Birthe Merete Henriksen

Reproducibility of ultrasound and magnetic resonance imaging measurements of tendon size

Purpose: To investigate the intra- and inter-tester reproducibility of measurements of the Achilles tendon, tibialis anterior tendon, and the tibialis posterior tendon in football players using ultrasound (US) and magnetic resonance imaging (MRI). Material and Methods: Eleven asymptomatic football players were examined. Using a standardized US scanning protocol, the tendons were examined by two observers with US for thickness, width, and cross-sectional area. One observer conducted the procedure twice. The subjects also underwent an MRI examination, and the assessment of tendon size was conducted twice by two observers. Results: The best reproducibility judged by coefficient of variation (CV) and 95% confidence interval was determined for the Achilles tendon on both US and MRI. The variability of US on measurements on the tibialis anterior and tibialis posterior tendons was less than that when using MRI. In 12 out of 18 measurements, there were systematic differences between observers as judged by one-sided F-test. Conclusion: The reproducibility of the three tendons was limited. Precaution should be taken when looking for minor quantitative changes, i.e., training-induced hypertrophy, and when doing so, the Achilles tendon should be used.

Characterization by biopsy or CEUS of liver lesions guided by image fusion between ultrasonography and CT, PET/CT or MRI.

PURPOSE The aim of this study was to show the number of cases in which the use of fusion-guided ultrasonography (US) provided conclusive diagnosis of lesions in the liver seen on CT or MRI or PET/CT. A lesion is defined as a region that has suffered damage due to injury or disease. MATERIALS AND METHODS Forty patients of whom 34 had confirmed neoplastic disease, referred to US evaluation or US-guided biopsy of liver lesions seen on CT (n = 35), MRI (n = 2) or PET/CT (n = 3), were prospectively included in the study. We used a LOGIQ prototype system with incorporated software for fusion imaging, and a convex-array 4 MHz transducer (GE Healthcare, Chalfont St. Giles, UK). All patients were initially examined with B-mode US, then by fusion-guided US and for some patients also with CEUS. All patients received follow-up after at least one year. RESULTS Twenty-six lesions were initially indistinguishable with US. Of these, 9 became visible with fusion-guided US and another 4 became visible with CEUS, which facilitated a final diagnosis in 11 of these 13 patients. The median tumor size for all lesions included in the study was 1.5 cm (interquartile range: 1.0 - 2.4). There was no statistically significant difference in tumor size between the groups. CONCLUSION We have successfully demonstrated an increase in the characterization of liver lesions by using fusion-guided US compared with conventional B-mode US.

Positron Emission Tomography/Computed Tomography in the Staging and Treatment of Anal Cancer

PURPOSE This study was intended to determine the role of PET/CT in the staging of anal cancer as a supplement to three-dimensional transanal ultrasound (TAUS) and inguinal ultrasound (US). The impact of the PET/CT on the initial stage and treatment plan proposed by TAUS/US was assessed. METHODS AND MATERIALS Ninety-five (95) patients referred to our clinic between July 1, 2005, and December 31, 2009, were retrospectively reviewed. All patients had biopsy-proven primary squamous cell cancer of the anal canal. There were 65 females (68%) and 30 males (32%), and the median age was 58 years (range, 35-88 years). Six (6%) of the patients were HIV positive. All patients were staged with TAUS/US and PET/CT. RESULTS Twenty-eight (28) patients were diagnosed with suspicious perirectal node metastases. TAUS visualized 24 of these, whereas PET/CT detected 15. Suspicious inguinal nodes were visualized on either US or PET/CT in 41 patients. Seventeen (17) of these had confirmed malignant disease on biopsy, and 15 had confirmed benign disease. All 17 patients (100%) with malignant inguinal nodes were diagnosed by PET/CT, whereas US identified 16 (94%). Ten patients were diagnosed with suspicious inguinal nodes on PET/CT that had not been seen on US. One of these was malignant, three were benign, and six were not biopsied. PET/CT diagnosed eight metastatic sites, whereas TAUS/US diagnosed three. PET/CT discovered three of the five synchronous cancers seen in this study. PET/CT upstaged the disease in 14% of the cases and changed the treatment plan proposed by TAUS/US in 17%. CONCLUSION PET/CT has great potential influence on the staging and treatment of anal cancer. TAUS is important in the staging of the primary tumor and N1-stage, whereas PET/CT seems necessary for the N2/3-stage, the M-stage and synchronous cancers.

Staging of Cervical Lymph Nodes in Oral Squamous Cell Carcinoma: Adding Ultrasound in Clinically Lymph Node Negative Patients May Improve Diagnostic Work-Up

Introduction Clinical staging of patients with oral squamous cell carcinoma (OSCC) is crucial for the choice of treatment. Computed tomography (CT) and/or magnetic resonance imaging (MRI) are typically recommended and used for staging of the cervical lymph nodes (LNs). Although ultrasonography (US) is a non-expensive, accessible and non-ionising imaging modality this method is not consistently used. This study aimed to investigate if addition of US of patients classified as clinically LN negative (cN0) by CT and/or MRI, increases the detection of LN metastases. Also, we aimed to identify which of the sonographic characteristics: echogenicity, border, shape, appearance of hilum and nodal blood-flow pattern best detect metastases in this patient group. Method Fifty-one patients with OSCC classified as cN0 by CT/MRI were consecutively included and prospectively examined with US prior to sentinel node biopsy or selective neck dissection. Localisation, size and sonographic characteristics were registered for each LN and compared with the pathological findings. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for different size measurements and sonographic characteristics. Results We found that short axial diameter was the best size criterion for detection of metastases. However, the sonographic characteristics were better predictors than size and the presence at least four of the sonographic characteristics: hypo-echoic or heterogeneous appearance; irregular border; spherical shape; absence of nodal hilum; and peripheral nodal blood-flow resulted in a sensitivity of 43.8; specificity 91.4; PPV 70.0; and NPV 78.0. The number of patients with occult metastases decreased from 16 out of 51 (31%) to nine out of 51 (18%). Three patients (6%) were over-staged by US. Conclusion The addition of US to the clinical work-up of patients with cN0 OSCC increases the detection of metastases, thus US potentially reduces the number of patients requiring a secondary neck surgery after sentinel node biopsy.

Improving Accuracy for Image Fusion in Abdominal Ultrasonography.

Image fusion involving real-time ultrasound (US) is a technique where previously recorded computed tomography (CT) or magnetic resonance images (MRI) are reformatted in a projection to fit the real-time US images after an initial co-registration. The co-registration aligns the images by means of common planes or points. We evaluated the accuracy of the alignment when varying parameters as patient position, respiratory phase and distance from the co-registration points/planes. We performed a total of 80 co-registrations and obtained the highest accuracy when the respiratory phase for the co-registration procedure was the same as when the CT or MRI was obtained. Furthermore, choosing co-registration points/planes close to the area of interest also improved the accuracy. With all settings optimized a mean error of 3.2 mm was obtained. We conclude that image fusion involving real-time US is an accurate method for abdominal examinations and that the accuracy is influenced by various adjustable factors that should be kept in mind.

Ultrasound Elastography Is Useful for Evaluation of Liver Fibrosis in Children-A Systematic Review.

Objectives: Adult studies have proven ultrasound elastography as a validated measure of liver fibrosis. The present study aimed to review the available literature on ultrasound elastography in children to evaluate the ability of the method to distinguish healthy from fibrotic liver tissue and investigate whether cutoff values for liver fibrosis in children have been established. Methods: A literature search was performed in MEDLINE, EMBASE, the Cochrane Library, and Web of Science to identify studies on ultrasound elastography of the liver in children. Only original research articles in English concerning ultrasound elastography in children with and without liver disease, younger than 18 years, were included. All reference lists of the included articles were hand-searched for further references. Results: Twenty-seven articles were included. Elastography in children without liver disease was investigated in 14 studies and the results were comparable to those existing for adults. Twelve studies compared elastography with liver biopsy in children with liver disease and found that cirrhosis was correctly diagnosed, whereas it was more difficult to assess severe fibrosis correctly. For the distinction between no, mild, and moderate fibrosis in children with liver disease the method was less accurate. Ultrasound elastography was able to differentiate between children with and without liver fibrosis. In children without liver disease ultrasound elastography showed consistent liver stiffness values comparable to those found in adults. No fibrosis-specific cutoffs were proposed. Conclusions: Ultrasound elastography was able to diagnose cirrhosis, distinguish healthy from fibrotic liver tissue, and showed consistent liver stiffness values in children without liver disease.

Transfer from point-of-care Ultrasonography training to diagnostic performance on patients—a randomized controlled trial

BACKGROUND Clinicians are increasingly using point-of-care ultrasonography for bedside examinations of patients. However, proper training is needed in this technique, and it is unknown whether the skills learned from focused Ultrasonography courses are being transferred to diagnostic performance on patients. METHODS Thirty-one physicians were randomized to participate in a focused Ultrasonography course or control circumstances before they examined 4 patients with different abdominal conditions by ultrasonography. Performance scores and diagnostic accuracy were compared using independent samples t test and binary logistic regression, respectively. RESULTS There was a significant difference in the performance score between the intervention group (27.4%) and the control group (18.0%, P = .004) and the diagnostic accuracy between the intervention group (65%) and the control group (39%, P = .014). CONCLUSIONS Clinicians could successfully transfer learning from an Ultrasonography course to improve diagnostic performance on patients. However, our results also indicate a need for more training when new technologies such as point-of-care ultrasonography are introduced.

Competency‐based assessment in surgeon‐performed head and neck ultrasonography: A validity study

Head and neck ultrasonography (HNUS) increasingly is used as a point‐of‐care diagnostic tool by otolaryngologists. However, ultrasonography (US) is a very operator‐dependent image modality. Hence, this study aimed to explore the diagnostic accuracy of surgeon‐performed HNUS and to establish validity evidence for an objective structured assessment of ultrasound skills (OSAUS) used for competency‐based assessment.

Dynamic Contrast-Enhanced Ultrasound of Colorectal Liver Metastases as an Imaging Modality for Early Response Prediction to Chemotherapy

Our aim was to investigate whether dynamic contrast-enhanced ultrasound (DCE-US) can detect early changes in perfusion of colorectal liver metastases after initiation of chemotherapy. Newly diagnosed patients with colorectal cancer with liver metastases were enrolled in this explorative prospective study. Patients were treated with capecitabine or 5-fluorouracil-based chemotherapy with or without bevacizumab. DCE-US was performed before therapy (baseline) and again 10 days after initiation of treatment. Change in contrast-enhancement in one liver metastasis (indicator lesion) was measured. Treatment response was evaluated with a computed tomography (CT) scan after three cycles of treatment and the initially observed DCE-US change of the indicator lesion was related to the observed CT response. Eighteen patients were included. Six did not complete three series of chemotherapy and the evaluation CT scan, leaving twelve patients for analysis. Early changes in perfusion parameters using DCE-US did not correlate well with subsequent CT changes. A subgroup analysis of eight patients receiving bevacizumab, however, demonstrated a statistically significant correlation (p = 0.045) between early changes in perfusion measures of peak enhancement at DCE-US and tumor shrinkage at CT scan. The study indicates that early changes in DCE-US perfusion measures may predict subsequent treatment response of colorectal liver metastases in patients receiving bevacizumab.

Importance of Comprehensive Molecular Profiling for Clinical Outcome in Children With Recurrent Cancer

Purpose: Pediatric cancers are often difficult to classify and can be complex to treat. To ensure precise diagnostics and identify relevant treatment targets, we implemented comprehensive molecular profiling of consecutive pediatric patients with cancer relapse. We evaluated the clinical impact of extensive molecular profiling by assessing the frequency of identified biological onco-drivers, altered diagnosis, and/or identification of new relevant targeted therapies. Patients and Methods: Forty-six tumor samples (44 fresh-frozen; two formalin-fixed paraffin embedded), two bone marrow aspirates, three cerebrospinal fluid samples, and one archived DNA were obtained from 48 children (0–17 years; median 9.5) with relapsed or refractory cancer, where the disease was rapidly progressing in spite of their current treatment or they had exhausted all treatment options. The samples were analyzed by whole-exome sequencing (WES), RNA sequencing (RNAseq), transcriptome arrays, and SNP arrays. Final reports were available within 3–4 weeks after patient inclusion and included mutation status, a description of copy number alterations, differentially expressed genes, and gene fusions, as well as suggestions for targeted treatment. Results: Of the 48 patients, 33 had actionable findings. The most efficient method for the identification of actionable findings was WES (39%), followed by SNP array (37%). Of note, gene fusions were identified by RNAseq in 21% of the samples. Eleven findings led to clinical intervention, i.e., oncogenetic counseling, targeted treatment, and treatment based on changed diagnosis. Four patients received compassionate use targeted therapy. Six patients experienced direct benefits in the form of stable disease or response. Conclusion: The application of comprehensive genetic diagnostics in children with recurrent cancers allowed for discovery and implementation of effective targeted therapies and hereby improvement of outcome in some patients.