs. RLN (p<0.0001) and DLN vs. RLN (p=0.0019). Strong correlations between VEGFR-2-IRS and perfusion parameters were observed for BF in HCC (r=0.88, p<0.01) and HPI in HCC and DLN (r=0.85, p<0.04; r=0.9, p<0.01). CONCLUSION Immunostaining revealed different VEGFR-2-expression levels in HCC, dysplastic and regenerative liver nodules. Perfusion markers blood flow, blood volume and hepatic perfusion index correlated well with VEGFR-2-immunostaining. This non-invasive discrimination between regenerative and dysplastic/HCC nodules might open new perspectives for diagnosis, therapy planning, and anti-VEGFR therapy monitoring.

Comparison of chest-CT findings of Influenza virus-associated pneumonia in immunocompetent vs. immunocompromised patients

PURPOSE To retrospectively compare CT-patterns of pulmonary infiltration caused by different Influenza virus types and subtypes in immunocompetent and immunocompromised patients for possible discrimination. MATERIALS AND METHODS Retrospective database search at our institution yielded 237 patients who were tested positive for Influenza virus type A or type B by bronchoalveolar lavage between January 2009 and April 2014. Fifty-six of these patients (female 26; male 30; median age 55.8 y, range 17-86 y; SD ± 14.4 y) underwent chest-HRCT due to a more severe clinical course of pulmonary infection. We registered all CT-findings compatible with pulmonary infection classifying them as airway predominant (tree-in-bud, centrilobular nodules, bronchial wall thickening ± peribronchial ground-glass opacity and consolidation) vs. interstitial-parenchymal predominant (bilateral, symmetrical GGO, consolidation, crazy paving and/or interlobular septal thickening). Twenty-six patients (46.4%) had follow-up CT-studies (0.78 mean, SD ± 5.8 scans). RESULTS Thirty-six patients were immunocompromised (group I) whereas 20 patients were immunocompetent (group II). An airway-centric pattern of infection was found in 15 patients (group I) and 14 patients (group II) whereas an interstitial-parenchymal predominant pattern was found in 14 patients (group I) and 2 patients (group II). Eleven patients had a mixed pattern with no clear assignment to one group. At FU, 12 patients from group I and 3 from group II showed transitional infiltration patterns: in 10 patients from interstitial-parenchymal into airway predominant pattern and in five patients from airway predominant into interstitial-parenchymal. No significant differences in the pattern of pulmonary infection were found between different types and subtypes of Influenza viruses. CONCLUSION Patterns of pulmonary infiltration caused by Influenza viruses do not significantly differ between immunocompetent and immunocompromised patients or between different types and subtypes of Influenza virus. One possible explanation for this could be the temporarily interchangeable character of pulmonary infiltration in this infection.

Discriminatory CT-textural features in splenic infiltration of lymphoma versus splenomegaly in liver cirrhosis versus normal spleens in controls and evaluation of their role for longitudinal lymphoma monitoring

PURPOSE To find CT-texture analysis (CTTA) features for the discrimination of splenomegaly due to diffuse lymphoma involvement and liver cirrhosis versus normal-sized spleens in controls and to assess their potential role for longitudinal lymphoma monitoring. MATERIAL AND METHODS We had retrospectively identified 74 subjects with diffuse splenic involvement due to lymphoma (n = 29) and liver cirrhosis (n = 30), and healthy controls (n = 15), who underwent contrast-enhanced abdominal CT between August 2013 and October 2017. CTTA evaluation included heterogeneity, intensity, average, deviation, skewness, entropy of co-occurrence, number non-uniformity (NGLDM) and entropy NGLDM. A greater than 50% reduction of spleen volume after chemotherapy was considered proof for splenic involvement. RESULTS There were significant differences of splenic CTTA-values before and after treatment of patients with lymphoma, including mean of entropy(p < .001), uniformity of average(p < .001), uniformity of deviation(p = .002) and entropy of skewness(p < .001). Significant differences of splenic CTTA-values in subjects with lymphoma vs. healthy controls were found for mean intensity(p < .001), mean average(p < .001), and entropy of deviation(p < .001). No significant differences in splenic CTTA-values were found in subjects with lymphoma that reached complete remission vs. controls. Splenic CTTA values mean intensity(p = .002) and mean average(p = .004) were significantly different between subjects with untreated lymphoma and subjects with liver cirrhosis. At end-of-treatment all lymphomas reached complete remission. Entropy/uniformity of heterogeneity(p < .001), mean intensity(p = .007), mean average (p = .007), uniformity of average(p = .008) and mean/entropy/uniformity of skewness(p = .001) measured at this time differed significantly from baseline. CONCLUSIONS CTTA features in subjects with splenomegaly due to lymphoma and liver cirrhosis differ significantly from those of healthy controls and can be also used for monitoring lymphoma treatment. Quantitative CTTA features may increase the accuracy of diagnosing causes of splenomegaly.

Results of quantitative chest-CT in chronic pulmonary graftvs.- host disease (cGvHD) 3 years after allogeneic stem cell transplantation

BACKGROUND To quantify lung parenchymal changes in symptomatic patients with chronic pulmonary graft-versus-host disease 3 years after allogeneic stem cell transplantation (allo-SCT) by means of CT-densitometry (CTD) and to compare results with those of established pulmonary function tests (PFT). METHODS The study group consisted of 26 patients with pulmonary cGvHD (19 males, 7 females; mean age, 49.29±15.89; range, 19-72 years). The diagnosis was based on clinical symptoms, PFT and chest-CT findings. CTD and PFT were performed both in the pre- and post-transplantation setting and results compared with each other. CT scans were obtained during suspended deep inspiration including the whole lungs. The mean lung attenuation (MLD), low attenuation values (LAV) and distribution of focal parenchymal abnormalities compatible with emphysema (HU <-950) were quantitatively calculated with histograms and graphics. On PFT, total lung capacity (TLC), residual volume (RV), vital capacity (VC), forced expiratory volume in 1 s (FEV1s) and diffusion capacity for carbon monoxide (DLCOSB) were registered. RESULTS Changes in end-inspiratory lung volume and density (MLD and LAV) in symptomatic cGvHD patients in mean three years after allo-SCT proved all not significant, but there was a clear trend towards an increase in lung volume and a decrease in lung attenuation. These results were similar throughout all classes of bronchiolitis obliterans (BO) by cGvHD. PFT showed a significant decrease in VC, FEV1s but only a minimal decrease in DLCOSB. Changes in FVC after stem cell transplantation correlated with changes in LAV (r=0.649, P=0.031). Predicted VC correlated with changes in LAV (r=0.771, P=0.005). There was a correlation between the absolute difference of FEV1 and DLCOSB (r=0.64, P=0.14) before and after stem cell transplantation. CONCLUSIONS End-inspiratory phase CT lung parenchyma quantification in symptomatic patients with pulmonary cGvHD 3 years after allo-SCT shows discrete changes over the pre-transplantation setting representing airway obstruction, mirroring airflow limitation on PFT. Its use enables exclusion of relevant parenchymal destruction (emphysema-equivalent lung density) at this time.

Repeated surgeries in invasive lobular breast cancer with preoperative MRI: Role of additional carcinoma in situ and background parenchymal enhancement

OBJECTIVES Analysing the influence of additional carcinoma in situ (CIS) and background parenchymal enhancement (BPE) in preoperative MRI on repeated surgeries in patients with invasive lobular carcinoma (ILC) of the breast. METHODS Retrospective analysis of 106 patients (mean age 58.6±9.9years) with 108 ILC. Preoperative tumour size as assessed by MRI, mammography and sonography was recorded and compared to histopathology. In contrast-enhanced MRI, the degree of BPE was categorised by two readers. The influence of additionally detected CIS and BPE on the rate of repeated surgeries was analysed. RESULTS Additional CIS was present in 45.4% of the cases (49/108). The degree of BPE was minimal or mild in 80% of the cases and moderate or marked in 20% of the cases. In 17 cases (15.7%) at least one repeated surgery was performed. In n=15 of these cases, repeated surgery was performed after BCT (n=9 re-excisions, n=6 conversions to mastectomy), in n=2 cases after initial mastectomy. The initial surgical procedure (p=0.008) and additional CIS (p=0.046) significantly influenced the rate of repeated surgeries, while tumour size, patient age and BPE did not (p=ns). CONCLUSIONS Additional CIS was associated with a higher rate of repeated surgeries, whereas BPE had no influence.