Georg Bier

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.

Simplified response monitoring criteria for multiple myeloma in patients undergoing therapy with novel agents using computed tomography

INTRODUCTION Multiple myeloma is a malignant hematological disorder of the mature B-cell lymphocytes originating in the bone marrow. While therapy monitoring is still mainly based on laboratory biomarkers, the additional use of imaging has been advocated due to inaccuracies of serological biomarkers or in a-secretory myelomas. Non-enhanced CT and MRI have similar sensitivities for lesions in yellow marrow-rich bone marrow cavities with a favourable risk and cost-effectiveness profile of CT. Nevertheless, these methods are still limited by frequently high numbers of medullary lesions and its time consumption for proper evaluation. OBJECTIVE To establish simplified response criteria by correlating size and CT attenuation changes of medullary multiple myeloma lesions in the appendicular skeleton with the course of lytic bone lesions in the entire skeleton. Furthermore to evaluate these criteria with respect to established hematological myeloma-specific parameters for the prediction of treatment response to bortezomib or lenalidomide. MATERIALS AND METHODS Non-enhanced reduced-dose whole-body CT examinations of 78 consecutive patients (43 male, 35 female, mean age 63.69±9.2years) with stage III multiple myeloma were retrospectively re-evaluated. On per patient basis, size and mean CT attenuation of 2-4 representative lesions in the limbs were measured at baseline and at a follow-up after a mean of 8 months. Results were compared with the course of lytical bone lesions as well with that of specific hematological biomarkers. Myeloma response was assessed according to the International Myeloma Working Group (IMWG) uniform response criteria. Testing for correlation between response of medullary lesions (Respmed) and response of all myeloma manifestations including osteolyses (Resptotal) was performed using the corrected contingency coefficient (Ccorr). RESULTS The correlation between Respmed based on length diameter and transverse diameter and Resptotal was perfect (Ccorr=1.0; p<0.0001) whereas the correlation based on density was moderate (Ccorr=0.54; p<0.0001). The evaluation of simplified response criteria with a measurement of only 2 medullary lesions yielded the best sensitivity and specificity valued for treatment-induced changes for the length diameter evaluation with 94.4%/95.7% for prediction of progressive disease and 78.6%/93.3% for prediction of therapy response. There were no significant differences between patients treated with bortezomib and lenalidomide (p>0.05). CONCLUSION Measurements of size of a minimum of two medullary lesions is sufficient for response assessment and correlates very well with the course of lytic bone lesions and that of hematologic parameters.

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.

Feasibility of CAIPIRINHA-Dixon-TWIST-VIBE for dynamic contrast-enhanced MRI of the prostate.

PURPOSE To evaluate the feasibility of a CAIPIRINHA-Dixon-TWIST (CDT)-VIBE sequence for improving image quality and temporal resolution in dynamic contrast-enhanced MRI (DCE-MRI) of the prostate. MATERIAL AND METHODS 44 male patients (age 63.9 ± 8.9 years) with clinically suspected prostate cancer underwent DCE-MRI at a 3T MRI scanner (Magnetom Skyra, Siemens Healthcare, Erlangen, Germany) using a CDT-VIBE sequence (spatial resolution=3×1.2×1.2mm(3), temporal resolution=5s, total scan duration=4:10 min) with body-weight-adapted administration of contrast agent (Gadobutrol, Bayer Healthcare, Berlin, Germany). To investigate effects on image quality, the same sequence was acquired three times per patient during the late phase: 1. with the same protocol as in the arterial phase (VS5), 2. without view-sharing (no view-sharing, NVS) using a 2-fold CAIPIRINHA acceleration R=2 (temporal resolution=15s, NVS15) and 3. NVS using a 6-fold CAIPIRINHA acceleration R=6 (temporal resolution=5s, NVS5). SNR and CNR were evaluated with the subtraction method. Image quality of the three sequences (VS5, NVS15, NVS5) was subjectively assessed by 2 blinded radiologists using a 5-point Likert scale (5 being excellent). Perfusion profiles of visually normal prostate and of malignant lesions as characterized by Wash-In, Wash-Out, time-to-peak (TTP) and initial area under the curve (iAUC) from the original datasets (temporal resolution=5s) and from datasets with a downsampled temporal resolution (15s) were compared. RESULTS In 20 of 44 included patients, potentially malignant lesions were identified in which 16 had histologically confirmed prostate cancer. SNR was highest for VS5 and NVS15, and lowest for NVS5 (p <.001). Concordantly, subjective image quality was comparable for VS5 and NVS15 (sum score 23.20 ± 1.03 vs 23.53 ± 1.34) and significantly lower for NVS5 (sum score 9.83 ± 2.32; p<.001). Perfusion parameters of macroscopically normal prostate tissue and suspect lesions differed significantly between original datasets and datasets with simulated lower temporal resolution, with the latter showing higher Wash-In (p=.002), lower Wash-Out (p=.003), higher Time-to-Peak (p<.001) and lower iAUC (p<.001). CONCLUSION CDT-VIBE can be readily exploited for DCE-MRI of the prostate preserving the diagnostic image quality while providing high temporal resolution for quantitative diagnostic assessment of enhancement curves in malignant lesions.

Accuracy of Non-Enhanced CT in Detecting Early Ischemic Edema Using Frequency Selective Non-Linear Blending.

Purpose Ischemic brain edema is subtle and hard to detect by computed tomography within the first hours of stroke onset. We hypothesize that non-enhanced CT (NECT) post-processing with frequency-selective non-linear blending (“best contrast”/BC) increases its accuracy in detecting edema and irreversible tissue damage (infarction). Methods We retrospectively analyzed the NECT scans of 76 consecutive patients with ischemic stroke (exclusively middle cerebral artery territory—MCA) before and after post-processing with BC both at baseline before reperfusion therapy and at follow-up (5.73±12.74 days after stroke onset) using the Alberta Stroke Program Early CT Score (ASPECTS). We assessed the differences in ASPECTS between unprocessed and post-processed images and calculated sensitivity, specificity, and predictive values of baseline NECT using follow-up CT serving as reference standard for brain infarction. Results NECT detected brain tissue hypoattenuation in 35 of 76 patients (46.1%). This number increased to 71 patients (93.4%) after post-processing with BC. Follow-up NECT confirmed brain infarctions in 65 patients (85.5%; p = 0.012). Post-processing increased the sensitivity of NECT for brain infarction from 35/65 (54%) to 65/65 (100%), decreased its specificity from 11/11 (100%) to 7/11 (64%), its positive predictive value (PPV) from 35/35 (100%) to 65/69 (94%) and increased its accuracy 46/76 (61%) to 72/76 (95%). Conclusions This post-hoc analysis suggests that post-processing of NECT with BC may increase its sensitivity for ischemic brain damage significantly.

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.

Improved CT Detection of Acute Herpes Simplex Virus Type 1 Encephalitis Based on a Frequency-Selective Nonlinear Blending: Comparison With MRI

OBJECTIVE The purpose of this study is to compare the diagnostic efficacy of a new CT postprocessing tool based on frequency-selective nonlinear blending (best-contrast CT) with that of standard linear blending of unenhanced head CT in patients with herpes simplex virus type 1 and herpes simplex virus encephalitis (HSE), using FLAIR MRI sequences as the standard of reference. MATERIALS AND METHODS Fifteen consecutive patients (six women and nine men; mean [± SD] age, 60 ± 19 years) with proven HSE (positive polymerase chain reaction results from CSF analysis and the presence of neurologic deficits) were retrospectively enrolled. All patients had undergone head CT and MRI (mean time interval, 2 ± 2 days). After standardized unenhanced head CT scans were read, presets of the best-contrast algorithm were determined (center, 30 HU; delta, 5 HU; slope, 5 nondimensional), and resulting images were analyzed. Contrast enhancement was objectively measured by ROI analysis, comparing contrast-to-noise ratios (CNRs) of unenhanced CT and best-contrast CT. FLAIR and DWI MRI sequences were analyzed, and FLAIR was considered as the standard of reference. For assessment of disease extent, a previously reported 50-point score (HSE score) was used. RESULTS CNR values for unenhanced head CT (CNR, 5.42 ± 2.77) could be statistically significantly increased using best-contrast CT (CNR, 9.62 ± 4.28) (p = 0.003). FLAIR sequences yielded a median HSE score of 9.0 (range, 6-17) and DWI sequences yielded HSE scores of 6.0 (range, 5-17). By comparison, unenhanced head CT resulted in a median HSE score of 3.5 (range, 1-6). The median best-contrast CT HSE score was 7.5 (range, 6-10). Agreement between FLAIR and unenhanced CT was 54.44%, that between DWI and best-contrast CT was 95.36%, and that between FLAIR and best-contrast CT was 85.21%. The most frequently overseen findings were located at the level of the upper part of the mesencephalon and at the subthalamic or insular level. CONCLUSION Frequency-selective nonlinear blending significantly increases contrast and detects brain parenchymal involvement in HSE more sensitively compared with unenhanced CT. The sensitivity of best-contrast CT seems to be equal to that of DWI and almost as good as that of FLAIR.

Perfusion-based assessment of disease activity in untreated and treated patients with aortitis and chronic periaortitis: correlation with CT morphological, clinical and serological data

OBJECTIVE To evaluate the role of perfusion-based assessment of inflammatory activity in patients with treated and untreated aortitis and chronic periaortitis as compared with clinical and serological markers. METHODS 35 patients (20 females; median age 66 years) with (peri) aortitis were retrospectively evaluated. All patients had clinical symptoms prompting at the time of imaging. All patients first underwent whole-body contrast-enhanced CT and subsequently segmental volume perfusion CT for assessment of the degree of vascularization of (peri) aortitis as a surrogate marker for inflammatory activity. Blood flow, blood volume, volume transfer constant (k-trans), time to peak and mean transit time were determined. The thickness of the increased connective tissue formation was measured. Perfusion data were correlated with clinical symptoms and acute-phase inflammatory parameters such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and leukocyte number. RESULTS 21 of 35 patients were untreated and 14 of 35 had previous/ongoing immunosuppression. The interobserver agreement was good (κ = 0.78) for all perfusion parameters. Average values of perfusion parameters were higher in untreated patients but remained abnormally elevated in treated patients as well. Perfusion data and ESR and CRP correlated well both in aortitis (p < 0.05) and in periaortitis (p < 0.05). In periaortitis, perfusion parameters agreed well with ESR and CRP values (p < 0.05) only in untreated patients. CONCLUSION Perfusion CT parameters in untreated aortitis and chronic periaortitis correlate well with serological markers with respect to disease activity assessment. However, in treated periaortitis, correlations were weak, suggesting an increased role for (perfusion-based) imaging. ADVANCES IN KNOWLEDGE Volume perfusion CT may be used for diagnosis of aortitis/periaortitis.

Histogram analysis of diffusion kurtosis imaging estimates for in vivo assessment of 2016 WHO glioma grades: A cross-sectional observational study

PURPOSE To assess the diagnostic performance of histogram analysis of diffusion kurtosis imaging (DKI) maps for in vivo assessment of the 2016 World Health Organization Classification of Tumors of the Central Nervous System (2016 CNS WHO) integrated glioma grades. MATERIALS AND METHODS Seventy-seven patients with histopathologically-confirmed glioma who provided written informed consent were retrospectively assessed between 01/2014 and 03/2017 from a prospective trial approved by the local institutional review board. Ten histogram parameters of mean kurtosis (MK) and mean diffusivity (MD) metrics from DKI were independently assessed by two blinded physicians from a volume of interest around the entire solid tumor. One-way ANOVA was used to compare MK and MD histogram parameter values between 2016 CNS WHO-based tumor grades. Receiver operating characteristic analysis was performed on MK and MD histogram parameters for significant results. RESULTS The 25th, 50th, 75th, and 90th percentiles of MK and average MK showed significant differences between IDH1/2wild-type gliomas, IDH1/2mutated gliomas, and oligodendrogliomas with chromosome 1p/19q loss of heterozygosity and IDH1/2mutation (p<0.001). The 50th, 75th, and 90th percentiles showed a slightly higher diagnostic performance (area under the curve (AUC) range; 0.868-0.991) than average MK (AUC range; 0.855-0.988) in classifying glioma according to the integrated approach of 2016 CNS WHO. CONCLUSIONS Histogram analysis of DKI can stratify gliomas according to the integrated approach of 2016 CNS WHO. The 50th (median), 75th, and the 90th percentiles showed the highest diagnostic performance. However, the average MK is also robust and feasible in routine clinical practice.

Enhanced reading time efficiency by use of automatically unfolded CT rib reformations in acute trauma.

Rationale of this study was to evaluate whether unfolded rib images enhance time efficiency in detection of rib fractures and time efficiency in patients with acute thoracic trauma. 51 subsequent patients with thoracic trauma underwent 64-slice computed tomography. 1mm thick axial slices were reformatted using a commercially available post-processing software application generating rotatable unfolded rib images. Diagnostic accuracy was evaluated by 3 readers and compared to multiplanar reformations of the original CT images. Reformation and evaluation times were recorded. 116 rib fractures were detected. The multiplanar reformation analysis yielded a sensitivity of 87.9%/93.9%/79.7% with a specificity of 97%/97%/82.2%, whilst the unfolded rib image analysis yielded a sensitivity of 94.8%/94.8%/92.2% and a specificity of 85.2/87.8%/82.4 (p=0.06/0.8/0.04) with high inter-observer agreement (k=0.79-0.85). The mean reading time for the multiplanar reformations was significantly longer (reader 1: 103.7 ± 27.1s/reader 2: 81.8 ± 40.6s/reader 3: 154.3 ± 39.2s) than the evaluation of the unfolded rib images (19.4 ± 4.9s/26.9 ± 15.0s/49.9 ± 18.7s; p<0.01). Concluding, the unfolded rib display reduces reading time for detection of rib fractures in acute thoracic trauma patients significantly and does not compromise the diagnostic accuracy significantly in experienced radiologists. However, unexperienced readers may profit from use of this display.