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.
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.
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.
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.
To determine morphological and functional cardiovascular magnetic resonance (CMR) patterns in histopathologically confirmed myocardial involvement in patients with systemic sclerosis (SSc).
Twenty patients (6 females; mean age 41 ± 11 years) with histopathologically proven cardiac involvement in SSc in the years 2008–2016 were retrospectively evaluated. Morphological, functional and late gadolinium enhancement (LGE) images were acquired in standard angulations at 1.5 T CMR. Pathologies were categorized: 1) Pericardial effusion; 2) pathologic left (LV) or right ventricular (RV) contractility (hypokinesia, dyssynchrony, and diastolic restriction); 3) reduced left (LV-EF) and right ventricular ejection fraction (RV-EF); 4) fibrosis and/or inflammation (positive LGE); 5) RV dilatation. 95 % confidence intervals (CI) were calculated for appearance of pathologic EF and RV dilatation.
Seven patients (35 %) had positive CMR findings in three categories, 9 patients (45 %) in four categories and 4 patients (20 %) in five categories. The distribution of pathologic findings was: minimal pericardial effusion in 7 patients (35 %), moderate pericardial effusion >5 mm in nine patients (45 %); abnormal LV or RV contractility in 19 patients (95 %), reduced LV or RV function in 14 patients (70 %; 95 % CI: 51–88 %), pathologic LGE in all patients, RV dilatation in 6 patients (30 %; 95 % CI: 15–54 %).
CMR diagnosis of myocardial involvement in SSc requires increased attention to subtle findings. Pathologic findings in at least three of five categories indicate myocardial involvement in SSc.
Electronic supplementary material
The online version of this article (doi:10.1186/s12968-016-0289-3) contains supplementary material, which is available to authorized users.
Systemic sclerosis; Cardiomyopathy; Rheumatic heart disease; Cardiovascular magnetic resonance
This study aims to evaluate immediate changes in perfusion parameters in hepatocellular carcinoma (HCC) to transarterial chemoembolization (TACE) in C-arm computed tomography (CT) and volume perfusion CT (VPCT) and prediction of midterm tumor response.
Twenty-five patients (median age 66, range 61 to 75 years) with 62 HCC lesions undergoing TACE received immediate pre- and post-interventional assessment by C-arm CT and VPCT. Cross-sectional imaging was analyzed at baseline and approximately 12 weeks after TACE according to modified RECIST criteria. Outcome was defined as objective response (OR, > 30 % reduction of viable tumor) or non-OR. Perfusion parameters were evaluated in C-arm CT [parenchymal blood volume (PBV)] and VPCT [blood volume (BV) and blood flow (BF)]. Ratios of perfusion parameters before and after TACE within the tumor and the non-affected liver parenchyma were calculated.
Correlation between tumor PBV and BV revealed a moderate correlation (rho = 0.45, p = 0.005). In non-affected liver parenchyma, a significant decrease in PBV was seen, compared to a significant increase in BF and BV. Perfusion ratios in HCC lesions were significantly (p < 0.05) increased in OR group compared to non-OR patients in C-arm CT and VPCT: PBV ratio (0.95 (0.06) to 0.67 (0.38), BV ratio 0.63 (0.34) to 0.15 (0.6), and BF ratio 0.6 (0.32) to 0.22 (0.51). Logistic regression including PBV and BF allowed prediction of OR (sensitivity 88 %/specificity of 83 %).
Perfusion parameters acquired by C-arm CT and VPCT cannot simply be substituted by each other, but show similar capability in prediction of midterm tumor response.
Hepatocellular carcinoma; Transarterial chemoembolization; Drug eluting beads; Volume perfusion computed tomography; C-arm computed tomography; Parenchymal blood volume; Treatment monitoring
To find out if magnetic resonance (MR)-signal characteristics of hepatocellular carcinomas (HCC) correlate with perfusion parameters assessed by volume perfusion computed tomography (VPCT).
From October 2009 to January 2014, 26 (mean age, 69.3 years) patients with 36 HCC lesions who underwent both VPCT and MR liver imaging were analysed. We compared signal intensity in the T1w- and T2w-images and wash-in/wash-out kinetics on post-contrast MR images with mean values of blood flow (BF, mL/100 mL per minute), blood volume (BV, mL/100 mL), k-trans (mL/100 mL per minute), arterial liver perfusion (mL/100 mL per minute), portal venous perfusion and hepatic perfusion index (HPI, %) obtained by VPCT. Signal intensity on magnetic resonance imaging (MRI) was classified hyper/iso/hypointense compared with surrounding liver parenchyma.
Signal intensity on native T1w- and T2w-images was hyper/iso/hypo in 4/16/16 and 21/14/1 lesions, respectively. Wash-in and wash-out contrast kinetics were found on MRI in 33 of 36 lesions (91.7%) and 25 of 36 lesions (69.4%), respectively. The latter was observed significantly more often in higher graded lesions (P < 0.005). HPI was 94.7% ± 6.5%. There was no significant relationship between lesion’s MR-signal intensity, MR signal combinations, size and any of the VPCT-perfusion parameters. However HPI was constantly high in all HCC lesions.
VPCT parameters add limited value to MR-lesion characterization. However in HCC lesions with atypical MR signal characteristics HPI can add a parameter to ensure HCC diagnosis.
Hepatocellular carcinoma; Volume perfusion computed tomography; Magnetic resonance imaging
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).
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.
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%).
This post-hoc analysis suggests that post-processing of NECT with BC may increase its sensitivity for ischemic brain damage significantly.
C-arm computed tomography (CT) guided intervention is an increasingly applied technique in transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). The aim of this study was to analyse the value of parenchymal blood volume (PBV) maps acquired during C-arm CT acquisition, for pre-treatment evaluation and planning of TACE in HCC patients.
A total of 64 HCC lesions in 29 patients (median age, 73 years, range, 62–77 years) were included in this retrospective study. All patients received cross-sectional imaging (MRI or CT) prior to TACE and C-arm CT PBV measurement acquisition before performing TACE. Results of cross-sectional imaging regarding the number of HCC lesions and maximum diameter were compared to PBV–maps. Number of lesions and tumour feeding vessels detected in PBV-maps were compared to conventional angiography. Results of PBV were analysed concerning different tumour morphologies (pre-treated, encapsulated and diffuse).
Pre-interventional cross-sectional imaging and PBV maps showed an excellent agreement in lesion diameter (p = 0.88, MD = −0.28 mm) and number of detected lesions (κ = 1.0). Compared to conventional angiography, PBV maps showed an increased number of detected lesions (κ = 0.77, p = 0.001) and tumour feeding vessels (κ = 0.71, p < 0.0001). Diffuse HCC lesion revealed a significantly lower PBV compared to encapsulated lesions (p = 0.0001).
C-arm CT acquired PBV measurements detect HCC tumours with a lesion detectability comparable to pre-interventional cross-sectional imaging. Furthermore, this technique facilitates TACE, allowing a more precise localization of HCC lesions and tumour feeding vessels compared to conventional angiography. Additionally, calculated PBV values enable a real time quantitative assessment of tumour perfusion.
Hepatocellular carcinoma; Transarterial chemoembolization; Drug eluting beads; C-arm computed tomography; Parenchymal blood volume
Renal cell carcinoma (RCC) is an immunogenic tumor for which immunotherapeutic approaches could be associated with clinically relevant responses. It was recently shown, that induction of T-cell responses against multiple tumor-associated antigen (TAA) epitopes results in prolonged overall survival in RCC patients. In 2003–2005, we performed a phase I/II trial testing an mRNA-based vaccine formulation consisting of a mixture of in vitro transcribed RNA coding for six different TAAs (MUC1, CEA, Her2/neu, telomerase, survivin, MAGE-A1) in 30 metastatic RCC (mRCC) patients. In the first 14 patients, vaccinations were applied i.d. on days 0, 14, 28, and 42. In the consecutive 16 patients, an intensified protocol consisting of i.d. injections (daily on days 0–3, 7–10, 28, and 42) was used. After the respective induction periods, patients in both cohorts were vaccinated monthly until tumor progression. At survival update performed in July 2015, one of the 30 patients was still alive. One patient was lost to follow-up. Median survival of 24.5 mo (all patients) and 89 mo (favorable risk patients) exceeded predicted survival according to Memorial Sloan Kettering Cancer Center (MSKCC) risk score. Impressively, long-term survivors displayed immunological responses to the applied antigens while vice versa no patient without detectable immune response had survived more than 33 mo. The current survival update shows a clear correlation between survival and immunological responses to TAAs encoded by the naked mRNA vaccine. This is one of the first vaccination studies and the only RNA trial that reports on safety and efficacy after a follow-up of more than 10 y.
Cancer; dendritic cell; human; immunotherapy; phase I/II; renal cell carcinoma; RNA; survival; trial; vaccine
Objectives: To compare the perfusion characteristics of mediastinal lymph node metastases with those of non-metastatic nodes in patients with newly diagnosed lung cancer using volume perfusion computed tomography (VPCT). Materials and methods: Between January 2010 and October 2011, 101 patients with histologically confirmed, untreated lung cancer received a 40-s VPCT of the tumor bulk; 32/101 patients had evident hilar/mediastinal metastatic disease and 17/101 patients had proven non-metastasized lymph nodes within the VPCT scan range. Validation or exclusion of metastatic node involvement was proven by mediastinoscopy, biopsy, positron emission tomography imaging and/or unequivocal volume dynamics on follow-up computed tomography. A total of 45 metastases and 23 non-metastatic lymph nodes were found within the scan range and subsequently evaluated. Blood flow (BF), blood volume (BV) and Ktrans were determined. Tumor volume was recorded as whole tumor volume. Results: In a comparison between metastatic and non-metastatic lymph nodes, we controlled for age, lymph node volume, lung tumor volume, lung tumor location, and histologic type effects and found no significant differences with respect to BF, BV, Ktrans or heterogeneity in nodal perfusion (P > 0.05, respectively), even after adjusting lymph node perfusion values to the perfusion parameters of the primary tumor (P > 0.05, respectively). Metastatic lymph node volume had a significant increasing effect on perfusion heterogeneity (P < 0.05, respectively) and BV in the primary was a highly significant factor for BV in metastatic disease (P < 0.001). Conclusion: Perfusion characteristics of mediastinal metastatic and non-metastatic lymph nodes in untreated lung cancer show considerable overlap, so that a reliable differentiation via VPCT is not possible.
Lung cancer; metastasis; volume perfusion CT; VPCT; Ktrans
Segmentation and diffusion-tensor-imaging of the corpus callosum (CC) have been linked to gait impairment. However, such measurements are impracticable in clinical routine. The purpose of this study was to evaluate the association between simple linear measurements of CC thickness with gait.
Two hundred and seventy-two community-dwelling subjects underwent neurological assessment and brain MRI. Mid-sagittal reformats of T1-weighted images were used to determine CC thickness. The association of measurements with clinical evaluation of gait was assessed by multivariate regression, controlling for numerous clinical and imaging confounders. Differences in CC thickness were, moreover, compared between subgroups with no, moderate or severe impairment of gait.
In univariate analyses, thickness of the genu and body of CC but not the splenium were associated with postural stability (P<0.01). Multivariate regression revealed thickness of CC genu as the only imaging variable independently associated with gait (P=0.01). Genu thickness was significantly different between subjects with high and low (P=0.0003) or high and moderate (P=0.001) risk of fall.
Atrophy of the CC genu is an imaging marker of gait impairment in the elderly suggesting higher risk of fall. Simple linear measurements of CC can help in MRI evaluation of patients with gait impairment.
Corpus callosum; Gait; Magnetic resonance imaging
While paraneoplastic leukocytosis is a common phenomenon in solid tumors, extreme elevations of white blood counts (WBC) in the range of more than 100,000/μl are uncommon in patients with non-hematologic malignancies. Leukocytosis with mature neutrophils due to a granulocyte colony-stimulating factor (G-CSF) producing tumor is only seen on rare occasions.
Massive neutrophil leukocytosis of approximately 100,000/μl was diagnosed in a 57-year-old Caucasian woman with metastatic undifferentiated endometrial sarcoma. A bone marrow trephine biopsy revealed massively increased granulopoiesis, but no evidence of monoclonal myeloproliferative disease. After the primary tumor had been resected, white blood count (WBC) plummeted and went back to nearly normal levels within one week. With progressive metastatic disease, granulocyte colony-stimulating factor (G-CSF) plasma levels were found to be increased by 10-fold. White blood count (WBC) strictly correlated with tumor burden and response to chemotherapy. In the final stage of treatment resistent disease, white blood count (WBC) approximated 300,000/μl.
We report on a granulocyte colony-stimulating factor (G-CSF) secreting undifferentiated endometrial sarcoma, which was associated with extreme neutrophil counts. White blood count (WBC) were closely correlated with tumor burden and associated with an aggressive clinical course. We suggest that paraneoplastic neutrophilia represents a poor prognostic sign in soft tissue sarcoma. In patients with similar constellations, antitumor therapy must not be delayed.
Paraneoplastic leukocytosis; Neutrophilia; G-CSF; Sarcoma
Purpose: To retrospectively determine the potential role of additional computed tomography (CT) attenuation measurements for interim response evaluation in residual masses of patients with Hodgkin disease (HD) and follicular non-Hodgkin lymphoma (NHL). Materials and methods: In this retrospective study, 39 patients with HD and 35 patients with NHL presented with residual masses at mid-treatment CT (after 2–4 cycles of chemotherapy) and were assessed via contrast-enhanced CT at baseline, mid-treatment and post-treatment. Volume was recorded as whole-tumour volume. A tumour attenuation ratio (TAR) was calculated as the quotient of attenuation between tumour and muscle at the respective point in time versus baseline. The standard deviation of attenuation values within the tumour volume was recorded to estimate tumour heterogeneity. Results were correlated with relapse-free survival determined at a minimum of 12 months after end-treatment CT. Results: Tumour volume and TAR at interim versus baseline control were significantly reduced in responders compared with non-responders, even after controlling for age, stage, treatment regimen, and baseline tumour volume. No significant differences with respect to the standard deviation of attenuation values within the tumour volumes (tumour heterogeneity) were observed. The volume and attenuation CT (VACT) criteria yielded the highest sensitivities and specificities for the identification of non-response at a threshold of a >20% increase in volume and an increase in TAR at interim control, i.e. 88% (NHL 80%, HD 100%) and 98% (NHL 97%, HD 100%), respectively. The negative predictive values reached by VACT analysis were ≥97%, according to both parameters. Conclusion: Mid-treatment response assessment of residual masses in patients with HD and NHL using VACT may aid in the risk stratification as an additional surrogate parameter.
Hodgkin disease; follicular lymphoma; volume and attenuation CT; VACT; interim response evaluation
Renal cell carcinoma can cause various paraneoplastic syndromes including metabolic and hematologic disturbances. Paraneoplastic hypereosinophilia has been reported in a variety of hematologic and solid tumors. We present the first case in the literature of severe paraneoplastic hypereosinophilia in a patient with renal cell carcinoma.
A 46 year-old patient patient with a history of significant weight loss, reduced general state of health and coughing underwent radical nephrectomy for metastasized renal cell carcinoma. Three weeks after surgery, the patient presented with excessive peripheral hypereosinophilia leading to profound neurological symptoms due to cerebral microinfarction. Systemic treatment with prednisolone, hydroxyurea, vincristine, cytarabine, temsirolimus and sunitinib led to reduction of peripheral eosinophils but could not prevent rapid disease progression of the patient. At time of severe leukocytosis, a considerable increase of cytokines associated with hypereosinophilia was measurable.
Paraneoplastic hypereosinophilia in patients with renal cell carcinoma might indicate poor prognosis and rapid disease progression. Myelosuppressive therapy is required in symptomatic patients.
Paraneoplastic; Hypereosinophilia; Leukocytosis; Renal cell carcinoma; Leukemoid reaction; Encephalopathy
We aimed to estimate the effective dose of 4D-Perfusion-CT protocols of the lung, liver, and pelvis for the assessment of tumor vascularity.
Materials and Methods
An Alderson-Rando phantom equipped with thermoluminescent dosimeters was used to determine the effective dose values of 4D-Perfusion-CT. Phantom measurements were performed on a 128-slice single-source scanner in adaptive 4D-spiral-mode with bidirectional table movement and a total scan range of 69 mm over a time period of nearly 120 seconds (26 scans). Perfusion measurements were simulated for the lung, liver, and pelvis under the following conditions: lung (80 kV, 60 mAs), liver (80 kV/80 mAs and 80 kV/120 mAs), pelvis (100 kV/80 mAs and 100 kV/120 mAs).
Depending on gender, the evaluated body region and scan protocol, an effective whole-body dose between 2.9-12.2 mSv, was determined. The radiation exposure administered to gender-specific organs like the female breast tissue (lung perfusion) or to the ovaries (pelvic perfusion) led to an increase in the female specific dose by 86% and 100% in perfusion scans of the lung and the pelvis, respectively.
Due to a significant radiation dose of 4D-perfusion-CT protocols, the responsible use of this new promising technique is mandatory. Gender- and organ-specific differences should be considered for indication and planning of tumor perfusion scans.
Perfusion CT; Tumor vascularity; Radiation exposure; Effective dose; 128-slice CT; Alderson-Rando phantom
New therapeutic principles in clinical oncology require the adjustment of response criteria to govern therapy decisions. For advanced hepatocellular carcinoma (HCC) a new era has recently begun by the approval of the multikinase inhibitor sorafenib. As a unique feature, HCC usually develops in a diseased liver and current imaging technologies employing classical response criteria have not been prospectively evaluated for this new treatment.
MRI signal patterns were assessed in 21 advanced HCC patients receiving sorafenib. MRI was performed at baseline and in short-term intervals thereafter. Signal changes under therapy on T1WI, T2WI and post-gadolinium images including necrosis volume and its ratio to the entire tumor volume were compared to baseline imaging. To assess the association between the categorical variables, Fisher's exact tests were applied for a statistical analysis. Survey time ranged from 2–65 weeks, and a total of 39 target lesions were evaluated.
Signal abnormalities during sorafenib therapy were disclosed by T1WI and T2WI in 15/21 patients. The predominant tumor signal change was hyperintensity on both T1WI and T2WI. Interestingly, most patients developed MRI signal changes within 4 weeks of therapy; in contrast, two non-responders did not show any signal alteration at follow-up. Under therapy, 16/21 patients presented with new or progressive necrosis, whereas 7 patients achieved temporarily >75% tumor necrosis under sorafenib. Significantly associated MRI variables were increase in T1WI signal and tumor necrosis (p = 0.017) as well as increase of tumor necrosis with an elevated ratio of necrotic to vital tumor areas (p = 0.002). Remarkably, some (3/13) of the patients developing necrotic tumor areas showed a relevant (>20%) increase in tumor volume, which should be considered in the assessment of imaging studies.
As sorafenib induces early intralesional necrosis with profound changes in T1WI/T2WI MRI signal intensities and measurable necrotic tumor areas in most HCC patients, early MRI-based evaluation could pave the way for its rationale and cost-effective application.