Joachim Hohmann

Ultrasonographic detection of focal liver lesions: increased sensitivity and specificity with microbubble contrast agents

Ultrasonography (US) is the first choice for screening patients with suspected liver lesions. However, due to a lack of contrast agents, US used to be less sensitive and specific compared with computed tomography (CT) and magnet resonance imaging (MRI). The advent of microbubble contrast agents increased both sensitivity and specificity dramatically. Rapid developments of the contrast agents as well as of special imaging techniques were made in recent years. Today numerous different US imaging methods exist which based either on Doppler or on harmonic imaging. They are using the particular behaviour of microbubbles in a sound field which varies depending on the energy of insonation (low/high mechanical index, MI) as well as on the properties of the agent themselves. Apart from just blood pool enhancement some agents have a hepatosplenic specific late phase. US imaging during this late phase using relatively high MI in phase inversion mode (harmonic imaging) or stimulated acoustic emission (SAE; Doppler method) markedly improves the detection of focal liver lesions and is also very helpful for lesion characterisation. With regards to detection, contrast enhanced US performs similarly to CT as shown by recent studies. Early results of studies using low MI imaging and the newer perfluor agents are also showing promising results for lesion detection. Low MI imaging with these agents has the advantage of real time imaging and is particularly helpful for characterisation of focal lesions based on their dynamic contrast behaviour. Apart from the techniques which based on the morphology of liver lesions there were some attempts for the detection of occult metastases or micrometastases by means of liver blood flow changes. Also in this field the use of US contrast agents appears to have advantages over formerly used non contrast-enhanced methods although no conclusive results are available yet.

A multicenter, randomized controlled trial of immediate total-body CT scanning in trauma patients (REACT-2)

BackgroundComputed tomography (CT) scanning has become essential in the early diagnostic phase of trauma care because of its high diagnostic accuracy. The introduction of multi-slice CT scanners and infrastructural improvements made total-body CT scanning technically feasible and its usage is currently becoming common practice in several trauma centers. However, literature provides limited evidence whether immediate total-body CT leads to better clinical outcome then conventional radiographic imaging supplemented with selective CT scanning in trauma patients. The aim of the REACT-2 trial is to determine the value of immediate total-body CT scanning in trauma patients.Methods/designThe REACT-2 trial is an international, multicenter randomized clinical trial. All participating trauma centers have a multi-slice CT scanner located in the trauma room or at the Emergency Department (ED). All adult, non-pregnant, severely injured trauma patients according to predefined criteria will be included. Patients in whom direct scanning will hamper necessary cardiopulmonary resuscitation or who require an immediate operation because of imminent death (both as judged by the trauma team leader) are excluded. Randomization will be computer assisted. The intervention group will receive a contrast-enhanced total-body CT scan (head to pelvis) during the primary survey. The control group will be evaluated according to local conventional trauma imaging protocols (based on ATLS guidelines) supplemented with selective CT scanning. Primary outcome will be in-hospital mortality. Secondary outcomes are differences in mortality and morbidity during the first year post trauma, several trauma work-up time intervals, radiation exposure, general health and quality of life at 6 and 12 months post trauma and cost-effectiveness.DiscussionThe REACT-2 trial is a multicenter randomized clinical trial that will provide evidence on the value of immediate total-body CT scanning during the primary survey of severely injured trauma patients. If immediate total-body CT scanning is found to be the best imaging strategy in severely injured trauma patients it could replace conventional imaging supplemented with CT in this specific group.Trial RegistrationClinicalTrials.gov: (NCT01523626).

Immediate total-body CT scanning versus conventional imaging and selective CT scanning in patients with severe trauma (REACT-2): a randomised controlled trial

BACKGROUND Published work suggests a survival benefit for patients with trauma who undergo total-body CT scanning during the initial trauma assessment; however, level 1 evidence is absent. We aimed to assess the effect of total-body CT scanning compared with the standard work-up on in-hospital mortality in patients with trauma. METHODS We undertook an international, multicentre, randomised controlled trial at four hospitals in the Netherlands and one in Switzerland. Patients aged 18 years or older with trauma with compromised vital parameters, clinical suspicion of life-threatening injuries, or severe injury were randomly assigned (1:1) by ALEA randomisation to immediate total-body CT scanning or to a standard work-up with conventional imaging supplemented with selective CT scanning. Neither doctors nor patients were masked to treatment allocation. The primary endpoint was in-hospital mortality, analysed in the intention-to-treat population and in subgroups of patients with polytrauma and those with traumatic brain injury. The χ(2) test was used to assess differences in mortality. This trial is registered with ClinicalTrials.gov, number NCT01523626. FINDINGS Between April 22, 2011, and Jan 1, 2014, 5475 patients were assessed for eligibility, 1403 of whom were randomly assigned: 702 to immediate total-body CT scanning and 701 to the standard work-up. 541 patients in the immediate total-body CT scanning group and 542 in the standard work-up group were included in the primary analysis. In-hospital mortality did not differ between groups (total-body CT 86 [16%] of 541 vs standard work-up 85 [16%] of 542; p=0.92). In-hospital mortality also did not differ between groups in subgroup analyses in patients with polytrauma (total-body CT 81 [22%] of 362 vs standard work-up 82 [25%] of 331; p=0.46) and traumatic brain injury (68 [38%] of 178 vs 66 [44%] of 151; p=0.31). Three serious adverse events were reported in patients in the total-body CT group (1%), one in the standard work-up group (<1%), and one in a patient who was excluded after random allocation. All five patients died. INTERPRETATION Diagnosing patients with an immediate total-body CT scan does not reduce in-hospital mortality compared with the standard radiological work-up. Because of the increased radiation dose, future research should focus on the selection of patients who will benefit from immediate total-body CT. FUNDING ZonMw, the Netherlands Organisation for Health Research and Development.

Colorectal cancer: current imaging methods and future perspectives for the diagnosis, staging and therapeutic response evaluation.

In the last 10 years the mortality rate of colorectal cancer (CRC) has decreased by more than 20% due to the rising developments in diagnostic techniques and optimization of surgical, neoadjuvant and palliative therapies. Diagnostic methods currently used in the evaluation of CRC are heterogeneous and can vary within the countries and the institutions. This article aims to discuss in depth currently applied imaging modalities such as virtual computed tomography colonoscopy, endorectal ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) in the diagnosis of CRC. Special focus is put on the potential of recent diagnostic developments as diffusion weighted imaging MRI, MRI biomarkers (dynamic enhanced MRI), positron emission tomography with 2-(fluorine-18)-fluoro-2-deoxy-D-glucose (FDG-PET) combined with computed tomography (PET/CT) and new hepatobiliary MRI contrast agents. The precise role, advantage and disadvantages of these modalities are evaluated controversially in local staging, metastatic spread and treatment monitoring of CRC. Finally, the authors will touch upon the future perspectives in functional imaging evaluating the role of integrated FDG-PET/CT with perfusion CT, MRI spectroscopy of primary CRC and hepatic transit time analysis using contrast enhanced ultrasound and MRI in the detection of liver metastases. Validation of these newer imaging techniques may lead to significant improvements in the management of patients with colorectal cancer.

Characterisation of focal liver lesions with unenhanced and contrast enhanced low MI real time ultrasound: on-site unblinded versus off-site blinded reading.

OBJECTIVE To compare on-site and blinded off-site reading of baseline ultrasound (US) and contrast enhanced ultrasound (CEUS) for classification and characterisation of focal liver lesions. MATERIALS AND METHODS 99 patients (57 women and 42 men, age range 18-89 years, mean age: 59 years) with 53 malignant and 46 benign liver lesions were studied with unenhanced US followed by contrast enhanced US after injection of 2.4 ml SonoVue® (Bracco, Milano, Italy). Image interpretation was performed on-site with clinical information available by consensus of two readers and off-site by two independent blinded readers at two different centers. Comparison of pre and post contrast scans and of the different readers was performed. Reference examinations were histology, intraoperative US, MRI or CT. RESULTS Sensitivity for malignancy improved from 81/89/66% (on-site/off-site reader 1/2) before to 100/96/96% post contrast administration (p<0.05, except for reader 1). Specificity improved from 48/48/54% on baseline US to 89/80/76% on CEUS (p<0.05). Accuracy for specific lesion diagnosis was 62/59/50% pre and 90/77/72% post contrast (p<0.05). Classification and characterisation post contrast were mildly inferior for off-site reading. Agreement between on-site and off-site readers of unenhanced scans was fair (κ=0.29-0.39) while it was good for CEUS (κ=0.63-0.79). CONCLUSIONS CEUS improves classification and characterisation of focal liver lesions and interobserver agreement compared to conventional US. Classification and characterisation post contrast were mildly but statistically significantly better for on-site than for off-site reading.

Detection of hepatocellular carcinoma and liver metastases with BR14: a multicenter phase IIA study.

The study was designed primarily to find the optimal dosage range of BR14 contrast-enhanced ultrasonography (CEUS) to detect malignant focal liver lesions. Secondary objectives were the evaluation of the safety profile and comparison with contrast-enhanced MRI (CE MRI). We studied 25 patients (9 females, 16 males, mean age, 66 years) with known hepatocellular carcinoma or liver metastases at 3 centers over a 3-month period. Each patient underwent a baseline examination and at least 3 CEUS examinations with ascending dose levels (0.25 mL; 1.0 mL; 4.0 mL) of BR14. CE MRI was performed 4 weeks before or after the CEUS examination. Dedicated liver maps were used to record the location, size, and type of detected lesions. Examination quality was documented and safety parameters were assessed. The number of lesions detected by BR14 CEUS increased with dosage, whereas the number of missed lesions and the lesion sizes decreased. Despite the increasing contrast enhancement, substantial differences among dosages were not seen for other image quality parameters. No significant changes were noted in safety parameters and no serious adverse events were reported. We conclude that the recommended dose level of BR14 is between 1 mL and 4 mL; at this dosage, lesion detection is comparable to that of CE MRI.

Serum creatinine measurements: evaluation of a questionnaire according to the ESUR guidelines:

Background The European Society of Urogenital Radiology (ESUR) propose measurements of serum creatinine levels in patients undergoing contrast-enhanced studies with a high probability of impaired renal function and therefore with a higher risk of CIN and NSF. Purpose To determine whether the recommended questionnaire is able to select these patients. Material and Methods Over a time period of 10 months the questionnaire was conducted in 1389 patients (725 women, 654 men) before contrast administration for computed tomography (CT) or magnetic resonance imaging (MRI) examination. Serum creatinine (SCr) measurements and calculation of estimated glomerular filtration rate (eGFR) values were performed when one or more answers were positive. Eighty-one patients were excluded due to incomplete data. Statistical evaluation of the questionnaire was done retrospectively. Results Four hundred and ninety-nine patients (38%) gave one or more positive answers to the questionnaire. Of these, 71 (14%) had an eGFR <60 mL/min/1.73 m2, 31 (6%) had an eGFR <45 mL/min/1.73 m2, and five (1%) had an eGFR <30 mL/min/1.73 m2. Only the question concerning previous renal disease showed a significant correlation to an eGFR <60 mL/min/1.73 m2 (P < 0.05) and <45 mL/min/1.73 m2. Slight correlations with some other risk factors (renal disease, family history of renal disease, arterial hypertension with medication, analgetic medication with nephrotoxic drugs) were found for either a threshold of 60 or 45 mL/min/1.73 m2. In addition, there was a positive correlation with patient age. Conclusion We propose to reduce the questionnaire to a smaller number of risk factors and consider a point-of-care (POC) SCr measurement for all patients aged >70 years without a recent eGFR value while referred for CT. For MRI a SCr measurement is not mandatory while using medium and lowest risk contrast agents.

Feasibility of Dose Optimization in a Second-Generation Dual-Source CT Scanner for a Manufacturer-Recommended Urolithiasis Protocol for Imaging Renal Stones

OBJECTIVE The purpose of this article is to investigate the magnitude of dose optimization for a manufacturer-recommended urolithiasis protocol in a second-generation dual-source CT scanner. MATERIALS AND METHODS Custom renal phantoms with 24 stones were scanned using the manufacturer-provided dual-energy CT protocol (tube A, 100 kVp and 210 reference mAs; tube B, 140 kVp and 162 reference mAs) and seven dose-optimized protocols in which the reference tube current-time product setting of tube A was reduced stepwise by 20 mAs. Detection and characterization of the stones was assessed. In the patient study, 25 patients underwent the manufacturer-provided dual-energy protocol and 25 patients underwent imaging with a dose-optimized protocol (tube A, 100 kVp and 90 reference mAs; tube B, 140 kVp and 70 reference mAs). Dose-length product (DLP), image noise, and contrast-to-noise ratio (CNR) were assessed. Subjective image quality was analyzed by three independent radiologists. RESULTS In the phantom study, the reference tube current-time product of tube A could be reduced from 210 to 90 mAs without losing the accuracy of detection or characterization of the calculi. In the patient study, the dose-optimized protocol resulted in a significant reduction of the average DLP by 51% compared with the standard protocol (219.4 vs 443.5 mGy·cm, respectively; p = 0.0001). The image noise was higher, and the CNR was lower, in the dose-optimized group than in the standard-dose group (p < 0.05). The subjective overall image quality of the dose-optimized CT examinations was rated as good, and that of the standard-dose CT examinations was rated as excellent (p = 0.001). CONCLUSION The in vitro and in vivo assessment revealed a potential for a 51% dose reduction of the manufacturer-recommended dual-energy CT protocol for urolithiasis without compromising the accuracy.

Hepatic transit time analysis using contrast enhanced MRI with Gd-BOPTA: A prospective study comparing patients with liver metastases from colorectal cancer and healthy volunteers.

To find out if the hepatic transit time (HTT) shortening, which was already proven in patients with liver metastases by other modalities, can also be detected with MRI.

Erratum to: High rates of clinically relevant incidental findings by total-body CT scanning in trauma patients: Results of the REACT-2 trial (vol 27, pg 2451, 2017)

A technical error led to incorrect rendering of the author group in this article. The correct authorship is as follows: K. Treskes1, S.A. Bos1, L.F.M. Beenen2, J.C. Sierink1, M.J.R. Edwards3, B.J.A. Beuker4 , G.S.R. Muradin5, J. Hohmann6, J.S.K. Luitse1, M.W. Hollmann7, M.G.W. Dijkgraaf8, J.C. Goslings1, on behalf of the REACT-2 study group The collaborators are: T.P. Saltzherr, T. Schepers, V.M. de Jong, R. van Vugt, M. Brink, J. Peters, M. El Moumni, J.S. Harbers, K.W. Wendt, E.M.M. van Lieshout, M.J. Elzinga, E.H. Jansen, C. Zahringer, N. Bless, R. Bingisser The original publication has been corrected.